@article {pmid41987206,
year = {2026},
author = {Zheng, M and Li, M and Liu, S and Guan, R and Liu, X},
title = {RNA-binding proteins: a comprehensive review of multifaceted regulatory mechanisms in neuroinflammation and implications in the pathogenesis of neurological disorders.},
journal = {Journal of neuroinflammation},
volume = {23},
number = {1},
pages = {},
pmid = {41987206},
issn = {1742-2094},
support = {82230063//National Natural Science Foundation of China/ ; },
abstract = {Neuroinflammation stands as a cornerstone pathological hallmark across a spectrum of neurological disorders, drawing intensified scientific scrutiny owing to its profoundly intricate and multi-layered regulatory networks. At the heart of this complexity, RNA-binding proteins (RBPs) emerge as masterful post-transcriptional orchestrators, exerting precise control over a vast array of neuroinflammatory cascades. Mounting evidence underscores that RBPs transcend their classical roles in RNA sensing and innate immune recognition, actively shaping pivotal biological pathways—ranging from inflammatory signal transduction and programmed cell death to metabolic reprogramming, epigenetic remodeling and dynamic crosstalk with non-coding RNAs. Furthermore, the functional versatility of RBPs is amplified by nuanced alterations in their nucleocytoplasmic trafficking, stress granule formation, post-translational modifications, and RNA-binding specificities, all of which intricately fine-tune their regulatory impact within the neuroinflammatory milieu. Strikingly, the cell type-specific actions of RBPs in neurons, microglia, and astrocytes unveil a sophisticated tapestry of molecular specialization, offering transformative insights into their context-dependent functions. Abnormal function of RNA-binding proteins is closely related to neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis. In addition, RNA-binding proteins are involved in various pathological processes, including central nervous system infections, stroke, high-altitude cerebral hypoxia, and traumatic brain injury. This review systematically organizes the multifaceted regulatory mechanisms of RNA-binding proteins in neuroinflammation. It deeply explores their key roles in the occurrence and development of nervous system diseases. The review aims to construct a comprehensive theoretical framework and provide a scientific basis for developing new diagnostic methods and targeted therapeutic strategies.},
}

@article {pmid42203747,
year = {2026},
author = {Esch, T},
title = {What's love got to do with it? The formula for love needs psychological and motivational neurobiological components.},
journal = {The Behavioral and brain sciences},
volume = {49},
number = {},
pages = {e7},
doi = {10.1017/S0140525X25102227},
pmid = {42203747},
issn = {1469-1825},
mesh = {*Love ; Humans ; *Motivation/physiology ; *Brain/physiology ; },
abstract = {Kruglanski et al.'s love model rightly highlights motivation and meaning as core to love, aligning with current research. However, this commentary expands the view, emphasizing love's biological basis in brain systems and evolving different types of motivation. Love fulfills both individual and species-level needs, promoting health, connection, and generativity. True love transcends ego, growing into unconditional, spiritually rich connectedness over time.},
}

*Love
Humans
*Motivation/physiology
*Brain/physiology

@article {pmid42203750,
year = {2026},
author = {Van Dessel, P and Boddez, Y},
title = {Extending the motivational model of love: A Goal-Directed Predictive Processing perspective.},
journal = {The Behavioral and brain sciences},
volume = {49},
number = {},
pages = {e19},
doi = {10.1017/S0140525X25102161},
pmid = {42203750},
issn = {1469-1825},
mesh = {*Love ; Humans ; *Goals ; *Motivation ; *Models, Psychological ; },
abstract = {We extend Kruglanski et al.'s model by embedding it within a Goal-Directed Predictive Processing framework. This perspective conceptualizes romantic love as arising from self-referential inferences tied to personal goals and reveals that love may include merit, appreciation, and significance, but is not defined or limited by them. It also explains love experiences that exceed the scope of the authors' model.},
}

*Love
Humans
*Goals
*Motivation
*Models, Psychological

@article {pmid42203757,
year = {2026},
author = {Lucchi Basili, L and Sacco, PL},
title = {Significance is not enough: The biopsychological foundations of romantic love.},
journal = {The Behavioral and brain sciences},
volume = {49},
number = {},
pages = {e2},
doi = {10.1017/S0140525X25102318},
pmid = {42203757},
issn = {1469-1825},
mesh = {Humans ; *Love ; Female ; Male ; Emotions/physiology ; },
abstract = {Kruglanski et al.'s significance-based model overlooks fundamental biopsychological mechanisms driving romantic love. The Tie-Up Theory reveals how women's subconscious biological compatibility assessments through physical, chemical, and behavioral signals operate independently of conscious significance calculations. Their gender-neutral framework ignores how men's receptive emotional orientation differs from women's active emotional competence. By reducing love to significance enhancement, the model cannot explain irrational attractions, persistent relationships despite low "merit," or gendered dissolution patterns determined by reward cycle breakdowns.},
}

Humans
*Love
Female
Male
Emotions/physiology

@article {pmid42204151,
year = {2026},
author = {Jia, Q and Zhu, L and Li, D and Nan, Z and Hou, J and Zhao, Y and Zhu, G and Ou, K and Guo, M and Dui, H and Liu, X and Yan, XX and Yang, S and Huang, L and Fan, D and Li, S and Li, XJ and Yin, P},
title = {Caspase-4 transgenic mice exhibit cytoplasmic TDP-43 accumulation and age-dependent neuropathology.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-73724-7},
pmid = {42204151},
issn = {2041-1723},
support = {32270564//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {TAR DNA-binding protein (TDP-43) is a multifunctional protein that binds DNA and RNA within the nucleus. In neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS), TDP-43 is mislocalized to the cytoplasm, forming inclusions. Current TDP-43 transgenic mouse models generally fail to exhibit significant cytoplasmic accumulation and loss of nuclear TDP-43, which hampers the investigation of cytoplasmic TDP-43 pathology. We previously discovered that primate-specific caspase-4 (CASP4) can cleave TDP-43, producing truncated fragments that are mislocalized to the cytoplasm. Here we show that a transgenic mouse model that expresses human CASP4 and recapitulates the cytoplasmic mislocalization of endogenous TDP-43 and motor dysfunction in an age-dependent manner. Moreover, CASP4 mice exhibited gene expression changes and neuropathology similar to patients with sporadic ALS. Inhibition of CASP4 by its antisense oligonucleotide ameliorated TDP-43 pathology and subsequent neurotoxicity in CASP4 mice. Thus, CASP4 mice present a valuable animal model for exploring endogenous TDP-43-mediated pathogenesis and therapeutics.},
}

@article {pmid42204279,
year = {2026},
author = {Fowler, M and Carr, JM and Gold, J and Walker, A and Rogers, ML},
title = {Evaluation of triumeq treatment on a TDP-43 mouse model of amyotrophic Lateral sclerosis.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-55433-9},
pmid = {42204279},
issn = {2045-2322},
support = {DIS-202303-00932//FightMND/ ; DIS-202303-00932//FightMND/ ; IG1950//Motor Neurone Disease Research Australia/ ; IG1950//Motor Neurone Disease Research Australia/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterised by the accumulation of TAR DNA Binding Protein (43 kDa; TDP-43) within the cytoplasm of neurons. Endogenous retroviruses (ERVs) have been implicated in ALS pathology and the application of antiretroviral therapy, specifically Triumeq, has been proposed for treatment of ALS. However, evidence to support the actions of Triumeq in ALS is lacking. This study investigates the effects of the antiretroviral treatment Triumeq on ALS disease that occurs through TDP-43 pathology by utilising the doxycycline (Dox)-suppressible rNLS8 TDP-43 expression mouse model. In this model, TDP-43 accumulation in the cytoplasm is induced after removal of Dox. Disease was assessed through measures of body weight, neurological score, motor function, urinary p75[ECD] and inflammatory marker expression. Mice were treated with Triumeq and TDP-43 pathology and inflammatory marker expression examined. Triumeq treatment significantly improved motor function early on in the disease course but did not impact other disease progression markers or disease endpoint. In this TDP-43 ALS mouse model, there was a positive association of TDP-43 mRNA levels with transcription factor ATF4, and inflammatory markers CXCL10 and IRF-1, and Triumeq treatment negated this association. Triumeq treatment transiently and modestly improved motor function and influenced TDP-43 associated inflammatory gene expression in an ALS mouse model. These findings support the potential use of Triumeq in treating TDP-43-associated ALS and supports further investigation to better understand if the beneficial actions of Triumeq are via disruption of TDP-43-driven inflammation in ALS.},
}

@article {pmid42204548,
year = {2026},
author = {Jin, X and Fu, Y and Qiu, T and Li, J and Zhang, H and Chen, Y and Chen, K and Zhang, Y and Wang, J and Yi, X and Palaniyappan, L and Braden, BB},
title = {Putative glymphatic dysfunction links extracellular fluid dysregulation to white matter degeneration and clinical impairment in amyotrophic lateral sclerosis.},
journal = {BMC medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12916-026-04948-z},
pmid = {42204548},
issn = {1741-7015},
support = {No. 2022LNJJ09//Project Program of National Clinical Research Center for Geriatric Disorders/ ; 2024ZZTS0954//Fundamental Research Funds for the Central Universities of Central South University/ ; U22A20377//National Natural Science Foundation of China/ ; No.2024PT5109//Scientific Research Program of FuRong Laboratory/ ; CB-C2022//Santé/ ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron degeneration and prominent extra-motor involvement. Impaired clearance of neurotoxic proteins has led to increasing interest in the brain glymphatic system; however, its in vivo associations with brain microstructure and clinical heterogeneity remain incompletely understood.

