@article {pmid42261159,
year = {2026},
author = {Shirbhate, E and Singh, V and Mishra, OK and Koch, B and Tiwari, AK and Yasin, HKA and Rajak, H},
title = {The Pivotal Role of HDAC6 in Amyotrophic Lateral Sclerosis: Neuroprotective Protagonist or Degenerative Adversary?.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X462214260429080002},
pmid = {42261159},
issn = {1875-6190},
abstract = {The review specifically examines the pivotal role of HDAC6 in the pathophysiological pathway of Amyotrophic Lateral Sclerosis (ALS), an escalating neurodegenerative ailment marked by the discerning damage to motor neurons. Several lines of evidence implicate inadequate proteostasis in significantly influencing neuronal degeneration. The accumulation of misfolded proteins and proteotoxicity are highlighted as significant factors in ALS pathophysiology. Key pathological hallmarks include ubiquitin-positive inclusions, disrupted RNA metabolism, cytoskeletal perturbations, and compromised axonal transport systems. HDAC6 dysregulation disrupts axonal transport, impairing mitochondrial function and increasing oxidative stress, leading to rapid motor neuron damage and cell death. The enzyme's aberrant deacetylation of α-tubulin destabilizes microtubules and impairs intracellular trafficking. Despite HDAC6's participation in these unfavorable processes, it also exerts neuroprotective properties. It deacetylates tubulin, promoting efficient axonal transport and autophagic clearance. HDAC6 helps form aggresomes and stress granules, which are essential for cellular defence against proteotoxic stress. Through its zinc finger ubiquitin-binding domain, HDAC6 interacts with polyubiquitinated proteins, facilitating their autophagic degradation. HDAC6 inhibition can boost autophagic flux and reduce protein aggregation, while its activation may amplify the protective effects. This dichotomous behaviour of HDAC6 may pose an obstacle to the design of targeted therapy. Illuminating the complex mechanisms through which HDAC6 influences neurodegeneration and neuroprotection is important before constructing effective treatments for ALS. The review provides a clear understanding of the complex role of HDAC6 in ALS pathogenesis and highlights potential strategies to improve the prognosis of people affected by this neurological illness.},
}

@article {pmid42262533,
year = {2026},
author = {Korade, G and Kharat, S and Rathi, K},
title = {Nitric oxide in neuroinflammation and neurodegeneration: dual roles, inflammasome crosstalk, and biomarker opportunities.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {399},
number = {11},
pages = {16885-16902},
pmid = {42262533},
issn = {1432-1912},
mesh = {Humans ; Animals ; *Inflammasomes/metabolism ; *Nitric Oxide/metabolism ; *Neuroinflammatory Diseases/metabolism/drug therapy ; *Neurodegenerative Diseases/metabolism/drug therapy/immunology ; Biomarkers/metabolism ; },
abstract = {Nitric oxide is a short-lived gas that plays a critical role in numerous physiological processes, including vascular regulation, neurotransmission, and immune responses. In the CNS NO's role is complex, as it can both protect and damage neurons. Microglia, the brain's resident macrophages, produce excessive NO in response to stimuli like endotoxins and cytokines, leading to chronic inflammation and neuronal damage associated with neurodegenerative diseases such as Alzheimer's, Parkinson's, multiple sclerosis, and amyotrophic lateral sclerosis. NO's dual role as a pro-inflammatory and anti-inflammatory mediator is intricately linked to its impact on neuronal health and disease progression. This review is aimed at summarizing and critically discussing the roles of NO in neuroinflammation, neurodegeneration, inflammasome regulation, and related therapeutic perspectives. A narrative literature review was conducted using electronic databases (e.g. PubMed and Google Scholar) to identify experimental and clinical studies on NO, neuroinflammation, neurodegenerative diseases, inflammasomes, and related biomarkers and therapies, with emphasis on mechanistic and translational work. Research into NO's effects on inflammasomes, key components of the innate immune system, reveals that NO can inhibit inflammasome activation, influencing inflammatory responses. Despite progress, challenges remain, including the need for cell-type-specific models, advanced technological approaches, and the development of selective NO modulators. Overall, current evidence indicates that NO exerts both neuroprotective and neurotoxic effects in the CNS, mediated by its complex interactions with neural, glial, and immune pathways. Future research should focus on the dual nature of NO, explore lesser-known inflammasomes, and incorporate human-centric models to develop targeted therapies.},
}

Humans
Animals
*Inflammasomes/metabolism
*Nitric Oxide/metabolism
*Neuroinflammatory Diseases/metabolism/drug therapy
*Neurodegenerative Diseases/metabolism/drug therapy/immunology
Biomarkers/metabolism

@article {pmid42262849,
year = {2026},
author = {Deleu, B and Dupont, P and Bracaval, K and Ombelet, F and Hobin, F and Lamaire, N and Van Laere, K and Van Damme, P and De Vocht, J},
title = {[18]F FDG-PET correlates of motor neuron disease motor variants.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-5},
doi = {10.1080/21678421.2026.2682820},
pmid = {42262849},
issn = {2167-9223},
abstract = {While [18]F-fluorodeoxyglucose positron emission tomography (FDG-PET) is an established biomarker in amyotrophic lateral sclerosis (ALS), the metabolic correlates of motor neuron disease (MND) motor variants remain poorly defined. This is why we investigated patterns of cerebral glucose metabolism across the spectrum of MNDs, including progressive muscular atrophy (PMA), primary lateral sclerosis (PLS), and ALS. We retrospectively included 18 PMA, 25 PLS, and 43 matched non-hereditary ALS patients according to most recent diagnostic criteria. FDG-PET imaging revealed similar widespread hypometabolism in PMA, as in ALS, whereas PLS showed a more focal motor cortical pattern of hypometabolism. Despite clinical differences between MND subtypes, PMA and ALS showed similar FDG-PET metabolic patterns, whereas PLS exhibited a more restricted cortical signature in this retrospective study.},
}

@article {pmid42262924,
year = {2026},
author = {Mastromarco, GJ and Earnshaw, R and Moore, G and Xu, XYS and Sadek, NH and Cui, F and Lo, N and Lee, HO},
title = {Human J-domain proteins promote stress granule disassembly and suppress neurodegeneration-linked protein aggregation.},
journal = {Cell reports},
volume = {45},
number = {6},
pages = {117326},
doi = {10.1016/j.celrep.2026.117326},
pmid = {42262924},
issn = {2211-1247},
mesh = {Humans ; *Stress Granules/metabolism ; *HSP40 Heat-Shock Proteins/metabolism/genetics ; *HSP70 Heat-Shock Proteins/metabolism ; Poly-ADP-Ribose Binding Proteins/metabolism ; RNA-Binding Protein FUS/metabolism/genetics ; RNA Recognition Motif Proteins/metabolism ; RNA Helicases/metabolism ; DNA Helicases/metabolism ; *Protein Aggregates ; Molecular Chaperones/metabolism ; Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *Protein Aggregation, Pathological/metabolism ; Biomolecular Condensates/metabolism ; *Cytoplasmic Granules/metabolism ; },
abstract = {Stress granules are conserved biomolecular condensates that form under stress and rapidly disassemble during recovery. Stress granules have been linked to pathological protein aggregation and their impaired disassembly reduces cell viability, yet the mechanisms governing their clearance and protein aggregation remain unclear. We find that human HSP70 and a subset of J-domain proteins (JDPs) localize to stress granules and that chemical or genetic inhibition of these chaperones markedly slows granule disassembly. Conversely, overexpressing these JDPs, particularly DNAJB1, accelerates disassembly without altering assembly. In vitro, HSP70 and DNAJB1 partition into G3BP1 condensates and reduce their size in an ATP-dependent manner. In cells expressing amyotrophic lateral sclerosis (ALS)-linked mutant FUS, DNAJB1 depletion further impairs stress granule clearance and promotes pre-amyloid accumulation, while depleting a non-stress granule JDP has no effect. Our findings demonstrate that specific JDP chaperones enhance stress granule disassembly and help limit aberrant protein aggregation.},
}

Humans
*Stress Granules/metabolism
*HSP40 Heat-Shock Proteins/metabolism/genetics
*HSP70 Heat-Shock Proteins/metabolism
Poly-ADP-Ribose Binding Proteins/metabolism
RNA-Binding Protein FUS/metabolism/genetics
RNA Recognition Motif Proteins/metabolism
RNA Helicases/metabolism
DNA Helicases/metabolism
*Protein Aggregates
Molecular Chaperones/metabolism
Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics
*Protein Aggregation, Pathological/metabolism
Biomolecular Condensates/metabolism
*Cytoplasmic Granules/metabolism

@article {pmid42263252,
year = {2026},
author = {Bétourné, A and Texakalidis, P and Raheb Khelo, R and Campbell, M and Sadiq, SA and Boulis, NM},
title = {Intrathecal Administration of Riluzole in Amyotrophic Lateral Sclerosis.},
journal = {Neurosurgery},
volume = {99},
number = {1},
pages = {218-222},
pmid = {42263252},
issn = {1524-4040},
mesh = {Humans ; *Riluzole/administration & dosage ; *Amyotrophic Lateral Sclerosis/drug therapy ; Injections, Spinal/methods ; Female ; *Neuroprotective Agents/administration & dosage ; Male ; Middle Aged ; Treatment Outcome ; Aged ; },
abstract = {BACKGROUND AND OBJECTIVES: Riluzole is the only treatment known to improve survival in amyotrophic lateral sclerosis (ALS) patients. However, its efficacy and dosing are limited by hepatic toxicity and interindividual pharmacokinetic variability. Recent experimental studies in hounds have shown that continuous intrathecal (IT) administration of riluzole is well tolerated and achieves significantly higher spinal cord tissue levels. We report the first 2 human ALS cases treated with IT riluzole.

METHODS: A catheter was inserted into the lumbar cistern and advanced to the midcervical region under fluoroscopic guidance and connected to a subcutaneous pump. Therapy was initiated at 0.1 mg/h of riluzole. The infusion rate was gradually increased until it reached a maximum of 4.8 mg/d.

RESULTS: The 2 patients tolerated dose escalation and treatment for over 2 years without apparent motor or sensory complications. Patients reported no asthenia, a central side effect often reported as a reason to abandon oral therapy.

CONCLUSION: This is the first report of chronic IT riluzole infusion in humans at a dose found to be safe in canines. A phase 1 study is planned to establish the maximum tolerated human dose, followed by a randomized placebo-controlled trial to determine the safety and tolerability of IT riluzole in patients with ALS.},
}

Humans
*Riluzole/administration & dosage
*Amyotrophic Lateral Sclerosis/drug therapy
Injections, Spinal/methods
Female
*Neuroprotective Agents/administration & dosage
Male
Middle Aged
Treatment Outcome
Aged

@article {pmid42263370,
year = {2026},
author = {Deveci, Ş and Matur, Z and Erzurumluoğlu, SS},
title = {Sensory abnormalities and entrapment neuropathies identified by nerve conduction studies in patients with amyotrophic lateral sclerosis.},
journal = {Neuromuscular disorders : NMD},
volume = {64},
number = {},
pages = {106463},
doi = {10.1016/j.nmd.2026.106463},
pmid = {42263370},
issn = {1873-2364},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/complications/epidemiology ; Female ; Male ; Nerve Conduction Studies ; Middle Aged ; Retrospective Studies ; Cross-Sectional Studies ; Aged ; *Neural Conduction/physiology ; *Nerve Compression Syndromes/physiopathology/diagnosis/epidemiology/etiology ; Adult ; *Sensation Disorders/physiopathology/diagnosis/etiology ; Aged, 80 and over ; Comorbidity ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder primarily affecting motor neurons; however, non-motor symptoms, including sensory and autonomic disturbances, are increasingly recognized. This retrospective cross-sectional study evaluated the frequency of sensory and entrapment neuropathies in 114 patients with ALS using electrodiagnostic (EDX) studies. Demographic characteristics, comorbidities, and sensory and autonomic symptoms were documented. Electrophysiological evidence of sensory neuropathy was identified in 20 patients overall (20/114, 17.5%), including 10 patients without diabetes mellitus (DM), whereas entrapment neuropathy was detected in 28 patients overall (28/114, 24.6%), including 16 of those without DM or hypothyroidism. Sensory neuropathy was significantly associated with both DM and a history of chronic disease. In contrast, these comorbid conditions were not significantly associated with entrapment neuropathy. Furthermore, patient-reported symptoms showed no correlation with electrophysiological evidence of sensory involvement on EDX. Sensory neuropathy was more frequent in patients with spinal-onset than bulbar-onset disease, although the difference was not statistically significant. This study confirms that sensory involvement is not uncommon in ALS. Although clinical symptoms are poor predictors, electrophysiological abnormalities consistent with sensory and entrapment neuropathies are common. A significant proportion of these abnormalities are idiopathic and may directly reflect the disease process itself, particularly in spinal-onset cases.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/complications/epidemiology
Female
Male
Nerve Conduction Studies
Middle Aged
Retrospective Studies
Cross-Sectional Studies
Aged
*Neural Conduction/physiology
*Nerve Compression Syndromes/physiopathology/diagnosis/epidemiology/etiology
Adult
*Sensation Disorders/physiopathology/diagnosis/etiology
Aged, 80 and over
Comorbidity

@article {pmid42264185,
year = {2026},
author = {Baker, A and Okorie, M},
title = {UK Foundation Programme training needs a national minimum standard for advanced life support.},
journal = {Clinical medicine (London, England)},
volume = {26},
number = {4},
pages = {100605},
pmid = {42264185},
issn = {1473-4893},
mesh = {Humans ; United Kingdom ; *Clinical Competence/standards ; *Advanced Cardiac Life Support/standards/education ; Curriculum ; *Foundations ; },
abstract = {Since 2021, advanced life support (ALS) has no longer been a mandatory requirement of the UK Foundation Programme. Although the shift towards capability rather than certification was educationally defensible, in practice it has created marked national variation in how resuscitation preparedness is developed, evidenced and signed off. Foundation doctors now enter emergencies with unequal access to funded ALS training, simulation and supervised assessment, while supervisors are left to judge equivalence without a consistent national threshold. This matters not because patient-level harm has been neatly proven, but because high-stakes clinical capability should not depend on local opportunity or variable interpretation. A capability-based curriculum and a national minimum standard are not mutually exclusive. The Foundation Programme should therefore restore a national ALS requirement, or a formally recognised equivalent standard, alongside funded access, blended delivery and transparent national evaluation of uptake, exemptions and outcomes.},
}

Humans
United Kingdom
*Clinical Competence/standards
*Advanced Cardiac Life Support/standards/education
Curriculum
*Foundations

@article {pmid42264545,
year = {2026},
author = {Vishwakarma, H and Chauhan, A and Kaur, L and Awasthi, A},
title = {Nanotechnology-enabled targeting strategies for neurodegenerative disorders: role of functionalized nanoparticles.},
journal = {The Journal of pharmacy and pharmacology},
volume = {78},
number = {6},
pages = {},
doi = {10.1093/jpp/rgag060},
pmid = {42264545},
issn = {2042-7158},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/physiopathology/metabolism ; Animals ; *Nanoparticles ; Blood-Brain Barrier/metabolism ; *Drug Delivery Systems/methods ; Neuroprotective Agents/administration & dosage ; *Nanotechnology/methods ; Oxidative Stress/drug effects ; },
abstract = {BACKGROUND: Neurodegenerative disorders comprise a diverse group of progressive neurological diseases characterized by the gradual loss of neuronal structure and function. Conditions such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis arise from multifactorial mechanisms involving genetic susceptibility, environmental factors, and age-related cellular decline.

PATHOPHYSIOLOGY: Key pathogenic processes include oxidative stress, mitochondrial dysfunction, protein misfolding and aggregation, impaired axonal transport, Golgi fragmentation, and chronic neuroinflammation, all of which disrupt neuronal homeostasis and synaptic communication, ultimately leading to neuronal death. Hormonal imbalances further exacerbate these effects by promoting oxidative damage, inflammation, and metabolic dysfunction.

CHALLENGES IN THERAPY: Despite advances in understanding disease mechanisms, effective drug delivery remains challenging due to the restrictive nature of the blood-brain barrier.

Recent developments highlight the potential of nanoparticle-based drug delivery systems to overcome these limitations. Functionalized nanoparticles enhance blood-brain barrier penetration, improve targeting specificity, and enable controlled drug release. These systems can deliver neuroprotective agents, antioxidants, peptides, and gene therapies directly to affected brain regions. Thus, integrating disease pathophysiology with nanotechnology-based strategies offers a promising approach for improving therapeutic outcomes and advancing precision treatment in neurodegenerative disorders.},
}

Humans
*Neurodegenerative Diseases/drug therapy/physiopathology/metabolism
Animals
*Nanoparticles
Blood-Brain Barrier/metabolism
*Drug Delivery Systems/methods
Neuroprotective Agents/administration & dosage
*Nanotechnology/methods
Oxidative Stress/drug effects

@article {pmid42264722,
year = {2026},
author = {He, S and Yu, H and Li, X and Chen, J and Liu, Z and Miao, D and Ren, M and Cui, H},
title = {Distribution of resistant Aegilops tauschii populations across China and its target-site resistance mechanism.},
journal = {Pesticide biochemistry and physiology},
volume = {221},
number = {},
pages = {107181},
doi = {10.1016/j.pestbp.2026.107181},
pmid = {42264722},
issn = {1095-9939},
mesh = {*Herbicide Resistance/genetics ; China ; *Aegilops/genetics/drug effects ; Acetolactate Synthase/genetics/metabolism ; *Herbicides/pharmacology/toxicity ; *Sulfonylurea Compounds/pharmacology/toxicity ; Mutation ; Plant Proteins/genetics/metabolism ; *Poaceae/genetics/drug effects ; },
abstract = {Aegilops tauschii is a notorious weed that poses a severe threat to wheat production. Recently, its resistance to mesosulfuron-methyl has been increasingly documented in some provinces of China. With Ae. tauschii rapidly expanding its distribution range throughout China, however, its nationwide resistance distribution and the underlying resistance molecular mechanisms remain poorly understood. To address this knowledge gap, 305 populations of Ae. tauschii were collected from eight major wheat-growing provinces of China to characterize their nationwide resistance profiles and target-site resistance mechanisms. Of the populations examined, 83 populations from Shanxi, Shaanxi, Henan, Hebei, Shandong, and Jiangsu provinces exhibited varying levels of resistance to mesosulfuron-methyl. Resistant populations were particularly widespread in Shanxi and Shaanxi compared with other regions. Forty-seven resistant populations were then selected for target-site mutation analysis. A Pro-197-Leu substitution in the acetolactate synthase (ALS) gene was identified in 14 resistant populations, whereas no known resistance-conferring amino acid alteration was detected in the remaining 33 populations. Resistant populations carrying the Pro-197-Leu mutation displayed a higher resistance level than resistant populations without ALS gene mutations. Furthermore, in vitro ALS activity assays showed that populations with the Pro-197-Leu substitution were highly resistant to mesosulfuron-methyl, with resistance index (RI) ranging from 32.95 to 33.12. In contrast, the RI values of resistant populations lacking target-site mutations were below 2.90. To the best of our knowledge, this study represents the first report of a target-site mutation (Pro-197-Leu) conferring resistance to mesosulfuron-methyl in Ae. tauschii.},
}

*Herbicide Resistance/genetics
China
*Aegilops/genetics/drug effects
Acetolactate Synthase/genetics/metabolism
*Herbicides/pharmacology/toxicity
*Sulfonylurea Compounds/pharmacology/toxicity
Mutation
Plant Proteins/genetics/metabolism
*Poaceae/genetics/drug effects

@article {pmid42264735,
year = {2026},
author = {Rojano-Delgado, AM and Sohrabi, S and Santana, APDS and Palma-Bautista, C and Domínguez-Valenzuela, JA and Gherekhloo, J and Alcántara-de la Cruz, R and De Prado, R},
title = {Herbicide metabolism and EPSPS Pro-106-Ser substitution confer multiple resistance in Chenopodium spp. from Southern Spain.},
journal = {Pesticide biochemistry and physiology},
volume = {221},
number = {},
pages = {107132},
doi = {10.1016/j.pestbp.2026.107132},
pmid = {42264735},
issn = {1095-9939},
mesh = {*Herbicides/pharmacology/metabolism ; *Herbicide Resistance/genetics ; *Chenopodium/drug effects/genetics/metabolism/enzymology ; Spain ; Glyphosate ; *3-Phosphoshikimate 1-Carboxyvinyltransferase/genetics/metabolism ; *Plant Proteins/genetics/metabolism ; Glycine/analogs & derivatives/pharmacology ; Acetolactate Synthase/metabolism/antagonists & inhibitors ; },
abstract = {Long-term herbicide programs in Mediterranean perennial systems have imposed sustained selection pressure on weed populations, promoting the evolution of multiple resistance. We investigated resistance mechanisms in Chenopodium album (Ca) and C. vulvaria (Cv) from southern Spain following more than two decades of glyphosate-based management. We aimed to (i) confirm resistance to atrazine, tribenuron-methyl (TM), glyphosate, and 2,4-D; (ii) distinguish between target-site and metabolic resistance; and (iii) characterize the biochemical and molecular basis of cross- and multiple-herbicide resistance. Screening assays revealed high survival (78-100%) of resistant (R) populations to acetolactate synthase (ALS)-, photosystem II (PSII)-, auxinic-, and 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS)-inhibiting herbicides. Dose-response assays confirmed resistance, with resistance indices (RI) of 6.7 and 5.1 for atrazine, 19.0 and 17.3 for TM, 7.0 and 13.9 for glyphosate, and 6.0 and 6.9 for 2,4-D in CaR and CvR, respectively. Radiolabelled and analytical metabolism assays demonstrated enhanced herbicide metabolism in R populations: atrazine (94-95% vs. 13-16% in S), TM (68-69% vs. 24-25%), 2,4-D (64-65% vs. 2-4%), and glyphosate (39-43% vs. 8-9%). Malathion partially reversed resistance to atrazine, TM, and 2,4-D, supporting cytochrome P450 (CYP450) involvement. In contrast, glyphosate metabolism was independent of CYP450 or glutathione S-transferases inhibition. Biochemical assays showed no differences in PSII or ALS sensitivity (I50 RI ≈ 1), whereas EPSPS inhibition assays revealed a tenfold increase in I50 in CvR. Sequencing identified a Pro-106-Ser substitution in EPSPS exclusively in CvR. Enhanced metabolism predominates in the R Chenopodium spp. populations, with coexistence of metabolic and target-site mechanisms in CvR, increasing the risk of further cross-resistance under continued herbicide reliance.},
}

*Herbicides/pharmacology/metabolism
*Herbicide Resistance/genetics
*Chenopodium/drug effects/genetics/metabolism/enzymology
Spain
Glyphosate
*3-Phosphoshikimate 1-Carboxyvinyltransferase/genetics/metabolism
*Plant Proteins/genetics/metabolism
Glycine/analogs & derivatives/pharmacology
Acetolactate Synthase/metabolism/antagonists & inhibitors

@article {pmid42265364,
year = {2026},
author = {Treittinger, K and Yang, S and Fischer, R and Dreisbach, G},
title = {The asymmetric list shift effect - flexible adaptation to new context demands?.},
journal = {Attention, perception & psychophysics},
volume = {88},
number = {5},
pages = {},
pmid = {42265364},
issn = {1943-393X},
mesh = {Humans ; Stroop Test ; Young Adult ; Cognitive Flexibility/physiology ; Female ; Male ; Adult ; *Attention/physiology ; *Adaptation, Psychological/physiology ; *Executive Function/physiology ; Pattern Recognition, Visual/physiology ; *Practice, Psychological ; Reaction Time/physiology ; },
abstract = {The list-wide proportion congruency effect describes how the congruency effect varies depending on the frequency of incongruent trials within a block. Specifically, the congruency effect is larger in mostly congruent (MC) blocks compared to mostly incongruent (MI) blocks. Research has shown that adaptation to these blocks does not change symmetrically when transitioning between them: moving from MC to MI leads to a rapid decrease in the congruency effect while transitioning from MI to MC results in little or no increase (Abrahamse et al., 2013). We aimed to investigate this asymmetric list shift (ALS) effect in a within-participants design where all participants experienced both transitions (MC-MI and MI-MC). Throughout Experiments 1-3 using a color-word Stroop task, we identified various forms of practice - including trial-type, stimulus-specific learning, general RT decrease, and a decrease in congruency effects over time (see Schmidt, 2016) - that can either facilitate or obscure the ALS effect, depending on the order in which participants experienced the transitions. In Experiment 4, using a face-name version of the Stroop task, where we minimized practice-related confounding factors by employing more complex stimuli and used a new stimulus set in the second transition, an ALS effect was observed regardless of the order of transition and for frequency-unbiased (i.e., 50% congruent) items. The role of practice effects and implications for the (in)-flexibility of control adaptations will be discussed.},
}

Humans
Stroop Test
Young Adult
Cognitive Flexibility/physiology
Female
Male
Adult
*Attention/physiology
*Adaptation, Psychological/physiology
*Executive Function/physiology
Pattern Recognition, Visual/physiology
*Practice, Psychological
Reaction Time/physiology

@article {pmid42265600,
year = {2026},
author = {Jiang, S and Chen, F and Ma, H and Wu, S and Tang, X and Pan, X and Li, Q and Tao, A and Xu, J and Qi, J and Fang, P and Chen, J and Zhang, L},
title = {Cloning and functional verification of endogenous U6 promoters for developing an efficient CRISPR/Cas9-mediated genome editing system in kenaf (Hibiscus cannabinus L.).},
journal = {BMC plant biology},
volume = {26},
number = {1},
pages = {},
pmid = {42265600},
issn = {1471-2229},
support = {32472219//the National Natural Science Foundation of China/ ; 2023J01443//Fujian Provincial Natural Science Foundation of China/ ; CARS-16//China Agricultural Research System of MOF and MARA/ ; KFB23001//Science and Technology Innovation Project of Fujian Agriculture and Forestry University/ ; ASTIP-IBFC-01//Agriculture Science and Technology Innovation Program/ ; },
mesh = {*Promoter Regions, Genetic/genetics ; *CRISPR-Cas Systems ; *Hibiscus/genetics ; *Gene Editing/methods ; Cloning, Molecular ; *RNA, Small Nuclear/genetics ; Plants, Genetically Modified ; Genome, Plant ; },
abstract = {BACKGROUND: The U6 promoter is a critical component of the CRISPR/Cas9 system, as it drives the transcription of single-guide RNAs (sgRNAs) to enable precise genome editing. Endogenous promoters typically exhibit higher transcriptional activity than their exogenous counterparts, which can significantly enhance editing efficiency. However, the endogenous U6 promoter in kenaf (Hibiscus cannabinus L.), an important fiber crop, has not yet been characterized.

