@article {pmid42670631,
year = {2026},
author = {Bischoff, KE and Leavell, YL and Besbris, JM and Lero, C and Noble, K and Grouls, A and Kurent, J and Kluger, BM and Pantilat, SZ and Mehta, AK and , },
title = {Priorities for Advancing Palliative Care for Amyotrophic Lateral Sclerosis: A Consensus Report From a Palliative Care for ALS Working Group in the United States.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70381},
pmid = {42670631},
issn = {1097-4598},
abstract = {Until there is a cure for amyotrophic lateral sclerosis (ALS), it is imperative that everyone facing this devastating illness receives care to alleviate symptoms and suffering and improve quality of life. Emerging evidence has demonstrated benefits of palliative care for people with ALS, but palliative care is not yet widely available or accessed by people with ALS throughout the disease course. The Palliative Care for ALS Working Group was formed within the International Neuropalliative Care Society, consisting of interprofessional ALS and palliative care clinicians, researchers, advocates, and patients and care partner representatives who are committed to improving palliative care for people living with ALS. The group engaged in a strategic planning process to determine what is needed to advance palliative care for people with ALS over the next 3-5 years. This report outlines the core recommendations from that strategic planning process. Recommendations are divided into five sections: (1) clinician education, (2) clinical service expansion, (3) research, (4) public awareness, and (5) policy change. The aim of this report is to provide ALS and palliative care clinicians, researchers, ALS advocacy organizations, and funders with a road map of priority areas where dedicated focus could significantly advance palliative care for people facing ALS, with the goals of relieving suffering and improving quality of life. The Palliative Care for ALS Working Group is making concrete steps toward these priority areas and will continue to serve as a convening and coordinating body for this work.},
}

@article {pmid42670660,
year = {2026},
author = {Basualdo Allende, AL},
title = {Comment on: 'Living in a world that's not about us': The impact of everyday life on the health and wellbeing of autistic women and gender diverse people.},
journal = {Women's health (London, England)},
volume = {22},
number = {},
pages = {17455057261484826},
pmid = {42670660},
issn = {1745-5065},
mesh = {Humans ; Female ; *Oral Health ; *Autistic Disorder/psychology ; *Women's Health ; Gender-Nonconforming Persons ; },
abstract = {This correspondence comments on Grove et al.'s autistic-led qualitative study on the health and wellbeing of autistic women and gender-diverse people. It argues that oral health should be considered within autism-aware women's healthcare because toothbrushing, dental attendance, oral pain, sensory distress, and communication barriers may affect daily living, access to care, and overall wellbeing. The letter proposes a practical integration pathway based on simple oral-health screening, autism-aware dental referral, sensory and communication adaptations, and collaboration with primary care, mental health, and women's health services. This approach does not imply causality, but supports more holistic, person-centred care.},
}

Humans
Female
*Oral Health
*Autistic Disorder/psychology
*Women's Health
Gender-Nonconforming Persons

@article {pmid42671301,
year = {2026},
author = {Burke, S and Skedros, SA and Carroll, BT},
title = {Comment on Dowdle et al.'s "National Trends in Repair Type Selection After Mohs Micrographic Surgery: A Benchmark Analysis Using TriNetX.".},
journal = {Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]},
volume = {},
number = {},
pages = {},
doi = {10.1097/DSS.0000000000005334},
pmid = {42671301},
issn = {1524-4725},
}

@article {pmid42671791,
year = {2026},
author = {Thomasen, MS and Brams, PH and Værbak, N and Cox, CMM and Parsons, CE},
title = {Daily emotion in fathers and mothers: Little evidence for greater paternal well-being during infant care.},
journal = {Emotion (Washington, D.C.)},
volume = {},
number = {},
pages = {},
doi = {10.1037/emo0001734},
pmid = {42671791},
issn = {1931-1516},
support = {//Carlsbergfondet/ ; },
abstract = {Parents' daily experience of childcare has garnered considerable attention following Kahneman et al.'s (2004) finding that childcare ranked among the least enjoyable daily activities. Subsequent studies have generally found that fathers report more positive valence during childcare compared to mothers. Here, we used experience sampling to examine daily experiences of first-time parents in Denmark between 2022 and 2024, where parental leave policies aim to promote involvement of fathers in infant care. Parents responded to 7 days of prompts during maternity and paternity leave, assessing valence (0-100 scale), sleepiness (Karolinska Sleepiness Scale), and current activities, including direct infant care, indirect care, and play (N = 227). Data were analyzed using Bayesian multilevel beta regression models. We found no credible evidence for the previously documented father advantage in valence during childcare. Mothers showed less positive valence during caregiving activities relative to other activities; effects for fathers were uncertain, and valence patterns differed across maternity and paternity leave. Sleepiness was strongly associated with less positive valence for both parents, with mothers showing steeper declines compared to fathers. Sleepiness moderated activity-valence associations in gender-specific ways: attenuating negative associations with direct care for mothers while reducing positive associations with play for fathers. In a country where paternal caregiving is supported through paid leave policies, mothers and fathers report largely similar valence patterns during infant care. The robust association between sleepiness and less positive valence points to sleep disruption as impacting parental emotion experiences, with mothers showing more vulnerability to its negative effects. (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}

@article {pmid42672036,
year = {2026},
author = {Krumina, M and Fernandes, S and Vilne, B and Baczyk, M},
title = {Computational Insights into Neuromodulation: How Electric Fields Shape Motor Neuron Excitability.},
journal = {IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/TNSRE.2026.3729166},
pmid = {42672036},
issn = {1558-0210},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is an incurable neurodegenerative disease characterized by the selective loss of spinal motor neurons (MN). Trans-spinal direct current stimulation (tsDCS) has emerged as a promising noninvasive neuromodulation technique that could provide neuroprotection and slow down disease progression. However, the mechanisms by which tsDCS affects individual MNs remain poorly understood. This study uses computational modeling to explore how low-intensity extracellular electric fields (EEFs), generated by tsDCS, influence the electrophysiological behavior of MNs. Morphologically realistic, multi-compartment models of neonate mouse alpha-MNs were developed in the NEURON simulation environment. Simulations were conducted under different EEF magnitudes, polarities and orientations. At the population level, consistent directional effects on excitability-related properties were limited and depended on stimulation condition. However, analyses of response magnitude showed that EEFs could modulate several properties, including resting membrane potential and rheobase, even when the direction of change varied across neurons. This heterogeneity was associated with neuronal morphology and its alignment with the applied field, with dendritic length and asymmetry affecting sensitivity. Overall, the results suggest that low-intensity EEFs produce modest, morphology-dependent modulation of MN electrophysiological properties, and that variability in neuronal structure and orientation may help explain discrepancies across previous experimental and modeling studies.},
}

@article {pmid42673727,
year = {2026},
author = {Aladwan, S and Jasim, A and Qassem, TA and Gajjar, TB and Hanumanthayya, M and Tripathi, V and Maharana, L and Bainsal, N},
title = {Human health risk assessment of toxic and non-toxic elements in various oily, cream, and powder cosmetics in Arab countries- A systematic literature review.},
journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)},
volume = {97},
number = {},
pages = {127946},
doi = {10.1016/j.jtemb.2026.127946},
pmid = {42673727},
issn = {1878-3252},
abstract = {Oily, cream, and powder cosmetics (OCPCs) are widely used worldwide, especially in Arab nations, highlighting the need for ongoing heavy metal (HM) monitoring. This systematic review examined 16 HM concentrations in 14 OCPC product categories across 11 of the 22 Arab countries, selected countries based on predefined inclusion and exclusion criteria, and evaluated their associated health risks for only 9 of the 14 OCPCs for which sufficient data were available. The analysis included 24 papers published between June 1, 2007, and January 30, 2026, selected according to prescribed inclusion and exclusion criteria. International authorities like the WHO and the EU set acceptable limits (ALs) for HM levels. According to EPA criteria, all detected HMs underwent a health risk assessment (HRA). Saudi Arabia and Jordan had the highest HM detection rates in OCPCs among the 11 Arab countries analyzed, underscoring the need for stronger regulation. Moisturizing creams, toners, cosmetic masks, and oils were mostly contaminated with non-toxic HMs, whereas facial foundation and face cream samples were contaminated with toxic HMs. Despite exceedances of WHO and EU ALs for several elements, the EPA-based dermal risk indices remained below acceptable thresholds, reflecting the distinction between concentration-based regulatory limits and exposure-based health risk assessment. Arab regulatory agencies should establish monitoring systems to limit HMs in OCPCs, in line with WHO and EU guidelines on HM ALs in cosmetics, before market access.},
}

@article {pmid42674126,
year = {2026},
author = {Raffaele, S and Bonifacino, T and Mannella, FC and Nguyen, N and Torazza, C and Marangon, D and Chinosi, EM and Schrøder, HD and Hejbøl, EK and Madsen, K and Marchetti, L and Trincavelli, ML and Milanese, M and Lecca, D and Lambertsen, KL and Bonanno, G and Abbracchio, MP and Fumagalli, M},
title = {Selective targeting of the oligodendroglial GPR17 receptor improves myelin integrity and motor function in female SOD1[G93A] mice.},
journal = {Pharmacological research},
volume = {232},
number = {},
pages = {108424},
doi = {10.1016/j.phrs.2026.108424},
pmid = {42674126},
issn = {1096-1186},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no definitive disease-modifying therapies available, underscoring the urgent need to identify novel druggable targets. The G protein-coupled receptor GPR17 is a critical regulator of oligodendrocyte maturation and has emerged as a candidate target in ALS, yet its relevance to human disease and its therapeutic potential remain unclear. Here, we demonstrate that pathological GPR17 upregulation defines a conserved, pathologically immature oligodendroglial state in human ALS that can be pharmacologically leveraged to restore myelin integrity and improve functional outcome in vivo. Publicly available transcriptomics datasets and histological analyses revealed an increased abundance of GPR17-expressing immature oligodendrocytes in post-mortem human spinal cord tissue from ALS cases. Moreover, sustained activation of GPR17 with a selective agonist induced GPR17 internalization in heterologous expression systems and promoted the differentiation of primary oligodendrocyte precursors derived from SOD1[G93A] mice. Translating these findings in vivo, chronic treatment with a brain-penetrant GPR17 agonist derived from the same pharmacological class significantly extended survival, delayed body weight loss, and improved motor performance in female SOD1[G93A] mice, whereas male mice showed no therapeutic benefit. These effects were associated with restored oligodendrocyte maturation, preserved myelin integrity, motor neuron survival, and attenuated reactive gliosis in the spinal cord of female SOD1[G93A] mice, while milder effects were observed in males. Together, these findings establish oligodendroglial GPR17 as a conserved and pharmacologically actionable target in ALS and show that sustained in vivo GPR17 agonism can reprogram altered oligodendroglial states and slow disease progression in a sex-dependent manner.},
}

@article {pmid42675240,
year = {2026},
author = {Ma, S and Luo, S and Zhong, H},
title = {Artificial Intelligence in Neuromuscular Diseases: Opportunities for a Data-Scarce Field.},
journal = {Neurology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42675240},
issn = {2193-8253},
support = {Open research fund: gect-2025-Z01//Shanghai Key Laboratory of Gene Editing and Cell Therapy for Rare Diseases/ ; },
abstract = {Neuromuscular diseases (NMDs) encompass over 800 distinct entities affecting approximately one in 1000 individuals worldwide, with progressive muscle weakness, atrophy, and motor impairment as primary clinical manifestations. The rarity of most NMDs creates fundamental challenges for artificial intelligence (AI) and machine learning (ML) applications that typically require large-scale datasets. In this narrative review we synthesize the literature published between 2018 and 2025 on AI applications across the NMD spectrum, organized by clinical application domain. We examine how AI has advanced diagnostic capabilities through genetic variant interpretation, muscle magnetic resonance imaging analysis, electromyography-based classification, and computational pathology. In disease monitoring and prognosis, wearable-derived digital biomarkers have achieved regulatory qualification (US Food and Drug Administration [FDA] and European Medicines Agency [EMA]) as clinical trial endpoints for Duchenne muscular dystrophy, while AI-driven survival models for amyotrophic lateral sclerosis (ALS) have been validated across 14 European centers. Proteomic and multi-omics analyses using ML have identified diagnostic panels for ALS. However, most reported models were developed and internally validated on single-center datasets, and few have undergone external or prospective validation or clinical implementation. Despite these achievements, research intensity varies dramatically across NMD subtypes, with ALS and Duchenne muscular dystrophy dominating while myotonic dystrophy, congenital myopathies, and metabolic myopathies remain virtually unexplored. Critical gaps persist in computational pathology, multi-center validation, and clinical translation. In this review, we discuss how federated learning, international collaborative networks (TREAT-NMD, Solve-RD, EURO-NMD), and foundation models can address these challenges, and propose directions for future AI-enhanced clinical studies in this data-scarce field.},
}

@article {pmid42676114,
year = {2026},
author = {Xu, J and Wu, X and Zhang, B and Wu, K},
title = {Ba4Al4SnS12: balancing bandgap and nonlinear optical performance in thioaluminate via multifunctional group engineering.},
journal = {Dalton transactions (Cambridge, England : 2003)},
volume = {},
number = {},
pages = {},
doi = {10.1039/d6dt01763k},
pmid = {42676114},
issn = {1477-9234},
abstract = {The exploration of infrared nonlinear optical (IR NLO) crystals with excellent performance has attracted increasing attention in view of the inherent drawbacks (low laser damage threshold (LDT) or harmful two-photon absorption (TPA)) of commercial NLO crystals. However, the critical performances (wide bandgap (>3.0 eV) and good nonlinearity (>0.5 × AgGaS2)) show an inverse relationship in IR NLO crystals; thus, the judicious selection and combination of functional motifs are critical, as performance is fundamentally governed by structure. For that reason, we propose a multifunctional group engineering strategy incorporating [AlS4] for a wide bandgap and [SnS4] for large nonlinearity to design a new NLO chalcogenide that affords the successful synthesis of thioaluminate, Ba4Al4SnS12. Experimental study shows that Ba4Al4SnS12 achieves an optimal performance balance between a wide bandgap (3.06 eV) and a moderate second-harmonic generation (SHG) response (0.56 × AgGaS2) with requisite phase-matching behavior (Δn = 0.042), further indicating that Ba4Al4SnS12 could be regarded as a potential IR NLO candidate. Theoretical analysis demonstrates the respective contributions of distinct tetrahedral groups to the bandgap and NLO coefficient and validates the feasibility of multifunctional group engineering. Therefore, this study provides a principle for selecting excellent functional groups and research systems, illuminating a feasible pathway toward future NLO crystals with superior performance.},
}

@article {pmid42676195,
year = {2026},
author = {Arbuzova, EE and Seksyaev, NE and Karakulova, YV and Selyanina, NV and Danilova, MA},
title = {[Atypical forms of amyotrophic lateral sclerosis].},
journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova},
volume = {126},
number = {8},
pages = {13-20},
doi = {10.17116/jnevro202612608113},
pmid = {42676195},
issn = {1997-7298},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology/classification ; Phenotype ; Diagnosis, Differential ; Disease Progression ; Motor Neurons/pathology ; },
abstract = {This article provides a comprehensive overview of contemporary concepts regarding the classical and atypical phenotypes of amyotrophic lateral sclerosis (ALS), with a particular focus on critical diagnostic challenges. The classical variant of the disease is characterized by the progressive involvement of both upper and lower motor neurons, typically presenting with an asymmetric onset and a predictable progression. However, several atypical phenotypes are identified, including syndromes predominantly affecting the lower motor neurons, such as the «hanging hands» and «hanging legs» syndromes, isolated bulbar paralysis, ALS with respiratory onset, and forms with a predominance of upper motor neuron involvement. These atypical variants often mimic other neurological conditions-such as cervical myelopathy, multifocal motor neuropathy, and myasthenia gravis-which can result in significant delays in the accurate diagnosis of ALS. Atypical forms of ALS represent a major source of diagnostic errors in clinical practice. Enhancing healthcare professionals' understanding of the spectrum of phenotypic presentations, alongside the application of contemporary diagnostic criteria, facilitates more timely diagnoses, optimized patient care pathways, and the prompt initiation of pathogenetic therapies, ultimately improving both survival rates and quality of life for affected individuals.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology/classification
Phenotype
Diagnosis, Differential
Disease Progression
Motor Neurons/pathology

@article {pmid42677779,
year = {2026},
author = {Ali, A and Arif, M and Ashraf, U and Elahi, S and Mustafa, A and Yasir, MB and Sarfraz, W and Ansari, AU and Masood, HMY and Shabbir, MA and Abdullah, A and Sharma, MK},
title = {CSF Tau and Amyloid Biomarkers in Cognitive Impairment Across the ALS-FTD Spectrum: A Systematic Narrative Review and Evidence Map.},
journal = {Brain and behavior},
volume = {16},
number = {9},
pages = {e71740},
pmid = {42677779},
issn = {2162-3279},
mesh = {Humans ; *tau Proteins/cerebrospinal fluid ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid/complications ; Biomarkers/cerebrospinal fluid ; *Frontotemporal Dementia/cerebrospinal fluid/complications ; *Amyloid beta-Peptides/cerebrospinal fluid ; *Cognitive Dysfunction/cerebrospinal fluid/etiology ; },
abstract = {INTRODUCTION: Cognitive impairment is an important non-motor manifestation of amyotrophic lateral sclerosis (ALS), particularly across the ALS-frontotemporal dementia (ALS-FTD) spectrum. Cerebrospinal fluid (CSF) tau and amyloid biomarkers may reflect nonspecific neurodegenerative injury, concomitant Alzheimer disease (AD) pathology, or distinct cognitive phenotypes. However, available evidence remains limited, fragmented, and methodologically heterogeneous.

METHODS: This systematic narrative review and semi-quantitative evidence map was conducted according to PRISMA 2020 recommendations. PubMed, Scopus, Web of Science, and Google Scholar were searched from database inception through May 2026. Eligible observational studies reported cognition-specific associations between CSF tau, amyloid, or related neurodegenerative biomarkers and cognitive outcomes in ALS-spectrum populations. Two reviewers independently screened studies, extracted quantitative effect estimates, and assessed risk of bias using the Newcastle-Ottawa Scale. Cross-study consistency was summarized using an exploratory semi-quantitative evidence-coding framework.

RESULTS: Four observational studies comprising 638 ALS-spectrum participants fulfilled the eligibility criteria. Total tau and p-tau181 showed the most reproducible associations with cognition. Total tau correlated with ECAS total (r = -0.398, P < 0.001) and ALS-specific cognition (r = -0.403, P < 0.001), while adjusted multicenter analyses demonstrated associations between p-tau181 and ECAS total (β = -0.03, p = 0.006) and memory performance (β = -0.04, p = 0.003). Both biomarkers received ++ evidence-map coding. Amyloid findings were more heterogeneous; lower Aβ42/Aβ40 was associated with poorer memory performance (β = 0.20, p = 0.044), but continuous amyloid-cognition associations were not consistently replicated across cohorts (± evidence). Broader CSF protein-ratio findings remained exploratory. Clinical, cognitive, assay, and analytical heterogeneity precluded meta-analysis.

CONCLUSIONS: The available evidence, although limited and heterogeneous, suggests that total tau may primarily reflect broader neurodegenerative injury, whereas p-tau181 and Aβ42/Aβ40 may be more informative for selected cognitive phenotypes or possible AD co-pathology. These biomarkers should remain research tools until larger, standardized, longitudinal multicenter studies establish their pathological specificity, predictive value, and clinical utility.},
}

Humans
*tau Proteins/cerebrospinal fluid
*Amyotrophic Lateral Sclerosis/cerebrospinal fluid/complications
Biomarkers/cerebrospinal fluid
*Frontotemporal Dementia/cerebrospinal fluid/complications
*Amyloid beta-Peptides/cerebrospinal fluid
*Cognitive Dysfunction/cerebrospinal fluid/etiology

@article {pmid42677823,
year = {2026},
author = {Chandran, D and Agrawal, U and Damayanthi, D and Nair, DT and Mandagini, G and Nair, SS and Narasimhaiah, D and Fernandez, FB and Thakur, P and Raghavan, CT and Krishnan, S and Gopala, S and Urulangodi, M},
title = {Cofilin 1 Is an Extracellular Vesicle-Associated Plasma Biomarker of Parkinson's Disease in Humans.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78348},
pmid = {42677823},
issn = {1531-8249},
abstract = {OBJECTIVE: Parkinson's disease (PD) lacks reliable, minimally invasive biomarkers for diagnosis. This study aimed to identify and validate PD-specific plasma extracellular vesicle (EV)-associated proteins.

METHODS: Plasma EVs were isolated by ultracentrifugation and characterized. Proteomic profiling of total plasma EVs from PD patients and healthy controls was performed, and a candidate protein identified after analysis was validated by enzyme-linked immunosorbent assay. Diagnostic accuracy was evaluated using receiver operating characteristic and precision-recall curve analysis. Disease specificity was examined in progressive supranuclear palsy and amyotrophic lateral sclerosis. Histochemical and immunofluorescence analyses were conducted in human and mouse PD brain tissue.

RESULTS: Proteomic analysis identified distinct PD-specific EV proteins, including cofilin 1 (CFL1), which was significantly enriched in EVs isolated from PD. EV-CFL1 levels were significantly elevated in PD compared with healthy controls (p < 0.0001). Receiver operating characteristic analysis showed strong diagnostic performance for EV-CFL1 (area under the curve 0.87). Also, EV CFL1 levels could distinguish PD from progressive supranuclear palsy patients (area under the curve 0.914). CFL1 was enriched in L1 cell adhesion molecule-positive EVs, indicating a possible neuronal origin. CFL1 was detected in both human and mouse PD brain sections. Importantly, EV-CFL1 levels were independent of age, disease stage, and motor severity.