METHODS: One hundred forty-six patients with ALS and 149 demographically matched healthy controls (HCs) underwent multimodal MRI and comprehensive clinical assessments. Putative glymphatic function was quantified using diffusion tensor imaging along perivascular space (DTI-ALPS). Extracellular free water fraction (FWF) and free-water-corrected fractional anisotropy (fwcFA) were derived to characterize extracellular fluid and white matter microstructure. Group differences were assessed using vertex-wise and voxel-wise analyses with correction for multiple comparisons. Associations among imaging metrics and clinical measures were evaluated using correlation and serial mediation analyses.

RESULTS: Compared with HCs, patients with ALS exhibited significantly reduced DTI-ALPS index, widespread increases in cortical FWF, bidirectional alterations in white matter FWF, and extensive reductions in fwcFA across major white matter tracts. Reduced DTI-ALPS was associated with changes in extracellular free water and white matter microstructural integrity, whereas FWF and fwcFA measures were associated with functional, cognitive, and emotional outcomes. Mediation analyses identified significant indirect associations between DTI-ALPS and both functional and cognitive measures through a pathway involving cortical FWF, white matter FWF, and fwcFA, although direct associations were not observed.

CONCLUSIONS: These findings provide in vivo evidence that putative glymphatic dysfunction co-occurs with extracellular fluid alterations, white matter microstructural changes, and clinical impairment in ALS. Multi-compartment diffusion imaging may offer complementary markers for characterizing brain microstructure and its clinical relevance in ALS.},
}

@article {pmid42190754,
year = {2026},
author = {Wu, X and Wang, X and Zhang, Z},
title = {Response to Chen et al., "Comments on Wu et al's "The efficacy and adverse reactions of 755 nm picosecond alexandrite laser on the treatment of nevus of Ota at different endpoints".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.05.061},
pmid = {42190754},
issn = {1097-6787},
}

@article {pmid42190894,
year = {2026},
author = {Oriquat, G and Abdulqader, AF and Farid, H and Ashurov, Z and Sottarov, A and Ghafl, NY and Bainsal, N and Singh, R},
title = {From protector to perpetrator: The cGAS-STING pathway at the intersection of neurodegeneration and neuroinflammation.},
journal = {Brain research bulletin},
volume = {241},
number = {},
pages = {111963},
doi = {10.1016/j.brainresbull.2026.111963},
pmid = {42190894},
issn = {1873-2747},
abstract = {The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, a cornerstone of the innate immune system designed to combat pathogens, is now implicated as a critical driver of sterile inflammation in the brain. This review synthesizes compelling evidence that in the aging and diseased central nervous system, endogenous cytosolic DNA, sourced from genomic instability, mitochondrial dysfunction, and activated retrotransposons, hijacks this pathway. Chronic cGAS-STING activation transforms microglia into inflammatory amplifiers, instigates neurotoxic astrocyte programs, and directly compromises neuronal health, creating a self-perpetuating cycle of neuroinflammation. We dissect the cell-type specific consequences within the neurovascular unit and establish the pathway's role in the pathogenesis of ALS/FTD, Alzheimer's, Parkinson's, and Huntington's diseases. Crucially, we evaluate the therapeutic potential of targeting this axis, discussing small-molecule inhibitors, oligonucleotide therapies, and upstream interventions to quell the source of immunogenic DNA. We also explicitly examine contradictory preclinical data, including the retracted PINK1-Parkin-STING report and context-dependent neurovascular findings, to provide a balanced appraisal of STING biology in the CNS. By reconciling its dual protective and pathogenic roles, this review posits cGAS-STING as a pivotal mechanism-based therapeutic node for halting the progression of neurodegenerative disorders.},
}

@article {pmid42191539,
year = {2026},
author = {Pérez-Bonilla, M and Díaz-Borrego, P and Mora-Ortiz, M and Mayordomo-Riera, FJ and Girela-López, E},
title = {Discovering Hidden Vocal Subtypes: An Unsupervised Acoustic-Biomechanical Exploration of Voice Profiles.},
journal = {Journal of voice : official journal of the Voice Foundation},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jvoice.2026.05.002},
pmid = {42191539},
issn = {1873-4588},
abstract = {OBJECTIVE: This study aims to explore latent acoustic-biomechanical patterns of voice production using an unsupervised multivariate approach, and to identify data-driven vocal profiles across individuals with amyotrophic lateral sclerosis (ALS) and nonneurological dysphonia.

METHODS: A cross-sectional sample of 100 individuals, including patients with ALS and individuals with nonneurological dysphonia, was analyzed. Sustained vowel phonation was recorded and characterized using 26 variables, including standard acoustic measures (fundamental frequency -fo-, jitter, shimmer, and harmonics-to-noise ratio (HNR)) and 22 biomechanical parameters. Principal component analysis was applied to investigate relationships among variables and reduce dimensionality. Unsupervised clustering was performed at both the variable level to identify functional groupings and the participant level to derive data-driven voice profiles. Cluster validity was assessed using internal indices. Post hoc statistical comparisons and chi-square tests were used descriptively to characterize between-cluster differences and their relationship with clinical categories.

RESULTS: The first five principal components explained 70.7% of the total variance, revealing structured relationships between acoustic and biomechanical features. Participant level clustering consistently supported a two-profile solution. Fifteen voice parameters differed significantly between profiles after false discovery rate correction, with the largest effects observed for shimmer, HNR, and the biomechanical parameter Pr11, reflecting differences in vocal stability and noise-related characteristics. The identified profiles were not significantly associated with clinical diagnostic categories.

CONCLUSIONS: An unsupervised multimodal analysis of sustained phonation revealed two coherent vocal profiles that transcend traditional diagnostic labels. These data-driven voice phenotypes may capture functional patterns of voice production and support future efforts toward more refined and personalized characterization of voice disorders.},
}

@article {pmid42191846,
year = {2026},
author = {Zhang, J and Tian, M and Niu, T and Li, R and Liu, Q and Liu, M and Zhou, X and Dong, H and Liu, Y},
title = {The role of adiponectin and cytokines in Amyotrophic lateral sclerosis: assessment of disease progression and survival status.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-54291-9},
pmid = {42191846},
issn = {2045-2322},
support = {H2023206055//Key Project of Natural Science Foundation of Hebei Province/ ; 20240391//Scientific Research Foundation of Health Commission of Hebei Province/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disorder. ALS typically progresses rapidly, leading to respiratory failure within 3 to 5 years of symptom onset. Identifying risk factors that influence disease progression and survival is critical for enhancing management strategies. The present study therefore investigated the roles of inflammatory factors and adipokines (especially adiponectin) in the progression and prognosis of ALS. The study included 80 ALS patients, with a follow-up period of 1.5 years. Survival analysis was performed using a Cox regression, with hazard ratios (HR) and 95% confidence intervals (CI) presented via forest plots. Our results indicated that ALS patients in the fast-progressing group exhibited lower levels of adiponectin (p < 0.001) and IL-10 (p < 0.001). The Cox regression and forest plot results suggest the potential of adiponectin (HR = 0.905, 95%CI: 0.866-0.946, p < 0.001), IL-10 (HR = 0.968, 95%CI: 0.951-0.986, p < 0.001), δFS (HR = 1.234, 95%CI: 1.065-1.430, p = 0.005) and ALSFRS-R (HR = 0.820, 95%CI: 0.765-0.878, p < 0.001) as potential risk factors. In addition, these risk factors are significantly associated with poor survival prognosis in high-risk populations (all p < 0.001). This study identifies adiponectin, IL-10, ALSFRS-R, and δFS as key risk factors influencing ALS progression and prognosis.},
}

@article {pmid42191932,
year = {2026},
author = {Heckmann, JM and Floudiotis, N and Makanjuola, A and Ogunniyi, A and Mochan, A and Mongwe, RR and Sokhi, DS and Nel, M},
title = {Motor neuron disease in Africa: a critical appraisal of the literature.},
journal = {Nature reviews. Neurology},
volume = {},
number = {},
pages = {},
pmid = {42191932},
issn = {1759-4766},
abstract = {Motor neuron disease (MND) refers to a group of neurodegenerative diseases that cause motor neuron degeneration and death. The most common subtype, amyotrophic lateral sclerosis (ALS), is characterized by both upper and lower motor neuron impairment, which can manifest clinically in the bulbar region or asymmetrically in a limb. Typically, the disease progresses over several months, and death from respiratory failure occurs within 2-5 years of onset. As we highlight in this Review, data on MND in Africa are sparse, although common observations in this region - and in other populations with relatively low life expectancy - include apparent earlier disease onset and lower disease incidence compared with the rest of the world. In view of the HIV epidemic in Africa, we critically examine the evidence for an association between ALS and HIV infection. We briefly discuss conditions that might be regarded as ALS mimics and summarize the limited data on MND genetics in this region. Other issues pertinent to people living with MND in Africa include the absence of cognitive and behavioural data and the limited access to multidisciplinary clinics, therapies and palliative care. We share our perspective on how the ALS Africa Network is coordinating a shift in the African MND landscape to improve patient care.},
}

@article {pmid42192558,
year = {2026},
author = {Aggad, WS and Ghosh, R and Almohaimeed, HM and Mohammedsaleh, ZM and Saleh, FM and Almars, AI and Jyothi, SR and Panigrahi, R and Kumer, A and Dhara, B},
title = {Exosome-mediated gut-brain axis signaling in neurodegenerative diseases: Mechanisms, experimental evidence, and therapeutic perspectives-A narrative review.},
journal = {Animal models and experimental medicine},
volume = {},
number = {},
pages = {},
doi = {10.1002/ame2.70226},
pmid = {42192558},
issn = {2576-2095},
support = {PNURSP2026R213//Princess Nourah Bint Abdulrahman University/ ; },
abstract = {The stomach and the brain are connected by a sophisticated two-way communication mechanism called the gut-brain axis. Extracellular vesicles, particularly exosomes, that move bioactive substances between the stomach and the brain, such as proteins, lipids, metabolites, and microRNAs, may improve the gut-brain axis. In the past years, the role of exosome-mediated communication has been recognized as significant in relation to the etiology, continued progression, and potential treatment of neurodegenerative disorders. The authors of this review article present a summary of the current understanding of the relationship of gut microbiome, exosome biogenesis, and the pathophysiological development of neurodegenerative diseases. Evidence from laboratory studies, animal studies, and newly emerging human studies suggests that microbiome-based metabolites and inflammatory mediators may modulate how exosomes are produced, what they carry, and how they interact with the blood-brain barrier. These exosomal signals may impact neuroinflammation, neuronal signaling, and the spread of pathological proteins of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. In addition, they examine some possible ways to target the gut-brain axis from a therapeutic perspective, including manipulating the gut microbiome, providing probiotics and/or prebiotics, performing fecal microbiota transplantation, and/or using engineered extracellular vesicles as vehicles for drug delivery. The authors also outline some of the methodological differences that make it difficult to assess the effects of exosomes.},
}