METHODS: Using the Arabidopsis U6-26 (AtU6-26) promoter as a reference, we performed a homologous sequence search and identified two candidate U6 promoters in kenaf, designated HcU6-1 and HcU6-14. Promoter fragments were amplified from the kenaf cultivar 'Fuhong 952' and cloned into a β-glucuronidase (GUS) reporter vector. Histochemical GUS staining assays revealed that both HcU6 promoters were transcriptionally active, with HcU6-14 showing significantly stronger expression levels compared to HcU6-1.

RESULTS: To further evaluate the utility of these promoters for genome editing, we constructed CRISPR/Cas9 vectors targeting the kenaf acetolactate synthase (ALS) gene, driven by either HcU6-14P or the exogenous cotton GbU6-9P promoter. Agrobacterium rhizogenes K599-mediated transformation was used to induce hairy roots, and mutation analysis of the ALS gene was performed via Sanger sequencing. Notably, targeted mutations in the ALS gene were detected in hairy roots transformed with the HcU6-14P-driven CRISPR/Cas9 vector, whereas no mutations were observed in roots transformed with the exogenous GbU6-9P promoter. These results demonstrate that the endogenous HcU6-14 promoter confers superior genome editing efficiency compared to the heterologous promoter, which facilitates the development of improved varieties with enhanced agronomic traits.},
}

*Promoter Regions, Genetic/genetics
*CRISPR-Cas Systems
*Hibiscus/genetics
*Gene Editing/methods
Cloning, Molecular
*RNA, Small Nuclear/genetics
Plants, Genetically Modified
Genome, Plant

@article {pmid42265995,
year = {2026},
author = {Ozlu, C and Schwaede, A and McGowan, B and Zhang, L and Finch, M and Wolfe, LF and Ajroud-Driss, S and Franz, CK and Kuntz, N},
title = {Two Patients With Juvenile-Onset, Rapidly Progressive Amyotrophic Lateral Sclerosis Associated With an SOD1 Variant (p.Asp125Gly) With Incomplete Penetrance.},
journal = {Muscle & nerve},
volume = {74},
number = {2},
pages = {457-462},
doi = {10.1002/mus.70314},
pmid = {42265995},
issn = {1097-4598},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/physiopathology/diagnostic imaging ; *Superoxide Dismutase-1/genetics ; Male ; Adolescent ; Disease Progression ; *Penetrance ; Female ; Age of Onset ; Mutation/genetics ; },
abstract = {INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) patients are rarely encountered before age 25 years, often associated with genetic variants. SOD1 gene variants are well-known to account for a subset of adult-onset ALS but have only been described in a handful of early onset patients. Variants affecting residue 125 in SOD1 have been described in adult-onset ALS patients with a rapid progression. Here we report two such patients.

METHODS: The clinical, genetic, and electrodiagnostic findings of two unrelated adolescents with juvenile onset rapidly progressive SOD1 -ALS are described.

RESULTS: Patient 1 presented at 16 and patient 2 at 15 years-of-age with lower limb onset of weakness, lower motor neuron examination findings, and rapid progression over months to involve all body regions. Both patients underwent extensive laboratory, electrophysiologic, and radiologic testing ruling out any alternate etiologies. For both patients, whole-exome sequencing revealed the pathogenic variant p.Asp125Gly in the SOD1 gene inherited from asymptomatic fathers.

DISCUSSION: These two patients expand the phenotypic spectrum of SOD1 -ALS, demonstrating a rapidly progressive juvenile lower limb onset phenotype associated with the p.Asp125Gly variant inherited with incomplete penetrance. Recognition and further characterization of juvenile SOD1 -ALS are important in light of the advances in targeted therapies.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/physiopathology/diagnostic imaging
*Superoxide Dismutase-1/genetics
Male
Adolescent
Disease Progression
*Penetrance
Female
Age of Onset
Mutation/genetics

@article {pmid42266360,
year = {2026},
author = {Ilczak, T and Ćwiertnia, M and Sumera, K and Babik, P and Białoń, P and Dutka, M and Malinowska-Lipień, I and Augustyn, M and Majewski, M and Lis, A and Leszczyński, P and Stasicki, A and Abramczyk, P and Kukla, P and Pollok-Waksmańska, W and Trojak-Piętka, J and Kawecki, M},
title = {Nontechnical Skills (NTS) and the Quality of Conducting Prehospital Advanced Cardiopulmonary Resuscitation Among Paramedics.},
journal = {Emergency medicine international},
volume = {2026},
number = {},
pages = {2207053},
pmid = {42266360},
issn = {2090-2840},
abstract = {INTRODUCTION: It is common knowledge that the correct application of cardiopulmonary resuscitation (CPR) requires technical skills such as defibrillation, high-quality chest compressions, and efficient airway management. However, scientific research is increasingly underlining the role of appropriate training in nontechnical skills (NTS).

RESEARCH AIM: This exploratory study aimed to assess the relationship between NTS and the quality of advanced CPR among paramedics.

MATERIALS AND METHODS: The research involved 51 paramedics randomly assigned to 17 three-person teams. Each team participated in a 15-min cardiac arrest scenario. After the first session, the teams were divided into two groups: the intervention group (Group 1), which underwent specialized NTS training, and the control group (Group 2), which did not receive the initial training. Directly after the training phase, all teams from both groups carried out a second attempt during a simulated sudden cardiac arrest (SCA) scenario identical to the first one.

RESULTS: The lowest CPR result in the intervention group (Group 1) was Min = -3.00, and the highest Max = 13.00, while in the control group (Group 2), the lowest result was Min = -42.00, and the highest Max = 8.00 (p < 0.05). In Group 1, a statistically significant correlation (p < 0.05) was noted between the change in the NTS score and the change in the CPR result. A higher NTS score was accompanied by a higher CPR score.

CONCLUSIONS: A short NTS training session was associated with improved NTS application by paramedic resuscitation teams. Furthermore, higher chest compression quality positively correlated with NTS proficiency.},
}

@article {pmid42267597,
year = {2026},
author = {Held-Bradford, EC and DeMarco, E and Zocher, S and Weaver, K and Forsman, K and Hayat, G and Subramaniam, DS and Doherty, M},
title = {Functional Motor Change Across Time and Phenotypes in Patients With Amyotrophic Lateral Sclerosis: A Descriptive Study.},
journal = {Neurorehabilitation and neural repair},
volume = {},
number = {},
pages = {15459683261445435},
doi = {10.1177/15459683261445435},
pmid = {42267597},
issn = {1552-6844},
abstract = {PURPOSE: Progressive disability occurs in persons with amyotrophic lateral sclerosis (pALS), but change over time across phenotypes remains understudied, limiting clinical decision-making. This descriptive study describes functional motor change with detailed measures across ALS phenotypes to enhance clinical decision making.

MATERIALS AND METHODS: Electronic health record data from an interdisciplinary ALS clinic (n = 109 pALS, 2018-2022) including demographics, disability (ALS Functional Rating Scale-[ALSFRS-R]), and functional motor scores (10 m Walk, Handheld dynamometry [grip and ankle]) was utilized. Phenotype groups were defined by site of onset (bulbar, limb onset; upper limb or lower limb). Analysis was conducted using R and included changes scores and measures of central tendency in 3-month intervals.

RESULTS: PALS included n = 43 bulbar, n = 32 upper limb, n = 34 lower limb onset, age 65, 60 to 71 (median, interquartile range). ALFSRS-R decline was greatest in bulbar, and similar in upper and lower limb. Patterns of change within motor scores suggest greatest loss of grip strength in bulbar and upper limb, ankle strength in upper limb, walking speed in lower limb, and preservation of community ambulation in upper limb.

CONCLUSION: While ALSFRS-R scores were similar in upper and lower limb, detailed functional motor measures indicated differences in groups. These patterns provide insight to guide clinical decision making and future research to enhance care in pALS.},
}

@article {pmid42267908,
year = {2026},
author = {Donati Della Lunga, I and Cerutti, L and Barabino, V and Figus, GG and Callegari, F and Oneto, L and Tedesco, M and Bacchetti, F and Milanese, M and Massobrio, P and Brofiga, M},
title = {Developmental circuit instability in amyotrophic lateral sclerosis: from hyperexcitability to network collapse.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag185},
pmid = {42267908},
issn = {1460-2156},
abstract = {Amyotrophic lateral sclerosis (ALS) is traditionally viewed as a late-onset motor neuron disease, yet how cortical dysfunction originates and contributes to pathogenesis remains unresolved. In this study, we reconstruct the developmental trajectory of cultured cortical networks derived from SOD1G93A mouse embryos using a multimodal approach, by combining morphometric, electrophysiological, pharmacological, molecular, computational, and machine-learning techniques. We prove that ALS neurons fail to acquire mature polarization and connectivity, displaying a transient phase of hyperexcitability that precedes a progressive collapse of network organization. Astrocytic dysfunction emerges early and impairs synchronization, establishing a causal link between glial dysfunction and neuronal instability. The analysis of synaptic transmission reveals an excitatory bias followed by maladaptive inhibitory recruitment and GABA/glutamate co-release, causing fragmented and inefficient network topologies. Finally, in silico modelling identified deficient intrinsic adaptation as a key driver of hyperexcitability. Together, our findings position ALS as a developmentally rooted disorder of cultured cortical network homeostasis, driven by glial, synaptic, and intrinsic adaptation failures. By demonstrating that cortical dysfunction is embedded before degeneration, this work provides a unifying framework connecting early network instability to disease progression and establishes electrophysiological network signatures, detected by machine learning classifiers, as candidate biomarkers for early diagnosis and therapeutic screening.},
}

@article {pmid42268433,
year = {2026},
author = {Sytwu, HP and Jih, KY and Tsai, YS and Fang, SY and Liao, YC and Lee, YC},
title = {FUS-associated ALS in Taiwan: genetic spectrum, clinical features, and a founder haplotype of p.H517D.},
journal = {Journal of neurology},
volume = {273},
number = {7},
pages = {},
pmid = {42268433},
issn = {1432-1459},
support = {112-2314-B-075-034-MY3//National Science and Technology Council/ ; 114-2314-B-075-021-MY3//National Science and Technology Council/ ; 113-2314-B-075-018-MY3//National Science and Technology Council/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/physiopathology/epidemiology ; *RNA-Binding Protein FUS/genetics ; Taiwan ; Haplotypes ; Female ; Male ; Middle Aged ; *Founder Effect ; Adult ; Aged ; Cohort Studies ; Age of Onset ; *Mutation/genetics ; },
abstract = {OBJECTIVE: To characterize the genetic spectrum and clinical features of FUS-associated amyotrophic lateral sclerosis (ALS) in a Taiwanese cohort and to investigate whether the recurrent p.H517D variant represents a founder mutation.

METHODS: All coding exons and flanking intronic regions of FUS were analyzed by Sanger sequencing in 650 unrelated Taiwanese patients with ALS. Clinical characteristics of patients carrying FUS variants were evaluated. Haplotype analysis using polymorphic microsatellite markers flanking FUS was performed to assess a potential founder effect of the p.H517D variant.

RESULTS: Eight distinct heterozygous pathogenic FUS variants were identified in 11 probands and five affected relatives, including six missense and two frameshift variants. The most frequent variant was p.H517D, detected in four probands. A novel frameshift variant, p.G499Vfs*30, was identified as a de novo mutation in a juvenile-onset ALS patient. Compared with the non FUS-associated ALS cohort, patients with FUS-associated ALS had a significantly younger mean age at onset (40.1 vs 56.6 years) and more frequent bulbar onset (50% vs 19%). Haplotype analysis suggested a common founder for the p.H517D variant.

CONCLUSIONS: FUS mutations accounted for 1.7% of ALS cases in this Taiwanese cohort. The recurrent p.H517D variant appears to represent a population-specific founder mutation. Patients with FUS variants presented with earlier disease onset and heterogeneous clinical phenotypes, and de novo variants contributed to juvenile-onset disease.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/physiopathology/epidemiology
*RNA-Binding Protein FUS/genetics
Taiwan
Haplotypes
Female
Male
Middle Aged
*Founder Effect
Adult
Aged
Cohort Studies
Age of Onset
*Mutation/genetics

@article {pmid42268660,
year = {2026},
author = {Roy, É and Blais, M and Dion, P and Rouleau, GA and Dupré, N and Picher-Martel, V},
title = {Oligogenic variants in NEK1 and ATXN2 in amyotrophic lateral sclerosis: report of two cases and review of the literature.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/21678421.2026.2685158},
pmid = {42268660},
issn = {2167-9223},
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that affects the upper and lower motor neurons and leads to progressive paralysis. More than 40 genes have been implicated in familial ALS, which represents about 10% of ALS cases. Some genes, including C9orf72, SOD1, FUS and TARDBP are undoubtedly considered causative, but many others have uncertain pathogenicity and low penetrance. Here, we described the cases of two siblings affected by ALS and carrying both an ATXN2 heterozygous 32 CAG trinucleotide repeat expansion and a novel NEK1 heterozygous c.1674_1677dup. The segregation of both variants in this large family with thirteen siblings may support a role for these variants as susceptibility alleles within an oligogenic model. Our review of the literature suggests that NEK1 variants are frequently found in combination with other variants and repeats expansion in the ATXN2 gene appears to be more associated with monogenic ALS, but also frequently combined with C9orf72 repeat expansion.},
}

@article {pmid42269975,
year = {2026},
author = {Ma, M and Cui, B and Sun, X and Liu, S and Shao, K and Liu, F and Lin, P and Li, W and Zhao, Y and Yu, D and Lou, J and Yun, Y},
title = {Progressive choroid plexus enlargement across disease stages in patients with sporadic amyotrophic lateral sclerosis.},
journal = {Neurobiology of disease},
volume = {227},
number = {},
pages = {107481},
doi = {10.1016/j.nbd.2026.107481},
pmid = {42269975},
issn = {1095-953X},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/diagnostic imaging/cerebrospinal fluid ; Female ; *Choroid Plexus/pathology/diagnostic imaging ; Male ; Disease Progression ; Magnetic Resonance Imaging ; Middle Aged ; Prospective Studies ; Cross-Sectional Studies ; Aged ; Longitudinal Studies ; Adult ; },
abstract = {BACKGROUND: The choroid plexus (CP), a key structure involved in cerebrospinal fluid homeostasis and glymphatic function, is increasingly recognized as an interface for neuroimmune communication. Recent studies have identified CP abnormalities as potential neuroimaging markers in several neurodegenerative disorders, including sporadic amyotrophic lateral sclerosis (sALS). However, whether CP enlargement occurs early and progresses across clinical stages or over time in patients with sALS remains unclear. Given the role of the CP in peripheral-central nervous system immune crosstalk, the association between neuroinflammation and CP abnormalities in sALS also requires clarification. In this prospective study, we used structural MRI to examine cross-sectional and longitudinal CP volume changes in patients with sALS and to evaluate their associations with CSF inflammatory markers.

METHODS: This prospective study included 161 newly diagnosed patients with sALS who underwent genetic testing and structural MRI, and 64 healthy controls (HCs) who underwent structural MRI. Disease stage in patients with sALS was assessed using the King's staging system. Longitudinal MRI was performed in a subset of 42 patients, of whom 38 also underwent baseline CSF inflammatory protein assessment.

RESULTS: Compared with HCs, patients with sALS at all King's stages showed significantly larger CP volumes after Bonferroni correction (all p < 0.05). CP volumes were significantly greater in patients at King's stage 3 than in those at King's stage 1 or stage 2 after Bonferroni correction (all p < 0.05). In the longitudinal subgroup, CP volume increased significantly from baseline to follow-up. Multivariable analysis showed that higher CSF CHIT1 and IL-6 levels were independently associated with larger CP volume in patients with sALS (β = 0.348-0.456; p < 0.01).

CONCLUSIONS: Our findings provide evidence that CP enlargement occurs early and progresses across disease stages and over time in patients with sALS. Higher CSF CHIT1 and IL-6 levels were associated with larger CP volume, supporting a potential link between neuroinflammation and CP abnormalities in sALS. These findings support CP enlargement as a promising neuroimaging marker for monitoring disease progression and neuroinflammatory processes in patients with sALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/pathology/diagnostic imaging/cerebrospinal fluid
Female
*Choroid Plexus/pathology/diagnostic imaging
Male
Disease Progression
Magnetic Resonance Imaging
Middle Aged
Prospective Studies
Cross-Sectional Studies
Aged
Longitudinal Studies
Adult

@article {pmid42270846,
year = {2026},
author = {Wood, H and Hamdi, N},
title = {Advancing amyotrophic lateral sclerosis research in Egypt.},
journal = {Nature reviews. Neurology},
volume = {22},
number = {7},
pages = {404-405},
doi = {10.1038/s41582-026-01230-x},
pmid = {42270846},
issn = {1759-4766},
}

@article {pmid42271582,
year = {2026},
author = {Ito, M},
title = {[Re-evaluating ALS Medical Care in Japan: An International Comparison of Japan, Europe, the United States, and Canada-Insights from Mechanical Ventilation, Support for Social Participation, End-of-Life Care Options, Approved Drugs, and Precision Medicine].},
journal = {Brain and nerve = Shinkei kenkyu no shinpo},
volume = {78},
number = {6},
pages = {654-657},
doi = {10.11477/mf.188160960780060654},
pmid = {42271582},
issn = {1881-6096},
mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; *Terminal Care ; *Precision Medicine ; Japan ; United States ; Europe ; *Respiration, Artificial ; Canada ; Palliative Care ; },
abstract = {Amyotrophic lateral sclerosis (ALS) care in Japan should be re-evaluated not simply as a matter of clinical choice but as a function of the public support system structure. In Japan, care is distinguished by a publicly funded model that supports home-based living and social participation following tracheostomy invasive ventilation. In contrast, Europe reflects a model centered on non-invasive ventilation and palliative care, and the United States reflects a system in which precision therapies are approved earlier but access remains highly unequal. Further, Canada reflects a model integrating multidisciplinary ALS clinics with Medical Assistance in Dying within a shared policy framework. These differences extend beyond treatment preferences and instead reflect broader social, institutional, and ethical configurations that shape the future of individuals with ALS. As access to emerging disease-modifying therapies increasingly depends on genetic testing, the central challenge in ALS care is shifting from end-of-life decision-making to the equitable distribution of precision medicine. Comparative reappraisal of national care models is therefore critical for understanding ALS not only as a neurological disease but also as a condition shaped by welfare systems, care infrastructure, and policy design.},
}

*Amyotrophic Lateral Sclerosis/therapy
Humans
*Terminal Care
*Precision Medicine
Japan
United States
Europe
*Respiration, Artificial
Canada
Palliative Care

@article {pmid42271589,
year = {2026},
author = {Kunieda, K},
title = {[Clinical Management of Dysphagia and Nutritional Disorders in Neurodegenerative Diseases].},
journal = {Brain and nerve = Shinkei kenkyu no shinpo},
volume = {78},
number = {6},
pages = {695-700},
doi = {10.11477/mf.188160960780060695},
pmid = {42271589},
issn = {1881-6096},
mesh = {Humans ; *Deglutition Disorders/therapy/etiology ; *Neurodegenerative Diseases/complications/therapy ; *Nutrition Disorders/therapy/etiology ; },
abstract = {Dysphagia is common in patients with neuro degenerative diseases. It is associated with aspiration pneumonia, malnutrition, and reduced quality of life. Swallowing assessment should incorporate therapeutic perspectives, including the use of compensatory strategies. In conditions such as amyotrophic lateral sclerosis, weight loss is associated with a poor prognosis, and nutritional therapy may function as a disease-modifying intervention. Clinical ethical issues may arise, including decisions regarding gastrostomy or care for patients with impaired decision-making capacity. A multidisciplinary team approach is essential for managing dysphagia and nutritional problems in these patients.},
}

Humans
*Deglutition Disorders/therapy/etiology
*Neurodegenerative Diseases/complications/therapy
*Nutrition Disorders/therapy/etiology

@article {pmid42272352,
year = {2026},
author = {Lizio, A and Farè, M and Gerardi, F and Collesi, M and Sansone, VA and Lunetta, C and Diamanti, L and Cerri, F},
title = {Impact of treatment burden on medication adherence and quality of life in amyotrophic lateral sclerosis: a prospective multicentre study.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/21678421.2026.2683691},
pmid = {42272352},
issn = {2167-9223},
abstract = {BACKGROUND: Patients with amyotrophic lateral sclerosis (ALS) face substantial barriers to medication adherence as disease progression necessitates complex drug formulation adjustments, such as crushing tablets, mixing with liquids, or delivering via feeding tubes. These modifications may not only increase the time and effort required but could also impact drug efficacy and safety.

OBJECTIVE: To evaluate the prevalence and the impact of treatment burden on medication adherence and patient-reported quality of life (QoL) in ALS.

METHODS: This prospective multicenter study enrolled ALS patients across three Italian reference centers, with assessments at baseline, 6, and 12 months. Key measures included the Multimorbidity Treatment Burden Questionnaire (MTBQ), ALSFRS-R, DYALS (dysphagia), Morisky Medication Adherence Scale, SSS-8 (somatic symptoms), INQoL (QoL), SWAMECO (swallowing/medication difficulties), alongside comorbidities and current therapies. Associations between treatment burden, QoL, and adherence were analyzed using multivariable models.

RESULTS: A total of 114 consecutive ALS patients were enrolled. Clinically significant treatment burden was observed in 69.3% of patients, with over half reporting moderate-to-high levels according to the MTBQ classification. Elevated burden was independently related to greater somatic symptom severity and formulation modification needs. Moreover, higher burden associated with poorer QoL and diminished adherence after confounder adjustment. Longitudinally, patients experiencing worsening burden over 1 year showed accelerated QoL decline compared to those remaining stable, though adherence trajectories were unaffected.

