@article {pmid42347833,
year = {2026},
author = {Wesenberg, J and Matthies, P and Schwiecker, K and Bittner, V and Hamzic, S and Vielhaber, S and Radakovic, R},
title = {Validation of the German version of the Dimensional Apathy Scale (G-DAS): Application in amyotrophic lateral sclerosis.},
journal = {Journal of neuropsychology},
volume = {},
number = {},
pages = {},
doi = {10.1111/jnp.70061},
pmid = {42347833},
issn = {1748-6653},
support = {//Center for Behavioral Brain Sciences/ ; },
abstract = {Apathy is a common behavioural impairment in neurodegenerative conditions and is conceptualized within the Dimensional Apathy Framework as comprising Executive, Emotional and Initiation subtypes. The Dimensional Apathy Scale (DAS) is widely used to assess these domains, yet no validated German version has been available. This study aimed to translate and validate the German DAS (G-DAS) in control participants (HC) and to characterize apathy profiles in German-speaking people with amyotrophic lateral sclerosis (pwALS). Seventy-seven HC and 32 pwALS completed self-rated and caregiver-rated measures of apathy, depression, disinhibition and executive dysfunction. The G-DAS was translated using a multi-round back-translation procedure. Psychometric validation was undertaken in the HC cohort. A subsample of HC matched to pwALS on age and sex was used for between-group comparisons and for deriving exploratory reference thresholds. The G-DAS demonstrated good to high internal consistency across subscales (α = .76-.85) and total scores (self-rated: α = .88; caregiver-rated: α = .86). Convergent validity was supported by significant correlations with the Apathy Evaluation Scale and Frontal Systems Behavior subscales, particularly for the Initiation and Executive subscales. Divergent validity was evidenced by the absence of associations with anxiety and depression. PwALS showed significantly higher Executive and Initiation apathy compared with matched HC, whereas Emotional apathy did not differ. Exploratory threshold scores derived from matched HC indicated that up to 47% of pwALS exhibited clinically elevated Initiation apathy. The G-DAS is a reliable and valid German-language measure of multidimensional apathy. It effectively captures the characteristic Executive and Initiation apathy profile in ALS, supporting its clinical and research utility.},
}

@article {pmid42348198,
year = {2026},
author = {Walter, KL},
title = {Amyotrophic Lateral Sclerosis.},
journal = {JAMA},
volume = {},
number = {},
pages = {},
doi = {10.1001/jama.2026.9755},
pmid = {42348198},
issn = {1538-3598},
}

@article {pmid42349387,
year = {2026},
author = {Pusic, MV and Ten Cate, O},
title = {Artificial Intelligence, Cognitive Abundance, and the Multi-Layered Competence of Health Professionals.},
journal = {The Journal of continuing education in the health professions},
volume = {},
number = {},
pages = {},
doi = {10.1097/CEH.0000000000000656},
pmid = {42349387},
issn = {1554-558X},
abstract = {Artificial intelligence (AI) is transforming how health care professionals develop, maintain, and express competence across the span of their careers. Traditional continuing professional development has been shaped by a paradigm of what has been called cognitive scarcity (or informational resource scarcity) where clinicians had limited opportunity to find, read, synthesize, and interpret evidence, and learning systems evolved to deliver knowledge in periodic, curated updates. Emerging AI systems-large language models, multimodal analytic tools, predictive algorithms, and reflective agents-disrupt this scarcity by creating cognitive abundance (or informational resource abundance). These systems generate real-time evidence syntheses, contextual insights, adaptive learning trajectories, and continuous performance feedback. Using ten Cate et al.'s (2024, Medical competence as a multilayered construct. Med Educ, 58, 93) multilayered model of competence-canonical, contextual, and personalized-this paper analyzes how AI can both enhance existing educational processes and fundamentally reshape the developmental landscape. AI shifts clinicians from being knowledge stewards to orchestrators of distributed cognition, from experiential learners to data-informed practitioners, and from using opportunistic continuous personal development to continuous reshaping of professional identity. Continuing professional development must evolve to cultivate AI literacy, hybrid reasoning, interprofessional coherence, and ethical stewardship in work environments where cognition is abundant. The contents of long-term memory of clinicians will shift from a predominance of biomedical facts needed to steer daily clinical work, to new procedural inquiry skills needed to find, select, and evaluate the validity of information for clinical decision making.},
}

@article {pmid42349418,
year = {2026},
author = {Heffner, CM and Starling, GP and Straker, LC and Hawes, PC and Isaacs, AM and Carlton, JG},
title = {The ALS- and FTD-associated proteins annexin A11 and CHMP2B act sequentially in plasma membrane repair.},
journal = {Developmental cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.devcel.2026.05.014},
pmid = {42349418},
issn = {1878-1551},
abstract = {Maintenance of plasma membrane integrity is essential for compartmentalization of the cytosol and for cellular viability. Upon membrane damage, several factors including endosomal sorting complex required for transport-III (ESCRT-III) proteins, annexins, stress granules, lipids, and membrane fusion proteins are mobilized to orchestrate membrane repair. However, whether these factors operate independently or act together is unclear. Here, using human cell lines, we expose temporal differences and interdependencies in the recruitment of ESCRT-III and annexin proteins to sites of plasma membrane damage. We show that annexin proteins are recruited immediately and form a plug at the damage site, restricting membrane permeability. We find that ESCRT-III assembles later and acts to release plug-containing damaged membranes from the cell. Further, frontotemporal dementia (FTD)- and amyotrophic lateral sclerosis (ALS)-associated mutations in the ESCRT-III protein, CHMP2B, and the annexin protein, ANXA11, compromise plasma membrane repair, suggesting that defects in this process may contribute to these pathologies. These data present an integrated "sealing and healing" model of membrane repair.},
}

@article {pmid42349421,
year = {2026},
author = {Aubry, L and Korolchuk, VI and Sarkar, S},
title = {Rewiring ALS by modulating the autophagy receptor SQSTM1.},
journal = {Stem cell reports},
volume = {},
number = {},
pages = {102976},
doi = {10.1016/j.stemcr.2026.102976},
pmid = {42349421},
issn = {2213-6711},
abstract = {Drug screening for genetic disorders is limited by difficulty identifying disease-relevant phenotypes. In this issue, Roussange et al., show that reverse phenotypic mapping could uncover therapeutic gene expression signatures. Using this approach, they identified prazosin, which increases SQSTM1 expression and rescues disease phenotypes in iPSC-derived motor neurons and zebrafish model of amyotrophic lateral sclerosis with SQSTM1 haploinsufficiency.},
}

@article {pmid42349423,
year = {2026},
author = {Roussange, F and Gide, J and Tournois, J and Cailleret, M and Boland, A and Battail, C and Deleuze, JF and Polvèche, H and Auboeuf, D and Brockmann, K and Kabashi, E and Marian, A and El Kassar, L and Blondel, S and Salachas, F and Bruneteau, G and Peschanski, M and Martinat, C and Baghdoyan, S},
title = {Integrative analysis of drug-gene signatures in human pluripotent stem cells reveals prazosin as a novel SQSTM1 regulator for ALS therapeutics.},
journal = {Stem cell reports},
volume = {},
number = {},
pages = {102977},
doi = {10.1016/j.stemcr.2026.102977},
pmid = {42349423},
issn = {2213-6711},
abstract = {The classical paradigm of drug screening often faces significant limitations due to the challenges associated with identifying molecular or cellular read-outs that are relevant to specific genetic diseases. To remedy this, an alternative approach of reverse phenotypic mapping was tested: Compounds were evaluated for their effects on gene expression and alternative splicing in a healthy cell model, and the resulting data were matched to molecular signatures of diseases. A subset of 50 drugs was tested on mesenchymal stem cells derived from a human pluripotent stem cell line. Over half of the compounds altered gene expression, many affecting pathways linked to monogenic diseases. One hit, increased SQSTM1 expression induced by prazosin, was further validated in FTD/ALS type 3 models caused by SQSTM1 haploinsufficiency, including patient-derived fibroblasts, SQSTM1-depleted hiPSC-derived motor neurons, and a zebrafish model. Extending this paradigm could involve testing diverse cell types and larger drug libraries.},
}

@article {pmid42350166,
year = {2026},
author = {Tikkinen, KAO and Tondroanamag, F and Parpia, S and Guyatt, GH and Violette, PD and , },
title = {Reply to Vallée M, Stangl FP, Wagenlehner F et al's Letter to the Editor re: Tikkinen KAO, Najafabadi BT, Hajebrahimi S, et al. A Multicenter Randomized Controlled Trial of Antimicrobial Prophylaxis to Prevent Urinary Tract Infections After Shockwave Lithotripsy for Urolithiasis: The APPEAL Trial. Eur Urol 2025;88(6):543-51.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2026.06.008},
pmid = {42350166},
issn = {1873-7560},
}

@article {pmid42350373,
year = {2026},
author = {Casterton, R and Martinez-Cotrina, A and Barnard, J and Wycherley, E and Hu, Y and Anderson, R and Janel, S and Byun, J and Houghton, O and Solomon, DA and Alcalde, J and Lafont, F and Ruepp, MD and Hirth, F and Tummers, B and Cho, YY and De Nicola, G and Mizielinska, S and Fanto, M},
title = {Karyoptosis mediates cell death and neurodegeneration upon proteotoxic stress.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {},
pmid = {42350373},
issn = {2041-1723},
support = {ARUK-PG2019B-008//Alzheimer's Research UK (ARUK)/ ; },
mesh = {Proteotoxic Stress ; Animals ; Humans ; Cell Death ; Neurons/metabolism/pathology ; Lamin Type B/metabolism/genetics ; Phosphorylation ; Alzheimer Disease/pathology/metabolism ; *Neurodegenerative Diseases/metabolism/pathology ; Nuclear Lamina/metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism ; Mice ; Frontotemporal Dementia/pathology/metabolism ; Cell Nucleus/metabolism ; },
abstract = {Neurodegenerative diseases are frequently associated with proteotoxic stress linked to disease specific proteins. The autophagy-lysosome system provides essential control of proteotoxic stress and its failure can lead to initiation of apoptosis. However, in aging and neurodegenerative diseases apoptosis is insufficient to account for all neuronal death, and several different cell death types have been reported in these contexts. Here we show that karyoptosis, a distinct form of cell death, can be induced by proteotoxic stress and then develops through nuclear degeneration and cellular expulsion of nuclear material. We establish that karyoptosis is regulated by the p38 kinase signalling pathway, which controls stability of the nuclear lamina protein LaminB1 via direct phosphorylation. We demonstrate that karyoptosis affects neurons in models of amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) pathology. Finally, we identify karyoptotic features in post-mortem frontal cortex of FTD and Alzheimer's disease (AD) patients. Together these findings characterise a form of cell death directly linked to proteotoxic stress and nuclear lamina stability that is associated with neurodegeneration.},
}

Proteotoxic Stress
Animals
Humans
Cell Death
Neurons/metabolism/pathology
Lamin Type B/metabolism/genetics
Phosphorylation
Alzheimer Disease/pathology/metabolism
*Neurodegenerative Diseases/metabolism/pathology
Nuclear Lamina/metabolism
p38 Mitogen-Activated Protein Kinases/metabolism
Mice
Frontotemporal Dementia/pathology/metabolism
Cell Nucleus/metabolism

@article {pmid42350385,
year = {2026},
author = {Wan, F and He, J and Ma, H and PiresFerreira, D and Kumanan, V and Lee, JS and Chen, X and He, R and Su, Q and Gallagher, TL and Zhu, S and Cabrera, GT and Zhao, L and Shen, J and Gruntman, A and Brown, RH and Xu, Z and Gao, G and Xie, J},
title = {Intravenous administration of an engineered AAV9-gene-silencing vector suppresses human SOD1 and extends survival in an ALS mouse model.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {},
pmid = {42350385},
issn = {2041-1723},
support = {AL240123//United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP)/ ; },
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/therapy/genetics ; *Dependovirus/genetics ; *Superoxide Dismutase-1/genetics/metabolism ; Humans ; Disease Models, Animal ; *Genetic Vectors/administration & dosage/genetics ; Mice ; Motor Neurons/metabolism/pathology ; *Genetic Therapy/methods ; *Gene Silencing ; Mice, Transgenic ; Administration, Intravenous ; MicroRNAs/genetics ; Neuromuscular Junction/metabolism ; Female ; Gene Therapy Agents ; Male ; },
abstract = {Adeno-associated virus (AAV)-mediated gene silencing offers a promising strategy for achieving durable therapeutic effects with a single administration. Mutations in the human superoxide dismutase 1 (hSOD1) gene, inherited in an autosomal dominant manner, lead to motor neuron degeneration in amyotrophic lateral sclerosis (ALS)-a fatal neurodegenerative disease with no effective treatment. In this study, we employed AAV9 to deliver to the SOD1[G93A] ALS mouse model artificial microRNAs targeting SOD1, embedded in dual miR-33 scaffolds driven by the promoter of the human survival motor neuron 1 (hSMN1) gene. A single intravenous injection achieved widespread and sustained suppression of SOD1, preserved α-motor neurons, maintained neuromuscular junctions (NMJs), and improved muscle function. These benefits are translated into significantly improved respiratory function, motor performance, and survival. Therapeutic efficacy was observed both when the treatment was administered pre-symptomatically and during symptomatic stages. Compared with previous AAV-based interventions, the survival benefit achieved in this IV delivery approach is unprecedented, supporting its potential for clinical translation in SOD1-linked ALS and other central nervous system (CNS) diseases caused by gain-of-toxicity gene mutations.},
}

Animals
*Amyotrophic Lateral Sclerosis/therapy/genetics
*Dependovirus/genetics
*Superoxide Dismutase-1/genetics/metabolism
Humans
Disease Models, Animal
*Genetic Vectors/administration & dosage/genetics
Mice
Motor Neurons/metabolism/pathology
*Genetic Therapy/methods
*Gene Silencing
Mice, Transgenic
Administration, Intravenous
MicroRNAs/genetics
Neuromuscular Junction/metabolism
Female
Gene Therapy Agents
Male

@article {pmid42351201,
year = {2026},
author = {Dominguez, GTY and Alarcan, H and Peralta, V and Labroche, N and Corcia, P and Marcel, P and Blasco, H},
title = {Learning a distance for the clustering of patients with amyotrophic lateral sclerosis.},
journal = {BioData mining},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13040-026-00579-5},
pmid = {42351201},
issn = {1756-0381},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with median survival of 3-5 years. Patient responses to treatments vary widely, highlighting the need for personalized care. Clustering patients based on disease progression could improve prognosis, guide clinical decision-making, and optimize clinical trial design. This study aimed to identify robust ALS patient clusters using ALS Functional Rating Scale-Revised (ALSFRS-R) scores and to determine diagnostic parameters predictive of cluster membership, enabling earlier stratification and targeted management.

METHODS: Data from the Tours ALS center registry (April 1997-October 2023) were analyzed; after preprocessing, 353 patients monitored every three months between January 2004 and July 2023 with ALSFRS-R, clinical, biological, and demographic data were retained. After preprocessing to handle missing or aberrant data, a weakly supervised approach labeled patient pairs based on their ALSFRS-R sequences. These labels were used to train a classifier to learn a distance for off-the-shelf clustering algorithms. Multiple configurations were tested, varying clustering algorithms, dimensionality reduction method, and number of clusters. Random Forest (RF) model predicted cluster membership from diagnostic parameters. Optimal clustering was selected using silhouette score, validated with Kaplan-Meier survival analysis. Stability and robustness were assessed with the Adjusted Rand Index (ARI) and silhouette score respectively. Predictive performance was evaluated using specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV). Diagnostic parameters associated with clusters were identified using Kruskal-Wallis and chi-squared tests for continuous and categorical variables.

RESULTS: Three clusters (n = 139, 121, 93) were identified, demonstrating strong separation (silhouette ≈ 0.6) and high stability of results (ARI ≈ 0.7). Survival differed significantly among clusters: over 50% of patients in the third cluster survived beyond 50 months, compared to less than 25% in the other clusters. Thirteen diagnostic parameters-including ALSFRS-R subscores, IgG levels, albumin quotient, and time to diagnosis-were key predictors of cluster membership. Cluster prediction achieved specificity and NPV ≈ 0.75, with close sensitivity and PPV compared to state-of-the-art methods.

CONCLUSION: This framework successfully stratifies ALS patients into clinically meaningful clusters, revealing underlying disease heterogeneity and providing strong prognostic insight. Such classification can facilitate personalized care, guide therapeutic decisions, and inform the design of targeted interventions to improve outcomes.

CLINICAL TRIAL NUMBER: Not applicable.},
}

@article {pmid42351263,
year = {2026},
author = {Riggio, F and Fenili, G and Caporossi, D and Paronetto, MP},
title = {Dynamic integration of skeletal muscle signals via extracellular vesicles in motor neuron diseases.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-026-02356-1},
pmid = {42351263},
issn = {2051-5960},
support = {PNRR-MR1-2022-12376821//Ministero della Salute/ ; },
abstract = {Extracellular vesicles (EVs) are heterogenous lipid bilayer-enclosed particles secreted by virtually all cell types. They encapsulate a diverse array of bioactive molecules, including proteins, lipids, nucleic acids, and metabolites, which can be transferred to recipient cells, thereby modulating their function and phenotype. In recent years, skeletal muscle-derived EVs (SkM-EVs) have emerged as key players in the bidirectional communication between skeletal muscle and motor neurons, contributing to the establishment and maintenance of neuromuscular homeostasis. Disruptions in this intercellular signalling have been implicated in the pathophysiology of motor neuron diseases (MNDs) such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). In these contexts, SkM-EVs may contribute to disease progression by delivering pathogenic cargo, including misfolded proteins and aberrant RNAs, to motor neurons. A comprehensive understanding of SkM-EV biology, particularly their roles in neuromuscular communication, could offer critical insights into disease mechanisms and identify novel opportunities for biomarker discovery and therapeutic intervention. This review synthesizes current knowledge on the functional roles of SkM-EVs in motor neuron health and disease and evaluates their potential as diagnostic tools and therapeutic vectors in the context of MNDs.},
}

@article {pmid42351313,
year = {2026},
author = {Brenner, D and Ponomarenko, A and Petrut, I and Beyrle, S and Contardo, M and Loss, I and Radke, C and Frank, J and Zimmer, E and Schlesner, M and Achenbach, P and Scheveneels, W and Aly, A and Nazlican, H and Hesebeck-Brinkmann, J and Oeckl, P and Müller, K and Siebert, R and Böckers, T and van Eijk, K and Veldink, J and Kleger, A and Mulaw, M and Andersen, PM and Forsberg, K and Weishaupt, JH and Loghmani, SB and Grehl, T and van Damme, P and Weis, J and Catanese, A},
title = {A rare missense variant impacting NEK1 kinase function is associated with ALS.},
journal = {Acta neuropathologica communications},
volume = {14},
number = {1},
pages = {},
pmid = {42351313},
issn = {2051-5960},
mesh = {*NIMA-Related Kinase 1/genetics/metabolism ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *Mutation, Missense/genetics ; Female ; Motor Neurons/pathology/metabolism ; Male ; Pedigree ; Animals ; },
abstract = {Heterozygous truncating loss-of-function (LoF) variants in NEK1 are a known cause of amyotrophic lateral sclerosis (ALS). NEK1 encodes the pleiotropic serine/threonine kinase NIMA-related kinase 1, and prior in vitro studies have implicated kinase dysfunction as the principal pathogenic mechanism underlying NEK1-associated ALS. However, bona fide pathogenic missense variants causally linked to ALS have not previously been reported, leaving this hypothesis unconfirmed. Here, we identify a rare NEK1 missense variant, p.N598S, that co-segregates with disease in a familial ALS pedigree and is enriched in European ALS cohorts. This variant exhibits normal protein expression levels, indicating a functional rather than quantitative defect. Using isogenic human motor neurons, we directly compared the effects of p.N598S with those of the ALS-associated truncating variant p.R812* to delineate disease mechanisms. The p.N598S variant induced pathological phenotypes consistent with NEK1 haploinsufficiency, including increased susceptibility to DNA damage, increased apoptosis, ciliary dysmorphia, and nucleocytoplasmic translocation of TDP-43. Importantly, p.N598S impaired NEK1 kinase activity, and pharmacological inhibition of NEK1 recapitulated the cellular phenotypes observed in both p.N598S- and p.R812*-mutant motor neurons. Collectively, these findings provide strong genetic and functional evidence for a disease-causing role of NEK1 kinase disruption in NEK1-ALS. Our findings provide immediate diagnostic and therapeutic implications, particularly for the functional interpretation of missense variants of uncertain significance and the development of targeted treatment strategies.},
}

*NIMA-Related Kinase 1/genetics/metabolism
Humans
*Amyotrophic Lateral Sclerosis/genetics/pathology
*Mutation, Missense/genetics
Female
Motor Neurons/pathology/metabolism
Male
Pedigree
Animals

@article {pmid42352309,
year = {2026},
author = {Morciano, G and Gorgoglione, R and Porcelli, V and Ahmed, A and Scarcia, P and Vozza, A and Lasorsa, FM and Fiermonte, G and Palmieri, L},
title = {Mitochondrial Dynamics and SLC25 Transporters in Neurodegeneration: From Mechanisms to Therapeutic Opportunities.},
journal = {Biomolecules},
volume = {16},
number = {6},
pages = {},
doi = {10.3390/biom16060842},
pmid = {42352309},
issn = {2218-273X},
support = {2020RRJP5L//Ministry of Universities and Research/ ; 2022ZY7ATN//Ministry of Universities and Research/ ; GR-2019-12369862//Italian Ministry of Health/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology/drug therapy ; *Mitochondrial Dynamics ; *Mitochondria/metabolism ; Animals ; *Mitochondrial Proteins/metabolism ; Energy Metabolism ; Mitochondrial Membrane Transport Proteins/metabolism ; },
abstract = {Neurodegenerative diseases are increasingly recognized as disorders of due to disrupted cellular homeostasis, with mitochondrial dysfunction playing a central and early role in disease progression. This review explores the intricate relationship between mitochondrial function and neuronal health, emphasizing the pivotal role of the solute carrier family 25 (SLC25) transporters in maintaining mitochondrial homeostasis. We provide a comprehensive overview of mitochondrial biology in the central nervous system, including energy metabolism, calcium signaling, redox regulation, organelle interactions and mitochondrial dynamics. We delve into the SLC25 transporter family, highlighting their transport mechanisms, substrates and roles in brain metabolism and neuroprotection. SLC25 on one hand and proteins involved in the regulation of mitochondrial morphology and calcium signaling on the other hand are two sides of the same coin influencing each other. A critical analysis follows, examining how mitochondrial dysfunction contributes to mitochondrial abnormalities in a spectrum of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, ALS and rare mitochondrial encephalopathies. Finally, we assess emerging therapeutic strategies targeting mitochondrial pathways and SLC25 function, including metabolic modulation, gene therapies, antioxidants and pharmacological agents. This review underscores mitochondria and the SLC25 transporters as promising targets for disease-modifying interventions in neurodegeneration and raises key questions about the causality between mitochondrial failure and neuronal death.},
}

Humans
*Neurodegenerative Diseases/metabolism/pathology/drug therapy
*Mitochondrial Dynamics
*Mitochondria/metabolism
Animals
*Mitochondrial Proteins/metabolism
Energy Metabolism
Mitochondrial Membrane Transport Proteins/metabolism