@article {pmid42192595,
year = {2026},
author = {Liu, Y and Wu, W},
title = {Clinical Value and Research Prospects of 1024 Matrix Optimization in 64-Slice Cerebral CTA for Perforating Artery Visualisation.},
journal = {Journal of medical radiation sciences},
volume = {},
number = {},
pages = {},
doi = {10.1002/jmrs.70101},
pmid = {42192595},
issn = {2051-3909},
abstract = {This letter comments on Nagumo et al.'s study evaluating 1024-matrix reconstruction for intracranial perforating artery visualisation in 64-slice cerebral CTA, affirming its cost-effective value for standard CT scanners (https://doi.org/10.1002/jmrs.70055). We endorse the key finding that 1024-matrix improves small artery detection via higher sampling density, while highlighting the need for cross-vendor validation, workflow impact quantification, and clinical outcome assessment. This simple post-processing strategy is highly scalable, and further multicentre studies are warranted to confirm its universal utility.},
}

@article {pmid42193936,
year = {2026},
author = {Sepehrimanesh, M and Melen, SV and Yeasmin, F and Ojo, VA and Walden, F and Urmee, H and Etheridge, J and Nasu, AK},
title = {Emerging Therapeutic Strategies for Neurodegenerative Diseases: A Comprehensive Review of Recent Advances and Future Directions.},
journal = {Cells},
volume = {15},
number = {10},
pages = {},
doi = {10.3390/cells15100928},
pmid = {42193936},
issn = {2073-4409},
mesh = {Humans ; *Neurodegenerative Diseases/therapy ; Animals ; Neuroprotective Agents/therapeutic use ; Genetic Therapy ; },
abstract = {Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS; Lou Gehrig's disease), represent a growing global health burden characterized by progressive neuronal loss and functional decline. Despite decades of intensive research, effective disease-modifying therapies remain limited, underscoring the urgent need for innovative therapeutic strategies. This review highlights recent advances in the understanding of disease etiology and emerging treatment approaches, with a particular focus on modalities with translational potential. We discussed novel disease-modifying interventions, including gene and cell therapies, RNA-targeting strategies, and immunotherapies aimed at clearing misfolded proteins such as amyloid-β, tau, and α-synuclein. In parallel, we examined the evolving recognition of neuroinflammation and mitochondrial dysfunction as actionable therapeutic targets, alongside progress in precision medicine and biomarker-guided approaches that enable early diagnosis and individualized treatment. Additionally, we summarized developments in repurposed pharmacological agents, neuroprotective compounds, and lifestyle interventions, emphasizing the importance of integrative, multimodal strategies. Across AD, PD, and ALS, convergent molecular mechanisms, including protein misfolding, oxidative stress, and disrupted proteostasis, present opportunities for cross-disease therapeutic targeting. Finally, we addressed key challenges and future directions, including translating preclinical efficacy into clinical success, optimizing CNS-targeted delivery systems, and navigating ethical considerations surrounding gene editing and stem cell therapies.},
}

Humans
*Neurodegenerative Diseases/therapy
Animals
Neuroprotective Agents/therapeutic use
Genetic Therapy

@article {pmid42194069,
year = {2026},
author = {Malá, P and Váňová, N and Malý, O and Vyšata, O},
title = {Oxidative-Nitrosative Stress and Routine Biochemical Parameters in Amyotrophic Lateral Sclerosis: Associations with Clinical Status and Disease Duration-A Pilot Study.},
journal = {Biomolecules},
volume = {16},
number = {5},
pages = {},
doi = {10.3390/biom16050721},
pmid = {42194069},
issn = {2218-273X},
support = {Cooperatio Program, research area NEUR//Charles University/ ; Grant No. DRO-UHHK 00179906//Ministry of Health of the Czech Republic/ ; },
mesh = {Humans ; Pilot Projects ; *Amyotrophic Lateral Sclerosis/blood/metabolism/pathology ; *Nitrosative Stress ; *Oxidative Stress ; Female ; Biomarkers/blood ; Middle Aged ; Male ; Tyrosine/analogs & derivatives/blood ; Aged ; 8-Hydroxy-2'-Deoxyguanosine/blood ; Glutathione/blood ; Malondialdehyde/blood ; },
abstract = {BACKGROUND: This pilot study examined whether oxidative-nitrosative stress is associated with clinical status in amyotrophic lateral sclerosis (ALS). We analyzed associations between plasma markers of oxidative-nitrosative imbalance and ALSFRS-R, disease duration, survival, and routine biochemical parameters.

METHODS: Twenty-nine ALS patients fulfilling the Gold Coast diagnostic criteria were enrolled. Plasma levels of 3-nitrotyrosine (3-NT), 8-oxo-2'-deoxyguanosine (8-oxodG), malondialdehyde (MDA), glutathione (GSH), non-protein thiols (NP-SH), and non-protein disulfides (NP-SS-NP), as well as creatinine, urea, uric acid and BMI, were measured. Associations with ALSFRS-R and disease duration were evaluated using non-parametric correlation analyses and second-order polynomial regression (adjusted R[2]), while survival was explored using Kaplan-Meier analysis and multivariable Cox regression. Given the modest sample, we considered statistical power and applied Benjamini-Hochberg false discovery rate (FDR) correction within marker families.

RESULTS: At the uncorrected significance level, 3-NT showed a positive correlation with ALSFRS-R and a negative correlation with disease duration, and NP-SH correlated negatively with disease duration; however, these associations did not remain significant after FDR correction (FDR-adjusted p ≥ 0.099). Other oxidative-nitrosative markers and biochemical parameters showed no robust relationships with clinical measures. In Cox models, 3-NT was not significantly associated with survival (HR 3.44 per 1 nM, 95% CI 0.25-47.97, p = 0.358), whereas older age predicted higher mortality (HR 1.05 per year, 95% CI 1.00-1.10, p = 0.036).

CONCLUSIONS: 3-NT and NP-SH exhibited the strongest trends among the investigated markers, but their clinical associations in this small cross-sectional cohort remain exploratory and require confirmation in larger longitudinal studies.},
}

Humans
Pilot Projects
*Amyotrophic Lateral Sclerosis/blood/metabolism/pathology
*Nitrosative Stress
*Oxidative Stress
Female
Biomarkers/blood
Middle Aged
Male
Tyrosine/analogs & derivatives/blood
Aged
8-Hydroxy-2'-Deoxyguanosine/blood
Glutathione/blood
Malondialdehyde/blood

@article {pmid42194544,
year = {2026},
author = {Nord-Bronzyk, A and Ng, B and Lan, T and Schaefer, GO and Takahashi, S},
title = {Guiding Policymakers Toward Better AI Ethics Integration in Healthcare Regulation-Lessons from Singapore.},
journal = {Journal of clinical medicine},
volume = {15},
number = {10},
pages = {},
doi = {10.3390/jcm15103576},
pmid = {42194544},
issn = {2077-0383},
support = {MOH-000951-00//Ministry of health singapore/ ; },
abstract = {In terms of rollout, comprehensiveness, and strategy, Singapore's regulatory landscape governing the ethical use of Artificial Intelligence (AI) in healthcare has generally kept pace with other global leaders in AI advancement. However, establishing a robust and holistic regulatory framework that evolves along with emerging technologies is not easy-especially in healthcare, where the stakes are high and resources may be limited. We conducted a structured scoping analysis of key AI regulatory and professional documents in Singapore, selected using predefined inclusion criteria. Documents were systematically mapped against Savulescu et al.'s nine categories of ethical risk, followed by cross-document comparison to identify integration gaps and inconsistencies, and benchmarking against international AI governance frameworks. These recommendations are generalizable beyond Singapore for developers, implementers, healthcare professionals and patients and include dealing with bias in AI, enhancing human productivity without deskilling, facilitating more informed decision-making, and cultivating greater knowledge exchange between clinicians and patients, to name a few.},
}

@article {pmid42195033,
year = {2026},
author = {Richard, E and Al-Hajj Vourc'h, S and Marouillat, S and Beltran, S and Blasco, H and Corcia, P and Vourc'h, P},
title = {From Mutation to Manifestation: Penetrance in Amyotrophic Lateral Sclerosis.},
journal = {Genes},
volume = {17},
number = {5},
pages = {},
doi = {10.3390/genes17050576},
pmid = {42195033},
issn = {2073-4425},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *Penetrance ; *Mutation ; Superoxide Dismutase-1/genetics ; RNA-Binding Protein FUS/genetics ; C9orf72 Protein/genetics ; Genetic Counseling ; DNA-Binding Proteins/genetics ; Genetic Predisposition to Disease ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by progressive loss of motor neurons in the brain and spinal cord. While most cases are sporadic, around 10% are familial. Recent genetic studies show that many apparently isolated cases carry pathogenic mutations, highlighting the importance of penetrance, the probability that a causal mutation manifests clinically. This review focuses on mutation penetrance in ALS (C9orf72, SOD1, TARDBP, FUS genes), its variability across genes, age, and environmental or genetic modifiers, and its implications for genetic counseling. Identification of pathogenic mutations informs the monitoring of relatives and, in some cases, gives access to targeted therapies or clinical trials. Counseling of asymptomatic relatives must consider incomplete penetrance, which can lead to delayed or absent disease manifestation. ALS exists on a clinical and genetic continuum including related disorders, such as frontotemporal dementia, further influencing risk interpretation. Advances in panel, whole-exome and whole-genome sequencing refine our understanding of penetrance and enable precise diagnostics, and potential tailored therapies. Understanding penetrance is therefore essential to translate mutation discovery into informed clinical decisions and genetic counseling in ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/pathology
*Penetrance
*Mutation
Superoxide Dismutase-1/genetics
RNA-Binding Protein FUS/genetics
C9orf72 Protein/genetics
Genetic Counseling
DNA-Binding Proteins/genetics
Genetic Predisposition to Disease