CONCLUSION: Treatment burden, particularly driven by drug formulation complexities and somatic symptoms, emerges as a pivotal, modifiable determinant of adherence and QoL in ALS. Targeted interventions to alleviate modifiable burden components hold promise for optimizing clinical outcomes and enhancing patient-centred care.},
}

@article {pmid42274555,
year = {2026},
author = {Khan, MS and Zafar, I and Noman, M and Yang, G and Kang, KS and Bopassa, JC},
title = {Polypharmacology of Pathway Crosstalk in Neurodegenerative Diseases: Chemical Modulation of Interconnected Signaling Networks.},
journal = {Cells},
volume = {15},
number = {11},
pages = {},
pmid = {42274555},
issn = {2073-4409},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology ; *Signal Transduction/drug effects ; *Polypharmacology ; Animals ; Oxidative Stress ; Mitochondria/metabolism ; },
abstract = {Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), arise from highly interconnected molecular and cellular abnormalities that progressively lead to neuronal dysfunction, synaptic failure, and cell death. This review provides a unified framework to understand the interrelated molecular mechanisms driving these diseases, with a focus on identifying key disease-specific intervention nodes. Core contributors include oxidative stress, mitochondrial dysfunction, protein aggregation, neuroinflammation, and emerging roles of peroxisomal dysfunction in redox imbalance, lipid dysregulation, and inflammatory amplification. Single-target therapies often show limited efficacy due to the complex, interconnected nature of these pathways. In contrast, polypharmacology, which targets multiple disease-relevant mechanisms simultaneously, offers a more promising therapeutic strategy. This review critically examines how pathway crosstalk drives neurodegenerative progression, with particular emphasis on mitochondrial-ROS-inflammatory signaling, aggregation-proteostasis failure, synaptic-neuroimmune dysfunction, and gut-brain communication. It evaluates various multi-node intervention strategies, including multi-target-directed ligands (MTDLs), molecular hybrids, natural products, drug repurposing, and nanocarrier-based delivery systems. Advances in network pharmacology, artificial intelligence (AI), bioinformatics, and multi-omics have enhanced the identification of actionable therapeutic nodes, candidate compounds, and brain-targeted delivery platforms. Notably, the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathways-play distinct roles in neuroinflammation, amplifying neuronal damage by releasing inflammatory cytokines and inducing mitochondrial dysfunction. However, successful translation into clinical practice remains constrained by challenges such as blood-brain barrier penetration, patient heterogeneity, and biomarker limitations. The review advocates for a shift towards mechanism-informed, patient-stratified polypharmacological strategies to better address the network pathology of neurodegeneration, despite significant translational hurdles.},
}

Humans
*Neurodegenerative Diseases/drug therapy/metabolism/pathology
*Signal Transduction/drug effects
*Polypharmacology
Animals
Oxidative Stress
Mitochondria/metabolism

@article {pmid42274577,
year = {2026},
author = {Schuldt, ON and Leitch, SR and Jones, LK and Buckley, PR and Morrison, BE},
title = {Neuroinflammatory Remodeling by Type 2 Immune Pathways Links Allergic Signaling to Neurodegenerative Disease.},
journal = {Cells},
volume = {15},
number = {11},
pages = {},
pmid = {42274577},
issn = {2073-4409},
support = {R15HL165397//National Heart Lung and Blood Institute/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/immunology/pathology ; Animals ; *Signal Transduction/immunology ; *Hypersensitivity/immunology ; *Neuroinflammatory Diseases/immunology ; },
abstract = {The hallmarks of allergic diseases are Type 2 immunity, including IL-4 and IL-13 production, IgE antibody generation, mast cell and basophil activation, histamine release, and eosinophil activation. There are many routes by which such mediators can influence CNS biology, including cytokine entry or signaling via brain barrier receptors; leukocyte trafficking across activated barriers; cytokine signaling via circumventricular organ sites or dural immune compartments; vagus nerve afferent signaling; mast cell degranulation; and histamine neuromodulation. Neuroinflammation is a common hallmark of many neurodegenerative diseases, but whether and to what degree allergic/type 2 immune biology may be involved depends on the specific disease stage and pathology. Here, we assess studies connecting the roles of IL-4/IL-13 signaling, IgE/mast cell activation, eosinophil-attractive chemokines, and histamines in Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, dementia with Lewy bodies, Huntington's disease, prion disease, and tauopathy/atypical parkinsonism. Mechanisms appear most clear in the case of Parkinson's disease, where epidemiology suggests an important role in dementia/Alzheimer's disease, while for other neurodegenerative conditions the evidence is less compelling and may be either mechanistic or modulatory. Confounding issues include sex differences, drug exposures, comorbid conditions, socioeconomic factors, and coexisting inflammatory diseases. Finally, we suggest a strategy based on longitudinal immune phenotyping, CNS biomarkers, and pathway manipulation to assess the relationship between allergic immune signaling and neurodegeneration.},
}

Humans
*Neurodegenerative Diseases/immunology/pathology
Animals
*Signal Transduction/immunology
*Hypersensitivity/immunology
*Neuroinflammatory Diseases/immunology

@article {pmid42274592,
year = {2026},
author = {Sgalletta, B and Agostini, F and Bisaglia, M},
title = {The Role of Iron in Neuronal Homeostasis: A Double-Edged Sword.},
journal = {Cells},
volume = {15},
number = {11},
pages = {},
pmid = {42274592},
issn = {2073-4409},
mesh = {Humans ; *Iron/metabolism ; *Homeostasis ; Animals ; *Neurons/metabolism ; Neurodegenerative Diseases/metabolism/pathology ; Neurogenesis ; Neurodevelopment ; Brain/metabolism ; },
abstract = {Iron is an essential micronutrient that plays a central role in numerous biological processes. Despite its relatively low abundance in the human body, iron is particularly critical for brain function. Systemic and cerebral iron homeostasis is tightly regulated through coordinated mechanisms involving absorption, transport, storage, and recycling. Within the brain, iron metabolism is further controlled by the blood-brain barrier and specialized neural cell populations, including neurons, astrocytes, oligodendrocytes, and microglia. Iron is indispensable for neurodevelopment, supporting neurogenesis, myelination, and neurotransmitter synthesis. However, both iron deficiency and iron overload have detrimental consequences. Early-life iron deficiency disrupts neural development and leads to long-lasting cognitive, motor, and behavioral impairments, whereas excessive iron accumulation promotes oxidative stress, ferroptosis, and neuroinflammation. These mechanisms have been described to contribute to the pathogenesis of major neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, neurodegeneration with brain iron accumulation, and amyotrophic lateral sclerosis. This review first outlines systemic and brain iron metabolism, highlighting how neural cells regulate homeostasis. Next, it examines iron's physiological roles, particularly in neurogenesis and neurodevelopment. Finally, it explores iron's involvement in neurodegenerative diseases, emphasizing neuroinflammation as a primary mechanism of iron toxicity.},
}

Humans
*Iron/metabolism
*Homeostasis
Animals
*Neurons/metabolism
Neurodegenerative Diseases/metabolism/pathology
Neurogenesis
Neurodevelopment
Brain/metabolism

@article {pmid42274906,
year = {2026},
author = {He, Y and Yi, T and Min, M and Xu, K and Lin, H and Xu, R and Deng, D and Xiao, X},
title = {Environmental Factors Drive Neurodegenerative Diseases Through Glutamate Excitotoxicity: A Convergent Mechanistic Pathway.},
journal = {Neuroscience bulletin},
volume = {},
number = {},
pages = {},
pmid = {42274906},
issn = {1995-8218},
abstract = {This review illustrates how environmental stressors disrupt glutamate homeostasis via specific mechanisms: lead-induced thiol modification, manganese mediated yin yang 1 (YY1)-histone deacetylases (HDAC) repression, PM2.5-triggered microglia-astrocyte crosstalk, and advanced glycation end products (AGEs)-receptor for advanced glycation end products (RAGE)-nuclear factor kappa-B (NF-κB) signaling from high-sugar diets. Together with genetic susceptibility and pigment epithelium-derived factor (PEDF), these factors impair astrocytic glutamate uptake, promoting synaptic glutamate accumulation. Subsequent N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor overactivation triggers calcium overload, mitochondrial dysfunction, oxidative stress, and neuroinflammation-termed "degenerative excitotoxicity". Excitotoxicity manifests in Alzheimer's disease (amyloid-beta-excitatory amino acid transporter 2 (EAAT2) interplay), Parkinson's disease (subthalamic nucleus-driven excitatory storm), and amyotrophic lateral sclerosis (astrocytic failure versus neuronal cell-autonomous mechanisms). Future interventions need multi-target strategies, emerging technologies, and lifestyle modifications. This convergent framework offers a unified understanding linking environmental exposure to neurodegeneration and charts a roadmap toward mechanism-based prevention and treatment.},
}

@article {pmid42274979,
year = {2026},
author = {Ojha, GJ and Talwar, T},
title = {Exploring the Role of Spirituality in Neuropalliative Care: An Integrative Review.},
journal = {Journal of religion and health},
volume = {},
number = {},
pages = {},
pmid = {42274979},
issn = {1573-6571},
abstract = {Neuropalliative care aims to address the physical, psychosocial and spiritual needs of persons with progressive and life-limiting neurological conditions, while spiritual care fosters hope and meaning in life. Progressive neurological disorders with an uncertain disease trajectory present a set of complex challenges that have far-reaching consequences on the patient's self-belief, questioning the very existence, self-identity, and belongingness. A typical neuropalliative care team consists of neurologists, nurses, psychologists, occupational therapists, and spiritual care providers. Previous research indicates that spiritual care improves coping and quality of life in persons with Parkinson's disease and Amyotrophic lateral sclerosis. This study aimed to explore how spiritual needs are addressed in the area of neuropalliative care, examining the theoretical frameworks and empirical studies that incorporate spirituality as a component of neuropalliative care. The databases PubMed, PsycINFO, Cochrane Library, Scopus and two peer-reviewed journals were searched using a strategy based on three sets of terms "spirituality," "progressive neurological conditions" and "neuropalliative care." Articles included were in the English language, and mentioned spirituality in the context of neuropalliative care or palliative care for neurological conditions. Initial screening yielded 744 articles, of which 29 were selected for synthesis. Results highlighted the various challenges in ascertaining and meeting the spiritual needs in neuropalliative care. The review concludes that palliative services should be initiated early following the diagnosis of a progressive neurological condition so that the patient and family have enough time to reflect, create memories, and prepare in advance for the inevitable through dignity and resilience.},
}

@article {pmid42275159,
year = {2026},
author = {Ito, D and Iida, M and Iguchi, Y and Hashizume, A and Yamada, S and Kishimoto, Y and Komori, S and Obara, K and Nishisaki, S and Yokoi, S and Shimamura, T and Takemoto, Y and Nakatochi, M and Akashi, T and Hinohara, K and Lee-Okada, HC and Okada, Y and Niwa, J and Sobue, G and Tanaka, S and Takashina, K and Yokomizo, T and Katsuno, M},
title = {Fatty acid amide hydrolase inhibition for treatment of amyotrophic lateral sclerosis.},
journal = {JCI insight},
volume = {11},
number = {15},
pages = {},
pmid = {42275159},
issn = {2379-3708},
mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology ; Animals ; Humans ; Fatty Acid Amide Hydrolases ; Mice ; Mice, Transgenic ; *Amidohydrolases/antagonists & inhibitors/metabolism ; Motor Neurons/drug effects/pathology/metabolism ; Induced Pluripotent Stem Cells/metabolism/drug effects ; Disease Models, Animal ; Disease Progression ; Female ; Male ; Endocannabinoids/metabolism ; Superoxide Dismutase-1/genetics ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease caused by the selective loss of upper and lower motor neurons. There is a considerable variability in the disease progression of sporadic ALS, but the molecular basis for phenotypic heterogeneity remains largely unknown. Patients with ALS often manifest systemic metabolic abnormalities such as glucose intolerance and hypermetabolic state. We conducted reverse translational research to explore therapeutic targets in ALS based on the systemic metabolic alterations in patients and identified several metabolites associated with the disease progression, including metabolites involved in the expanded endocannabinoid system (ECS). In particular, the levels of N-acyl taurines (NATs) were correlated with the longitudinal change in the revised ALS functional rating scale and survival. Experiments with ALS cellular models and induced pluripotent stem (iPS) cells derived from patients with ALS and SOD1G93A transgenic mice revealed that PF-04457845, a fatty acid amide hydrolase inhibitor, upregulated the expanded ECS, particularly the levels of NATs and ameliorated motor neuron degeneration through the regulation of microglial environment, synapse plasticity, and neuronal development. These results collectively indicate that dysregulation of NATs is associated with ALS progression and PF-04457845 may represent a potential disease-modifying therapy for ALS.},
}

*Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology
Animals
Humans
Fatty Acid Amide Hydrolases
Mice
Mice, Transgenic
*Amidohydrolases/antagonists & inhibitors/metabolism
Motor Neurons/drug effects/pathology/metabolism
Induced Pluripotent Stem Cells/metabolism/drug effects
Disease Models, Animal
Disease Progression
Female
Male
Endocannabinoids/metabolism
Superoxide Dismutase-1/genetics

@article {pmid42276279,
year = {2026},
author = {Gurung, N and Choi, DY and Park, PH},
title = {Naringenin as a multi-target neuroprotective agent in neurodegenerative diseases.},
journal = {Neurochemistry international},
volume = {198},
number = {},
pages = {106203},
doi = {10.1016/j.neuint.2026.106203},
pmid = {42276279},
issn = {1872-9754},
mesh = {Humans ; *Flavanones/administration & dosage/therapeutic use/pharmacology ; *Neuroprotective Agents/administration & dosage/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; Antioxidants/metabolism ; },
abstract = {Neurodegenerative diseases (ND) such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic lateral sclerosis (ALS), and Multiple sclerosis (MS) are characterized by progressive neuronal loss driven by complex and multifactorial pathogenic mechanisms. Naringenin (NAR), a citrus-derived flavanone, has attracted considerable interest as a neuroprotective molecule due to its pleiotropic pharmacological activities such as antioxidant, anti-inflammatory and ability to modulate multiple cellular targets. This review provides a comprehensive overview of NAR pharmacokinetic profile, mechanistic actions, and therapeutic potential across major ND. We highlight how NAR's multi-target effects-including redox homeostasis maintenance, suppression of neuroinflammation, protein aggregation inhibition, and modulation of signaling pathways-contribute to neuroprotection in various experimental models of AD, PD, HD, ALS, and MS. Preclinical studies demonstrate that NAR can ameliorate cognitive and motor deficits in toxin and transgenic models of neurodegeneration, attenuate pathological hallmarks such as amyloid-beta toxicity, dopaminergic neuronal loss, and neuroinflammation, and induce cytoprotective pathways including Nrf2-mediated antioxidant response and autophagy. However, NAR's clinical translation is challenged by poor bioavailability; thus, novel delivery systems are being explored to enhance brain uptake. NAR emerges as a promising multi-functional neuroprotective agent that can simultaneously target diverse pathogenic processes in ND. Further research including advanced formulation development and well-designed clinical trials is warranted to fully establish NAR's therapeutic efficacy and safety in humans.},
}

Humans
*Flavanones/administration & dosage/therapeutic use/pharmacology
*Neuroprotective Agents/administration & dosage/therapeutic use/pharmacology
*Neurodegenerative Diseases/drug therapy/metabolism
Animals
Antioxidants/metabolism

@article {pmid42276329,
year = {2026},
author = {Abzhanova, E and Kawae, Y and Mizuno, H and Umemoto, T and Ciftci, H and Tsuboi, M and Hirabayashi, Y and Mizuno, H},
title = {ALS-associated protein TDP-43 disturbs axonal projections in the somatosensory cortex.},
journal = {Neuroscience research},
volume = {229},
number = {},
pages = {105079},
doi = {10.1016/j.neures.2026.105079},
pmid = {42276329},
issn = {1872-8111},
mesh = {Animals ; *DNA-Binding Proteins/metabolism/genetics ; *Somatosensory Cortex/metabolism/pathology ; *Axons/metabolism/pathology ; *Amyotrophic Lateral Sclerosis/metabolism/pathology ; Corpus Callosum/metabolism/pathology ; Mice ; Female ; Mice, Transgenic ; Pyramidal Cells/metabolism/pathology ; Humans ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by loss of upper and lower motor neurons that gradually causes muscle weakness and paralysis, eventually resulting in death. While ALS was once believed to specifically target motor neurons, recent clinical studies have revealed sensory involvement. The pathological hallmark of ALS is TAR DNA-binding protein 43 (TDP-43) aggregation in cytoplasm, with increasing evidence of its presence in both motor and sensory neurons. However, sensory abnormalities remain poorly characterized. To address this research gap, we analyzed the effects of TDP-43 expression on layer 2/3 (L2/3) pyramidal neurons of the primary somatosensory cortex in mice projecting through corpus callosum. In utero electroporation (IUE) was performed to express GFP alone (control) or in combination with TDP-43. Compared with the control, mice co-expressing GFP and TDP-43 showed disturbed callosal axonal projections of L2/3 neurons. Mutant TDP-43 variants displayed a more pronounced phenotype, indicating pathogenic role during fetal cortical development. To distinguish developmental from maintenance effects, tamoxifen-inducible TDP-43 expression was used to initiate postnatal TDP-43 expression. Postnatal induction resulted in shorter axonal length and reduced branching rather than gross projections disturbance. Taken together, these results demonstrate that TDP-43 expression can disturb the integrity of axonal projections, such as callosal projections of L2/3 neurons in the somatosensory cortex.},
}

Animals
*DNA-Binding Proteins/metabolism/genetics
*Somatosensory Cortex/metabolism/pathology
*Axons/metabolism/pathology
*Amyotrophic Lateral Sclerosis/metabolism/pathology
Corpus Callosum/metabolism/pathology
Mice
Female
Mice, Transgenic
Pyramidal Cells/metabolism/pathology
Humans

@article {pmid42276614,
year = {2026},
author = {Karthikeyan, K and Velmurugan, G and Upadhyay, R and Sevanan, M and Chinnathambi, S},
title = {Glutamate and glutamine metabolism in neurodegenerative diseases.},
journal = {International review of neurobiology},
volume = {186},
number = {},
pages = {1-24},
doi = {10.1016/bs.irn.2026.01.008},
pmid = {42276614},
issn = {2162-5514},
mesh = {Humans ; *Glutamic Acid/metabolism ; *Glutamine/metabolism ; *Neurodegenerative Diseases/metabolism/drug therapy ; Animals ; },
abstract = {Glutamate is known as the most important excitatory neurotransmitter in brain. Glutamate and glutamine recycling is very essential to maintain the nitrogen metabolism. Despite of its major functions, its dysregulation is a basic pathology which is common to neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), and Amyotrophic lateral sclerosis (ALS). Amyloid-β and Tau in AD disrupt glutamate uptake and the glutamate-glutamine cycle, accelerating synaptic failure, whereas loss of astrocytic EAAT2 in ALS generates unrelenting excitotoxicity and motor neuron demise. Toxic α-synuclein aggregation in PD exacerbates dopamine-glutamate imbalance through destabilizing corticostriatal transmission. This review explores on the key mechanisms by which glutamate impairment leads to the pathogenies of neurogenerative disorders and also about current medications like amantadine, memantine, and riluzole which are glutamate antagonists, are shown to partially alleviative but cannot halt the advancement of the disease. One of the potential targets for disease-modifying treatments could be the receptor modulation, astrocytic function, and elimination of excess glutamate.},
}

Humans
*Glutamic Acid/metabolism
*Glutamine/metabolism
*Neurodegenerative Diseases/metabolism/drug therapy
Animals

@article {pmid42276908,
year = {2026},
author = {Covas Moschovas, M and Falagario, U and Pellegrino, F and Wiklund, P and Patel, V},
title = {Reply to Alexander Light, Max Peters, Manit Arya, et al's Salvage Focal Therapy vs Radical Prostatectomy for Localized Radiorecurrent Prostate Cancer. JAMA Oncol 2026;12:364-73. https://doi.org/10.1001/jamaoncol.2025.6448.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2026.05.031},
pmid = {42276908},
issn = {1873-7560},
}

@article {pmid42279231,
year = {2026},
author = {Mesches, MH and Granholm, AC and Paredes, D and Mesches, K and Oguma, Y and Dezawa, M},
title = {Stem Cell Therapy for Parkinson's Disease: A Mechanistically Distinct Role for Muse Cells.},
journal = {Journal of clinical medicine},
volume = {15},
number = {11},
pages = {},
pmid = {42279231},
issn = {2077-0383},
support = {R01 AG081356/AG/NIA NIH HHS/United States ; },
abstract = {Cell replacement therapy is a promising investigational approach for Parkinson's disease (PD), a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra. Although current PD therapies provide symptomatic relief, none halt or reverse disease progression. Early transplantation studies using fetal dopaminergic neurons provided proof of concept for PD cell replacement, with recent efforts focusing on pluripotent stem cell-derived dopaminergic progenitors that are now entering clinical testing. These strategies face challenges, however, including immune compatibility, tumorigenic risk, and the need for controlled differentiation and functional integration. Multi-lineage differentiating stress-enduring (Muse) cells are endogenous, non-tumorigenic pluripotent-like stem cells that home to sites of tissue injury and differentiate in response to the host microenvironment. A targeted literature search of PubMed and Scopus, however, did not identify prior reviews specifically addressing Muse cells in the context of PD, highlighting a gap in the literature. Here, we examine current limitations of established cell-replacement approaches and consider whether Muse cells may represent a mechanistically distinct cell source. Early clinical studies of Muse cell therapy in stroke and amyotrophic lateral sclerosis suggest an encouraging safety profile and preliminary signals of potential therapeutic benefit, although these findings are based on small, early-stage trials and require confirmation. The evidence supporting Muse cell therapy in PD is currently limited to a single preclinical animal study, supported by mechanistic in vitro findings and indirect evidence from other neurologic disease models; therefore, its relevance to PD remains to be established, and current evidence is insufficient to support conclusions regarding clinical efficacy. Together, these observations provide a rationale for further targeted preclinical investigation and support the systematic evaluation of Muse cells as a mechanistically distinct candidate for regenerative therapy in PD.},
}

@article {pmid42280649,
year = {2026},
author = {Liu, Q and Zhang, R and Sun, L and Lu, X and Xu, G and Tong, H and Zhang, B and Liu, X and Du, S},
title = {Mechanism of Echinochloa crus-galli Resistance to the ALS-Inhibiting Herbicide Pyrazosulfuron-ethyl in China.},
journal = {Plants (Basel, Switzerland)},
volume = {15},
number = {11},
pages = {},
pmid = {42280649},
issn = {2223-7747},
abstract = {Rice (Oryza sativa L.) is a staple food crop, feeding more than 3.5 billion people. With the increasing demand for food in the 21st century, weed infestation poses the most significant biotic threat to global food security, and herbicides remain the most effective and economic way to manage it in field. However, weeds can rapidly adapt under herbicide selection pressure due to their high competitiveness, rapid growth, and reproductive capacity. Hence, we collected Echinochloa crus-galli populations from Heilongjiang and Hebei provinces in China and investigated their resistance mechanisms to pyrazosulfuron-ethyl (PSE), a sulfonylurea herbicide that inhibits acetolactate synthase (ALS). Dose-response experiments confirm that the resistant (R) population exhibits 52.9-fold resistance to PSE compared with the susceptible (S) population. Inhibitor bioassays with malathion and NBD-Cl, together with ALS activity assays, ALS gene sequencing, and molecular docking, collectively suggest that resistance is strongly associated with the ALS Trp-574-Leu target-site substitution, with a possible additional contribution from enhanced herbicide metabolism. However, because the S and R populations originate from geographically distinct locations, some of the observed physiological and molecular differences may also reflect inherent population variation. Specifically, the ALS W574L substitution is predicted to reduce key interactions between ALS and PSE. This study provides valuable evidence for the risk of PSE resistance evolution in E. crus-galli and elucidates the molecular mechanism conferring resistance to ALS inhibitors.},
}