INTERPRETATION: EV-associated CFL1 represents a PD-specific, blood-based marker with strong diagnostic accuracy and can distinguish PD from atypical parkinsonism. The presence of CFL1 was confirmed in human and mouse PD brain tissue, and its accumulation in PD brain suggests a possible role in disease pathogenesis. ANN NEUROL 2026.},
}

@article {pmid42677831,
year = {2026},
author = {Basak, B and Riley, JF and Nataraj, NM and Holzbaur, EL},
title = {Mitophagy in neuronal health and disease: from mechanisms to neurodegeneration.},
journal = {The Journal of clinical investigation},
volume = {136},
number = {17},
pages = {},
pmid = {42677831},
issn = {1558-8238},
mesh = {Humans ; *Mitophagy ; Animals ; *Neurons/pathology/metabolism ; *Mitochondria/pathology/metabolism/genetics ; PTEN-Induced Putative Kinase ; *Neurodegenerative Diseases/metabolism/pathology/genetics ; Protein Kinases/metabolism/genetics ; Ubiquitin-Protein Ligases/metabolism/genetics ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; Signal Transduction ; },
abstract = {Regulation of mitochondrial health is critical for maintaining cellular homeostasis in the nervous system. Damaged mitochondria can have detrimental effects on neuronal health and are thought to be key contributors to the progression of neurodegenerative disorders including Parkinson's disease and amyotrophic lateral sclerosis. To mitigate this damage, multiple quality control mechanisms have evolved to eliminate aged or damaged mitochondria. One such quality control process is autophagy, a process that involves turnover of mitochondria at presynaptic sites and the axon terminal under basal conditions. This highly conserved mechanism sequesters mitochondria from the cytosol within autophagosomes followed by degradation upon fusion with a lysosome. Acute mitochondrial damage activates a selective form of autophagy called mitophagy that involves receptor-mediated engulfment and degradation of the damaged organelle. Multiple mechanisms have been shown to drive efficient mitophagy in neurons and glia, including PTEN induced kinase 1 (PINK1)/Parkin-dependent mitophagy and receptor-mediated mitophagy. Genetic, pathological, and experimental evidence all implicate defects in the removal of damaged mitochondria in the onset or progression of neurodegenerative disease. Both the initiation of PINK1/Parkin-dependent mitophagy and deficits in the removal of damaged mitochondria are linked to activation of neuroinflammatory pathways, including NF-κB and cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling. In this Review, we discuss the molecular pathways governing mitophagy in neurons and glial cells and how deficits in these pathways may lead to neurodegeneration. We also highlight emerging therapeutic strategies aimed at restoring mitophagy to preserve neuronal homeostasis and function.},
}

Humans
*Mitophagy
Animals
*Neurons/pathology/metabolism
*Mitochondria/pathology/metabolism/genetics
PTEN-Induced Putative Kinase
*Neurodegenerative Diseases/metabolism/pathology/genetics
Protein Kinases/metabolism/genetics
Ubiquitin-Protein Ligases/metabolism/genetics
*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics
Signal Transduction

@article {pmid42677900,
year = {2026},
author = {Chan, KH and Ha, Y and Islegen-Wojdyla, A and Leon, S and Garces, M and McReynolds, D and Chong, X and Sriramoju, RV and Mahl, J and Guenzing, D and Koepp, W and Hexemer, A and Hellert, T and Chavez, T},
title = {Orchestrating agentic systems at ALS beamline 5.3.1 with Osprey and Bluesky.},
journal = {Journal of synchrotron radiation},
volume = {},
number = {},
pages = {},
doi = {10.1107/S1600577526007836},
pmid = {42677900},
issn = {1600-5775},
support = {107514//US Department of Energy, Office of Science/ ; DE-AC02-05CH11231//US Department of Energy, Office of Science/ ; },
abstract = {Modern synchrotron beamlines support increasingly complex experiments, but their operation remains strongly dependent on facility-specific control interfaces and workflows. This reliance creates a significant barrier to entry for new users and limits the portability of experimental procedures across beamlines. Here, we present a minimal, agent-agnostic orchestration architecture for AI-assisted beamline operation, deployed at Advanced Light Source beamline 5.3.1. The approach introduces a capability-based abstraction layer that exposes beamline functionality as a set of predefined operations. Within this framework, AI agents translate natural-language user requests into structured experimental plans composed of these capabilities. All plans are executed through the Bluesky Queue Server, ensuring deterministic operation within existing control and safety constraints without modification of the underlying beamline control system. The framework is defined by three key elements: (i) a portable capability layer that decouples user intent from beamline-specific implementation, (ii) a hybrid interaction framework combining AI-assisted workflow composition with graphical user interface (GUI)-based monitoring and control, and (iii) constrained execution that restricts all actions to predefined capabilities and requires user approval prior to execution. We demonstrate the architecture using grazing-incidence scattering (GISAXS), multi-edge X-ray absorption spectroscopy (XANES), and cross-beamline deployment scenarios. In each case, the system generates physically meaningful experimental plan, adapts to local hardware constraints, and preserves experimental intent across different instruments. These results demonstrate a practical and scalable approach for integrating AI into synchrotron experimentation, enabling intent-driven, portable, and safe beamline operation.},
}

@article {pmid42678414,
year = {2026},
author = {Henne, C and Sigfridsson, I and Brännström, T and Forsberg, KME and Marklund, SL and Zetterström, P and Andersen, PM},
title = {Seeds from ALS patients homozygous for the SOD1 D90A mutation transmit two types of SOD1 aggregation and motor neuron disease.},
journal = {Acta neuropathologica},
volume = {152},
number = {1},
pages = {},
pmid = {42678414},
issn = {1432-0533},
mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *Superoxide Dismutase-1/genetics/metabolism ; Mice, Transgenic ; *Mutation/genetics ; Homozygote ; Mice ; Spinal Cord/pathology/metabolism ; Disease Models, Animal ; Female ; Male ; Motor Neurons/pathology ; *Protein Aggregation, Pathological/genetics/pathology ; Middle Aged ; },
abstract = {Mutations in superoxide dismutase-1 (SOD1) are a common cause of amyotrophic lateral sclerosis (ALS). Inheritance is as a rule dominant, but in carriers of the most prevalent mutation, D90A, disease primarily develops in homozygotes. Increasing evidence suggests that prion-like propagation of SOD1 aggregation is the central pathogenic mechanism. Two structurally different strains of aggregates have been found to arise in human SOD1 (hSOD1) transgenic (Tg) mouse models of ALS. Strain A is formed by most mutants including hSOD1[G85R] and homozygous hSOD1[WT] Tg mice, whereas homozygous hSOD1[D90A] Tg mice form a distinct strain B, but also A. Inoculation of strain A and B seed preparations from Tg mice into lumbar spinal cord of adult hSOD1[G85R] mice induced templated spreading hSOD1 aggregation and premature ALS-like disease. Seeds from an ALS patient carrying the hSOD1[G127X] truncation mutation likewise transmitted strain A aggregation and disease. In the present study, we investigated whether seeds prepared from spinal ventral horns from six patients homozygous for the hSOD1[D90A] mutation could transmit aggregation and disease to adult hSOD1[G85R] Tg mice. Despite the extensive degeneration and loss of motor neurons in the long-lived D90A patients, two of the seeds significantly shortened the survival of the Tg mice, one transmitting A and the other B-pattern hSOD1 aggregation. Nine different preparations from four human controls lacked effects. The results demonstrate that two distinct aggregate strains can arise and propagate in homozygous hSOD1[D90A] ALS patients, further supporting the hypothesis that prion-like transmission of hSOD1 aggregation is the primary pathogenic mechanism in SOD1-linked ALS.},
}

Animals
Humans
*Amyotrophic Lateral Sclerosis/genetics/pathology
*Superoxide Dismutase-1/genetics/metabolism
Mice, Transgenic
*Mutation/genetics
Homozygote
Mice
Spinal Cord/pathology/metabolism
Disease Models, Animal
Female
Male
Motor Neurons/pathology
*Protein Aggregation, Pathological/genetics/pathology
Middle Aged

@article {pmid42666355,
year = {2026},
author = {Wei, Y and Wang, J and Ji, Y and Shang, T and Shen, Y and Sun, H and Cai, Y},
title = {Therapeutic Challenges and Future Breakthroughs in Amyotrophic Lateral Sclerosis: From Precision Medicine to Innovative Trial Design.},
journal = {Drug design, development and therapy},
volume = {20},
number = {},
pages = {626069},
pmid = {42666355},
issn = {1177-8881},
mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/therapy ; Humans ; *Precision Medicine ; Animals ; *Clinical Trials as Topic ; *Neuroprotective Agents/therapeutic use ; *Research Design ; Genetic Therapy ; Drug Development ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a highly heterogeneous and fatal neurodegenerative disorder, for which clinical management and drug development have long faced formidable challenges. Since the approval of riluzole and edaravone, dozens of promising drug candidates that showed efficacy in preclinical models have failed in Phase III trials, highlighting an urgent need for systematic re-evaluation of the field. This review provides a comprehensive summary of the major limitations of current clinical therapies for ALS. These include the modest survival benefit of riluzole, the narrow eligible population for edaravone, and the complex trajectory of sodium phenylbutyrate-taurursodiol, which received accelerated approval but was subsequently voluntarily withdrawn after its confirmatory Phase III trial failed to meet its primary endpoints. On this basis, we discuss four major challenges that contribute to clinical trial failures: disease heterogeneity, paucity of reliable biomarkers, insufficient translational validity of preclinical models, and inherent flaws in conventional trial designs. Subsequently, we discuss emerging therapeutic strategies, encompassing precision medicine and gene therapy (exemplified by the development of the antisense oligonucleotide tofersen for SOD1-ALS), targeting protein homeostasis, modulation of neuroinflammation, metabolic and energetic support, neuroprotection and regeneration, as well as multi-target combination approaches. Innovative trial designs, including adaptive platform trials (exemplified by the HEALEY ALS Platform Trial), enrichment designs, sequential designs, N-of-1 trials, and virtual clinical trials are fundamentally reshaping the drug development paradigm in ALS. In conclusion, ALS treatment is at a historic turning point from a "one-size-fits-all" approach toward "precisely stratified" medicine. Future success depends on establishing multimodal biomarker panels, implementing genetic testing-guided individualized therapy, developing combination regimens, and integrating patient-reported outcomes with palliative care. Although substantial challenges remain, the clinical success of Tofersen provides evidence that precision therapeutic strategies may gradually transform ALS management toward a more individualized and disease-modifying approach.},
}

*Amyotrophic Lateral Sclerosis/drug therapy/therapy
Humans
*Precision Medicine
Animals
*Clinical Trials as Topic
*Neuroprotective Agents/therapeutic use
*Research Design
Genetic Therapy
Drug Development

@article {pmid42666931,
year = {2026},
author = {Laffita-Mesa, JM and Paucar, M and Svenningsson, P},
title = {ATXN2 Spectrum Disorders: Genetic Complexity Beyond Dominant Inheritance.},
journal = {Neurology. Genetics},
volume = {12},
number = {5},
pages = {e200428},
pmid = {42666931},
issn = {2376-7839},
abstract = {The genetic complexity of ATXN2 challenges conventional paradigms in neurodegeneration. While initially linked to autosomal dominant spinocerebellar ataxia type 2, ATXN2 CAG expansions have emerged as a major risk factor for amyotrophic lateral sclerosis. In a recent article, Saucier et al. describe an Acadian family with a recessive inheritance pattern of ATXN2-related disease, challenging the long-held assumption of a predominantly autosomal dominant, gain-of-function-driven mechanism. Here, we analyze how ATXN2's inheritance mode may shift based on repeat interruptions, somatic mosaicism, and gene dosage, suggesting that loss-of-function mechanisms contribute to pathogenesis in certain contexts. We discuss implications for disease classification, genetic counseling, and therapeutic strategies, emphasizing the need for genetic stratification.},
}

@article {pmid42667453,
year = {2026},
author = {Liu, C and Zhang, Y},
title = {Ginsenosides: potential therapeutic implications in neurodegenerative diseases by inhibiting ferroptosis.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {},
pmid = {42667453},
issn = {1573-4978},
mesh = {Humans ; *Ginsenosides/pharmacology/therapeutic use ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Ferroptosis/drug effects ; Animals ; Neuroprotective Agents/pharmacology/therapeutic use ; Amyotrophic Lateral Sclerosis/drug therapy ; },
abstract = {A positive correlation exists between the accelerating pace of population aging and the increasing prevalence of neurodegenerative diseases. Conditions such as Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) profoundly compromise patient quality of life, yet efficacious clinical interventions remain notably limited. The prevention and management of neurodegenerative diseases represent a critical global public health imperative. A comprehensive literature search was performed across PubMed, Web of Science, and Scopus to identify studies on the biological functions, molecular mechanisms, and clinical implications of ginsenosides. The search strategy incorporated MeSH terms and free-text keywords, encompassing "neurodegenerative disease", "ferroptosis", "ginsenosides", "Parkinson's disease", "Alzheimer's disease", "amyotrophic lateral sclerosis", "Huntington's disease" and "multiple sclerosis". From an initial pool of over 400 papers (1998-2026), 107 were selected in this narrative review. Ferroptosis is intricately linked to the pathogenesis of neurodegenerative diseases. Ginsenosides constitute the principal bioactive triterpenoid saponins extracted from plants of the Panax genus, demonstrating broad-spectrum pharmacological efficacy encompassing antitumor, immunomodulatory, anti‑inflammatory, anti‑allergic, anti‑atherosclerotic, antihypertensive, antidiabetic, antistress, and neuroprotective activities. Ginsenosides exert their neuroprotective effects against AD, PD, and ALS predominantly through the modulation of ferroptosis. Herein, this article provides a review of the molecular mechanisms, genetic determinants, signaling cascades, and functional implications of ferroptosis. Ginsenosides represent promising therapeutic agents in neurodegenerative diseases via modulation of iron homeostasis; this paper elucidates mechanistic insights into disease pathogenesis and evaluates their translational therapeutic potential. This narrative review highlights emerging insights that provide novel therapeutic perspectives for neurodegenerative diseases.},
}

Humans
*Ginsenosides/pharmacology/therapeutic use
*Neurodegenerative Diseases/drug therapy/metabolism
*Ferroptosis/drug effects
Animals
Neuroprotective Agents/pharmacology/therapeutic use
Amyotrophic Lateral Sclerosis/drug therapy

@article {pmid42667624,
year = {2026},
author = {Bues, B and Sasmita, AO and Mao, S and Komarek, L and O'Mahony, K and Burk, K},
title = {Axonal pathology and impaired axo-glial crosstalk as early drivers of neurodegeneration.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-26-00462},
pmid = {42667624},
issn = {1673-5374},
abstract = {Axonal dysfunction is a critical event in neurodegenerative diseases, which can precede neuronal loss. For instance, in multiple sclerosis, chronic demyelination leads to axonal transection and downstream neurological deficits, yet in other neurodegenerative conditions, the causal relationship between axonal pathology and disease progression remains elusive. While defects in axonal transport, cytoskeletal integrity, and organelle trafficking are observed in Alzheimer's disease and the frontotemporal dementia-amyotrophic lateral sclerosis spectrum, a question remains: Are axonal defects merely downstream consequences of somatic neurodegeneration, or do they actively drive pathogenesis? Emerging evidence suggests that early axonal dysfunction may accelerate disease progression through disrupted connectivity, retrograde degeneration, and neuroinflammation. Here, we highlight current evidence on axonal pathophysiology across Alzheimer's disease and frontotemporal dementia-amyotrophic lateral sclerosis. We first outline the makeup of the mature axonal compartment, as well as the processes related to axonal maintenance, which include myelination, glial support, and microtubule-dependent transport mechanisms. We further compare axonal perturbations in Alzheimer's disease and frontotemporal dementia-amyotrophic lateral sclerosis, exploring commonalities as potential convergent mechanisms. Therapeutic strategies to stabilize axons by maintaining microtubule dynamics, restoring energetics, or modulating glial support could therefore theoretically offer neuroprotection if performed selectively on vulnerable neuronal subsets and early in the disease course. Ultimately, by reframing axonal pathology as a primary driver rather than an epiphenomenon, this review underscores the importance of targeting axonal health in neurodegenerative diseases.},
}

@article {pmid42667698,
year = {2026},
author = {Rey, V and Feijoó, MEG and Vittar, EE and Morales, JMN and Fernández, JM and Morán Vieyra, FE and Tuttolomondo, ME and Borsarelli, CD},
title = {Photoreductive synthesis and analytical performance of silver nanoparticles stabilized with humic acids for selective and sensitive colorimetric detection of mercury (II) ions.},
journal = {Colloids and surfaces. B, Biointerfaces},
volume = {269},
number = {},
pages = {116112},
doi = {10.1016/j.colsurfb.2026.116112},
pmid = {42667698},
issn = {1873-4367},
abstract = {This study presents the one-step photoreductive synthesis and characterization of humic acid-stabilized silver nanoparticles (AgNP@HA) via the reduction of Ag[+] ions by ketyl radicals generated by UVA-light using the water-soluble photoinitiator Irgacure® 2959 (I-2959) as a function of pH and HA concentration. The formation and properties of the AgNP@HA were characterized by several techniques, including UV-Vis, FTIR, and Raman spectroscopies, as well as transmission electron microscopy (TEM) and dynamic light scattering (DLS). The UV-Vis absorption spectrum changes occurring during the formation of the AgNP@HA were modeled with the multivariate curve fitting using alternating least squares (MCR-ALS) method. The kinetic profiles of each observed species suggested that AgNP@HA are produced through a mechanism of nucleation and aggregation. The AgNP@HA solutions were evaluated as colorimetric sensors for the selective detection of Hg[2+] ions at different pH. The changes in the surface plasmon band absorbance of AgNP@HA induced by Hg[2+], irrespective of the presence of other interfering ions and pH, indicated that AgNP@HA specifically interacts with Hg[2+] to form an amalgam with silver, with remarkable analytical performance, detecting Hg[2+] in the sub ppm range. These results indicate that AgNP@HA prepared by photoreduction with I-2959 can be used as a suitable, simple, economical, and environmentally friendly plasmonic sensor for the detection of mercury in water samples.},
}

@article {pmid42667936,
year = {2026},
author = {Zhu, J and Zhang, Y and Yang, B and Xiang, Q and Hu, S and Wei, W and Zhou, H and Yang, G and Zhang, H},
title = {Associations of cumulative exposure and longitudinal trajectories of neurofilament light chain with 1-year adverse events in amyotrophic lateral sclerosis: A prospective cohort study.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107584},
doi = {10.1016/j.nbd.2026.107584},
pmid = {42667936},
issn = {1095-953X},
abstract = {BACKGROUND: Baseline neurofilament light chain (NFL) predicts amyotrophic lateral sclerosis (ALS) outcomes, but it does not summarize early repeated biomarker information. We evaluated whether cumulative NFL exposure (cuNFL), calculated over an early monitoring window, and longitudinal NFL trajectory groups were associated with subsequent adverse events in a prospective cohort.

METHODS: This prospective study enrolled patients with ALS from 32 provinces in China between January 2024 and January 2025. Plasma NFL was measured at baseline, month 1, and month 2. We used K-means clustering to describe longitudinal NFL patterns and multivariable survival models to evaluate prognostic associations. Inverse-probability weighting and causal-forest analyses were used as exploratory, confounding-adjusted analyses of high versus low cuNFL.

RESULTS: K-means clustering identified three longitudinal NFL groups: Low-Stable (n = 183), Moderate (n = 225), and High-Progressive (n = 100). The High-Progressive group had the shortest event-free survival (P < 0.001). Each 1-SD increment in cuNFL was associated with higher odds of adverse events (adjusted OR 1.99; 95% CI 1.52-2.60; P < 0.001). Using the manuscript-defined 127-event outcome, apparent discrimination was AUC 0.730 for cuNFL and 0.717 for baseline NFL. The paired DeLong comparison was not statistically significant (P = 0.084). Exploratory machine-learning analyses suggested heterogeneity in the association of high cuNFL with outcome by age and respiratory function.

CONCLUSION: Early repeated NFL measurements summarized as cuNFL and longitudinal trajectory groups were associated with short-term adverse events in this cohort. These findings support further external validation of longitudinal NFL-based risk stratification. They do not establish a causal biological effect or a basis for routine repeated measurement.},
}

@article {pmid42668676,
year = {2026},
author = {Varon-Vega, F and Franco Parra, CE and Adame Ochoa, DF and Uricoechea, N and Tuta-Quintero, E and Martinez Ayala, MC},
title = {Use of High-Flow Nasal Cannula in Amyotrophic Lateral Sclerosis Patients Intolerant to Non-Invasive Ventilation: A Case Series.},
journal = {Respirology case reports},
volume = {14},
number = {9},
pages = {e70744},
pmid = {42668676},
issn = {2051-3380},
abstract = {Non-invasive ventilation (NIV) is standard respiratory support for amyotrophic lateral sclerosis (ALS), but intolerance may limit its use. High-flow nasal cannula (HFNC) has emerged as a potential alternative in selected patients, but evidence regarding its use remains scarce. We describe 18 ALS patients' management with HFNC between 2014 and 2024 after documented intolerance to NIV. Mean age at HFNC initiation was 65.1 ± 12.5 years, and 66.7% of patients were female. Partial NIV intolerance occurred in 38.9% of cases, while 33.3% tolerated intermittent combined NIV and HFNC. During follow-up, 50.0% of patients required hospitalization, 33.3% experienced respiratory infections, and 27.8% died. Arterial blood gas parameters remained stable, including PaCO2 (p = 0.314). Functional status declined significantly, with Barthel Index decreasing (35.0 ± 20.5 vs. 11.7 ± 11.3; p < 0.001), whereas respiratory muscle strength remained unchanged. HFNC was feasible as home-based support in ALS patients intolerant to NIV, warranting prospective comparative evaluation.},
}

@article {pmid42669596,
year = {2026},
author = {Horton, DK and Raymond, J and Larson, T and Weisskopf, MG and Howard, I and Mehta, P},
title = {Military Service and Survival Among Persons With ALS in the U.S. National ALS Registry, 2011-2023.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70390},
pmid = {42669596},
issn = {1097-4598},
support = {//CDC/ATSDR National ALS Registry/ ; },
abstract = {INTRODUCTION/AIMS: Military service has been associated with increased risk of amyotrophic lateral sclerosis (ALS) but less is known about survival after diagnosis. We evaluated the association between military service and survival after ALS diagnosis among U.S. National ALS Registry participants.

METHODS: Participants who completed the Registry's Military History Survey between 2011 and 2023 and had valid ALS diagnosis and mortality follow-up information were eligible. Military service was classified as veteran or nonveteran. Mortality was ascertained through National Death Index linkage. Kaplan-Meier methods evaluated survival distributions, and Cox proportional hazards models estimated adjusted mortality associations.

RESULTS: Among 8643 participants, 1735 (20.1%) were veterans and 6908 (79.9%) were nonveterans. Veterans were older at diagnosis and reported greater smoking and alcohol use. The median observed time from ALS diagnosis to death or censoring was 3.77 years among veterans and 4.79 years among nonveterans, an approximate 1-year difference; Kaplan-Meier estimated 5-year survival was 47.1% and 57.4%, respectively. Veterans experienced significantly poorer survival than nonveterans (log-rank χ[2] = 113.45, p < 0.0001). In the primary adjusted Cox model, military service remained associated with increased mortality (HR 1.25, 95% CI 1.15-1.35; p < 0.0001). Findings were consistent across sensitivity analyses accounting for disease severity, symptom onset site, and delayed Registry entry.

DISCUSSION: Military service was associated with poorer survival after ALS diagnosis. Veterans had lower 5-year survival and higher mortality hazards than nonveterans, suggesting military history may be an important prognostic factor in ALS.},
}

@article {pmid42669806,
year = {2026},
author = {Rogala, O and Tarach, KA and Kordek, A and Shu, Y and Gilson, JP and Lakiss, L and Góra-Marek, K},
title = {Commercial Fluid Catalytic Cracking Catalysts for Polymers Chemical Recycling.},
journal = {ChemSusChem},
volume = {19},
number = {17},
pages = {e71002},
doi = {10.1002/cssc.71002},
pmid = {42669806},
issn = {1864-564X},
support = {2021/43/B/ST4/00307//Narodowe Centrum Nauki/ ; 2023/49/B/ST4/02340//Narodowe Centrum Nauki/ ; },
abstract = {Commercial FCC catalysts (fresh and equilibrated) and laboratory made catalysts from Y type zeolite and γ-Al2O3 are characterized by standard techniques and evaluated in the cracking of pure PP, LDPE, and PS polymers as well as coprocessing PP/LDPE mixture in TGA (light-off curves) and a unique operando FTIR & GC-MS set-up. Conversions, products selectivities as well as coke deposition and removal are studied as a function of temperature. In spectroscopic operando investigations, MCR-ALS analysis provides significant insight into the observed results. The equilibrium FCC catalyst (Cat-Eq800) differs markedly from its fresh counterpart (Cat-F800) in product selectivity. Regardless of the polyolefin feed, Cat-Eq800 exhibits higher olefinicity in the C4 fraction. In both commercial catalysts, coke precursor formation proceeds predominantly via paraffin consumption. In situ FTIR analysis revealed valuable information regarding reactant diffusion and catalyst acidity. Despite undergoing severe deactivation treatments, the equilibrium catalyst displays the highest Brønsted-to-Lewis acid site ratio while maintaining efficient mass transport through its hierarchical pore structure. Important information to better design FCC catalysts can be derived, as the exact composition of these important catalysts are often tailored for specific families of heavy oil fractions.},
}

@article {pmid42669892,
year = {2026},
author = {Zanovello, M and Serani, F and Bebeti, A and Paredi, F and Quadrio, G and Fortuna, A and Minicuci, GM and Pegoraro, E and Cagnin, A and Cecchin, D and Sorarù, G},
title = {Metabolic and Fluid Biomarkers Support Microglia Activation in Amyotrophic Lateral Sclerosis.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
pmid = {42669892},
issn = {2328-9503},
abstract = {Amyotrophic lateral sclerosis is an incurable neurodegenerative disease involving motor neuron degeneration and metabolic and immune dysfunction. We combined clinical data, cerebrospinal fluid biomarkers and fluorodeoxyglucose positron emission tomography with magnetic resonance imaging to investigate the role of reactive microglia in disease pathogenesis. Patients showed increased cerebrospinal fluid levels of neurofilament light chain and chitinases, along with hypermetabolism in the medulla oblongata. Chitinase levels correlated with brainstem metabolism and clinical severity. These findings suggest a link between microglial activation, brainstem hypermetabolism and disease progression in amyotrophic lateral sclerosis, supporting a central role for neuroinflammation in disease pathogenesis.},
}

@article {pmid42669933,
year = {2026},
author = {Milella, G and Vacchiano, V and Velucci, V and Zoccolella, S and Liguori, R and Defazio, G},
title = {Data-Driven SuStaIn Model of Disability Progression in Amyotrophic Lateral Sclerosis.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
pmid = {42669933},
issn = {2328-9503},
abstract = {OBJECTIVE: To determine whether ordinal Subtype and Stage Inference (SuStaIn) applied to routine ALSFRS-R item scores can identify reproducible disability progression patterns in amyotrophic lateral sclerosis (ALS) and provide clinically meaningful staging.

METHODS: We analysed baseline ALSFRS-R item responses from 866 PRO-ACT participants. Ordinal SuStaIn inferred subtype-specific sequences of functional deterioration and assigned each participant to a subtype and a SuStaIn-derived functional stage. Longitudinal stability was assessed across 3625 consecutive follow-up visit pairs from 697 participants. Structural reproducibility was evaluated in an independent cohort of 301 consecutive ALS patients. Associations of baseline subtype and stage with survival and subsequent ALSFRS-R decline were examined using Cox and piecewise-linear models.

RESULTS: A three-subtype solution identified fine motor-, gross motor- and bulbar-predominant patterns of early disability. Within each subtype, SuStaIn reconstructed ordered multidomain sequences of functional deterioration and assigned each participant a SuStaIn-derived stage. Subtype assignment was stable across 90.4% of consecutive visit pairs, and stage was non-decreasing in 98.8%. Subtype-specific event ordering was reproduced in the validation cohort. Higher baseline stage was associated with increased mortality risk in the fine motor- and gross motor-predominant subtypes, but not clearly in the bulbar-predominant subtype. Baseline stage showed subtype-dependent, non-linear associations with subsequent functional decline, with acceleration up to mid-stage breakpoints in the fine motor- and gross motor-predominant subtypes and less evident stage-dependent acceleration in the bulbar-predominant subtype.