@article {pmid42196191,
year = {2026},
author = {Giordano, A and Mandrioli, J and Cerri, F and Lunetta, C and Saebfar, H and Catania, M and Battipaglia, C and Leone, L and Trojsi, F and Vizziello, M and Gerardi, F and Farè, M and Zulueta, A and Piras, R and Giacchino, M and Gianferrari, G and Dalla Bella, E and Domi, T and Bonanomi, D and Ganci, G and Lombardi, R and Lauria, G and Riva, N},
title = {Longitudinal CSF and Serum Biomarker Dynamics in Tofersen-Treated SOD1-ALS: A Real-World Multicentre Cohort Study.},
journal = {International journal of molecular sciences},
volume = {27},
number = {10},
pages = {},
doi = {10.3390/ijms27104208},
pmid = {42196191},
issn = {1422-0067},
support = {IDEALS//AriSLA/ ; RF-2021-12373036//Ministero della salute Ricerca Finalizzata bando 2021/ ; Neurobiobanca di Modena//Fondazione Cassa di Risparmio di Modena/ ; Giovanni Marazzina Project//Giovanni Marazzina Foundation/ ; },
mesh = {Humans ; *Biomarkers/blood/cerebrospinal fluid ; *Superoxide Dismutase-1/genetics ; Female ; *Amyotrophic Lateral Sclerosis/drug therapy/blood/cerebrospinal fluid/genetics ; Longitudinal Studies ; tau Proteins/blood/cerebrospinal fluid ; Ubiquitin Thiolesterase/blood/cerebrospinal fluid ; Male ; Glial Fibrillary Acidic Protein/blood/cerebrospinal fluid ; Middle Aged ; Neurofilament Proteins/blood/cerebrospinal fluid ; Retrospective Studies ; Aged ; },
abstract = {Tofersen is a gene-targeted therapy for superoxide dismutase 1 (SOD1)-associated amyotrophic lateral sclerosis (ALS), but neurofilament light chain (NfL) may not fully capture the biological response to treatment. We performed a multicentre retrospective longitudinal study including 24 patients with SOD1-ALS treated with intrathecal tofersen at four Italian referral centres between 2022 and 2025. Cerebrospinal fluid (CSF) and serum biomarkers were assessed at baseline, month 3, month 6, and last available administration using single-molecule array assays to quantify NfL, glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCHL-1), and total Tau. NfL decreased after treatment initiation in both CSF and serum, providing the clearest pharmacodynamic signal. In contrast, CSF GFAP increased progressively over follow-up, while CSF total Tau and UCHL-1 rose mainly at later timepoints; serum GFAP, total Tau, and UCHL-1 also showed increases during follow-up. ALS Functional Rating Scale-Revised trajectories were broadly stable, whereas disease progression rate was lower at last follow-up than at baseline. Greater reductions in CSF NfL were observed in pathogenic versus uncertain SOD1 variants, and early serum NfL and UCHL-1 changes were associated with longer-term changes in disease progression. These findings suggest that longitudinal multi-analyte profiling may refine biological response stratification beyond NfL alone in tofersen-treated SOD1-ALS.},
}

Humans
*Biomarkers/blood/cerebrospinal fluid
*Superoxide Dismutase-1/genetics
Female
*Amyotrophic Lateral Sclerosis/drug therapy/blood/cerebrospinal fluid/genetics
Longitudinal Studies
tau Proteins/blood/cerebrospinal fluid
Ubiquitin Thiolesterase/blood/cerebrospinal fluid
Male
Glial Fibrillary Acidic Protein/blood/cerebrospinal fluid
Middle Aged
Neurofilament Proteins/blood/cerebrospinal fluid
Retrospective Studies
Aged

@article {pmid42196458,
year = {2026},
author = {Prodromos, CC and Del Villar, R and Striegel, A and Pena, G and Dixit, R},
title = {The Molecular Basis of Partial Reversal or Significant Slowing of ALS, Parkinson's Disease, and Lewy Body Dementia by Mesenchymal Exosomes/Secretome.},
journal = {International journal of molecular sciences},
volume = {27},
number = {10},
pages = {},
doi = {10.3390/ijms27104483},
pmid = {42196458},
issn = {1422-0067},
mesh = {Humans ; *Exosomes/metabolism/transplantation ; *Amyotrophic Lateral Sclerosis/therapy/metabolism ; *Parkinson Disease/therapy/metabolism ; Female ; Male ; *Lewy Body Disease/therapy/metabolism ; Aged ; *Mesenchymal Stem Cells/metabolism ; Middle Aged ; *Secretome/metabolism ; Case-Control Studies ; Administration, Intranasal ; },
abstract = {Neuromuscular and neurodegenerative (NMND) disorders are diseases that cause progressive damage to the central nervous system leaving patients with symptoms that negatively affect everyday living with death almost inevitable. These include amyotrophic lateral sclerosis (ALS), Lewy body dementia (LBD), and Parkinson's disease (PD) with cases expected to increase in the future. Intranasally administered stem cell-derived exosomes/secretome have been seen as potential therapeutic options for these disorders in preclinical animal models. This study sought to observe the efficacy of mesenchymal stem cell-derived exosomes/secretome in patients with ALS, LBD, and PD. Based off these preclinical studies, we conducted a case-controlled series experiment with 86 patients with ALS, LBD, or PD, with the independent variable being the treatment and the dependent variable being the clinical response. These patients were recruited and given intranasal instillations of various MSC-derived exosome/secretome products. Subsequent treatments were given to patients who did not have a response to one product. Patients were followed up at one week, one, two, three, and six months post-treatment. Historical external controls were used for comparison to clinical outcomes. There were no serious adverse events in any patient. A total of 67 of 86 (77%) patients showed a positive clinical response to at least one product. Outcomes were strongly associated with greater treatment frequency for ALS and LBD. Intranasal administration of MSC-derived exosome/secretome products were safe, and most patients showed overall improvement with at least one product. Some patients also saw a substantial decrease in the rate of decline compared to historical controls. These results also give rise to the hypothesis: do MSC-derived exosomes/secretome treatments show efficacy in other NMND disorders? The primary limitation of this study is the 6-month follow-up.},
}

Humans
*Exosomes/metabolism/transplantation
*Amyotrophic Lateral Sclerosis/therapy/metabolism
*Parkinson Disease/therapy/metabolism
Female
Male
*Lewy Body Disease/therapy/metabolism
Aged
*Mesenchymal Stem Cells/metabolism
Middle Aged
*Secretome/metabolism
Case-Control Studies
Administration, Intranasal

@article {pmid42197088,
year = {2026},
author = {Herrmann, C and Satari, S and Weber, A and Ruschitzka, T and Jagodzinski, L and Elmas, Z and Becker, F and Richter, L and Wiesenfarth, M and Michels, S and Weishaupt, JH and Schuster, J and Dorst, J},
title = {Feasibility and Tolerability of Ketogenic Interventions in Amyotrophic Lateral Sclerosis-A Dose-Finding Case Series.},
journal = {Nutrients},
volume = {18},
number = {10},
pages = {},
doi = {10.3390/nu18101628},
pmid = {42197088},
issn = {2072-6643},
support = {N/A//Nutricia (Germany)/ ; N/A//KetoneAid/ ; N/A//KetoForce/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diet therapy/blood ; *Diet, Ketogenic/methods/adverse effects ; Female ; Male ; Middle Aged ; Feasibility Studies ; Aged ; Adult ; 3-Hydroxybutyric Acid/blood/administration & dosage ; Ketone Bodies/administration & dosage/blood ; Treatment Outcome ; },
abstract = {Background/Objectives: Weight loss and hypermetabolism are negative prognostic factors in amyotrophic lateral sclerosis (ALS). Ketone bodies (β-hydroxybutyrate, βHB) as high-energy substrates may compensate for this energy deficit, since a ketogenic diet (KD) has been shown to increase survival and stabilize body weight in the SOD1 mouse model. In this case series, we tested exogenous ketone salts (KS), ketone esters (KE), and a KD, in patients with ALS and in healthy subjects to identify novel therapeutic interventions for subsequent clinical studies. Methods: KS (KetoForce[®] (KetoSports, Frisco, TX, USA)) were tested in healthy subjects (11.7 g and 15.6 g βHB) and patients (15.6 g βHB 3×/day over 3 days). KE (KE4[®] (KetoneAid, Falls Church, VA, USA)) containing 10.0 g βHB were applied in healthy subjects (once) and in patients (3×/day over 2 days). For the KD, KetoCal[®] 2.5:1 LQ MCT MF Vanilla (Nutricia, Frankfurt, Germany) was applied via percutaneous endoscopic gastrostomy over four weeks. Regular capillary βHB measurements were conducted, and adverse events were recorded. Results: Between January 2021 and March 2025, we treated nine patients with ALS and two healthy subjects at the Department of Neurology of Ulm University, Germany. KE and KS increased βHB temporarily. However, the elevation was more pronounced following KE (maximum 2.2-2.7 mmol/L vs. 0.8-1.2 mmol/L). The KD increased βHB levels continuously with nighttime fluctuations. No adverse events occurred under KE. KS caused diarrhea in 3/5 patients and 1/2 healthy subjects. The KD was well tolerated, with mild gastrointestinal symptoms occurring in all patients. Conclusions: All ketogenic approaches increased βHB blood levels. While the KD and KE provided good tolerability, KS caused significant gastrointestinal side effects. KD seems to be an interesting candidate for future clinical studies, as it prompted a long-term increase in βHB while providing satisfying tolerability. Since maintaining a KD long-term is difficult for oral-feeding patients, KE may constitute a feasible alternative.},
}