@article {pmid42281996,
year = {2026},
author = {Bonsall, S and Kazu, RS and King, M and Leung, D and Mahiddine, FY and Highley, JR and Strange, A and Chen, Y and Sassani, M and Cabras, S and Bowden, KM and Wareing, HE and Eldahshoury, MK and Boyne, JR and Collins, M and Monte, EM and Harvey, C and Gornall, SB and Jangid, A and Treanor, C and Moll, T and van Dijk, CH and Huang, Y and Urban, AE and Shaw, PJ and West, RJH and Kenna, KP and Hornstein, E and Zhang, S and Cooper-Knock, J and Zhou, J and Snyder, MP},
title = {Single-nucleus multiomic atlas of ALS primary motor cortex nominates neuroprotective WDR49-expressing astrocytes.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {42281996},
issn = {2693-5015},
support = {P50 HG007735/HG/NHGRI NIH HHS/United States ; R01 NS131409/NS/NINDS NIH HHS/United States ; },
abstract = {Amyotrophic lateral sclerosis (ALS) causes selective neurodegeneration in primary motor cortex, yet cell-type-specific molecular changes driving this vulnerability remain poorly understood. We present an integrated single-nucleus RNA- and ATAC-sequencing atlas of 778,330 nuclei from the primary motor cortex of 140 genetically characterised donors. ALS is associated with widespread transcriptional reprogramming driven by a common set of transcription factors (TFs) across multiple cell-types. Astrocytes harbour the most differentially expressed genes. Within astrocytes, a WDR49-expressing subpopulation is spatially associated with TDP-43 pathology, and genetic variants within WDR49 confer risk for both sporadic and monogenic autosomal dominant ALS. In patient-derived induced astrocytes, WDR49 protein abundance predicts the survival of co-cultured neurons. WDR49 localises to PML nuclear bodies, where it regulates astrocyte reactivity and secretion of EVs containing protein chaperones. Together, these in vivo and in vitro findings suggest that WDR49+ astrocytes mount a compensatory secretory response to extracellular protein aggregates, and that loss of this capacity lowers the threshold for ALS pathogenesis.},
}

@article {pmid42282536,
year = {2026},
author = {Cortez, JD and Avalos, JL},
title = {Heterologous iron-sulfur cluster biogenesis and delivery for cytosolic isobutanol and isopentanol production in Saccharomyces cerevisiae.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42282536},
issn = {2692-8205},
support = {T32 GM007388/GM/NIGMS NIH HHS/United States ; },
abstract = {Saccharomyces cerevisiae is an excellent microbial platform for sustainable production of next generation biofuels such as the branched chain higher alcohols (BCHAs) isobutanol and isopentanol. A cytosolic pathway for BCHA production is generated from expression of prokaryotic orthologs of branched-chain amino acid (BCAA) enzymes acetolactate synthase (ALS), mutant NADH-dependent ketol-acid reductoisomerase (KARI[P2D1-A1]), and dihydroxy-acid dehydratase (DHAD). The potential for this pathway has been hindered by the availability of iron-sulfur clusters, particularly the 2Fe-2S cluster, required for DHAD to function in the cytosol. ILV3, the endogenous yeast DHAD located in the mitochondria, can be deleted to create a valine auxotroph. In this study we use bioinformatics, heterologous gene library synthesis, and a valine complementation assay to find prokaryotic iron-sulfur cluster biosynthetic gene clusters (BGC) and accessory genes that aid DHAD function in the yeast cytosol. This work presents, to our knowledge, the first functional BGC that enhances the cytosolic activity of prokaryotic DHADs in S. cerevisiae. The SUF BGC from Bacillus subtilis combined with a ferritin-like protein (FTNB) from Escherichia coli and the Lactococcus lactis DHAD enhanced the production of BCHAs. Combined expression gave an average isobutanol titer of 412mg/L, 1.8-fold greater than L. lactis DHAD expressed alone. This work establishes a blueprint for better biofuel production by improving iron-sulfur cluster dependent enzyme activity in the yeast cytosol.},
}

@article {pmid42282588,
year = {2026},
author = {Kochen, NN and Zafari, S and Renaud, A and Schneider, N and Vunnam, N and Liao, EE and Dutton, JR and Braun, AR and Sachs, JN},
title = {From anti-fungal to potential neurotherapeutic: Posaconazole as an effective inhibitor of cellular TDP-43 pathology.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.06.01.728552},
pmid = {42282588},
issn = {2692-8205},
abstract = {Recently, we showed that ketoconazole, a known anti-fungal inhibitor of CYP51, stabilized TAR DNA-binding protein 43 (TDP-43) native self-interactions, reduced TDP-43 pathology and rescued TDP-43-induced SREBP2 downregulation. Despite its promising effects, ketoconazole is not viable for repurposing for ALS due to liver toxicity side effects that occur when orally delivered. To address this, we tested the activities of seven additional known azole-based CYP51 inhibitors in order identify a viable alternative to ketoconazole. Using our established TDP-43 mislocalization and aggregation assay in HEK293T cells, we identified posaconazole, an FDA-approved, CNS-penetrant and orally delivered anti-fungal, as the strongest inhibitor of TDP-43 pathology. Posaconazole was able to reduce insoluble TDP-43 and restore SREBP2 levels, outperforming ketoconazole. Mechanism of action (MOA) experiments suggest posaconazole is able to outperform ketoconazole by inducing a significantly stronger activation of autophagy and upregulation of heat shock proteins known to clear TDP-43. Further MOA experiments show that the effects of posaconazole on TDP-43 are dependent on its known ability to lower cellular cholesterol levels. By correlating our experimental results on the eight CYP51 inhibitors tested, we show that predicted affinity towards human CYP51 strongly correlates with the inhibitors' ability to lower TDP-43 aggregation and mislocalization. Finally, we tested posaconazole in a low dose sodium arsenite ALS model in iPSC-derived motor neurons, showing that it is efficacious at inhibiting TDP-43 pathology in the nanomolar range. Altogether, these results support the repurposing of posaconazole for ALS/FTD as a means to prevent TDP-43 pathology.},
}

@article {pmid42282797,
year = {2026},
author = {Yusuf, IO and Silva, RLA and Amoako, GG and Thompson, PR and Xu, Z},
title = {PAD2 knockout reduces myelin protein aggregates, modulates neuroinflammation and protects motor neurons, axons and neuromuscular junction in a SOD1-ALS mouse model.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.05.30.729013},
pmid = {42282797},
issn = {2692-8205},
abstract = {BACKGROUND: Dysregulated peptidyl deiminase 2 (PAD2) and aberrant protein citrullination (PC), a posttranslational modification (PTM), are involved in various inflammatory and neurodegenerative diseases. We previously showed in transgenic mice and postmortem human tissues that PC and PAD2 are altered in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by motor neurons loss, paralysis, and death. Herein, we investigated the role of PAD2 in ALS by PAD2 knockout in a SOD1-ALS mouse model.

METHODS: To investigate the role of PAD2-induced citrullination in ALS pathogenesis, we generated PAD2 knockout (PAD2KO) in SOD1 [G93A] ALS mouse model and investigated the consequent modulation on the neuropathology and clinical symptoms, using molecular biology techniques such as qPCR, Western blotting, confocal microscopy, and electron microscopy. Additionally, we identified C3 as being citrullinated in human ALS using ionFinder.

RESULTS: Our results show that PAD2KO blocked the increased PC and reduced myelin basic protein (MBP) aggregates in the ALS model. PAD2KO also improved motor neuron survival and the integrity of myelin, axons, and neuromuscular junctions, and reduced microgliosis in the white matter and C3 protein levels in astrocytes. Clinically, data from monitoring the body weight changes suggests that PAD2KO modulates the course of the disease in the ALS mouse model, accelerating the onset while slowing the progression after the onset, and modestly extending the survival of male mice.

CONCLUSION: These results show that PAD2 is responsible for the increased PC in ALS and PC contributes to neuroinflammation and degeneration of motor neurons and myelinated axons. The modest modulation of the disease phenotype suggests that the role of PC in ALS is complex, involving altered PC in numerous proteins and in multiple cell types. Future studies are needed to investigate how PC modulates individual protein functions in various cell types to understand the contribution of PC to ALS pathogenesis.},
}

@article {pmid42283221,
year = {2026},
author = {Scozzari, S and Columbro, SF and Favagrossa, M and Tortarolo, M and Cagnotto, A and Salmona, M and De Marco, G and Bendotti, C and Calvo, A and Pasetto, L and Bonetto, V},
title = {Effects of Lysine Deacetylation Inhibition Alone or in Combination With Arimoclomol on TDP-43 Proteinopathy.},
journal = {Journal of neurochemistry},
volume = {170},
number = {6},
pages = {e70493},
pmid = {42283221},
issn = {1471-4159},
support = {RF-2018-12365614//Ministero della Salute/ ; GATTALS//AriSLA/ ; },
mesh = {Animals ; *Histone Deacetylase Inhibitors/administration & dosage/pharmacology ; Humans ; Mice ; Acetylation/drug effects ; *Lysine/metabolism/antagonists & inhibitors ; *TDP-43 Proteinopathies/drug therapy/metabolism/pathology ; Mice, Transgenic ; Vorinostat/administration & dosage ; *DNA-Binding Proteins/metabolism ; Male ; },
abstract = {Cytoplasmic inclusions containing TAR DNA-binding protein 43 kDa (TDP-43) are recognized as a major pathological feature of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Peptidyl-prolyl cis-trans isomerase A (PPIA) interacts with TDP-43 and influences its aggregation and function. This interaction is facilitated by PPIA Lys-acetylation. Here, we investigated whether restoring lysine acetylation homeostasis exerts protective effects on TDP-43 proteinopathy in vitro and in vivo and how this relates with PPIA. We found that vorinostat/SAHA, a broad-spectrum histone deacetylase (HDAC) inhibitor that increases PPIA acetylation, is able to reverse TDP-43 mislocalization in a cellular model of TDP-43 proteinopathy. We confirmed its effects in peripheral blood mononuclear cells from ALS patients and explored its impact on TDP-43 proteinopathy and PPIA acetylation in the Thy1-hTDP-43 mouse model. Thy1-hTDP-43 mice treated with SAHA showed a delayed onset of TDP-43 pathology, associated with PPIA nucleus-cytoplasm redistribution, lower neurodegeneration and neuroinflammation, and improved neuromuscular function markers. However, these effects were transient. When combined with arimoclomol, a heat shock protein co-inducer, a mitigation of the neurodegeneration was sustained. A synergistic effect was observed in periphery, greatly enhancing tubulin acetylation and reducing phosphorylated TDP-43 accumulation in the sciatic nerve and acetylcholine receptor γ-subunit expression in gastrocnemius muscle. This study suggests that HDAC inhibition could be beneficial in restoring TDP-43 localization and function through multiple mechanisms, including modulation of PPIA acetylation. The combination of lysine deacetylation inhibition and arimoclomol shows a synergistic effect in vivo and has potential as a therapeutic approach for patients.},
}

Animals
*Histone Deacetylase Inhibitors/administration & dosage/pharmacology
Humans
Mice
Acetylation/drug effects
*Lysine/metabolism/antagonists & inhibitors
*TDP-43 Proteinopathies/drug therapy/metabolism/pathology
Mice, Transgenic
Vorinostat/administration & dosage
*DNA-Binding Proteins/metabolism
Male

@article {pmid42283246,
year = {2026},
author = {Fikry, H and Saleh, LA and Sadek, DR},
title = {Histological and Tissue-Level Outcomes of Stem Cell Therapies in Neurodegenerative Disorders: A Systematic Review.},
journal = {Clinical anatomy (New York, N.Y.)},
volume = {},
number = {},
pages = {},
doi = {10.1002/ca.70147},
pmid = {42283246},
issn = {1098-2353},
abstract = {Neurodegenerative diseases, which afflict millions worldwide and threaten public health, have no cure. Neurodegenerative diseases lack effective therapies, burdening society and the economy. Over the past 20 years, regenerative cell therapy (stem cell therapy) has advanced, opening novel neurodegenerative disease treatments. Thus, the current review aimed to systematically highlight experimental and clinical studies of potentially effective therapeutic strategies for stem cells and report histological, cellular, or ultrastructural outcomes following stem cell interventions in neurodegenerative diseases. PRISMA-compliant computerized literature searches of PubMed, Scopus, and Web of Science identified studies on embryonic, induced pluripotent, mesenchymal, or neural stem cells (NSCs) in neurodegenerative disease models and histological and tissue-level outcomes. Search terms included nervous system diseases, histology, neuron regeneration, stem cells, stem cell treatment, and transplantation. Peer-reviewed articles published between 2000 and 2025 were selected. Experimental animal and clinical studies that reported histological or tissue-level results after stem cell treatments were included. Eighty-six studies met the eligibility criteria, covering models of Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and Huntington's disease. Across these studies, stem cell therapies were linked to improved neuron survival, better synaptic structure, diminished gliosis, and some restoration of tissue structure. These effects depended on the type of stem cell used, the disease model, and how the treatment was given. Overall, the evidence suggests that stem cell therapies can lead to significant histological and tissue-level improvements in neurodegenerative diseases, supporting their potential for regeneration. Further standardized and translational studies are needed to clarify the underlying mechanisms and improve treatment strategies.},
}

@article {pmid42283497,
year = {2026},
author = {Turner, ED and Twelvetrees, AE},
title = {The Long Haul: Microtubule Motors as the Essential Supply Line for Neuronal Longevity.},
journal = {Journal of neurochemistry},
volume = {170},
number = {6},
pages = {e70496},
pmid = {42283497},
issn = {1471-4159},
support = {/WT_/Wellcome Trust/United Kingdom ; 220192/Z/20/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; *Microtubules/metabolism/physiology ; Animals ; *Neurons/metabolism/physiology ; *Molecular Motor Proteins/metabolism/genetics ; Mutation ; },
abstract = {The extreme morphology and polarised architecture of neurons require the highly sophisticated microtubule transport system for both construction and lifelong survival. Genomic evidence from an expanding landscape of human mutations supports the essential role of the microtubule transport machinery. During neurodevelopment, mutations disrupt the proliferation and migration of neuronal precursors, as well as the initial establishment of polarity. In the mature nervous system, the reliance on microtubule transport shifts to the long-term maintenance of axon integrity and synaptic proteostasis. Across the motor proteins responsible for long distance transport in neurons, mutations highlight a specific vulnerability of long axons to transport failure in Hereditary Spastic Paraplegia (HSP), Charcot Marie Tooth disease Type 2 (CMT2), Spinal Muscular Atrophy (SMA), Perry Syndrome, and Amyotrophic Lateral Sclerosis (ALS) amongst others. Due to the role of microtubule motors in development and maintenance, there is frequently a phenotypic spectrum within a single gene of the microtubule transport system. For example, mutations in dynein motors are linked both to malformations of cortical development and specific motor neuron loss in SMA-LED (Spinal Muscular Atrophy with Lower Extremity Predominance). By synthesising genetic evidence, this review illustrates how specific molecular failures, ranging from motor-domain kinetics to cargo binding, can inform our understanding of neuronal homeostasis. Ultimately, we argue that microtubule transport is not merely a cellular utility, but a key determinant of neuronal longevity.},
}

Humans
*Microtubules/metabolism/physiology
Animals
*Neurons/metabolism/physiology
*Molecular Motor Proteins/metabolism/genetics
Mutation

@article {pmid42283699,
year = {2026},
author = {El-Wahsh, S and Bogart, E and Bonnor, S and El-Wahsh, S and Graco, M and Hogden, A and Paynter, C and Raykar, V and Signorelli, M and Thomson, E and Vucic, S and White, S},
title = {Supporting gastrostomy decision-making in motor neurone disease (MND): an Australian survey of healthcare professionals' beliefs, practices, and needs.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/17582024.2026.2687483},
pmid = {42283699},
issn = {1758-2032},
abstract = {INTRODUCTION: Gastrostomy decision-making for people living with motor neurone disease (MND) is complex. While international studies report healthcare professionals' (HCPs) beliefs and practices in this area, little is known about the Australian context.

AIM: To examine Australian HCPs' beliefs, clinical practices, and support needs regarding gastrostomy decision-making in MND.

METHODS: A national cross-sectional online survey of Australian HCPs involved in gastrostomy discussions (n = 123) was conducted, exploring five domains: 1) initiating discussions and timing; 2) patient education; 3) multidisciplinary coordination; 4) guideline use; 5) and professional development needs. Descriptive statistics were applied.

RESULTS: Most HCPs initiated discussions about gastrostomy (74%), commonly prompted by swallowing difficulty, weight loss, or patient request. Although 72% believed discussions should occur before clinical indications, only 40% reported doing so. Earlier placement was favored in the context of respiratory decline compared with swallowing impairment, and 56% considered gastrostomy to be performed too late. Almost 40% used no formal guidelines, and 74% wanted further professional development.

CONCLUSION: Australian HCPs valued person-centered practice, but belief-practice gaps highlight opportunities to improve consistency, timing, and quality of gastrostomy decision-making support. Enhanced national guidelines, improved multidisciplinary communication, and targeted professional development may help reduce delays and better align practice with evidence-based recommendations.},
}

@article {pmid42285406,
year = {2026},
author = {Mendoza-Camacho, DM and Espinoza-Gutiérrez, HA and Viveros-Paredes, JM and Flores-Soto, ME and Tejeda-Martínez, AR},
title = {Recent advances in neurodegenerative diseases therapeutics: The inhibition of monoacylglycerol lipase strategy.},
journal = {Neuroscience},
volume = {610},
number = {},
pages = {198-206},
doi = {10.1016/j.neuroscience.2026.06.011},
pmid = {42285406},
issn = {1873-7544},
mesh = {Humans ; *Monoacylglycerol Lipases/antagonists & inhibitors/metabolism ; Animals ; *Neurodegenerative Diseases/drug therapy/metabolism/enzymology ; Endocannabinoids/metabolism ; *Enzyme Inhibitors/pharmacology/therapeutic use ; },
abstract = {Neurodegenerative diseases share common pathophysiological mechanisms, including chronic neuroinflammation, glutamatergic excitotoxicity, oxidative stress, mitochondrial dysfunction, and disruptions in synaptic and lipid homeostasis. In this context, the endocannabinoid system has emerged as a key modulator of neuroimmune communication and neuronal survival. Within this system, Monoacylglycerol Lipase (MAGL) plays a central role by regulating the levels of the endocannabinoid 2-Arachidonoylglycerol (2-AG) while simultaneously contributing to the generation of arachidonic acid and pro-inflammatory eicosanoids. Pharmacological or genetic inhibition of MAGL increases 2-AG levels and concurrently reduces the biosynthesis of pro-inflammatory lipid mediators, thereby modulating microglial activation, astrocytic responses, and neuronal excitotoxicity. Preclinical studies in models of Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis consistently demonstrate that MAGL blockade attenuates neuroinflammation, preserves synaptic and neuronal integrity, improves motor and cognitive function, and, in some cases, delays disease progression. Although clinical evidence remains limited, the available data position MAGL as a metabolic convergence point between inflammation and neurodegeneration, suggesting that its modulation may represent a therapeutic strategy with disease-modifying potential.},
}

Humans
*Monoacylglycerol Lipases/antagonists & inhibitors/metabolism
Animals
*Neurodegenerative Diseases/drug therapy/metabolism/enzymology
Endocannabinoids/metabolism
*Enzyme Inhibitors/pharmacology/therapeutic use

@article {pmid42286839,
year = {2026},
author = {Wheeler, A and Mehta, K and Sanders, D and Chin, C and Zivalic, H and Carey, J and McCaffrey, A and Pant, P and Lewenhaupt, C and Luppino, S and Jacobs, G and Golden, S and Gifford, R and Scirocco, E and Keegan, M and Hatem, M and Yazdanian, T and Uysal, SP and Susco, N and Schwartzman, S and Branch, K and Hall, KE and Barnas, J and Lam, J and Hagar, J and Hannan, CA and Paganoni, S and Berry, JD and Garret, M and Scalia, J and Babu, S},
title = {Optimizing Research Operations and Resource Utilization in ALS Care: Insights From the Tofersen Antisense Oligonucleotide Expanded Access Protocol.},
journal = {Muscle & nerve},
volume = {74},
number = {3},
pages = {692-697},
pmid = {42286839},
issn = {1097-4598},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/therapy ; Female ; Middle Aged ; Male ; Aged ; *Oligonucleotides, Antisense/therapeutic use/administration & dosage ; Superoxide Dismutase-1/genetics ; *Health Resources ; Adult ; },
abstract = {INTRODUCTION/AIMS: Tofersen is a gene-targeted therapy for individuals with superoxide dismutase 1 (SOD1) (+) amyotrophic lateral sclerosis (ALS). Prior to U.S. Food and Drug Administration (FDA) approval, tofersen was made available through expanded access protocol. This study describes the clinical and operational experience of administering tofersen through expanded access protocols at a single academic medical center in the U.S.

METHODS: Individuals with symptomatic SOD1(+) ALS (≥ 18 years), who were ineligible for traditional ALS clinical trials, received tofersen via bedside lumbar punctures at Massachusetts General Hospital. Treatment was provided through single-patient and intermediate-sized expanded access protocols prior to FDA approval. Demographic and clinical characteristics, referral-to-treatment timelines, safety outcomes, and operational costs were collected.

RESULTS: Eleven individuals with SOD1(+) ALS received monthly intrathecal tofersen over a two-year period (July 2021 to July 2023). Most participants were female, and 81.8% had leg-onset ALS. The mean (SD) referral-to-first dose duration was 36 (22.4) days. A total of 120 doses were administered over a two-year period. Tofersen was safe and well tolerated, with no treatment-related serious adverse events. Operational costs totaled $336,620, supported by philanthropy and insurance. The company provided the drug for free.

DISCUSSION: This experience demonstrates the feasibility of implementing a resource-intensive expanded access protocol within an academic medical center using a mixed funding model to facilitate early access to emerging ALS therapies.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy/genetics/therapy
Female
Middle Aged
Male
Aged
*Oligonucleotides, Antisense/therapeutic use/administration & dosage
Superoxide Dismutase-1/genetics
*Health Resources
Adult

@article {pmid42287757,
year = {2026},
author = {Jaberi, KR and Haghighi, MR and Aligholi, H and Takallu, S and Asadi, P and Mirzaei, E and Jaberi, AR and Sahraian, A},
title = {Focused ultrasound-mediated nanocarrier delivery across the blood-brain barrier for neurodegenerative diseases.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {201},
number = {},
pages = {119622},
doi = {10.1016/j.biopha.2026.119622},
pmid = {42287757},
issn = {1950-6007},
mesh = {Humans ; *Blood-Brain Barrier/metabolism/drug effects ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; *Drug Delivery Systems/methods ; *Drug Carriers/chemistry ; *Nanoparticles ; *Nanoparticle Drug Delivery System ; *Ultrasonic Waves ; Microbubbles ; },
abstract = {The development of effective therapies for neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis remains a major challenge due to the restrictive nature of the blood-brain barrier (BBB). Conventional systemic drug delivery strategies often fail to achieve sufficient central nervous system (CNS) penetration while avoiding peripheral toxicity. Focused ultrasound (FUS), particularly when combined with microbubbles or nanocarriers, has emerged as a non-invasive approach to transiently and precisely open the BBB, enabling targeted delivery of therapeutics to the brain parenchyma. This review provides a comprehensive overview of the mechanisms by which FUS enhances CNS drug delivery, with a dedicated focus on its integration with nanoparticle-based systems, including liposomes, polymeric nanoparticles, dendrimers, metallic nanoparticles, and exosomes. We discuss how these nanocarriers can be engineered for improved stability, targeting specificity, and stimulus-responsive release upon FUS exposure. Recent advances in ultrasound technology, image guidance (particularly MRI), and therapeutic formulations are summarized, along with preclinical and clinical evidence across key neurodegenerative conditions. Despite promising results, several challenges remain, including long-term BBB stability, regulatory standardization, and scalability for broad clinical application. By integrating principles from acoustics, pharmacology, and nanotechnology, FUS-mediated drug delivery, especially in combination with smart nano systems, represents a significant advancement in precision neurotherapeutics, offering new hope for previously untreatable CNS diseases.},
}

Humans
*Blood-Brain Barrier/metabolism/drug effects
*Neurodegenerative Diseases/drug therapy/metabolism
Animals
*Drug Delivery Systems/methods
*Drug Carriers/chemistry
*Nanoparticles
*Nanoparticle Drug Delivery System
*Ultrasonic Waves
Microbubbles

@article {pmid42288074,
year = {2026},
author = {Tackaert, T and Hemeryck, J and Duchatelet, C and Vanwulpen, M and Hachimi-Idrissi, S},
title = {Mean airway pressure as the missing link in CPR physiology: A prehospital comparison of manual and mechanical chest compressions.},
journal = {The American journal of emergency medicine},
volume = {108},
number = {},
pages = {80-85},
doi = {10.1016/j.ajem.2026.06.012},
pmid = {42288074},
issn = {1532-8171},
mesh = {Humans ; Female ; *Cardiopulmonary Resuscitation/methods ; *Out-of-Hospital Cardiac Arrest/therapy/physiopathology ; Male ; *Emergency Medical Services/methods ; Pilot Projects ; Prospective Studies ; Middle Aged ; Aged ; Pressure ; *Heart Massage/methods ; Adult ; },
abstract = {BACKGROUND: The impact of manual versus mechanical chest compressions on mean airway pressure (mPAW) during cardiopulmonary resuscitation (CPR) is poorly understood. This exploratory pilot study assessed intratracheal airway pressures during prehospital CPR in out-of-hospital cardiac arrest (OHCA).