@article {pmid42352358,
year = {2026},
author = {Lee, BC and Hwang, JJ and Tsai, HJ},
title = {Extracellular Pgk1 or Its Derived Short Peptide Interacted with Membrane-Associated Enolase 2 Receptor: A Potential Therapy for ALS Motor Neuron Degeneration.},
journal = {Biomolecules},
volume = {16},
number = {6},
pages = {},
doi = {10.3390/biom16060893},
pmid = {42352358},
issn = {2218-273X},
support = {NSTC-114-2313-B-030-001//National Science and Technology Council/ ; F630410//USA FJCU Alumni Foundation/ ; CPL-202508003//Collaborative Research Project between FJUH and FJU/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology ; Humans ; *Phosphopyruvate Hydratase/metabolism ; Animals ; *Phosphoglycerate Kinase/metabolism ; *Motor Neurons/metabolism/pathology/drug effects ; *Peptides/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS) remains an intractable motor neuron (MN) disease with a growing patient population and few effective treatments. Here, we review how extracellular phosphoglycerate kinase 1 (ePgk1) improves neurite outgrowth of MNs (NOMN) and axonal growth, both in vitro and in vivo. Our group first elucidated a novel non-canonical function of ePgk1 as a cross-tissue mediator between nerve and muscle tissues. We then discovered that neural membranous Enolase 2 (Eno2) serves as a receptor of ligand ePgk1 and that ePgk1-Eno2 interaction suppresses the Rac1-GTP/p-Pak1-T423/p-P38-T180/pMK2-T334/p-Limk1-S323 axis, reducing p-Cofilin and promoting NOMN and axonal growth, finally suggesting that the 419th aspartic acid residue of Eno2 mediates this interaction. In a crucial preclinical step, we truncated two short 16-amino-acid derivatives from Pgk1, FD-1/-2, each mediating neuroprotection comparable to that of full-length 417-amino-acid Pgk1 in ALS animal models, in terms of improvements of innervated neuromuscular junction, MN cell bodies, motor performance, and endpoint prolongation. In this context, we also discuss the opposite function driven by Eno1-plasminogen interaction and by Eno2-ePgk1 interaction; the latter results in unfavorable for tumorigenesis. Unlike intracellular Pgk1 roles, ePgk1 is an extracellular factor with anti-angiogenic properties, further positioning ePgk1 and its FD-1/-2 as promising protein/peptide drugs for ALS treatment.},
}

*Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology
Humans
*Phosphopyruvate Hydratase/metabolism
Animals
*Phosphoglycerate Kinase/metabolism
*Motor Neurons/metabolism/pathology/drug effects
*Peptides/metabolism

@article {pmid42352620,
year = {2026},
author = {De Luca, E and Saba, A and Bertarini, L and Brusini, A and Artioli, G and Dellafiore, F},
title = {Spiritual Care Needs and Challenges Among Caregivers and Families of People with Neurodegenerative Diseases in Palliative and End-of-Life Care: A Scoping Review.},
journal = {Brain sciences},
volume = {16},
number = {6},
pages = {},
doi = {10.3390/brainsci16060611},
pmid = {42352620},
issn = {2076-3425},
abstract = {Background/Objectives: Spirituality is increasingly recognised as a core dimension of holistic and palliative care. Neurodegenerative diseases such as dementia, amyotrophic lateral sclerosis and Parkinson's disease involve prolonged trajectories of loss, uncertainty and relational change, which may heighten spiritual and existential needs for patients, particularly among those involved in caregiving, such as family caregivers and, to a lesser extent, healthcare professionals. However, evidence on how spirituality is understood, experienced and addressed within neurodegenerative palliative care remains fragmented and conceptually heterogeneous. This scoping review aimed to map the literature on caregivers' spiritual needs and challenges. Methods: A scoping review was conducted in accordance with the Joanna Briggs Institute (JBI) methodology for scoping reviews and the Preferred Reporting Items for Systematic Reviews and Meta Analyses extension for Scoping Reviews (PRISMA ScR). Searches were conducted across PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), APA PsycINFO, and Scopus, with no date or geographical restrictions. Grey literature was searched through Google Scholar and relevant organisational and policy sources in the field of palliative care and spirituality. Reference list screening of included studies and relevant reviews was also conducted. Quantitative, qualitative, and mixed methods studies published in English or Italian were included. Results: Twenty-four studies published between 2007 and 2025 were included. Findings were organised into three interconnected domains: spiritual needs, spiritual processes and spiritual care. Spirituality emerged as a dynamic, relational and context-dependent dimension of caregiving, encompassing meaning, identity, connection and coping with vulnerability and loss. Spiritual needs and processes were widely described, while spiritual care was inconsistently recognised within healthcare systems. Conceptual ambiguity, under-representation of end-of-life dementia and cultural imbalances were evident. The evidence predominantly focused on family caregivers, with limited representation of healthcare professionals. Conclusions: This scoping review highlights a persistent gap between caregivers' lived spiritual experiences and system-level responses in neurodegenerative palliative care in caregiving contexts globally. The findings support integrated, caregiver-inclusive and culturally responsive approaches to spiritual care.},
}

@article {pmid42352782,
year = {2026},
author = {Hümpfer-Gerhards, L and Schwager, S and Benecke, M and Fuhrmann, S and Kunert, J and Knigge, M},
title = {Reducing Barriers in Neurodiverse Schools-schAUT: A Program to Identify and Reduce Barriers for Autistic and All Students.},
journal = {Behavioral sciences (Basel, Switzerland)},
volume = {16},
number = {6},
pages = {},
doi = {10.3390/bs16060949},
pmid = {42352782},
issn = {2076-328X},
support = {01NV2104//Federal Ministry of Education and Research Germany/ ; },
abstract = {This paper presents results from the project schAUT, a participatory research project initiated by Humboldt University Berlin, Goethe University Frankfurt a.M. and White Unicorn e.V., funded by the German Federal Ministry of Education and Research (BMBF; FKZ: 01NV2104). It aimed to identify and reduce barriers to learning and participation in mainstream schools, with a particular focus on autistic students. This paper introduces a questionnaire and a program to support School Organizational Development (SOD), aiming to provide equitable and accessible learning environments grounded in international frameworks on inclusive education. This study combines qualitative and quantitative approaches to examine the subjective experiences of barriers. We present data obtained through a multi-phase development and validation phase. The results show that neurodivergent participants generally experienced higher subjective barriers, although we observed that barriers affect neurotypical students as well, highlighting a subjective nature. We argue that these findings support neurodiversity as a relevant concept, especially in educational contexts. This supports Larrauri et al.'s Big-Tent approach to neurodiversity, emphasizing individual variability while acknowledging structural biases towards neurotypical norms in educational environments. The study highlights the value of multiperspective approaches in (participatory) research and SOD, to develop strategies for an inclusive educational environment through neurodiversity-informed decision processes and enable equitable learning environments for all students.},
}

@article {pmid42352907,
year = {2026},
author = {Scrivo, A and Bernardino, L and Consiglio, A},
title = {The Dual Role of Glial Extracellular Vesicles in Neurodegeneration: Insights from iPSC-Based Models.},
journal = {International journal of molecular sciences},
volume = {27},
number = {12},
pages = {},
doi = {10.3390/ijms27125182},
pmid = {42352907},
issn = {1422-0067},
support = {2023 BP 00242//Agència de Gestió d'Ajuts Universitaris i de Recerca/ ; },
abstract = {Extracellular vesicles (EVs) have emerged as key mediators of intercellular communication in the brain, with glial cell-derived EVs increasingly recognized for their roles in maintaining brain homeostasis and contributing to the progression of neurodegenerative diseases. By transferring a diverse cargo of bioactive molecules, including proteins, RNAs, and organelles, EVs influence recipient cell behavior and overall brain function. In neurodegenerative conditions, glial EVs can either propagate pathogenic signals or deliver neuroprotective and regenerative cues, depending on their cellular origin and molecular composition. This context-dependent heterogeneity highlights the need for physiologically relevant human models to investigate EVs biology. Human induced pluripotent stem cell (iPSC)-derived glial models provide a disease-relevant platform, as they recapitulate key pathological features of Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). When further integrated with brain organoid platforms, these iPSC-based systems enable the generation of three-dimensional environments that closely resemble in vivo EVs dynamics. Importantly, glial EVs can modulate cellular pathways involved in neuronal survival and function. Indeed, their potential to interact with and, under specific experimental conditions, traverse the blood-brain barrier (BBB) has contributed to growing interest in their application for biomarker discovery and therapeutic development. Engineered and patient-specific EVs derived from iPSCs are emerging as promising tools for targeted, cell type-specific, therapeutic approaches, although their clinical applicability still requires further validation. This review discusses the emerging evidence supporting the dual role of iPSC-derived glial EVs in health and disease, underscores the translational potential of iPSC-based platforms for mechanistic studies, and outlines their promise as precision medicine tools for diagnostics and therapy.},
}

@article {pmid42353064,
year = {2026},
author = {Reedich, EJ and Chen, YT and Imhoff-Manuel, R and Li, D and Manuel, M},
title = {Chronic Diazepam Reveals Excessive Homeostatic Gain in SOD1[G93A] Mouse Spinal Motoneurons.},
journal = {International journal of molecular sciences},
volume = {27},
number = {12},
pages = {},
doi = {10.3390/ijms27125342},
pmid = {42353064},
issn = {1422-0067},
support = {1R01NS110953-05/NS/NINDS NIH HHS/United States ; },
mesh = {Animals ; *Motor Neurons/drug effects/metabolism/physiology ; *Diazepam/pharmacology ; Mice ; *Homeostasis/drug effects ; *Amyotrophic Lateral Sclerosis/genetics/drug therapy/metabolism/physiopathology/pathology ; *Spinal Cord/drug effects/metabolism ; *Superoxide Dismutase-1/genetics ; Mice, Transgenic ; Action Potentials/drug effects ; Disease Models, Animal ; Synaptic Transmission/drug effects ; },
abstract = {Motoneurons are under strong pressure to maintain stable motor output throughout an individual life, through homeostatic regulation of their electrical properties. Dysregulated spinal motoneuron excitability has long been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Recent work in SOD1[G93A] mice suggests that the homeostatic response of motoneurons becomes dysregulated as cellular processes are disrupted by the disease, causing fluctuations in motoneuron electrical properties. Yet, few studies directly test whether ALS motoneurons respond differently than wild-type motoneurons to a common chronic perturbation. Here, we used in vivo electrophysiology to test whether motoneurons from pre-symptomatic SOD1[G93A] mice modulate excitability differently than wild-type motoneurons in response to the same homeostatic perturbation: chronic inhibition exerted by the benzodiazepine diazepam. Using linear mixed-effects statistical models, we assessed whether diazepam treatment differentially modulated passive properties, firing behavior, spike properties, and/or synaptic inputs in SOD1[G93A] versus wild-type motoneurons. We identified a significant genotype × treatment interaction effect selectively for properties related to passive membrane integration and spike initiation, including membrane time constant, peak input resistance, and recruitment current. In contrast, firing gain, spike waveform characteristics, and synaptic inputs were largely unaffected. These findings indicate that sustained inhibitory perturbation selectively triggered overactive intrinsic compensatory mechanisms in SOD1[G93A] motoneurons rather than inducing widespread changes in firing or synaptic transmission. Together, our results provide direct evidence for over-active homeostatic control of motoneuron excitability and support a view of motoneuron dysfunction in ALS as a problem of altered feedback regulation rather than simply hyper- or hypo-excitability.},
}

Animals
*Motor Neurons/drug effects/metabolism/physiology
*Diazepam/pharmacology
Mice
*Homeostasis/drug effects
*Amyotrophic Lateral Sclerosis/genetics/drug therapy/metabolism/physiopathology/pathology
*Spinal Cord/drug effects/metabolism
*Superoxide Dismutase-1/genetics
Mice, Transgenic
Action Potentials/drug effects
Disease Models, Animal
Synaptic Transmission/drug effects

@article {pmid42353079,
year = {2026},
author = {Romano, G and Klima, R and Feiguin, F},
title = {Loss of TDP-43 Drives Innate Immune Activation Through Relish in Drosophila.},
journal = {International journal of molecular sciences},
volume = {27},
number = {12},
pages = {},
doi = {10.3390/ijms27125359},
pmid = {42353079},
issn = {1422-0067},
mesh = {Animals ; *Drosophila Proteins/genetics/metabolism/immunology ; *DNA-Binding Proteins/genetics/metabolism ; *Immunity, Innate/genetics ; *Transcription Factors/genetics/metabolism ; Signal Transduction ; *Drosophila melanogaster/immunology/genetics ; },
abstract = {Inflammatory and immune alterations are increasingly recognized as components of ALS pathology, yet whether they arise as a direct consequence of TDP-43 dysfunction or as a downstream response to neurodegeneration remains unresolved. To address this question, we profiled adult head transcriptomes of Drosophila lacking TBPH, the fly homolog of TDP-43, and identified marked overactivation of the conserved Toll/Imd/NF-κB (Relish) innate immune pathway, including increased expression of antimicrobial effector genes and inflammatory genes. We further found that TDP-43/TBPH regulates the NF-κB homolog Relish by associating with its mRNA and that its loss permits Relish-dependent immune overactivation. Genetic reduction in Relish in TDP-43-deficient flies suppressed inflammatory signaling and ameliorated neurological defects in vivo, indicating that immune dysregulation contributes to TDP-43 loss-associated phenotypes.},
}

Animals
*Drosophila Proteins/genetics/metabolism/immunology
*DNA-Binding Proteins/genetics/metabolism
*Immunity, Innate/genetics
*Transcription Factors/genetics/metabolism
Signal Transduction
*Drosophila melanogaster/immunology/genetics

@article {pmid42353250,
year = {2026},
author = {Sharma, N and An, SSA},
title = {Microglial Dysfunction Induced by C9ORF72 Dipeptide Repeat Proteins: Biomarker and Therapeutic Perspectives.},
journal = {International journal of molecular sciences},
volume = {27},
number = {12},
pages = {},
doi = {10.3390/ijms27125537},
pmid = {42353250},
issn = {1422-0067},
support = {RS-2021-NR060117//National Research Foundation of Korea/ ; RS-2025-02292973//Korea Institute of Marine Science and Technology Promotion/ ; },
mesh = {*C9orf72 Protein/genetics/metabolism ; Humans ; *Microglia/metabolism/pathology ; Biomarkers/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology/therapy ; *Frontotemporal Dementia/genetics/metabolism/pathology/therapy ; *Dipeptides/genetics/metabolism ; Animals ; DNA Repeat Expansion ; Autophagy ; },
abstract = {The GGGGCC hexanucleotide repeat expansion (HRE) in C9ORF72 was recognized as the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Repeat-associated non-AUG (RAN) translation of the expanded repeat generated dipeptide repeat proteins (DPRs), which disrupted multiple cellular processes and contributed to neurodegeneration. Emerging evidence indicated that disease pathogenesis involved both gain-of-function (GOF) and loss-of-function (LOF) mechanisms. DPR-mediated GOF toxicity induced ribosomal dysfunction, nucleolar stress, proteostatic impairment, and neuronal injury, whereas C9ORF72 LOF disrupted lysosomal and autophagic pathways in microglia, impairing the immune homeostasis. Neuronal injury further promoted the release of damage-associated signals that triggered secondary microglial activations and chronic neuroinflammations. This review summarized current knowledge of DPR biology, microglial dysfunction, and their contributions to disease progression in C9ORF72-associated ALS/FTD. Therapeutic strategies targeting repeated RNA, DPR productions, proteostasis, autophagy, and neuroinflammatory pathways were also discussed. In addition, the potentials of fluid biomarkers, including cerebrospinal fluid poly (GP) and blood neurofilament light chain (NfL), for diagnosis, disease monitoring, and therapeutic assessment were shown. Together, these findings provided important insights into disease mechanisms and potential avenues for improved clinical management.},
}

*C9orf72 Protein/genetics/metabolism
Humans
*Microglia/metabolism/pathology
Biomarkers/metabolism
*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology/therapy
*Frontotemporal Dementia/genetics/metabolism/pathology/therapy
*Dipeptides/genetics/metabolism
Animals
DNA Repeat Expansion
Autophagy

@article {pmid42355891,
year = {2026},
author = {Calabrese, L and Mion, M and Mandrini, A and Primi, R and Bendotti, S and Ulmanova, L and Currao, A and Morena, A and Dossi, F and Fogagnolo, L and Pizzi, F and Fava, C and Ghiraldin, D and Battioni, A and Genoni, P and Madonini, EMP and Maffeo, D and Dossena, C and Affinito, S and Bertazzoli, G and Pellegrino, M and Papi, G and Frattini, S and Della Torre, M and Fantoni, C and Praderio, A and Tarantino, L and Mongiovì, S and Politi, P and Savastano, S and Baldi, E and All The LombardiaCARe Researchers, },
title = {The Early Implementation of a Hub-and-Spoke Survivorship Pathway for Out-of-Hospital Cardiac Arrest Survivors: A 12-Month Formative Evaluation of the REVIVE Project.},
journal = {Journal of clinical medicine},
volume = {15},
number = {12},
pages = {},
doi = {10.3390/jcm15124722},
pmid = {42355891},
issn = {2077-0383},
support = {8049724//Italian Ministry of Health - Ricerca Corrente/ ; },
abstract = {Background/Objectives: A structured follow-up after out-of-hospital cardiac arrest (OHCA) is recommended, but implementation across regional networks remains challenging. REVIVE introduced a hub-and-spoke survivorship pathway in Lombardy. This 12-month formative implementation evaluation aimed to describe staged pathway progression, operational reach, attrition points, centre-level variation, and documented barriers to assessment completion. Methods: Adult OHCA survivors with Cerebral Performance Category (CPC) 1-2 or Modified Rankin Scale (mRS) ≤ 3 were considered eligible. The evaluation was structured using Proctor et al.'s implementation outcomes framework. Implementation outcomes were operationalised using prospectively collected pathway indicators: eligibility ascertainment, successful contact, T0 assessment completion, completion of planned assessment components, timeliness where available, and documented reasons for non-progression. Analyses were descriptive and used chi-square or Fisher's exact tests for unadjusted centre-level comparisons. Results: Of the 1663 patients hospitalised, 1458 (87.7%) were recorded as deceased or having an unfavourable neurological outcome and were therefore outside the intended REVIVE target population. Among the remaining 205 patients, eligibility could not be determined for 78 (4.7% of the total cohort), and 127 (7.6%) met eligibility criteria. Of eligible survivors, 96 (75.6%) were contacted and 64 completed the T0 assessment (66.7% of contacted; 50.4% of eligible). Pavia showed higher observed rates of eligibility ascertainment, contact, and assessment completion than spoke centres, but these differences were unadjusted and should be interpreted as centre-level implementation variation rather than evidence of causal superiority. Conclusions: REVIVE initiated a structured regional pathway for post-OHCA follow-up, but first-year implementation was partial rather than definitive. The 50.4% T0 completion rate among eligible survivors should be interpreted as an initial internal implementation indicator, not as evidence of established feasibility, effectiveness, or regional benchmarking. Priorities for further optimisation include eligibility ascertainment, transfer of contact information, patient engagement, and spoke-site support for assessment delivery.},
}

@article {pmid42356052,
year = {2026},
author = {Manay, B and Aygün, D and Şentürk, A and İbas, M and Güven, R and Belli, Ş},
title = {Association Between Clinical Dysphagia Assessment Tools and Videofluoroscopic Findings in Amyotrophic Lateral Sclerosis: A Retrospective Study.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {62},
number = {6},
pages = {},
doi = {10.3390/medicina62061039},
pmid = {42356052},
issn = {1648-9144},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/physiopathology ; Retrospective Studies ; *Deglutition Disorders/diagnosis/etiology/physiopathology ; Female ; Male ; Middle Aged ; Aged ; Fluoroscopy/methods ; ROC Curve ; Video Recording/methods ; },
abstract = {Background and Objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease frequently associated with dysphagia and aspiration risk. This study aimed to investigate the relationship between clinical dysphagia assessment tools (EAT-10, GUSS, RSST, and sialorrhea severity) and videofluoroscopic swallowing study (VFSS) findings in patients with ALS. Materials and Methods: This retrospective observational study included 60 patients with ALS classified as spinal-onset (n = 38) or bulbar-onset (n = 22). Relationships between clinical assessments and VFSS findings were analysed using Spearman correlation analysis. Exploratory multivariable regression and receiver operating characteristic (ROC) analyses were performed to evaluate associations and aspiration risk discrimination. Results: Strong negative correlations were observed between PAS-Liquid and RSST and GUSS scores, whereas EAT-10 showed a strong positive correlation (all p < 0.001). ROC analyses demonstrated good discriminative ability for aspiration risk for GUSS (AUC = 0.89), RSST (AUC = 0.88), and EAT-10 (AUC = 0.82). Patients with bulbar-onset ALS demonstrated higher penetration-aspiration severity and lower functional oral intake. Conclusions: Clinical dysphagia assessment tools showed significant associations with instrumental swallowing findings in ALS. GUSS and RSST demonstrated good discriminative ability for aspiration risk and may be clinically useful bedside screening tools. However, instrumental swallowing assessment remains essential whenever feasible.},
}

Humans
*Amyotrophic Lateral Sclerosis/complications/physiopathology
Retrospective Studies
*Deglutition Disorders/diagnosis/etiology/physiopathology
Female
Male
Middle Aged
Aged
Fluoroscopy/methods
ROC Curve
Video Recording/methods

@article {pmid42357346,
year = {2026},
author = {Costanzi, E and Fontana, L and Giroldo, F and Coco, S},
title = {Advancing MSC-EV Therapies: Harnessing Preconditioning and Mito-EVs to Tackle Neuroinflammation and Neurodegeneration.},
journal = {Pharmaceutics},
volume = {18},
number = {6},
pages = {},
doi = {10.3390/pharmaceutics18060730},
pmid = {42357346},
issn = {1999-4923},
support = {P2022LR49L//Ministry of Universities and Research/ ; 202229X8HW//Ministry of Universities and Research/ ; },
abstract = {Neuroinflammation plays a central role in the onset and progression of neurodegenerative disorders. Several disease-modifying therapies have been developed to target neuroinflammatory pathways in specific disorders. However, their ability to stop disease progression or restore neuronal and mitochondrial homeostasis remains limited. This is still a major unmet clinical need. In this context, mesenchymal stromal cell (MSC)-derived Extracellular Vesicles (EVs) have emerged as a promising cell-free therapeutic strategy due to their ability to modulate immune responses and promote neuroprotection through the delivery of bioactive cargo. Recent evidence has identified a distinct subset of EVs, known as mitochondrial EVs (mito-EVs), which carry mitochondrial DNA, proteins, and functional components. These vesicles may uniquely influence cellular bioenergetics, redox balance, and neuroinflammatory signaling, offering additional therapeutic potential compared to conventional MSC-EVs. This review summarizes the role of MSC-derived EVs in neuroinflammatory disorders, with a particular focus on mito-EVs. It also discusses preconditioning strategies to enhance EV efficacy, including hypoxic, inflammatory, pharmacological priming and genetic engineering approaches. Finally, we critically evaluate current preclinical evidence regarding the treatment of major neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, and Amyotrophic Lateral Sclerosis, as well as Traumatic Injury, highlighting the key challenges for clinical translation.},
}

@article {pmid42358489,
year = {2026},
author = {Lepski, G and Arévalo, A},
title = {Mesenchymal stromal/stem cells for neurological disorders in humans: an evidence-mapped clinical review.},
journal = {Frontiers in cellular neuroscience},
volume = {20},
number = {},
pages = {1844360},
pmid = {42358489},
issn = {1662-5102},
abstract = {Mesenchymal stromal/stem cells (MSCs) have been tested clinically across a wide spectrum of neurological disorders, motivated by their immunomodulatory and trophic ("bystander") mechanisms rather than durable neural replacement. Here, we synthesize human prospective clinical trials that administered MSC products for neurological indications, prioritizing study design/goals, disease stage/severity, cell source/manufacturing, dose/route, detailed clinical assessments, quantified score changes, and adverse events (AEs). Across indications, trials frequently demonstrate feasibility and short-term safety, while efficacy signals are heterogeneous and strongly dependent on disease stage and endpoint selection criteria. The most methodologically rigorous signals with quantified motor outcomes include stereotactic intracerebral implantation of SB623 for chronic motor deficits after traumatic brain injury (TBI). In amyotrophic lateral sclerosis (ALS), randomized evidence supports safety and early slope-based signals in selected subgroups after intrathecal MSC regimens, but durable clinical benefit remains unproven. In hypoxic-ischemic encephalopathy (HIE), controlled data suggest functional improvements in small cohorts, and neonatal studies support feasibility adjunctive to hypothermia. We highlight design features most likely to de-risk efficacy interpretation: adequately powered randomized controlled trials, disease-stage stratification, prespecified clinically meaningful change thresholds, standardized rehabilitation co-interventions, and transparent AE adjudication.},
}

@article {pmid42359101,
year = {2026},
author = {Carder, P and Smith, L and Bunker, JN and Hua, CL and Hsu, EC and Boun, I and Ainsworth, OM and Thomas, KS and Jutkowitz, E},
title = {How do US states define person-centered and family-involved care in assisted living regulations.},
journal = {Frontiers in dementia},
volume = {5},
number = {},
pages = {1824907},
pmid = {42359101},
issn = {2813-3919},
abstract = {INTRODUCTION: A large share of assisted living (AL) residents have a diagnosis of dementia or cognitive impairment, and these individuals can benefit from person-centered care and family-involved care. This study examines whether and how states' AL licenses address these topics.