INTERPRETATION: Routine ALSFRS-R item-level data can define clinically interpretable ALS progression subtypes and latent SuStaIn-derived functional stages. Joint subtype-stage modelling may refine prognostic stratification and support prognosis-informed trial enrichment.},
}

@article {pmid42670527,
year = {2026},
author = {Pan, L and Liu, B and Xu, J and Mu, X and Fan, L},
title = {Mesenchymal Stem Cells and Extracellular Vesicles for Neurodegenerative Diseases: Therapeutic Advances and Challenges.},
journal = {International journal of nanomedicine},
volume = {21},
number = {},
pages = {628071},
pmid = {42670527},
issn = {1178-2013},
mesh = {Humans ; *Neurodegenerative Diseases/therapy ; *Extracellular Vesicles/transplantation ; *Mesenchymal Stem Cells/cytology ; *Mesenchymal Stem Cell Transplantation/methods ; Animals ; },
abstract = {Mesenchymal stem cells (MSCs), as a type of adult stem cells, exhibit robust self-renewal, multi-lineage differentiation, paracrine and immunomodulatory capacities, demonstrating broad application prospects in the treatment of neurodegenerative diseases. This review systematically summarizes the mechanisms of action, therapeutic advances and comparative analyses of various MSCs and their derived extracellular vesicles (EVs) in Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), and discusses the optimization effects of gene modification and pretreatment on therapeutic efficacy. This article not only highlights the advantages of various MSCs and their corresponding EVs, but also provides unique insights into their differentiated therapeutic potential and mechanism of action, which have not been fully elucidated in previous studies. Meanwhile, although current research results are encouraging, this paper also critically points out that existing studies suffer from insufficient elucidation of mechanisms and lack of large-scale clinical trials. Finally, the article prospects future directions of MSC-based therapeutic strategies, including mechanism deepening, treatment optimization and standardization system construction, to promote their translation into clinical application. However, most of the current evidence is still preclinical, and the recognized clinical efficacy in humans is still limited. This is a narrative review. Literature was screened from Web of Science and PubMed by thematic relevance and research quality, without systematic review protocol or meta-analysis.},
}

Humans
*Neurodegenerative Diseases/therapy
*Extracellular Vesicles/transplantation
*Mesenchymal Stem Cells/cytology
*Mesenchymal Stem Cell Transplantation/methods
Animals

@article {pmid42661580,
year = {2026},
author = {O'Farrell, S and Holland, MC and Peelo, C and McLaughlin, R and Heverin, M and Hardiman, O and Costello, E and Pender, N},
title = {Cognitive and behavioral manifestations of the C9orf72 mutation in Amyotrophic Lateral Sclerosis: an age, education, and gender-matched cohort study.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/21678421.2026.2721333},
pmid = {42661580},
issn = {2167-9223},
abstract = {OBJECTIVES: The presence of a hexanucleotide expansion in the gene C9orf72 confers a higher risk of developing ALS and FTD with associated cognitive and behavioral change, although penetrance is incomplete, and many gene carriers never exhibit any clinical signs during their lifetime. To date, there have been few studies investigating additional factors such as age, years of education, gender, and their influence on cognition and behavior in people with ALS (pwALS), particularly those with a hexanucleotide expansion in the gene C9orf72.

METHODS: We selected 104 consenting pwALS from the Irish ALS register, comprising 52 C9orf72 positive participants and 52 C9orf72 negative controls matched on age, years of education, and gender. Cognitive functioning was assessed using the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), while behavioral changes were examined using the Beaumont Behavioral Inventory (BBI).

RESULTS: No significant differences in ECAS performance were observed across the two groups, with the exception of visuospatial performance, which was more impaired in those carrying the C9orf72 repeat expansion (p = .001). Similarly, there was no difference in behavoural scores between the 2 groups.

CONCLUSIONS: These findings suggest that the presence of the C9orf72 repeat expansion does not presage the development of significant cognitive or behavioral impairment early in the disease stage when controlled for age, years of education, and gender. When interpreting these results, it is important to consider the relatively small sample size, and the exclusion criteria of previous clinically significant comorbidities.},
}

@article {pmid42661656,
year = {2026},
author = {Praharaj, S and Chakraborty, E and Mahalingam, G},
title = {Ultraviolet radiation and neurodegeneration: molecular mechanisms underlying dual neuroprotective and neurotoxic effects.},
journal = {Frontiers in cellular neuroscience},
volume = {20},
number = {},
pages = {1909393},
pmid = {42661656},
issn = {1662-5102},
abstract = {Ultraviolet radiation exhibits a complex, often contradictory link to neurodegeneration risk/progression, spanning clinically diagnosed diseases [Parkinson's Disease (PD), Alzheimer's Disease (AD), Multiple Sclerosis (MS) and Amyotrophic Lateral Sclerosis (ALS)] or intermediate phenotypes (decreased neurogenesis, loss of hippocampal volume). The aim of this review is to highlight the dual impact of UV radiation by collecting and synthesizing experimental (preclinical and translational) evidence as well as epidemiological evidence. Current literature exhibits a clear dichotomy: while Vitamin D is capable of exerting a potent neuroprotective effect via anti-oxidant and anti-inflammatory pathways, chronic and intense UV radiation exposure actually hastens the progression or even drives neurodegeneration via a variety of mechanisms. UV radiation exerts its effects through various interconnected pathways: DNA damage pathways, ROS mediated pathways, vitamin D signaling and the skin-brain axis, which unifies both protective and degenerative effects of UV radiation. Owing to the increasing occurrence of neurodegenerative diseases in the general population, these pathways and mechanisms must be leveraged in future research to develop novel therapeutic and preventive strategies. Investigation of biomarkers linked to certain genetic and environmental factors that could provide a link to predisposition toward neurodegeneration and standardization of UV radiation dosimetry (exposure dose/duration) across experimental or pre-clinical studies must also be prioritized.},
}

@article {pmid42662266,
year = {2026},
author = {Dresel, FC and Michaelis, M and Gourlay, CW},
title = {The HDAC Inhibitor Butyrate Reduces SOD1 Aggregation and Improves Motor Function in C. elegans and Cellular Models of ALS.},
journal = {International journal of cell biology},
volume = {2026},
number = {},
pages = {3022967},
pmid = {42662266},
issn = {1687-8876},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterised by motor neuron loss and protein aggregation, commonly driven by mutations in superoxide dismutase 1 (Sod1). Recent evidence implicates gut microbiota-derived metabolites, such as butyrate, in modulating neurodegeneration, but the underlying mechanisms remain unclear. Here, we demonstrate that sodium butyrate (NaB), a histone deacetylase inhibitor and microbial metabolite, ameliorates ALS-related phenotypes in C. elegans and mammalian cell models expressing mutant isoforms of Sod1 linked to ALS. NaB treatment prevented Sod1 aggregation and restored motor function and axonal integrity in transgenic worms overexpressing Sod1[G85R]. Mechanistically, NaB recapitulated the effects of the pan-HDAC inhibitor trichostatin A, suggesting HDAC inhibition as key to reducing Sod1 aggregation and its downstream effects. Application of NaB or the HDAC inhibitor valproic acid also prevented aggregation of Sod1[A4V], Sod1[G85R] or Sod1[G37R] in transfected human neuroblastoma cells. These findings support a conserved neuroprotective role for NaB and HDAC inhibitors via their antiaggregation activity. Our findings also verify C. elegans and neuroblastoma cell lines as excellent research tools to explore the mechanisms underlying the antiaggregation action of NaB and HDAC inhibitors, as well as their potential for future therapeutic development.},
}

@article {pmid42663687,
year = {2026},
author = {Hu, N and Zhang, L and Tian, H and Ding, J and Shen, D and Yang, X and Cui, L and Niu, J and Liu, M},
title = {Exploration of reliable assessment of respiratory function in amyotrophic lateral sclerosis.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {9},
pages = {},
pmid = {42663687},
issn = {1590-3478},
support = {CIFMS 2021-I2M-1-003//Chinese Academy of Medical Sciences Initiative for Innovative Medicine/ ; 2022-PUMCH-B-017, 2022-PUMCH-D-002//National High Level Hospital Clinical Research Funding/ ; 2022ZD0118003//National Key Transform Program/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/complications/diagnosis ; Female ; Male ; Middle Aged ; Aged ; Disease Progression ; Phrenic Nerve/physiopathology ; Ultrasonography ; Diaphragm/diagnostic imaging/physiopathology ; *Respiration Disorders/etiology/diagnosis/physiopathology ; Respiratory Function Tests ; Nerve Conduction Studies ; Fasciculation/physiopathology/etiology/diagnostic imaging ; },
abstract = {OBJECTIVE: To identify potentially useful objective indicators for early assessment of respiratory dysfunction in amyotrophic lateral sclerosis (ALS).

METHODS: Forty ALS patients were enrolled and followed every 3 months for one year. Baseline assessments included dyspnea complaints, ALSFRS-R, the ALS Respiratory Symptom Score (ARES), physical examination (including lower lung mobility), phrenic nerve conduction studies, diaphragm ultrasound, and multi-region ultrasound fasciculation detection. Forced vital capacity (FVC%) was also measured. Logistic regression (binary outcomes) and linear regression (continuous outcomes) were used to identify predictors of respiratory decline at 6 and 12 months.

RESULTS: At 6 months, decreased right lower lung mobility (β = 1.771, 95%CI:1.047-2.495, p = 0.038), bulbar fasciculations (OR = 2.198, 95%CI:1.527-2.868, p = 0.001), and lumbosacral fasciculations (OR = 2.117, 95%CI:1.516-2.839, p = 0.001) independently predicted a higher post-progression rate. At 12 months, cervical fasciculations predicted a higher post-progression rate (OR = 1.644, 95%CI:1.130-2.157, p = 0.017). Traditional measures (FVC%, diaphragm ultrasound, phrenic CMAP) showed limited short-term predictive value.

CONCLUSION: Lower lung mobility on physical examination and ultrasound-detected fasciculations in bulbar, cervical, and lumbosacral regions are potentially valuable objective markers for predicting disease progression in ALS. These exploratory findings suggest they may complement conventional pulmonary function tests, but require validation in larger independent cohorts.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/complications/diagnosis
Female
Male
Middle Aged
Aged
Disease Progression
Phrenic Nerve/physiopathology
Ultrasonography
Diaphragm/diagnostic imaging/physiopathology
*Respiration Disorders/etiology/diagnosis/physiopathology
Respiratory Function Tests
Nerve Conduction Studies
Fasciculation/physiopathology/etiology/diagnostic imaging

@article {pmid42664170,
year = {2026},
author = {Saucier, D and Bélanger, M and Liu, Z and Lavigne, E and O Apos Connell, C},
title = {Associations between level of urbanization and greenness and the development of amyotrophic lateral sclerosis: A matched case-control study.},
journal = {Neuroepidemiology},
volume = {},
number = {},
pages = {1},
doi = {10.1159/ned/adwag011},
pmid = {42664170},
issn = {1423-0208},
abstract = {INTRODUCTION: Previous studies have considered level of urbanization when evaluating the role of place of residence in ALS. However, these studies have been subject to recall bias regarding previous exposures to urban characteristics owing to a lack of historical geospatial measures on urban form indicators.

METHODS: Thus, we created a robust database from multiple sources and conducted a matched case-control study in New Brunswick, Canada to investigate the association between long-term exposure to various local climate zones, as well as greenness, at place of residence and the development of ALS.

RESULTS: Odds of ALS were not significantly associated with the dense urban (1.1, 0.6 - 2.0 [95% CI]), open urban (0.5, 0.2 - 1.3 [95% CI]), residential (1.0, 0.9 - 1.1 [95% CI]), industrial (0.8, 0.6 - 1.2 [95% CI]), natural (1.0, 0.9 - 1.1 [95% CI]), or water (1.0, 0.9 - 1.1 [95% CI]) local climate zone classification categories per ten percentage increase in influence in the adjusted regression models. Exposure to greenness (1.7, 0.5 - 6.2 [95% CI]) was also not significantly associated to ALS in the adjusted regression models.

CONCLUSION: While not significantly associated to ALS, urban influence and greenness need to be further explored. Future studies should consider traffic-related pollutants as it pertains to urban density, while considering vegetation type and industry practices, such as farming and spraying, alongside greenness exposure measures.},
}

@article {pmid42664377,
year = {2026},
author = {Escobar-Villegas, PA and Realpe-Camelo, AI and Arana-Salas, DA and Velásquez, JG and Paulo, M and Martínez-Cajas, CH and Amaya-Sanchez, S and Gómez-Mesa, JE},
title = {Endodontic status of patients with coronary atherosclerosis: A cross-sectional study.},
journal = {Dental and medical problems},
volume = {63},
number = {4},
pages = {885-891},
doi = {10.17219/dmp/205472},
pmid = {42664377},
issn = {2300-9020},
mesh = {Humans ; Cross-Sectional Studies ; Female ; Male ; *Coronary Artery Disease/epidemiology/complications/diagnostic imaging ; Middle Aged ; Colombia/epidemiology ; Aged ; *Root Canal Therapy ; Adult ; Prevalence ; Coronary Angiography ; },
abstract = {BACKGROUND: There are no studies in the Colombian population assessing the prevalence and severity of apical lesions (ALs), or the relationship between the frequency and quality of endodontic treatment (ET) obturation and the presence of ALs in patients with coronary atherosclerosis (CA).

OBJECTIVES: The present study aimed to estimate the frequency of ALs and ET in Colombian patients with CA, and to identify a possible association between the frequency and severity of ALs and CA.

MATERIAL AND METHODS: The study had a cross-sectional design. We included patients with the evidence of CA diagnosed by coronary angiography. The main outcome variables were the number of compromised coronary arteries and their degree of obstruction, as well as ET, including ALs and previously treated teeth (PTT). The periapical index (PAI) was assessed using periapical radiographs.

RESULTS: A total of 1,394 teeth from 69 patients were evaluated (δ = 20.2 teeth/patient). The frequency of ALs and ET was 5.7% and 10.1%, respectively, considering all teeth evaluated, with a greater presence in the maxilla (50.6% and 51.4%, respectively). Apical lesions were most frequently observed in premolars and molars (35.4%), whereas ET was more frequent in molars (38.6%). Among teeth with ALs, PAI 3 was the most frequent score. Apical lesions were present in 40.0% of endodontically treated teeth; 79.2% of these teeth had inadequate obturation, of which 40 (39.2%) had ALs (p = 0.021).

CONCLUSIONS: In patients with CA, a high incidence of ALs and ET was observed, with no evidence of an association between the frequency of ALs, the severity of coronary vessel occlusion, and the number of coronary arteries affected. More ALs were observed in teeth with inadequate ET. However, as we did not have a control group for comparison, these findings should be interpreted with caution.},
}

Humans
Cross-Sectional Studies
Female
Male
*Coronary Artery Disease/epidemiology/complications/diagnostic imaging
Middle Aged
Colombia/epidemiology
Aged
*Root Canal Therapy
Adult
Prevalence
Coronary Angiography

@article {pmid42664852,
year = {2026},
author = {Rogayan, DV and Tamoria, FV and Jaballa, JA and Andres, KP and Dantic, MJP and Tamoria, JR and Sahagun, RLA},
title = {TikTok for HIV prevention among Filipino youth: A behavioral economics approach.},
journal = {Patient education and counseling},
volume = {152},
number = {},
pages = {109833},
doi = {10.1016/j.pec.2026.109833},
pmid = {42664852},
issn = {1873-5134},
abstract = {This correspondence responds to Guss et al.'s study on using behavioral economics and TikTok for HIV pre-exposure prophylaxis (PrEP) education among youth. It expands the discourse to the Philippine context, where limited health literacy and rising HIV cases remain pressing concerns. With over 62 million TikTok users, the Philippines presents a critical opportunity to promote PrEP through gain-framed, authentic messaging. The commentary highlights the potential of social media as a tool for health education and calls for culturally relevant, youth-centered strategies to strengthen HIV prevention efforts among Filipino adolescents and young adults.},
}

@article {pmid42665553,
year = {2026},
author = {Zhu, CW and Curtis, G and Joseph, J and Wecht, JM and Galea, MD and Harel, NY},
title = {Factors Affecting Disease Progression, Survival, and Caregiver Burden in United States Veterans at a Multidisciplinary Veterans Affairs ALS Center.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70385},
pmid = {42665553},
issn = {1097-4598},
support = {24-TC-705//ALS Association/ ; },
abstract = {INTRODUCTION/AIMS: Though studies of Veterans with ALS have reported survival rates, scant literature reports longitudinal symptom progression in Veterans using the ALS Functional Rating Scale-revised (ALSFRS-R). In the absence of an existing national database tracking disease progression in Veterans, we sought to use local medical records to characterize a cohort of Veterans with ALS treated at our VA ALS clinic.

METHODS: We examined demographic and clinical factors of 216 Veterans with ALS treated at the James J. Peters VA Medical Center (2012-2025) including race, ethnicity, region of symptom onset, and medication use as predictors of diagnostic delay, functional decline (ALS Functional Rating Scale-Revised (ALSFRS-R)), survival, and caregiver burden (Zarit Caregiver Burden Interview). Joint linear mixed modeling estimated longitudinal functional trajectories and survival simultaneously.

RESULTS: The cohort was 96.8% male and 74.5% White. Median age at symptom onset was 69.3 years. Mean baseline ALSFRS-R was 30.7. Median survival from symptom onset was 4.4 years. Median age at symptom onset was younger for Black (60.8 years) and Hispanic (62.5 years) Veterans than Whites (70.1 years). Blacks had faster initial ALSFRS-R progression than Whites (mean 1.9 vs. 0.9 points per month). Blacks and Hispanics had 2.8-fold and 2.3-fold higher adjusted mortality hazard than Whites, respectively. Forty-nine percent of caregivers reported high caregiver burden at first assessment, rising to 66.2% at subsequent assessments.

DISCUSSION: Racial and ethnic disparities in ALS progression and survival are pronounced in this single-site Veteran cohort. Standardized ALS-specific data collection across the VHA is needed to enable system-wide analyses.},
}

@article {pmid42665653,
year = {2026},
author = {Shaji, V and Jain, R and Puthumadathil, N and Jana, K and T S, V and Kleinekathöfer, U and Chattopadhyay, K and Mahendran, KR},
title = {A self-assembled peptide forms α-helical nanopores for ultrasensitive biomarker profiling.},
journal = {Nature nanotechnology},
volume = {},
number = {},
pages = {},
pmid = {42665653},
issn = {1748-3395},
support = {BT/PR53613/BMS/85/242/2024//Department of Biotechnology, Ministry of Science and Technology (DBT)/ ; IIRPIG-2024-01-00131//Indian Council of Medical Research (ICMR)/ ; IIRPSG-2024-01-01188//Indian Council of Medical Research (ICMR)/ ; INST 676/7-1 FUGG//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; OLP-120//Council of Scientific and Industrial Research (CSIR)/ ; },
abstract = {α-Helical nanopores are attractive molecular sensors, yet their rational design and assembly remain challenging. Here we show that the single peptide pPorA, derived from porin PorACj, self-assembles into flexible α-helical nanopores, inserts in lipid membranes and exists in distinct small- and large-conductance states. By strategically incorporating unnatural amino acids, we engineered small- and large-diameter pores exhibiting single-channel conductances of 2.4 nS and 3.5 nS in 1 M KCl, respectively, while retaining a common octameric architecture. These nanopores enabled the detection of sugars, peptide enantiomers and intrinsically disordered disease proteins that form dynamic, heterogeneous assemblies. The large pores detected multiple α-synuclein (α-syn) variants, including a pathogenic Parkinson's disease-associated C-terminal deletion mutant with nanomolar affinity (KD ≈ 20 nM). Selective electrostatic trapping of the α-syn N-terminus enabled charge-resolved identification of individual α-syn species within heterogeneous mixtures. The nanopores further resolved time-dependent and inhibitor-modulated α-syn aggregation pathways from monomers to toxic oligomers and fibrils. The small pores detected humanin and superoxide dismutase peptides associated with apoptosis and amyotrophic lateral sclerosis, demonstrating tunable sensing through pore-size control. These conformationally programmable α-helical nanopores provide a versatile platform for ultrasensitive profiling of disease biomarkers.},
}

@article {pmid42665659,
year = {2026},
author = {Shi, P and Melillo, B and McHenry, MW and Camara, CM and Yang, K and Njomen, E and Godes, M and Pazyra-Murphy, MF and Branch, MR and Tesar, B and Segal, RA and Rubin, LL and Cameron, MD and Bird, GH and Wales, TE and Gygi, SP and Cravatt, BF and Walensky, LD},
title = {An enantioselective covalent inhibitor of BAX confers cytoprotection in vivo.},
journal = {Nature chemical biology},
volume = {},
number = {},
pages = {},
pmid = {42665659},
issn = {1552-4469},
support = {R35CA197583//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; R50CA211399//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; R35CA231991//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
abstract = {No therapies directly block apoptosis in tissue injury or the many diseases driven by cell loss. The BCL-2 family protein BAX is a central mediator of this pathway and C126 resides within a key regulatory region where physiologic or pharmacologic ligands can activate or inhibit its function. Here, we report enantioselective covalent BAX inhibitors that site-specifically react with C126 and confer cytoprotection across multiple cell types. These ligands constrain BAX conformation and suppress apoptosis in a strictly BAX-dependent manner. Medicinal chemistry optimization yielded covalent BAX inhibitor 3 (CBI-3), an analog with pharmacokinetics suitable for in vivo studies. In a murine model of Fas-induced fulminant hepatic failure, CBI-3 reduced hepatocyte apoptosis and preserved liver histology and survival. CBI-3 also conferred cytoprotection of motor neurons derived from human induced pluripotent stem cells of healthy and amyotrophic lateral sclerosis donors. These findings establish covalent BAX inhibition as a therapeutic strategy to directly block pathologic cell death.},
}

@article {pmid42666334,
year = {2026},
author = {Garbey, M and Lesport, Q and Öztosun, G and Heidebrecht, M and Pirouz, K and Bayat, E},
title = {Feasibility study on a noninvasive assessment of ALS patient emotional state.},
journal = {Frontiers in digital health},
volume = {8},
number = {},
pages = {1886561},
pmid = {42666334},
issn = {2673-253X},
abstract = {INTRODUCTION: Objective assessment of emotional responsiveness in Amyotrophic Lateral Sclerosis (ALS) remains limited despite its importance for personalized care. This study investigated whether non-invasive speech analysis could identify digital biomarkers associated with emotional coping behaviors in ALS patients.

METHODS: We analyzed 28 ALS patient visits using clinician-rated emotional concern scores, ALS Functional Rating Scale-Revised (ALS-FRS-R), forced vital capacity (FVC), and speech acoustic features. We also evaluated the reliability of large language models (LLMs), including ChatGPT, Gemini, and Claude, for automated concern assessment. Patients were classified relative to functional impairment as congruent, muted, or excessive responders.

RESULTS: LLMs failed to provide reliable or reproducible assessments of patient concern without expert clinical supervision. Subjective concern levels also showed discordance with objective respiratory measures such as FVC. Excessive responders were predominantly male and required significantly greater clinician interaction time, while muted responders were predominantly female. Acoustic analysis revealed distinct vocal profiles between groups. Muted responders demonstrated high loudness and sharpness with low roughness and fluctuation, whereas excessive responders showed the opposite profile. These findings suggest that dysarthria may function as an acoustic filter modulating emotional expression.

DISCUSSION: Speech-derived acoustic biomarkers may enable objective identification of emotional coping phenotypes in ALS and support earlier, personalized psychosocial interventions. The findings also highlight important limitations of current LLM-based clinical interpretation tools in unsupervised settings.},
}

@article {pmid42661070,
year = {2026},
author = {Abel Jopaul, VP and Lingaraj, M},
title = {Comment on "Artificial intelligence construction: a review of the bridge between CT imaging features of lung ground-glass nodules adenocarcinoma and carcinogenic driver genes".},
journal = {Journal of cancer research and clinical oncology},
volume = {152},
number = {8},
pages = {},
pmid = {42661070},
issn = {1432-1335},
mesh = {Humans ; *Tomography, X-Ray Computed/methods ; *Lung Neoplasms/genetics/diagnostic imaging/pathology ; *Adenocarcinoma of Lung/genetics/diagnostic imaging/pathology ; *Artificial Intelligence ; },
abstract = {Xue and Chen et al.'s review connects AI-derived CT features of lung ground-glass nodule adenocarcinoma to driver gene status. Three aspects are missing. There is no stated search strategy no databases, date range, or inclusion criteria despite drawing on more than 150 references, so readers cannot tell whether weaker or null results were sought out or just left aside. Individual studies are cited by their best accuracy or AUC figures, from approximately 0.64 to above 0.95, with no attempt to weigh them by sample size, design, or validation status. The framing does not match the evidence the review cites: the text calls AI transformative, but a systematic review it references reports a mean AUC of only ~0.64 for driver gene prediction from imaging. None of this undercuts the review's usefulness as a starting map of the field, but a stated search process, some quality-weighting of the cited numbers, and framing that matches the aggregate evidence would make it more reliable.},
}

Humans
*Tomography, X-Ray Computed/methods
*Lung Neoplasms/genetics/diagnostic imaging/pathology
*Adenocarcinoma of Lung/genetics/diagnostic imaging/pathology
*Artificial Intelligence

@article {pmid42661170,
year = {2026},
author = {Wolf, J and Safer, A and Stefenelli, U and Woehrle, JC and Maschke, M and Nix, WA and Grau, AJ},
title = {Long-term survival in amyotrophic lateral sclerosis - data from a population-based registry in Rhineland-Palatinate, Germany.},
journal = {BMC neurology},
volume = {26},
number = {1},
pages = {},
pmid = {42661170},
issn = {1471-2377},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/epidemiology/diagnosis ; Female ; Germany/epidemiology ; Male ; Registries ; Middle Aged ; Aged ; Adult ; Aged, 80 and over ; Young Adult ; Kaplan-Meier Estimate ; Disease Progression ; Prospective Studies ; },
abstract = {BACKGROUND: Data on long-term survival in amyotrophic lateral sclerosis (ALS) is scarce. In a population-based ALS cohort in Germany we evaluated long-term survival and assessed key factors influencing long-term survival, including demographic and clinical variables that are available at an early stage of the disease.