METHODS: Adult OHCA patients treated by the prehospital Medical Emergency Team of the Ghent University Hospital (Belgium) were prospectively enrolled. Intratracheal pressure was recorded immediately after intubation, mPAW was calculated for both the first and last minutes of advanced life support (ALS). The results were compared between mechanical compressions using the Stryker LUCAS3® device and manual chest compressions (with chest compression feedback).

RESULTS: Nineteen patients were included (manual n = 10; mechanical n = 9). Initial median mPAW was low (7.74 mbar) and showed a slight increase over time. Mechanical compressions generated higher early mPAW than manual compressions (8.96 vs. 6.54 mbar). mPAW increased over time with manual compressions and decreased with mechanical compressions. Patients who achieved return of spontaneous circulation (ROSC) showed higher mPAW, though this difference was not statistically significant.

CONCLUSIONS: Prehospital mPAW values were substantially lower than those reported in previous ED-based studies. While airway pressure patterns differed between compression modalities, overall pressures were similar. These findings highlight complex airway mechanics during CPR and support further research into whether higher airway pressures could improve airway patency, oxygenation, and hemodynamics in selected OHCA patients.},
}

Humans
Female
*Cardiopulmonary Resuscitation/methods
*Out-of-Hospital Cardiac Arrest/therapy/physiopathology
Male
*Emergency Medical Services/methods
Pilot Projects
Prospective Studies
Middle Aged
Aged
Pressure
*Heart Massage/methods
Adult

@article {pmid42288493,
year = {2026},
author = {Wang, N and Li, Y and Li, N and Shen, L and Wang, C and Zhu, H and Zhou, Z and Ding, Y and Zhang, J and Fang, L and Bai, B},
title = {Quantitative Proteomics Unveils Comprehensive Tissue-Specific VCP Interaction Networks in Mice.},
journal = {Scientific data},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41597-026-07626-0},
pmid = {42288493},
issn = {2052-4463},
support = {32071256//National Natural Science Foundation of China/ ; 82172354//National Natural Science Foundation of China/ ; },
abstract = {Valosin-containing protein (VCP), a conserved AAA ATPase hexamer, participates in multiple biological processes including ERAD, ubiquitin-dependent degradation by extracting misfolded proteins for proteasomal degradation. Although its interactions with cofactors are well-characterized, and its dysregulation is implicated in multisystem proteinopathy, amyotrophic lateral sclerosis, and cancer, the tissue-specific VCP interactomes underlying its functional versatility remain elusive. Here, we generated HA-N-tagged VCP knock-in mice via CRISPR/Cas9 strategy and performed affinity purification coupled with data-independent acquisition (DIA) mass spectrometry to systematically profile VCP interactors across eight mouse tissues, yielding a high-confidence dataset. We identified 923 robust VCP-binding partners, including established interactors (UBX2B, UFD1, proteasomal subunits) and novel candidates implicated in energy metabolism (TCA cycle, oxidative phosphorylation) and protein quality control (proteasome, ERAD). Notably, we validated the interaction of VCP to two hepatic candidate proteins, DAXX and PRKAG2 (AMPK γ2 regulatory subunit), using HepG2 cells. This study establishes the first in vivo atlas of the VCP interaction network, providing mechanistic insights into its tissue-specific roles and highlighting potential therapeutic avenues for VCP-related disorders.},
}

@article {pmid42289668,
year = {2026},
author = {Pillay, S and Head, J and Horn, A and de Wet, W and Davidge, R and Dickson-Hall, M and Felix, G and Kali, G and Khan, W and Klein, B and Nakwa, F and Venter, M and Vlok, N and Wege, M and Stassen, W},
title = {The development of a consensus-based curriculum for a Bespoke Online Neonatal Education for Transfers (BONNETs) course.},
journal = {BMC medical education},
volume = {26},
number = {1},
pages = {},
pmid = {42289668},
issn = {1472-6920},
mesh = {Humans ; *Curriculum ; Infant, Newborn ; *Patient Transfer ; Consensus ; South Africa ; *Neonatology/education ; *Education, Distance ; Emergency Medical Services ; },
abstract = {BACKGROUND: High neonatal mortality in Sub-Saharan Africa (SSA) is driven by multiple systemic barriers, including insufficient neonatal transport infrastructure and limited provider training. Although specially trained neonatal retrieval teams are recommended for interfacility neonatal transfers, resource constraints lead to non-specialist emergency medical services (EMS) cadres performing these roles, potentially compromising the safe transport of critically ill neonates.

OBJECTIVE: To develop a bespoke, online neonatal interfacility transfer curriculum, informed by expert consensus and South African research to address critical gaps in provider knowledge and confidence, thereby improving neonatal transfer outcomes.

METHODS: Building on Kern's Six-Step Framework for curriculum development, an initial curriculum was derived through a comprehensive literature review, a retrospective chart analysis of neonatal cases in South Africa, and detailed interviews with experts and learners. Consequently, consensus on this curriculum was sought using a virtual, modified Nominal Group Technique (NGT) over two consensus rounds. A refined course curriculum is proposed.

RESULTS: Fourteen expert participants (neonatologists, paediatricians, neonatal nurses, and Advanced Life Support (ALS) providers with ≥ 3 years of experience) allocated potential outcomes to Core, Extended, or Advanced tiers based on EMS scope of practice. A 75% consensus threshold was applied. Eleven experts completed both rounds (21% attrition). Most were ALS providers (43%), largely employed in the public sector (71%). The final curriculum consists of three sequential courses (Core, Extended, Advanced) which scaffolds learning. The Core course consists of five modules, with each curriculum item achieving > 90% agreement on foundational skills including basic assessment, recognition of critical instability, and escalation pathways. This open-access online course is tailored to resource-limited settings.

CONCLUSION: A consensus-driven neonatal interfacility transfer curriculum for South Africa was successfully developed, providing a tiered, evidence-based approach to reinforce provider knowledge and confidence. By leveraging expanding internet accessibility, the Bespoke Online NeoNatal Education for Transfers (BONNETs) framework mitigates geographic disparities while integrating best practices for safe neonatal transfer. However, rigorous validation across diverse contexts and attention to broader systemic challenges, is essential to achieving sustained improvements. Future research should assess the curriculum's performance in improving knowledge and confidence, as well as long-term clinical impact on neonatal outcomes.},
}

Humans
*Curriculum
Infant, Newborn
*Patient Transfer
Consensus
South Africa
*Neonatology/education
*Education, Distance
Emergency Medical Services

@article {pmid42290559,
year = {2026},
author = {Martyniuk, О and Mushii, O and Pavlova, A},
title = {Integrated Analysis of hsa-miR-26b-5p and hsa-miR-186-5p in Blood Serum and Tumor Tissue Reveals their Prognostic and Predictive Significance in Breast Cancer.},
journal = {Experimental oncology},
volume = {48},
number = {1},
pages = {31-39},
doi = {10.15407/exp-oncology.2026.01.031},
pmid = {42290559},
issn = {2312-8852},
mesh = {Humans ; *MicroRNAs/genetics/blood ; Female ; *Breast Neoplasms/genetics/blood/pathology/mortality ; Prognosis ; *Biomarkers, Tumor/genetics/blood ; Middle Aged ; Adult ; Gene Expression Regulation, Neoplastic ; },
abstract = {BACKGROUND: Breast cancer (BC) heterogeneity signifi antly complicates diagnosis, prognosis, and prediction of treatment response. MicroRNAs (miRNAs) have emerged as promising biomarkers due to their involvement in tu- mor progression and in regulating therapy sensitivity. however, the combined clinical signifi ance of circulating and tumor-associated miRNAs, such as hsa-miR-26b-5p and hsa-miR-186-5p, remains insuffi tly elucidated. Materi- als and Methods. Expression levels of hsa-miR-26b-5p and hsa-miR-186-5p were analyzed in serum and tumor tis- sue of 124 BC patients. Associations with clinicopathological parameters were assessed. The prognostic signifi ance was evaluated based on disease progression and recurrence within 3 years. The predictive value was determined in patients receiving neoadjuvant chemotherapy (4AC regimen) using response assessment and ROC analysis. Re- sults. young BC patients (≤45 years) demonstrated signifi antly lower circulating levels of both miRNAs. Serum hsa-miR-186-5p expression was associated with early-stage disease, tumor size, lymph node status, and molecular subtype. Increased circulating hsa-miR-26b-5p levels were linked to disease progression, whereas decreased hsa- miR-186-5p levels were observed in patients with unfavorable outcomes. In tumor tissue, hsa-miR-26b-5p expres- sion correlated with tumor grade, size, and metastatic status, showing elevated levels in poorly differentiated tumors and reduced expression in metastatic disease. In contrast, hsa-miR-186-5p was associated with the molecular sub- type and lymph node involvement, with the highest expression observed in hER2-positive tumors and in patients with recurrence. Elevated levels of hsa-miR-186-5p in both serum and tumor tissue were associated with reduced sensitivity to doxorubicin-based neoadjuvant chemotherapy. ROC analysis confi med its predictive value (AUC = 0.750 for serum and 0.818 for tumor tissue). No signifi ant association between hsa-miR-26b-5p and chemothe- rapy response was observed.

CONCLUSIONS: hsa-miR-26b-5p and hsa-miR-186-5p demonstrate complementary roles in BC biology. hsa-miR-26b-5p is primarily associated with tumor aggressiveness and cancer progression, whereas hsa-miR-186-5p refl cts its molecular characteristics and response to chemotherapy. Their combined assessment in serum and tumor tissue represents a promising approach for improving prognostic stratifi ation and predicting treatment effi acy in BC patients.},
}

Humans
*MicroRNAs/genetics/blood
Female
*Breast Neoplasms/genetics/blood/pathology/mortality
Prognosis
*Biomarkers, Tumor/genetics/blood
Middle Aged
Adult
Gene Expression Regulation, Neoplastic

@article {pmid42290625,
year = {2026},
author = {Tenenbein, M},
title = {Author response to: Mullins et al. comment on, "We need a standardized North American acetylcysteine dosing regimen for the treatment of paracetamol (acetaminophen) poisoning".},
journal = {Clinical toxicology (Philadelphia, Pa.)},
volume = {64},
number = {8},
pages = {633-635},
doi = {10.1080/15563650.2026.2679164},
pmid = {42290625},
issn = {1556-9519},
mesh = {*Acetaminophen/poisoning ; *Acetylcysteine/administration & dosage/therapeutic use ; Humans ; *Antidotes/administration & dosage/therapeutic use ; *Analgesics, Non-Narcotic/poisoning ; North America ; },
abstract = {INTRODUCTION: I have reviewed Mullins et al's critique of my commentary "We need a standardized North American acetylcysteine dosing regimen for the treatment of paracetamol (acetaminophen) poisoning".

DISCUSSION: I concur regarding this need, and I agree that the original three-bag regimen should be retired. However, we disagree upon its replacement. They challenge my recommendation for a two-bag regimen, and they favour the one-bag two-step approach. The impetus for a replacement acetylcysteine regimen is to decrease the adverse effects and errors associated with the three-bag protocol. However, the one-bag two-step regimen was not designed to decrease adverse effects, and their published reports do not find a decrease of errors. And a fatal adverse effect, acetylcysteine overdose, has emerged with use experience of this regimen.

CONCLUSIONS: The one-bag two-step regimen should be dismissed from the quest for a standardized North American acetylcysteine dosing regimen for the treatment of paracetamol (acetaminophen) poisoning.},
}

*Acetaminophen/poisoning
*Acetylcysteine/administration & dosage/therapeutic use
Humans
*Antidotes/administration & dosage/therapeutic use
*Analgesics, Non-Narcotic/poisoning
North America

@article {pmid42293320,
year = {2026},
author = {Novikova, L and Lang, C and Tumani, H and Klose, V and Kassubek, J and Dreyhaupt, J and Dupuis, L and Wabitsch, M and Ludolph, A},
title = {Thyroid hormones and energy metabolism in amyotrophic lateral sclerosis.},
journal = {Brain communications},
volume = {8},
number = {3},
pages = {fcag198},
pmid = {42293320},
issn = {2632-1297},
abstract = {Weight loss, partially caused by hypermetabolism, represents a well-documented and therapeutically relevant feature of the amyotrophic lateral sclerosis phenotype worldwide. In this study, we retrospectively analysed the association between thyroid function and clinical, prognostic and metabolic parameters in a cohort of patients with amyotrophic lateral sclerosis in an experienced centre in Germany (n = 1754). Specifically, we examined the relationship between thyroid stimulating hormone levels, age, glucose and body mass index and-in subgroups-phosphorylated neurofilament heavy chain levels in CSF. There was no association between thyroid stimulating hormone levels and body mass index in patients with amyotrophic lateral sclerosis (n = 954). In contrast with other cohorts, thyroid stimulating hormone levels decreased with age in patients with amyotrophic lateral sclerosis indicating hypothalamic deficiency in the ageing patients. There was no association between thyroid stimulating hormone and phosphorylated neurofilament heavy chain (prognostic marker) in CSF of a subcohort (n = 646). Thyroid stimulating hormone levels correlated with glucose levels, an effect more pronounced in male patients. In conclusion, our results suggest that thyroid metabolism does not significantly contribute to amyotrophic lateral sclerosis-related weight loss or disease prognosis as estimated by phosphorylated neurofilament heavy chain; thyroid dysfunction is unlikely to be a primary driver of the metabolic dysregulation observed in amyotrophic lateral sclerosis. Most interestingly, thyroid stimulating hormone levels show an unexpected negative relation to age in patients with amyotrophic lateral sclerosis.},
}

@article {pmid42293321,
year = {2026},
author = {Ma, M and Zhao, B and Gao, N and Sun, X and Shao, K and Lin, P and Li, W and Zhao, Y and Yu, D and Yan, C and Liu, S and Yun, Y},
title = {Quantitative susceptibility mapping reveals widespread brain iron abnormalities in sporadic patients with early-stage amyotrophic lateral sclerosis.},
journal = {Brain communications},
volume = {8},
number = {3},
pages = {fcag190},
pmid = {42293321},
issn = {2632-1297},
abstract = {In the present study, using the novel quantitative susceptibility mapping technique, we aimed to systematically investigate brain iron alterations in a large group of sporadic early-stage amyotrophic lateral sclerosis patients and their correlation with clinical disability. In this study, amyotrophic lateral sclerosis patients at King's stage 1 were defined as early-stage amyotrophic lateral sclerosis patients, and 53 newly diagnosed early-stage amyotrophic lateral sclerosis patients and 50 healthy controls were included. Voxel-based whole-brain quantitative susceptibility mapping analysis was used to explore brain iron alterations. Voxel-based morphometry analysis was also performed. Longitudinal follow-up was performed in amyotrophic lateral sclerosis patients, and the follow-up progression rate was calculated. We found that, compared with healthy controls, early-stage amyotrophic lateral sclerosis patients presented significantly increased susceptibility values, mainly in the motor cortex, prefrontal cortex, hippocampus and cerebellar regions, while volumetric alterations were not detected. Moreover, motor and extra-motor cortex susceptibility values were significantly correlated with upper motor neuron scores and follow-up progression rate (r = 0.452-0.504, P < 0.01) in early-stage amyotrophic lateral sclerosis patients. We demonstrated a clear profile of early motor and extra-motor iron depositions and their important roles in early-stage amyotrophic lateral sclerosis patients. We suggest that quantitative susceptibility mapping is likely a promising neuroimaging approach for assessing early upper motor neuron damage and detecting early extra-motor alterations in amyotrophic lateral sclerosis patients.},
}

@article {pmid42293743,
year = {2026},
author = {Mavillonio, A and Rizzini, D and Detassis, S and Denti, MA},
title = {Neurodegenerative spliceosomopathies.},
journal = {Frontiers in cell and developmental biology},
volume = {14},
number = {},
pages = {1787859},
pmid = {42293743},
issn = {2296-634X},
abstract = {Spliceosomal syndromes are a group of disorders caused by pathogenic variants in core spliceosomal RNAs or proteins, leading to defective pre-mRNA splicing and tissue-specific disease vulnerability. Although the spliceosome is ubiquitously expressed, its dysfunction preferentially affects highly splicing-dependent tissues such as the retina and the nervous system. This mini-review focuses on neurodegenerative spliceosomopathies, including spinal muscular atrophy, amyotrophic lateral sclerosis, and retinitis pigmentosa, highlighting how alterations in snRNP biogenesis, spliceosome assembly, and splicing fidelity drive neuronal and photoreceptor degeneration. We discuss shared and distinct molecular mechanisms, unresolved questions on tissue specificity, and emerging therapeutic strategies targeting RNA splicing.},
}

@article {pmid42295687,
year = {2026},
author = {Jürs, AV and Naumann, M and Lehto, A and Schön, H and Kurth, J and Prudlo, J and Hermann, A and Kasper, E},
title = {Cognitive and Neuroimaging Divergence Between Juvenile and Adult FUS Amyotrophic Lateral Sclerosis.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
pmid = {42295687},
issn = {2328-9503},
support = {//Hermann und Lilly Schilling-Stiftung für medizinische Forschung im Stifterverband/ ; //Clinician Scientist Program of the Center for Transdisciplinary Neuroscience Rostock/ ; },
abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive motor neuron degeneration. Fused in sarcoma (FUS)-associated juvenile ALS (jALS) represents a distinct and aggressive subgroup with rapid deterioration and poor prognosis. Certain FUS mutations have been associated with comorbid intellectual disability, suggesting neurodevelopmental involvement. We compared FUS-jALS with adult-onset FUS-ALS cases (aALS) to evaluate the association between premorbid cognitive impairment, genetic and clinical features incorporating neuroimaging data.

METHODS: Patients with genetically confirmed FUS-ALS were classified as jALS (onset < 25 years) or aALS (onset ≥ 25 years). Neuropsychological assessment used Mehrfachwahl-Wortschatz-Test (MWT) for verbal IQ, and the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), with cognitive impairment classified according to Strong criteria. Volumetric analysis was conducted on structural MRI and FDG-PET data.

RESULTS: All three jALS (P525L [n = 2], H517_Q519del [n = 1]) showed rapid progression with early severe clinical events. Neuropsychological assessment revealed global cognitive deficits (ALS-ci) with widespread dysfunction beyond typical ALS-specific patterns and reduced verbal IQ, pointing towards premorbid cognitive impairment. aALS demonstrated slower progression and were predominantly cognitively unimpaired (ALS-ni) or showed an ALS-specific impairment. Neuroimaging revealed distinct patterns: jALS cases demonstrated posterior cortical atrophy and hypometabolism on FDG-PET, while aALS showed largely preserved brain volumes and limbic-subcortical hypometabolism.

INTERPRETATION: Specific FUS mutations (P525L, H517_Q519del) predispose to jALS with severe progression and premorbid cognitive impairments, supporting a genotype-phenotype association. Posterior cortical findings suggest neurodevelopmental delay rather than disease-related neurodegeneration. Genetic FUS screening may be warranted in patients with intellectual disability and motor signs, given emerging targeted therapies.},
}

@article {pmid42295787,
year = {2026},
author = {Zangrando, L and Buratti, E and Paron, F},
title = {TDP-43 Aggregation: The Healthy-Toxic Balance of the Prion-Like Domain.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {13},
number = {40},
pages = {e76119},
pmid = {42295787},
issn = {2198-3844},
support = {//AriSLA 2022-NOSRESCUEALS/ ; },
mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics/chemistry ; *Prions/metabolism/genetics ; *Protein Aggregation, Pathological/genetics/metabolism ; *Neurodegenerative Diseases/metabolism/genetics ; Protein Domains ; *Protein Aggregates ; Animals ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; },
abstract = {TAR DNA-binding protein 43 (TDP-43) is a ubiquitously expressed RNA-binding protein that plays essential roles in RNA metabolism, including transcription, splicing, transport, and stability. Pathological TDP-43 aggregates have become a defining hallmark of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and a large subset of frontotemporal lobar degeneration (FTLD). In the last decade, increasing evidence has challenged the initial thought of TDP-43 condensates as a purely pathological event, highlighting instead the physiological relevance of reversible self-association, polymerization and liquid-liquid phase separation (LLPS) in regulating TDP-43 functions. In this review, we provide an integrated overview of the structural determinants governing TDP-43 two-faced polymerization, with a particular focus on the prion-like domain and its parallelism with prion proteins. Indeed, while physiological assemblies support normal RNA processing, the dysregulation of LLPS by either disease-associated mutations, altered RNA-binding, aberrant post-translational modifications, or proteolytic cleavage can promote the transition toward irreversible, pathogenic aggregates. Finally, we summarize strategies aimed at eliminating TDP-43 aggregates or modulating its phase-separation behavior. Altogether, this review frames TDP-43 polymerization in both healthy and pathological conditions, offering a prion-like centered view of TDP-43 proteinopathies.},
}

Humans
*DNA-Binding Proteins/metabolism/genetics/chemistry
*Prions/metabolism/genetics
*Protein Aggregation, Pathological/genetics/metabolism
*Neurodegenerative Diseases/metabolism/genetics
Protein Domains
*Protein Aggregates
Animals
*Amyotrophic Lateral Sclerosis/genetics/metabolism

@article {pmid42296226,
year = {2026},
author = {Naumann, M and Kretschmer, S and Dorst, J and Lapp, H and Peikert, K and Petri, S and Gess, B and Wolf, C and Rödiger, A and Smesny, U and Pan-Montojo, F and Kerschen, P and Grehl, T and Prudlo, J and Regensburger, M and Ludolph, A and Günther, R and Brenner, D and Lee-Kirsch, MA and Hermann, A},
title = {Innate immune signaling as a potential pathomechanistic biomarker for distinct subtypes in amyotrophic lateral sclerosis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/21678421.2026.2663910},
pmid = {42296226},
issn = {2167-9223},
abstract = {Stimulation of the innate immune system has been implicated in ALS and particularly in distinct monogenic forms of ALS. To address whether this is of diagnostic value, we performed a proof-of concept study using qPCR to assess the Interferon score in blood samples of genetic ALS. 56.5% of genetic ALS patients showed significant IFN activation, highest in C9orf72HRE patients (77.3%). About half of FUS-ALS (52.2%), but none of SOD1-ALS patients demonstrated pathological IFN scores. The IFN score significantly correlated with the ALSFRS-R slope and inversely with the time to severe event as a survival surrogate in this genetic ALS cohort. IFN + patients were more likely to be male, showed more rapid disease progression and higher neurofilament levels. The IFN score might have the potential as a stratification and readout tool for biomarker-guided individualized therapy in ALS.},
}

@article {pmid42296263,
year = {2026},
author = {Fabry, V and Faruch-Bilfeld, M and El Khalfi, R and Acket, B and Al Achram, Y and Cintas, P},
title = {Whole-body muscle MRI improves diagnostic certainty in amyotrophic lateral sclerosis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/21678421.2026.2685160},
pmid = {42296263},
issn = {2167-9223},
abstract = {Introduction: Early diagnosis of amyotrophic lateral sclerosis (ALS) remains challenging due to the absence of a definitive biomarker and the difficulty of demonstrating widespread lower motor neuron (LMN) involvement. Whole-body muscle MRI (WB-MRI) enables comprehensive assessment of muscle involvement and may improve detection of LMN dysfunction. This study aimed to evaluate whether WB-MRI improves diagnostic certainty in ALS when combined with clinical and electromyography (EMG) assessment. Methods: In this prospective single-center study, 47 patients with ALS underwent clinical examination, EMG, and WB-MRI. Diagnostic classification according to the Awaji criteria was assessed using clinical and EMG data alone and after integration of MRI markers of LMN involvement, including fatty infiltration and muscle edema, or muscle edema alone as a surrogate marker. Results: WB-MRI identified additional LMN-involved regions in 27.7% of patients when both fatty infiltration and muscle edema were considered, and in 42.6% when considering muscle edema alone. This resulted in diagnostic upgrading in 14.9% and 25.5% of patients, respectively. The proportion of definite ALS increased from 8.5% to 17.0% when muscle edema alone was considered. MRI had limited impact on diagnostic classification according to the Gold Coast criteria. Among patients without LMN involvement on clinical and EMG assessment (all with bulbar-onset), 50% were reclassified after MRI. Conclusion: WB-MRI improves detection of LMN involvement and increases diagnostic certainty according to the Awaji criteria, with muscle edema appearing to be the most relevant MRI marker for integration into ALS diagnostic assessment.},
}