Humans
*Amyotrophic Lateral Sclerosis/diet therapy/blood
*Diet, Ketogenic/methods/adverse effects
Female
Male
Middle Aged
Feasibility Studies
Aged
Adult
3-Hydroxybutyric Acid/blood/administration & dosage
Ketone Bodies/administration & dosage/blood
Treatment Outcome

@article {pmid42197516,
year = {2026},
author = {Tavares, GC and Carneiro, SP and Barbanti, ACC and Rosário, AECD and Matos, HC and Maia, CRMDS and Costa, HL and Egger, RC and Nogueira, LFF and Rosa, JCC and Pereira, FL and Pilarski, F and Gallani, SU and Soto, E and Leal, CAG and Figueiredo, HCP},
title = {Multilocus Sequence Typing Reveals New Insights into the Population Structure and Genetic Diversity of Lactococcus spp. from Brazilian Fish.},
journal = {Microorganisms},
volume = {14},
number = {5},
pages = {},
doi = {10.3390/microorganisms14051131},
pmid = {42197516},
issn = {2076-2607},
support = {88881.200614/2018-01//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; APQ-01227-22, APQ-04309-22 and PPM-00779-18//Fundação de Amparo à Pesquisa do Estado de Minas Gerais/ ; 01.02.016301.03071/2022-11//Fundação de Amparo à Pesquisa do Estado do Amazonas/ ; },
abstract = {Lactococcosis has emerged as an economically and ecologically significant disease in aquatic animals worldwide. This study employed multilocus sequence typing (MLST) to investigate the genetic diversity of Lactococcus spp. strains from Brazilian fish species and evaluate their phylogenetic relationships with global isolates to elucidate potential epidemiological connections involving multiple host species and distinct geographic regions. A total of 55 isolates from different laboratories had their DNA extracted, followed by the amplification and sequencing of the internal fragments of seven housekeeping genes (als, atpA, tuf, gapC, gyrB, rpoC and galP). Sequence types (STs) and clonal complexes (CCs) were defined. An unrooted neighbor-joining phylogenetic tree was generated using allele profiles from this study and those previously reported from other aquatic animal species. The isolates comprised 29 STs (11 previously reported, 18 novel ones), which were grouped into species-specific CCs: CC5 (L. formosensis); CC4, CC17, CC62 (L. garvieae); CC24, CC29, CC97 (L. petauri). Considerable genetic divergence was observed, with L. formosensis and L. garvieae forming heterogeneous populations, while L. petauri was more homogeneous. These findings describe the MLST structure of the sampled isolates and should be interpreted as hypothesis-generating rather than population-level estimates of genotype prevalence. Phylogenetics confirmed groupings within the CCs and revealed additional phylogenetic clustering patterns. In conclusion, the Brazilian Lactococcus spp. strains analyzed in this study constitute a genetically diverse population based on their STs. MLST and phylogenetic analysis demonstrated genetic relatedness between the L. garvieae and L. formosensis isolates from this study and those from other aquatic animal species. In contrast, all the STs identified for L. petauri in this study were unrelated to the MLST lineages responsible for outbreaks in Brazilian Nile tilapia (Oreochromis niloticus) and North American rainbow trout (Oncorhynchus mykiss). This suggests that piscine L. petauri populations in the Americas evolved from distinct ancestral origins.},
}

@article {pmid42198024,
year = {2026},
author = {Aminfar, K and Scafide, K and Wojtusiak, J and Lattanzi, D},
title = {Evaluation Framework for Bruise Detection: Systematic ALS/White-Light Training and Skin-Tone Balancing with Deep Learning.},
journal = {Sensors (Basel, Switzerland)},
volume = {26},
number = {10},
pages = {},
doi = {10.3390/s26103215},
pmid = {42198024},
issn = {1424-8220},
support = {1625039//National Science Foundation/ ; 2018631//National Science Foundation/ ; 15PNIJ-21-GG-04145-SLFO//National Institute of Justice/ ; },
mesh = {Humans ; *Deep Learning ; *Contusions/diagnosis/diagnostic imaging ; Image Processing, Computer-Assisted/methods ; Forensic Imaging ; *Skin Pigmentation/physiology ; Algorithms ; Lighting ; },
abstract = {Accurate and consistent forensic bruise assessment is critical in ensuring positive clinical and legal outcomes for victims of violence. In this study, a framework for automated bruise detection is presented that, for the first time, integrates narrowband alternate-light-source (ALS) forensic imaging and ambient white light imaging. This evaluation framework is designed to address long-standing issues with respect to equitable performance across skin tones and lighting scenarios via a combination of novel model diagnostic strategies. In particular, skin-tone balancing during training and testing, threshold-sensitivity analysis, and embedding-similarity partitioning are employed to quantify the model robustness and deployment trade-offs that arise in forensic image analysis. Models were implemented with ImageNet-pretrained backbones and trained on a unique, multi-annotator full-consensus dataset comprising both white-light and ALS (415 nm and 450 nm) images. The protocol emphasizes three axes of operational relevance: (1) illumination composition in training (W/ALS ratio); (2) subgroup fairness via targeted balancing; and (3) model operating-point selection (confidence and IoU thresholds) informed by confidence-stability metrics and bootstrapped uncertainty estimates. Systematic W/ALS ratio sweeps indicate peak accuracy under ALS-dominant training and declining performance as the proportion of white-light images increases within the training set. Skin-tone balancing reduced failure rates for darker skin tones but increased overprediction in some demographic subgroups. Embedding-similarity and seen/unseen injury analyses demonstrate inflated generalization under image-level partitioning. Ultimately, the findings suggest that future researchers and developers should employ injury-level data partitioning and ensure a weighted balance of ALS images during training.},
}

Humans
*Deep Learning
*Contusions/diagnosis/diagnostic imaging
Image Processing, Computer-Assisted/methods
Forensic Imaging
*Skin Pigmentation/physiology
Algorithms
Lighting

@article {pmid42199117,
year = {2026},
author = {Zhou, Q and Gong, T and Liu, J and Ma, J and Zheng, M and Zhong, Z and Deng, H and Lin, H and Feng, N and Lei, X and Zhang, C},
title = {An integrated single-nucleus ribonucleic acid sequencing and spatial transcriptomic atlas reveals stage-specific neuronal and glial trajectories in a mouse model of amyotrophic lateral sclerosis.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00859},
pmid = {42199117},
issn = {1673-5374},
abstract = {Amyotrophic lateral sclerosis is a progressive multifocal neurodegenerative condition involving motor neurons and other cell types. To analyze spatiotemporal cellular dynamics in amyotrophic lateral sclerosis, we performed single-nucleus ribonucleic acid sequencing and spatial transcriptomics analysis of cervical spinal cords from wild-type control mice and SOD1-G93A transgenic mice in the pre-symptomatic (d50), early symptomatic (d90), and late-stage (d130) phases of disease. Single-nucleus ribonucleic acid sequencing identified 17 cell clusters and showed that progressive neuronal loss occurred over time, paralleled by glial expansion. Spatial transcriptomics mapped these clusters anatomically onto oligodendrocytes in white matter, neurons in horns, and diffuse astrocytes/microglia. Subcluster analysis demonstrated neuronal heterogeneity, with early mitochondrial stress in ventral motor neurons evolving into synaptic dysfunction, transient maturation peaks in interneurons, and amplified age-related decline in amyotrophic lateral sclerosis. Astrocyte and oligodendrocyte subclusters, which were originally misclustered due to spot-level contamination, were reinterpreted to highlight A1-reactive states and progenitor expansions, validated by immunohistochemistry detection of serum/glucocorticoid regulated kinase 1. Temporal profiles tracked the transition from compensatory to inflammatory gliosis, while gene signatures were linked to human amyotrophic lateral sclerosis cohorts, including complement activation and mitochondrial dysfunction. This study provides a high-resolution spatiotemporal cellular map of amyotrophic lateral sclerosis pathogenesis through the integration of single-nucleus and spatial transcriptomics, uncovering early mitochondrial impairment in neurons, delineating the trajectory of neurotoxic glial states, and identifying compensatory progenitor responses, to highlight the highly intricate interaction between glial reactivity and neuronal susceptibility that drives the pathogenesis of ALS.},
}

@article {pmid42199142,
year = {2026},
author = {Gerbino, V},
title = {Targeting the type-I interferon response in amyotrophic lateral sclerosis.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-26-00133},
pmid = {42199142},
issn = {1673-5374},
}