METHODS: This research analyzed a national database of 249 unique licensing requirements that govern 35,602 ALs in all states and associated regulations, including those that govern memory care (MC) services. We reviewed each regulation for the presence of person-centered or family involved care and then used content analysis of license requirements with at least one relevant policy to identify key categories and regulatory specificity.

RESULTS: A larger share of AL with licenses that govern MC services are covered by person-centered care policies (44%) and family-involved policies (62%), compared to AL without MC-specific requirements (20 and 32% respectively). Key categories of person-centered care included staff training, care planning procedures, and social activities; and family-involved care included care planning, direct involvement in providing care, and support for families. Few states' licenses contained highly specific regulations.

DISCUSSION: This study reveals substantial variation in whether and how states define and regulate person-centered and family-involved care for people living with dementia in AL. MC-specific licenses are roughly twice as likely to require these policies, but fewer than two-thirds of MC-AL communities are covered. State licenses take different approaches to categorizing and specifying these policies. These findings suggest uneven application of core principles of AL associated with quality of life and satisfaction.},
}

@article {pmid42359165,
year = {2026},
author = {Morimoto, S and Kato, C and Takahashi, S and Okano, H},
title = {Therapeutic frontiers in ALS: iPSC-based drug discovery, cell therapy, and gene therapy-Advances through 2026.},
journal = {Regenerative therapy},
volume = {33},
number = {},
pages = {101150},
pmid = {42359165},
issn = {2352-3204},
abstract = {Three converging therapeutic paradigms-iPSC-based drug discovery, cell transplantation, and gene therapy-have substantially expanded the therapeutic pipeline for amyotrophic lateral sclerosis (ALS) between 2020 and 2026. The FDA's accelerated approval of tofersen (Qalsody) in April 2023 marked the first treatment targeting a genetic cause of ALS. iPSC-derived drug candidates, including ropinirole and bosutinib, have completed early-phase clinical trials led by Japanese institutions. Cell therapies targeting neuroinflammation through regulatory T cells are being actively explored as immunomodulatory strategies, although efficacy remains to be established in adequately powered trials. Next-generation gene-silencing approaches-including RNA interference (RNAi) therapeutics and AAV-delivered microRNA-entered first-in-human trials in 2024-2025. The identification of STMN2 as a downstream target of TDP-43 dysfunction has opened a potential TDP-43-downstream nucleic acid therapeutic avenue for sporadic ALS, which constitutes approximately 90% of all cases, with company-reported interim data suggesting target engagement in the ongoing Phase 1/2 ANQUR trial (QRL-201). This review synthesizes the latest evidence across all three therapeutic domains, with attention to the hierarchy of evidence, regulatory milestones, and the pioneering contributions of Japanese research groups.},
}

@article {pmid42359357,
year = {2026},
author = {Shu, X and Yu, X and Xu, P and Wang, A},
title = {Innate immune crosstalk in ALS/FTD pathogenesis.},
journal = {Cell insight},
volume = {5},
number = {4},
pages = {100340},
pmid = {42359357},
issn = {2772-8927},
abstract = {Marked by protein aggregation, impaired proteostasis, organelle stress, and chronic neuroinflammation, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) form a clinically, genetically, and pathologically overlapping disease spectrum. Increasing evidence indicates that innate immune activation is not merely a secondary response to neuronal injury, but an active driver of disease progression. In this review, we elaborate on how ALS/FTD-associated genetic lesions and pathogenic protein aggregates, including TDP-43, SOD1, FUS, and C9orf72-derived dipeptide repeat proteins, engage three interconnected innate immune pathways: cGAS-STING, NLRP3 inflammasomes, and TREM2-DAP12 signaling. We further highlight emerging crosstalk among these pathways, in which cGAS-STING and NLRP3 reinforce inflammatory signaling, while NLRP3-driven TREM2 shedding may impair microglial clearance and perpetuate proteostatic failure. Understanding this immune network may help define disease subtypes, identify biomarkers, and guide combinatorial therapeutic strategies that suppress harmful inflammation while preserving protective microglial functions.},
}

@article {pmid40506596,
year = {2025},
author = {Sajjad, MW and Muzamil, F and Naqvi, RZ and Amin, I},
title = {QBEmax redefines the precise base editing in crop plants.},
journal = {Functional & integrative genomics},
volume = {25},
number = {1},
pages = {127},
pmid = {40506596},
issn = {1438-7948},
abstract = {Hu et al.‘s new study, published in Nature Biotechnology, introduces QBEmax; a tiny, conformationally sound editing tool with a cytidine deaminase buried within a looping permuted Cas9 (cpCas9). Supported by molecular dynamics models and AlphaFold3 structural predictions, this unique internal fusion creates a structurally protected complex that improves editing accuracy and lowers typical artifacts such as indels and impure base conversions (Hu et al. Nature Biotechnology:1-7, 2025). High precision editing (up to 99.8% purity), lower indels, and lower off target impacts well suit imminent plant transformation events. Its tiny, stable architecture and wider editing window at PAM sites increase its ability for precise and adaptable trait change in complex plant genomes.},
}

@article {pmid40764894,
year = {2025},
author = {Sah, AK and Srinivasarao, D and Dey, P},
title = {Comment on "clinicopathological features of fatal mushroom poisoning: a 10-year retrospective autopsy-based study".},
journal = {Forensic science, medicine, and pathology},
volume = {},
number = {},
pages = {},
pmid = {40764894},
issn = {1556-2891},
abstract = {This commentary evaluates Dogan et al.‘s autopsy-based study on fatal mushroom poisoning in Türkiye, highlighting its forensic insights and public health implications. We address potential selection bias and lack of confounder adjustment, advocating for broader surveillance and early intervention. The study advances understanding of amatoxin toxicity and informs targeted prevention efforts.},
}

@article {pmid41088288,
year = {2025},
author = {Ikezoe, H and Horiuchi, S},
title = {A qualitative exploration of the mistreatment of women during childbirth in a rural Guatemalan hospital.},
journal = {Reproductive health},
volume = {22},
number = {1},
pages = {197},
pmid = {41088288},
issn = {1742-4755},
support = {Core-to-Core Program, Asia-Africa Science Platforms [(2021-2024) PI: Shigeko Horiuchi]//Japan Society for the Promotion of Science/ ; },
abstract = {BACKGROUND: In Guatemala, many women still give birth together with traditional birth attendants at home particularly in rural settings even though births attended by skilled birth attendants in healthcare facilities have been recommended. Mistreatment of women during childbirth is recognized as one of the obstacles to childbirth in healthcare facilities. However, little research has been conducted on childbirth care and the mistreatment of women during facility-based childbirth in Guatemala. Thus, this study aimed to explore women’s experiences of care during childbirth in a rural Guatemalan hospital. The women narrated their experiences from which themes were derived (whether mistreatment or not, and if mistreatment prevailed, the type). METHODS: This qualitative study involved interviews with 20 women of reproductive age who had given birth in a hospital in Quiché Department, Guatemala, within the past six months. Data were collected by semistructured interviews between December 2022 and February 2023. The contents of the semistructured interviews were past birth experiences, a recent birth experience in a hospital, and care received from healthcare providers. Thematic analysis was performed with deductive and inductive approaches using Bohren et al.’s typology of the mistreatment of women during childbirth. The study was approved by St. Luke’s International University Research Ethics Committee and the study hospital. RESULTS: Women reported experiencing various forms of mistreatment during childbirth in the rural Guatemalan hospital. These included six of the seven categories from Bohren et al.’s typology including physical abuse, verbal abuse, stigma and discrimination, failure to meet professional standards of care, poor rapport between women and providers, and health system conditions and constraints. Specifically, the participants reported experiences of reprimands and neglect by healthcare providers, as well as discrimination of those who do not speak Spanish. It became evident that mistreatment of women by healthcare providers had become normalized, and that culturally appropriate care was not adequately provided. CONCLUSIONS: Eliminating or reducing mistreatment requires a multilevel approach. Healthcare providers must acquire up-to-date knowledge and skills and develop appropriate professional attitudes. Both healthcare providers and women should have increased awareness of women’s rights and mistreatment.},
}

@article {pmid41697496,
year = {2026},
author = {Quinn, CJ and Velasco, ES and Wehrens, XHT},
title = {Mitochondria at the Heart of Ischemia-Reperfusion (I/R) Injury: the HOXB5-Sirt5 Axis.},
journal = {Cardiovascular drugs and therapy},
volume = {40},
number = {3},
pages = {805-808},
pmid = {41697496},
issn = {1573-7241},
support = {R01HL153350/NH/NIH HHS/United States ; R01HL153350/NH/NIH HHS/United States ; },
abstract = {Ischemic cardiomyopathy (ICM) arises from restricted myocardial blood flow, leading to ischemia/reperfusion (I/R) injury, mitochondrial dysfunction, and heart failure. This commentary highlights the role of mitochondrial homeostasis in cardiac health, emphasizing dysregulated dynamics, ROS production, and mitophagy in ICM and related conditions like diabetic cardiomyopathy. Li et al.‘s study identifies the HOXB5–Sirt5 signaling axis as a key regulator that protects against I/R injury by reducing apoptosis, oxidative stress, ferroptosis, and mitochondrial fragmentation in vitro and in vivo. Future research should explore cell-specific roles and human models to enhance translational potential.},
}

@article {pmid41961214,
year = {2026},
author = {King, H and Derrett, S and Wyeth, EH and Cunningham, R and Peterson, D},
title = {Integrated Care Within New Zealand's Specialist Mental Health and Addiction Services: Qualitative Research to Inform a New Model.},
journal = {Community mental health journal},
volume = {},
number = {},
pages = {},
pmid = {41961214},
issn = {1573-2789},
abstract = {Internationally, and within New Zealand (NZ), specialist mental health and addiction service-users (SMHAS-users) experience increased risks of comorbidities and premature mortality, and poorer health outcomes, compared to the general population. In particular, Indigenous Māori SMHAS-users face significant inequities compared to non-Māori. Integrated care has been found to improve outcomes by improving quality and coordination between services. This research aimed to develop a model of integrated care relevant to SMHAS-users in a NZ context, to inform the development of a questionnaire intended to assess SMHAS-users experiences of integrated care, support SMHAS to improve their services, and in turn, improve outcomes for SMHAS-users. Key informants working for, and/or with lived experience of, SMHAS were interviewed about existing integrated and people-centred care concepts. Barriers to integration were identified. The team met frequently to review and discuss coding, themes, and model development. Ten informants from across NZ were recruited, including five with lived experience of mental distress, and three who were Māori. Singer et al.,’s (Medical Care Research and Review, 68(1), 112–127, 2011) integrated patient care framework and the World Health Organization’s (2016) concept of people-centred care were found to be acceptable, although people-centred constructs were needed more clearly at a model’s core. SMHAS-user controlled funding and participation in multi-disciplinary team meetings were identified as key opportunities alongside other concepts such as cultural responsiveness, de-centralising services (to re-centralise people), and peer navigators. The resulting People-Centred Joined Up Care (PCJUC) model is proposed to convey a paradigm shift from a service-centric system, organised around the efficiencies and needs of services, to a people-centred system. Irrespective of the health workforce’s best intentions, the current service-centric orientation does not empower SMHAS-users. A people-centred model requires power structures to be inverted and the paramount authority of health professionals as the ‘decision-making experts’ to be challenged. Research is now underway exploring the use of a questionnaire developed to measure the concepts within the PCJUC model, to inform service improvements.},
}

@article {pmid41961447,
year = {2026},
author = {Tarzian, AJ},
title = {From Wise Counselors to Clinical Ethicists: Historical Milestones and Their Impact on Professional Identity Formation.},
journal = {HEC forum : an interdisciplinary journal on hospitals' ethical and legal issues},
volume = {},
number = {},
pages = {},
pmid = {41961447},
issn = {1572-8498},
abstract = {This paper explores how historical bioethics milestones have shaped the professional identity of clinical ethicists, discussing both the benefits and challenges of professionalizing the role of the clinical ethicist by comparing how a “wise counselor,” an ethics consultant, and a clinical ethicist provide healthcare ethics guidance. I examine the evolution of clinical ethics as a sub-category of bioethics, tracing its origins and key milestones in its development toward professionalization. These include the American Society for Bioethics and Humanities’ (ASBH) Core Competencies for Health Care Ethics Consultation reports, ASBH’s Code of Ethics and Professional Responsibilities for Healthcare Ethics Consultants, Fox et al.’s national surveys of healthcare ethics consultation in the United States, and the emergence of the Healthcare Ethics Consultant Certification (HEC-C) program. Practicing as a clinical ethicist requires mastery of a wide scope of knowledge, skills, and attitudes reflected in each stage of the field’s development. Reflecting on this history may yield clues for how clinical ethicists position themselves for the next phase of the field’s evolution.},
}

@article {pmid42339807,
year = {2026},
author = {Jewer, M and Snyder, J and Caulfield, T and Zenone, M},
title = {The connection between unproven stem cell-based interventions and complementary and alternative medicine in crowdfunding for Amyotrophic Lateral Sclerosis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/21678421.2026.2685157},
pmid = {42339807},
issn = {2167-9223},
abstract = {UNLABELLED: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disease associated with substantial medical and non‑medical costs. In the absence of effective treatments, patients and families may turn to crowdfunding to finance care, including unproven stem cell‑based interventions (SCBIs) that are frequently marketed directly to consumers.

OBJECTIVE: conduct content analysis of English‑language GoFundMe campaigns seeking funds for SCBIs for ALS to better understand the market for unproven direct‑to‑consumer SCBIs.

METHODS: 247 campaigns were identified, and their data were collected and analyzed to determine the characteristics of the campaigns, campaigners, and their desired treatments.

RESULTS: ALS crowdfunding campaigns that collectively requested over $16 million USD. In addition to SCBIs, campaigns frequently requested funding for international travel to access these treatments. Campaigners express relatively high confidence that stem cell treatments would slow disease progression, improve symptoms, or, in some cases, cure or reverse ALS; conclusions that exceed the scientific evidence. Confidence in SCBIs is linked to requests for other alternative therapies and unsupported causes of ALS, supporting an emerging link between proponents of alternative medicines and unproven stem cell therapies.

CONCLUSION: Crowdfunding for unproven stem cell interventions exposes ALS patients and donors to financial risk, misinformation, and medical exploitation. The frequent linkage between SCBIs, CAM, and exaggerated claims highlights gaps in regulation, patient protection, and access to credible treatment options. These findings underscore the need for stronger oversight of direct‑to‑consumer stem cell markets and greater support for patients facing catastrophic illness.},
}

@article {pmid42339846,
year = {2026},
author = {Burchert, HH and Stringer, WW and Dash, RK},
title = {Single-O2ligation of hemoglobin links aerobic and anaerobic metabolism.},
journal = {Journal of applied physiology (Bethesda, Md. : 1985)},
volume = {},
number = {},
pages = {},
doi = {10.1152/japplphysiol.00454.2026},
pmid = {42339846},
issn = {1522-1601},
abstract = {Oxygen (O2) binding and release by hemoglobin (Hb) are governed by cooperative interactions among its four subunits. During incremental workload exercise, femoral venous oxyhemoglobin (O2Hb) saturation exhibits a reproducible, momentary increase at the gas exchange threshold-coinciding with the inflection point of the in vivo O2 non-equilibrium curve (ONC). This suggests a transient shift in Hb's binding dynamics. We hypothesized that at this threshold, Hb tetramers carrying ≤1 bound O2 become predominant. In this state, the last bound O2 promotes further cooperative binding, but its release confers no cooperative advantage for unloading, biasing toward O2 rebinding. Using the O2 equilibrium curve models of Dash et al. (2016) and Adair, we computed the distribution of Hb's O2 ligation states across 12 pooled mean femoral venous blood samples from incremental workload cardiopulmonary exercise testing of five healthy male participants. At the gas exchange threshold-where the ONC inflects and flattens-tetramers with ≤1 O2 indeed dominated. This ligation-state distribution is consistent with Perrella et al.'s (1999) cryogenic resolution of native human Hb, which shows that carbon monoxide-ligated Hb tetramers peak at ~15-20% saturation, matching femoral venous ranges at the gas exchange threshold. Our results suggest that, at sufficiently low O2Hb saturation, Hb may favor O2 rebinding over cooperative unloading. We propose that glycolytic proton production and other Bohr effectors may counter this predicted binding bias supporting continued O2 unloading. If confirmed, this mechanism unifies long-standing controversies in O2 transport physiology, framing the Hb-Bohr system as a proportional-integral controller of tissue oxygenation.},
}

@article {pmid42341041,
year = {2026},
author = {Liu, D and Li, Y and Huang, S and Xu, Y and Sun, L and Li, W and O'Kane, CJ and Rubinsztein, DC and Lu, B and Li, S},
title = {IRE1 regulates the proteostasis of TDP-43/TARDBP in ALS/FTD through ribosome-associated quality control.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {26},
pages = {e2610001123},
doi = {10.1073/pnas.2610001123},
pmid = {42341041},
issn = {1091-6490},
support = {32270825//MOST | National Natural Science Foundation of China (NSFC)/ ; 2023HWYQ-013//| Natural Science Foundation of Shandong Province ()/ ; tsqn202306046//Taishan Scholar Project of Shandong Province/ ; R01AG089752 R01NS084412 and R37NS083417//HHS | National Institutes of Health (NIH)/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *DNA-Binding Proteins/metabolism/genetics ; Animals ; *Protein Serine-Threonine Kinases/metabolism/genetics ; Humans ; *Frontotemporal Dementia/metabolism/genetics/pathology ; Mice ; *Ribosomes/metabolism ; *Proteostasis ; *Endoribonucleases/metabolism/genetics ; Proteotoxic Stress ; },
abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive neurodegenerative disorders characterized by motor neuron degeneration, leading to muscle weakness, atrophy, and cognitive impairments. A defining pathological hallmark of ALS/FTD is the cytosolic mislocalization and accumulation of TAR DNA-binding protein 43 (TDP-43), highlighting its critical role in ALS pathogenesis. However, the molecular mechanisms underlying TDP-43 proteostasis remain poorly understood. Through a genetic screening approach, we identify inositol-requiring enzyme 1 (IRE1), an endoplasmic reticulum-resident transmembrane protein, as a potent suppressor of TDP-43 protein levels. Furthermore, we show that ribosome-associated quality control (RQC) factors play a crucial role in regulating TDP-43 proteostasis and cellular toxicity. Activation of the RQC pathway prevents excessive accumulation of TDP-43 and associated toxicity. Mechanistically, our findings suggest that IRE1 regulates TDP-43 protein level by promoting the degradation of aberrant TDP-43 translation product through the RQC pathway. IRE1 acts canonically to enhance the transcription of the RQC core component Clbn/NEMF and noncanonically to physically interact with Clbn/NEMF, thereby ameliorating TDP-43-induced proteotoxicity. Moreover, ectopic expression or pharmacological activation of IRE1 alleviates TDP-43 pathology and restores cognitive function in the TDP-43 A315T ALS mouse models. Collectively, our study identifies a role for IRE1 in the translational quality control of TDP-43 and establishes its potential as a therapeutic target for ALS/FTD.},
}

*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology
*DNA-Binding Proteins/metabolism/genetics
Animals
*Protein Serine-Threonine Kinases/metabolism/genetics
Humans
*Frontotemporal Dementia/metabolism/genetics/pathology
Mice
*Ribosomes/metabolism
*Proteostasis
*Endoribonucleases/metabolism/genetics
Proteotoxic Stress

@article {pmid42341118,
year = {2026},
author = {Copley, KE and Dykstra, MM and Miller, MR and Linsenmeier, M and Lai, L and Wang, Y and Chang, YW and Barmada, SJ and Shorter, J},
title = {Isoform-specific steric zippers drive aberrant assembly and mislocalization of shortened TDP-43.},
journal = {Science advances},
volume = {12},
number = {26},
pages = {eady0256},
pmid = {42341118},
issn = {2375-2548},
mesh = {*DNA-Binding Proteins/metabolism/chemistry/genetics ; Protein Isoforms/metabolism/chemistry/genetics ; Humans ; Animals ; Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Protein Domains ; Protein Transport ; },
abstract = {Prion-like domain (PrLD)-mediated aggregation and concomitant dysfunction of the essential RNA-binding protein transactive response (TAR) DNA-binding protein of 43 kilodaltons (TDP-43) is a common feature of multiple debilitating neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). However, shortened TDP-43 (sTDP-43) splice isoforms where the PrLD is largely replaced by an 18-residue carboxyl-terminal tail also contribute to ALS pathophysiology and are enriched in motor neurons. Curiously, despite lacking most of the PrLD, sTDP-43 exhibits pronounced insolubility in cells and tissue of patients with ALS. Here, we establish that the short, isoform-specific carboxyl-terminal tail of sTDP-43 confers high aggregation propensity, which is encoded by two clusters of steric zippers, and can be mitigated by short RNA chaperones. Disrupting these zippers enhances sTDP-43 solubility at the pure protein level and in neurons. Notably, these steric zippers, rather than a predicted nuclear export signal in the carboxyl-terminal tail, drive cytoplasmic mislocalization and aggregation of sTDP-43 in neurons. Thus, we define the sequence-encoded determinants of aberrant sTDP-43 assembly and provide mechanistic insights into sTDP-43 disease pathology.},
}

*DNA-Binding Proteins/metabolism/chemistry/genetics
Protein Isoforms/metabolism/chemistry/genetics
Humans
Animals
Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology
Protein Domains
Protein Transport

@article {pmid42341897,
year = {2026},
author = {Hopkins, EL and Williams, PA},
title = {Programmed axon degeneration gene variants in human disease.},
journal = {Experimental neurology},
volume = {},
number = {},
pages = {115891},
doi = {10.1016/j.expneurol.2026.115891},
pmid = {42341897},
issn = {1090-2430},
abstract = {BACKGROUND: Programmed axon degeneration (PAD; also known as Wallerian degeneration) is a conserved pathway controlling axon breakdown following injury or metabolic stress. PAD is driven by the depletion of nicotinamide adenine dinucleotide (NAD) through loss of the pro-survival enzyme NMNAT2 and activation of the pro-degenerative NADase SARM1. Recent genetic studies have identified pathogenic variants in PAD pathway enzymes associated with severe neurodegenerative phenotypes.

MAIN BODY: Pathogenic variants in NAMPT, NMNAT1, NMNAT2, and SARM1 have been identified and will be discussed in this review. NAMPT variants cause sensory and motor neuropathy with neurodevelopmental symptoms. NMNAT1 variants are well-characterized causes of Leber Congenital Amaurosis type 9, while NMNAT2 variants result in peripheral neuropathies with childhood onset. SARM1 gain-of-function variants with constitutively active NADase activity are enriched in amyotrophic lateral sclerosis patients.