METHODS: Data from patients in the prospective, population-based ALS-registry Rhineland-Palatinate were analyzed. Survival was evaluated separately for time from symptom onset and time from diagnosis. Patient demographic and disease-related variables were analyzed in relation to survival probability using the Kaplan-Meier method and Cox proportional hazards regression.

RESULTS: Data from 200 incident ALS patients (106 men and 94 women) were included in the study. The median age of the patients was 68 years (range 23-85 years; mean age 65.8 years; standard deviation 10.5 years). The median survival time was 2.5 years from symptom onset and 1.5 years from diagnosis. 12% of the patients survived for at least ten years from first manifestation of symptoms. Multivariate statistics revealed that younger age, a low progression rate, the absence of frontotemporal dementia and a long interval between symptom onset and diagnosis were predictors of long survival.

CONCLUSIONS: 12% of ALS patients are still alive ten years after the onset of symptoms, which is important for advance planning of patient care. In our analysis demographic and clinical variables available at an early stage of the disease have emerged as valuable predictive factors.

TRIAL REGISTRATION: ClinicalTrials.gov (NCT01955369; registered retrospectively 28/09/2013).},
}

Humans
*Amyotrophic Lateral Sclerosis/mortality/epidemiology/diagnosis
Female
Germany/epidemiology
Male
Registries
Middle Aged
Aged
Adult
Aged, 80 and over
Young Adult
Kaplan-Meier Estimate
Disease Progression
Prospective Studies

@article {pmid42652933,
year = {2026},
author = {Ilias, I and Keskinidou, C and Poupouzas, G and Issaris, V and Lotsios, NS and Botoula, E and Tzanela, M and Vassiliadi, DA and Kokkoris, S and Vrettou, CS and Vassiliou, AG and Dimopoulou, I},
title = {Growth Hormone-Insulin-like Growth Factor Axis and GDF-15 in Critical Illness: Implications for Survival Stratification.},
journal = {Life (Basel, Switzerland)},
volume = {16},
number = {8},
pages = {},
pmid = {42652933},
issn = {2075-1729},
abstract = {Background: The growth hormone (GH)-insulin-like growth factor (IGF) axis is profoundly dysregulated in critical illness. GDF-15 and individual IGF-binding proteins (IGFBPs) have separately been proposed as prognostic biomarkers, but to our knowledge, no prior study has simultaneously characterized all major GH-IGF axis components and GDF-15 in the same critically ill cohort, precluding assessment of their joint intercorrelation structure. Aim: To provide the first simultaneous characterization of the intercorrelation structure among ten GH-IGF axis components and GDF-15 in a single ICU cohort, testing whether this structure is robust to adjustment for illness severity; and, secondarily, to describe admission discriminatory performance relative to APACHE II and SOFA. Methods: This was a prospective observational pilot study of 43 critically ill adults with admission (T01) measurement of ten GH-IGF axis biomarkers and longitudinal follow-up to day 15. Spearman correlations and hierarchical clustering characterized the admission intercorrelation structure; partial correlations adjusting for APACHE II and SOFA, and bootstrap confidence intervals, assessed robustness. Secondary analyses included the examination of admission discrimination (ROC/AUC), a leave-one-out cross-validated combined model, and longitudinal trajectories. All analyses were exploratory, hypothesis-generating, and unadjusted for multiple comparisons unless stated. Results: Hierarchical clustering identified a coherent cluster comprising GDF-15, IGFBP-1, IGFBP-2, and growth hormone-binding protein (GHBP), distinct from classical GH-resistance markers (GHR vs. healthy controls, GHR vs. admission) and from GH, IGF-1, acid-labile subunit (ALS), and IGFBP-3. Within this cluster, GDF-15 correlated with IGFBP-1 (ρ = 0.65, 95% bootstrap CI 0.44-0.78), IGFBP-2 (ρ = 0.50, CI 0.19-0.71), and GHBP (ρ = 0.47, CI 0.20-0.68); GDF-15 showed no correlation with classical GH-resistance markers. These correlations were essentially unchanged after adjusting for APACHE II or SOFA (partial ρ within 0.03-0.16 of unadjusted values), indicating the structure is not attributable to shared confounding by illness severity. This robustness extended to further adjustment for IL-6, age, BMI, and mechanical-ventilation duration, and results from all 45 pairwise T01 correlations were re-examined with Benjamini-Hochberg false-discovery-rate correction (9 of 11 nominally significant pairs retained q < 0.05). However, the GDF-15-GHBP correlation, unlike the GDF-15-IGFBP-1/IGFBP-2 correlations, attenuated substantially after adjustment for IL-6 and was not consistent across a brain-injury/non-brain-injury subgroup sensitivity analysis, indicating this specific link is less specific than the others. In secondary exploratory analyses, GDF-15 had the highest individual admission AUC (0.74) among biomarkers but was substantially outperformed by APACHE II (AUC 0.90) and SOFA (AUC 0.81); a combined GDF-15 + IGFBP-2 model did not improve on GDF-15 alone. Conclusions: This study identifies a severity-independent intercorrelation structure linking GDF-15 to inhibitory IGFBPs, distinct from classical GH-resistance signaling, in critically ill patients. Although the findings do not support any clinical application at this stage, further study in adequately powered, multicenter cohorts can be contemplated.},
}

@article {pmid42653169,
year = {2026},
author = {Terribile, G and Pedrinazzi, M and Frigerio, I and Sancini, G and Combi, R},
title = {Theranostic Innovative Strategies for Brain Diseases: New Insights on Neurovascular Unit-Associated Pathological Changes in Neurodegenerative Disorders and Aging.},
journal = {International journal of molecular sciences},
volume = {27},
number = {16},
pages = {},
pmid = {42653169},
issn = {1422-0067},
mesh = {Humans ; *Neurodegenerative Diseases/therapy/pathology/diagnosis ; *Aging/pathology ; Animals ; Blood-Brain Barrier/metabolism/pathology ; *Theranostic Nanomedicine/methods ; *Brain Diseases/therapy/diagnosis/pathology ; Nanoparticles ; MicroRNAs/genetics ; Nanotechnology ; },
abstract = {Central nervous system (CNS) disorders represent a significant healthcare challenge, with aging as the primary risk factor. Current clinical management remains predominantly symptomatic, as late-stage diagnosis and the blood-brain barrier (BBB) limit therapeutic efficacy. This review synthesizes emerging innovations in neurotheranostics-integrated diagnostic and therapeutic platforms-focusing on the neurovascular unit (NVU) as a central pathogenic driver and target. Evidence indicates that NVU and BBB dysfunction are early events in Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and Huntington's diseases, often preceding classic neuropathological hallmarks. The review highlights the potential of nanotechnology, engineered nanoparticles (NPs) and microRNAs (miRNAs) as precision tools for early detection and targeted CNS delivery. Additionally, it discusses the transformative impact of artificial intelligence (AI) in facilitating personalized, predictive care. Transitioning from a generic "one-pill-for-one-disease" model to a patient-centered strategy targeting early NVU alterations is essential. Integrating AI, nanotechnology and NVU-focused strategies offers a promising path toward effective, personalized disease-modifying therapies.},
}

Humans
*Neurodegenerative Diseases/therapy/pathology/diagnosis
*Aging/pathology
Animals
Blood-Brain Barrier/metabolism/pathology
*Theranostic Nanomedicine/methods
*Brain Diseases/therapy/diagnosis/pathology
Nanoparticles
MicroRNAs/genetics
Nanotechnology

@article {pmid42653407,
year = {2026},
author = {Rosenfeld, J and Salomon-Zimri, S and Tracik, F},
title = {Combination Pharmacology for ALS: A Mechanistic Rationale.},
journal = {International journal of molecular sciences},
volume = {27},
number = {16},
pages = {},
pmid = {42653407},
issn = {1422-0067},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology ; Animals ; Drug Therapy, Combination ; Oxidative Stress/drug effects ; Mitochondria/metabolism/drug effects ; },
abstract = {Amyotrophic lateral sclerosis (ALS) involves multiple converging pathogenic mechanisms, including glutamate excitotoxicity, oxidative and endoplasmic-reticulum stress, mitochondrial dysfunction, neuroinflammation, iron dysregulation, and altered microRNA processing. Expecting a single pharmacologic intervention to meaningfully alter such a complex disease has proven overly optimistic and is reflected by the modest clinical benefits of approved monotherapies. This review outlines the mechanistic foundation and translational rationale for combination pharmacology in ALS. Drawing from paradigms in oncology, infectious disease, and other neurological disorders, it explores how rational multi-target strategies, whether synergistic, complementary, or pathway-divergent, may better address the multifactorial biology of ALS. The review also discusses recent mechanistic examples and design principles for advancing this therapeutic paradigm.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology
Animals
Drug Therapy, Combination
Oxidative Stress/drug effects
Mitochondria/metabolism/drug effects

@article {pmid42656624,
year = {2026},
author = {Soberano, JI and Montayre, J},
title = {Social frailty and related social vulnerabilities among older adults in the Philippines: A narrative review.},
journal = {International journal of nursing studies advances},
volume = {11},
number = {},
pages = {100655},
pmid = {42656624},
issn = {2666-142X},
abstract = {OBJECTIVES: To synthesize the evidence on social frailty among older adults in the Philippines, with attention to sociocultural and structural determinants, assessment approaches, and policy and program responses, and to derive implications for nursing practice and research.

METHODS: A narrative review with scoping elements was informed by the Scale for the Assessment of Narrative Review Articles (SANRA), with selected PRISMA-ScR items used to enhance reporting transparency. Electronic searches of PubMed, CINAHL, Web of Science, PsycINFO, and Google Scholar identified peer-reviewed and relevant verifiable discussion papers written in English from January 2015 to December 2025 (final search: 5 January 2026). The search, title, and abstract screening, full-text review, and data extraction were performed independently by two reviewers, with disagreements resolved through consensus. Eligible studies focused on community-dwelling Filipinos aged ≥60 years and examined social frailty or closely related constructs, including social networks, participation, support, isolation, loneliness, and social determinants of health and functioning. Data were synthesized thematically using Bunt et al.'s four domains of social frailty.

RESULTS: Thirty-five studies were included, most using qualitative or cross-sectional designs. Evidence clustered in the domains of general resources and social behavior activities, particularly access, participation, mobility, disaster related disruption, and emerging digital engagement. Fewer studies addressed social resources and self-management abilities. Family, kinship, and faith-based networks, and community organization were important protective systems, but were increasingly strained by migration, economic insecurity, service limitations, and environmental disruption.

CONCLUSIONS: Social frailty among older Filipinos emerges at the intersection of structural disadvantage, changing informal support systems, community participation, digital access, and self-management capacities. Addressing social frailty requires multidimensional assessment, culturally grounded measurement, and coordinated nursing, community and policy responses.},
}

@article {pmid42656814,
year = {2026},
author = {Fent, M and Farkas, A and Pataki, H and Nagy, ZK and Csontos, I},
title = {Spectroscopic Monitoring and Chemometric-Based Feedback Control of the Diazotization Reaction.},
journal = {Organic process research & development},
volume = {30},
number = {8},
pages = {2149-2158},
pmid = {42656814},
issn = {1083-6160},
abstract = {Inline Raman spectroscopy-based monitoring enables the development of control systems that allow the implementation of Process Analytical Technology (PAT) principles even in chemical reactions, thereby improving quality, efficiency, and safety. There are only a few articles in the literature that discuss such control systems. This may be due to the numerous challenges involved, including the need for robust measurement setups and the development of chemometric algorithms capable of delivering accurate and stable real-time evaluations. Thus, this study presents the Raman spectroscopic monitoring and chemometric-based feedback control of a highly exothermic and potentially hazardous diazotization reaction, namely, the synthesis of phenyldiazonium chloride from aniline, hydrochloric acid, and sodium nitrite. Raman spectra were analyzed offline using Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) and in real-time using Classical Least Squares (CLS) chemometric methods to monitor and control key reaction components. The developed feedback system successfully controlled concentration levels during both acid-base and diazotization phases. The reduction of the Raman signal-to-noise ratio, induced by the decomposition of the diazonium salt, was also observed. This factor significantly affected the monitoring of the diazotization experiment. Furthermore, a calibration was established to quantify the molar concentrations of key components based on Raman spectra. The calibration experiment successfully demonstrated well-fitted linear molar-spectral relationships for both aniline (R [2] homogeneous = 0.997; R [2] heterogeneous = 0.9947) and aniline hydrochloride (R [2] = 0.9987). For aniline, the molar-spectral relationship exhibited a distinct change in tendency that precisely correlated with its solubility limit in water, marking the transition from homogeneous solution to emulsion.},
}

@article {pmid42656917,
year = {2026},
author = {Zhang, J and Tang, P and Huang, L and Lv, J and Chen, Y and Wang, Y and Luo, Y},
title = {Multifaceted roles of S100A6 in neurological disorders: expression, interaction networks, and clinical implications.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1890559},
pmid = {42656917},
issn = {1663-9812},
abstract = {S100A6 (calcyclin) is a multifunctional Ca[2+]/Zn[2+]-binding protein of the S100 family, widely expressed in neurons and glia with a developmentally regulated and cell-type-specific pattern. This review synthesizes current knowledge on its roles in the nervous system. We detail its complex interactome, which includes cytoskeletal regulators, molecular chaperones, nuclear transport proteins, and cell surface receptors, positioning S100A6 as a central signaling hub. Furthermore, we examine its dynamic and context-dependent involvement in major neurological disorders. In Alzheimer's disease and amyotrophic lateral sclerosis, it functions as a glial-derived factor linking protein aggregation, metal dyshomeostasis, and neuroinflammation. In neuro-oncology, S100A6 exhibits dual roles, acting as a promoter of malignancy and immunosuppression in glioblastoma, an epigenetically silenced marker in medulloblastoma, and a diagnostic aid for peripheral nerve sheath tumors. Its expression is also altered in epilepsy, traumatic brain injury, and autoimmune encephalitis. Understanding the nuanced functions of S100A6 offers significant potential for developing novel diagnostic biomarkers and targeted therapeutic strategies for a range of challenging neurological conditions.},
}

@article {pmid42657306,
year = {2026},
author = {Xie, J and Shao, J and Wang, C and Shi, X and Miao, Q and Yip, CC and Ye, J},
title = {Visual cueing and adaptive learning for teaching thyroid eye disease diagnostic assessment to ophthalmology residents.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1934529},
pmid = {42657306},
issn = {2296-858X},
abstract = {BACKGROUND: Thyroid eye disease (TED) diagnosis requires residents to interpret subtle clinical and imaging findings for activity and severity assessment. Guided by Cognitive Load Theory, visual cueing may support attention to diagnostically relevant features, whereas adaptive learning may tailor practice to learner performance. This pilot study compared visual cueing, adaptive learning, and traditional static case review for TED diagnostic training.

METHODS: Forty-five ophthalmology residents were randomised equally to static case review (SCR), an adaptive learning system (ALS), or a visual cueing atlas (VCA). Following a 45-minute intervention, residents completed immediate and two-week delayed tests. The primary outcome was immediate overall diagnostic accuracy. Secondary outcomes were Clinical Activity Score (CAS) accuracy, severity-grading accuracy, delayed-test performance (2 weeks post-intervention), and performance decline from immediate to delayed testing. Educational materials were validated by ten expert ophthalmologists. Item-level content validity indices and the scale-level content validity index were calculated from expert ratings.

RESULTS: All residents completed the study. Expert validation showed excellent content validity for the educational materials, with the Item-level Content Validity Index for all components and the overall Scale-level Content Validity Index both reaching 1.00. At the immediate post-test, VCA achieved higher CAS accuracy than SCR (84.7% vs. 64.7%, p < 0.001). ALS and VCA achieved higher severity-grading accuracy than SCR (83.3% and 78.7% vs. 66.7%; p = 0.004 and p = 0.025, respectively), and both achieved higher overall diagnostic accuracy than SCR (66.0% each vs. 51.3%; p = 0.014 and p = 0.008, respectively). At two weeks, ALS showed higher severity-grading accuracy than SCR (74.0% vs. 56.0%, p < 0.001), while both ALS and VCA maintained higher overall diagnostic accuracy than SCR (54.0% and 52.7% vs. 41.3%; p = 0.014 and p = 0.008, respectively).

CONCLUSION: In this pilot study, visual cueing was associated with higher immediate CAS accuracy, whereas adaptive learning was associated with higher severity-grading accuracy on the two-week delayed test, relative to static case review. These approaches may have complementary roles in TED diagnostic education. Larger studies using equivalent instructional exposure, matched assessment forms, and longer follow-up are needed before a staged hybrid approach is recommended.},
}

@article {pmid42657487,
year = {2026},
author = {da Silva, AA and Pupe, CCB and Dos Santos, JCC},
title = {High-dose methylcobalamin in amyotrophic lateral sclerosis: mechanistic rationale, translational evidence, and clinical implications.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/17582024.2026.2713755},
pmid = {42657487},
issn = {1758-2032},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disorder characterized by selective degeneration of upper and lower motor neurons, driven by converging mechanisms including glutamatergic excitotoxicity, mitochondrial dysfunction, oxidative stress, calcium dyshomeostasis, impaired RNA metabolism, and neuroinflammation. In the absence of effective disease-modifying therapies, high-dose methylcobalamin has emerged as a candidate intervention based on its pleiotropic neurobiological effects. A structured literature search was conducted in PubMed/MEDLINE and ScienceDirect to identify peer-reviewed studies published between January 2017 and December 2025 addressing the mechanistic, preclinical, and clinical effects of methylcobalamin in ALS. Preclinical evidence suggests that methylcobalamin modulates homocysteine metabolism, supports S-adenosylmethionine-dependent methylation pathways, preserves mitochondrial integrity, attenuates oxidative stress, and promotes axonal regeneration. Experimental and translational findings further indicate that its therapeutic effects may be strongly dose dependent, particularly under ultra-high-dose regimens capable of overcoming limitations in central nervous system delivery. Clinical trials evaluating ultra-high-dose methylcobalamin demonstrate a potential attenuation of functional decline in patients treated during early disease stages, although effects on survival and respiratory outcomes remain inconsistent. This narrative review integrates molecular mechanisms, experimental evidence, biomarker research, and clinical trial data to examine the translational relevance, stage dependency, and therapeutic implications of high-dose methylcobalamin in ALS.},
}

@article {pmid42658841,
year = {2026},
author = {Carbayo, Á and Turon-Sans, J and Alcolea, D and Cortés-Vicente, E and Cabezas-Torres, M and Alvarez-Sanchez, E and Muñoz, L and Rubio-Guerra, S and García-Castro, J and Selma-González, J and Bernal, S and Gonzalez-Quereda, L and Bejanin, A and Aranha, MR and Santos-Santos, M and Belbin, O and Vesperinas-Castro, A and Collet-Vidiella, R and Caballero-Ávila, M and Llansó, L and Querol, L and Lleó, A and Fortea, J and Gelpí, E and Dols-Icardo, O and Illán-Gala, I and Rojas-Garcia, R},
title = {Methodological insights and clinical outcomes in ALS and FTLD: lessons from the SPIN cohort.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {8},
pages = {e71777},
pmid = {42658841},
issn = {1552-5279},
support = {AACSF-21-850193/ALZ/Alzheimer's Association/United States ; AARF-22-924456/ALZ/Alzheimer's Association/United States ; 201437.10;20141210//Fundació la Marató de TV3/ ; 044412//Fundació la Marató de TV3/ ; 20142610//Fundació la Marató de TV3/ ; PI23/00845//Instituto de Salud Carlos III/ ; PI19/01543//Instituto de Salud Carlos III/ ; PI15/01618//Instituto de Salud Carlos III/ ; PI13/00772//Instituto de Salud Carlos III/ ; FISEC08/00077//Instituto de Salud Carlos III/ ; PMPER24/0017//Instituto de Salud Carlos III/ ; PI14/01126//Instituto de Salud Carlos III/ ; PI17/01019//Instituto de Salud Carlos III/ ; PI18/00335//Instituto de Salud Carlos III/ ; PI19/00882//Instituto de Salud Carlos III/ ; PI18/00435//Instituto de Salud Carlos III/ ; PI22/00611//Instituto de Salud Carlos III/ ; INT19/00016//Instituto de Salud Carlos III/ ; INT23/00048//Instituto de Salud Carlos III/ ; PI17/01896//Instituto de Salud Carlos III/ ; PI22/00307//Instituto de Salud Carlos III/ ; AC19/00103//Instituto de Salud Carlos III/ ; PI18/00335//Instituto de Salud Carlos III/ ; PI22/00758//Instituto de Salud Carlos III/ ; ICI23/00032//Instituto de Salud Carlos III/ ; INT21/00073//Instituto de Salud Carlos III/ ; PI20/01473//Instituto de Salud Carlos III/ ; PI23/01786//Instituto de Salud Carlos III/ ; PI21/00791//Instituto de Salud Carlos III/ ; AUL2025.1//Fundación Luzón/ ; //Fundación HNA/ ; DABNIproject//Fundació Bancaria "La Caixa"/ ; //Fundació Catalana Síndrome de Down/ ; //Fundació Víctor Grífols i Lucas/ ; //Fondo Europeo de Desarrollo Regional (FEDER)/ ; //FUNDELA/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/cerebrospinal fluid ; *Frontotemporal Lobar Degeneration/genetics/pathology/cerebrospinal fluid ; Biomarkers/cerebrospinal fluid ; Cohort Studies ; Neuroimaging ; Male ; Female ; Longitudinal Studies ; Precision Medicine ; Aged ; Middle Aged ; },
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) constitute a clinico-genetic-neuropathological continuum with marked heterogeneity. Reliable in vivo biomarkers of the disease are lacking. Large, multimodal cohorts are needed to advance biomarker discovery and precision medicine.

METHODS: We describe the structure and results derived from the Sant Pau Initiative on Neurodegeneration (SPIN)-ALS-FTLD subcohort, a longitudinal, multimodal platform that integrates clinical, cognitive, genetic, biofluid, neuroimaging, and neuropathological data within a unified framework embedded in routine care.

RESULTS: The cohort includes over 1000 participants, 800 blood, 400 CSF, and 800 DNA samples, neuroimaging in over 250 cases, and 66 neuropathological studies. Harmonized longitudinal data and biospecimen collection have enabled substantial clinical, molecular, and translational research output.

DISCUSSION: SPIN-ALS-FTLD extends the original SPIN framework to the ALS-FTLD continuum, enabling deep phenotyping and multimodal biomarker discovery. This scalable model supports patient stratification, longitudinal monitoring, and the development of precision medicine approaches in neurodegenerative diseases.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/pathology/cerebrospinal fluid
*Frontotemporal Lobar Degeneration/genetics/pathology/cerebrospinal fluid
Biomarkers/cerebrospinal fluid
Cohort Studies
Neuroimaging
Male
Female
Longitudinal Studies
Precision Medicine
Aged
Middle Aged

@article {pmid42651198,
year = {2026},
author = {Harris, KE and Lascaratos, G and Chau, KY},
title = {Mitochondrial Complex V Dysfunction in Neurodegeneration: Secondary Bystander or Primary Driver?.},
journal = {Brain sciences},
volume = {16},
number = {8},
pages = {},
pmid = {42651198},
issn = {2076-3425},
abstract = {BACKGROUND/OBJECTIVES: Mitochondrial Complex V (Complex V [CX-V], or ATP synthase) is the terminal enzyme of oxidative phosphorylation and is responsible for the majority of cellular ATP production. An increasing body of evidence suggests that CX-V dysfunction may contribute to mitochondrial impairment observed in neurodegenerative disease. This review evaluated current research on the structure, regulation, and function of CX-V, examined the consequences of CX-V dysfunction, and assessed its proposed role in neurodegenerative disorders.

METHODS: A comprehensive review of the published literature was carried out, with emphasis on primary research investigating CX-V structure and function, inherited CX-V disorders, and experimental evidence linking CX-V dysfunction to neurodegenerative disease. The reviewed studies used a range of experimental approaches, including structural biology, biochemical studies, patient-derived cellular models, animal models and post-mortem human tissue.

RESULTS: Current evidence demonstrates that disruption of CX-V impairs ATP production, alters mitochondrial membrane potential, and oxidative phosphorylation, and that pathogenic variants cause primary mitochondrial disease. Across Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis/frontotemporal dementia, glaucoma and inherited optic neuropathies, alterations in CX-V activity, regulation and structural integrity are consistently associated with mitochondrial dysfunction. Direct evidence supporting CX-V as a primary driver of neurodegeneration remains very limited, with many observations originating from broader studies of general mitochondrial dysfunction.