@article {pmid42200208,
year = {2026},
author = {Peerbhai, N and Ramsunder, N and Europa, T and Heckmann, J and Nel, M},
title = {Expanding African contributions to ClinVar through genetic counselor-led variant curation.},
journal = {Journal of genetic counseling},
volume = {35},
number = {3},
pages = {e70235},
doi = {10.1002/jgc4.70235},
pmid = {42200208},
issn = {1573-3599},
support = {226519/Z/22/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; *Genetic Counseling ; *Genetic Variation ; *Databases, Genetic ; African People ; *Black People/genetics ; *Data Curation ; },
abstract = {Global variant databases such as ClinVar are vital in linking genetic variation to clinical significance and enabling shared interpretation across laboratories. However, African genetic variants remain underrepresented, comprising under 2% of global ClinVar submissions. This gap reflects inequities in access to genome sequencing, workforce capacity, and data-sharing systems, which limit visibility, contextual interpretation, and re-evaluation of African genetic variation. We describe our experiences of genetic counselor-led variant curation, ClinVar submissions, and ongoing monitoring of germline genetic variants identified in African neuromuscular and amyotrophic lateral sclerosis research cohorts. Between March 2023 and August 2025, the Clinical Omics and Informatics Unit (University of Cape Town) submitted 93 DNA sequence variants to ClinVar spanning 58 genes, including 27 first-time submissions to the database. ClinVar submissions require valid Monarch Disease Ontology (Mondo) identifiers; gaps or inaccuracies were identified (n = 3) and updated, or Mondo disease entities were created to ensure gene-disease pairs were correctly represented. Using African Genome Variation Database frequencies to guide variant classification provided sub-regional context, highlighting population differences and refining interpretations. Furthermore, we maintained a structured follow-up of variant records using ClinVar's "follow" feature. This enabled passive monitoring of new submissions or classification changes, which were evaluated to assess whether reinterpretation or resolution of variants of uncertain significance or those with conflicting assertions were warranted. This work highlights the critical role that African genetic counselors can play as contributors to variant curation in an underrepresented geography, given their expertise in human genetics and clinical reasoning. By embedding African-specific frequency data and locally trained expertise into variant curation pipelines, a sustainable, equity-driven model for genomic knowledge production in Africa is developed. African-led ClinVar contributions can strengthen interpretative accuracy, foster collaborative curation, and position genetic counselors as active agents in global genomic data sharing and interpretation.},
}

Humans
*Genetic Counseling
*Genetic Variation
*Databases, Genetic
African People
*Black People/genetics
*Data Curation

@article {pmid42200920,
year = {2026},
author = {An, Y and Lan, H and Xiong, J and Jing, R and Gu, D and Zhang, H and Liu, X and Zhao, Q and Wang, F},
title = {From Axonal Growth to Neurodegeneration: The Dual Role of Neurofilament Dynamics in Health and Disease.},
journal = {NeuroSci},
volume = {7},
number = {3},
pages = {},
doi = {10.3390/neurosci7030058},
pmid = {42200920},
issn = {2673-4087},
support = {ZR2025MS434//Natural Science Foundation of Shandong Province/ ; },
abstract = {Neurofilaments (NFs) are the predominant type IV intermediate filaments in differentiated neurons, functioning not just as static scaffolds, but as active drivers of radial axonal growth and nerve conduction velocity. While their physical properties are well characterized, a critical gap remains in synthesizing how their dynamic assembly and developmental subunit switching directly dictate neurodegenerative outcomes. This review breaks down the molecular architecture and stepwise kinetic assembly of NFs, detailing their role in polarized transport and the formation of a protective viscoelastic gel network within axons. We specifically highlight the physiological expression switching of early subunits, such as alpha-internexin and peripherin, during neuronal maturation, a process often overlooked in traditional structural reviews. By examining how specific gene mutations and aberrant hyperphosphorylation trigger axonal transport jams and protein aggregation, we map the direct pathways leading to amyotrophic lateral sclerosis (ALS) and Charcot-Marie-Tooth (CMT) disease. Finally, we emphasize that a precise mechanistic decoding of NF structural dynamics and their pathological disruption is essential for understanding the fundamental etiology of these neurodegenerative conditions.},
}

@article {pmid42201810,
year = {2026},
author = {Gibbons, GM and Fuchsberger, T and Abdelgawad, M and Giandomenico, SL and Szebényi, K and Petrova, V and Wenger, LMD and Olschewski, DN and Chabros, J and Muresan, L and Feord, RC and Asif, M and Fawcett, JW and Mierau, SB and Paulsen, O and Lancaster, MA and Lakatos, A},
title = {A human corticospinal organoid-slice connectoid model informs enhancer strategies for post-injury axon regrowth.},
journal = {Cell reports},
volume = {45},
number = {6},
pages = {117399},
doi = {10.1016/j.celrep.2026.117399},
pmid = {42201810},
issn = {2211-1247},
abstract = {Axon elongation in the mammalian central nervous system (CNS) declines during development, limiting regenerative capacity after birth. Intrinsic regulators of this process are promising repair targets, as immature axons can regrow in tissues otherwise not conducive to regeneration. Yet the precise timing and mechanisms underlying the cessation of axon growth in the human CNS remain unresolved. Here, we developed a three-dimensional human corticospinal motor organoid-slice connectoid platform mimicking the developmental axon elongation program and its subsequent restriction through maturation. Cortical and spinal slices establish functional connections while remaining spatially segregated, enabling cortical cell-type-specific observations without direct confounding effects by spinal cells. Using single-cell transcriptomics, computational analyses, axon regrowth assays, and live imaging, we identified transcriptional alterations contributing to decreased axon growth in maturing human cortical projection neurons. We further demonstrate that this decline can be reversed using compounds and repurposable drugs targeting a maturation-associated transcriptional shift, promoting post-injury axon repair.},
}

@article {pmid42202251,
year = {2026},
author = {Ronquillo, CE},
title = {Beyond Time Saved: Implementation, Equity, and the Utility Threshold for Nursing AI Scribes.},
journal = {Journal of medical Internet research},
volume = {28},
number = {},
pages = {e101190},
doi = {10.2196/101190},
pmid = {42202251},
issn = {1438-8871},
mesh = {Humans ; *Artificial Intelligence ; *Documentation ; Long-Term Care ; },
abstract = {Schwabe et al's pre-post time-motion study of a domain-specific artificial intelligence (AI) speech assistant used by nurses in German long-term care provides one of the few real-world, full-shift evaluations of an AI scribe deployed to a nonphysician workforce, with paired objective observation and self-reported outcomes. This commentary points to the implications of these findings that extend well beyond the time savings headline. The study reports substantial reduction in self-reported documentation time and increased satisfaction with the documentation system, yet workplace satisfaction and the perception that AI scribes are "a good idea to implement" did not improve. Taken together, these findings show three undertheorized issues for AI scribe implementation in nursing and long-term care. First, postimplementation increases in time spent reviewing entries and retrieving information indicate that AI scribes redistribute cognitive effort from authoring to verification, with unknown consequences for satisfaction, mastery, and error detection. Second, the apparent paradox of rising documentation satisfaction alongside falling expectations of AI quality represents user calibration. Third, the substantial equity considerations of automatic speech recognition documentation reflect a broader trend of AI scribe studies that treat equity as a caveat, rather than treating equitable performance as empirically measurable and testable across variations in linguistic styles, dialects, and social linguistic dimensions. To advance the field, the next generation of nursing AI scribe research must treat documentation as a heterogeneous bundle of authoring, reviewing, retrieving, and verifying activities with distinct satisfaction and error profiles; specify and validate end-user-defined anchor utilities, rather than having a narrow focus on diffuse improvement; and treat equity testing and reporting of both automatic speech recognition systems and workforce adoption as standard reporting expectations, rather than caveats.},
}

Humans
*Artificial Intelligence
*Documentation
Long-Term Care

@article {pmid42202610,
year = {2026},
author = {Doğan, V and Sinanoğlu, GK},
title = {2D:4D ratio, affective lability, and impulsivity in men with cannabinoid and methamphetamine use disorders: A comparative analysis with healthy controls.},
journal = {Early human development},
volume = {221},
number = {},
pages = {106587},
doi = {10.1016/j.earlhumdev.2026.106587},
pmid = {42202610},
issn = {1872-6232},
abstract = {The second-to-fourth digit ratio (2D:4D) is considered a non-invasive marker of prenatal androgen exposure and has been proposed as a developmental indicator of behavioral vulnerability; however, findings in substance use disorders remain inconsistent. This study aimed to examine whether 2D:4D ratios are associated with substance use disorders and to compare their relative contribution with psychological factors, including affective lability, impulsivity, and anxiety. In this cross-sectional case-control study, male participants with cannabinoid use disorder (CUD; n = 47), methamphetamine use disorder (MUD; n = 48), and healthy controls (n = 53) were included. The mean age of participants was 32.7±8.95 years. All participants were assessed using the Structured Clinical Interview for DSM-5 (SCID-5), Affective Lability Scale-18 (ALS-18), Barratt Impulsiveness Scale-11 (BIS-11), and Generalized Anxiety Disorder-7 (GAD-7). The 2D:4D ratio was measured with a digital caliper by two trained psychiatrists, and 2D:4D ratios and right-left differences (Dr-I) were calculated. No significant group differences were observed in left or right 2D:4D ratios or Dr-I; however, a consistent trend toward lower 2D:4D values, particularly for right-hand 2D:4D, was observed in the CUD and MUD groups compared with controls. In contrast, affective lability, impulsivity, and anxiety scores were significantly elevated in both patient groups (p <0.05). In univariate logistic regression analyses, affective lability, impulsivity, anxiety, and lower right-hand 2D:4D were associated with substance use disorder; however, right-hand 2D:4D showed the weakest association among these predictors. In the multivariate model, lower right-hand 2D:4D, impulsivity, lower educational attainment, and smoking remained independently associated with substance use disorder. These findings suggest that while 2D:4D may reflect a distal developmental vulnerability, psychological factors, particularly impulsivity, have a more direct and clinically relevant role in substance use disorders. Incorporating the assessment of impulsivity into clinical evaluation and intervention strategies may improve risk identification and treatment planning.},
}