CONCLUSION: These findings demonstrate that maintaining proper NAD homeostasis is crucial for axon survival, and disruption through genetic variants leads to distinct neurodegenerative outcomes. Understanding these rare variants provides insight into PAD mechanisms and supports development of broad-spectrum neuroprotective therapies targeting this pathway. Current therapeutic approaches include SARM1 inhibitors in clinical trials, gene therapy, and NAD precursor supplementation, offering hope for treating multiple neurodegenerative diseases.},
}

@article {pmid42342533,
year = {2026},
author = {Brodribb, L and Camden, P and Dharmadasa, T and Blizzard, C},
title = {Amyotrophic lateral sclerosis: A rare but aggressive adult-onset disease.},
journal = {Trends in molecular medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.molmed.2026.06.001},
pmid = {42342533},
issn = {1471-499X},
}

@article {pmid42342547,
year = {2026},
author = {Messina, E and Borrelli, A and Panebianco, V},
title = {Reply to Andrew R. A. Godtman et al.'s Letter to the Editor re: The PROSA Trial: Some Prosaic Comments. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2026.03.036.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2026.06.010},
pmid = {42342547},
issn = {1873-7560},
}

@article {pmid42342625,
year = {2026},
author = {Forstmann, M and Weiss, A},
title = {Outsourcing moral cognition: Delegation, diffusion of responsibility, and coalitional exclusion.},
journal = {The Behavioral and brain sciences},
volume = {49},
number = {},
pages = {e141},
doi = {10.1017/S0140525X25101556},
pmid = {42342625},
issn = {1469-1825},
mesh = {Humans ; *Morals ; *Decision Making ; *Cognition ; *Outsourced Services ; Cooperative Behavior ; },
abstract = {Levine et al.'s resource-rational contractualism (RRC) models moral judgment as a cost-sensitive approximation to ideal bargaining among stakeholders. We identify three strategies agents use to reduce moral costs by outsourcing or bypassing virtual bargaining: strategic delegation, diffusion of responsibility, and coalitional boundary-setting. We propose extending RRC with parameters for agency transfer, responsibility tracking, and stakeholder inclusion to better capture real-world moral decision-making.},
}

Humans
*Morals
*Decision Making
*Cognition
*Outsourced Services
Cooperative Behavior

@article {pmid42342627,
year = {2026},
author = {Kuhlmeier, VA and Dunfield, KA},
title = {The third axis: partner choice.},
journal = {The Behavioral and brain sciences},
volume = {49},
number = {},
pages = {e146},
doi = {10.1017/S0140525X25101684},
pmid = {42342627},
issn = {1469-1825},
mesh = {Humans ; *Choice Behavior ; *Morals ; *Interpersonal Relations ; *Cooperative Behavior ; },
abstract = {Though we find the 'triple theory' of moral cognition, with its emphasis on resource-rational contractualism, to be well argued, we suggest that Levine et al.'s model starts too late in the process. That is, we agree that their proposed abstractions and heuristics can help to develop mutually beneficial arrangements, but effective contracts also require the identification of reliable actors.},
}

Humans
*Choice Behavior
*Morals
*Interpersonal Relations
*Cooperative Behavior

@article {pmid42342630,
year = {2026},
author = {Bystranowski, P},
title = {The veil and the deal: Bargaining between case-specific solutions and unknown rules.},
journal = {The Behavioral and brain sciences},
volume = {49},
number = {},
pages = {e136},
doi = {10.1017/S0140525X25101490},
pmid = {42342630},
issn = {1469-1825},
mesh = {Humans ; *Morals ; *Decision Making ; },
abstract = {Levine et al.'s resource-rational contractualism omits how people decide that a situation demands rule-, not case-based, guidance. I propose that moral cognition first tags contexts as rule-governed, then either uncovers an existing norm or forges a plausible one. Coordination stakes and the private-public divide likely trigger this tag. Distinguishing discovery from invention invites targeted experiments and refines the framework.},
}

Humans
*Morals
*Decision Making

@article {pmid42343420,
year = {2026},
author = {Morisaki, Y and Nomura, N and Ohshima, M and Matsuda, M and Komine, O and Okuda, T and Yamanaka, K and Misawa, H},
title = {Immune checkpoint LAG-3 governs stage-dependent and disease-associated microglial modules in ALS model mice.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-026-03919-8},
pmid = {42343420},
issn = {1742-2094},
support = {JP26K10309//Japan Society for the Promotion of Science/ ; JP22K06634//Japan Society for the Promotion of Science/ ; },
abstract = {Immune checkpoint molecules, inhibitory receptors originally characterized in T cell biology, have recently emerged as regulators of microglial function in neurodegeneration, yet their roles in amyotrophic lateral sclerosis (ALS) remain unexplored. Here, we investigated LAG-3, an inhibitory immune checkpoint receptor, in microglial regulation during ALS pathogenesis using SOD1[G93A] mice. LAG-3 expression was progressively upregulated in spinal cord microglia during disease progression, and LAG-3-high microglia exhibited a disease-associated microglia (DAM) transcriptional signature. Genetic deletion of LAG-3 produced a biphasic phenotype, with accelerated disease onset but significantly prolonged disease duration. LAG-3 deficiency enhanced inflammatory microglial responses at the early disease stage, whereas at the late stage it suppressed inflammatory signaling while selectively preserving phagocytic effector gene expression, demonstrating that LAG-3 dissociates the inflammatory and phagocytic modules within the DAM program in a stage-dependent manner. These transcriptional changes translated into enhanced phagocytic capacity in primary microglia and amelioration of the spinal cord environment through suppression of inflammatory pathways and restoration of oxidative phosphorylation. Our findings identify LAG-3 as a stage-dependent regulator of microglial functional states in ALS and support the concept that immune checkpoint molecules constitute a class of module-level regulators of microglial function in neurodegeneration.},
}

@article {pmid42343520,
year = {2026},
author = {Sun, L and Chen, J and Wu, Y and Bian, S and Wang, Q and Ha, L},
title = {[Effect of electroacupuncture at "Zusanli" (ST36) on TREM2-mediated microglial activation in amyotrophic lateral sclerosis mice].},
journal = {Zhongguo zhen jiu = Chinese acupuncture & moxibustion},
volume = {46},
number = {6},
pages = {948-955},
doi = {10.13703/j.0255-2930.20250113-k0001},
pmid = {42343520},
issn = {0255-2930},
mesh = {Animals ; *Electroacupuncture ; *Amyotrophic Lateral Sclerosis/therapy/genetics/metabolism/immunology ; Male ; Mice ; *Microglia/metabolism/immunology ; *Receptors, Immunologic/genetics/metabolism/immunology ; Humans ; *Membrane Glycoproteins/genetics/metabolism/immunology ; *Acupuncture Points ; Disease Models, Animal ; Mice, Transgenic ; Interleukin-4/genetics/metabolism ; Spinal Cord/metabolism ; Interleukin-1beta/genetics/metabolism ; },
abstract = {OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli" (ST36) on amyotrophic lateral sclerosis (ALS) in mouse models based on myeloid cell trigger receptor 2 (TREM2)-mediated microglial activation.

METHODS: Thirty-six SPF-grade male human mutant superoxide dismutase 1 (SOD1-G93A) transgenic mice were divided into a model group, an EA group, and a drug group, 12 mice in each group. Besides, 12 wide-type littermates were collected as a control group. In the EA group, EA was performed at the "Zusanli" (ST36), with an intermittent wave, at the frequency of 15 Hz, and for 10 min each intervention; once every other day, 3 interventions a week and for 4 continuous weeks. In the drug group, the intragastric administration of riluzole solution was given at 8 mg/kg, once daily, for 4 continuous weeks. After intervention completion, behavioral assessment of mice was conducted using rotarod test and wire hang test. With HE and Nissl staining adopted, morphology of motor neurons in the anterior horn of the spinal cord was observed. Immunofluorescence was used to detect the fluorescence intensity of TREM2 in the anterior horn of spinal cord. Western blot analysis was performed to measure the protein expression of interleukin (IL)-1β, γ interferon (IFN-γ), IL-4 and IL-10 in spinal cord tissue. Flow cytometry was used to analyze the proportion of CD86[+] and CD206[+] in spinal cord monocyte suspension.

RESULTS: Compared with the control group, in the model group, motor neurons in the anterior horn of the spinal cord exhibited disordered arrangement; accompanied by nuclear pyknosis and cytoplasmic shrinkage; the latency to fall in the rotarod test and the cut-off time in the wire hang test were shortened, fluorescence intensity of TREM2 in the spinal anterior horn, the protein expression of IL-1β, IFN-γ, IL-4, and IL-10, and the proportion of CD86[+] and CD206[+] in spinal cord tissue increased(P<0.01). When compared with the model group, in the EA and drug groups, motor neurons in the anterior horn of the spinal cord were arranged regularly; nuclear pyknosis and chromatolysis were attenuated, and the structural integrity of neurons was improved; the latency to fall and the the cut-off time were prolonged, fluorescence intensity of TREM2 in the spinal anterior horn was reduced, the protein expression of IL-1β and IFN-γ decreased, and that of IL-4, and IL-10 increased in the spinal cord tissue; the proportion of CD86[+] in spinal cord tissue was reduced and that of CD206[+] elevated(P<0.01, P<0.05). Compared with the drug group, the EA group showed the increase of protein expression of IL-1β,and the decrease of IL-4, IL-10 in the spinal cord tissue and the proportion of CD206[+] (P<0.05).

CONCLUSION: Electroacupuncture at "Zusanli" (ST36) exhibits a certain improvements in motor function of SOD1-G93A transgenic mice. The underlying mechanism may be related to attenuating neuroinflammation via the modulation of microglial activation mediated by TREM2.},
}

Animals
*Electroacupuncture
*Amyotrophic Lateral Sclerosis/therapy/genetics/metabolism/immunology
Male
Mice
*Microglia/metabolism/immunology
*Receptors, Immunologic/genetics/metabolism/immunology
Humans
*Membrane Glycoproteins/genetics/metabolism/immunology
*Acupuncture Points
Disease Models, Animal
Mice, Transgenic
Interleukin-4/genetics/metabolism
Spinal Cord/metabolism
Interleukin-1beta/genetics/metabolism

@article {pmid42343570,
year = {2026},
author = {Ellis, BCS and Avila, AS and Huang, WP and John, SJ and Bonsall, S and Hodgson, RE and Kumar, V and Nolan, M and West, RJH and Campbell, SG and De Vos, KJ and Lagier-Tourenne, C and Robin Highley, J and Cooper-Knock, J and Shelkovnikova, TA},
title = {STMN2 protein depletion via translation deficits and stress granules in amyotrophic lateral sclerosis.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag222},
pmid = {42343570},
issn = {1460-2156},
abstract = {STMN2 is an abundant neurospecific protein dysregulated in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). We previously reported that cellular stress can lead to STMN2 loss due to TDP-43 nuclear condensation. Here, using human and murine neuronal cell models, multiple pharmacological tools, in situ single-molecule analysis of translation and RNA localisation, and longitudinal analysis of neuronal fitness/survival, we establish TDP-43-independent mechanisms of STMN2 depletion under stress. We find that human STMN2 protein level is extremely labile under acute high-magnitude stress. Early in stress, STMN2 is suppressed via activated proteasomal degradation, phosphorylation and translation repression by stress granules, independently of TDP-43 loss of function in splicing. We further show that STMN2 protein level is highly sensitive to chronic translation deficits, such as those elicited by prolonged low-grade stress. We find that low pre-stress STMN2 sensitises neuronal cells to stress-induced apoptosis, whereas moderately increased STMN2 is protective under stress. Finally, we demonstrate that STMN2 mRNA is upregulated in non-TDP ALS (ALS-FUS) models, which may compensate for translation/stress granule defects in this disease subtype. Consistent with the compensation hypothesis, STMN2 mRNA is also upregulated in the relatively spared (cortex), but not severely affected (spinal cord), CNS regions in ALS-TDP. In conclusion, our study implicates two common denominators in neurodegeneration - dysregulation of translation and stress granules - in STMN2 depletion, independent of TDP-43 loss of function. It also describes an RNA-based compensatory mechanism in ALS underling the unique vulnerability of neurons with developing TDP-43 pathology.},
}

@article {pmid42344043,
year = {2026},
author = {Mantell, JE and Masvawure, TB and Thomas, NA and George, G and Howard, AA and Strauss, M and Ndagije, F and Lethoko, M and Low, A and Hirsch-Moverman, Y},
title = {Health system support and strengthening for cross-border HIV services: key informants' perspectives on testing and linkage for Lesotho-South Africa migrant workers.},
journal = {BMJ public health},
volume = {4},
number = {2},
pages = {e003284},
pmid = {42344043},
issn = {2753-4294},
abstract = {INTRODUCTION: Cross-border migrants, especially those in destination countries with high HIV burden and high population mobility, often face structural challenges in accessing HIV testing and linkage-to-care. There is limited research on the most effective HIV testing and linkage-to-care strategies tailored to cross-border migrants. We conducted a qualitative study to explore barriers and facilitators to HIV testing and linkage-to-care among Lesotho-South Africa cross-border migrant workers.

METHODS: We conducted in-depth interviews with 15 purposively selected stakeholders from Lesotho who interfaced with migrants, namely administrative and programme staff from the Ministry of Health, non-governmental organisations, community counsellors and testers and migrant advocates. We captured diverse perspectives on barriers and facilitators to HIV services among migrant workers. Template analysis, a rapid form of thematic analysis, was used to synthesise the data. We applied Chee et al's health systems framework differentiating health system support and health system strengthening to analyse our findings and guide actionable programme and policy strategies.

RESULTS: Participants recommended strategies that both support the health system by improving service provision and strengthen the health system by implementing structural and policy-level changes. Support strategies included expanding migrant-centred access to HIV testing and prevention services, reducing structural and economic barriers to service utilisation and strengthening community-based services. Strengthening strategies included cross-border collaboration and harmonised referral systems for continuity of care, expanding differentiated HIV care models for mobile populations, integrating HIV services into general healthcare, establishing workplace HIV policies for migrant workers and flexible cross-border funding for migrant health.

CONCLUSIONS: Chee et al's framework allows policymakers and programme implementers to more intentionally distinguish and plan for solutions that merely support versus actually strengthen health systems. Strengthening approaches, in contrast to supporting ones, have the potential to transform HIV services for migrants by ensuring continuity of services in both home and destination venues butrequire greater commitment and action from politicians, policymakers, funders and advocacy groups to implement.},
}

@article {pmid42345500,
year = {2026},
author = {Drążyk, M and Pyc, Z and Pietrzyk, SJ and Gajda-Janiak, A and Godziszewski, F and Pioterek, O and Tulski, M and Mazurek, M and Domagała, ZA},
title = {Formaldehyde neurotoxicity: Effects on the mammalian brain, cognitive function, and neurodegenerative risk. A scoping review.},
journal = {Advances in clinical and experimental medicine : official organ Wroclaw Medical University},
volume = {},
number = {},
pages = {},
doi = {10.17219/acem/209617},
pmid = {42345500},
issn = {1899-5276},
abstract = {Aqueous formaldehyde (FA) solution, known as formalin, is currently the primary agent used for preserving tissue samples and anatomical specimens. Formaldehyde is widely used in laboratories and the chemical industry; it also occurs as an air pollutant and endogenous cellular metabolite. The potential carcinogenic effects of formalin on the respiratory tract are well documented. A less recognized consequence of occupational exposure to FA is its detrimental effect on the central nervous system (CNS) and brain function. A literature review was conducted to investigate the effects of FA on the brain. Five databases were searched: PubMed, Web of Science (WoS), Embase, ScienceDirect, and Google Scholar. To describe the effects of FA exposure and endogenous FA generation, 35 relevant publications were collected and analyzed. The literature review demonstrated that inhalation is the most common route of FA exposure. Several studies have shown that FA may cause hippocampal damage, disrupt melatonin secretion, and induce a wide range of cognitive disorders with varying characteristics and severity. These disorders include memory impairment, disturbances in balance and spatial orientation, learning difficulties, sleep disturbances, impaired judgment, and prolonged reaction times to stimuli. Increased endogenous FA concentration has also been associated with a higher risk of neurodegenerative diseases, such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis. The literature analysis demonstrated the high neurotoxicity of FA, which may lead to numerous neuropsychiatric disorders. We aim to draw attention to the risks associated with the routine use of formalin, particularly among anatomists and pathologists, and to encourage consideration of less harmful alternative preservation agents.},
}

@article {pmid42345595,
year = {2026},
author = {de Sousa, SF and Marques, MDCMP and da Silva Amaral, GMM},
title = {Factors Influencing the Maintenance of Advanced Life Support Competencies Among Critical Care Professionals: A Scoping Review.},
journal = {Nursing in critical care},
volume = {31},
number = {4},
pages = {e70545},
doi = {10.1111/nicc.70545},
pmid = {42345595},
issn = {1478-5153},
support = {UID/06291/2025//Fundação para a Ciência e a Tecnologia/ ; },
mesh = {Humans ; *Clinical Competence/standards ; *Critical Care/standards ; *Advanced Cardiac Life Support/standards ; },
abstract = {BACKGROUND: Advanced life support (ALS) competence may deteriorate within months after certification, but what supports ongoing competence in critical care remains unclear.

AIM: To map factors influencing maintenance of ALS competence among critical care professionals working in critical care settings.

STUDY DESIGN: Scoping review conducted in accordance with Joanna Briggs Institute guidance and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. MEDLINE, CINAHL and the Cochrane Library were searched (from February to March 2025). We included peer-reviewed and grey sources from hospital-based critical care settings that assessed ALS competencies over time. Data were synthesised using inductive thematic analysis.

RESULTS: Twenty-five sources were included (19 peer-reviewed, 6 grey). Factors were mapped to three domains. Educational factors were most frequently reported and centred on simulation-based rehearsal, structured feedback and debriefing and spaced refreshers delivered in brief, frequent sessions. Institutional determinants related to protected training time, access to resources, standardised roles and content and monitoring through audit and feedback. Individual determinants included clinical exposure and experience, perceived preparedness and self-confidence, stress and cognitive load, engagement in ongoing learning and non-technical behaviours. Outcomes were largely simulation-based or self-reported, and longer-term durability was inconsistently assessed.

CONCLUSIONS: Maintenance of ALS competence appears to require coordinated educational and organisational supports; longitudinal evaluations with explicit definitions and validated outcomes are needed.

Critical care services may strengthen ALS competence maintenance by embedding recurrent, context-aligned rehearsal with feedback, supported by protected training time, accessible training infrastructure and ongoing performance monitoring.

REVIEW REGISTRATION: The review protocol was prospectively registered on the Open Science Framework https://doi.org/10.17605/OSF.IO/PEQJH.},
}

Humans
*Clinical Competence/standards
*Critical Care/standards
*Advanced Cardiac Life Support/standards

@article {pmid42346159,
year = {2026},
author = {Verde, EM and Secco, V and Ghezzi, A and Mandrioli, J and Carra, S},
title = {Correction: Verde et al. Molecular Mechanisms of Protein Aggregation in ALS-FTD: Focus on TDP-43 and Cellular Protective Responses. Cells 2025, 14, 680.},
journal = {Cells},
volume = {15},
number = {12},
pages = {},
doi = {10.3390/cells15121053},
pmid = {42346159},
issn = {2073-4409},
abstract = {In order to facilitate readers' better understanding, some language descriptions and grammar as well as the layout of some chapters have been modified [...].},
}

@article {pmid42347120,
year = {2026},
author = {Alves Ferreira, JM and Tukaiev, S and Giannouli, V},
title = {RNA-Binding Proteins in Ageing and Age-Related Disease.},
journal = {Neurology international},
volume = {18},
number = {6},
pages = {},
doi = {10.3390/neurolint18060112},
pmid = {42347120},
issn = {2035-8385},
abstract = {RNA-binding proteins (RBPs) are essential regulators of all aspects of RNA metabolism, including splicing, stability, localisation, translation, and degradation. Through their ability to recognise specific cis-elements in target transcripts, often via RNA-recognition motifs or other conserved domains, RBPs enable rapid cellular adaptation to stress and maintain proteostasis, particularly in post-mitotic tissues with limited transcriptional flexibility. Accumulating evidence positions RBPs as both modulators and drivers of the molecular hallmarks of ageing, including genomic instability, loss of proteostasis, mitochondrial dysfunction, cellular senescence, and chronic inflammation. This review synthesises peer-reviewed studies on the multifaceted roles of RNA-binding proteins in organismal ageing and age-related diseases. Key themes include the tissue- and age-dependent changes in expression of turnover and translation regulatory RBPs such as HuR (ELAVL1), AUF1 (HNRNPD), TIA-1, and tristetraprolin (ZFP36), which alter the stability of mRNAs encoding cell-cycle regulators, pro-inflammatory cytokines, and stress-response proteins. Systematic downregulation of core splicing factors, including PTBP1 and several heterogeneous nuclear ribonucleoproteins, drives widespread senescence-associated splicing alterations in pathways governing cell division, autophagy, DNA repair, and mitochondrial function, suggesting a causal contribution to the senescent phenotype. Prion-like RBPs such as TDP-43 and FUS exhibit age-dependent mislocalisation, nuclear depletion, and cytoplasmic aggregation, contributing to splicing defects, impaired RNA transport, and neurodegeneration in amyotrophic lateral sclerosis, frontotemporal dementia, and limbic-predominant age-related TDP-43 encephalopathy. Interactions between RBPs and non-coding RNAs, together with disrupted liquid-liquid phase separation dynamics, further exacerbate age-related decline. By integrating mechanistic studies from cellular and animal models with observations in human cohorts, this review underscores RBPs as central nodes linking multiple ageing hallmarks and highlights their potential as biomarkers and therapeutic targets to promote healthy ageing. Limitations of current models and priorities for future translational research are discussed.},
}

@article {pmid42347662,
year = {2026},
author = {Breuer, A and Raeder, V and Pernice, HF and Boesl, F and Prüss, H and Audebert, H and Hahn, K and Franke, C},
title = {Fasciculations Following COVID-19 Vaccination-A Case Series of Ten Patients.},
journal = {Vaccines},
volume = {14},
number = {6},
pages = {},
doi = {10.3390/vaccines14060541},
pmid = {42347662},
issn = {2076-393X},
abstract = {Introduction: Vaccination against COVID-19 has been crucial in controlling the pandemic. While side effects are typically mild, rare neurological complications have been reported. This is a case series of ten patients who reported of persistent fasciculations after COVID-19 vaccination. Methods: We describe the clinical presentation and diagnostic work-up of ten patients with new-onset fasciculations in temporal proximity to COVID-19 vaccination. Patients with prior SARS-CoV-2 infection or known alternative causes of fasciculations were excluded. Routine clinical data, including neurological examination, laboratory results, and electrophysiology (electromyography and nerve conduction studies), were analyzed. Results: Ten patients (5 male, 5 female; mean age 42.4 years) reported fasciculations beginning within 6 h to 13 days post-vaccination and persisting for 2-12 months at the time of presentation. Fasciculations were accompanied by additional symptoms such as paresthesia and fatigue. Laboratory results were mostly unremarkable; two patients had positive myositis antibodies without clinical correlates. Electrophysiology was unremarkable in six patients, while fasciculation potentials were detected in four patients. Nine were diagnosed with probable benign fasciculation syndrome (BFS), and one met diagnostic criteria for amyotrophic lateral sclerosis (ALS). Discussion: In this small, retrospective case series, most cases of post-vaccination fasciculations were benign and compatible with BFS. Whether BFS onset was causally linked to vaccination or due to a nocebo effect remains unclear. One patient was diagnosed with ALS, though a causal link remains speculative given the study's limitations and rarity of similar reports. Larger, prospective studies are needed to validate these observations and explore underlying pathophysiological mechanisms.},
}

@article {pmid42333772,
year = {2026},
author = {Amarni, M and Ladjel-Mendil, A and Allala, F and Cherifi, F and Bouanane-Darenfed, A and Moussaoui, H and Merzouagui, R and Ahras-Sifi, N and Laraba-Djebari, F},
title = {Thymol Attenuates Klebsiella pneumoniae Induced Lung Injury via Modulation of Peroxidase-Driven Oxidative Stress and Host-Pathogen Interactions: In Vivo and In Silico Insights.},
journal = {Journal of biochemical and molecular toxicology},
volume = {40},
number = {7},
pages = {e70997},
doi = {10.1002/jbt.70997},
pmid = {42333772},
issn = {1099-0461},
mesh = {Animals ; *Oxidative Stress/drug effects ; *Klebsiella pneumoniae ; Mice ; *Thymol/pharmacology ; *Host-Pathogen Interactions/drug effects ; *Acute Lung Injury/drug therapy/microbiology/pathology/metabolism ; *Klebsiella Infections/drug therapy/metabolism/pathology ; *Peroxidase/metabolism ; Molecular Docking Simulation ; Male ; },
abstract = {Klebsiella pneumoniae pneumonia drives excessive inflammatory and oxidative responses that culminate in acute lung injury (ALI) and impaired bacterial clearance. Effective therapies capable of restoring host-pathogen balance remain limited, particularly in the context of multidrug-resistant strains. This study investigated the therapeutic efficacy of thymol in a murine model of K. pneumoniae-induced ALI. Oral thymol (5-20 mg/kg) markedly reduced lung injury, suppressed leukocyte infiltration, improved pulmonary histoarchitecture, and significantly enhanced bacterial clearance. Thymol reshaped systemic and local immune responses by decreasing tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP), increasing interleukin-10 (IL-10), and limiting macrophage and granulocyte recruitment. Mechanistically, thymol attenuated heme peroxidase-driven oxidative stress, as evidenced by reduced myeloperoxidase (MPO) and eosinophil peroxidase (EPO) activities, decreased malondialdehyde (MDA), hydrogen peroxide (H2O2), and nitric oxide (NO), along with restoration of catalase activity and glutathione levels. Complementary in silico docking predicted stable interactions of thymol with MPO and EPO, as well as essential bacterial metabolic enzymes, including deoxy-D-xylulose-5-phosphate synthase (DXS), acetolactate synthase (ALS), and dihydrodipicolinate synthase (DHDPS). Collectively, these findings suggest that thymol may act as a multi-target bioactive compound capable of modulating host inflammatory and redox pathways while potentially impairing bacterial metabolic fitness, thereby mitigating pneumonia-associated ALI.},
}