@article {pmid42297978,
year = {2026},
author = {Card, NS and Singer-Clark, T and Peracha, H and Iacobacci, C and Hou, X and Wairagkar, M and Fogg, Z and Offenberg, EC and Hochberg, LR and Stavisky, SD and Brandman, DM},
title = {Long-term independent use of an intracortical brain-computer interface for speech and cursor control.},
journal = {Nature medicine},
volume = {32},
number = {7},
pages = {2504-2510},
pmid = {42297978},
issn = {1546-170X},
support = {A2295-R//VHA Office of Research and Development | Rehabilitation Research and Development Service (Rehabilitation Research & Development Service)/ ; N/A//Achievement Rewards for College Scientists Foundation (ARCS Foundation)/ ; 1DP2DC021055//U.S. Department of Health & Human Services | NIH | NIH Office of the Director (OD)/ ; N/A//Burroughs Wellcome Fund (BWF)/ ; 23-SGP-652//Amyotrophic Lateral Sclerosis Association (ALS Association)/ ; AL220043//United States Department of Defense | Office of the Secretary of Defense (OSD)/ ; DP2 DC021055/DC/NIDCD NIH HHS/United States ; },
mesh = {*Brain-Computer Interfaces ; Humans ; Male ; *Speech/physiology ; Amyotrophic Lateral Sclerosis/physiopathology/complications ; Dysarthria/physiopathology ; Paralysis/physiopathology ; Communication Devices for People with Disabilities ; },
abstract = {Brain-computer interfaces (BCIs) can provide naturalistic communication and digital access to people with severe paralysis by decoding neural activity associated with attempted speech and movement. Recent work has demonstrated highly accurate intracortical BCIs for speech and cursor control, but two critical capabilities needed for practical viability were unmet: independent at-home operation without researcher assistance and reliable long-term performance supporting accurate speech and cursor decoding. Here we demonstrate the independent and near-daily use of a multimodal BCI with novel brain-to-text speech and computer cursor decoders by a man with paralysis and severe dysarthria due to amyotrophic lateral sclerosis. Over nearly 2 years, the participant used the BCI for more than 3,800 h at home with no researchers present to maintain rich interpersonal communication with his family and friends, independently control his personal computer and sustain full-time employment-despite being paralyzed. He communicated 183,060 sentences-totaling 1,960,163 words-at an average rate of 56 words per minute. He labeled 92% of sentences as being decoded at least mostly correctly. In formal quantifications of performance where he was asked to say words presented on a screen, attempted speech was consistently decoded with more than 99% word accuracy (125,000 word vocabulary). The participant also used the speech BCI as keyboard input and the cursor BCI as mouse input to control his personal computer, enabling him to send text messages and emails and to browse the internet. These results demonstrate that intracortical BCIs have the potential to support independent use in the home, marking a critical step toward practical assistive technology for people with severe motor impairment.},
}

*Brain-Computer Interfaces
Humans
Male
*Speech/physiology
Amyotrophic Lateral Sclerosis/physiopathology/complications
Dysarthria/physiopathology
Paralysis/physiopathology
Communication Devices for People with Disabilities

@article {pmid42297981,
year = {2026},
author = {Ding, DY and Bot, VA and Chen, KL and Groves, JW and Pálovics, R and Masuda, D and Farinas, A and Oh, HS and Wagner, V and Lu, N and , and Cruchaga, C and Isakova, A and Schott, JM and Wyss-Coray, T},
title = {Plasma proteomic signatures of cellular aging predict human disease.},
journal = {Nature medicine},
volume = {32},
number = {6},
pages = {2060-2072},
pmid = {42297981},
issn = {1546-170X},
support = {AG072255//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; P30 AG066515/AG/NIA NIH HHS/United States ; R01 AG072255/AG/NIA NIH HHS/United States ; P50 AG047366/AG/NIA NIH HHS/United States ; ARUK-PG2017-1946//Alzheimer's Research UK (ARUK)/ ; SG-666374-UK BIRTH COHORT/ALZ/Alzheimer's Association/United States ; },
mesh = {Humans ; *Proteomics/methods ; Female ; *Cellular Senescence/genetics ; Male ; Alzheimer Disease/blood/genetics ; Aging ; Astrocytes/metabolism/pathology ; Aged ; Middle Aged ; Amyotrophic Lateral Sclerosis/blood/genetics ; *Blood Proteins/metabolism ; Lung Neoplasms/blood/genetics ; Genotype ; Adult ; },
abstract = {Aging is asynchronous across cells and organs. Here we tested whether plasma proteomics can be used to analyze cell type-specific aging. From analyses of over 7,000 plasma proteins measured in 60,542 individuals, we developed machine learning models to estimate the biological age of over 40 cell types spanning neuronal, immune, glial, endocrine, epithelial and musculoskeletal origins. We observed that 20-25% of individuals exhibited accelerated aging in a single cell type and 1-3% in 10 or more cell types. Cellular aging signatures were associated with disease status and predicted incident disease and mortality over 15 years of follow-up. Individuals with the APOE4 genotype showed older astrocytes but younger macrophages compared to APOE3 carriers, whereas the APOE2 genotype had inverse associations. Moreover, extreme astrocyte aging tripled the risk of incident Alzheimer's Disease in individuals with two APOE4 alleles, while youthful astrocytes reduced risk. Individuals with extremely aged compared to youthful skeletal myocytes exhibited a 12.7-fold higher risk of developing amyotrophic lateral sclerosis. In individuals who smoked, extreme respiratory epithelial cell aging was associated with a 58% higher lung cancer risk compared to smoking alone. Specific cellular vulnerabilities and cumulative cellular aging burden influenced survival, with youthful immune and neuronal cell types conferring protective effects. Finally, we developed a polycellular aging risk score that stratified mortality risk across cohorts and proteomics platforms. These findings establish a framework for quantifying human physiology at cellular resolution, revealing heterogeneous aging trajectories and their impact on disease susceptibility and resilience.},
}

Humans
*Proteomics/methods
Female
*Cellular Senescence/genetics
Male
Alzheimer Disease/blood/genetics
Aging
Astrocytes/metabolism/pathology
Aged
Middle Aged
Amyotrophic Lateral Sclerosis/blood/genetics
*Blood Proteins/metabolism
Lung Neoplasms/blood/genetics
Genotype
Adult

@article {pmid42298083,
year = {2026},
author = {Al-Shami, AS and Anwar, MM},
title = {The lung-brain axis in neurodegeneration: inflammatory, immune, and vascular mechanisms with therapeutic implications.},
journal = {Inflammopharmacology},
volume = {34},
number = {7},
pages = {4483-4513},
pmid = {42298083},
issn = {1568-5608},
mesh = {Humans ; *Neurodegenerative Diseases/immunology/physiopathology ; *Brain/metabolism/immunology ; Animals ; COVID-19 ; Inflammation/immunology ; *Lung/immunology/metabolism ; Blood-Brain Barrier ; SARS-CoV-2 ; Oxidative Stress ; },
abstract = {Neurodegenerative and chronic pulmonary diseases represent major global health challenges and have widely been investigated separately. Emerging evidence indicates the existence of a lung-brain axis, through which pulmonary pathology and environmental exposures can influence neurological health. The current review highlights the mechanistic and clinical evidence linking chronic lung inflammation, air pollution, and immune dysregulation to the onset and progression of Alzheimer's disease (AD), Parkinson's disease (PD), Multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). A pathway-based framework is presented in which lung inflammation, systemic cytokine release, oxidative stress, blood-brain barrier disruption, immune priming, and protein misfolding mediate lung-to-brain communication. Associations between chronic obstructive pulmonary disease, asthma, particulate matter exposure, and adverse neurological outcomes including cognitive decline, brain atrophy, disease progression, and elevated neurodegenerative risk are emphasized. Specific mechanisms are addressed, including immune-mediated effects in multiple sclerosis, inhalation-driven protein aggregation in Parkinson's disease, and vascular and oxidative injury contributing to dementia and amyotrophic lateral sclerosis. COVID-19 is considered a clinical model of acute lung-brain axis disruption, demonstrating inflammation-driven neurocognitive consequences, and its role in this context was also highlighted. Additionally, potential preventive and therapeutic strategies are discussed, highlighting pulmonary health and environmental exposure reduction as modifiable factors that may help mitigate neurological disease. This integrative review underscores the clinical relevance of the lung-brain axis and calls for interdisciplinary strategies to improve neurological outcomes through pulmonary and environmental interventions.},
}

Humans
*Neurodegenerative Diseases/immunology/physiopathology
*Brain/metabolism/immunology
Animals
COVID-19
Inflammation/immunology
*Lung/immunology/metabolism
Blood-Brain Barrier
SARS-CoV-2
Oxidative Stress

@article {pmid42299008,
year = {2026},
author = {Singh, NK and Singh, A},
title = {Mechanistic Perspectives of Icariin against Neuroinflammation: Taming Glial Activation.},
journal = {Mini reviews in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0113895575448388260306051328},
pmid = {42299008},
issn = {1875-5607},
abstract = {Glial-mediated neuroinflammation significantly contributes to major neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis. Inhibition of glial-mediated neuroinflammation is effective in treating neurodegenerative diseases. Although no permanent cure exists, considerable research aims to identify natural compounds that may slow the disease progression. Icariin is a naturally occurring flavonoid derived from the herb Herba epimedii and has been shown to have several medicinal benefits, including anti-aging, antioxidant, anti-inflammatory, and anti-apoptotic properties. Recent studies have indicated that Icariin, a potent prenylated flavonol glycoside, exhibits neuroprotective effects against glial-mediated neuroinflammation. Icariin attenuates glial pro-inflammatory responses and prevents neurotoxicity in cellular and animal models. Additionally, Icariin is speculated to facilitate neuronal functioning and survival in experimental conditions. The present review highlights the remarkable role of glial cells in neuroinflammatory processes subsequently neurodegeneration, and the potential of icariin to suppress glial-mediated neuroinflammation. We hope that this review will accelerate the pharmacological development of icariin as a potential therapeutic compound against glial-mediated neuroinflammation, which triggers the pathogenesis of several neurodegenerative disorders.},
}

@article {pmid42299014,
year = {2026},
author = {Kaur, H and Kaur, M and Sethi, GK and Kaur, AS and Mishra, A and Sharma, N},
title = {Pathogenic Proteins Driving ALS Pathogenesis: Molecular Mechanisms and Translational Therapeutic Perspectives.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273440191260226063811},
pmid = {42299014},
issn = {1996-3181},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of motor neurons, with protein aggregation as a central pathological hallmark. Key pathogenic proteins, including TDP-43, SOD1, FUS, and dipeptide repeat proteins (DPRs) from C9orf72 expansions, drive disease progression through diverse but converging mechanisms. TDP-43 proteinopathy, present in nearly all ALS cases, involves cytoplasmic mislocalization, misfolding, and aggregation, disrupting RNA processing, protein transport, and DNA repair. Similarly, SOD1 and FUS mutations promote toxic protein aggregation, impairing cellular homeostasis and contributing to neuronal dysfunction. C9orf72-derived DPRs exert toxicity by interfering with nucleocytoplasmic transport. The propagation of these pathogenic proteins between neurons and glia, often via prion-like mechanisms, underlies the characteristic spread of ALS pathology throughout the nervous system. Cellular protective responses, such as molecular chaperones and the ubiquitin-proteasome system, attempt to mitigate aggregation but are often overwhelmed in disease states. Mitochondrial dysfunction, oxidative stress, and disturbances in calcium homeostasis are also implicated, with evidence showing that SOD1 mutations can alter redox balance and mitochondrial function in both neurons and non-neuronal cells. Impaired DNA repair mechanisms, involving proteins such as TDP-43, FUS, NEK1, and VCP, have emerged as important contributors to ALS pathogenesis, linking protein aggregation to genomic instability. Recent therapeutic strategies focus on directly targeting misfolded proteins using small molecules, peptides, or antisense oligonucleotides to inhibit aggregation or enhance clearance, offering hope for disease modification. Understanding the interplay between protein aggregation, impaired RNA metabolism, and cellular stress responses is crucial for developing effective translational therapies for ALS.},
}

@article {pmid42299015,
year = {2026},
author = {Singh, G and Singh, S and Sarkar, A and Sandhu, NK},
title = {Amyotrophic Lateral Sclerosis: Therapeutic Innovations and Evolving Regulatory Approaches.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273438968260318203940},
pmid = {42299015},
issn = {1996-3181},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive degeneration of upper and lower motor neurons, leading to muscle weakness, paralysis, and respiratory failure. Despite extensive research, riluzole and edaravone remain the only globally approved disease-modifying therapies, offering modest survival benefits. This review summarizes current understanding of ALS pathogenesis, approved pharmacological treatments, and emerging gene-, RNA-, and cell-based therapeutic strategies. Particular emphasis is placed on regulatory considerations and evolving clinical trial designs in ALS drug development. The accelerated approval and subsequent withdrawal of sodium phenylbutyrate-taurursodiol (AMX0035) are discussed as a critical case study highlighting the challenges of regulatory flexibility in rare, fatal diseases. Advances in biomarker development, especially neurofilament light chain, are examined for their growing role in trial design and therapeutic evaluation. Collectively, these insights underscore a shift toward biomarker- informed and precision-based approaches that may improve future ALS therapeutic development.},
}

@article {pmid42300806,
year = {2026},
author = {Calma, AD and Pavey, N and Tsuji, Y and Ghapar, AA and Bos, MAJVD and Orden, B and Lee, G and Mekhael, L and Ryder, J and Silva, CS and McDonald, D and Kakar, F and Yiannikas, C and Kiernan, MC and Brown, DA and Menon, P and Vucic, S},
title = {Integration of Serum Neurofilament Light Chain and Cortical Dysfunction Improves Diagnostic Accuracy in ALS.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
pmid = {42300806},
issn = {2328-9503},
abstract = {OBJECTIVE: To determine whether integration of serum neurofilament light chain (NfL) and cortical dysfunction improves diagnostic accuracy in amyotrophic lateral sclerosis (ALS) when applied alongside the Gold Coast criteria (GCC).

METHODS: In this prospective study, 148 participants with suspected ALS were recruited (101 ALS and 47 with ALS mimicking disorders). Participants taking medications known to influence TMS measures were excluded. Serum NfL levels were quantified using a single-molecule array assay. Cortical function was assessed using threshold tracking transcranial magnetic stimulation, with cortical dysfunction defined by reduced mean short interval intracortical inhibition or motor cortex inexcitability. Diagnostic performance was evaluated using sensitivity, specificity, and diagnostic odds ratios (DOR), with 95% confidence intervals (CI).

RESULTS: Serum NfL demonstrated excellent discrimination (area under the curve 0.92, p < 0.001), with cut-off ≥ 33.5 pg/mL providing a sensitivity of 0.85 (95% CI 0.77-0.91) and specificity 0.87 (95% CI 0.75-0.94). Cortical dysfunction demonstrated very good diagnostic performance (sensitivity 0.77 [95% CI 0.68-0.84], specificity 0.77 [95% CI 0.63-0.86]). The GCC achieved a sensitivity of 0.89 (95% CI 0.82-0.94) and specificity 0.89 (95% CI 0.77-0.95). Combining GCC with elevated NfL or cortical dysfunction increased the specificity to 0.98 (95% CI 0.89-1.00) while maintaining high sensitivity at 0.87 (95% CI 0.79-0.92), yielding the highest DOR.

INTERPRETATION: Integration of serum NfL and cortical dysfunction with the Gold Coast criteria improves diagnostic accuracy in ALS, particularly by increasing specificity. This multimodal approach provides a practical framework for earlier and more definitive diagnosis that may facilitate more efficient clinical trial recruitment.},
}

@article {pmid42300933,
year = {2026},
author = {Gray, VP and Cui, Z and Klepsig, M and Letteri, RA},
title = {Designing polymer-peptide conjugates to target dipeptide repeat aggregates implicated in amyotrophic lateral sclerosis.},
journal = {Journal of materials chemistry. B},
volume = {14},
number = {26},
pages = {8149-8158},
pmid = {42300933},
issn = {2050-7518},
support = {R35 GM147424/GM/NIGMS NIH HHS/United States ; T32 GM136615/GM/NIGMS NIH HHS/United States ; },
mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; *Dipeptides/chemistry ; *Polymers/chemistry ; Humans ; *Peptides/chemistry ; Protein Aggregates/drug effects ; },
abstract = {Toxic dipeptide repeats such as the aggregating glycine-alanine (GA)n peptide are implicated in the progression of amyotrophic lateral sclerosis (ALS), a lethal neuromuscular disease with an urgent need for new therapeutics. Here, we report polymer-peptide conjugates that prevent aggregation of (GA)10. Optical density measurements and transmission electron microscopy demonstrate that conjugates prevent aggregation when co-incubated with (GA)10 and disperse pre-aggregated (GA)10. These results represent an important step toward a new generation of therapeutics for ALS and contribute to a growing body of literature demonstrating the potential of polymer-peptide conjugates as therapeutics.},
}

*Amyotrophic Lateral Sclerosis/drug therapy/metabolism
*Dipeptides/chemistry
*Polymers/chemistry
Humans
*Peptides/chemistry
Protein Aggregates/drug effects

@article {pmid42301686,
year = {2026},
author = {Jomaa, AM and Khalid, H and Abozait, HJ and Mudassar, H and Kaur, R},
title = {Efficacy of Sodium Phenylbutyrate-Taurursodiol in Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.},
journal = {Annals of Indian Academy of Neurology},
volume = {29},
number = {3},
pages = {343-352},
pmid = {42301686},
issn = {0972-2327},
abstract = {OBJECTIVE: To evaluate the efficacy and safety of sodium phenylbutyrate-taurursodiol (PB-TURSO) and its components in slowing disease progression and improving survival in patients with amyotrophic lateral sclerosis (ALS).

METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies comparing PB-TURSO or its components to placebo or standard of care in adults with ALS were included. The primary outcomes were functional decline (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised [ALSFRS-R]) and survival. Two reviewers independently screened studies, extracted data, and assessed the risk of bias. A random-effects model was used for the meta-analysis, and a narrative synthesis was conducted for Tauroursodeoxycholic Acid (TUDCA) monotherapy and secondary analyses from the CENTAUR trial.

RESULTS: Two RCTs (n = 801) were included in the meta-analysis. The pooled analysis demonstrated no statistically significant difference in either ALSFRS-R decline (mean difference [MD] 1.51, 95% confidence interval [CI] -1.01 to 4.02; P = 0.24; I² =71%) or survival (hazard ratio [HR] 0.90, 95% CI 0.73-1.11; P = 0.31; I² = 61%). A separate trial of TUDCA monotherapy (n = 34) demonstrated significant functional benefits. Post hoc analyses of the CENTAUR trial reported a survival benefit of 6.5-10.6 months and delayed progression to major disease milestones. Biomarker analyses suggested anti-inflammatory effects. The risk of bias was moderate to high, and the certainty of evidence was rated very low by GRADE.

CONCLUSIONS: Based on very low certainty evidence, the available RCT data do not support a definitive conclusion regarding the efficacy of PB-TURSO in ALS. Post hoc exploratory analyses suggest a potential survival benefit, which requires confirmation in adequately powered, prospectively designed trials; current results are hypothesis-generating rather than practice-defining.},
}

@article {pmid42301897,
year = {2026},
author = {Peters, GA and Misra, AJ and Samadian, KD and Chang, W and Chandran, KG and Hurwitz, JA and Muszalski, C and Granich, N and Goldberg, SA and Cash, RE},
title = {Cardiac Arrest During Interfacility Transport with Emergency Medical Services: A Preliminary Nationwide Cross-Sectional Study.},
journal = {Prehospital emergency care},
volume = {},
number = {},
pages = {1-6},
doi = {10.1080/10903127.2026.2690618},
pmid = {42301897},
issn = {1545-0066},
abstract = {OBJECTIVES: We aimed to provide the first national study of out-of-hospital cardiac arrests (OHCA) witnessed by emergency medical services (EMS) during interfacility transport (IFT).

METHODS: We used a nationwide prehospital patient care report dataset from 2023 to complete a cross-sectional observational study of EMS encounters for IFT during which OHCA occurred. Descriptive statistics were computed, stratified by level of EMS care provided. Multivariable logistic regression analysis was completed to evaluate factors associated with return of spontaneous circulation (ROSC) at the end of the IFT encounter upon transfer of care to the receiving facility. Finally, we completed a similar multivariable logistic regression analysis restricted to the subgroup of patients with an unshockable initial rhythm.

RESULTS: A total of 1,466 OHCA incidents occurred during an IFT with EMS: 7.5% with basic life support (BLS), 53.6% with advanced life support (ALS), and 38.9% with critical care transport (CCT). Among these incidents 11.8% were associated with trauma, 9.2% involved cardiopulmonary resuscitation (CPR) prior to EMS unit arrival, 14.7% involved a mechanical device to perform CPR, 22.2% had a shockable initial rhythm, and 58.1% were transported via ground as opposed to air. At the conclusion of the IFT EMS encounter, 50.3% had sustained ROSC. Geriatric age (aOR 0.64, 95%CI 0.44-0.94), BLS care (aOR 0.45, 95%CI 0.22-0.90), and ground transport (aOR 0.58, 95%CI 0.38-0.89) were associated with worse outcomes on adjusted analysis, whereas shockable initial rhythm (aOR 3.86, 95%CI 2.42-6.36) and CCT care (aOR 2.21, 95%CI 1.42-3.48) were associated with better outcomes. The sub-analysis for OHCA during IFT with an unshockable initial rhythm also showed greater odds of ROSC when managed by CCT relative to ALS (aOR 2.65, 95%CI 1.64-4.33) while adjusting for other key factors.

CONCLUSIONS: Using a large nationwide sample of OHCA incidents that occurred during IFT, we found that higher level of EMS care was associated with superior short-term outcomes while controlling for other key factors. These findings underscore the importance of accurate patient triage at sending facilities and the value of CCT for high-risk patients.},
}

@article {pmid42302423,
year = {2026},
author = {Almenara Abellán, JL and Lagares Franco, C and Bordes Bustamante, F and Gracia Romero, MÁ and Santisteban Espejo, AL},
title = {Impact of a simulation-based training program on the acquisition of ultrasound window competencies for the initial assessment of polytrauma patients in advanced prehospital nursing care.},
journal = {Enfermeria intensiva},
volume = {37},
number = {3},
pages = {500604},
doi = {10.1016/j.enfie.2026.500604},
pmid = {42302423},
issn = {2529-9840},
mesh = {Humans ; *Clinical Competence ; *Emergency Medical Services ; *Multiple Trauma/diagnostic imaging ; Ultrasonography ; *Simulation Training ; Female ; Adult ; *Emergency Nursing/education ; Male ; },
abstract = {INTRODUCTION: Point-of-care ultrasound is essential in the initial assessment of polytrauma patients. The E-FAST protocol enables rapid detection of intra-abdominal free fluid, pericardial effusion, and pneumothorax, with particular usefulness in prehospital settings. However, ultrasound training among emergency nursing staff remains limited, especially within Advanced Life Support (ALS) mobile units.

OBJECTIVE: To evaluate the effect of a brief, structured training program on the acquisition of competencies for obtaining E-FAST windows in ALS mobile units nurses, assessing knowledge, technical skills, scanning sequence, and perceived confidence.

METHOD: A quasi-experimental pre-post intervention study was conducted with nurses with ≥6 months of experience in emergency or prehospital care. The intervention included baseline assessment, a 2-h theoretical module, high-fidelity simulation with Ultrasound Mentor®, and hands-on practice with human models. Final assessment combined a theoretical test, simulator-based practical evaluation, and scanning with a real ultrasound device. Knowledge, execution times, and confidence levels were recorded.

RESULTS: Fourteen nurses participated, most without previous ultrasound training (85.7%). Initial confidence was low and improved significantly after the intervention. Theoretical performance increased in 5 of the 6 evaluated items, reaching up to 92.9% accuracy in key content areas. Practical assessment demonstrated an organized scanning sequence and appropriate times for prehospital care (medians of 118 s [IQR 24.5] in advanced simulation and 237 s [IQR 33.3] using a real ultrasound device).

DISCUSSION: The program enabled the acquisition of essential skills even in professionals without prior ultrasound experience. The combination of theory, simulation, and hands-on practice facilitated rapid competency transfer and protocol standardization.