@article {pmid42202831,
year = {2026},
author = {Gorenshtein, A and Omar, M and Barash, Y and Nadkarni, G and Klang, E},
title = {Large Language Models Integrated into Brain-Computer Interfaces for Communication and Control: A Systematic Review.},
journal = {Biomedical physics & engineering express},
volume = {},
number = {},
pages = {},
doi = {10.1088/2057-1976/ae737b},
pmid = {42202831},
issn = {2057-1976},
abstract = {Large language models (LLMs) are starting to be coupled with brain-computer interfaces (BCIs) for assistive communication, but the resulting systems differ widely in where the model sits in the pipeline and in what they actually measure. We performed a systematic review, prepared according to PRISMA, of eleven studies that combine an LLM with a BCI for communication or control. The included work covers P300, SSVEP, cVEP, passive affective and auditory paradigms, and five integration patterns: autocomplete, post-edit correction, intent expansion, dynamic interface generation and affective support. For each study we extracted the hardware and decoding pipeline, the LLM and prompting strategy, latency reporting and outcomes; we used scenario-appropriate metrics rather than a single common metric. Risk of bias was judged with an adapted ROBINS-I framework that stratified studies into online, offline-simulation and system-proposal categories. In the copy-spelling scenario, two studies that measured keystroke savings directly reported values above 50%, with one study exceeding 60% in a multi-turn condition; on an intent-based ALS message-bank task, one online study reached 42 characters per minute with a semantic accuracy of 88%. None of the eleven studies enrolled motor-impaired patients, seven of eleven relied on remote OpenAI endpoints, and reporting of end-to-end latency and failure modes was sparse. We propose a five-category taxonomy of BCI/LLM integration, separate findings that are supported from those that are still speculative, and give a checklist of metrics that should be reported by future studies. The taxonomy and the reporting checklist are the main contributions; clinical benefit for the target population remains to be shown.},
}

@article {pmid42203709,
year = {2026},
author = {Topal, MA and Park, HG and Impett, EA},
title = {Beyond significance: Toward a more dynamic, relational, and culturally inclusive framework on love.},
journal = {The Behavioral and brain sciences},
volume = {49},
number = {},
pages = {e18},
doi = {10.1017/S0140525X25102197},
pmid = {42203709},
issn = {1469-1825},
mesh = {*Love ; Humans ; *Culture ; *Interpersonal Relations ; },
abstract = {Kruglanski et al.'s "love as a quest" model casts romantic love as a path to personal significance. We argue this framing misrepresents love's core nature, overlooking relational, emotional, and cultural dimensions. Love is not merely a reflection of individual validation but is dynamic and co-constructed. We advocate for a more relationally grounded and culturally inclusive framework on love.},
}

*Love
Humans
*Culture
*Interpersonal Relations

@article {pmid42203724,
year = {2026},
author = {Zeigler-Hill, V},
title = {Seeking significance from significant others: Rethinking romantic love.},
journal = {The Behavioral and brain sciences},
volume = {49},
number = {},
pages = {e22},
doi = {10.1017/S0140525X25102203},
pmid = {42203724},
issn = {1469-1825},
mesh = {*Love ; Humans ; Narcissism ; Self Concept ; Object Attachment ; *Interpersonal Relations ; Models, Psychological ; },
abstract = {Kruglanski et al.'s model redefines love as a pathway to personal significance, offering a compelling new lens through which to understand romantic relationships. This commentary explores the model's implications for areas of the literature, including mate value, attachment styles, self-esteem, and narcissism. It also outlines promising directions for future research, emphasizing love's role in fulfilling the need to feel significant.},
}

*Love
Humans
Narcissism
Self Concept
Object Attachment
*Interpersonal Relations
Models, Psychological

@article {pmid42203737,
year = {2026},
author = {Fowers, BJ},
title = {Are merit and appreciation instrumental aims?.},
journal = {The Behavioral and brain sciences},
volume = {49},
number = {},
pages = {e10},
doi = {10.1017/S0140525X25102264},
pmid = {42203737},
issn = {1469-1825},
mesh = {Humans ; *Love ; },
abstract = {This commentary responds to Kruglanski et al.'s paper, which theorizes that love is one means that can result in significance. The commentary's first focus is whether love is well conceptualized as an instrumental activity (a means-end relation) and concludes that a constitutive-ends conceptualization is necessary (love helps to constitute significance). Secondly, the evidence base for their hypotheses appears thin.},
}

Humans
*Love

@article {pmid42203744,
year = {2026},
author = {Boudesseul, J and Cova, F and Lantian, A},
title = {Beyond the equation: An evolutionary reassessment of the love formula.},
journal = {The Behavioral and brain sciences},
volume = {49},
number = {},
pages = {e4},
doi = {10.1017/S0140525X25102276},
pmid = {42203744},
issn = {1469-1825},
mesh = {Humans ; *Love ; *Biological Evolution ; *Sexual Behavior/psychology ; },
abstract = {Kruglanski et al.'s love formula - partner merit, appreciation, and the quest for meaning - offers a novel perspective but overlooks key evolutionary insights. It oversimplifies mating preferences, neglects contextual flexibility, and downplays reproductive signals crucial to partner selection. While innovative, the model fails to account for the complexity of human romantic behavior shaped by ecological, social, and developmental factors.},
}

Humans
*Love
*Biological Evolution
*Sexual Behavior/psychology

@article {pmid42020662,
year = {2026},
author = {Abati, E and Saccomanno, D and Alberti, C and Anastasia, A and Gagliardi, D and Ferri, E and Arosio, B and D Angelo, G and Cima, R and Bassi, MT and Oldoni, S and Comi, GP and Rizzo, F and Corti, SP},
title = {Investigating the role of serum NfL, FGF21, NCAM1 and GDF15 as disease biomarkers for Charcot-Marie-Tooth type 2A.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {42020662},
issn = {2045-2322},
support = {GMR23T2153//Fondazione Telethon/ ; Ricerca Corrente 2024 MoH//Ministero della Salute/ ; GR-2018-12365358//Ministero della Salute/ ; },
mesh = {*Charcot-Marie-Tooth Disease/blood/diagnosis/genetics ; Humans ; Biomarkers/blood ; *Growth Differentiation Factor 15/blood ; Female ; *Fibroblast Growth Factors/blood ; Male ; Animals ; Middle Aged ; Adult ; *Neurofilament Proteins/blood ; Mice ; Mice, Transgenic ; Aged ; Case-Control Studies ; Neural Cell Adhesion Molecules/blood ; },
abstract = {Charcot-Marie-Tooth disease type 2A (CMT2A) is the most common axonal form of inherited peripheral neuropathy, caused by mutations in the mitofusin 2 (MFN2) gene that impair mitochondrial fusion and axonal transport, ultimately leading to progressive neurodegeneration. The identification of accessible molecular biomarkers may improve diagnostic accuracy, enable patient stratification, and support the development and monitoring of emerging therapies. We investigated serum levels of neurofilament light chain (NfL), neural cell adhesion molecule 1 (NCAM1), growth differentiation factor 15 (GDF15), and fibroblast growth factor 21 (FGF21) in CMT2A patients (n = 15), healthy controls (n = 10), and neurological disease controls (n = 16; amyotrophic lateral sclerosis [ALS], n = 10, spinal muscular atrophy type 3 [SMA3], n = 6), evaluating their utility as diagnostic and monitoring biomarkers. In parallel, serum NfL levels were assessed in transgenic Thy1-MFN2*R94Q mice, a validated preclinical model of CMT2A. Serum NfL levels were significantly elevated in CMT2A patients compared to healthy controls, a finding corroborated in transgenic mice. Notably, NfL levels in CMT2A patients were higher than in SMA3 but lower than in ALS patients, supporting the ability of this biomarker to discriminate between clinically overlapping neuromuscular conditions. Higher NfL levels were associated with younger age, earlier disease onset, and shorter disease duration, suggesting a role as a marker of early disease burden. However, no significant correlation was observed with clinical severity scores or electrophysiological measures. Serum FGF21 levels were also significantly elevated in CMT2A patients compared to controls, whereas NCAM1 and GDF15 levels did not differ significantly between groups. These findings support the role of serum NfL as a translational biomarker of axonal damage in CMT2A, capable of distinguishing affected individuals from both healthy and neurological disease controls. The concomitant elevation of FGF21 further underscores the contribution of mitochondrial dysfunction to CMT2A pathophysiology. Together, these results highlight the potential of serum biomarkers to refine diagnostic workflows and facilitate therapeutic development and future clinical trials for CMT2A.},
}

*Charcot-Marie-Tooth Disease/blood/diagnosis/genetics
Humans
Biomarkers/blood
*Growth Differentiation Factor 15/blood
Female
*Fibroblast Growth Factors/blood
Male
Animals
Middle Aged
Adult
*Neurofilament Proteins/blood
Mice
Mice, Transgenic
Aged
Case-Control Studies
Neural Cell Adhesion Molecules/blood

@article {pmid42183628,
year = {2026},
author = {Wei, Z and Zhang, M and Tang, W and Singh, BK and Zhiwei, Z and Lei, Z and Goh Kim Wee, J and Tan Rui En, F and Jingxiu, H and Qiaoyang, S and Bin, X and Priyanka, G and Xuyang, AS and Li, Z and Han-Ming, S and King, TE},
title = {CHCHD2 and CHCHD10 promoted autophagic clearance of protein aggregates via GABARAPs.},
journal = {Autophagy},
volume = {},
number = {},
pages = {},
doi = {10.1080/15548627.2026.2678427},
pmid = {42183628},
issn = {1554-8635},
abstract = {Mutations in mitochondrial protein CHCHD2 and its paralog CHCHD10 were identified in patients with Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) or Alzheimer disease (AD). CHCHD2 and CHCHD10 mutations caused neurodegeneration in model animals as seen in patients, but their pathophysiological roles remain elusive. Here we reported a direct role of CHCHD2 and CHCHD10 in autophagy. We identified a protein complex composing of CHCHD2-CHCHD10-C1QBP/p32-Atg8-family proteins (ATG8s), in which each molecule interacted with another. CHCHD2, CHCHD10 and C1QBP/p32 associated with ATG8s, preferentially, GABARAPs. Disease-associated CHCHD2 and CHCHD10 mutations exhibited varied interaction with ATG8s. By binding to GABARAPs, CHCHD2 and CHCHD10 underwent autophagic degradation, and recruited the ULK1 complex. Autophagy initiation defects occurred upon transient knockdown of CHCHD2, and also in human iPSC-derived CHCHD2[-/-] or CHCHD2[T61I] dopaminergic neurons. Importantly, CHCHD2 and CHCHD10 promoted autophagy. CHCHD2 reduced protein aggregates in cells and toxic SNCA/α-synuclein species in mouse striatum. Our study thus revealed mitochondrial proteins CHCHD2 and CHCHD10 as both autophagy substrates and autophagy activators and laid groundwork for therapy targeting patients with neurodegeneration.},
}