Animals
*Oxidative Stress/drug effects
*Klebsiella pneumoniae
Mice
*Thymol/pharmacology
*Host-Pathogen Interactions/drug effects
*Acute Lung Injury/drug therapy/microbiology/pathology/metabolism
*Klebsiella Infections/drug therapy/metabolism/pathology
*Peroxidase/metabolism
Molecular Docking Simulation
Male

@article {pmid42333954,
year = {2026},
author = {Harrison, MD and Bradsby, JE and , and Kalra, S and Bouvier, L},
title = {Thinning of the oral motor cortex is linked to impaired speech in amyotrophic lateral sclerosis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/21678421.2026.2688247},
pmid = {42333954},
issn = {2167-9223},
abstract = {Most individuals with amyotrophic lateral sclerosis (ALS) develop bulbar impairment as their disease progresses. The ALS Functional Rating Scale-Revised (ALSFRS-R) bulbar subscore and neurological examination of upper (UMN) and lower motor neurons (LMN) are routinely used to assess this dysfunction but have inherent limitations. Speech‑derived measures have shown promise for capturing bulbar decline with greater sensitivity, but their neurobiological correlates remain unclear. This study examined the associations between quantitative speech measures and cortical thinning in ALS. Data from the Canadian ALS Neuroimaging Consortium were analyzed. Speech measures were extracted from audio recordings of the standardized "Bamboo Passage". Cortical thickness was calculated from T1‑weighted MRI scans. General linear models first compared cortical thickness between patients with ALS and healthy controls. Associations between the speech measures and cortical thickness were then assessed within the ALS group. Patients with ALS showed cortical thinning across bilateral frontotemporal regions, with the largest clusters in the bilateral motor cortices. Reduced speaking and articulation rates were associated with thinning in both oral motor cortices. In contrast, the ALSFRS-R bulbar subscore and UMN and LMN bulbar burden showed no significant associations. Measures of pausing behavior were negatively associated with frontal cortical regions. Thinning of the oral motor cortex in ALS was linked to reduced oral motor function, supporting speaking and articulation rate as sensitive markers of bulbar motor neuron degeneration. These measures demonstrated neuroanatomical associations that the ALSFRS-R bulbar subscore and neurological examination findings did not, highlighting their potential value for monitoring bulbar dysfunction in ALS.},
}

@article {pmid42334216,
year = {2026},
author = {Riva, N and Schito, P and Russo, T and Ferraro, OE and Durante, G and Tettamanti, A and Riboldi, E and Domi, T and Pozzi, L and Quattrini, A and Comola, M and Agosta, F and Cremona, G and Filippi, M},
title = {Tolerability, Safety and Effectiveness of Sigh Introduction During Non-Invasive Mechanical Ventilation Cycles in Patients With Amyotrophic Lateral Sclerosis.},
journal = {European journal of neurology},
volume = {33},
number = {6},
pages = {e70660},
pmid = {42334216},
issn = {1468-1331},
support = {//AriSLA - Fondazione Italiana di ricerca per la SLA/ ; //Giovanni Marazzina Foudation/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/complications/physiopathology ; Female ; Male ; Middle Aged ; Aged ; *Noninvasive Ventilation/methods/adverse effects ; *Respiratory Insufficiency/therapy/etiology ; Treatment Outcome ; },
abstract = {BACKGROUND: Respiratory failure is the main cause of death in Amyotrophic lateral sclerosis (ALS), in which the physiological sigh reflex is impaired due to inspiratory muscle weakness. Aim of this study is to assess the tolerability, safety, and effectiveness of adding a sigh cycle to non-invasive mechanical ventilation (NIMV) settings in ALS patients.

METHODS: In this randomized, blind-controlled proof-of concept study, 44 consecutive ALS patients with indication for NIMV were randomized to: Group I: NIMV with Sigh cycles; Group II: NIMV without Sigh. The primary outcome was the reduction in the Oxygen Desaturation Index (ODI); secondary outcomes included: Overnight Oximetry (OvOx), Arterial blood gas (ABG), and Visual Analog Scale (VAS; 0-10) scores to assess sleep quality, symptom intensity, mask interface, and NIMV tolerance. Assessments were conducted at baseline, after NIMV adaptation (T1) and at 1-month follow-up (T2).

RESULTS: The Sigh cycle was safe and well tolerated. No significant group differences were observed at T1 or T2 in the primary outcome ODI (median ΔODI: Group A:-4.2; Group B:-4.6: p = 0.54), as well as in the OvOx parameters and pO2 and pCO2 ABG values. At T2, secondary analysis showed a significant difference in HCO₃[-] in favor of the Sigh arm (ΔHCO3 [-]: -1.60 vs. 1.35 mmol/L, p = 0.042). Exploratory Cox-regression models suggested a potential independent effect of SIGH on survival.

CONCLUSIONS: Sigh is safe, well tolerated in ALS patients. Although this study did not reach the primary outcome, we also cannot rule out that sigh doesn't benefit the patient.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/complications/physiopathology
Female
Male
Middle Aged
Aged
*Noninvasive Ventilation/methods/adverse effects
*Respiratory Insufficiency/therapy/etiology
Treatment Outcome

@article {pmid42334507,
year = {2026},
author = {Turkmenel, N and Uskun, E},
title = {Associations influencing quality of life in caregivers of patients with amyotrophic lateral sclerosis: a stress-process model approach.},
journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation},
volume = {35},
number = {8},
pages = {},
pmid = {42334507},
issn = {1573-2649},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/nursing/psychology ; *Quality of Life/psychology ; Female ; Male ; *Caregivers/psychology ; Cross-Sectional Studies ; Middle Aged ; Social Support ; *Stress, Psychological/psychology ; Aged ; Adult ; Cost of Illness ; Adaptation, Psychological ; Surveys and Questionnaires ; },
abstract = {BACKGROUND: Caring for patients with amyotrophic lateral sclerosis (ALS) involves demands that reduce caregivers' quality of life. Although caregiver burden and perceived social support was conceptualized as an independent correlate of quality of life rather than a factor operating primarily through caregiver burden. This study examined these associations within a stress-process framework in which perceived social support was conceptualized as an independent correlate rather than a buffering factor.

METHODS: This cross-sectional analytical study included 118 informal caregivers of patients with ALS. Primary stressors were defined as patient functional status (ALSFRS-R), caregiving duration, and communication difficulty. Caregiver burden (Zarit Burden Interview) was considered a secondary stressor. Physical and mental quality of life were assessed using the SF-12, and perceived social support was measured with the Multidimensional Scale of Perceived Social Support. Hierarchical regression analyses were performed to examine associations specified in the conceptual model while controlling for caregiver sociodemographic and socioeconomic variables. Additional mediation analyses were conducted to examine whether caregiver burden mediated the relationship between perceived social support and quality of life.

RESULTS: Poorer patient functional status was significantly associated with higher caregiver burden, whereas communication difficulty showed a positive but non-significant association after adjustment for caregiver characteristics. Caregiver burden showed negative associations with both physical and mental quality of life. Perceived social support remained positively associated with quality of life after adjustment for caregiver burden and contributed additional explained variance in the models. Mediation analyses showed no evidence that caregiver burden mediated the association between perceived social support and either physical or mental quality of life.

CONCLUSIONS: The findings are consistent with a stress-process framework in ALS caregiving, in which caregiver burden represents a central factor statistically associated with both caregiving stressors and quality of life, while perceived social support shows an independent association with quality of life. These findings suggest that both caregiver burden and perceived psychosocial resources may be relevant to caregiver well-being, although causal and intervention-related implications require further investigation.},
}

Humans
*Amyotrophic Lateral Sclerosis/nursing/psychology
*Quality of Life/psychology
Female
Male
*Caregivers/psychology
Cross-Sectional Studies
Middle Aged
Social Support
*Stress, Psychological/psychology
Aged
Adult
Cost of Illness
Adaptation, Psychological
Surveys and Questionnaires

@article {pmid42334646,
year = {2026},
author = {Totuk, O and Sahin, S},
title = {Behavioral variant frontotemporal dementia associated with a NEK1 missense variant: exploring a possible phenotypic association.},
journal = {Neurogenetics},
volume = {27},
number = {1},
pages = {},
pmid = {42334646},
issn = {1364-6753},
mesh = {Humans ; *Frontotemporal Dementia/genetics/pathology ; *NIMA-Related Kinase 1/genetics ; Male ; Aged ; *Mutation, Missense ; Phenotype ; Amyotrophic Lateral Sclerosis/genetics ; Exome Sequencing ; },
abstract = {NEK1 variants are recognized genetic contributors to amyotrophic lateral sclerosis (ALS) and have occasionally been reported within the ALS-frontotemporal dementia (FTD) spectrum. However, their association with isolated behavioral variant frontotemporal dementia (bvFTD) remains unclear. Here, we describe a 69-year-old man who developed progressive behavioral symptoms beginning in his early 60s. Cognitive evaluation demonstrated reduced verbal fluency with relative preservation of memory functions. Structural and functional neuroimaging demonstrated right-predominant frontotemporal atrophy and hypometabolism. Genetic testing for common FTD-associated genes (MAPT, GRN, and C9orf72) was negative. Whole-exome sequencing identified a heterozygous NEK1 c.899T > C (p.Ile300Thr) missense variant, currently classified as a variant of uncertain significance. This observation raises the possibility that NEK1-associated disease may extend beyond ALS or ALS-FTD phenotypes and may include isolated bvFTD presentations. However, further genetic and functional studies are required to clarify the clinical significance of this variant.},
}

Humans
*Frontotemporal Dementia/genetics/pathology
*NIMA-Related Kinase 1/genetics
Male
Aged
*Mutation, Missense
Phenotype
Amyotrophic Lateral Sclerosis/genetics
Exome Sequencing

@article {pmid42335378,
year = {2026},
author = {Rahimi, K and Gupta, A and Malekzadeh, K and Zerze, GH},
title = {Stabilizing Effect of Neighboring Disordered RGG Domain on the Folded State of FUS-RRM.},
journal = {The journal of physical chemistry. B},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jpcb.6c02052},
pmid = {42335378},
issn = {1520-5207},
abstract = {Fused in Sarcoma (FUS) is an RNA-binding protein essential for RNA processing, yet its RNA-recognition motif (RRM) is prone to irreversible unfolding and amyloid aggregation, which is associated with the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although the isolated RRM is experimentally known to adopt a stable folded structure, its response to long-range interdomain interactions remains poorly understood. In this work, we address this gap by performing rare-event sampling atomistic molecular dynamics simulations of two systems: isolated RRM and RRM with the flanking RGG sequence using multithermal-multiumbrella on-the-fly probability enhanced sampling (MM-OPES). These simulations allow us to characterize the folding landscape of FUS RRM and examine the specific interactions between the RRM and the adjacent RGG region and how they affect the stability of RRM. Our findings reveal that the disordered RGG segment enhances the stability of the folded RRM by forming stabilizing intramolecular contacts that wrap around the domain. This stabilization is driven by increased fractions of the α1 helix, β2, β3, and the KK loop through a network of targeted multivalent contacts between the RGG and RRM residues. This work reveals how a disordered region stabilizes a folded RNA-binding domain, underscoring the importance of disordered-ordered interdomain coupling in shaping the folding landscape of FUS RRM. These results suggest that disruption of such interactions could destabilize the RRM fold and may contribute to misfolding-prone states relevant to FUS dysfunction.},
}

@article {pmid42335819,
year = {2026},
author = {Cheng, Y and Tian, T and Song, D and Ma, Y and Bi, Z and Zhang, X and Zhang, L and Li, Y and Huang, H},
title = {Bionic nanozyme arrays for selective identifying and discriminating sulfonylurea herbicides via recognition site mimicry.},
journal = {Journal of hazardous materials},
volume = {514},
number = {},
pages = {142800},
doi = {10.1016/j.jhazmat.2026.142800},
pmid = {42335819},
issn = {1873-3336},
abstract = {Sulfonylurea herbicides (SUs) are widely used in agriculture owing to their high herbicidal efficacy and low mammalian toxicity. However, their persistence results in residues that pose potential risks to the environment and human health, making it essential to develop rapid and accurate detection techniques for these herbicides. Herein, we designed bionic nanozymes inspired by the structure of acetolactate synthase (ALS), the primary target enzyme of SUs in plants. Using the ALS cofactor thiamine diphosphate and key binding amino acids (arginine, proline, and tryptophan) as ligands, we synthesized bionic nanozymes that exhibited excellent peroxidase-like activity. SUs significantly enhanced the activity of the bionic nanozymes, and the degree of enhancement varied among different SUs. In contrast, organophosphate pesticides (OPs), carbamate pesticides (CPs), and other tested pesticides did not induce such enhancement. Therefore, we constructed a six-channel colorimetric sensor array and achieved 100% accurate discrimination of five SUs across a concentration range of 1-100 µg/mL. Furthermore, the SUs in the four real grain samples and the blind sample were also accurately distinguished by the array. This study not only provides an efficient method for rapid detection of SUs, but also opens new avenues for the bionic design of nanozymes aimed at the precise identification of specific pesticide molecules in complex matrices.},
}

@article {pmid42335888,
year = {2026},
author = {Gautier, O and Blum, JA and Nguyen, TP and Cao, S and Klemm, S and Yamakawa, M and Huh, D and Hurt, JA and Sinnott-Armstrong, N and Zeng, Y and Davis, CO and Bombosch, J and Liu, C and Encarnacion, LN and Guttenplan, KA and Chen, D and Kathiria, A and Zhao, L and Moore, S and Meng, A and Ong, K and Cleveland, DW and Ravits, J and Rexach, JE and Greenleaf, WJ and Gitler, AD},
title = {An emergent disease-associated motor neuron state precedes cell death in ALS.},
journal = {Cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cell.2026.05.047},
pmid = {42335888},
issn = {1097-4172},
abstract = {To define molecular determinants of motor neuron degeneration in amyotrophic lateral sclerosis (ALS), we generated longitudinal single-nucleus transcriptomes and chromatin accessibility profiles of spinal motor neurons together with spatial transcriptomics from the SOD1-G93A mouse model. Vulnerable alpha motor neurons showed thousands of molecular changes, marking a transition into a distinct cell state we named "disease-associated motor neurons" (DMs). We identified transcription factor networks that govern how healthy cells transition into DMs and those associated with motor neuron subtype-selective vulnerability. Upregulation of DM-associated transcription factors in human motor neurons induced key features of DMs, demonstrating an active regulatory component. Human ALS spinal cord single-nucleus RNA sequencing data demonstrated conservation of the DM signature in alpha motor neurons, and human orthologs of regions differentially accessible in SOD1-G93A mouse motor neurons were enriched for ALS genetic risk variants. Together, these findings establish a conserved, genetically linked motor neuron signature in ALS.},
}

@article {pmid42336241,
year = {2026},
author = {Stavroulakis, T and White, S and Musson, L and Kime, J and , and McDermott, C},
title = {A multi-centre prospective evaluation of post-gastrostomy outcomes in patients with amyotrophic lateral sclerosis.},
journal = {Clinical nutrition ESPEN},
volume = {},
number = {},
pages = {103360},
doi = {10.1016/j.clnesp.2026.103360},
pmid = {42336241},
issn = {2405-4577},
abstract = {INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) often causes significant nutritional decline and weight loss, which negatively impacting prognosis. Gastrostomy is a standard intervention to provide long-term nutritional support, yet its efficacy in stabilising nutritional status and preventing post-procedure weight loss is uncertain. This study explored factors influencing weight change post-gastrostomy.

METHODS: This multicentre, prospective observational cohort study was conducted across 17 UK sites and involved longitudinal assessments at placement (M0) and at three (M3), six (M6), and nine (M9) months. Data collection included nutritional, clinical and functional parameters. The primary outcome was the percentage weight change between M0 and M3. Secondary outcomes included nutritional intake, functional decline, and survival. Statistical analysis employed hierarchical logistic regression to identify independent predictors of weight change post-gastrostomy.

RESULTS: Successful gastrostomy was performed in 155 included participants, of which 64 had complete M0 and M3 weight data. Mean percentage weight change from M0 to M3 was -3.3% (SD 7.4%), with 51.6% losing >1 kg in the first three months (p<0.01). Amongst those with available dietary data weight loss (n=21/43) was associated with lower mean daily energy (1620 kcal vs 2022 kcal, p=0.017) and protein intake (64g vs 77g, p=0.048) compared to those who maintained stable or gained weight (n=22/43). At M3, 50% (n=29/58) used a combination of oral and gastrostomy intake, 27.6% (n=16/58) used gastrostomy only, and 22.4% (13/58) were not using the gastrostomy. Based on available data for total daily expenditure energy expenditure (TDEE) calculation (n=39), 61.5% did not meet predicted total daily energy expenditure. Participants who lost weight (>1kg) post-gastrostomy had shorter median survival (270 days) compared to the weight stable/gain group (p=0.018). Hierarchical logistic regression suggested that mean daily water intake may potentially be an independent predictor of weight maintenance or gain, though this finding should be considered exploratory due to the limitations of our study (OR=1.003, p=0.040).

DISCUSSION: Despite gastrostomy placement, over half of participants in our final analytical cohort continued to lose weight. For a smaller subset of participants, for whom nutritional intake were available, this was potentially due to insufficient energy, macronutrient, and fluid intake, alongside disease-specific catabolism. As post-gastrostomy weight loss negatively impacts survival, these findings highlight a need for proactive, tailored, and ongoing nutritional support and monitoring, to optimise post-gastrostomy outcomes and survival in ALS.},
}

@article {pmid42336630,
year = {2026},
author = {Bosó Pérez, R and Littlejohn, J and Willis, M and Lewis, R and Mitchell, KR},
title = {Young people's sexual wellbeing: a systematic review of qualitative studies.},
journal = {BMJ sexual & reproductive health},
volume = {},
number = {},
pages = {},
doi = {10.1136/bmjsrh-2025-203161},
pmid = {42336630},
issn = {2515-2009},
abstract = {BACKGROUND: Young people's adverse sexual experiences contribute to a significant global mental health burden and detract from their quality of life. Sexual wellbeing connects sexual and mental health and can offer a novel perspective on drivers and impacts of young people's sexual behaviour. It is a promising means through which to shift public health focus from risk to aspects of sex relevant to broader wellbeing.

METHODS: This systematic review aimed to characterise sexual wellbeing for adolescents and emerging adults (aged 16-24 years). We searched four databases for peer-reviewed qualitative literature on young people's accounts relevant to sexual wellbeing published between 1988 and 2025. We intensity sampled and thematically synthesised studies against Mitchell et al's Sexual Wellbeing Conceptual Framework. PROSPERO registration: CRD42022315593.

RESULTS: We thematically synthesised 93 papers, representing 3152 participants across 25 countries. Our synthesis characterises youth sexual wellbeing as feeling: congruence between one's sexual thoughts, feelings, values, behaviours and emerging identities; driven by curiosity or desire; capable of advocating for one's wants and boundaries; able to authentically express oneself; deserving of care, respect and support; and expectant of a positive sexual future. Women, sexual and gender minorities, sexual violence survivors, youth with disabilities or health conditions, and those in deprived or sexually conservative communities report additional barriers to wellbeing.

CONCLUSIONS: This first-ever review of youth sexual wellbeing underscores its significance during this life stage, and outlines similarities and differences compared with adults. The findings demand a stronger focus on young people's priorities for sexual wellbeing to support their healthy development.},
}

@article {pmid42337904,
year = {2026},
author = {Morimoto, S and Okano, H},
title = {Are patient-derived models of amyotrophic lateral sclerosis a game changer for novel drug discovery?.},
journal = {Expert opinion on drug discovery},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/17460441.2026.2689746},
pmid = {42337904},
issn = {1746-045X},
abstract = {INTRODUCTION: ALS drug discovery has long depended on model systems that incompletely capture human disease heterogeneity, aging, and TDP-43 proteinopathy. Patient-derived platforms have therefore emerged as increasingly important human-relevant complements to animal and molecular models.

AREAS COVERED: This Critical Perspective examines when patient-derived ALS models genuinely change therapeutic decision-making rather than merely add mechanistic insight. The authors then propose a heuristic framework based on disease-relevant phenotype recapitulation, capture of patient-to-patient heterogeneity, and generation of findings that influence therapeutic prioritization or clinical translation. Furthermore, the authors evaluate iPSC-derived motor neurons, directly reprogrammed neurons, glial co-cultures, organoids, neural networks, and organ-chip systems against these conditions, while also addressing aging fidelity, reproducibility, upper motor neuron modeling, and regulatory implementation.

EXPERT OPINION: Patient-derived models are not yet standalone decision-grade tools for ALS drug development. Their present value lies in functioning as a human-biology filter for target discovery, reverse translation, biomarker development, and patient stratification when used within rigorous, standardized, and clinically linked workflows. The strongest current evidence supports proof-of-principle rather than generalized predictive validity.},
}

@article {pmid42338703,
year = {2026},
author = {Mndolo, NCM and Baluwa, MA and Yeboa, NK and Kazembe, A and Chirwa, E},
title = {Acceptability of Modified Early Obstetric Warning Systems Among Midwives in Malawi; An Exploratory Qualitative Study.},
journal = {International journal of women's health},
volume = {18},
number = {},
pages = {605608},
pmid = {42338703},
issn = {1179-1411},
abstract = {BACKGROUND: The Modified Early Obstetric Warning systems (MEOWS) has received global endorsement as a key strategy for reducing maternal mortality over the past decade. However, evidence on MEOWS acceptability among midwives in sub-Saharan Africa, including Malawi, remains limited. Understanding how potential users perceive a newly introduced intervention is required to assess acceptability prior to implementation.

PURPOSE: To explore the acceptability of MEOWS among midwives using Sekhon's Theoretical Framework of Acceptability.

METHODS: We conducted an exploratory qualitative study between June and August 2025. Using purposive sampling, midwives across practicing, supervisory and policy making levels from Bwaila Hospital and Kamuzu Central Hospital were recruited for in-depth interviews. Data were analyzed using a deductive thematic approach with a priori coding guided by Sekhon et al's Theoretical Framework of Acceptability (TFA).

RESULTS: Thirty participants were interviewed. MEOWS was found acceptable across the seven domains of Sekhon et al's TFA. Participants reported that MEOWS could guide clinical judgement and ease the workload. However, inadequate stationery and equipment were identified as key sources of burden that may threaten sustained use.

CONCLUSION: This study demonstrated that MEOWS was broadly acceptable among the various levels of midwives. The study identified inadequate stationery and equipment as potential barriers. Addressing these challenges may sustain MEOWS adaptation and implementation,enable early identification of maternal critical illness and reduction of maternal deaths.},
}

@article {pmid42338888,
year = {2026},
author = {Sanchis-Sanchis, CE and Sancho-Cantus, D and Sanchis-Sanchis, E and Privado, J and Roig, FJ and Cuerda-Ballester, M and Bargues-Navarro, G and Cubero-Plazas, L and Martínez Bolós, P and Cárdenas Salazar, RG and Ortí, JER},
title = {Interplay between B vitamins, fiber, and Bacteroides abundance: a predictive model for anxiety and depression in amyotrophic lateral sclerosis.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1815390},
pmid = {42338888},
issn = {1664-302X},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive and incurable neurodegenerative disease that not only affects motor function but is also associated with gastrointestinal and emotional disturbances. Recent research highlights the potential role of gut microbiota and diet in modulating these symptoms, suggesting a complex interaction between nutrition, intestinal health, and presence of anxiety and depression in ALS patients. This study aims to investigate the relationship between dietary intake, gut microbiota composition, and presence of anxiety and depression in patients with amyotrophic lateral sclerosis (ALS).