CONCLUSIONS: CX-V dysfunction represents a recurring feature of mitochondrial impairment across a variety of neurodegenerative disorders and may exacerbate neuronal vulnerability by disrupting cellular bioenergetics. Current evidence indicates that CX-V may serve as a common downstream target of multiple pathological pathways rather than acting as a primary pathological factor. Future studies require direct assessment of CX-V activity in clinically relevant human models and patient tissues to determine its contribution to disease progression and examine its potential as a therapeutic target.},
}

@article {pmid42651202,
year = {2026},
author = {Alshehri, S and Atabek, B and Heiman-Patterson, T and Ayaz, H},
title = {Task-Evoked Prefrontal Hemodynamics During Cognitive Assessment in Amyotrophic Lateral Sclerosis Using fNIRS.},
journal = {Brain sciences},
volume = {16},
number = {8},
pages = {},
pmid = {42651202},
issn = {2076-3425},
abstract = {Background/Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease increasingly recognized for extra-motor manifestations, including cognitive dysfunction involving frontal cortical systems. Conventional clinical assessments are primarily behavioral and may not capture subtle alterations in the neural systems that support cognitive performance. This pilot study examined whether wearable functional near-infrared spectroscopy (fNIRS) could detect task-evoked prefrontal hemodynamic differences during the King-Devick Task (KDT), a rapid oculomotor number-naming task that engages visual scanning, attention, processing speed, and verbal response production. Methods: Sixteen participants, including seven individuals with ALS and nine age-matched healthy controls (HC), completed four progressively difficult KDT conditions while prefrontal cortical activity was recorded. Results: As task difficulty increased, response times became slower across participants, while accuracy remained preserved and behavioral performance did not differ significantly between groups. Prefrontal oxygenated hemoglobin (HbO) responses increased with task difficulty across all prefrontal optodes, supporting task-evoked cortical engagement. In contrast, deoxygenated hemoglobin (HbR) responses showed a group-specific pattern in the left dorsolateral prefrontal cortex: individuals with ALS demonstrated progressively increasing HbR responses across difficulty conditions, whereas HC showed relatively stable responses, with group differences emerging at higher difficulty levels. Conclusions: These findings suggest a dissociation between preserved behavioral performance and altered prefrontal hemodynamic regulation in ALS. The observed HbR pattern may reflect differences in cortical recruitment, neurovascular coupling, oxygen extraction, vascular responsiveness, or the efficiency of cortical resource allocation during increasing cognitive-motor demands. Wearable fNIRS may therefore complement behavioral assessments by revealing task-evoked neural alterations that are not evident from performance measures alone.},
}

@article {pmid42651367,
year = {2026},
author = {Alshaibany, FF and Almutairy, BM and Alghamdi, A and Alshehri, WM and Aljabri, MM and Alharbi, A and Alharbi, BS and Alodhailah, AM},
title = {A Resilience-Based Nursing Intervention Framework for Internet Gaming Disorder in Saudi University Health Settings.},
journal = {Healthcare (Basel, Switzerland)},
volume = {14},
number = {16},
pages = {},
pmid = {42651367},
issn = {2227-9032},
support = {ORF-2026-1712//Ongoing Research Funding Program/ ; },
abstract = {Background/Objectives: Internet Gaming Disorder (IGD) is included in ICD-11 and poses a substantial risk to Saudi university students, yet no structured nursing intervention framework exists within Saudi higher education health services. This paper presents the Resilience-Based Nursing Intervention Framework (RBNIF), a three-tiered, theory-driven nursing architecture translating evidence on impulsivity, resilience, and IGD into practice specifications for this setting. Methods: Using secondary analysis of a dataset of 207 gaming students from four King Saud University colleges, framework development followed a four-phase Medical Research Council (MRC) process: theoretical identification (I-PACE, Dual Process Theory, COM-B), evidence synthesis, Behavior Change Wheel/Intervention Mapping, and cultural adaptation via Bernal et al.'s Ecological Validity Framework. Results: The sample (58.9% male; 20-25 years, 61.4%; bachelor's level, 73.9%) yielded three tiers differentiated by a dual-domain screening rule (elevated impulsivity and/or low resilience, rather than a single combined score): Tier 1 (universal psychoeducation); Tier 2 (six-session group program, S-UPPS-P ≥ 52 and/or CD-RISC-10 ≤ 20; 63 of 207 participants [30.4%]); and Tier 3 (10-session RIRDH clinical program, IGDS9-SF ≥ 36, met by 38 of 207 participants [18.4%]). Fifty-two participants (25.1%) met the elevated-impulsivity criterion, and 51 (24.6%) met the low-resilience criterion. Each tier specifies nursing competencies and behavior change techniques, with cultural adaptation integrating Islamic values concepts (sabr, mizan, tawakkul), family protocols, and single-sex delivery. Conclusions: To our knowledge, the RBNIF is the first theory-driven, culturally adapted nursing intervention architecture for IGD in Saudi university health services; a focused, non-systematic search of PubMed, Scopus, and CINAHL identified no directly comparable published framework. It is pre-implementation and requires feasibility testing, pilot evaluation, and a cluster-randomized controlled trial (c-RCT).},
}

@article {pmid42651639,
year = {2026},
author = {Ciuro, M and Rovetto, C and Sirna, AA and Giunta, S and Leanza, G and Gulino, R},
title = {Targeting Mitochondrial Fission Produces Both Neuroprotective and Detrimental Effects in the SOD1 Mouse Model of Amyotrophic Lateral Sclerosis.},
journal = {Biology},
volume = {15},
number = {16},
pages = {},
pmid = {42651639},
issn = {2079-7737},
support = {PG_6/2022//Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease characterized by progressive motor neuron (MN) degeneration and severe skeletal muscle atrophy. Despite extensive research, the mechanisms driving disease onset and progression remain incompletely understood. While MN loss is a defining feature of ALS, increasing evidence indicates that mitochondrial dysfunction contributes to disease pathogenesis. Here, we investigated the hypothesis that Mdivi-1, a pharmacological inhibitor of mitochondrial fission protein Drp-1, may exert neuroprotective properties in the SOD1[G93A] mouse model of ALS. Treatment was initiated prior to symptomatic onset to assess its potential disease-modifying effects. Mdivi-1 administration resulted in partial preservation of spinal MNs, however, this benefit did not translate into functional improvement. Moreover, treated animals exhibited exacerbated muscle atrophy, increased cytoplasmic localization of TDP-43 in MNs and compromised synaptic plasticity. Drp-1 expression was reduced in SOD1 mice and further decreased following Mdivi-1 treatment, suggesting that mitochondrial dynamics may already be compromised in this model. Overall, our results also highlight possible off-target effects of Mdivi-1 and point to a context-dependent role of mitochondrial dynamics in ALS.},
}

@article {pmid42651822,
year = {2026},
author = {Satoh, K and Shimamura, MI and Fujimoto, T and Kitayama, M and Akagi, A and Iwasaki, Y and Satoh, Y and Ichinose, K and Satoh, A and Iwata, IT and Yabe, I},
title = {Detection of TDP-43 Proteinopathies in Brain and Cerebrospinal Fluid Using Seed Amplification Assay.},
journal = {Current issues in molecular biology},
volume = {48},
number = {8},
pages = {},
pmid = {42651822},
issn = {1467-3045},
support = {JP 21K07417 and JP 25K02582//Japan Society for the Promotion of Science/ ; //TaNeDS Funding for Daiichi Sankyo Co/ ; 2023088970//Takeda Science Foundation/ ; 25dk0207077h0001//Japan Agency for Medical Research and Development/ ; },
abstract = {Misfolded TAR DNA-binding protein 43 (TDP-43) is the primary pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). While seed amplification assays (SAAs), such as real-time quaking-induced conversion (RT-QuIC), have shown promise in detecting misfolded TDP-43 in cerebrospinal fluid (CSF) and olfactory mucosa, technically accessible methodologies are urgently required for widespread clinical application. We developed a streamlined, non-immunoprecipitation-based TDP-43 RT-QuIC assay to assess seeding activity in brain tissue and CSF. We evaluated its diagnostic performance using CSF from patients with TDP-43 proteinopathies and control subjects, and further examined its association with neurofilament light chain (NfL) and tau-related biomarkers. In CSF analysis, the assay demonstrated positive seeding activity in 70% (21/30) of patients with ALS and dementia, 50% (5/10) of patients with FTLD, and 40% (8/20) of patients with ALS alone. The assay exhibited excellent specificity, yielding negative results in >99% (199/200) of control samples, including those with autoimmune or electrophysiological abnormalities. Furthermore, CSF analysis demonstrated significantly higher NfL levels in TDP-43 SAA-positive cases compared to SAA-negative cases (p < 0.0008). The highest NfL concentrations were observed in the SAA-positive ALS with dementia and ALS cohorts, contrasting with lower levels in FTLD. Tau-related biomarkers exhibited no significant differences between the groups. Our streamlined, non-immunoprecipitation TDP-43 RT-QuIC assay provides highly specific detection of pathological TDP-43 seeding activity. While the assay detects the underlying TDP-43 proteinopathy rather than distinguishing between ALS and FTLD clinical phenotypes, its technical simplicity and combined utility with NfL measurements offer a robust, scalable framework for biomarker development. This approach provides a practical foundation for future multi-center validation and international standardization efforts.},
}

@article {pmid42652164,
year = {2026},
author = {Karbownik, M and Fidura, M and Perlikowska, R},
title = {Are Signal Peptides Hidden Regulators of Neurodegenerative Disease?.},
journal = {Biomedicines},
volume = {14},
number = {8},
pages = {},
pmid = {42652164},
issn = {2227-9059},
support = {564-20-100//Medical University of Lodz/ ; },
abstract = {Canonical signal peptides (SPs) are short N-terminal sequences that direct nascent proteins into the secretory pathway, but their role extends far beyond protein targeting. Advances in sequencing and computational tools have enabled their systematic identification across proteomes, highlighting SPs as critical regulators of protein biogenesis, including endoplasmic reticulum (ER) targeting, translocation, folding, and proteostasis. Clinically, mutations affecting SP function underlie a distinct group of human disorders, while SP-derived fragments are emerging as diagnostic biomarkers and therapeutic targets. In biotechnology, SPs are engineered to enhance recombinant protein production and serve as molecular tags for intracellular delivery. Together, these developments position SPs at the intersection of fundamental cell biology, medicine, and biotechnology. While this review primarily focuses on canonical SPs, it also considers selected non-canonical targeting and topogenic sequences whose dysfunction contributes to protein misfolding, impaired ER translocation, disrupted degradation pathways, and altered intracellular trafficking in neurodegenerative diseases. Aberrations involving both conventional SPs and alternative targeting/topogenic elements contribute to pathological protein aggregation, a hallmark of major neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington Disease (HD), prion diseases, and amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD); in multiple sclerosis (MS) is primarily an inflammatory demyelinating disease, where abnormal protein exposure, potentially linked to misprocessed SPs, can activate immune responses. By synthesizing current knowledge, the review explores how alterations in targeting determinants influence key proteostasis pathways, acting as upstream modulators of disease-relevant molecular cascades. It further discusses the emerging concept that SP-derived fragments may participate in intercellular communication, adding an additional layer of regulatory complexity.},
}

@article {pmid42652219,
year = {2026},
author = {Sousa-Catita, D and Mascarenhas, P and Oliveira, C and Grunho, M and Gonçalves, F and Fonseca, J},
title = {Clinical, Social, and Healthcare Factors Associated with Nutritional Status in Amyotrophic Lateral Sclerosis: A Multidimensional Approach.},
journal = {Biomedicines},
volume = {14},
number = {8},
pages = {},
pmid = {42652219},
issn = {2227-9059},
abstract = {Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease where malnutrition significantly worsens clinical outcomes. We performed a multidimensional analysis to identify clinical, social, and healthcare factors associated with nutritional vulnerability in a real-world setting. Methods: This cross-sectional study included 97 adults with ALS recruited through a national association (APELA) and a hospital-based outpatient consultation (ANOC). Nutritional status was assessed using the Mini Nutritional Assessment (MNA[®]), Body Mass Index (BMI), and Global Leadership Initiative on Malnutrition (GLIM) criteria. Associations with total MNA[®] scores were evaluated using a prespecified multivariable linear model with HC3 robust standard errors and bootstrap validation to assess inferential stability. Results: Malnutrition prevalence was high, with 42.3% of participants classified as moderately malnourished and 43.3% as severely malnourished under GLIM criteria. Mean MNA[®] score was 19.69 (SD 4.53). In the adjusted model, ANOC recruitment was associated, after adjustment, with a 4.477-point lower MNA[®] score compared with APELA (HC3 95% CI -7.071 to -1.884; p<0.001). Other sociodemographic and clinical factors yielded imprecise estimates. Although explanatory power was modest (Adjusted R2=0.067; optimism-corrected R2=-0.005), the recruitment setting remained a robust correlate across sensitivity analyses. Conclusions: Recruitment setting emerged as the most consistent adjusted correlate of MNA[®] scores, likely reflecting differences in clinical case mix and referral pathways in the Portuguese healthcare context. These findings highlight nutritional vulnerability in ALS as a multifaceted construct that should be interpreted in relation to both clinical and healthcare-contextual factors. This study supports considering systemic factors and the need for longitudinal research that incorporates comprehensive functional and social metrics to optimize multidisciplinary nutritional interventions.},
}

@article {pmid42652396,
year = {2026},
author = {Bhardwaj, S and Chakraborty, A and Mead, J and Stilos, K},
title = {Palliative Care Involvement in Hospitalized Amyotrophic Lateral Sclerosis Patients.},
journal = {International journal of environmental research and public health},
volume = {23},
number = {8},
pages = {},
pmid = {42652396},
issn = {1660-4601},
mesh = {Humans ; *Palliative Care/statistics & numerical data ; *Amyotrophic Lateral Sclerosis/therapy/mortality ; Female ; Male ; *Hospitalization ; Retrospective Studies ; Aged ; Middle Aged ; Referral and Consultation ; Aged, 80 and over ; Adult ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease associated with significant physical, psychological, and social distress. Given its terminal nature and high symptom burden, early integration of palliative care is essential. The inpatient Palliative Care Consult Team (PCCT) provides specialist palliative care to hospitalized patients with ALS. Hospitalizations are common throughout the ALS disease trajectory, particularly as patients experience progressive functional decline, respiratory compromise, and increasing care needs, making inpatient encounters important opportunities for specialist palliative care involvement. To extend palliative care beyond the inpatient setting and facilitate earlier involvement, an ALS ambulatory clinic was established in 2018. Despite the importance of palliative care, limited data describes its involvement among hospitalized ALS patients. This retrospective review examines the relationship between the PCCT and ALS patients admitted to a tertiary care facility between 2006-2019. Data collected included patient demographics, referral indications, clinical course, and disposition. Most patients referred to the PCCT had poor functional status and a guarded prognosis at initial consultation. Symptom management and support for complex decision-making were leading reasons for referral. Approximately half of patients died in the hospital within three months of referral. Most deaths occurred within one week, underscoring the importance of timely palliative care.},
}

Humans
*Palliative Care/statistics & numerical data
*Amyotrophic Lateral Sclerosis/therapy/mortality
Female
Male
*Hospitalization
Retrospective Studies
Aged
Middle Aged
Referral and Consultation
Aged, 80 and over
Adult

@article {pmid42652600,
year = {2026},
author = {Davies, A and Bentley, A and Bikov, A},
title = {The Role of Neurofilaments in Diagnosis and Monitoring of Amyotrophic Lateral Sclerosis.},
journal = {Journal of clinical medicine},
volume = {15},
number = {16},
pages = {},
pmid = {42652600},
issn = {2077-0383},
abstract = {Background: Amyotrophic lateral sclerosis (ALS), the most common type of motor neurone disease (MND), is a devastating diagnosis that often leads to mortality within 2-5 years of symptom onset. Respiratory failure and aspiration pneumonia both associated with respiratory muscle weakness are the most common causes of death. Difficult to diagnose and devastating in its prognosis, much research has aimed to identify a reliable biomarker to diagnose ALS, prognosticate and improve enrolment into clinical trials to further research efforts. Over the last few decades, neurofilaments (NFs) have emerged as promising biomarkers, especially neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH). This review aims to summarise the current evidence for use of NFs as biomarkers in ALS. Current Evidence: Higher levels of NFL and pNFH are measured in CSF than in serum, and levels in CSF and serum are correlated. High CSF NFL, serum NFL and CSF pNFH levels could differentiate patients with ALS from healthy controls, other neurological disease, neurodegenerative controls (without MND), other MND subtypes and ALS disease mimics; however, studies reported a high degree of heterogeneity irrespective of which media or NFs have been used. The number of studies examining NFs to predict respiratory failure in patients with ALS is low. Conclusions and Future Directions: Despite numerous studies consistently reporting higher NF levels in ALS compared to various controls, their clinical value is limited due to high heterogeneity of the results and inconsistencies in proving its prognostic value. Further understanding the relationship between NF levels and respiratory failure is paramount to improve the quality of life of patients with ALS and increase survival.},
}

@article {pmid42652767,
year = {2026},
author = {Friebel, J and Manni, M and Gozdowsky, SC and Brettschneider, P and Grün, D and Baumann, AM and Spielmann, E},
title = {Reorganisation of the Basic Life Support Segment in a Physician-Led Emergency Medical Service: A Retrospective Evaluation of Operational and Clinical Characteristics.},
journal = {Journal of clinical medicine},
volume = {15},
number = {16},
pages = {},
pmid = {42652767},
issn = {2077-0383},
abstract = {Background: Increasing demand for emergency medical services (EMS) challenges prehospital resource availability, particularly for time-critical emergencies requiring advanced life support (ALS). Although tiered BLS and ALS response models are established in many non-physician-led EMS systems, evidence regarding qualification-based dispatch stratification within physician-led EMS systems remains limited. This study evaluated the clinical and operational characteristics of an expanded BLS dispatch segment in Berlin EMS. Methods: A retrospective observational study analysed 2,132,246 EMS missions in Berlin, Germany, between 2020 and 2024. Missions were retrospectively classified according to dispatch codes included in the expanded BLS segment, designed to allocate incidents with lower expected requirements for ALS-level interventions to appropriately qualified EMS personnel. Analyses included dispatch characteristics, clinical findings from electronic patient care records, observed safety-related indicators, and ALS response intervals. Results: Overall, 28.7% of EMS missions were classified within the expanded BLS segment. Traumatic and psychiatric presentations represented the most frequent diagnostic groups. Based on predefined clinical indicators, no immediately life-threatening condition was documented in more than 95% of missions. Cardiopulmonary resuscitation occurred in 0.03% of cases, and emergency physician involvement was documented in approximately 3% of cases. Conclusions: A substantial proportion of EMS missions represented a population with predominantly lower expected prehospital treatment complexity within a qualification-based dispatch framework. Structured emergency call interrogation combined with dispatch classification and linked clinical data enabled retrospective evaluation of this approach. Further validation against independent clinical reference standards and linkage with downstream outcomes are required to determine broader applicability.},
}

@article {pmid42639443,
year = {2026},
author = {Potla, KM and Justin Nathaniel, CM and Parameshwar Adimule, S and Vincent Raj Shanthi, JR and Bilal, H and Tawfeek, AM and Islam, MS},
title = {Electron-withdrawing group effects on the structural, electronic, reactivity, and binding characteristics of triazolopyrimidine herbicides: a comparative study of diclosulam, cloransulam-methyl, and cloransulam.},
journal = {RSC advances},
volume = {},
number = {},
pages = {},
pmid = {42639443},
issn = {2046-2069},
abstract = {Diclosulam (DS, I), cloransulam-methyl (CSM, II), and cloransulam (CS, III) are widely used herbicidal inhibitors of the AHAS/ALS enzyme for selective weed control. In the present work, a comparative experimental and theoretical study has been conducted on the impact of substituents on their structural, electronic, and reactive properties. Structural differences have been established using single-crystal X-ray diffraction. The crystal packing and interaction energy have been investigated using the Hirshfeld surface approach, while density functional theory confirmed the experimental geometry. The analysis of the electronic structure, reactivity descriptors, localization of electrons, and non-covalent interactions was carried out by the methods of frontier molecular orbitals, MEP, ELF/LOL, and RDG calculations. The binding interactions of compounds with AHAS/ALS protein targets were determined using molecular docking. The combined results reveal clear interdependencies between the structure, electronic properties, non-covalent interactions, and the behavior of molecules upon the interaction with enzymes.},
}

@article {pmid42640367,
year = {2026},
author = {Iacono, D and Feltis, GC},
title = {Beyond the Ribosome: The Expanding Role of the Nucleolus in Neurodegenerative Pathways.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42640367},
issn = {1559-1182},
mesh = {*Cell Nucleolus/metabolism/pathology ; Humans ; Animals ; *Neurodegenerative Diseases/metabolism/pathology ; *Ribosomes/metabolism ; Signal Transduction ; Aging/metabolism/pathology ; },
abstract = {The nucleolus, long defined by its canonical role in ribosome biogenesis, has emerged as a critical nexus for cellular homeostasis, stress sensing, and disease pathogenesis. This article synthesizes a broad range of evidence to construct a comprehensive model of the nucleolus in the context of aging and neurodegeneration. We begin by detailing its fundamental architecture and the intricate process of ribosome production, before exploring the paradigm-shifting discovery of its vast, non-canonical proteome, which implicates it in DNA repair, cell cycle control, and genome stability. A central theme is the nucleolus's function as a primary cellular stress sensor, which, upon disruption by genetic, metabolic, or proteotoxic insults, initiates the nucleolar stress response. We provide a detailed examination of the downstream signaling cascades, focusing on the canonical p53-MDM2 axis and the interconnected mTOR pathway, which together translate nucleolar status into decisions of cell fate, including apoptosis and cell cycle arrest. We then focus on the brain, presenting the neuropathological and morphological alterations of the nucleolus-such as atrophy, fragmentation, and changes in volume-that serve as hallmarks of normal aging and neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease, and C9orf72-linked ALS/FTD. We explore the deep regulatory layers of epigenetics, where DNA methylation and histone modifications of ribosomal DNA genes are dysregulated in disease, and discuss how multi-omics approaches are unraveling the complex molecular landscape of nucleolar function. Finally, we introduce the emerging concept of a gut-brain-nucleolus axis, proposing how systemic factors like the gut microbiome may influence neuronal health by triggering nucleolar stress through inflammatory and metabolic mediators. Overall, by highlighting the nucleolus as a convergence point for diverse pathogenic pathways, we frame it as a promising and druggable target for novel therapeutic strategies aimed at promoting neuronal resilience and combating neurodegenerative diseases.},
}

*Cell Nucleolus/metabolism/pathology
Humans
Animals
*Neurodegenerative Diseases/metabolism/pathology
*Ribosomes/metabolism
Signal Transduction
Aging/metabolism/pathology

@article {pmid42640452,
year = {2026},
author = {Copenhaver, AE and Puglisi, C and Eslami, MA},
title = {Comparison of classic statistical methods and machine learning approaches to classify readiness.},
journal = {Bioinformatics (Oxford, England)},
volume = {},
number = {},
pages = {},
doi = {10.1093/bioinformatics/btag585},
pmid = {42640452},
issn = {1367-4811},
abstract = {MOTIVATION: Predicting physical and cognitive readiness in warfighters is critical for mission success. These predictions can be improved by identifying key biomarkers using multiple omics modalities. The MASTR-E study conducted by McKetney and colleagues is one of the most comprehensive multi-omics studies of saliva samples collected from warfighters, which also applied classic linear statistical (CLS) techniques to discover key biomarkers of readiness. Aligning with McKetney et al.'s assumptions, we operationalize readiness as a binary proxy, where pre-mission samples are labeled as 'ready' to reflect a rested, unstressed physiological baseline, while post-mission samples are labeled 'not ready' to reflect cumulative physical and cognitive load from the mission. As such, readiness here is not a direct biological or physiological construct, but an inferred state likely dominated by stress-related physiological changes. This assumption and definition is discussed further in the Introduction and Limitations sections. Here, we apply machine learning (ML) analyses to better assess generalizability, consider hidden interactions, and identify nonlinear patterns in the data. We investigated whether ML approaches could predict readiness and identify relevant biomarkers. ML models were trained on proteomics-only or metabolomics-only datasets to classify participants as ready or not ready and important model features were considered as putative biomarkers. Training and testing datasets were curated for two objectives: 1) recognize biomolecular signatures indicative of readiness within the same donor and 2) assess generalizability across warfighters by withholding donors for testing.

RESULTS: Proteomics-based models achieved AUCs of 0.907±0.034 and 0.860±0.063 for Objectives 1 and 2, respectively. Metabolomics-based models achieved Objective 1 AUC of 0.994±0.007 and Objective 2 AUC of 0.993±0.010. Comparative analysis with existing literature validates the model's feature importances, but the identified putative biomarkers significantly differ from those discovered through CLS analyses, as only one ML-identified biomarker overlapping with those identified through CLS methods. We show that these ML models and identified features are more robust to noise and generalizable across participants than those identified using CLS methods.