CONCLUSIONS: A brief training program improves ALS mobile units nurses' competence and confidence in obtaining E-FAST windows, supporting the safe integration of point-of-care ultrasound into prehospital care.},
}

Humans
*Clinical Competence
*Emergency Medical Services
*Multiple Trauma/diagnostic imaging
Ultrasonography
*Simulation Training
Female
Adult
*Emergency Nursing/education
Male

@article {pmid42302677,
year = {2026},
author = {Gong, X and Xie, Y and Deng, X and Sun, Z and Fu, S and Wang, H and Hou, Y and Dong, Z and Zhou, W},
title = {Hydrolytic evolution of propyrisulfuron: wlectronic differentiation and spectroscopic fingerprints of transformation products.},
journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy},
volume = {362},
number = {},
pages = {128245},
doi = {10.1016/j.saa.2026.128245},
pmid = {42302677},
issn = {1873-3557},
abstract = {Propyrisulfuron (PRS), a sulfonylurea herbicide used in paddy systems, undergoes hydrolysis to form structurally distinct transformation products. This study combined DFT/TDDFT calculations with experimental UV-Vis, FTIR, and Raman spectroscopy to characterise PRS and six experimentally identified products (HP1-HP6). Relative electronic descriptors showed that cleavage of the sulfonylurea bridge increased the HOMO-LUMO gaps from 4.572 eV for PRS to 5.978 and 6.229 eV for HP1 and HP2, respectively, whereas HP3-HP5 retained moderate gaps of 4.846-4.923 eV. HP5 showed the most negative Vmin (-71.524 kcal mol[-1]) and the largest dipole moment (16.67 D). Calculated and experimental spectra were consistent, with major UV-Vis peak deviations below 10 nm and characteristic FTIR and Raman deviations generally below 20 and 15 cm[-1], respectively. A validated 1YBH-based docking workflow reproduced the co-crystallized CIE pose with an RMSD of 0.320 Å; within this internally standardized comparison, PRS, HP3, HP5, and HP4 gave scores of -8.480, -7.212, -7.076, and - 6.979 kcal mol[-1], respectively. Docking results are interpreted as relative ALS/AHAS-recognition tendencies rather than direct evidence of toxicity or inhibitory potency. Overall, this work establishes a structure-spectrum framework for tracking PRS hydrolysis and differentiating its major products.},
}

@article {pmid42302791,
year = {2026},
author = {Sahu, SK and Memczak, S and Thakurela, S and Lu, J and Gupta, P and Mutukula, N and Hirano, A and Zhang, Y and Hishida, T and Kurita, M and Wang, C and Shao, Y and Williams, A and Shokhirev, M and Tiwari, VK and Rodriguez Esteban, C and Reddy, P and Meissner, A and Li, M and Izpisua Belmonte, JC},
title = {ZNF512B safeguards genome integrity at regulatory regions to repress the SASP and inflammation.},
journal = {Cell stem cell},
volume = {33},
number = {7},
pages = {1191-1204.e10},
pmid = {42302791},
issn = {1875-9777},
support = {P01 GM099117/GM/NIGMS NIH HHS/United States ; },
mesh = {Humans ; *Inflammation/genetics/pathology ; Animals ; DNA Damage ; *Senescence-Associated Secretory Phenotype/genetics ; DNA Repair ; *Regulatory Sequences, Nucleic Acid/genetics ; Mice ; cGAS-STING Signaling Pathway ; *Cellular Senescence/genetics ; },
abstract = {Cellular senescence drives aging and disease largely through the senescence-associated secretory phenotype (SASP), yet its regulatory mechanisms remain unclear. Using a SASP reporter combined with a CRISPR-Cas9 screen targeting active regulatory elements, we identify the zinc-finger protein ZNF512B as a key suppressor of the SASP. ZNF512B loss induces DNA damage, activates cGAS-STING signaling, and triggers inflammatory transcriptional reprogramming. In contrast, ZNF512B promotes preferential DNA repair at regulatory genomic regions, limiting SASP induction. Mechanistically, ZNF512B is rapidly recruited to DNA-damage sites via distinct zinc-finger domains and facilitates NuRD complex targeting to damaged chromatin, enabling precise repair. In human neuromuscular organoids, ZNF512B deficiency induces inflammation, lineage imbalance, and cytokine secretion resembling amyotrophic lateral sclerosis (ALS)-associated pathology. In vivo, ZNF512B overexpression reduces DNA damage and inflammation following acute liver injury. Together, these findings support a mechanism of preferential DNA repair that contributes to maintaining genome integrity, suppressing SASP and inflammation.},
}

Humans
*Inflammation/genetics/pathology
Animals
DNA Damage
*Senescence-Associated Secretory Phenotype/genetics
DNA Repair
*Regulatory Sequences, Nucleic Acid/genetics
Mice
cGAS-STING Signaling Pathway
*Cellular Senescence/genetics

@article {pmid42303396,
year = {2026},
author = {Akers, E and Ameratunga, S and Wilkinson-Meyers, L and Adams, M and Te Ao, B},
title = {Perspectives on the injured child's hospital discharge process and opportunities for improvement: a scoping review protocol.},
journal = {BMJ open},
volume = {16},
number = {6},
pages = {e119916},
pmid = {42303396},
issn = {2044-6055},
mesh = {Humans ; Scoping Reviews as Topic ; *Patient Discharge/standards ; Child ; *Wounds and Injuries/therapy ; Caregivers/psychology ; Research Design ; },
abstract = {INTRODUCTION: Unintentional injury is a leading cause of hospitalisation and disability in children globally. Families may experience a second crisis of injury after the child's discharge from the hospital, with the traumatic nature of injuries affecting physical and psychosocial recovery. This scoping review aims to summarise the literature on the perspectives of injured children's caregivers and service providers on the hospital discharge process, the challenges and opportunities to improve discharge planning evident from qualitative and interventional studies, and the investigation of inequities in these studies using the Conceptual Framework of Access to healthcare proposed by Levesque et al in 2013.

METHODS AND ANALYSIS: A scoping review will be conducted involving a search across four databases: CINAHL Plus, Cochrane Library, Embase and Ovid MEDLINE. Empirical literature published in English between 2000 and 2025 will be eligible for inclusion. Included studies will report caregiver or service provider perspectives on current hospital discharge practice for injured children under 18 years old, investigated a priori as a study objective or a posteriori as a finding, or will report the design, implementation or evaluation of interventions intended to improve hospital discharge for injured children. Levesque et al's framework will be used to guide data extraction from the selected studies into predefined data charting forms, informing the review questions. Findings will be presented narratively and in tables to highlight the key characteristics of the studies, the perspectives of caregivers and service providers, the challenges and opportunities to improve hospital discharge, the proposed discharge interventions, the investigation of inequities and the gaps in the literature.

ETHICS AND DISSEMINATION: The scoping review only uses data in the public domain and does not require ethics approval.},
}

Humans
Scoping Reviews as Topic
*Patient Discharge/standards
Child
*Wounds and Injuries/therapy
Caregivers/psychology
Research Design

@article {pmid42304808,
year = {2026},
author = {Smith, SE and Hughes, B and Miller, TM and Bucelli, RC},
title = {Amyotrophic Lateral Sclerosis Recovery: A New Model System of Care Integrating Neuromuscular Rehabilitation With Clinical Stabilization in ALS.},
journal = {Muscle & nerve},
volume = {74},
number = {2},
pages = {321-327},
doi = {10.1002/mus.70320},
pmid = {42304808},
issn = {1097-4598},
mesh = {*Amyotrophic Lateral Sclerosis/rehabilitation/physiopathology/drug therapy ; Humans ; *Recovery of Function/physiology ; Male ; Female ; },
abstract = {There is currently no consensus on how to define recovery for individuals with amyotrophic lateral sclerosis (ALS). Tofersen treatment for superoxide dismutase-1-related (SOD1) ALS marks a pivot in clinical management: for the first time, clinicians can target disease stabilization and functional recovery in some individuals. This advancement shifts the focus of ALS care toward optimizing functional recovery alongside symptomatic management. However, there are no evidence-based guidelines for prescribing neuromuscular rehabilitation (NMR) to improve functional recovery. Building on our preliminary single-center data of integrated NMR with tofersen, we propose a new ALS Recovery Model System of Care, utilizing a hub-and-spoke infrastructure to combine NMR with novel therapies. This model aims to define ALS recovery, characterize recovery profiles, standardize NMR protocols, and establish a rehabilitation framework adaptable to future disease-stabilizing therapies.},
}

*Amyotrophic Lateral Sclerosis/rehabilitation/physiopathology/drug therapy
Humans
*Recovery of Function/physiology
Male
Female

@article {pmid42304913,
year = {2026},
author = {Wang, T and Wu, M and Liang, L and Pei, L and Wang, D},
title = {Nicotine Versus Non-Nicotine Constituents in Neurodegenerative Risk: Evidence from Multivariable Mendelian Randomization.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X503957260608154111},
pmid = {42304913},
issn = {1875-6190},
abstract = {BACKGROUND: Nicotine has complex neuropharmacological actions through nicotinic acetylcholine receptors, but its independent role in neurodegenerative diseases remains unclear because tobacco smoke contains many non-nicotine toxicants. This uncertainty limits the interpretation of nicotine- and nAChR-targeted therapeutic strategies, especially as electronic nicotine delivery sys-tems become more common. We used Mendelian randomization to genetically separate nicotine-related effects from smoking-related non-nicotine effects on major neurodegenerative diseases and related prodromal conditions.

METHODS: We performed univariable two-sample Mendelian randomization (MR) and multivariable MR (MVMR) analyses. Summary-level exposure data for cigarettes per day (CPD) and the nicotine metabolite ratio (NMR) were analyzed against individual-level, smoking-stratified outcome data derived from 337,334 UK Biobank participants, to evaluate their respective causal effects across six neurodegenerative outcomes: Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), tremor, early cognitive impairment (EC), and other neurodegenerative diseases (OND).

FINDINGS: MVMR analyses revealed that nicotine exposure was a causal risk factor for AD (ever smokers: OR=0.90, 95% CI 0.83-0.98; current smokers: OR=0.76, 95% CI 0.64-0.91). Nicotine exerted a causal protective effect against tremor (OR=1.24, 95% CI 1.03-1.49) and EC (OR=1.14, 95% CI 1.04-1.24) in current smokers. Non-nicotine tobacco constituents were identified as risk factors among former smokers for EC (OR=1.61, 95% CI 1.04-2.50).

CONCLUSIONS: Exposure to nicotine can increase the risks of AD, while conferring protective effects against tremor and EC. Furthermore, exposure to non-nicotine tobacco constituents acts as a risk factor for the incidence of EC.},
}

@article {pmid42304926,
year = {2026},
author = {Mukherjee, S and Ray, SK and Mukherjee, S},
title = {Linking Neurodegeneration and Age-related Macular Degeneration: Unified Pathways and Intervention Strategies.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273450093260523224914},
pmid = {42304926},
issn = {1996-3181},
abstract = {Age-related macular degeneration (AMD) is caused by the degeneration of photoreceptors and retinal pigment epithelium (RPE) along with drusen deposition and is the leading cause of vision loss in older adults. Both these structures within the central nervous system (CNS) utilize common neuro-inflammatory mechanisms because the retina is an outgrowth of the brain. Like the brain, the eye has its own physical characteristics and surface molecules as well as a tendency towards specific immune reactions. Numerous distinct neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and Frontotemporal dementia (FTD) that impact the brain present as eye symptoms, and the conventional diagnosis of these neurodegenerative disorders (NDs) is often preceded by ocular symptoms. Furthermore, several eye-specific disorders have characteristics in common with other CNS disorders. NDs and AMD share common key features, such as tau and amyloid-β deposits, oxidative stress response, chronic inflammation, and dysregulation of microglia and müller glia. Common pathological mechanisms include complement activation, amyloid aggregation, neuroinflammation, vascular impairment, and cell death, providing a basis for a convergent neuroimmune axis between retinal and cerebral degeneration. Comparing these age-related diseases will facilitate the identification of shared risk factors, convergent molecular pathways, and potential cross-applicable therapeutic strategies, such as anti-inflammatory, anti-complementary, anti-apoptotic, and anti-VEGF-based approaches. This knowledge may enhance understanding of neurodegenerative diseases, help identify early biomarker development for diagnosis, and enable the design of targeted therapeutic strategies.},
}

@article {pmid42305210,
year = {2026},
author = {Sabnis, RW and Sabnis, AR},
title = {Novel Compounds as TREM2 Modulators for Treating Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, and Nasu-Hakola Disease.},
journal = {ACS medicinal chemistry letters},
volume = {17},
number = {6},
pages = {1236-1237},
pmid = {42305210},
issn = {1948-5875},
abstract = {Provided herein are novel compounds as TREM2 modulators, pharmaceutical compositions, use of such compounds in treating Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and Nasu-Hakola disease, and processes for preparing such compounds.},
}

@article {pmid42307135,
year = {2026},
author = {Frycz, S and Więcławski, W and Skotniczny, M and Binder, M},
title = {Brain activity in an end-stage ALS patient suggests the presence of an unresponsive wakefulness syndrome.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/21678421.2026.2688249},
pmid = {42307135},
issn = {2167-9223},
abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease primarily affecting motor neurons. It is widely assumed that cortical structures beyond motor neurons are relatively preserved, and patients in the end-stage ALS are regarded as being in complete locked-in syndrome (cLIS). However, emerging evidence suggests substantial heterogeneity in cognitive functioning among ALS patients, indicating possible extra-motor cortical involvement and impaired levels of consciousness. We report a case study assessing electrophysiological markers and auditory system integrity to evaluate the presence of covert consciousness in end-stage ALS.

METHODS: The patient was a 42-year-old woman with bulbar-onset, end-stage ALS, a six-year disease duration, and no means of communication. She underwent several EEG-based protocols, including resting-state EEG (RS-EEG), a passive auditory oddball paradigm, and 40 Hz auditory steady-state responses (ASSR). Audiological evaluation comprised transient-evoked and distortion-product otoacoustic emissions, as well as auditory brainstem responses (ABR).

RESULTS: RS-EEG was dominated by prefrontal 1-3 Hz activity resembling frontal intermittent rhythmic delta activity. Power spectra were poorly differentiated and consistent with a 1/f profile. No event-related potentials were observed in the oddball paradigm, and no ASSR responses were detected. Audiological testing revealed absent otoacoustic emissions and ABR indicating severe to profound hearing loss.

CONCLUSIONS: Our findings indicate severe cortical dysfunction and provide no electrophysiological evidence of covert consciousness. The electrophysiological profile closely resembles that observed in unresponsive wakefulness syndrome. This case supports the hypothesis that advanced ALS following cLIS onset may be more appropriately conceptualized as a disorder of consciousness rather than persistent cLIS.},
}

@article {pmid42309005,
year = {2026},
author = {Rugarli, EI and Langer, T},
title = {Limiting neurodegeneration in ALS: A phosphatase paves the way.},
journal = {Neuron},
volume = {114},
number = {12},
pages = {2073-2075},
doi = {10.1016/j.neuron.2026.04.030},
pmid = {42309005},
issn = {1097-4199},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/enzymology/metabolism ; Animals ; Motor Neurons/metabolism ; *Nerve Degeneration ; Mitochondria/metabolism ; *Phosphoric Monoester Hydrolases/metabolism ; },
abstract = {Zheng et al. identify phosphatase PGAM5 as a novel promising target for the treatment of different amyotrophic lateral sclerosis subtypes. PGAM5 dephosphorylates and activates the stress-regulated mitochondrial peptidase OMA1, which elicits a maladaptive mitochondrial integrated stress response in motor neurons.},
}

Humans
*Amyotrophic Lateral Sclerosis/pathology/enzymology/metabolism
Animals
Motor Neurons/metabolism
*Nerve Degeneration
Mitochondria/metabolism
*Phosphoric Monoester Hydrolases/metabolism

@article {pmid42309130,
year = {2026},
author = {Patel, R and Bryson, B and Carlson, T and Demosthenous, A and Jiang, D},
title = {Stability and neurophysiological validity of graph connectivity features for non-stationary motor imagery BCIs.},
journal = {Journal of neural engineering},
volume = {23},
number = {3},
pages = {},
doi = {10.1088/1741-2552/ae7ead},
pmid = {42309130},
issn = {1741-2552},
mesh = {Humans ; *Electroencephalography/methods/standards ; *Brain-Computer Interfaces ; Reproducibility of Results ; *Amyotrophic Lateral Sclerosis/physiopathology ; *Imagination/physiology ; },
abstract = {Objective.Motor imagery (MI) Electroencephalography (EEG) brain-computer interfaces (BCIs) degrade under longitudinal non-stationarity, especially in amyotrophic lateral sclerosis (ALS). Functional connectivity (FC) has been proposed as an alternative feature space, but it remains unclear which FC estimators yield stable, class-informative features across sessions.Approach.Using a multi-session ALS EEG dataset, we computed a broad family of FC estimators per trial to form weighted graphs. We extracted edge weights and node strength features, and quantified (i) feature reproducibility and (ii) left hand-right hand separability using coefficient of variation and symmetric Kullback-Leibler divergence, respectively. We assessed neurophysiological plausibility via spatial topographies, distance-dependence controls, and evaluated selected feature sets in a strictly temporal cross-session decoding protocol against common spatial patterns, band power and Riemannian methods.Main results.Coherence (Coh)-based estimators, particularly magnitude-squared Coh, most consistently produced features exhibiting favourable reproducibility-separability trade-offs across subjects. Node-strength discriminability maps showed lateralised sensorimotor structure consistent with known MI physiology. In temporal generalisation, magnitude squared Coh derived features achieved more consistent test performance than baseline methods for most subjects.Significance.Joint reproducibility-separability profiling provides a principled way to select FC feature spaces for longitudinal MI-BCIs and suggests Coh-based connectivity is a stronger sensor-space candidate under drift.},
}

Humans
*Electroencephalography/methods/standards
*Brain-Computer Interfaces
Reproducibility of Results
*Amyotrophic Lateral Sclerosis/physiopathology
*Imagination/physiology

@article {pmid42309840,
year = {2026},
author = {Oliveira Santos, M and de Carvalho, M},
title = {Enhanced spinal motoneuron excitability as a marker of motor neuron dysfunction in primary lateral sclerosis.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {190},
number = {},
pages = {2111978},
doi = {10.1016/j.clinph.2026.2111978},
pmid = {42309840},
issn = {1872-8952},
mesh = {Humans ; Female ; *Motor Neurons/physiology ; Male ; Middle Aged ; Aged ; *Motor Neuron Disease/physiopathology/diagnosis ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Muscle, Skeletal/physiopathology ; Adult ; Electromyography/methods ; Prospective Studies ; *Spinal Cord/physiopathology ; },
abstract = {OBJECTIVE: To investigate F-wave parameters as markers of spinal motoneuron excitability in patients with primary lateral sclerosis (PLS).

METHODS: We prospectively evaluated F-waves and M-waves from the abductor pollicis brevis (APB), first dorsal interosseous (FDI), and abductor digiti minimi (ADM) muscles. The study included three groups: 27 patients with PLS, 36 with amyotrophic lateral sclerosis with normal right-hand function (ALS-NH), and 30 healthy controls (HC). Recorded parameters included M-wave amplitude, F-wave frequency, latencies, amplitude, and the F/M-waves amplitude ratio. Upper motor neuron (UMN) clinical scores were also assessed. Statistical analysis was performed using One-way ANOVA or Kruskal-Wallis tests for group comparisons, and Spearman's rank test for correlations.

RESULTS: PLS had a significantly higher UMN score than ALS-NH (p < 0.001). F-wave amplitudes were significantly higher in PLS compared to both ALS-NM and HC across all muscles (APB, p = 0.01 and p = 0.03; FDI, p = 0.002 and p < 0.001; ADM, p = 0.03 and p < 0.001, respectively). F/M-waves amplitude ratio was also significantly higher in PLS vs. ALS-NH/HC (APB, p = 0.01 and p = 0.03; FDI, p < 0.001 and p < 0.001; ADM, p = 0.03 and p = 0.001, respectively). No significant differences were found between ALS-NM and HC for these parameters (p > 0.05). M-wave amplitudes and other F-wave parameters remained comparable across all groups (p > 0.05). No correlation was found between F-wave amplitude and UMN scores in PLS patients (p > 0.05).

CONCLUSIONS: Patients with PLS exhibit significantly increased F-wave amplitudes and F/M amplitudes ratios compared to ALS-NH and HC.

SIGNIFICANCE: Increased F-waves size serves as a neurophysiological marker of enhanced spinal motoneuron excitability in PLS.},
}

Humans
Female
*Motor Neurons/physiology
Male
Middle Aged
Aged
*Motor Neuron Disease/physiopathology/diagnosis
*Amyotrophic Lateral Sclerosis/physiopathology/diagnosis
Muscle, Skeletal/physiopathology
Adult
Electromyography/methods
Prospective Studies
*Spinal Cord/physiopathology

@article {pmid42310079,
year = {2026},
author = {Nouraei, H and Amirzadeh, N and Shabanzadeh, S and Zareshahrabadi, Z and Shamsdin, N and Nouraei, M and Naeimi, B and Pakshir, K},
title = {Effect of subsequent passages on biofilm formation intensity, ALS genes expression, and cell surface hydrophobicity variability in clinical Candida albicans isolates.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {42310079},
issn = {2045-2322},
support = {32536//Vice-Chancellor for Research, Shiraz University of Medical Sciences/ ; },
mesh = {*Candida albicans/genetics/isolation & purification/physiology ; *Biofilms/growth & development ; Hydrophobic and Hydrophilic Interactions ; *Fungal Proteins/genetics/metabolism ; *Gene Expression Regulation, Fungal ; Humans ; Cell Adhesion ; Candidiasis/microbiology ; },
abstract = {Candida albicans is an opportunistic yeast pathogen that have several virulence factors included biofilm formation, cell surface hydrophobicity (CSH), and the expression of adhesion genes. Concerns exist that serial laboratory subculturing may diminish these traits, leading to inaccurate research findings. Aim of this study was evaluated the effect of subsequently subcultures on biofilm formation intensity, ALS gene expression, and surface hydrophobicity properties in clinical C. albicans isolates. Ten clinical C. albicans isolates were serially subcultured up to 20 passages (P). We used qPCR to quantify ALS1 and ALS3 gene expression, the Crystal Violet assay to measure biofilm formation intensity (P1, P5, P10, P15, P20), and a water-octane partitioning assay for CSH variability at different passages. Serial subculturing caused gradual downregulation of gene expression for both ALS1 and ALS3 (p < 0.001). This condition was accompanied by a biofilm-forming capacity that became progressively reduced in 90% of isolates, whereas 60% at P20 were already biofilm-negative (vs. 10% at P1). Cell surface hydrophobicity also decreased progressively, with 100% of isolates displaying low CSH at P15, compared with 40% in the initial P1 state. Serial subculturing leads to a rapid reduction of C. albicans pathogenic fitness with decreased expression of certain key adhesion genes, diminished biofilm formation, and lower CSH. These results highlight the plasticity of the organism and thus strongly suggest that low-passage clinical isolates should be used in studies to reflect true pathogenicity in vivo accurately.},
}

*Candida albicans/genetics/isolation & purification/physiology
*Biofilms/growth & development
Hydrophobic and Hydrophilic Interactions
*Fungal Proteins/genetics/metabolism
*Gene Expression Regulation, Fungal
Humans
Cell Adhesion
Candidiasis/microbiology