METHODOLOGY: A cross-sectional study conducted with a sample of 48 patients with bulbar-onset or spinal-onset ALS from different regions of Spain. Dietary intake was assessed through 24-h records and food frequency questionnaires, while anxiety and depression were evaluated using validated scales that formed a latent factor called emotional distress. Stool consistency was assessed following the Bristol Stool Scale and the abundance of bacterial microbiota was quantified.

RESULTS: Confirmatory factor analysis identified a nutritional factor composed of vitamins B1, B2, B9, C, and fiber, revealing a significant inverse association with anxiety and depression levels. The predictive model revealed both direct and indirect effects of this factor on presence of anxiety and depression, mediated by Bacteroides abundance and stool consistency.

CONCLUSION: This model explained 19% of the variance in psychological distress. Our findings suggest that a diet rich in B vitamins, C vitamin and fiber may help improve emotional well-being in patients with ALS, highlighting the importance of nutritional strategies, as well as the role of Bacteroides related to stool consistency in patients with ALS.},
}

@article {pmid42324612,
year = {2026},
author = {Alwarnaidu Vijayarajan, VB and Vijayakumar, I and Ruiz-Partida, R and Runge, F and Torra, J and Lozano-Juste, J and Forristal, PD},
title = {Pro-197 mutations confer resistance to thiencarbazone but not to foramsulfuron in ALS-resistant Poa annua populations.},
journal = {Pest management science},
volume = {},
number = {},
pages = {},
doi = {10.1002/ps.71051},
pmid = {42324612},
issn = {1526-4998},
support = {//Department of Agriculture, Food and the Marine, Ireland/ ; //European Regional Development Fund/ ; //European Union (FEDER), 'ERDF A way of making Europe'/ ; },
abstract = {BACKGROUND: Poa annua is currently a lower-priority arable weed in Ireland; however, increasing target-site resistance to acetolactate synthase (ALS) inhibitors and declining availability of non-ALS herbicides highlight emerging control challenges. ALS-inhibiting co-formulations of foramsulfuron + thiencarbazone have been specifically developed for use in herbicide-tolerant beet varieties. While foramsulfuron can control grass weeds carrying specific target-site mutations, its efficacy within the co-formulation on ALS-resistant populations remains unknown. We addressed this knowledge gap using genetic characterisation, dose-response and interaction analyses, and ligand docking modelling in 12 independently evolved, ALS-resistant, Poa annua populations carrying Pro-197 or Trp-574 mutations.

RESULTS: All Pro-197 variants (Thr, Gln or Ala) were thiencarbazone-resistant (resistance index (RI) = 20.9-33.3) but remained foramsulfuron-sensitive (2.5-4), while the co-formulation showed reduced efficacy (5.5-6.2). Interaction analyses showed no overall deviation from additivity for Pro-197 populations (P > 0.05), although antagonism occurred at reduced rates (P < 0.05). Structural modelling and ligand docking analyses indicated that most Pro-197 substitutions did not alter the ALS catalytic tunnel. Foramsulfuron retained extensive hydrogen-bonding and electrostatic interactions, with a more favourable binding free energy than thiencarbazone, which showed fewer interactions and a less favourable free energy. Trp-574-Leu variants exhibited cross-resistance to all treatments, consistent with disruption of key binding interactions.

CONCLUSION: This study demonstrates that foramsulfuron + thiencarbazone efficacy on Pro-197-resistant Poa annua populations is poor, despite these populations being sensitive to foramsulfuron used alone. Consequently, this co-formulation, developed for ALS-tolerant beet, should be restricted to fields without ALS-resistant weeds to ensure effective in-crop control and avoid selection for resistance. © 2026 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.},
}

@article {pmid42324839,
year = {2026},
author = {Felice, KJ and Leighton, DB and Daniel, AS and Cartwright, NI and Benchaya, LM},
title = {The Impact of Sponsored Genetic Testing in 170 Consecutive Consenting Patients With Amyotrophic Lateral Sclerosis: A Single-Site Retrospective Review.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70313},
pmid = {42324839},
issn = {1097-4598},
abstract = {INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) is often categorized as sporadic (sALS) or familial (fALS) based on the family history. Several recent genetic studies have found disease-causing variants in 50%-85% of patients with fALS and 10%-15% of those with sALS. The aim of our study is to review our clinical experience with sponsored genetic testing (i.e., pharmaceutical company-sponsored and cost-free to patient) since its inception.

METHODS: We reviewed the medical records on all ALS patients seen at our Center who consented to sponsored genetic testing from August 2021 through October 2025.

RESULTS: Of the 170 medical records reviewed, 22 patients (12.9%) tested positive for a disease-causing variant in a known autosomal dominant disorder. Thirteen of 35 patients with fALS (37.1%) were found to have a disease-causing variant, in contrast to 9 of 135 patients (6.7%) with sALS. Of the 22 disease-causing variants found, the following genes were involved in decreasing frequency: C9orf72 11 (50%), SOD1 6 (27.3%), FUS 2 (9.1%), and one each (4.5%) of SQSTM1, TARDBP, and TBK1. Twenty-eight patients (16.5%) harbored 29 variants of uncertain significance (VUS).

DISCUSSION: Results of testing led to medically actionable activities including genetic counseling for patients and at-risk family members with positive results, and treatment (i.e., intrathecal tofersen) for the two patients harboring pathogenic SOD1 variants. The lower diagnostic yields than previously published for fALS and sALS patients likely are related to lower numbers of genes tested in the sponsored genetic panels, and these are expected to improve as more genes are added.},
}

@article {pmid42324866,
year = {2026},
author = {Hannaford, AM and Supnet, IE and Pavey, N and Menon, P and van den Bos, MAJ and Kiernan, MC and van Alfen, N and Simon, NG and Vucic, S},
title = {Muscle Ultrasound Is a Sensitive Outcome Measure in ALS.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70317},
pmid = {42324866},
issn = {1097-4598},
abstract = {INTRODUCTION/AIMS: Muscle ultrasound is a potential outcome measure in amyotrophic lateral sclerosis (ALS), although prospective, multicenter longitudinal studies are lacking. This study aimed to evaluate muscle ultrasound as an outcome in ALS and compare its sensitivity with clinical and neurophysiological metrics.

METHODS: In this prospective two-center cohort study, adults with ALS underwent baseline and follow-up assessments at least 3 months apart. Clinical measures included the ALS Functional Rating Scale-Revised (ALSFRS-R) and Medical Research Council sum scores. Median nerve abductor pollicis brevis and ulnar nerve first dorsal interosseous compound motor action potential (CMAP) amplitudes were recorded. Muscle ultrasound of 11 bulbar and limb muscles was performed using harmonized protocols, with offline analysis of muscle thickness and echogenicity. Longitudinal change and effect sizes were calculated.

RESULTS: Twenty-two patients were included (median age 59.3 years, follow-up 9.6 months, disease duration 23.1 months). ALSFRS-R declined by -3.0 points (-0.7% per month; effect size 0.84). Median nerve CMAP amplitude decreased by -1.6 mV (-1.2% per month; effect size 0.77). Muscle echogenicity increased by 0.8 units (+6.0% per month), yielding the largest effect size (1.09), with increases across multiple muscles. Responsiveness improved with onset-specific muscle selection, with biceps brachii (effect size 1.12) and gastrocnemius (1.18) showing the strongest changes. Muscle thickness and fasciculation frequency did not change.

DISCUSSION: Muscle ultrasound echogenicity is a sensitive structural biomarker of ALS progression, demonstrating greater responsiveness than ALSFRS-R and CMAP over 3-12 months. Its accessibility and sensitivity support its utility as an outcome measure in clinical trials.},
}

@article {pmid42325426,
year = {2026},
author = {Luitel, NP and Sainju, P and Lamichhane, B and Khadgi, R and Gautam, K},
title = {Breaking down barriers: A qualitative study of demand- and supply-side barriers to depression care in Nepal.},
journal = {Global mental health (Cambridge, England)},
volume = {13},
number = {},
pages = {e121},
pmid = {42325426},
issn = {2054-4251},
abstract = {Despite global initiatives like WHO's mhGAP, mental health treatment gaps remain substantial, especially in LMICs. Barriers are often presented collectively, with an emphasis on supply-side solutions, while demand-side factors are frequently overlooked. Distinguishing these barriers and implementing tailored strategies is critical for improving access and utilization. This study explores stakeholders' perceptions and experiences of demand- and supply-side barriers to mental healthcare in Nepal. Qualitative interviews were conducted with 65 community stakeholders, including people with lived experience, using vignettes and the McGill Illness Narrative Interview (MINI) guide. Data were analyzed thematically in NVivo and interpreted through Levesque et al.'s access framework, which examines health system characteristics and individual capabilities. Demand-side barriers included spiritual attributions of mental illness, stigma, low perceived need, financial hardship, lack of family support and limited awareness of conditions and available services. These factors hindered recognition, help-seeking, affordability and engagement. Supply-side barriers involved frequent staff transfers, inadequate training, lack of privacy, poor infrastructure and irregular psychotropic medicine supply, affecting service acceptability, availability and appropriateness. Access to mental healthcare in Nepal is shaped by interconnected demand- and supply-side barriers. Addressing these requires culturally sensitive stigma-reduction, mental health literacy programs, workforce stabilization, reliable medication supply, privacy-friendly facilities and financial protection.},
}

@article {pmid42327318,
year = {2026},
author = {Mot, AI and Li, Y and Dibaj, P and Tzvetanova, ID and Gerwig, UC and Bogale, TA and Goebbels, S and Möbius, W and Bergles, DE and Morrison, BM and Rothstein, JD and Cleveland, DW and Edgar, JM and Nave, KA},
title = {Mutant SOD1 expressed by oligodendrocytes aggregates in myelinic nanochannels and accelerates disease progression in familial ALS mice.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.06.09.731100},
pmid = {42327318},
issn = {2692-8205},
abstract = {UNLABELLED: Amyotrophic lateral sclerosis (ALS) is a highly debilitating and fatal disease characterized by the progressive loss of motor neurons. Reduced oligodendroglial support has been implicated in ALS progression but remains mechanistically unexplained. Here, using a mutant superoxide dismutase 1 (SOD1-G37R) mouse model of familial ALS, Cre-mediated excision of the mutant SOD1 gene within the oligodendrocyte lineage prior to myelin compaction is shown to slow disease onset, improve motor performance, and prolong survival. In contrast, silencing mutant SOD1 expression within oligodendrocytes after myelin compaction failed to ameliorate disease phenotype. Electron microscopy is used to identify aggregation of mutant SOD1 within paranodal loops and the inner periaxonal tongue of 'myelinic nanochannels', narrow cytosolic compartments for the diffusion of metabolites and motor-driven transport processes. In a second mouse model (SOD1-G93A) of familial, SOD1 mutant-mediated ALS, we show that induction of excessive myelin compaction and myelinic channel collapse (by depletion of CNP from myelin) accelerates disease and diminishes survival. Our data support loss of myelinic channel integrity as a contributor to familial ALS disease initiation and progression, findings likely relevant to neurodegenerative disease involving other aggregation prone proteins that are expressed in myelinating oligodendrocytes.

SIGNIFICANCE STATEMENT: Oligodendrocytes have been implicated in the progression of amyotrophic lateral sclerosis (ALS) but the underlying mechanisms have remained obscure. Here we show in genetic mouse models that the familial ALS causing isoform of a ubiquitously expressed mutant enzyme (SOD1) aggregates in cytosolic channels within myelin that are responsible for delivery of transporters and nutrients necessary to support the axonal compartment. ALS disease progression was accelerated in mice when myelinic channels were collapsed by deleting CNP, a structural protein necessary for myelinic channel maintenance. Disruption of transport through myelinic channels by aggregation of mutant SOD1 may perturb oligodendrocyte support of motor axons and contribute to disease in this form of ALS.},
}

@article {pmid42327368,
year = {2026},
author = {Gatt, A and Buhidma, Y and Fodder, K and Humphrey, J and Foti, SC and Frias, B and Benson, BC and Gami-Patel, P and Gittings, LM and Toomey, CE and Lashley, T},
title = {Transcriptomic and pathological analysis of the hnRNP network reveals glial involvement in frontotemporal lobar degeneration pathological subtypes.},
journal = {Brain communications},
volume = {8},
number = {3},
pages = {fcag197},
pmid = {42327368},
issn = {2632-1297},
abstract = {Frontotemporal dementia is a neurodegenerative disorder with a strong heritable component. Frontotemporal lobar degeneration refers to the pathological changes seen in frontotemporal dementia, characterized by atrophy of the frontal and temporal lobes and the presence of abnormal protein inclusions. In the case of frontotemporal lobar degeneration with hyperphosphorylated TDP-43 positive inclusions (FTLD-TDP), five pathological subtypes (A, B, C, D and E) are observed based on the types and distribution of inclusions found in the brain. In all subtypes, there tends to be a large variability in the number of pathological inclusions observed between cases, with limited correlation to clinical manifestations. TDP-43 is an RNA-binding protein belonging to the heterogeneous nuclear ribonucleoprotein (hnRNP) family, which along with other hnRNPs, modulates multiple aspects of RNA processing. HnRNPs other than TDP-43 have been implicated in several neurological diseases, including Amyotrophic Lateral Sclerosis, FTLD-TDP, frontotemporal lobar degeneration with fused in sarcoma (FTLD-FUS) and Alzheimer's disease. Multiple hnRNPs have been found in pathological inclusions in specific subtypes of FTLD-TDP, suggesting potential roles in the disease process. The role of the hnRNP network in frontotemporal lobar degeneration disease pathogenesis, however, has not yet been investigated. This study aimed to comprehensively evaluate the presence and expression of hnRNP proteins in two pathological subtypes of sporadic FTLD-TDP (A and C) as well as the genetic form FTLD-TDP A C9orf72 using immunohistochemistry and gene expression analysis by single-nuclei RNA-sequencing. We found that there was great variability in the frequency of TDP-43 pathology across and within FTLD-TDP pathological subtypes. Our findings suggest that distinct global transcriptomic profiles may underlie the different pathological subtypes of FTLD-TDP. The most prominent transcriptomic changes were observed in oligodendrocytes and astrocytes, involving multiple hnRNPs across frontotemporal lobar degeneration subtypes compared to controls. Transcriptomic co-expression analysis further revealed that glial clusters were more strongly associated with RNA-processing dysfunction and contributed to disease classification. Together, these findings highlight the involvement of the hnRNP network and glial-specific RNA-processing alterations in FTLD-TDP pathophysiology, offering new insight into the molecular distinctions between pathological subtypes and potential targets for future investigation.},
}

@article {pmid42328197,
year = {2026},
author = {Safir, AH and Blackwell, AF and Debnath, R},
title = {Resisting epistemic loss in AI image generation.},
journal = {Patterns (New York, N.Y.)},
volume = {7},
number = {6},
pages = {101568},
pmid = {42328197},
issn = {2666-3899},
abstract = {Hintze et al.'s recent study highlights the tendency of current-generation vision-language models to converge on overly generic outputs. We argue that considering AI imageries as epistemic artefact and AI-driven artistic practices as socio-cultural processes can provide better understandings around the implications of such conditions beyond merely technical aspects of image generation. Drawing from our ongoing research, we highlight the necessity of bringing the epistemic vulnerability of marginalized artists and users and their hierarchical relations with these tools into sociotechnical design conversations, and by doing so, to explore the possibility for pluriversal and just AI futures, particularly in the Global South.},
}

@article {pmid42328245,
year = {2026},
author = {Dong, J and Lu, M and Chen, Y and Zisman-Ilani, Y and Feng, Y and Zhang, S and Huang, H and Zhou, Y},
title = {Bridging the Gap Between Efficacy and Practice: A Systematic Review of Shared Decision-Making in Severe Mental Illness.},
journal = {Journal of multidisciplinary healthcare},
volume = {19},
number = {},
pages = {610845},
pmid = {42328245},
issn = {1178-2390},
abstract = {Shared decision-making (SDM) is recommended for preference-sensitive treatment decisions in severe mental illness, but its routine use in psychiatric services remains inconsistent. This systematic review synthesized evidence published between 2014 and 2024 and examined clinical, cultural, and organizational factors associated with SDM implementation. We searched PubMed, Embase, CINAHL, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP for studies published from January 2014 to November 2024. Forty-two studies involving 8798 participants were included. Reporting followed PRISMA 2020 and SWiM guidance. Study quality was assessed with design-specific Joanna Briggs Institute tools, and certainty of key findings was appraised using a combined GRADE-CERQual approach. Because of heterogeneity in study design, interventions, outcomes, and settings, findings were synthesized narratively using Popay et al's framework. Patient decision aids were generally associated with lower decisional conflict, greater readiness, satisfaction, involvement, or autonomy, with little evidence of meaningful consultation-time extension. Clinician training and SDM interventions improved short-term engagement and information sharing, but evidence for sustained improvements in adherence, decisional conflict, and clinician behavior was mixed or low certainty. Family-mediated or triadic decision-making was prominent in East and Southeast Asian studies and may support adherence and participation, although it can also create tension between patient autonomy and family preferences. Across studies, clinicians and patients often emphasized different treatment priorities, particularly symptom control versus side-effect tolerability. Evidence was concentrated in Europe and East Asia, with limited data from low-resource regions. SDM in psychiatric care appears most reliable for improving immediate decision processes rather than long-term outcomes. Future implementation should test culturally adapted triadic decision aids, workflow-integrated prompts, and interprofessional decision coaching while using cautious, context-sensitive outcome evaluation.},
}

@article {pmid42329291,
year = {2026},
author = {Sathick Batcha, BR and Amarnath, DP and Srinivasan, D and Ramakrishnan, P},
title = {Targeting mitochondrial dysfunction and neuroprotection in neurodegenerative disorders: emerging therapeutic potential of berberine and polymeric nanoparticle-based delivery systems.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {42329291},
issn = {1568-5608},
abstract = {Major neurodegenerative disorders, such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis, are pathologically driven by mitochondrial failure and persistent neuroinflammation. Defects in oxidative phosphorylation, excess Reactive Oxygen Species (ROS), and impaired mitophagy cause an imbalance in neuronal energy and promote the release of mitochondrial Damage-Associated Molecular Patterns (DAMPs) that activate microglial inflammasomes and enhance inflammatory signalling. Current therapeutic strategies have largely targeted individual pathways and have been unable to effectively modulate this interrelated mitochondrial immune axis or achieve efficient delivery to the Central Nervous System (CNS). This review addresses the dual promise of berberine therapy, a biologically active plant alkaloid that enhances mitochondrial production via AMPK/PGC-1α and SIRT1, restores membrane potential, promotes mitophagy, and inhibits NF-κB and NLRP3-mediated inflammation. Nevertheless, this compound's weak solubility, limited bioavailability, and extremely poor Blood-Brain Barrier (BBB) penetration limit its therapeutic application. Encapsulation of berberine in polymeric nanoparticles, including Polyethylene glycol (PEG)-based polymeric nanoparticle systems, offers improved stability, bioavailability, and targeted mitochondrial delivery. An effective method for reducing neuroinflammation and mitochondrial dysfunction is this comprehensive phytochemical nanotechnology technique.},
}

@article {pmid42329964,
year = {2026},
author = {Fernandes, APM and Bertucci Borges, LH and Holanda, LJ and Bezerra, BHES and Lopes, ACSM and Silva, MCFD and Valentim, RAM and Bougrain, L and Vasiljevic, GAM and Rodrigues Lindquist, AR},
title = {Applications of electromyography in Amyotrophic Lateral Sclerosis: A systematic review.},
journal = {PloS one},
volume = {21},
number = {6},
pages = {e0350029},
pmid = {42329964},
issn = {1932-6203},
mesh = {*Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Humans ; *Electromyography/methods ; Motor Neurons/physiology ; Muscle, Skeletal/physiopathology ; },
abstract = {This systematic review examined the use of surface electromyography (sEMG) for the neuromuscular assessment of individuals with Amyotrophic Lateral Sclerosis (ALS), focusing on clinical parameters, the muscle groups evaluated, acquisition protocols, technical properties of the recording systems, integration with other technologies, and signal processing strategies. We included observational studies that applied sEMG to individuals diagnosed with ALS, with or without comparison to healthy controls, and without restrictions on publication year. The analyses included signals recorded at rest and during voluntary contractions, with or without the use of biofeedback. Most studies employed conventional or high-density surface electrodes, with sampling frequencies ranging from 500 Hz to 3000 Hz. The results showed that the primary parameters assessed were muscle fatigue, fasciculation patterns, the number of motor units (MUNE/MUNIX), motor unit firing rates, and signal complexity. These parameters demonstrated sensitivity to disease progression and may contribute to early diagnosis, phenotypic stratification, and functional monitoring of ALS. Additionally, the studies highlighted the increasing use of advanced computational approaches, such as machine learning, for feature extraction and automated classification. In conclusion, sEMG is a promising tool for functional assessment in ALS, with the potential to improve diagnostic accuracy and support new therapeutic strategies based on electrophysiological biomarkers. However, despite technological advances, the included studies displayed substantial methodological heterogeneity and limited protocol standardization. Integration with other neurophysiological modalities also remains underexplored, despite its significant clinical potential.},
}

*Amyotrophic Lateral Sclerosis/physiopathology/diagnosis
Humans
*Electromyography/methods
Motor Neurons/physiology
Muscle, Skeletal/physiopathology

@article {pmid42332177,
year = {2026},
author = {Tang, M and Fleming, E and Gu, J and Shi, H and Xu, Y and Gong, X},
title = {Trace Elements Dyshomeostasis and Toxic Metals Neurotoxicity in Neurodegenerative Diseases.},
journal = {Biological trace element research},
volume = {},
number = {},
pages = {},
pmid = {42332177},
issn = {1559-0720},
support = {Grant No. SH2023078//the Zhenjiang Science and Technology Plan Project/ ; Grant No. JDYY2023009//the Medical Education Collaborative Innovation Fund of Jiangsu University/ ; Grant No. 32002235//the National Natural Science Foundation of China/ ; },
abstract = {Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, are defined by the progressive loss of neurons through interconnected pathological mechanisms, including oxidative stress, mitochondrial dysfunction, protein aggregation, and neuroinflammation. Accumulating evidence implicates metal dyshomeostasis as a central and multifaceted contributor to these mechanisms, with roles ranging from a primary pathogenic driver in AD and PD, to a secondary amplifier of genetic pathology in HD and ALS, and as a contextual risk modifier in the presence of toxic metals. Essential trace metals such as iron, zinc, copper, manganese, selenium, iodine, and molybdenum are vital for neurotransmission, antioxidant defense, and cellular metabolism. Dysregulation of these metals disrupts redox balance, impairs proteostasis, and activates regulated cell death pathways, including ferroptosis and cuproptosis. Toxic metals, such as lead, cadmium, and mercury, exacerbate neurodegeneration by displacing essential metals, inducing oxidative injury, and promoting protein misfolding and neuroinflammation. This narrative review synthesizes mechanistic, experimental, genetic epidemiological, and clinical evidence to critically evaluate the contributions of both essential and toxic metals to neurodegeneration in AD, PD, HD, and ALS. We examine the genetic, environmental, and physiological determinants of metal homeostasis; the analytical techniques for quantifying metals in clinical samples; and clinical trial data on metal-targeted therapeutic strategies. Notably, iron chelation with deferiprone consistently reduces brain iron on neuroimaging but worsens clinical outcomes in both PD and AD, presenting a translational paradox that requires mechanistic re-evaluation. We also provide methodological recommendations for interpreting Mendelian randomization studies of metal exposures and propose translational priorities to advance metal-targeted diagnostics and therapeutics for neurodegenerative diseases.},
}