AVAILABILITY: The analysis pipelines are provided as Jupyter notebooks, including all code and documentation, and are available publicly on GitHub at {{https://github.com/netrias/ReadinessClassification}}
.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.},
}

@article {pmid42641169,
year = {2026},
author = {Kodama, K and Ando, M and Higuchi, Y and Yuan, JH and Yoshimura, A and Samukawa, M and Suzuki, M and Ogaya, S and Kawata, Y and Gamo, N and Hisahara, S and Yano, C and Nagatomo, R and Hobara, T and Kojima, F and Hiramatsu, Y and Nozuma, S and Sakiyama, Y and Mitsui, J and Tsuji, S and Takashima, H},
title = {Biallelic SIGMAR1 variants in early-onset distal hereditary motor neuropathy: A Japanese case series.},
journal = {Journal of neuromuscular diseases},
volume = {},
number = {},
pages = {22143602261477464},
pmid = {42641169},
issn = {2214-3602},
abstract = {BackgroundDistal hereditary motor neuropathy (dHMN) is characterized by slowly progressive distal muscle weakness and amyotrophy, and it exhibits clinical overlap with Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis (ALS). Biallelic variants in SIGMAR1, encoding sigma nonopioid intracellular receptor 1, have been linked to autosomal recessive dHMN with pyramidal features. This study investigated the clinical and genetic features of patients with dHMN associated with SIGMAR1 variants in Japan.MethodsWe conducted genetic screening of Japanese patients with clinically suspected inherited peripheral neuropathies using targeted gene panels and whole-exome sequencing. SIGMAR1 variants were evaluated via segregation analysis using Sanger sequencing. Detailed clinical and electrophysiological data were systematically reviewed.ResultsBiallelic SIGMAR1 variants, including three novel variants and one previously reported variant, were identified in six patients from five unrelated families. The genotypes comprised compound heterozygous variants in four patients and homozygous variants in two patients. All patients presented with early-onset distal muscle weakness and atrophy. Enhanced tendon reflexes and pyramidal tract signs were frequently observed, whereas bulbar or respiratory involvement was absent. Nerve conduction studies consistently revealed motor-predominant axonal neuropathy with minimal sensory involvement. Disease progression was slow, and all patients remained ambulatory for years to decades after onset.ConclusionOur findings expand the clinical and genetic spectrum of SIGMAR1-associated disease and support its classification as dHMN rather than ALS. SIGMAR1 variants should be considered in the genetic evaluation of early-onset motor neuropathies, particularly in patients with dHMN accompanied by pyramidal features.},
}

@article {pmid42641283,
year = {2026},
author = {Yoo, HE and Issenberg, SB and Roh, YS},
title = {Psychometric evaluation and responsiveness of the resuscitation self-efficacy scale among ward nurses: A pretest-posttest study.},
journal = {Nurse education in practice},
volume = {96},
number = {},
pages = {104954},
doi = {10.1016/j.nepr.2026.104954},
pmid = {42641283},
issn = {1873-5223},
abstract = {AIM: To evaluate the psychometric properties and responsiveness of the Resuscitation Self-Efficacy Scale (RSES) among ward nurses before and after simulation-based advanced life support (ALS) training.

BACKGROUND: Although the RSES was developed to measure nurses' perceived capability in resuscitation, evidence regarding its psychometric evaluation among ward nurses participating in ALS training remains limited.

DESIGN: Secondary psychometric analysis of data obtained from a simulation-based ALS training study.

METHODS: Ward nurses (N = 191) from general hospitals completed the RSES before and immediately after participation in a simulation-based ALS training program. Psychometric evaluation included item analysis, internal consistency reliability, evidence based on internal structure, construct validity through convergent and discriminant validity, relations with an external performance measure and responsiveness.

RESULTS: The RSES demonstrated good internal consistency, with a Cronbach's α of.80 for the total scale and.88-.91 across the four factors. Factor analysis supported the original four-factor structure, with satisfactory model fit (CFI =.958, TLI =.949, RMSEA =.052 and SRMR =.072). Evidence of convergent and discriminant validity met recommended criteria. Individual resuscitation self-efficacy showed modest positive associations with team-level ALS performance and the RSES demonstrated moderate responsiveness to change (standardized response mean =.77).

CONCLUSIONS: The findings provide psychometric evidence supporting the use of the RSES for assessing resuscitation self-efficacy among ward nurses participating in simulation-based ALS training. The RSES may be useful for evaluating educational outcomes and monitoring changes in learners' self-efficacy following educational interventions.},
}

@article {pmid42642835,
year = {2026},
author = {Aldaghi, FS and Siahpoosh, Z and Salehi, Z and Mashayekhi, F and Sohrabnezhad, S},
title = {Unraveling Neurodegeneration: Common Molecular Mechanisms and Novel Therapeutic Concepts in Major Neurodegenerative Disorders.},
journal = {Brain and behavior},
volume = {16},
number = {8},
pages = {e71615},
pmid = {42642835},
issn = {2162-3279},
mesh = {Humans ; *Neurodegenerative Diseases/metabolism/therapy ; Oxidative Stress/physiology ; Animals ; *Neuroinflammatory Diseases/metabolism ; Mitochondria/metabolism ; Amyotrophic Lateral Sclerosis/metabolism ; Alzheimer Disease/metabolism ; Multiple Sclerosis/metabolism ; Parkinson Disease/metabolism ; Huntington Disease/metabolism ; Inflammasomes/metabolism ; },
abstract = {PURPOSE: Although Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Huntington's disease (HD) present with markedly different clinical phenotypes, these neurodegenerative diseases (NDDs) appear to converge on a shared set of underlying molecular disturbances. This review sought to integrate disease-specific causative triggers with shared pathogenic pathways, focusing on neuroinflammatory signaling, oxidative imbalance, mitochondrial impairment, and disrupted protein homeostasis, in order to support multi-target, disease-modifying therapeutic strategies.

METHOD: Relevant classical and contemporary literature, encompassing original research and review articles on the molecular basis of AD, PD, ALS, MS, and HD, was reviewed and synthesized narratively, with attention to how neuroinflammatory and oxidative stress pathways intersect, reinforce one another through mitochondrial and inflammasome-driven feedback, and recur across the five conditions.

FINDING: In each disorder, persistently activated microglia and astrocytes secreted inflammatory mediators and reactive oxygen species, engaged the NLRP3 inflammasome, and progressively destabilized cellular homeostasis through a self-perpetuating cycle linking neuroinflammation and oxidative stress. Disease-specific lesions nonetheless persisted: amyloid-β and tau pathology in AD; α-synuclein aggregation with iron-driven mitochondrial damage in PD; RNA-binding protein dysfunction, proteostatic collapse, and excitotoxicity in ALS; inflammatory demyelination and axonal bioenergetic failure in MS; and mutant huntingtin-driven transcriptional and mitochondrial disruption in HD. These distinct triggers ultimately converged on shared downstream cascades.

CONCLUSION: Recognizing this shared pathogenic foundation supports multi-target therapies-such as Nrf2 activation, NLRP3 inhibition, mitochondria-targeted antioxidants, and gene-based interventions-that extend across diagnostic boundaries, though challenges in intervention timing, patient stratification, and clinical translation remain unresolved.},
}

Humans
*Neurodegenerative Diseases/metabolism/therapy
Oxidative Stress/physiology
Animals
*Neuroinflammatory Diseases/metabolism
Mitochondria/metabolism
Amyotrophic Lateral Sclerosis/metabolism
Alzheimer Disease/metabolism
Multiple Sclerosis/metabolism
Parkinson Disease/metabolism
Huntington Disease/metabolism
Inflammasomes/metabolism

@article {pmid42642938,
year = {2026},
author = {Zou, L and Song, L and Yin, P and Cui, H and Lian, L and Peng, X and Jin, T and Wang, H and Liu, W},
title = {Glutathione S-transferase genes PfGSTU6 and PfGSTL1 involved in mesosulfuron-methyl resistance in Polypogon fugax.},
journal = {Pest management science},
volume = {},
number = {},
pages = {},
doi = {10.1002/ps.71227},
pmid = {42642938},
issn = {1526-4998},
support = {//National Natural Science Foundation of China (32372570, 32572857)/ ; //Shandong Provincial Natural Science Foundation (ZR2025MS289)/ ; },
abstract = {BACKGROUND: Polypogon fugax is a major weed in wheat and winter canola fields in China. Two populations, SD-4 and JS-13, showing resistance to the ALS inhibitor mesosulfuron-methyl, were collected from winter wheat fields. This study aimed to characterize their resistance level and cross-resistance profile, investigate the resistance mechanism and identify its functional genes.

RESULTS: Dose-response assays showed that SD-4 and JS-13 have high-level resistance to mesosulfuron-methyl (15.9-and 16.4-fold, respectively) and cross-resistance to the ACCase inhibitors clodinafop-propargyl, fenoxaprop-P-ethyl, quizalofop-p-ethyl, and the PDS inhibitor diflufenican. Sequencing of the ALS gene revealed no known target-site mutations within the eight conserved resistance-associated regions. Pre-treatment with the cytochrome P450 monooxygenase (P450) inhibitor malathion or the glutathione S-transferase (GST) inhibitor NBD-Cl increased herbicide sensitivity in resistant plants. The resistant plants showed higher inducible GST activity. Herbicide residues analysis observed that resistant plants exhibiting increased mesosulfuron-methyl metabolism, and the enhanced metabolism could be reduced by both inhibitors. Integrated transcriptomic and qRT-PCR analysis identified 17 stably upregulated genes, including PfGSTU6 and PfGSTL1. Escherichia coli and rice callus overexpressing PfGSTU6 and PfGSTL1 exhibit significantly enhanced herbicide tolerance to mesosulfuron-methyl, and molecular docking analysis confirmed the strong binding affinity of GST proteins to the target herbicide.

CONCLUSIONS: The P450s and GSTs mediated herbicide metabolism confer mesosulfuron-methyl resistance in P. fugax. This study elucidates the resistance mechanism and provides genetic resources for resistance monitoring and crop breeding. In addition, we characterized the cross-resistance profile of the resistant P. fugax population, which provides guidance for developing targeted field weed resistance management strategies. © 2026 Society of Chemical Industry.},
}

@article {pmid42643027,
year = {2026},
author = {Christen, AL and Sobanski, E and Bitto, H and Abt-Mörstedt, B and Stieglitz, RD and Corbisiero, S},
title = {Emotional Dysregulation, Emotional Lability, Emotional Impulsiveness and Emotion in Adults with ADHD: Do All Scales Define the Same Concept?.},
journal = {Journal of attention disorders},
volume = {},
number = {},
pages = {10870547261475724},
doi = {10.1177/10870547261475724},
pmid = {42643027},
issn = {1557-1246},
abstract = {BACKGROUND: Various studies highlight emotional symptoms as a crucial component of ADHD in adulthood, suggesting independent diagnostic approaches that incorporate patients' emotional experiences into the assessment. However, the emotional symptomatology appears to be defined differently within the disorder's different constructs: Emotional Dysregulation (ED), Emotional Lability (EL), Emotional Impulsiveness (EI) and Emotion (E). Hence, the question arises: Do these symptom domains represent the same psychopathological spectrum?

METHOD: A total of 1240 adults seeking diagnostic evaluation at the ADHD specialist consultation in two different clinics (University Psychiatric Clinics (UPK) in Basel and Central Institute of Mental Health in Mannheim) were examined, whereas 611 participants were diagnosed with ADHD. They were further assessed in regard of their emotional symptoms using the following scales: ED, EL, EI and E. Additionally, affective lability was measured as a control using the Affective Lability Scale (ALS-18).

RESULTS AND DISCUSSION: The convergent and construct validity using correlations and principal component analysis (PCA) revealed that individuals with ADHD experience distinct emotional symptoms divergent from a general concept of affective lability as assessed by the ALS-18. The PCA shows that the ADHD-specific emotional symptoms may be classified into (1) difficulties with temper control and anger, (2) emotional distress and (3) emotional overreactivity and mood changes.},
}

@article {pmid42643197,
year = {2026},
author = {Sigala, N and Cobandag, M and Leppard, L and Medford, N},
title = {Insight and executive functions in acquired brain injury: empirical evidence and theoretical frameworks.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1884495},
pmid = {42643197},
issn = {1664-2295},
mesh = {Humans ; *Brain Injuries/physiopathology/psychology/complications ; *Executive Function/physiology ; *Awareness/physiology ; *Prefrontal Cortex/physiopathology ; Cognitive Flexibility ; },
abstract = {Impaired self-awareness affects 30-50% of patients with moderate to severe acquired brain injury (ABI) and represents one of the most clinically consequential obstacles to effective rehabilitation. Despite substantial evidence that self-awareness and executive functions share neural substrates in prefrontal cortex, the mechanisms linking these two functions remain incompletely specified. This paper reviews the empirical evidence for the relationship between executive functions and insight in ABI, and evaluates four theoretical frameworks: the Cognitive Awareness Model, the Dynamic Comprehensive Model of Awareness, Mograbi et al.'s predictive coding framework, and Duncan's adaptive coding model. It then proposes a novel integration of the latter two as a mechanistically grounded account of why executive dysfunction and impaired self-awareness co-occur following prefrontal damage. We argue that adaptive coding describes the representational flexibility of prefrontal neurons in coding self-relevant information, whilst predictive coding provides the computational logic, driven by precision-weighted prediction errors, through which this adaptive selection is updated. We conclude by discussing assessment and rehabilitation implications in ABI.},
}

Humans
*Brain Injuries/physiopathology/psychology/complications
*Executive Function/physiology
*Awareness/physiology
*Prefrontal Cortex/physiopathology
Cognitive Flexibility

@article {pmid42645064,
year = {2026},
author = {Sonkar, KS and Levi D'Ancona, V and Cramp, J and Shilling, H and Giles, E and Howell-Bray, T and Fillingham, B and Cudkowicz, ME and Nath, A and Rothstein, JD and Bowser, R and Borroni, B and Berry, JD and Sadri-Vakili, G and Buratti, E and Thrippleton, IP},
title = {Functional Activity of TDP-43: A Direct Biomarker for ALS.},
journal = {Biosensors},
volume = {16},
number = {8},
pages = {},
pmid = {42645064},
issn = {2079-6374},
mesh = {*Amyotrophic Lateral Sclerosis/blood/diagnosis ; Humans ; *DNA-Binding Proteins/blood/metabolism ; Biomarkers/blood ; Fluorescence Resonance Energy Transfer ; *Biosensing Techniques ; C9orf72 Protein/genetics ; },
abstract = {TDP-43 dysfunction is a defining feature of amyotrophic lateral sclerosis (ALS), yet no biofluid biomarker directly measures its functional activity. We developed a serum-based homogeneous time-resolved FRET (hTR-FRET) assay that quantifies TDP-43 RNA binding activity using synthetic UU-rich RNA probes. We analyzed 1080 serum samples from controls, sporadic ALS, and genetic subgroups (C9orf72, SOD1) across multiple biorepositories. Cross-sectionally, TDP-43 functional activity was elevated in ALS (mean 390 a.u.) versus controls (302 a.u.), yielding AUC = 0.79. Genotype means were 392 a.u. (sporadic), 382 a.u. (C9orf72), and 323 a.u. (SOD1); a 366 a.u. threshold achieved 95% specificity against controls. Longitudinally, Target ALS showed a modest but significant inverse correlation between TDP-43 activity and ALSFRS-R, while other cohorts exhibited similar non-significant trends. Elevated signal in serum likely reflects increased extracellular release of probe-competent TDP-43 species during cell death and exosomal shedding, rather than restored intracellular nuclear splicing function. This assay provides a proof-of-concept platform for the direct functional measurement of probe-competent TDP-43 species in serum. While it demonstrates moderate group-level discrimination, individual diagnostic performance requires prospective validation. The assay may support exploratory applications in genotype stratification and progression monitoring in future clinical studies.},
}

*Amyotrophic Lateral Sclerosis/blood/diagnosis
Humans
*DNA-Binding Proteins/blood/metabolism
Biomarkers/blood
Fluorescence Resonance Energy Transfer
*Biosensing Techniques
C9orf72 Protein/genetics

@article {pmid42645160,
year = {2026},
author = {Leggett, S and Sanghai, N and Ru, C and Marcogliese, PC and Tranmer, GK},
title = {Drosophila: An Emerging New Approach Method (NAM) for Studying Amyotrophic Lateral Sclerosis (ALS).},
journal = {Cells},
volume = {15},
number = {16},
pages = {},
pmid = {42645160},
issn = {2073-4409},
support = {202210PJT-495295/CAPMC/CIHR/Canada ; RGPIN-2017-05938//Natural Sciences and Engineering Research Council of Canada/ ; },
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/pathology/drug therapy/metabolism ; *Drosophila melanogaster/genetics/metabolism ; Humans ; Disease Models, Animal ; DNA-Binding Proteins/metabolism/genetics ; Superoxide Dismutase-1/metabolism/genetics ; Drug Evaluation, Preclinical ; },
abstract = {Drosophila melanogaster (D. melanogaster), or fruit flies, are a commonly used model organism in the study of neurodegenerative diseases (NDs). Their short lifespan, low cost, genetic tractability, and conserved signaling and developmental pathways make them ideal for studying NDs and associated biochemical pathways. Further, flies offer the advantage of high-throughput exploratory drug and genetic screening without stringent ethical constraints. Therefore, D. melanogaster serves as an ideal organism for preliminary drug screening before transitioning to toxicity and efficacy studies in vertebrate models. Following the recent plan by the United States FDA (US FDA) and the National Institutes of Health (NIH) to progressively phase out preclinical drug testing in vertebrate animals and introduce New Approach Methodologies (NAMs), D. melanogaster has the potential to become part of the conventional drug testing pipeline in the future. This literature review focuses on the use of D. melanogaster models as a powerful, low-cost model organism to study superoxide dismutase 1 (SOD1)- and TAR DNA-binding protein 43 (TDP-43)-linked Amyotrophic Lateral Sclerosis (ALS), as well as previous efforts to screen drugs in SOD1- and TDP-43-expressing Drosophila models.},
}

Animals
*Amyotrophic Lateral Sclerosis/genetics/pathology/drug therapy/metabolism
*Drosophila melanogaster/genetics/metabolism
Humans
Disease Models, Animal
DNA-Binding Proteins/metabolism/genetics
Superoxide Dismutase-1/metabolism/genetics
Drug Evaluation, Preclinical

@article {pmid42646366,
year = {2026},
author = {Anwar, AI and Hegazi, AA and Bhuchakra, HP and Nelson, JR and Birdsong, TL and Fontenot, CJ and Zeibo, M and Fazal-Ur-Rehman, MM and Bieber, HP and Spring, CJ and Smith, JL and Hachem, IA and Singh, T and Sawaya, MF and Murnane, KS and Kaye, AD},
title = {Pridopidine Mediated Sigma-1 Receptor Activation and Therapeutic Implications in Neurodegenerative Diseases.},
journal = {Neurology international},
volume = {18},
number = {8},
pages = {},
pmid = {42646366},
issn = {2035-8385},
abstract = {Neurodegenerative diseases are targets for pridopidine therapy, which aims to improve quality of life through neuroprotective mechanisms that involve sigma-1 receptor (S1R) activation. Neurodegenerative motor and cognitive diseases are influenced by dopamine imbalance, where disruptions in pathways contribute to states that are hyperkinetic or hypokinetic, while current dopaminergic treatments are symptomatic rather than disease-modifying, especially for Huntington's disease and Amyotrophic lateral sclerosis. This review summarizes the mechanisms underlying pridopidine-mediated neuroprotection and examines the current evidence supporting its therapeutic potential. The S1R is an endoplasmic reticulum-mitochondria-associated chaperone involved in homeostasis of calcium, stress regulation, and mitochondrial function. Pridopidine is a small lipophilic molecule that crosses the blood-brain barrier and acts as an S1R agonist, with minimal dopamine D2 receptor occupancy. Activation of S1R by pridopidine modulates calcium signaling and enhances anti-apoptotic activity. Collectively, available evidence suggests that pridopidine may improve motor outcomes and slow disease progression in Huntington's disease and amyotrophic lateral sclerosis, supporting its promise as a disease-modifying therapeutic strategy.},
}

@article {pmid42646494,
year = {2026},
author = {Shevchuk, D and Kuzmenko, Y and Zakharova, M and Karpov, V and Starodubova, E and Latanova, A},
title = {NLRP3 Inflammasome and Inflammation-Related Proteins Expression Characterized in Non-Cultivated Versus Cultivated Peripheral Blood Cells of Patients with Amyotrophic Lateral Sclerosis.},
journal = {NeuroSci},
volume = {7},
number = {4},
pages = {},
pmid = {42646494},
issn = {2673-4087},
support = {25-74-10090//Russian Science Foundation/ ; },
abstract = {BACKGROUND: Cell and mouse models studies demonstrate NLRP3 inflammasome involvement in amyotrophic lateral sclerosis (ALS) neuroinflammation. Peripheral blood mononuclear cells (PBMCs) are a promising, yet understudied, source of in vivo inflammasome activation biomarkers. Our study reviewed the literature on PBMC-based inflammasome studies of ALS and other neurodegenerative diseases and tested different conditions for PBMC handling to evaluate inflammasome and inflammation-related protein expression in these cells.

METHODS: Expression of NLRP3 inflammasome components and inflammation-related proteins was analyzed by Real-time qPCR and Western blot in non-cultivated/cultivated PBMCs of 23 ALS patients and 20 Healthy controls. IL-1β and IL-18 levels were measured in plasma and cultivated PBMC supernatants by ELISA.

RESULTS: Cultivation of PBMCs decreased expression of inflammasome components and inflammation-related cytokines on the mRNA but not protein level. NLRP3 mRNA expression was significantly higher in ALS-cultivated PBMCs. In both ALS and Healthy controls, IL-18 was detected in plasma, and IL-1β in supernatants of cultivated PBMCs.

CONCLUSIONS: Our findings suggest that PBMC handling conditions, i.e., cell cultivation, may determine particular parameters associated with NLRP3 inflammasome expression and activation pathway, so they should be carefully selected for PBMC-based studies of inflammasome in neurodegenerative and non-neurological disorders and taken into account when interpreting the study results.},
}

@article {pmid42646579,
year = {2026},
author = {Calabrò, RS and Calderone, A and Ravi, D and Galipò, C and Crupi, MF and Quartarone, A},
title = {Hospital-to-Home Neurological Transition Care: A Scoping Review Across Selected Chronic Neurological Disorders.},
journal = {Medical sciences (Basel, Switzerland)},
volume = {14},
number = {4},
pages = {},
pmid = {42646579},
issn = {2076-3271},
mesh = {Humans ; *Nervous System Diseases/therapy ; *Transitional Care ; Multiple Sclerosis ; Hospitalization ; Chronic Disease ; Amyotrophic Lateral Sclerosis ; },
abstract = {BACKGROUND: Returning home after neurological hospitalization, rehabilitation, or specialist care transfers responsibility to patients, caregivers, and community services. We mapped mechanisms and gaps across dementia/Alzheimer's disease and related dementias (ADRD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS).

METHODS: Following JBI guidance and PRISMA-ScR, eligibility was derived using population-concept-context. We included empirical reports involving adults with a target condition, a post-discharge, return-home, rehabilitation, telehealth, caregiver, treatment, respiratory, or palliative continuity component, and post-transition patient, caregiver, service, safety, rehabilitation, equity, or implementation outcomes. Five databases were searched through to 11 May 2026. Two reviewers independently screened records; charting and classification were verified by R.S.C., A.C., and A.Q.

RESULTS: Of 24,417 records, 69 reports were included: Dementia/ADRD, 28; PD, 10; MS, 9; and ALS, 22. Eighteen were core transition reports (26.1%), 14 return-home/community re-entry reports (20.3%), 16 adjacent continuity reports (23.2%), and 21 companion/secondary reports (30.4%). Dementia/ADRD provided discharge-anchored evidence; PD and MS mapped functional carry-over; ALS mapped adjacent respiratory, telehealth, and palliative continuity.