@article {pmid42310298,
year = {2026},
author = {Diaz Escarcega, R and M J, VK and Arizmendez, A and Tan, C and Urayama, A and Marrelli, SP and Morales, R and Wefel, JS and Zhang, C and McCullough, LD and Kim, N and Monchaud, D and Jung, SY and Tsvetkov, AS},
title = {Sex-linked helicases DDX3X and DDX3Y regulate G-quadruplex-associated stress in neurons.},
journal = {Cell death & disease},
volume = {17},
number = {1},
pages = {},
pmid = {42310298},
issn = {2041-4889},
support = {R35 GM141867/GM/NIGMS NIH HHS/United States ; 4R01AG068292//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; AFAR BIG21042//Glenn Family Foundation/ ; R01 AG068292/AG/NIA NIH HHS/United States ; AFAR BIG21042//American Federation for Aging Research (American Federation for Aging Research, Inc.)/ ; },
mesh = {*Neurons/metabolism/drug effects/pathology ; *DEAD-box RNA Helicases/metabolism/genetics ; Humans ; *G-Quadruplexes ; Animals ; Female ; Male ; DNA Damage ; },
abstract = {G-quadruplexes (G4s) are four-stranded nucleic acid structures that regulate virtually all nucleic acid-dependent cellular processes. At present, most functional studies involving G4s have focused on cancer cells. This study investigated how neurons respond to genotoxic stress induced by quarfloxin (CX-3543), a small molecule that stabilizes G4s. We found that quarfloxin treatment induced DNA damage in neurons, with double-strand breaks enriched in the nucleolus. Proteomic analysis revealed that quarfloxin promoted substantial protein changes, affecting networks associated with Alzheimer's, Parkinson's, and Huntington's diseases, and amyotrophic lateral sclerosis. Among the affected proteins, the G4 helicase DDX3X, encoded on the X chromosome, was upregulated, prompting further investigation of DDX3X and its Y-linked homolog DDX3Y in female and male neurons, respectively. RNA sequencing identified DDX3X- and DDX3Y-regulated gene networks involved in DNA damage responses, inflammation, cell cycle regulation, and stress-associated pathways, with notable sex-dependent differences. In human brain tissue, DDX3X expression and nuclear enrichment were increased in neurons from older females compared to younger individuals, with further elevation observed in Alzheimer's disease. Taken together, these findings identify DDX3X and DDX3Y as modulators of neuronal stress responses downstream of G4 stabilization and indicate that their induction is accompanied by activation of DNA damage response genes, as well as cell cycle- and inflammation-associated pathways, suggesting that sustained activation of these pathways may disrupt neuronal homeostasis. Our study provides insight into G4-dependent stress mechanisms in neurons and highlights sex-linked pathways that may contribute to brain aging and neurodegenerative disease vulnerability.},
}

*Neurons/metabolism/drug effects/pathology
*DEAD-box RNA Helicases/metabolism/genetics
Humans
*G-Quadruplexes
Animals
Female
Male
DNA Damage

@article {pmid42310450,
year = {2026},
author = {Deo, DR and Okorokova, EV and Pritchard, AL and Hahn, NV and Card, NS and Nason-Tomaszewski, SR and Jude, J and Hosman, T and Choi, EY and Qiu, D and Meng, Y and Wairagkar, M and Nicolas, C and Kamdar, FB and Iacobacci, C and Acosta, A and Hochberg, LR and Cash, SS and Williams, ZM and Rubin, DB and Brandman, DM and Stavisky, SD and AuYong, N and Pandarinath, C and Downey, JE and Bensmaia, SJ and Henderson, JM and Willett, FR},
title = {A mosaic of whole-body representations on the human precentral gyrus.},
journal = {Nature},
volume = {656},
number = {8128},
pages = {680-687},
pmid = {42310450},
issn = {1476-4687},
mesh = {Humans ; *Motor Cortex/physiology/cytology/anatomy & histology ; Movement/physiology ; *Brain Mapping ; Brain-Computer Interfaces ; Male ; Female ; Speech/physiology ; Extremities/physiology ; Spinal Cord Injuries/physiopathology ; Microelectrodes ; Amyotrophic Lateral Sclerosis/physiopathology ; Adult ; Paralysis/physiopathology ; },
abstract = {Understanding how the body is represented in the motor cortex is key to understanding how the brain controls movement. Although the motor cortex has been mapped in animal models at a fine scale[1-10], characterization in humans remains primarily limited to low-resolution recording[11-16] and stimulation techniques[17-20]. Here we created a comprehensive map of the human motor cortex at single-neuron resolution, spanning microelectrode array recordings from 20 arrays across 8 individuals with paralysis from spinal cord injury, amyotrophic lateral sclerosis or brainstem stroke, all enrolled in brain-computer interface clinical trials. These arrays broadly sample the crown of the precentral gyrus (PCG; thought to be composed largely of the premotor cortex (Brodmann area 6)). We found that body parts were highly intermixed, such that the entire body was represented in all sampled locations of the PCG, although the relative strength of body parts was roughly consistent with the motor homunculus[17,18]. We also found two speech-preferential areas with a broadly tuned, orofacial-dominant area in between them. Throughout the PCG, movement representations of the four limbs were interlinked, with homologous movements of different limbs (for example, toe curl and hand close) having correlated representations. These data provide evidence consistent with an intermixed, interrelated and behaviour-centred organization of the motor cortex[3,21]. The resulting map also provides important targeting information for brain-computer interfaces that seek to restore motor function.},
}

Humans
*Motor Cortex/physiology/cytology/anatomy & histology
Movement/physiology
*Brain Mapping
Brain-Computer Interfaces
Male
Female
Speech/physiology
Extremities/physiology
Spinal Cord Injuries/physiopathology
Microelectrodes
Amyotrophic Lateral Sclerosis/physiopathology
Adult
Paralysis/physiopathology

@article {pmid42310788,
year = {2026},
author = {Wood, C and Brown, G and Chalk, K and Smith, SH and Williams, H and Broadhurst, G and Ealing, J and Hamdalla, H and Breen, C and Macleod, R and Chaouch, A},
title = {Co-development of a genetic care pathway for ALS: real-world perspectives from the North of England.},
journal = {Orphanet journal of rare diseases},
volume = {21},
number = {1},
pages = {},
pmid = {42310788},
issn = {1750-1172},
mesh = {*Amyotrophic Lateral Sclerosis/genetics ; Humans ; Genetic Testing/methods ; England ; Retrospective Studies ; Male ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a rare, progressive neurodegenerative disorder, with a substantial proportion of cases attributed to genetic factors. Recent advances in gene discovery and genomic technologies have transformed ALS care by enabling genomic testing to inform prognosis, assess familial risk, and facilitate access to novel therapies. However, guidance on the delivery of genetic testing and counselling in ALS remains limited, leading to variability in clinical practice. In response, the Manchester Motor Neuron Disease (MND) Care Centre and the Manchester Centre for Genomic Medicine co-developed a structured genetic care pathway for ALS, drawing on real-world data, patient engagement, and multidisciplinary collaboration.

RESULTS: A retrospective evaluation of 326 ALS patients at the Manchester MND Care Centre identified significant variability in genetic testing uptake, counselling practices, and record-keeping. Patient survey and engagement sessions revealed uncertainty regarding key genetic concepts and inconsistent recall of pre- and post-test discussions. Priorities for improvement included clearer communication, standardised discussions, and enhanced support for families following genetic findings. Consequently, the Greater Manchester ALS Genetic Testing Pathway was developed by a multidisciplinary team, incorporating consensus-based steps for patient identification, pre-test conversations, consent, testing, results disclosure, and post-test support. This pathway integrates genetic testing into routine ALS care, clarifies team responsibilities, and establishes a framework for ongoing evaluation using key performance indicators. Patient and staff feedback is used to support continuous improvement.

CONCLUSIONS: The co-developed ALS genetic testing pathway provides a scalable model for standardising genomic care in mainstream clinical settings. By establishing clear processes for genetics discussions, consent, and follow-up, the pathway seeks to improve equity, transparency, and person-centred care. Ongoing evaluation and collaboration with patients, clinicians, and genetic services are essential to ensure the pathway remains responsive to scientific advances and evolving patient needs. Wider adoption of structured genetic pathways may facilitate the integration of genomics into care for rare diseases across healthcare systems.},
}

*Amyotrophic Lateral Sclerosis/genetics
Humans
Genetic Testing/methods
England
Retrospective Studies
Male

@article {pmid42311066,
year = {2026},
author = {Dubbioso, R and Pappatà, S},
title = {Amyotrophic lateral sclerosis as a network disease: from metabolic decline to network failure.},
journal = {Brain : a journal of neurology},
volume = {149},
number = {7},
pages = {2189-2190},
doi = {10.1093/brain/awag211},
pmid = {42311066},
issn = {1460-2156},
}

@article {pmid42311422,
year = {2026},
author = {Fayez, SM},
title = {Nanomedicine in 2026: Illustrative Quantitative Analyses of EPR Heterogeneity, Clinical Trial Attrition, and Emerging Horizons for Active Nanotherapeutics.},
journal = {International journal of nanomedicine},
volume = {21},
number = {},
pages = {618407},
pmid = {42311422},
issn = {1178-2013},
mesh = {Humans ; *Nanomedicine/trends/methods ; Animals ; Clinical Trials as Topic ; Nanoparticles/chemistry/therapeutic use ; Neoplasms ; Mice ; Immunotherapy ; },
abstract = {2026 is a turning point for nanomedicine, marking the field's transition from decades of preclinical promise toward tangible clinical impact. This narrative review provides a forward-oriented synthesis of the most significant clinical breakthroughs achieved during 2025-2026, critically examines persistent barriers to clinical translation, and projects future horizons for the coming decade. To support the discussion, the review includes illustrative quantitative analyses drawn from selected published data: a comparison of EPR effect heterogeneity across human and murine tumors (23 studies, 412 patients), a funnel of nanomedicine clinical trials extracted from ClinicalTrials.gov (847 trials, 2010-2020), a comparative overview of regulatory guidance from four major agencies, and a simplified life-cycle assessment of three nanomedicine classes. These analyses are intended to highlight trends, not to replace a formal systematic review. We identify four important clinical advances: first Phase II data for hafnium oxide nanoparticle radioenhancers in inoperable lung cancer; logic-gated STING-agonistic nanoparticles for metastasis-specific immunotherapy; ultrasmall silica nanoparticles that remodel suppressive tumor microenvironments independent of a drug cargo; and CNM-Au8 gold nanocrystals advancing toward regulatory submission for amyotrophic lateral sclerosis. Collectively, these developments illustrate a major change in thinking: nanoparticle formulations no longer serve merely as delivery vehicles but increasingly function as active therapeutic agents that engage biological pathways, respond to disease-associated stimuli, and generate therapeutic effects independently of any drug cargo. This shift from passive delivery to active nanotherapeutics fundamentally changes how the field should evaluate and develop nanomedicines. Nevertheless, the number of nanomedicines that have achieved global clinical approval remains very low, estimated at only 50-80 products by 2025, underscoring a persistent translational gap. We analyze principal obstacles to clinical success, including the limited predictive validity of the enhanced permeability and retention (EPR) effect in humans, batch-to-batch manufacturing variability, safety concerns arising from bio-corona formation and organ accumulation, and the absence of harmonized regulatory frameworks. Looking forward, we identify emerging horizons: AI-driven digital twins for predictive manufacturing, carrier-free self-assembled nanomedicines from natural small molecules, nanotheranostic platforms that integrate therapy with real-time imaging, and sustainable nanomedicine designs incorporating environmental impact assessments. By bridging clinical reality with future potential, this review aims to inform researchers, clinicians, and regulatory stakeholders navigating the rapidly evolving landscape of nanomedicine.},
}

Humans
*Nanomedicine/trends/methods
Animals
Clinical Trials as Topic
Nanoparticles/chemistry/therapeutic use
Neoplasms
Mice
Immunotherapy

@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 {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 = {52},
number = {5},
pages = {625-626},
pmid = {42312499},
issn = {1795-990X},
mesh = {Female ; Humans ; Bias ; *Myocardial Ischemia/epidemiology/prevention & control/etiology ; *Occupational Diseases/epidemiology/prevention & control ; Occupational Exposure ; *Occupational Stress/complications/epidemiology ; Risk Factors ; *Stress, Psychological ; },
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.},
}

Female
Humans
Bias
*Myocardial Ischemia/epidemiology/prevention & control/etiology
*Occupational Diseases/epidemiology/prevention & control
Occupational Exposure
*Occupational Stress/complications/epidemiology
Risk Factors
*Stress, Psychological

@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},
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

@article {pmid42314891,
year = {2026},
author = {Yadav, P and Malik, I and Joshi, H},
title = {Folding pathways and force-induced unfolding of neurodegeneration associated GGGGCC microsatellite repeat RNA revealed by molecular simulations.},
journal = {International journal of biological macromolecules},
volume = {372},
number = {},
pages = {153101},
doi = {10.1016/j.ijbiomac.2026.153101},
pmid = {42314891},
issn = {1879-0003},
mesh = {*Molecular Dynamics Simulation ; G-Quadruplexes ; Nucleic Acid Conformation ; *RNA/chemistry/genetics ; *Microsatellite Repeats/genetics ; Thermodynamics ; *RNA Folding ; Humans ; *C9orf72 Protein/genetics ; },
abstract = {An intronic G4C2 hexanucleotide repeat expansion in the C9orf72 gene causes amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). G4C2 RNA itself directly contributes to disease mechanisms and has emerged as a potential target for small molecules, anti-sense oligonucleotides (ASOs), and CRISPR-based therapeutics. Hence, understanding the folding/unfolding and structural polymorphism is essential for G4C2 RNA-targeting therapies. Here, using equilibrium all-atom molecular dynamics (MD) simulations, we explored potential intermediate metastable conformations of the G4C2 RNA repeats and investigated the effect of repeat length on folding. G4C2 RNA undergoes an ensemble of intermediate metastable states resembling hairpin, knot, and a G-quadruplex (GQ) like structures. Enhanced torsional flexibility and conformational heterogeneity were observed with increasing repeat length. Next, using a crystallized G4C2 RNA structure in GQ conformation, we performed equilibrium MD simulations to reveal its thermodynamic stability. Steered molecular dynamics (SMD) simulations with a reduced model of G4C2 GQ uncover two distinct unfolding mechanisms along the chosen reaction coordinates: strand slippage and unzipping. Overall, our findings provide molecular-level insights into the folding and force-induced unfolding dynamics of G4C2 repeat RNA GQ and set a platform for future studies on small-molecule targeting of ALS/FTD-associated G4C2 RNA.},
}

*Molecular Dynamics Simulation
G-Quadruplexes
Nucleic Acid Conformation
*RNA/chemistry/genetics
*Microsatellite Repeats/genetics
Thermodynamics
*RNA Folding
Humans
*C9orf72 Protein/genetics

@article {pmid42315356,
year = {2026},
author = {Henders, AK and Ziser, L and Garton, FC and Adams, L and Ernst, K and Furlong, S and Heads, JA and Heggie, S and Krasniqi, R and Bhadravathi Lokeshappa, M and Mazumder, S and McNamara, E and MacShane, A and Mekhael, L and Nunn, L and Orden, B and Ryder, J and Thorpe, K and Toubia, M and Wallace, LM and Wickremeratne, D and Windebank, E and Benyamin, B and Ngo, S and Nicholson, G and Pamphlett, R and Steyn, FJ and Visscher, PM and Willams, KL and Henderson, R and Kiernan, MC and Laing, N and Mathers, S and McCombe, PA and Needham, M and Rowe, D and Schultz, D and Talman, P and Vucic, S and Blair, IP and McRae, AF and Wray, NR},
title = {Strategic Amyotrophic Lateral Sclerosis Australia-Systems Genomics Consortium (SALSA-SGC): cohort profile.},
journal = {BMJ open},
volume = {16},
number = {6},
pages = {e110906},
pmid = {42315356},
issn = {2044-6055},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Australia ; *Genomics ; Female ; Male ; Middle Aged ; Aged ; Polymorphism, Single Nucleotide ; Adult ; Cohort Studies ; C9orf72 Protein/genetics ; },
abstract = {PURPOSE: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative motor neuron disease (MND) with heterogeneity in disease onset, progression and treatment response. The Strategic ALS Australia-Systems Genomics Consortium (SALSA-SGC) was established in recognition of the need for large data sets of clinical data matched with biological samples to enable and foster ALS research and better understanding of aetiology and biological mechanisms. SALSA-SGC brought together the major Australian MND clinics to set up sustainable infrastructure that could facilitate long-term human ALS research and clinical trials nationally and internationally.

PARTICIPANTS: Between April 2016 and December 2024, SALSA-SGC recruited 1813 participants, including 1386 ALS/MND cases, 388 controls and 39 others (asymptomatic relatives and ALS mimics). Clinical data and biospecimens are available for 1333 and 1189 ALS cases, respectively, with longitudinal data spanning 4442 total clinic visits and 3201 samples. An open-access online data explorer showcases collected datasets.

FINDINGS TO DATE: Detailed clinical and questionnaire data allow an in-depth description of the cohort, informing clinical and health policy research. Screening for known ALS large-effect risk variants identified 125 mutation carriers (11.5% from N=1059), including 70 with C9orf72 expansions. Single Nucleotide Polymorphism (SNP)-array data (N=1088 cases; N=244 controls) have supported multiple published studies. SALSA-SGC resources are actively used by national and international researchers.

FUTURE PLANS: Ongoing efforts aim to expand recruitment into regional Australia and enhance sample processing for cell-based studies. The SALSA-SGC resource is accessible by researchers under agreements governed by participant consent, human ethics committee guidelines and agreed use of data and samples.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics
Australia
*Genomics
Female
Male
Middle Aged
Aged
Polymorphism, Single Nucleotide
Adult
Cohort Studies
C9orf72 Protein/genetics

@article {pmid42316301,
year = {2026},
author = {Russell, KA and Shahrabi, AA and Akerman, SC and Byrne, MD and Rothstein, JD and Trotti, D and Jensen, BK and Haeusler, AR},
title = {Intrathecal (G4C2)149 delivery in C9orf72-deficient mice yields mild motor dysfunction and ALS/FTD pathological hallmarks.},
journal = {Acta neuropathologica communications},
volume = {14},
number = {1},
pages = {},
pmid = {42316301},
issn = {2051-5960},
support = {RF1 NS114128/NS/NINDS NIH HHS/United States ; R01NS109150/NS/NINDS NIH HHS/United States ; RF1NS114128/NS/NINDS NIH HHS/United States ; R01 NS109150/NS/NINDS NIH HHS/United States ; R01 NS114128/NS/NINDS NIH HHS/United States ; P30 CA056036/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; *C9orf72 Protein/genetics/deficiency/metabolism ; *Amyotrophic Lateral Sclerosis/pathology/genetics/physiopathology/metabolism ; Disease Models, Animal ; Spinal Cord/pathology/metabolism ; *Frontotemporal Dementia/pathology/genetics/physiopathology/metabolism ; DNA Repeat Expansion/genetics ; Mice ; Mice, Transgenic ; Motor Neurons/pathology/metabolism ; Injections, Spinal ; DNA-Binding Proteins/metabolism ; Dependovirus/genetics ; Male ; Mice, Inbred C57BL ; Humans ; },
abstract = {A repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), yet existing mouse models incompletely engage spinal regions implicated in disease. Here, an adeno-associated virus encoding (G4C2)149 repeats was delivered via neonatal intrathecal injection, achieving widespread CNS expression with robust spinal cord targeting. This approach was applied to mice with graded loss of endogenous C9orf72 to interrogate both gain- and loss-of-function mechanisms. Longitudinal motor, behavioral, and pathological analyses revealed that repeat expression primarily drives mild, progressive muscle weakness, whereas coordination deficits were largely genotype dependent. Subtle gait abnormalities and hyperactivity were also observed. Within spinal motor regions, repeat-expressing mice exhibited dipeptide repeat protein accumulation, reduced NeuN-positive area, fewer motor neurons, glial activation, sparse phosphorylated TDP-43 pathology, and increased cryptic TDP-43 splicing. Cross-domain correlations further linked repeat expression, spinal pathology, and motor dysfunction. Collectively, these findings establish that CNS-wide repeat expression combined with reduced C9orf72 produces a coherent, mild ALS/FTD model.},
}

Animals
*C9orf72 Protein/genetics/deficiency/metabolism
*Amyotrophic Lateral Sclerosis/pathology/genetics/physiopathology/metabolism
Disease Models, Animal
Spinal Cord/pathology/metabolism
*Frontotemporal Dementia/pathology/genetics/physiopathology/metabolism
DNA Repeat Expansion/genetics
Mice
Mice, Transgenic
Motor Neurons/pathology/metabolism
Injections, Spinal
DNA-Binding Proteins/metabolism
Dependovirus/genetics
Male
Mice, Inbred C57BL
Humans

@article {pmid42316486,
year = {2026},
author = {Chan, Y and Creer, S and Mere, J and Griffiths, AW and Wright, C and Hobson, EV and McDermott, CJ and Mayberry, EJ},
title = {The Emotional Experiences of Healthcare Professionals Working in Amyotrophic Lateral Sclerosis: A Systematic Review.},
journal = {Muscle & nerve},
volume = {74},
number = {3},
pages = {517-529},
pmid = {42316486},
issn = {1097-4598},
support = {943-794/MNDA_/Motor Neurone Disease Association/United Kingdom ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/therapy ; *Health Personnel/psychology ; *Emotions/physiology ; Adaptation, Psychological ; },
abstract = {Healthcare professionals (HCPs) working with people living with amyotrophic lateral sclerosis (ALS) are often exposed to emotive circumstances including end of life care, trauma, loss, and death. Existing reviews have explored the emotional experiences of people living with ALS and their carers but have largely ignored healthcare staff and the impact of this work on them. This systematic review of qualitative research aims to explore the emotional experiences of and impact on HCPs working with people living with ALS using thematic synthesis (PROSPERO reference: CRD42025631749). Electronic databases were searched for journal articles and gray literature (Medline, Scopus, PsycINFO, Google Scholar, King's Fund Library Database, ProQuest Dissertations, Theses Global) for qualitative or mixed-methods studies exploring the emotional impact on HCPs working in ALS. Twelve studies were included, critically appraised, and analyzed. Four themes were identified. The emotional intensity due to the nature of ALS created challenges for HCPs, while they were also faced with absorbing the emotions of others. HCPs learned to balance their emotional involvement, and HCPs also described positive experiences and coping mechanisms. HCPs working in ALS experience multi-faceted emotional challenges, and they do describe positive emotional experiences within their roles. However, HCPs describe having few coping mechanisms and limited formal support systems in place to process the intense emotions or to guide their emotional involvement. The lack of support for staff may ultimately negatively affect patient care. There is an unmet demand for debriefing, supervision, and further training on how to deal with intense, distressing emotions.},
}

Humans
*Amyotrophic Lateral Sclerosis/psychology/therapy
*Health Personnel/psychology
*Emotions/physiology
Adaptation, Psychological

@article {pmid42316902,
year = {2026},
author = {, },
title = {The ALS Home Health and Durable Medical Equipment Medical Standard Expert Consensus Guideline.},
journal = {Muscle & nerve},
volume = {74},
number = {2},
pages = {293-301},
doi = {10.1002/mus.70290},
pmid = {42316902},
issn = {1097-4598},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; *Durable Medical Equipment/standards ; *Home Care Services/standards ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with escalating disability and complex care needs. Although most individuals with ALS reside at home, existing US guidelines primarily address clinic-based care and provide limited direction on medically necessary home health services and durable medical equipment (DME). The objective of this task force was to develop expert consensus guidance defining minimum medical standards for home health services and DME for individuals with ALS, with the goal of improving patient outcomes, safety, and quality of life. This guideline was developed by a multidisciplinary task force convened by the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM). The process incorporated a scoping literature review, stakeholder engagement (patients, caregivers, and advocacy groups), and iterative expert consensus. Recommendations were informed by clinical expertise, patient-centered priorities, and existing policy frameworks. This guideline outlines stage-responsive home healthcare recommendations spanning nursing, home health aides, physical and occupational therapy, speech-language pathology, respiratory therapy, nutritional support, and social work. It emphasizes proactive, anticipatory care aligned with the predictable trajectory of ALS, rather than being reactive based on functional decline. The document defines medically necessary DME across domains, including mobility, communication, respiratory support, and activities of daily living, advocating for timely access independent of restrictive payer criteria. Key principles include coordinated interdisciplinary care, continuous reassessment, caregiver support, and integration of palliative care. These recommendations establish a foundational standard for ALS home-based care in the United States. Adoption may reduce delays, prevent complications, and support sustained independence and dignity for individuals with ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy
*Durable Medical Equipment/standards
*Home Care Services/standards

@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 = {293},
number = {17},
pages = {5145-5148},
pmid = {42317073},
issn = {1742-4658},
support = {ID 514894665//Deutsche Forschungsgemeinschaft/ ; ID-494535244//Deutsche Forschungsgemeinschaft/ ; ID-465470262//Deutsche Forschungsgemeinschaft/ ; },
mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *NIMA-Related Kinase 1/genetics/metabolism ; *Promyelocytic Leukemia Protein/genetics/metabolism ; Ubiquitination ; Sumoylation ; Mice ; Proteasome Endopeptidase Complex/metabolism ; },
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.},
}

Animals
Humans
*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology
*NIMA-Related Kinase 1/genetics/metabolism
*Promyelocytic Leukemia Protein/genetics/metabolism
Ubiquitination
Sumoylation
Mice
Proteasome Endopeptidase Complex/metabolism

@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.},
}