@article {pmid42333562,
year = {2026},
author = {Srivastava, V and Chakraborty, S and Srivastava, R},
title = {Toll-Like Receptor-Mediated Neuroinflammation and Its Role in Neurocognitive Functions.},
journal = {Current reviews in clinical and experimental pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/0127724328415188260605204430},
pmid = {42333562},
issn = {2772-4336},
abstract = {Toll-like receptors (TLRs) are a family of pattern recognition receptors that recognise both pathogen-associated and damage-associated molecular patterns. While their expression was initially believed to be restricted to immune cells, accumulating evidence now demonstrates their presence across multiple neural cell types. Due to their significant involvement in neuroinflammatory and neurodegenerative processes, TLRs have garnered growing attention for their potential contributions to neurocognitive disorders, including Alzheimer's disease, Parkinson's disease, stroke, amyotrophic lateral sclerosis, and other forms of dementia. Potential treatment targets for lowering neuroinflammation and slowing the evolution of neurocognitive diseases include TLR signalling pathways, namely the MYD88-dependent and TRIF-dependent cascades. To initiate signalling, Toll-like receptors (TLRs) recruit specific adaptor molecules that activate the transcription factors NF-κB and IRFs, which regulate the induction of innate immune responses. Over the past decade, a combination of genetic, biochemical, structural, cellular, and bioinformatics approaches has been utilised to elucidate the detailed molecular mechanisms underlying TLR signalling. These studies have clarified how TLRs interact with cytosolic innate immune sensors to orchestrate effective immunological reactions. The function of different TLRs expressed in various brain immune cells and their contribution to the pathophysiology of neuroinflammation are described. This paper discusses the involvement of TLRs in autoimmune and neuroinflammatory circumstances like multiple sclerosis (MS), bacterial meningitis, viral encephalitis, stroke, Alzheimer's disease, and Parkinson's disease. It is intended for TLR biologists and immunologists studying neuroinflammation, as well as neuroscientists delving into central nervous system processes mediated by TLRs.},
}

@article {pmid42318821,
year = {2026},
author = {Preetam, S and Mishra, R and Thapliyal, S and Mondal, S and Rustagi, S and Govindarajan, RK and Pandit, S and Bora, J and Talukdar, N and Rabbee, MF and Malik, S},
title = {3D-printed lab-on-chip platforms for the detection of neurodegenerative diseases: opportunities and challenges.},
journal = {Journal of materials chemistry. B},
volume = {},
number = {},
pages = {},
doi = {10.1039/d6tb00381h},
pmid = {42318821},
issn = {2050-7518},
abstract = {Neurodegenerative diseases (NDs) such as Alzheimer's, Parkinson's, and ALS remain some of the most challenging disorders to diagnose at an early stage. Conventional approaches rely on costly neuroimaging or invasive cerebrospinal fluid sampling, which limit accessibility and early intervention. Recent advances in 3D printing have enabled rapid prototyping of lab-on-chip (LOC) platforms that integrate microfluidics, biosensors, and biological models to detect disease-specific biomarkers with high sensitivity and throughput. Herein, we explore the synergistic role of 3D printing technologies and biomaterials in fabricating LOC systems for NDs. We highlight key biomarkers, and neuron- and organoid-on-chip platforms, and discuss the challenges and opportunities in clinical translation. By combining technical innovation in additive manufacturing with biological relevance, 3D-printed LOC devices represent a transformative approach toward precision diagnostics in neuro-medicine.},
}

@article {pmid42319999,
year = {2026},
author = {Pacheco-Ortega, GA and Esquivel-Zapata, O and Piña-Rosales, E and Davila-Ortíz de Montellano, DJ and Yescas Gomez, P and Medina-Rioja, R},
title = {Teaching Video NeuroImage: Beyond Cognition: Amyotrophic Lateral Sclerosis-Like Disease in PSEN1 c.1292C>A (Jalisco Founder Effect) Variant.},
journal = {Neurology},
volume = {107},
number = {2},
pages = {e218247},
doi = {10.1212/WNL.0000000000218247},
pmid = {42319999},
issn = {1526-632X},
}

@article {pmid42320255,
year = {2026},
author = {Waqar, K and Shaqfeh, M and Mittal, SO},
title = {POLG-associated Parkinson's disease-ALS overlap: A novel variant and first reported use of continuous subcutaneous foslevodopa/foscarbidopa infusion in Brait-Fahn-Schwartz disease.},
journal = {Parkinsonism & related disorders},
volume = {149},
number = {},
pages = {108398},
doi = {10.1016/j.parkreldis.2026.108398},
pmid = {42320255},
issn = {1873-5126},
abstract = {A 38-year-old Emirati man developed levodopa-responsive young-onset parkinsonism followed by electrophysiologically confirmed amyotrophic lateral sclerosis consistent with Brait-Fahn-Schwartz disease. Whole-genome sequencing identified a novel heterozygous POLG variant (c.2620T > A; p. Leu874Met). Motor fluctuations on oral therapy prompted escalation to continuous subcutaneous foslevodopa/foscarbidopa infusion, achieving near-complete motor normalization at twelve months. This is the first reported use of device-aided therapy in POLG-associated parkinsonian-ALS overlap.},
}

@article {pmid42320366,
year = {2026},
author = {Lee, BC and Tsai, JC and Chang, WZ and Wang, CC and Hour, AL and Wang, CC and Tsai, HJ},
title = {Administration of Pgk1 missense mutation leads to more effective mitigation of neurodegenerative effects observed in ALS mice and transgenic zebrafish.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {201},
number = {},
pages = {119674},
doi = {10.1016/j.biopha.2026.119674},
pmid = {42320366},
issn = {1950-6007},
abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of motor neurons (MNs) with few available therapeutic options. Previous ALS studies demonstrated a decrease in phosphoglycerate kinase 1 (Pgk1) secreted from NogoA-overexpressing muscle cells, thus reducing interaction between extracellular Pgk1 (ePgk1) and neural membranous Enolase 2 (Eno2) with consequent inhibition of neurite outgrowth of MNs (NOMN). The negatively charged 419th aspartic acid of receptor Eno2 (Eno2-D419) is a critical residue interacting with the positively charged 353rd lysine of ligand ePgk1-K353. To strengthen the charge attraction, we mutated ePgk1-K353 to arginine (ePgk1-K353R). Compared to wild-type Pgk1, supplementary mutant Pgk1-K353R proved more effective in increasing NOMN derived from NSC34 neural cells cultured in Sol8-vector condition medium. In vivo, Pgk1-K353R-immersed zebrafish embryos exhibited increased caudal primary MNs branching. Intravenous injection of Pgk1-K353R into ALS-mice exhibited more preservative in innervated neuromuscular junctions in gastrocnemius muscle and diaphragm, increased grip strength, higher rearing frequency, 1.6-fold greater locomotive distance and longer survival. For example, median survival days for the control, Pgk1 and Pgk1-K353R groups were 131, 137.5 and 148, respectively. Collectively, we found a single-amino-acid mutant Pgk1-K353R that exhibits higher efficacy to ameliorate neurodegeneration in ALS-mice by delaying disease progression compared to that driven by wild-type Pgk1. We suggest this outcome might be due to more electrostatic attraction between ePgk1-K353R and Eno2-D419 region predicted by in silico analysis. Therefore, mutant Pgk1-K353R protein should be considered a promising neuroprotective drug for ALS treatment.},
}

@article {pmid42320854,
year = {2026},
author = {Pagliarello, C and Girardelli, CR},
title = {Response to Zhang X et al.'s "Effectiveness and Tolerability of Baricitinib with or without Prior Corticosteroids in Alopecia Areata: A Retrospective Cohort Study".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.05.128},
pmid = {42320854},
issn = {1097-6787},
}

@article {pmid42321151,
year = {2026},
author = {Jewett, G and Ferber, R and Josephson, CB and Korngut, L and Lee, J},
title = {Comparison of Consumer Smartwatch and Research-Grade Accelerometer-Derived Step Counts in Amyotrophic Lateral Sclerosis.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70323},
pmid = {42321151},
issn = {1097-4598},
support = {//ALS Canada/ ; },
abstract = {INTRODUCTION/AIMS: Objective, scalable measures of function are needed in amyotrophic lateral sclerosis (ALS). Research-grade accelerometers are promising but may be difficult to deploy for prolonged remote monitoring, whereas consumer smartwatches offer a practical alternative. We evaluated the feasibility of long-term smartwatch monitoring in ALS and compared smartwatch- and accelerometer-derived daily step counts.

METHODS: In this single-centre prospective observational study, participants wore a Fitbit Sense (smartwatch) on the wrist longitudinally and an ActiGraph GT9X Link (accelerometer) on the opposite wrist during clinic-aligned assessment periods. Device comparison was restricted to concurrent valid days (≥ 10 h wear) and included paired comparison of mean daily step counts, Pearson correlation, Bland-Altman analysis, and proportional bias assessment.

RESULTS: Forty participants were enrolled and 39 contributed data across 8093 smartwatch and 915 accelerometer days. Step count comparison included 503 concurrent valid days from 34 participants. Mean daily step counts were 3480 (SD 4365) for smartwatch and 4066 (SD 4797) for accelerometer (p < 0.0001), with strong correlation (r = 0.91, p < 0.0001). Mean bias was -586 steps for smartwatch, with 95% limits of agreement from -4193 to 3021. Among participants with ≥ 6 months of concurrent data, devices showed similar decline over time (interaction p = 0.76).

DISCUSSION: Long-term remote monitoring using a smartwatch was feasible in ALS. Smartwatch-derived step counts were strongly correlated with accelerometer-derived estimates but were systematically lower and showed wide day-level limits of agreement. Smartwatch-derived step counts may be useful for group-level analyses and longitudinal monitoring, though device-specific bias should be considered in interpretation.},
}

@article {pmid42322032,
year = {2026},
author = {de Gea Neves, M and Unger, M and Siesler, HW},
title = {EXPRESS: Monitoring a Polyurethane Synthesis by Fiber-Coupled Attenuated Total Reflection Fourier Transform Infrared Spectroscopy and Multivariate Curve Resolution-Alternating Least Squares.},
journal = {Applied spectroscopy},
volume = {},
number = {},
pages = {37028261464644},
doi = {10.1177/00037028261464644},
pmid = {42322032},
issn = {1943-3530},
abstract = {The step-growth polymerization of 1,4-butanediol with 4,4'-diphenylmethanediisocyanate (MDI) was monitored in situ by fiber-coupled attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy between 40 and 70 °C. In contrast to previous kinetic and two-dimensional correlation spectroscopy (2D-COS) studies of this system, the present work applies multivariate curve resolution alternating least squares (MCR-ALS) to temperature-dependent spectral data. The method enables decomposition of overlapping urethane-related bands and extraction of concentration profiles for chemically and physically distinct species, including dissolved and precipitated polymer phases. The MCR-ALS results are consistent with previously reported kinetic trends while providing additional quantitative insight into transient species and phase evolution. These findings demonstrate the added value of multivariate analysis for the concise interpretation of complex polymerization processes.},
}

@article {pmid42322392,
year = {2026},
author = {Poletti, B and Aiello, EN and Consonni, M and Iazzolino, B and Torre, S and Faltracco, V and Telesca, A and Palumbo, F and Curti, B and De Luca, G and Moreschi, A and Frisco, F and Dalla Bella, E and Bersano, E and Riva, N and Verde, F and Messina, S and Doretti, A and Maranzano, A and Morelli, C and Cappa, SF and Calvo, A and Strong, MJ and Silani, V and Lauria, G and Chiò, A and Ticozzi, N},
title = {ECAS-Based Neuropsychological Phenotyping in Amyotrophic Lateral Sclerosis: A Retrospective Study Comparing Different Algorithms.},
journal = {Neurology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42322392},
issn = {2193-8253},
support = {TRANS-ALS//Agenzia Nazionale di Valutazione del Sistema Universitario e della Ricerca/ ; grant number: 2015-0023//Agenzia Nazionale di Valutazione del Sistema Universitario e della Ricerca/ ; POR FESR 2014-2020//Fondo Europeo di Sviluppo Regionale, Regione Lombardia/ ; grant number: 1157625//Fondo Europeo di Sviluppo Regionale, Regione Lombardia/ ; grant: RF-2016-02362405//Ricerca Sanitaria Finalizzata - Ministero della Salute/ ; grant: 2017SNW5MB//"Progetti di Rilevante Interesse Nazionale" programme of the Ministry of Education, University and Research/ ; grant: RF H2020-SC1-DTH2020-1//Horizon 2020/ ; grant agreement ID: 101017598//Horizon 2020/ ; },
abstract = {INTRODUCTION: This study aimed to compare different algorithms based on the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) to classify patients with amyotrophic lateral sclerosis (ALS) according to their neuropsychological phenotype to identify possible discrepancies among these systems.

METHODS: ECAS-Cognitive and -Carer Interview (ECAS-C/-CI) scores of N = 901 patients with ALS without a formal diagnosis of dementia were retrospectively retrieved. Patients were classified, pursuant to Strong et al.'s criteria, as cognitively and behaviourally normal (ALScbn), cognitively and/or behaviourally impaired (ALSci/bi/cbi), or Possible ALS-FTD, according the following ECAS-based algorithms: (1) Abrahams', solely addressing ECAS-C total and ALS-Specific subtotals; (2) Poletti et al.'s, addressing single task-level ECAS-C scores; (3) "Subscale", addressing ECAS-C subscales (i.e., Language, Executive, Fluency, Memory and Visuospatial). All algorithms relied on single-item-level ECAS-CI scores for behavioural classifications.

RESULTS: Whilst agreement rates among these classifications were moderate to high (84-86%; Cohen's k = 0.78-0.81), and some discrepancies emerged: (1) "ALScbn-to-ALSci" and "ALSci-to-ALScbn" re-classifications occurred across the three comparisons, ranging from ~ 11% to ~ 24%; (2) the most classificatory disagreements (~ 43%) occurred for the ALScbi category when comparing single task-level (Poletti) to total-level (Abrahams) algorithms, with patients being re-classified as either ALSbi or Possible ALS-FTD; (3) ~ 24% of Abraham's Possible ALS-FTD cases were re-classified as either ALScbi or ALSbi by the Subscale approach.

CONCLUSIONS: Different ECAS-based algorithms for deriving Strong's phenotypes might yield slight discrepancies that could under- or overestimate a given classification.},
}

@article {pmid42323602,
year = {2026},
author = {Moll, L and Riessen, R and Dahlmann, P and Häske, D},
title = {Effect of low-dose, high-frequency advanced life support training versus annual full-day training on simulation-based resuscitation performance: a randomized controlled trial.},
journal = {BMC medical education},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12909-026-09717-3},
pmid = {42323602},
issn = {1472-6920},
abstract = {BACKGROUND: Skill decay in advanced life support (ALS) is well documented, yet optimal training frequency remains unclear. This trial compared low-dose, high-frequency ALS training with annual full-day training regarding simulation-based resuscitation performance after one year.

METHODS: In this randomized, controlled, simulation-based trial, 35 emergency medical services (EMS) professionals were allocated to either low-dose, high-frequency ALS training (intervention group, n = 18) or a single annual full-day ALS training (control group, n = 17). Performance was assessed at baseline and after 12 months using a validated 29-item rating instrument covering technical and non-technical skills (NTS), with items rated on a 5-point Likert scale (1 = poor performance, 5 = excellent performance). The primary endpoint was the overall performance score for resuscitation management, defined as the mean across all items. Secondary endpoints included domain-specific performance scores (NTS, defibrillation-related, and cardio-pulmonary resuscitation [CPR] items), calculated as the mean scores for each domain, as well as time to key interventions.

RESULTS: After 12 months, the intervention group showed significantly higher overall performance scores than the control group (4.7 ± 0.2 vs. 4.2 ± 0.3; p < 0.001). The largest between-group difference was observed for NTS (4.8 ± 0.2 vs. 3.9 ± 0.5; p < 0.001). Scores for defibrillation-related and CPR-related items were also significantly higher in the intervention group. Time to CPR initiation (13 ± 2 s vs. 18 ± 7 s; p = 0.015), rhythm analysis (29 ± 9 s vs. 45 ± 24 s; p = 0.015), supraglottic airway insertion (51 ± 13 s vs. 68 ± 30 s; p = 0.013), as well as hands-off time (4 ± 1 s vs. 6 ± 3 s; p = 0.002) were significantly shorter in the intervention group. The rating instrument demonstrated good reliability (Cronbach's alpha 0.793; intraclass correlation coefficient 0.794, 95% confidence interval 0.718-0.854).

CONCLUSION: Low-dose, high-frequency ALS training resulted in higher simulation-based resuscitation performance scores than annual full-day training, particularly for non-technical skills and time-critical processes.

TRIAL REGISTRATION: The study is registered in the German Register of Clinical Studies under the ID DRKS00024822.},
}

@article {pmid42323648,
year = {2026},
author = {Girling, C and Ryan, G and Bradburn, M and Caprioli, T and Dawson, S and Fisher, E and Haynes, N and Herbert, E and Hill, H and Hind, D and May, C and Bianchi, S and Cox, M and Kaltsakas, G and Massey, C and Mayberry, E and Messer, B and Needham, D and Playle, R and McDermott, C and Griffiths, AW and Hobson, E},
title = {Delivering effective non-invasive ventilation in amyotrophic lateral sclerosis using intensive remote support (DENIM): protocol for an embedded process evaluation in a hybrid type 3 implementation-effectiveness trial.},
journal = {Implementation science communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s43058-026-01023-9},
pmid = {42323648},
issn = {2662-2211},
support = {NIHR158715//Health Services and Delivery Research Programme/ ; },
abstract = {BACKGROUND: Non-invasive ventilation (NIV) is the only intervention that significantly improves survival and quality of life in motor neuron disease, extending life by 8-13 months. However, at least half of patients are unable to reach the recommended ≥ 4 h daily NIV use, and current NHS services provide insufficient follow-up for intensive optimisation. Delivering Effective Non-Invasive ventilation in Motor neuron disease using intensive remote support (DENIM) is a stepped-wedge cluster randomised trial. This protocol describes a process evaluation embedded within DENIM aiming to understand how and why the implementation strategy works (or does not work) across different contexts.

METHOD: The process evaluation employs a convergent mixed-methods multiple-case study design across twelve NHS ventilation services. We developed a programme theory informed by Normalization Process Theory (NPT), the Consolidated Framework for Implementation Research and Expert Recommendations for Implementing Change, which states how the DENIM implementation strategy is expected to achieve normalisation of evidence-based NIV practice. Data collection across twelve sites include: ethnographic observations of patient-staff interactions; semi-structured interviews with staff (n = 24-48) and patients/carers (n = 24) exploring implementation experiences; the NoMAD questionnaire measuring normalisation perceptions from healthcare professionals within the services and NIV adherence data from participants' ventilators. Barriers and facilitators to research participation for underserved populations including ethnic minorities, those with low digital literacy, and women over 80 with bulbar onset disease will also be identified. Qualitative data will be analysed using NPT-informed thematic analysis. Integration occurs at three levels (design, methods, interpretation) with joint display tables presenting quantitative and qualitative findings alongside meta-inferences.

DISCUSSION: This process evaluation will generate explanatory insights into how implementation strategies can address the evidence-to-practice gap in complex, technology-supported care for progressive diseases, with implications for health equity and wider NHS digital transformation.

TRIAL REGISTRATION: ISRCTN10105285. 16/04/2025.},
}

@article {pmid42324254,
year = {2026},
author = {Di Lazzaro, V and Pellegrino, G and Corp, DT and Musumeci, G and Capone, F and Pilato, F and Mazzone, P and Insola, A and Ranieri, F},
title = {Direct evidence of upper motor neuron excitability changes in a patient with ALS.},
journal = {Journal of neurophysiology},
volume = {},
number = {},
pages = {},
doi = {10.1152/jn.00208.2026},
pmid = {42324254},
issn = {1522-1598},
support = {T4-AN-09//Ministero della Salute (Italy Ministry of Health)/ ; },
abstract = {A key feature of amyotrophic lateral sclerosis (ALS) pathophysiology is motor neuron hyperexcitability. However, the mechanisms of hyperexcitability are not well understood. Prior studies have used transcranial magnetic stimulation (TMS) to demonstrate increased motor cortex excitability and reduced intracortical inhibition in human ALS. Yet interpretation of these findings is limited because measurement of muscles responses cannot disentangle specific contribution of upper and lower motor neurons and of cortical interneurons to excitability changes. We had the rare opportunity to record directly the corticospinal output evoked by TMS upstream of the spinal circuitry in an ALS patient who had undergone epidural electrode implantation for intractable pain. Single pulse stimulation was performed both with a coil orientation inducing a current that activates corticospinal neurons directly, and with a coil orientation inducing a current that activates corticospinal neurons trans-synaptically. Short interval intracortical inhibition (SICI) was also studied using paired pulse stimulation. Data obtained in the patient were compared with those recorded in 10 conscious control subjects. Compared to control subjects, patient showed a reduced amplitude in response to direct corticospinal neuron activation, yet an enhanced amplitude of corticospinal output after trans-synaptic corticospinal neuron activation together with a SICI reduction. Present findings provide direct evidence of hyperexcitability of monosynaptic glutamatergic inputs to corticospinal neurons that, in association with reduced intracortical inhibition, can trigger neurodegeneration. Taken together with the extensive body of evidence generated by non-invasive TMS studies, the findings from this single-case study may provide valuable insights into the pathophysiological mechanisms of the disease.},
}

@article {pmid42317831,
year = {2026},
author = {Afshar, AS and Statland, J and Song, X},
title = {Towards Early Prediction of Amyotrophic Lateral Sclerosis Empowered by Machine Learning and Clinical Big Data.},
journal = {AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science},
volume = {2026},
number = {},
pages = {623-632},
pmid = {42317831},
issn = {2153-4063},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by substantial symptom heterogeneity and overlap with other neurological conditions, often delaying diagnosis. This study developed a consensus-based feature selection framework to identify a stable and parsimonious minimal feature set for early ALS prediction using large-scale observational data. Using multi-year medical claims and multi-site EHRs, we identified 1,716 ALS cases with matched controls. The approach integrated variability across sample, task, and model dimensions to isolate features predictive up to 18 months before diagnosis. Predictive models using LASSO regression and GBT were evaluated with AUROC and classification metrics. The resulting nine-feature set achieved AUROC values above 0.85 across time windows. The GBT model was further evaluated in musculoskeletal, nervous system, and limb or bulbar subgroups, demonstrating reliable discrimination and preserved sensitivity and specificity. These findings highlight the potential of stable minimal feature sets to support earlier ALS identification.},
}

@article {pmid42317872,
year = {2026},
author = {Singh, G and Singh, G and Shreya, and Kumari, A and Aran, KR},
title = {Nutrients and bioactive compounds as modifiers of neurodegenerative trajectories: molecular mechanisms, translational barriers, and precision nutrition.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1819432},
pmid = {42317872},
issn = {2296-861X},
abstract = {The Neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), Multiple sclerosis (MS), and Amyotrophic lateral sclerosis (ALS) are a growing health burden across the world with minimal disease-modifying treatment and therapy. It is emerging that neurodegeneration is not only a progressive loss of neurons, but also a nutrient-sensitive systems-level dysfunction that takes the form of redox imbalance, chronic neuroinflammation, mitochondrial dysfunction, impaired proteostasis, and synaptic loss. The aging brain are more prone to metabolic vulnerability, and subclinical deficiencies in essential nutrients and bioactive dietary compounds may exacerbate cellular stress responses that contribute to disease progression. It summarizes the existing data on the effects of nutrients like vitamins, minerals, polyunsaturated fatty acids, and various phytochemicals in modulating neuronal homeostasis by regulating oxidative signaling, inflammatory cascades, mitochondrial resilience, autophagy, and synaptic plasticity. These nutrient-mediated effects collectively influence neuronal survival, synaptic integrity, and cognitive function by affecting disease susceptibility and progression. Additionally newer metabolites of the marine and microbiome act as new neuroactive agents. The evidence from in-vitro and preclinical models, translation to clinical benefit remains inconsistent due to heterogeneity in study design, bioavailability, blood- brain barrier penetration, dosing strategies and disease stage. This review highlights emerging potential of precision nutrition frameworks that integrate nutrigenomics, metabolomics, and microbiome interactions, and individualized metabolic profiling to enable context-dependent and stage-specific interventions. Moreover, conceptualizing neurodegeneration as a nutrient-sensitive, systems level disorder, propose a mechanistically informed and integrative approach that combine targeted nutritional strategies with pharmacological and lifestyle therapies to more effectively modify neurodegenerative trajectories.},
}