CONCLUSIONS: The main contribution is an operational cross-disease framework separating direct discharge, return-home, adjacent-continuity, and companion evidence while linking mechanisms to disease-specific pathways. This framework maps disease-specific functions, not comparative effectiveness. The proposed frameworks are author-derived and hypothesis-generating. Future studies should use explicit anchors, standardized outcomes, longer follow-up, and equity-sensitive implementation measures addressing caregiver workload, digital access, feasibility, and sustainability. They inform testable, context-sensitive intervention designs for future neurological transition-care research and practice.},
}

Humans
*Nervous System Diseases/therapy
*Transitional Care
Multiple Sclerosis
Hospitalization
Chronic Disease
Amyotrophic Lateral Sclerosis

@article {pmid42647236,
year = {2026},
author = {Sanchis-Sanchis, E and de la Rubia Ortí, JE and Sancho-Cantus, D and Cunha-Pérez, C and Casaña-Mohedo, J},
title = {The Microbiota-Gut-Brain Axis and Nutritional Interventions in Amyotrophic Lateral Sclerosis: Pathophysiological Mechanisms, Neuroinflammation, and Non-Motor Manifestations-Scoping Review.},
journal = {Pathophysiology : the official journal of the International Society for Pathophysiology},
volume = {33},
number = {3},
pages = {},
pmid = {42647236},
issn = {1873-149X},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder in which systemic pathophysiological alterations significantly contribute to disease progression and non-motor manifestations, such as depression and anxiety. The microbiota-gut-brain axis represents a critical bidirectional pathway in which intestinal dysbiosis and epithelial barrier disruption catalyze central neuroinflammation. This scoping review synthesizes evidence from 43 empirical and analytical studies across 28 countries and maps the findings under the WHO International Classification of Functioning (ICF) framework. Pathophysiological data reveal a profound taxonomic shift in patients with ALS, characterized by severe depletion of neuroprotective, butyrate-producing genera (Akkermansia and Prevotella) and enrichment of pro-inflammatory Enterobacteriaceae. This dysbiotic state leads to structural damage to the intestinal mucosa, alteration of Paneth cells, and downregulation of tight junction proteins (zonulin), triggering a "leaky gut" phenomenon. Subsequent systemic translocation of lipopolysaccharides (LPS) induces TLR4-mediated endotoxemia, microglial hyperactivation, and accelerated motor neuron apoptosis. Conversely, therapeutic modulation via Fecal Microbiota Transplantation (FMT), psychobiotics, and metabolic interventions (ketogenic or Mediterranean diets) has demonstrated significant efficacy in restoring epithelial integrity, mitigating mitochondrial hypermetabolism, and reducing emotional distress. This review identifies a critical research gap in the microstructural characterization of the enteric nervous system in ALS. Incorporating microbiome-targeted biomarkers into clinical protocols is crucial for implementing a stratified, multi-systemic therapeutic strategy aimed at enhancing patient prognosis and psychological well-being.},
}

@article {pmid42647657,
year = {2026},
author = {Denčevski, A and Bataveljić, D and Bogdanović Pristov, J and Krmpot, AJ and Rabasović, MD and Nikolić, L},
title = {Characterizing Single-Cell Differences in Aquaporin-4 and Glutamate Transporter-1 Between Control and hSOD1G93A Astrocytes Using Integrated Epifluorescence and Structured Illumination Microscopy.},
journal = {Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada},
volume = {32},
number = {4},
pages = {},
doi = {10.1093/mam/ozag095},
pmid = {42647657},
issn = {1435-8115},
support = {451-03-33/2026-03/200053//Ministry of Science, Technological Development and Innovation of Republic of Serbia/ ; 451-03-33/2026-03/200178//Ministry of Science, Technological Development and Innovation of Republic of Serbia/ ; 451-03-33/2026-03/200007//Ministry of Science, Technological Development and Innovation of Republic of Serbia/ ; //Institute of Physics Belgrade/ ; //Science Fund of the Republic of Serbia/ ; },
mesh = {*Astrocytes/chemistry/metabolism ; *Aquaporin 4/analysis/metabolism ; Animals ; *Excitatory Amino Acid Transporter 2/analysis ; Microscopy, Fluorescence/methods ; *Single-Cell Analysis/methods ; Cells, Cultured ; Humans ; },
abstract = {Astrocytes, the abundant glial cells of the central nervous system (CNS), maintain water and glutamate homeostasis through aquaporin-4 (AQP4) and glutamate transporter-1 (EAAT2). In the hSODG93A animal model of amyotrophic lateral sclerosis, astrocytes exhibit alterations in these homeostatic proteins. AQP4 and EAAT2 changes are observed in both hSODG93A-expressing astrocytes in the CNS and in cell cultures. Here, we provide a detailed analysis of differences between cultured control and hSOD1G93A astrocytes in AQP4 and EAAT2 fluorescence patterns, subcellular localization, and spatial overlap, using side-by-side epifluorescence and structured illumination microscopy modes of a custom imaging system [two-dimensional structured illumination microscopy (2D SIM)]. 2D SIM system characterization and fluorescence signal analysis demonstrated uniform epifluorescence illumination and high-contrast SIM patterns, enabling whole-cell imaging of AQP4 and EAAT2 and resolving their signals into distinct puncta in both control and hSOD1G93A astrocytes with SIM. Compared with control astrocytes, AQP4 expression increased and EAAT2 expression decreased in the plasma membrane and cytoplasm of hSOD1G93A astrocytes at both diffraction-limited and superresolution scales. Subdiffraction-scale analysis revealed differences in the spatial distributions of AQP4 and EAAT2, showing increased colocalization between these proteins in hSOD1G93A astrocytes. These findings demonstrate the utility of integrated imaging approaches for quantitative, single-cell-resolution analysis of disease-associated protein alterations in astrocytes.},
}

*Astrocytes/chemistry/metabolism
*Aquaporin 4/analysis/metabolism
Animals
*Excitatory Amino Acid Transporter 2/analysis
Microscopy, Fluorescence/methods
*Single-Cell Analysis/methods
Cells, Cultured
Humans

@article {pmid42648119,
year = {2026},
author = {Wu, D and Kojic, A and Ross, JP and Li, D and Walther, P and Goyal, N and Sampson, J and Wu, JC},
title = {Generation of two iPSC lines from ALS patients harboring C9orf72 hexanucleotide repeat expansions.},
journal = {Stem cell research},
volume = {95},
number = {},
pages = {104085},
doi = {10.1016/j.scr.2026.104085},
pmid = {42648119},
issn = {1876-7753},
abstract = {The GGGGCC hexanucleotide repeat expansion (HRE) within the C9orf72 gene constitutes the leading genetic driver of amyotrophic lateral sclerosis (ALS). This fatal neurodegenerative disorder is characterized by the systematic loss of both the upper and lower motor neurons across both the central and peripheral nervous systems. This work describes the successful reprogramming of two human induced pluripotent stem cell (iPSC) lines originating from two independent ALS patients, both of whom carry a C9orf72 HRE mutation. Validation of the two established iPSC lines confirmed the expression of pluripotency markers, normal karyotypes, and successful trilineage differentiation. Consequently, these lines provide a robust in vitro platform to model ALS and study C9orf72-mediated disease mechanisms.},
}

@article {pmid42648633,
year = {2026},
author = {Akamatsu, H and Kodama, Y and Terai, A and Imamura, M and Oda, K and Jono, H and Ohyama, K},
title = {Development and validation of machine learning model for selecting the optimal population pharmacokinetic model for vancomycin.},
journal = {Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy},
volume = {},
number = {},
pages = {103058},
doi = {10.1016/j.jiac.2026.103058},
pmid = {42648633},
issn = {1437-7780},
abstract = {INTRODUCTION: Therapeutic drug monitoring (TDM) of vancomycin is recommended based on the area under the concentration-time curve (AUC). The Practical Antimicrobial TDM (PAT) software incorporates two population pharmacokinetic (popPK) models developed by Oda et al. and Yasuhara et al.; however, no objective criteria for model selection have been established. This study aimed to develop and validate a machine learning (ML) model to optimize popPK model selection for initial vancomycin dosing.

METHODS: The primary outcome was comparison of the two models to identify which yielded a lower absolute relative prediction error for AUC in each patient. Thirty-three clinical variables were screened using Lasso regression to select predictors. Six ML algorithms were compared using nested cross-validation. Performance was evaluated using the area under the receiver operating characteristic curve (AUROC), accuracy, sensitivity, specificity, calibration plots, and decision curve analysis (DCA).

RESULTS: Among 531 patients, Oda et al.'s model was more accurate in 60.1% of cases. Lasso selected 22 predictors. Among the algorithms, logistic regression showed the highest mean AUROC (0.720±0.084), whereas the support vector machine demonstrated favorable calibration performance (intercept=0.01, slope=0.97). The multi-layer perceptron achieved the lowest Brier score (0.307). Longer hospitalization, lower C-reactive protein (CRP), and female sex were associated with a high predictive probability of accuracy for Oda et al.'s model. DCA suggested the clinical utility of ML-based model selection.

CONCLUSION: We developed an ML model for selecting between two popPK models for planning vancomycin dosing regimens in PAT. Considering length of hospital stay, CRP levels, and sex may aid accurate popPK model selection.},
}

@article {pmid42649099,
year = {2026},
author = {, and Kassardjian, CD and Desai, U and Živković, SA and Simmons, Z and Narayanaswami, P},
title = {It's Virtually Here: Telemedicine, Virtual Care, and Neuromuscular Disease.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70382},
pmid = {42649099},
issn = {1097-4598},
abstract = {The COVID-19 pandemic forced a partial shift in neuromuscular clinical practice away from in-person care to remote means. However, this shift was unexpected, abrupt, reactive to the emergency of a pandemic, and disruptive to the usual manner of care, without adequate time to adapt or study the optimal manner to provide care remotely. While traditionally associated with hub-and-spoke telemedicine models, the pandemic popularized direct-to-home virtual care, mostly unsupported by on-site examiners or standardized platforms. In chronic neuromuscular disorders such as amyotrophic lateral sclerosis (ALS) and myasthenia gravis (MG), virtual care has demonstrated feasibility, patient satisfaction, and potential cost savings, particularly for geographically or functionally disadvantaged populations. Disease-specific adaptations such as the Myasthenia Gravis Core Exam and wearable-based assessments (e.g., home spirometry, grip strength monitoring, and digital outcome measures) have enabled more structured remote evaluations. However, diagnostic accuracy may be compromised by the inability to perform detailed neurological examinations or electrodiagnostic studies. Equity concerns persist due to variability in digital literacy, internet and digital device access, and socioeconomic status. Post-pandemic, patients with disabilities may continue to benefit in a combined virtual/in-person paradigm of care. More evidence is required to evaluate the impact of virtual care on neuromuscular practice quality of care and outcomes. We outline some of the questions that require further study, hoping to spur research and quality improvement investigations of these new care models.},
}

@article {pmid42649384,
year = {2026},
author = {Guo, H and Savard, A and Manser, C and Dutta, K and Taylor, JA and Rousseaux, MWC and Pozzi, S and Julien, JP and Baird, S and Gibbings, D},
title = {Engineered autophagy receptors administered with extracellular vesicles eliminate pathological Tau and TDP-43.},
journal = {Nature biomedical engineering},
volume = {},
number = {},
pages = {},
pmid = {42649384},
issn = {2157-846X},
support = {183767//Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)/ ; TR180076//Weston Brain Institute/ ; },
abstract = {In neurodegenerative diseases such as frontotemporal dementia and amyotrophic lateral sclerosis, pathological forms of proteins such as Tau and TDP-43 accumulate within large heterogeneous inclusions inside cells. Current strategies to eliminate such aberrant protein species in patients encounter three main challenges: crossing the blood-brain barrier and plasma membrane, specifically recognizing pathological forms of proteins, and engaging mechanisms to eliminate large entities. Here we fuse LC3A, a central protein in the recruitment of substrates into autophagosomes, to cytoplasm-stable antibodies. These engineered autophagy receptors, targeting Tau or TDP-43, are delivered using small extracellular vesicles and reduce pathology in models, including Tau P301S adult primary mouse neurons, TDP-43[G298S] iPSC-derived motor neurons and after intravenous injection in Tau P301S mice. Similarly, adeno-associated-virus-mediated delivery in TDP-43[ΔNLS] mice enhances clearance of pathological TDP-43. This targeted degradation strategy allows delivery into the brain while capitalizing on the specificity of antibodies and the ability of autophagy to degrade large intracellular entities.},
}

@article {pmid42650212,
year = {2026},
author = {Varrassi, G and Tran, YV and Farì, G and Narvaez Encinas, M and Corriero, A and Puntillo, F and Pham, PV and Leoni, MLG},
title = {The Eye as a Window to Neurodegeneration: Oxidative Stress, Optic Nerve Vulnerability, and Retinal Biomarkers-A Scoping Review.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/antiox15080948},
pmid = {42650212},
issn = {2076-3921},
support = {//Tam Anh General Hospital, Ha Noi/ ; },
abstract = {Neurodegenerative diseases represent a major and growing global health burden characterized by progressive neuronal dysfunction, axonal degeneration, and irreversible neural tissue loss. Increasing evidence identifies oxidative stress as one of several interacting pathogenic mechanisms in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and several optic neuropathies. Interest has increasingly focused on the brain-retina axis, as the retina and optic nerve share structural, metabolic, and molecular features with the central nervous system and may provide accessible insights into neurodegeneration. This scoping review mapped current evidence on oxidative stress in neurodegeneration, emphasizing cranial nerve involvement, optic nerve vulnerability, retinal ganglion cell degeneration, visual dysfunction, oxidative biomarkers, and emerging therapeutic strategies. The review followed established methodological frameworks and PRISMA-ScR recommendations; no formal risk-of-bias appraisal was undertaken, consistent with scoping-review methodology. The literature shows that oxidative stress interacts with mitochondrial dysfunction, neuroinflammation, impaired mitophagy, ferroptosis, and altered bioenergetics, contributing to neuronal injury in cerebral and retinal disorders. Retinal ganglion cells appear particularly vulnerable because of their high metabolic demands and reliance on oxidative phosphorylation. Glaucoma and other optic neuropathies share molecular signatures with central neurodegenerative diseases. Retinal imaging and oxidative biomarkers show promise for diagnosis, monitoring, and stratification. The evidence base is nonetheless dominated by preclinical work; biomarker performance is inconsistent across matrices and assay platforms and most antioxidant clinical trials have been negative. Oxidative stress is therefore best regarded as one interacting node of a broader pathogenic network rather than a universal or predominant driver and the brain-retina continuum as a mechanistically plausible but not yet clinically validated framework for biomarker-guided neuroprotection.},
}

@article {pmid42650794,
year = {2026},
author = {Mitsumoto, H and Blasco, H and Corcia, P and Silani, V},
title = {ALS: An Organism-Wide Bioenergetic Failure Due to Mitochondrial Dysfunctions?.},
journal = {Biomolecules},
volume = {16},
number = {8},
pages = {},
doi = {10.3390/biom16081126},
pmid = {42650794},
issn = {2218-273X},
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; Humans ; *Mitochondria/metabolism/pathology ; *Energy Metabolism ; Animals ; Oxidative Stress ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating and invariably fatal disease for which currently available disease-modifying therapies provide only modest benefit. Defining its underlying pathogenesis is therefore essential for the development of effective treatments. Increasing evidence indicates that ALS is not restricted to motor neurons but involves multiple neuronal and glial systems, extending to peripheral organs, often at subclinical levels. These multisystem alterations may precede overt neurological symptoms by years and are accompanied by metabolic disturbances, including progressive weight loss and hypermetabolism. In peripheral tissues, ongoing cellular turnover and associated immune and inflammatory responses may further increase energy demand. Within this framework, mitochondrial dysfunction emerges as a central mechanism underlying impaired bioenergetics and systemic metabolic failure. Mitochondria not only regulate energy production but also contribute to oxidative stress, which in turn exacerbates mitochondrial injury, creating a self-amplifying cycle. Importantly, many genetic forms of familial ALS directly affect mitochondrial pathways, and similar biochemical abnormalities are observed in sporadic ALS. These shared features suggest that mitochondrial dysfunction represents a common pathway across ALS subtypes. Targeting upstream mechanisms of mitochondrial impairment may therefore provide a unifying strategy for understanding ALS pathogenesis and developing effective therapies.},
}

*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics
Humans
*Mitochondria/metabolism/pathology
*Energy Metabolism
Animals
Oxidative Stress

@article {pmid42650874,
year = {2026},
author = {Wang, Z and Fu, Y and Li, S and Zhang, Y and Sun, T and Miao, N},
title = {The Prospective Regulatory Functions of lncRNAs and Their ceRNA Networks in the Development of Motor Neurons and Associated Diseases.},
journal = {Biomolecules},
volume = {16},
number = {8},
pages = {},
doi = {10.3390/biom16081208},
pmid = {42650874},
issn = {2218-273X},
mesh = {Humans ; *RNA, Long Noncoding/genetics/metabolism ; *Motor Neurons/metabolism/pathology ; RNA, Competitive Endogenous ; Animals ; *Gene Regulatory Networks ; *Motor Neuron Disease/genetics/pathology/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *Muscular Atrophy, Spinal/genetics/pathology/metabolism ; },
abstract = {Motor neurons form a highly specialized network composed of α-, β-, and γ-subtypes that coordinate skeletal muscle activity. Motor neuron diseases (MNDs), including amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), are characterized by the progressive degeneration of this network, resulting in motor dysfunction. Emerging evidence underscores the significant roles of long non-coding RNAs (lncRNAs) in motor neuron development and disease. However, only a few have been experimentally confirmed as true ceRNA regulators, highlighting the need to differentiate validated mechanisms from mere associations or predictions. This review summarizes the regulatory roles of lncRNA-associated ceRNA networks in motor neuron development, evaluates the evidence for their involvement in MNDs, and explores their potential impact on disease progression. It also addresses current challenges, knowledge gaps, and future research directions for understanding ceRNA-mediated mechanisms and developing therapeutic strategies for MNDs.},
}

Humans
*RNA, Long Noncoding/genetics/metabolism
*Motor Neurons/metabolism/pathology
RNA, Competitive Endogenous
Animals
*Gene Regulatory Networks
*Motor Neuron Disease/genetics/pathology/metabolism
*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism
*Muscular Atrophy, Spinal/genetics/pathology/metabolism

@article {pmid42651103,
year = {2026},
author = {Costa, IM and Kanashiro, A and Barros, GSF and Monteiro, AJ and Bonilha, CS and Galdino, G and Veras, FP},
title = {Targeting Neutrophil Extracellular Traps in Neuroinflammation: A Therapeutic Perspective on Neurodegenerative Diseases.},
journal = {Brain sciences},
volume = {16},
number = {8},
pages = {},
doi = {10.3390/brainsci16080792},
pmid = {42651103},
issn = {2076-3425},
abstract = {Neuroinflammation is a complex process involved in the pathogenesis of several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington's disease, and amyotrophic lateral sclerosis. Neutrophils, although traditionally considered peripheral immune cells, have emerged as active participants in the immunopathology of the central nervous system (CNS) through the release of neutrophil extracellular traps (NETs), structures composed of decondensed chromatin embedded with pro-inflammatory proteins. Evidence suggests that NETs play a dual role: they are protective against pathogens but can also induce tissue damage when produced in excess. Several pathways are involved in their formation, including vesicle-mediated release (vital NETs), the lytic NADPH oxidase (NOX)-dependent pathway, and the mitochondrial pathway. Targeting NETs therapeutically, through the use of NETosis inhibitors, NET-degrading strategies, or blockade of neutrophil migration, has shown promise in reducing neuroinflammation/neurodegeneration and improving neurological outcomes in experimental models. This review aims to investigate both the protective and deleterious roles of NETs and how this knowledge may reveal new therapeutic strategies to modulate neurodegenerative diseases and preserve neural integrity, offering valuable insights for potential applications in clinical practice.},
}

@article {pmid42651138,
year = {2026},
author = {Lu, S and Chen, Z and Wang, Y and Bian, H and Yu, S and Huang, L},
title = {Brain O-GlcNAcylation in Neurodegenerative Diseases: Context-Dependent Mechanisms and Precision Therapeutic Translation.},
journal = {Brain sciences},
volume = {16},
number = {8},
pages = {},
doi = {10.3390/brainsci16080828},
pmid = {42651138},
issn = {2076-3425},
support = {LH2019H106//Natural Science Foundation of Heilongjiang Province/ ; YQJH2023152//Excellent Young Teachers Basic Research Support Program" for Provincial Undergraduate Colleges in Heilongjiang Province/ ; ZHY2025-009//Heilongjiang Province Traditional Chinese Medicine Research Project/ ; },
abstract = {O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) is a dynamic, nutrient-sensitive post-translational modification that couples hexosamine biosynthesis pathway flux to protein function in neurons and glia. This reversible cycling, catalyzed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), integrates glucose, glutamine, acetyl-CoA, and nucleotide metabolism with synaptic activity, mitochondrial adaptation, transcriptional regulation, proteostasis, and neuroimmune signaling. Dysregulated O-GlcNAc cycling has been implicated in major neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Huntington's disease (HD), through effects on disease-related proteins, autophagy, mitochondrial function, and inflammatory networks. However, available evidence does not support a universal model in which global O-GlcNAc elevation is uniformly protective or global reduction is uniformly pathogenic. In this mechanistic narrative review, we integrate disease-specific and substrate-focused findings while distinguishing relatively mature translational evidence from model-based or hypothesis-generating observations. We propose a state-resolved framework in which disease-relevant O-GlcNAc states are interpreted across biological contexts, substrate/site specificity, and intervention dynamics. This framework helps reconcile divergent findings across experimental systems and highlights the limitations of indiscriminate global pathway modulation. Although OGA inhibitors represent the most advanced therapeutic strategy, their broad substrate effects underscore the need for pharmacodynamic biomarkers, human validation, brain-targeted delivery, and state-resolved approaches. Moving from bulk O-GlcNAc measurements toward precise correction of disease-relevant O-GlcNAc states across defined biological contexts will be essential for translating this biology into clinically meaningful interventions.},
}

@article {pmid41387577,
year = {2026},
author = {Major, AJ and Abdaltawab, A and Phillips, JM and Wang, T and Lee, EK and Lichtenfeld, MJ and Chandrasekaran, C and Saalmann, YB and Maier, A and Desimone, R and Miller, EK and Bastos, AM and Mendoza-Halliday, D},
title = {A. J. Major et al. reply.},
journal = {Nature neuroscience},
volume = {29},
number = {2},
pages = {284-286},
pmid = {41387577},
issn = {1546-1726},
support = {R01 MH110311/MH/NIMH NIH HHS/United States ; R01MH110311//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; NS135361//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 1R01MH131715//U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)/ ; R21 NS135361/NS/NINDS NIH HHS/United States ; R01 EY029666/EY/NEI NIH HHS/United States ; NS121409//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R00 NS092972/NS/NINDS NIH HHS/United States ; CAREER 2339210//National Science Foundation (NSF)/ ; P51 OD011106/OD/NIH HHS/United States ; R01 MH131715/MH/NIMH NIH HHS/United States ; R01 NS121409/NS/NINDS NIH HHS/United States ; R00 MH116100/MH/NIMH NIH HHS/United States ; R00NS092972//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; Young Investigator Award//Brain and Behavior Research Foundation (Brain & Behavior Research Foundation)/ ; NS122969//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R00MH116100//U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)/ ; R01 NS122969/NS/NINDS NIH HHS/United States ; },
abstract = {Our study made two contributions: (1) discovery of a ubiquitous cortical motif and (2) a tool derived from it—the Frequency-based Layer Identification Procedure (FLIP and vFLIP). Mackey et al. critique the tool, questioning its advantage over classic current source density (CSD) analysis, and reason backwards to challenge the motif’s ubiquity. In our rebuttal, we confirm the spectrolaminar motif in diverse cortical areas using data from multiple research groups (who joined us in this rebuttal) as well as Mackey et al.’s own dataset. Additionally, we introduce vFLIP2, an improved version of our tool that addresses their comments. It reliably identified and localized the motif in our data and Mackey et al.’s data. Our findings reaffirm the motif’s ubiquity. We value Mackey et al.’s comments, which helped refine our tool.},
}

@article {pmid42635322,
year = {2026},
author = {Palumbo, F and Iazzolino, B and Canosa, A and Manera, U and Vasta, R and Grassano, M and Matteoni, E and Cabras, S and Maccabeo, A and Pellegrino, G and Giai Merlera, F and Dei Giudici, A and Callegaro, S and Balz, L and Moglia, C and Chiò, A and Calvo, A and Lulé, D},
title = {Theory of mind impairment related to C9orf72 repeat expansion in amyotrophic lateral sclerosis: a case-control study.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/21678421.2026.2694499},
pmid = {42635322},
issn = {2167-9223},
abstract = {Objective: To investigate cognitive and affective theory of mind (ToM) in amyotrophic lateral sclerosis (ALS) patients carrying the C9orf72 repeat expansion (C9orf72+), compared with matched non-mutated (C9orf72-) ALS patients and healthy controls (HCs). Methods: We assessed 34 C9orf72+ ALS patients, 34 C9orf72- ALS patients matched for sex, age, education, and cognitive category, and 34 HC matched for sex, age, and education. Participants underwent neuropsychological evaluation, including the Story-Based Empathy Task (SET), assessing cognitive ToM (Intention Attribution, IA), affective ToM (Emotion Attribution, EA), and Causal Inference (CI). Results: C9orf72+ patients showed lower SET-global score than C9orf72- patients (p = 0.028). Compared with HC, C9orf72+ showed lower score in SET-global score and all SET subtests (all p < 0.05). C9orf72+ cognitively normal differed from HC in SET-global score, IA, and EA (all p < 0.038), whereas C9orf72- cognitively normal did not differ from HC. Multiple linear regression analyses indicated that ALS-specific cognitive domains only explained ∼25% of ToM variance, with no association with demographic, clinical, or behavioral variables. Cluster analysis identified three cognitive profiles based on SET performance, with the most impaired cluster showing the highest proportion of C9orf72+ patients (68%). Conclusion: C9orf72-mutated ALS patients showed more pronounced impairment in cognitive and affective ToM than non-mutated ALS patients, independent of demographic, clinical, and cognitive features. These findings, although requiring confirmation on larger samples, suggest that ToM dysfunction may represent a sensitive marker of cognitive involvement in ALS-C9orf72-associated disease, particularly in its affective component.},
}

@article {pmid42635866,
year = {2026},
author = {Chakraborty, S and Manickam, V},
title = {Decoding the Neuroinflammatory Potential of Non-Nutritive Sweeteners Through An Integrative Computational Approach.},
journal = {Neurotoxicity research},
volume = {44},
number = {5},
pages = {},
pmid = {42635866},
issn = {1476-3524},
support = {F.N. 5/9/1328/2020-Nut//Indian Council of Medical Research/ ; SG20250066//VIT University/ ; },
mesh = {Humans ; *Non-Nutritive Sweeteners/adverse effects/metabolism/chemistry ; *Neuroinflammatory Diseases/chemically induced/metabolism/genetics ; Molecular Docking Simulation/methods ; Molecular Dynamics Simulation ; Animals ; },
abstract = {Non-nutritive sweeteners (NNS) are commonly used in the beverage, food, and pharmaceutical industries, however, their possible link to neuroinflammation remains a contentious issue. Hence, to investigate this potential association and identify the molecular pathways involved, targets of the most frequently consumed NNSs, namely sucralose, aspartame, acesulfame, cyclamate, and saccharin, were extracted from the STITCH, Super-PRED, STP, SEA and CTD databases, while neuroinflammatory targets were extracted from GeneCards, OMIM, and NCBI databases. A total of 124 targets were obtained by overlapping NNS and neuroinflammatory targets, of which 20 key targets, including CASP3, PPARγ, MTOR, and MMP9, were identified for further analysis. KEGG enrichment analysis suggested a significant association of these targets with pathways related to Alzheimer's disease and neuroactive ligand-receptor interaction. Gene Ontology analysis revealed enrichment in biological processes associated with inflammatory response and reactive oxygen species. The associated cellular components were primarily localised in the axon, dendrite, and synaptic membrane. Molecular docking followed by molecular dynamics simulations was performed to evaluate the stability of the NNS-key target complexes, revealing favourable binding affinities and stable interaction profiles. Gene expression analysis of these key targets predicted their differential regulation across four majorly recognised neuroinflammatory disorders, including Alzheimer's disease, multiple sclerosis, Parkinson's disease, and amyotrophic lateral sclerosis, with a significant up or downregulation of these key targets. Results of this study suggest that NNS may be associated with neuroinflammatory processes through these key targets and identified pathways, highlighting the need for improving the standards in food safety.},
}

Humans
*Non-Nutritive Sweeteners/adverse effects/metabolism/chemistry
*Neuroinflammatory Diseases/chemically induced/metabolism/genetics
Molecular Docking Simulation/methods
Molecular Dynamics Simulation
Animals

@article {pmid42636000,
year = {2026},
author = {Benatar, M and Barmada, S and Jicha, GA and Lagier-Tourenne, C and Gregory, J and Al-Chalabi, A and Boeve, BF and Jack, CR and Seeley, WW and Maragakis, NJ and Wuu, J and Zeier, Z and Onyike, C and Lewcock, J and Hovinga, C and Jafar-Nejad, P and Uspenskaya, O and Simmons, A and Browne, SE and Rohrer, J and Petrucelli, L and Shapiro, J and Scharper, D and Boxer, A and Ostrow, LW and Staffaroni, AM and Dacks, P and Turner, MR and Dave, KD and de Majo, M and Mitic, L and Fradette, S and Budd Haeberlein, S and Simuni, T and Dunn, B and McMillan, CT and Lee, EB},
title = {TDP-43-Associated Neurodegenerative Disease Conceptualization and Integrated Staging: A Review.},
journal = {JAMA neurology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaneurol.2026.2812},
pmid = {42636000},
issn = {2168-6157},
abstract = {IMPORTANCE: Classifying disease based on underlying pathobiology rather than clinical phenotype has implications for the development of biomarkers and therapy development.