@article {pmid42318818,
year = {2026},
author = {Bailey, F and Eun, MW and Hobson, E and McDermott, C and Knox, L},
title = {Understanding apathy in people with amyotrophic lateral sclerosis using motivational theories.},
journal = {Journal of health psychology},
volume = {},
number = {},
pages = {13591053261454342},
doi = {10.1177/13591053261454342},
pmid = {42318818},
issn = {1461-7277},
abstract = {Apathy-a reduction in goal-directed behaviour, cognition, and emotional responsiveness-is a highly prevalent, debilitating symptom in people with amyotrophic lateral sclerosis (pwALS). This study investigated the association between apathy in 69 pwALS and their 54 informal caregivers and constructs from social cognitive theory and self-determination theory. Participants also provided subjective accounts of apathy in semi-structured interviews. Multiple regression analysis demonstrated that constructs from both motivational theories were significant predictors of overall apathy scores and its sub-domains (executive, emotional, initiation), accounting for 32%-64% of the variance. Specifically, frustration of the basic psychological need for competence was a consistent and prominent predictor of greater apathy. Qualitative findings revealed that pwALS lack a clear awareness of apathy, often experiencing it as a manifestation of activities requiring increased physical and temporal effort. Future research should use psychosocial theories to understand apathy and develop interventions.},
}

@article {pmid42317073,
year = {2026},
author = {Stark, T and Müller, S},
title = {PML as a neuroprotective guardian: Leveraging nuclear protein quality control to mitigate neurotoxicity of an ALS-associated NEK1 variant.},
journal = {The FEBS journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/febs.70630},
pmid = {42317073},
issn = {1742-4658},
support = {ID 514894665//Deutsche Forschungsgemeinschaft/ ; ID-494535244//Deutsche Forschungsgemeinschaft/ ; ID-465470262//Deutsche Forschungsgemeinschaft/ ; },
abstract = {Insoluble protein aggregates are a hallmark of neurodegenerative diseases like amyotrophic lateral sclerosis (ALS). The ubiquitin-proteasome system (UPS) serves as a neuroprotective quality control mechanism that clears aggregates. PML nuclear bodies (NBs) were proposed to serve as hubs for SUMO-primed ubiquitylation and degradation of misfolded proteins. Georgiadou et al. provide evidence that an ALS-linked NEK1 truncation mutant is recruited to PML NBs, where it likely undergoes SUMOylation and ubiquitylation. In mice, PML loss exacerbates ALS-like symptoms, while induced PML expression delays disease onset. These findings establish PML as a key regulator of proteostasis and highlight PML induction as a potential therapeutic strategy for ALS and related proteinopathies.},
}

@article {pmid42311464,
year = {2026},
author = {Li, P and Gao, Y and Liu, W},
title = {GLP-1 Receptor Agonists in Neurological Disorders: From Mechanisms to Clinical Translation.},
journal = {Drug design, development and therapy},
volume = {20},
number = {},
pages = {613616},
pmid = {42311464},
issn = {1177-8881},
mesh = {Humans ; *Glucagon-Like Peptide-1 Receptor Agonists ; Animals ; *Nervous System Diseases/drug therapy/metabolism ; *Neuroprotective Agents/pharmacology/therapeutic use ; Glucagon-Like Peptide-1 Receptor/metabolism ; },
abstract = {Glucagon-like peptide-1 receptor agonists, or GLP-1RAs, have been used for years to treat type 2 diabetes and obesity. More recently, it has become clear that these receptors are widely distributed throughout the central nervous system (CNS), which has raised the possibility of repurposing these drugs for neurological disorders. In this review we go through the evidence across a range of neurological conditions, discuss the main mechanisms thought to explain their neuroprotective effects, and point out the hurdles that still need to be cleared before they can be used in the clinic. Preclinical work has been fairly consistent. These drugs activate the cAMP/PKA/CREB pathway to boost BDNF expression. They also turn on the PI3K/Akt pathway, which reins in GSK-3β and cuts down tau hyperphosphorylation. At the same time, they put the brakes on NLRP3 inflammasome activation in microglia and get AMPK dependent mitochondrial biogenesis and autophagy going. In animal models of Alzheimer's disease (AD), Parkinson's disease (PD), ischemic stroke, intracerebral hemorrhage (ICH), Huntington's disease (HD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), depression, epilepsy, and spinal cord injury (SCI), these cellular changes add up to less protein aggregation, less neuron loss, and better functional outcomes. Clinical data are harder to interpret. Some trials have shown modest improvements in cognition or motor function, but others have found no meaningful effect on disease progression. One thing that does not get enough attention is that different GLP-1 receptor agonists cross the blood-brain barrier at widely varying rates, and these differences could well explain why trial results have been so mixed. Looking ahead, getting these drugs into the clinic will depend on choosing the ones that actually reach the CNS, developing biomarkers that can predict who will respond, and designing trials that take disease heterogeneity into account. Seen this way, this review offers a practical framework for turning mechanistic insights into real patient benefit.},
}

Humans
*Glucagon-Like Peptide-1 Receptor Agonists
Animals
*Nervous System Diseases/drug therapy/metabolism
*Neuroprotective Agents/pharmacology/therapeutic use
Glucagon-Like Peptide-1 Receptor/metabolism

@article {pmid42311809,
year = {2026},
author = {Sakakibara, R and Ozono, H},
title = {Affective Forecasting and Memory Biases during the Tokyo and Beijing Olympics.},
journal = {Affective science},
volume = {7},
number = {2},
pages = {273-281},
pmid = {42311809},
issn = {2662-205X},
abstract = {UNLABELLED: This study examined how people predicted and recalled their emotional experiences during the Tokyo and Beijing Olympics, which were held during the COVID-19 pandemic. Building on the theoretical framework proposed by Buechel et al. (2017), which explains how people are likely to overestimate or underestimate their future emotions depending on outcome specifications (e.g., psychological distance, magnitude, and duration), we extended this approach in our study. We investigated whether this model could be applied to real-world public events. Using longitudinal online surveys conducted in Japan before, during, and after the two Olympics, we analyzed the responses of 2,059 participants in the Tokyo Games and 2,595 participants in the Beijing Games. Consistent with Buechel et al.'s framework, the results showed that positive emotions experienced during the Olympics were generally underestimated beforehand, especially among individuals who initially opposed the events. Furthermore, the recollection of emotional experiences was influenced by contextual factors such as the perceived infection situation at the time of recall. These findings contribute to a deeper understanding of affective forecasting and memory biases in the context of real-world events, and demonstrate the applicability of existing theoretical models to large-scale societal situations outside the laboratory.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42761-026-00361-0.},
}

@article {pmid42312499,
year = {2026},
author = {Lavigne-Robichaud, M and Landsbergis, P and Brisson, C and Sembajwe, G and Gilbert-Ouimet, M and Li, J and Milot, A and Trudel, X},
title = {Job strain and ischemic heart disease: the balance of methodological bias and implications for prevention. Response to: Bonde JP et al. The demands-control-support work stress model and risk of ischemic heart disease: causal inference based on observational epidemiology.},
journal = {Scandinavian journal of work, environment & health},
volume = {},
number = {},
pages = {},
doi = {10.5271/sjweh.4315},
pmid = {42312499},
issn = {1795-990X},
abstract = {We read with interest Bonde et al's (1) recent review. We agree with their premise: strengthening causal inference is an important objective for occupational epidemiology. However, we believe the conclusion that "at most, any true effect [of job strain on ischemic heart disease (IHD)] appears to be small" is not supported by a valid appraisal of the available evidence. The pooled relative risk estimate (RRE) of 1.14 is most likely underestimated, as common limitations in the available literature tend to bias results toward the null. The authors acknowledge underestimation sources: nondifferential exposure misclassification, overadjustment for cardiometabolic risk factors, and healthy-worker survivor selection (1). Additional sources of underestimation are not discussed. Dichotomizing exposure by combining active and passive exposures into a single "non-high-strain" category may attenuate risk estimates by increasing heterogeneity in the reference group. Indeed, workers with passive exposure may also be at increased IHD risk (2). The pooled RRE may further be attenuated by sex: women develop IHD at older ages partly due to pre-menopausal estrogen cardioprotection, thus working-age follow-up captures fewer events, reducing pooled estimates and precision (3). Sources of overestimation raised also warrant closer scrutiny. For instance, lower estimates in job-exposure matrix (JEM) studies are interpreted as evidence of upward bias in self-reported studies. However, even when exposure values are imputed within subgroups defined by sex and age, JEM do not fully capture individual-level variability in exposure within occupational categories (4). The resulting non-differential misclassification likely attenuates estimates, a limitation the authors acknowledge but do not take into account in their conclusion. The supporting reference for overestimation relies on a 4-item measure of perceived stress (5), limiting its relevance to job strain. An additional source of overestimation is negative affectivity, in which adverse health perceptions inflate individual-level exposure reports. However, this mechanism is not supported in prospective studies with control for anger, hostility, and cynicism (6, 7). Finally, the authors raise concerns about a health-reporting bias: workers with prodromal IHD symptoms may over-report perceived job strain, inflating observed associations. In prospective studies excluding early incident IHD events, associations were not attenuated and, if anything, marginally strengthened (6, 8), providing no support for reverse causation as a source of overestimation. More broadly, methodological characteristics are presented as isolated binary indicators rather than as interdependent dimensions. This hinders the overall appraisal of study quality. These methodological considerations have implications for burden estimation. There has been considerable debate about whether the population attributable fraction (PAF) of 3.4% that the IPD-Work Consortium reported for job strain and IHD (8) was an underestimate when accounting for exposure misclassification, alternative referent group definitions, and other sources of attenuation identified in the literature (9, 10). A subsequent prospective cohort study designed to address several of the sources of underestimation discussed here estimated that 18.2% of incident IHD were attributable to job strain exposure (11). In sum, while we share Bonde et al's emphasis on causal inference, the balance of methodological bias in this literature is more plausibly downward than unpredictable. Given the substantial burden of IHD, debates about the precise magnitude should not delay the development and evaluation of workplace interventions to reduce job strain and improve cardiovascular health. References 1. Bonde JP, Skaaby S, Flachs EM, Dollard M, Keyes K, Rosengren A et al. The demands-control-support work stress model and risk of ischemic heart disease: causal inference based on observational epidemiology. Scand J Work Environ Health 2026 Apr. [Epub ahead of print]. https://doi.org/10.5271/sjweh.4299. 2. Xu S, Huang Y, Xiao J, Zhu W, Wang L, Tang H et al. The association between job strain and coronary heart disease: a meta-analysis of prospective cohort studies. Ann Med 2015;47(6):512-8. https://doi.org/10.3109/07853890.2015.1075658. 3. Zahiriharsini A, Gilbert-Ouimet M, Hervieux V, Trudel X, Matteau L, Jalbert L et al. Incorporating sex and gender considerations in research on psychosocial work exposures and cardiovascular diseases: A systematic review of 55 prospective studies. Neurosci Biobehav Rev 2024 Dec;167:105916. https://doi.org/10.1016/j.neubiorev.2024.105916. 4. Schwartz JE, Pieper CF, Karasek RA. A procedure for linking psychosocial job characteristics data to health surveys. Am J Public Health 1988 Aug;78(8):904-9. https://doi.org/10.2105/AJPH.78.8.904. 5. Metcalfe C, Davey Smith G, Macleod J, Heslop P, Hart C. Self-reported stress and subsequent hospital admissions as a result of hypertension, varicose veins and haemorrhoids. J Public Health Med 2003 Mar;25(1):62-8. https://doi.org/10.1093/pubmed/fdg013. 6. Lavigne-Robichaud M, Trudel X, Talbot D, Milot A, Gilbert-Ouimet M, Vézina M et al. Psychosocial stressors at work and coronary heart disease risk in men and women: 18-year prospective cohort study of combined exposures. Circ Cardiovasc Qual Outcomes 2023 Oct;16(10):e009700. https://doi.org/10.1161/CIRCOUTCOMES.122.009700. 7. Tiwa Diffo E, Lavigne-Robichaud M, Milot A, Brisson C, Gilbert-Ouimet M, Vézina M et al. Psychosocial stressors at work and atrial fibrillation incidence: An 18-year prospective study. J Am Heart Assoc 2024 Aug;13(16):e032414. https://doi.org/10.1161/JAHA.123.032414. 8. Kivimäki M, Nyberg ST, Batty GD, Fransson EI, Heikkilä K, Alfredsson L et al.; IPD-Work Consortium. Job strain as a risk factor for coronary heart disease: a collaborative meta-analysis of individual participant data. Lancet 2012 Oct;380(9852):1491-7. https://doi.org/10.1016/S0140-6736(12)60994-5. 9. Choi BK, Schnall P, Landsbergis P, Dobson M, Ko S, Gómez-Ortiz V et al. Recommendations for individual participant data meta-analyses on work stressors and health outcomes: comments on IPD-Work Consortium papers. Scand J Work Environ Health 2015 May;41(3):299-311. https://doi.org/10.5271/sjweh.3484. 10. Kivimäki M, Singh-Manoux A, Virtanen M, Ferrie JE, Batty GD, Rugulies R; IPD-Work consortium. IPD-Work consortium: pre-defined meta-analyses of individual-participant data strengthen evidence base for a link between psychosocial factors and health. Scand J Work Environ Health 2015 May;41(3):312-21. https://doi.org/10.5271/sjweh.3485. 11. Lavigne-Robichaud M, Trudel X, Talbot D, Milot A, Pena-Gralle AP, Mésidor M et al. Coronary heart disease attributable to psychosocial stressors at work. JACC Adv 2025 Oct;4(10 Pt 2):102160. https://doi.org/10.1016/j.jacadv.2025.102160.},
}

@article {pmid42312942,
year = {2026},
author = {Zinn, KM and McLaren, MW and Imai, MT and Jayaram, MM and Rothstein, JD and Elrick, MJ},
title = {Enterovirus D68 2A protease causes nuclear pore complex dysfunction and independently contributes to motor neuron toxicity.},
journal = {eLife},
volume = {14},
number = {},
pages = {},
pmid = {42312942},
issn = {2050-084X},
support = {5K12NS098482/NS/NINDS NIH HHS/United States ; K08NS124989/NS/NINDS NIH HHS/United States ; R01NS143998/NS/NINDS NIH HHS/United States ; P50HD103538//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; },
mesh = {*Motor Neurons/virology/pathology ; Humans ; *Enterovirus D, Human/enzymology ; *Nuclear Pore/metabolism ; *Viral Proteins/metabolism ; Nuclear Pore Complex Proteins/metabolism ; *Cysteine Endopeptidases/metabolism ; Myelitis/virology/pathology ; Neuromuscular Diseases ; Central Nervous System Viral Diseases ; },
abstract = {Enterovirus D68 (EV-D68) is an important pathogen associated with acute flaccid myelitis (AFM). The pathogenesis of AFM involves infection of spinal motor neurons and motor neuron death; however, the mechanisms linking EV-D68 infection to selective neurotoxicity are not well understood. Dysfunction of the nuclear pore complex (NPC) has been implicated in motor neuron injury in neurodegenerative diseases such as amyotrophic lateral sclerosis, and the NPC is also modified by picornavirus proteases during infection. We therefore sought to determine the impact of EV-D68 proteases on NPC composition and function. We demonstrate widespread disruption of NPC composition by EV-D68 2A and 3C proteases via direct cleavage of a relatively small number of nucleoporins, notably Nup98 and POM121, by 2A[pro]. Using reporter systems, we demonstrate that 2A[pro] inhibits nuclear transport of protein cargoes and disrupts the permeability barrier of the NPC, while having no apparent effect on RNA export. Independently, we show 2A[pro] is toxic to induced pluripotent stem cell-derived motor neurons by demonstrating a rescue of toxicity with the 2A[pro] inhibitor telaprevir at concentrations insufficient to inhibit viral replication. These findings expand our understanding of EV-D68 neuropathogenesis and provide a rationale for studying the NPC or 2A[pro] as therapeutic targets in AFM.},
}

*Motor Neurons/virology/pathology
Humans
*Enterovirus D, Human/enzymology
*Nuclear Pore/metabolism
*Viral Proteins/metabolism
Nuclear Pore Complex Proteins/metabolism
*Cysteine Endopeptidases/metabolism
Myelitis/virology/pathology
Neuromuscular Diseases
Central Nervous System Viral Diseases

@article {pmid42313222,
year = {2026},
author = {Deng, P and Deng, W and Wang, L and Ye, W and Li, S},
title = {Exercise-Driven NRF2 Activation as a Systemic Neuroprotective Strategy: Integrating Redox Biology, Muscle-Brain Crosstalk, and Therapeutic Targeting in Neurodegeneration.},
journal = {Biochemical genetics},
volume = {},
number = {},
pages = {},
pmid = {42313222},
issn = {1573-4927},
abstract = {Neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's diseases, are characterized by progressive neuronal dysfunction and loss. Recent evidence highlights the importance of the nuclear factor erythroid 2-related factor 2 (NRF2) pathway, a key regulator of cellular defense mechanisms, in maintaining neuronal health and function. A narrative literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar to identify relevant experimental, clinical, and review studies on NRF2 signaling, physical exercise, oxidative stress, muscle-brain crosstalk, and neurodegenerative diseases. Keywords included "NRF2", "Nrf2/Keap1/ARE", "physical exercise", "exercise-induced oxidative stress", "myokines", "exerkines", "Alzheimer's disease", "Parkinson's disease", "Huntington's disease", and "amyotrophic lateral sclerosis". NRF2 modulates the expression of a variety of antioxidant and cytoprotective genes, contributing to the protection of neurons against oxidative stress, inflammation, and protein aggregation, processes central to the pathogenesis of neurodegenerative diseases. Additionally, physical activity has been identified as a powerful modulator of NRF2 activation, with exercise offering neuroprotective effects through the induction of NRF2-mediated pathways. This review explores the interplay between NRF2 activation and physical exercise in the context of neurodegenerative diseases, detailing the molecular mechanisms by which exercise influences NRF2 activity to combat cellular damage and enhance neuroprotection. We discuss the therapeutic potential of combining exercise regimens with NRF2-targeted therapies, highlighting the promise of this dual approach in slowing disease progression, improving cognitive function, and enhancing quality of life in affected individuals. Furthermore, we examine the challenges and future directions for clinical implementation, including optimal exercise protocols and the development of NRF2-based pharmacological interventions. This review underscores the importance of NRF2 as a central mediator of neuroprotection and the therapeutic promise of physical activity in the management of neurodegenerative diseases.},
}

@article {pmid42313307,
year = {2026},
author = {Saini, K and Dhiman, P},
title = {Microglia-driven neuroinflammatory signaling in neurodegeneration: mechanisms and therapeutic opportunities.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {},
pmid = {42313307},
issn = {1573-4978},
mesh = {Humans ; *Microglia/metabolism/pathology/immunology ; *Neurodegenerative Diseases/metabolism/therapy/pathology/immunology ; Animals ; Signal Transduction ; *Neuroinflammatory Diseases/metabolism/pathology/immunology ; Blood-Brain Barrier/metabolism ; Cytokines/metabolism ; Astrocytes/metabolism ; },
abstract = {Neuroinflammation has been identified as a major component to the pathogenesis and progression of many neurodegenerative illnesses, going beyond its traditional role as a protective immune response within central nervous system (CNS). There is growing evidence that persistent activation of peripheral immune pathways, microglia and astrocytes causes progressive neurodegeneration, synaptic loss and progressive neurodegeneration. This review examines the mechanisms of microglia- driven neuroinflammatory signaling and its involvement in major neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Huntington's disease. Key neuroinflammatory mechanisms covered in depth including microglial activation, astrocyte reactivity, peripheral immune cell infiltration, cytokine dysregulation, and blood brain barrier (BBB) disruption. This review also emphasizes the role of neuroinflammation in acute neurological symptoms and mental and cognitive impairments. Glial activation markers, inflammatory cytokines, BBB proteins and kynurenine pathway metabolites are emerging as promising biomarkers for disease diagnosis and monitoring. Additionally, the potential of new mathematical and systems level computational models to describe intricate neuroimmune interactions and forecast the course of disease and treatment results is investigated. Current and emerging therapies targeting neuroinflammation include anti-inflammatory and immunomodulatory drugs, lifestyle interventions, stem cell approaches, gene-editing technologies and nanoparticle-based drug delivery systems. Despite significant progress, translating preclinical findings into effective clinical therapies remains challenging. Future developments in integrative neuroimmune modeling, biomarker-guided therapies and precision medicine may make it possible to create individualized treatments plans targeted at reducing neuroinflammation and enhancing the course of neurodegenerative illnesses.},
}

Humans
*Microglia/metabolism/pathology/immunology
*Neurodegenerative Diseases/metabolism/therapy/pathology/immunology
Animals
Signal Transduction
*Neuroinflammatory Diseases/metabolism/pathology/immunology
Blood-Brain Barrier/metabolism
Cytokines/metabolism
Astrocytes/metabolism

@article {pmid42313873,
year = {2026},
author = {Rohan, H and Bochner, AF and Brown, L and Ortiz, EM and McClelland, A},
title = {COVID-19 alert level systems-Lessons learnt for future public health emergencies: A qualitative study.},
journal = {PloS one},
volume = {21},
number = {6},
pages = {e0351209},
doi = {10.1371/journal.pone.0351209},
pmid = {42313873},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; *Public Health ; Pandemics/prevention & control ; Qualitative Research ; SARS-CoV-2/isolation & purification ; Emergencies ; Public Health Infrastructure ; },
abstract = {BACKGROUND: During the COVID-19 pandemic, Alert Level Systems (ALS) were widely implemented as public health tools to communicate risk levels and recommend public health and social measures (PHSMs). However, the efficacy of ALS in mitigating disease spread and their impact on public health responses have not been systematically evaluated. This study aims to assess perceptions of ALS implementation across diverse jurisdictions and derive lessons for future public health emergencies.

METHODS: Key informant interviews were conducted remotely between December 2023 and March 2024 with senior stakeholders who were involved in ALS development and implementation during the COVID-19 pandemic, from eight jurisdictions: California (US), New Zealand, the Philippines, Rio Grande do Sul (Brazil), Singapore, South Africa, the United Kingdom, and the United States. A thematic analysis approach was applied to synthesize insights, focusing on the strengths, challenges, and key lessons from ALS implementation.

RESULTS: ALS were generally perceived by key informants as useful tools for communicating risk and supporting adherence to PHSMs due to their simplicity and transparency. However, significant challenges were identified, including difficulties in accessing reliable data, lack of clear ALS objectives, and insufficient community engagement. The study highlights the need for ALS to integrate social, economic, and epidemiological data in decision-making processes. Jurisdictions also reported that pre-existing ALS governance structures and stronger community feedback mechanisms could have improved implementation outcomes.

CONCLUSIONS: ALS can serve as valuable public health communication tools in future epidemics, but their success depends on clear objectives, evidence-based PHSMs, and robust community engagement. Pre-emptive development of ALS structures and governance will improve preparedness for future epidemics. Transparent and flexible decision-making processes will be crucial for sustaining public trust.},
}

Humans
*COVID-19/epidemiology/prevention & control
*Public Health
Pandemics/prevention & control
Qualitative Research
SARS-CoV-2/isolation & purification
Emergencies
Public Health Infrastructure

@article {pmid42314654,
year = {2026},
author = {Yang, R and Fang, Y},
title = {S-acylation of TDP-43: PALMing down aggregation?.},
journal = {Cell chemical biology},
volume = {33},
number = {6},
pages = {742-744},
doi = {10.1016/j.chembiol.2026.05.009},
pmid = {42314654},
issn = {2451-9448},
mesh = {Acylation ; Humans ; *DNA-Binding Proteins/metabolism/chemistry ; Poly Adenosine Diphosphate Ribose/metabolism ; Amyotrophic Lateral Sclerosis/metabolism/pathology ; Protein Aggregates ; },
abstract = {S-acylation is well known for regulating protein stability and trafficking. In a recent issue of Molecular Cell, Xu et al.[1] reveal a distinct, aggregation-suppressing function of this posttranslational lipid modification: S-acylation of the RNA-binding protein TDP-43 antagonizes poly(ADP-ribose)-driven condensation. Moreover, reduced S-acylation levels are linked to ALS pathogenesis.},
}

Acylation
Humans
*DNA-Binding Proteins/metabolism/chemistry
Poly Adenosine Diphosphate Ribose/metabolism
Amyotrophic Lateral Sclerosis/metabolism/pathology
Protein Aggregates