OBSERVATIONS: Transactive response DNA-binding protein 43 kDa (TDP-43) pathology is observed across a range of clinically defined neurodegenerative disorders including limbic predominant age-related encephalopathy (LATE), most cases of amyotrophic lateral sclerosis (ALS), inclusion body myositis, multisystem proteinopathy, and approximately half the cases of frontotemporal dementia (FTD). Despite this shared biology, the current nosology for these neurodegenerative disorders is based on their distinct clinical phenotypes. An alternative approach recognizes the central role of TDP-43 pathology in disease pathogenesis, reserving the use of clinical terms like ALS, FTD, or LATE to describe phenotypic manifestations of underlying pathobiology. This approach also recognizes the converging biomarker and neuropathological data indicating that pathology begins presymptomatically, before the overt clinical manifestations of disease appear.

CONCLUSIONS AND RELEVANCE: In proposing a pathobiological definition of disease, the goal is to provide a road map for developing biomarkers that accurately reflect the underlying pathobiology of disease and for advancing therapeutic candidates that effectively target fundamental disease mechanisms.},
}

@article {pmid42636496,
year = {2026},
author = {Jonsdottir, G and Vilhjalmsson, R and Sigurdardottir, V and Hjaltason, H and Klinke, ME and Jonsdottir, H},
title = {End-of-Life Care in an Acute Neurological Ward: A Retrospective Analysis of Clinical Practices During the Last Week of Life.},
journal = {The Journal of neuroscience nursing : journal of the American Association of Neuroscience Nurses},
volume = {},
number = {},
pages = {},
doi = {10.1097/JNN.0000000000000906},
pmid = {42636496},
issn = {1945-2810},
support = {//Icelandic Nurses Association, University of Iceland Research Fund of Ingibjorg R. Magnusdottir, Landspitali, National University Hospital of Iceland/ ; },
abstract = {BACKGROUND: The care of patients with neurological diseases near the end of life (EOL) is challenging and often complicated by prognostic uncertainty. Difficulty recognizing the terminal phase may delay transitions to EOL care, leading to continued use of diagnostic procedures and medical interventions with a limited focus on comfort.

METHODS: This retrospective observational study included medical records of 209 deceased patients with neurological diseases who died in an acute hospital ward. Diagnostic procedures and medical and supportive interventions delivered during the final 7 days of life were extracted. Patients were categorized into 2 groups: acute neurological diseases (ischemic stroke and hemorrhagic stroke) and progressive neurological diseases (Parkinson disease or extrapyramidal and movement disorders, and amyotrophic lateral sclerosis). Frequencies of interventions were compared between diagnostic groups and according to documented EOL decision status.

RESULTS: In both groups, documented EOL decisions were associated with reduced use of diagnostic procedures and increased use of support measures. Medication administration and supportive care patterns differed between the acute and progressive disease groups and were related to documented EOL decisions. The most frequently administered interventions were oral suctioning (97%), intravenous fluids (70%), antibiotics (45%), pain relief medications (98%), and benzodiazepines (93%). Patients with progressive neurological diseases received more respiratory support interventions than those with acute neurological diseases.

CONCLUSIONS: Our findings suggest that documenting EOL decisions was related to comfort-focused care, although the frequency varied by disease group. Neurological disease-specific EOL guidelines should be implemented to identify the terminal phase in alignment with the goals of comfort-focused care in a timely manner.},
}

@article {pmid42636890,
year = {2026},
author = {Guha, L and Malik, JA and Bose, B},
title = {Living drug carriers: Microbial and bioengineered platforms redefining precision therapeutic and immunomodulatory delivery.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {},
number = {},
pages = {115274},
doi = {10.1016/j.jconrel.2026.115274},
pmid = {42636890},
issn = {1873-4995},
abstract = {Microbial living therapeutics are a new class of drug-delivery materials that combine synthetic biology, immunomodulation, and advanced formulations to achieve controllable therapeutic effects in space and time. In the broad field of living drug-delivery systems, therapeutic platforms include engineered microorganisms, mammalian immune cells, stem cells, viral vectors, extracellular-vesicle-producing cells, and hybrid bioengineered living materials. This review focuses on engineered microbial living drug carriers, including genetically modified bacteria and probiotic platforms, because these systems uniquely integrate programmable biosensing, in situ therapeutic synthesis, adaptive immunomodulation, and controllable drug delivery within a single living chassis. Designed microbes and consortia possess other unique functions, such as microenvironment sensing, programmed control of gene expression, and long-lasting in situ manufacturing of therapeutic payloads not available with small-molecule or biologic drugs. Recent progress in microbial chassis engineering, genetic circuit design, and biocontainment has enabled fine-tuning of immune responses, metabolic pathways, and tissue-specific signaling in a wide range of diseases from cancer to autoimmune and inflammatory diseases, to metabolic and endocrine disorders, neuro-immunological conditions (e.g., amyotrophic lateral sclerosis), infectious diseases including infectious threats without existing approved vaccines (Zika virus) as well as rare genetic disorders. Advances in formulation science, including encapsulation technologies, biomaterial-microbe hybrids, and stimuli-responsive release platforms, have enabled overcoming key translation challenges concerning microbial viability, biodistribution, safety, and controlled activation in complex physiological milieus like the gut (for enteric pathogens), tumor microenvironment (for oncolytic organisms), or injured tissues (for tissue-targeting organisms). Increasing numbers of clinical-stage LBP studies are now conducted under good manufacturing practice, standardized QC, and clinical conditions, ranging from emerging PK, biodistribution, and biomarker-driven studies to those adapted to living entities. The addition of host microbiome profiling, multi-omics analysis, and computational modeling is anticipated to increase therapeutic predictability and patient stratification. Taken together, these advances position live microbial therapeutics as programmable biological medicines with the potential for adaptive, context-specific administration and warrant further clinical development and increased integration within precision medicine-informed therapeutic approaches.},
}

@article {pmid42637046,
year = {2026},
author = {Lauck, KC and Ahmed, A and Tolkachjov, SN},
title = {Response to Jean et al's "Alopecia after glucagon-like peptide-1 agonist therapy: A TriNetX Database active comparator retrospective cohort study".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.08.074},
pmid = {42637046},
issn = {1097-6787},
}

@article {pmid42637106,
year = {2026},
author = {Heinsinger, N and Wang, Y and Grauer, S and Zhang, Z and Wong, J and Simov, V and Bukhtiyarova, M and Ai, X and Parish, C and Klein, RM and Uslaner, J and Smith, S and Tian, Y},
title = {Splicing modulation of ATXN2 as a therapeutic strategy to regulate Ataxin-2 protein levels in ALS.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107582},
doi = {10.1016/j.nbd.2026.107582},
pmid = {42637106},
issn = {1095-953X},
abstract = {ATXN2 is associated with an increased risk of Amyotrophic Lateral Sclerosis (ALS), while down-regulation of ATXN2 has been shown to mitigate TDP-43 proteinopathy in ALS models. In this study, we demonstrated that Ataxin-2 protein levels were upregulated in rNLS8 mice following doxycycline withdrawal, which coincided with TDP-43 overexpression, phosphorylation, and aggregation. To reduce Ataxin-2 protein levels, we explored the approach of splicing modulation at the RNA level. Through bioinformatical analysis, we identified an alternative 5' splicing site of ATXN2 in intron 8. This alternative splicing results in an additional 47 base pairs at the 3' end after Exon 8. The insertion of the extra nucleotides causes a frameshift that leads to reduced mRNA production and, consequently, protein levels. Following the discovery of this alternative splicing site, we conducted an antisense oligonucleotide (ASO) micro-walk to screen ASOs targeting this region. We identified ASOs that specifically modulate this splicing, including those that either enhance or inhibit alternative splicing. We validated that the ASOs that promote alternative splicing and reduce constitutive splicing can lower Ataxin-2 protein levels, which in turn decreases TDP-43 aggregation and stress granule formation in a cell-based model of TDP-43 toxicity. Furthermore, we confirmed that reducing Ataxin-2 levels via previously validated ASO delivery ameliorated TDP-43 pathology in rNLS8 mice. The discovery of ATXN2 alternative splicing, along with the confirmation of splicing modulation using ASOs in human cell-based assays, provides evidence for a proof-of-principle strategy to modulate Ataxin-2 protein levels for the treatment of ALS.},
}

@article {pmid42637886,
year = {2026},
author = {Rashed, AM and El-Sayed, IET and Lu, X and Abdel-Bary, HM and Fouad, MK and Tony, MA},
title = {Re-engineering alum sludge using choline-glycine ionic liquid for enhanced dewatering and dye adsorption in wastewater treatment.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {42637886},
issn = {2045-2322},
abstract = {Large quantities of by-product alum sludge (Al-S) generated from drinking water treatment plants pose significant environmental and disposal challenges due to their high water content and large volume. This study aims to develop a sustainable conditioning and valorization strategy for Al-S using a choline-glycine ionic liquid ([Ch]-[AA]). The ionic liquid was synthesized and applied as a sludge conditioner to enhance dewatering performance. Under optimized conditions, the dewatering efficiency reached 47%, accompanied by a notable zeta potential shift, indicating partial charge neutralization and improved floc structure. To enable sludge valorization, the conditioned sludge was reused as an adsorbent, either directly or after thermal treatment. The modified materials exhibited high adsorption capacities toward Synozol KHL dyes, reaching 43.6 and 90.1 mg g[-][1] for Red and Blue dyes, respectively. Adsorption behavior was well described by the Langmuir isotherm and pseudo-second-order kinetic model. Thermodynamic analysis indicated an exothermic adsorption process, with spontaneity dependent on operating conditions. Overall, the results demonstrate an effective waste-to-resource approach in which enhanced dewatering facilitates the conversion of alum sludge into a functional adsorbent for wastewater treatment, supporting sustainable sludge management.},
}

@article {pmid42638006,
year = {2026},
author = {Sreekanth, D and Singh, C and Pawar, DV and Yadav, MK and Sahadeo, IK and Basavaraj, PS and Kumar, R and Mahesh, S},
title = {CRISPR/Cas-Mediated Genome Editing for Developing Herbicide Tolerant Rice: A Step-by-Step Protocol.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {3017},
number = {},
pages = {47-57},
pmid = {42638006},
issn = {1940-6029},
mesh = {*Oryza/genetics/drug effects/growth & development ; *CRISPR-Cas Systems ; *Gene Editing/methods ; *Herbicides/pharmacology ; *Herbicide Resistance/genetics ; Acetolactate Synthase/genetics ; Plants, Genetically Modified/genetics ; Benzoates ; Pyrimidines ; },
abstract = {Weed management in rice cultivation has predominantly relied on acetolactate synthase (ALS) and acetyl-CoA carboxylase (ACCase) inhibiting herbicides, particularly against Echinochloa spp. (watergrass). However, these herbicides carry a high risk of resistance evolution, as evidenced by the numerous resistant biotypes reported worldwide. The emergence of herbicide resistance necessitates innovative and sustainable weed control strategies. Genome editing, particularly through the CRISPR/Cas system, provides a precise and efficient platform for introducing targeted genetic modifications to develop herbicide-tolerant (HT) rice cultivars. In this protocol, we present a step-by-step approach for generating bispyribac sodium-tolerant rice using the CRISPR/Cas-mediated editing of the ALS gene. The method encompasses guide RNA design, vector construction, transformation, selection of edited plants, and molecular confirmation of targeted mutations. This approach offers a robust framework for producing HT rice lines, potentially reducing reliance on conventional herbicide regimes and mitigating the risk of resistance development in weed populations.},
}

*Oryza/genetics/drug effects/growth & development
*CRISPR-Cas Systems
*Gene Editing/methods
*Herbicides/pharmacology
*Herbicide Resistance/genetics
Acetolactate Synthase/genetics
Plants, Genetically Modified/genetics
Benzoates
Pyrimidines

@article {pmid42638120,
year = {2026},
author = {Tang, L and Fan, D},
title = {Bridging the gap: neuroinflammation and the dawn of precision medicine in amyotrophic lateral sclerosis.},
journal = {Translational neurodegeneration},
volume = {15},
number = {1},
pages = {},
pmid = {42638120},
issn = {2047-9158},
support = {CX25YZ13//the Chinese Institutes for Medical Research, Beijing/ ; 2022YFA1303003//National Key Research and Development Program of China/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/immunology/therapy ; *Precision Medicine/methods/trends ; *Neuroinflammatory Diseases/immunology/therapy ; Animals ; Immunotherapy/methods ; },
abstract = {Neuroinflammation is no longer a secondary feature of amyotrophic lateral sclerosis (ALS), but rather a disease-modifying process that actively shapes the motor neuron vulnerability from the earliest stages of pathology. Central and peripheral immune cells, including microglia, astrocytes, and infiltrating T lymphocytes, adopt context-dependent states that can be neuroprotective or neurotoxic depending on disease stage and genetic background. These states are driven by discrete molecular programs, such as cGAS-STING-mediated innate immune sensing, NLRP3 inflammasome activation, and RIPK1-dependent necroptotic signaling, which represent tractable therapeutic targets. The repeated failure of broad-spectrum immunosuppressive trials reflects a fundamental mismatch between the non-selective interventions and the mechanistically distinct immune states of diseases. Converging transcriptomic, genetic, and immunophenotypic evidence supports the existence of putative neuroimmune endotypes in ALS, though this framework remains a working hypothesis pending prospective validation in biomarker-stratified cohorts. Advances in the following three domains are needed for realizing precision immunotherapy: standardized biomarker panels (including cerebrospinal fluid chitinases and TSPO-PET) to stratify patients by inflammatory subtype; pharmacodynamic readouts to confirm target engagement before interpreting clinical outcomes; and adaptive platform trial designs capable of evaluating mechanism-matching interventions in defined subgroups. This review integrates ALS-associated neuroinflammation with emerging precision medicine strategies, arguing that the central translational question is no longer whether or not to target neuroinflammation, but how, when, and in whom neuroinflammation should be targeted.},
}

Humans
*Amyotrophic Lateral Sclerosis/immunology/therapy
*Precision Medicine/methods/trends
*Neuroinflammatory Diseases/immunology/therapy
Animals
Immunotherapy/methods

@article {pmid42638122,
year = {2026},
author = {Zhang, Y and Liu, Y and Shi, S and Li, Q and Huo, Y and You, P and Shu, M and Cheng, X and Zhang, J and Liang, D and Zhang, A and Lu, C and Shen, B and Zhou, J and Niu, Q},
title = {JP1 peptide modulates oxidative stress and autophagy via Keap1-Nrf2-ARE in ALS model mice.},
journal = {BMC medicine},
volume = {24},
number = {1},
pages = {},
pmid = {42638122},
issn = {1741-7015},
support = {82071434//the National Natural Science Foundation of China/ ; DL202410//the clinical Research Disease Project of Jiangsu Provincial People's Hospital/ ; LC202404//Jiangsu Provincial People's Hospital-Zero magnetic Medicine Special Project/ ; JSPH-MA-2023-5//Jiangsu Province Hospital Clinical Capacity Enhancement Project/ ; },
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; *Oxidative Stress/drug effects ; *NF-E2-Related Factor 2/metabolism ; *Autophagy/drug effects ; *Kelch-Like ECH-Associated Protein 1/metabolism ; Disease Models, Animal ; Mice ; Mice, Transgenic ; Antioxidant Response Elements ; Signal Transduction/drug effects ; *Oligopeptides/pharmacology ; Male ; Humans ; Spinal Cord/metabolism ; },
abstract = {BACKGROUND: The simultaneous modulation of oxidative stress and autophagy represents a potential therapeutic strategy for amyotrophic lateral sclerosis (ALS), yet agents capable of coordinately regulating both processes remain scarce. The Keap1‑Nrf2‑ARE pathway serves as a critical hub linking redox homeostasis and autophagic regulation, making it an attractive target for ALS intervention. JWA is a stress‑responsive protein involved in cellular protection against oxidative injury, and its neuroprotective effects have been shown to depend on activation of the MEK/ERK‑Nrf2 axis. JP1 is a functional oligopeptide derived from the JWA protein that has been engineered to cross the blood-brain barrier and specifically target integrin αVβ3. Based on the link between JWA and Nrf2 signaling, we hypothesized that JP1 activates the Keap1‑Nrf2‑ARE pathway to coordinate antioxidant defense and autophagic clearance. Here, we evaluated this hypothesis in the SOD1‑G93A mouse model, a well‑established transgenic model of familial ALS, and elucidated the underlying mechanisms.

METHODS: We evaluated the efficacy of JP1 in the SOD1-G93A mice model using behavioral phenotyping and survival analysis. The coordinated mechanism was investigated in spinal cord tissues by profiling the Keap1-Nrf2-ARE pathway and oxidative stress, quantifying autophagic flux (by Western blotting and transmission electron microscopy) and neuronal apoptosis, and evaluating histology (by Nissl staining and immunofluorescence). Integrated transcriptomic and proteomic analyses further elucidated the global molecular landscape underlying the therapeutic effects of JP1.

RESULTS: JP1 treatment ameliorated motor deficits and extended survival in SOD1-G93A mice without adversely affecting liver or kidney function. JP1 crossed the blood-brain barrier, targeted motor neurons expressing integrin αVβ3, and activated the ERK pathway. This promoted Keap1/Cul3 degradation and Nrf2 nuclear translocation, thereby activating the Keap1-Nrf2-ARE pathway to alleviate oxidative stress. Concurrently, JP1 restored autophagic flux, increased autophagic activity, attenuated motor neuron injury, suppressed neuronal apoptosis, and preserved neuronal structural integrity. The Nrf2 inhibitor ML385 reversed the protective effects of JP1 on survival, motor function, autophagy, oxidative stress, and neuronal apoptosis, which confirms that JP1 acts via the Nrf2 pathway.

CONCLUSIONS: JP1 acts as a promising coordinator of antioxidant and autophagic processes by targeting the Keap1-Nrf2-ARE pathway, thus highlighting its therapeutic potential for ALS.},
}

Animals
*Amyotrophic Lateral Sclerosis/drug therapy/metabolism
*Oxidative Stress/drug effects
*NF-E2-Related Factor 2/metabolism
*Autophagy/drug effects
*Kelch-Like ECH-Associated Protein 1/metabolism
Disease Models, Animal
Mice
Mice, Transgenic
Antioxidant Response Elements
Signal Transduction/drug effects
*Oligopeptides/pharmacology
Male
Humans
Spinal Cord/metabolism

@article {pmid42638891,
year = {2026},
author = {Wollmann, L and Wolf, A and Cooke, L and Santana, M},
title = {The patient as teacher: a four-phase blueprint for institutional change.},
journal = {Frontiers in health services},
volume = {6},
number = {},
pages = {1920768},
pmid = {42638891},
issn = {2813-0146},
abstract = {INTRODUCTION: Over recent decades, patient involvement in medical education has shifted from passive case demonstrations toward active partnerships in teaching, assessment, and curriculum design, a transition that must recognize patients and relatives as persons with experiential knowledge, not merely as educational instruments. This perspective article argues that accumulated evidence now justifies a deliberate shift from scattered, champion-driven initiatives to embedded institutional strategy.

EVIDENCE AND GAPS: The evidence supports meaningful benefits across stakeholders: learners develop stronger clinical reasoning, communication skills, and empathy; patient educators report empowerment and enhanced self-esteem; and institutions advance their social accountability mission. However, the field continues to struggle with inconsistent terminology, fragmented implementation, short-term satisfaction-based outcomes, underexplored ethical considerations, and weak institutional commitment.

PROPOSED ROADMAP: To address these gaps, we propose a four-phase implementation roadmap. Phase 1 (Institutional Diagnosis) maps current practices against Towle et al.'s six-level taxonomy and establishes an institutional position statement. Phase 2 (Role Definition and Phased Goal-Setting) advocates stepwise progression, typically starting at Levels 3-4, where patients share experiences or act as trained teachers, advancing toward full curriculum governance partnership. Phase 3 (Implementation Planning and Capacity Building) addresses curriculum integration, resource allocation, faculty development, and community partnerships. Phase 4 (Outcomes Monitoring and Evaluation) calls for multilevel, longitudinal evaluation frameworks, including systematic assessment of patient educators' experiences.

DISCUSSION: We present this roadmap as an evidence-informed conceptual synthesis whose implementation depends on continued institutional commitment. Cross-cutting principles include incrementalism, sustained institutional commitment, patient co-production, representative recruitment, and rigorous longitudinal research.},
}

@article {pmid42639115,
year = {2026},
author = {Harbert, DH},
title = {EIF2S1-PELO co-expression architecture in human brain: pairing-family decomposition reveals constitutive transcriptional coupling and functional layer separation.},
journal = {Frontiers in molecular neuroscience},
volume = {19},
number = {},
pages = {1817096},
pmid = {42639115},
issn = {1662-5099},
abstract = {EIF2S1 (eIF2α, translation initiation surveillance) and PELO (Pelota, ribosome rescue) operate within established ribosome-associated quality control and translation-initiation surveillance pathways. Direct cross-talk between these systems is mediated through ZAK/GCN-mediated eIF2α phosphorylation under ribosome-stall stress. At the transcriptional layer, however, EIF2S1-PELO co-regulation has not been quantitatively characterized. Using pairing-family architectural decomposition on multi-region GTEx co-expression and BA9 prefrontal cortex RNA-seq from Parkinson's disease and control donors (GSE68719, n = 44 controls, n = 29 PD), we find: (1) EIF2S1 and PELO share near-identical genome-wide co-expression architecture (continuous Weighted Jaccard = 0.914) with substantial top-partner overlap (binary Jaccard at top 5% = 0.490), producing a Type 1 dissociation gap of 0.424, significantly smaller than 200 random gene-pair gaps (mean 0.644, z = -2.57, permutation p = 0.015), and the lowest gap in a 21-pair quality-control gene panel; (2) the relationship is approximately linear-monotonic (Type 6 Pearson-Spearman gap ≈ 0.004); (3) cellular functional co-dependency in DepMap CRISPR screens is essentially zero (Jaccard = 0.006, gene-effect Pearson r = -0.07), consistent with layer separation between regulatory architecture and cellular phenotype; (4) in an exploratory single-cohort comparison of PD versus control prefrontal cortex, the dissociation gap was larger in PD (0.536 versus 0.424 in control), but this between-group difference did not reach statistical significance under a group-label permutation test (p = 0.40; bootstrap 95% CI on the difference [-0.14, 0.29]), so we present it as a hypothesis for replication rather than an established effect. These findings characterize EIF2S1-PELO transcriptional co-regulation as a constitutive architectural feature distinct from the ZAK/GCN-mediated direct mechanism. The constitutive coupling replicated in independent Alzheimer's disease and ALS frontal-cortex cohorts and across microarray and RNA-seq platforms; a disease-associated weakening of the coupling was directionally consistent across all three diseases but did not reach statistical significance. We note that co-expression patterns are consistent with shared upstream regulatory programs but do not by themselves establish direct co-regulation; the architectural findings reported here are correlational at the transcriptional layer.},
}

@article {pmid42627134,
year = {2026},
author = {Mahjoubin-Tehran, M and Sahebkar, A},
title = {RNA interference (RNA)-based therapeutics for treating neurodegenerative diseases.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/17582024.2026.2722300},
pmid = {42627134},
issn = {1758-2032},
}

@article {pmid42628519,
year = {2026},
author = {Mohassel, P},
title = {Rethinking ALS through the spatiotemporal vulnerability of the entire motor unit.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2026.08.011},
pmid = {42628519},
issn = {1525-0024},
support = {R01 NS138167/NS/NINDS NIH HHS/United States ; },
}