@article {pmid42183665,
year = {2026},
author = {Tavaglione, L and Madonia, N and Corrado, L and Comi, C and D'Alfonso, S and Mazzini, L and De Marchi, F},
title = {Expanding the phenotypic spectrum of SOD1‑related ALS: upper motor neuron predominance in a p.D91A case.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-5},
doi = {10.1080/17582024.2026.2676822},
pmid = {42183665},
issn = {1758-2032},
abstract = {Mutations in superoxide dismutase 1 SOD1 are the second most common genetic cause of ALS, usually associated with prevalent lower motor neuron phenotypes. We describe a 66-year-old woman with slowly progressive spastic paraparesis, initially diagnosed as primary lateral sclerosis, who carried a heterozygous p.D91A mutation. Clinical and neurophysiological findings indicated predominant upper motor neuron involvement, an unusual presentation for this mutation. This case broadens the SOD1 phenotypic spectrum and highlights the importance of early genetic testing in atypical motor syndromes, given the availability of targeted therapies where diagnostic delay may limit benefit.},
}

@article {pmid42183747,
year = {2026},
author = {Ma, G and Shi, Y and Qiu, J and Ren, C and Shao, K and Shu, X},
title = {Cumulative Environmental Burden and Neurodegenerative Disease Mortality: A National Ecological Study in the United States.},
journal = {American journal of epidemiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/aje/kwag114},
pmid = {42183747},
issn = {1476-6256},
abstract = {Neurodegenerative diseases (NDDs) represent a growing cause of mortality and disability among aging populations worldwide. However, the relationship between cumulative, multi-domain environmental exposures and NDD mortality remains poorly characterized. This study aimed to examine the association between comprehensive environmental quality and NDD mortality in the United States. We used the Environmental Quality Index (EQI) from 2000 to 2005 to characterize cumulative environmental exposure. Associations between EQI quintiles and NDD mortality, including dementia, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, were examined using Bayesian interval-censored mixed-effects models. During 2006-2020, among 3.66 million NDD deaths, poorer environmental quality (Q5 vs. Q1) was associated with mortality rate differences of 24.72 (95% CrI: 22.43, 27.06) per 100,000 at 5-year lag, 26.74 (95% CrI: 24.34, 29.21) at 10-year lag, and 22.74 (95% CrI: 20.49, 25.13) at 15-year lag. Within each lag period, a clear dose-response pattern was consistently observed across EQI quintiles. Furthermore, associations were most pronounced for the air quality, followed by sociodemographic disadvantage. In addition, demographic and geographic heterogeneity was observed across sex, race, census regions, urbanicity, climate zone and county economic type. These findings underscore the need for integrated, place-based environmental health policies targeting neurodegeneration prevention.},
}

@article {pmid42183749,
year = {2026},
author = {Trad, G and Lenglet, T and Querin, G and Blancho, S and Marchand-Pauvert, V and Hogrel, JY and Pradat, PF},
title = {Beyond outcomes: patients' lived experience of exoskeleton-assisted gait training in amyotrophic lateral sclerosis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/21678421.2026.2674021},
pmid = {42183749},
issn = {2167-9223},
abstract = {OBJECTIVES: To explore patients' expectations and lived experience of Atalante exoskeleton-assisted gait training in amyotrophic lateral sclerosis (ALS).

METHODS: In the EXALS study (NCT06199284), 10 ambulatory ALS participants completed 18 sessions of Atalante exoskeleton-assisted gait training. After completion of the intervention phase, post-training semi-structured interviews were audio-recorded, transcribed verbatim, and analyzed using inductive qualitative content analysis approach. Structured interview items were summarized descriptively.

RESULTS: Ten participants reported positive expectations and experiences. Initial expectations most often included contributing to research (5/10), maintaining walking ability (4/10), and improving gait quality/balance (3/10). Expectation fulfillment was high (very satisfied: 7/10). The rehabilitative aspect was most frequently ranked as most reflective of the experience (rank 1: 4/10), followed by motivational/recreational (rank 2: 4/10), psychological/emotional was most often ranked last (rank 5: 5/10). Participants described perceived benefits including improved upright posture, stability, reduced stiffness, smoother gait, and reduced fear of falling, though some effects were described as short-lived. Three-word summaries were predominantly positive (8/10), commonly "interesting" and "motivating," with occasional negatives (tiring/heavy/repetitive/disappointing; 2/10). Compared with conventional physiotherapy, sessions were perceived as more dynamic and walking-focused, with a structured, innovative, closely supervised set-up. Suggested improvements centered on increasing access/dose, expanding walking space and training content, and enhancing safety/user control. Most participants would continue training if available (8/10), most commonly preferring two sessions per week (4/8).

CONCLUSIONS: Exoskeleton-assisted gait training was experienced as acceptable and meaningful. Translating this into practice will require aligning future protocols with patient priorities, autonomy/safety, access and delivery logistics, and broader functional content alongside quantitative evaluation.},
}

@article {pmid42185781,
year = {2026},
author = {Fujiwara, Y and Hashiguchi, A and Yamashiro, S and Seno, H and Ohya, Y and Yasutomi, D and Fujisaki, N and Kido, M and Suwazono, S and Tokashiki, T},
title = {Association between creatinine-to-cystatin C ratio and ALSFRS-R across clinical phenotypes.},
journal = {BMC neurology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12883-026-04983-6},
pmid = {42185781},
issn = {1471-2377},
abstract = {BACKGROUND: Reliable and accessible biomarkers for amyotrophic lateral sclerosis (ALS) are scarce. Creatinine (Cre) reflects muscle mass, whereas cystatin C (CysC) may reflect neurodegeneration without being directly influenced by muscle mass; however, both have limitations. We aimed to investigate whether the creatinine-to-cystatin C ratio (Cre/CysC) was cross-sectionally associated with functional status in patients with ALS.

METHODS: We retrospectively analyzed 30 patients diagnosed with ALS at the National Organization Hospital Okinawa Hospital between 2021 and 2024. Baseline ALS Functional Rating Scale-Revised (ALSFRS-R) scores and serum Cre and CysC levels were recorded. Associations with the ALSFRS-R were assessed using Spearman's correlation, with subgroup analyses by sex, site of onset, age at diagnosis, body mass index (BMI), and diagnostic delay. Multivariable analyses were performed to examine the independent association between Cre/CysC and ALSFRS-R while accounting for relevant clinical covariates.

RESULTS: Cre/CysC showed a stronger cross-sectional correlation with ALSFRS-R (rs=0.648, p = 0.0001) than Cre alone (rs =0.427) or CysC (rs =-0.119). Exploratory subgroup analyses showed generally positive associations in several subgroups, although no statistically significant association was observed in the small bulbar-onset subgroup. In multivariable analysis adjusted for age at onset and diagnostic delay, Cre/CysC remained independently associated with ALSFRS-R (β = 20.1, 95% CI 6.41-33.9, p = 0.006). Given the small sample size and cross-sectional design, these findings should be interpreted as exploratory.

CONCLUSIONS: Cre/CysC showed a stronger cross-sectional association with functional status than either marker alone. Because it is derived from routine laboratory tests, Cre/CysC may represent a simple exploratory measure associated with functional status in ALS. However, the present findings do not establish prognostic utility or fully account for disease stage and biological heterogeneity. Prospective longitudinal studies incorporating disease progression measures and broader clinical and genetic characterization are warranted.},
}

@article {pmid42186042,
year = {2026},
author = {Salgueiro, AM and Ferreira-Marques, M and Ribeiro, RFN and Lopes, SM and Pereira, D and Costa, DG and Santana, MM and de Almeida, LP and Cavadas, C},
title = {Ketogenic diet as a therapeutic strategy for neurodegenerative diseases: from mechanisms to translational challenges.},
journal = {Translational neurodegeneration},
volume = {15},
number = {1},
pages = {},
pmid = {42186042},
issn = {2047-9158},
support = {UIDB/04539/2020//Fundação para a Ciência e a Tecnologia/ ; UIDP/04539/2020//Fundação para a Ciência e a Tecnologia/ ; LA/P/0058/2020(JPND/ 0001/2022//Fundação para a Ciência e a Tecnologia/ ; DOI: 10.54499/JPND/0001/2022; JPND/0002/2022//Fundação para a Ciência e a Tecnologia/ ; DOI: 10.54499/JPND/0002/2022//Fundação para a Ciência e a Tecnologia/ ; SFRH/BD/120023/2016; 2020.04850.BD//Fundação para a Ciência e a Tecnologia/ ; 2022.11293.BD//Fundação para a Ciência e a Tecnologia/ ; GeneT project-The Gene Therapy CoE at the Center of Portugal (Project ID: 101059981//HORIZON EUROPE Widening participation and spreading excellence/ ; DOI: 10.3030/101059981); GCure - From Gene to Cure//HORIZON EUROPE Widening participation and spreading excellence/ ; ID: 101186929//HORIZON EUROPE Widening participation and spreading excellence/ ; DOI:10.3030/101186929; GeneH - Excellence Hub for Advancing Innovation in Gene Therapy//HORIZON EUROPE Widening participation and spreading excellence/ ; ID: 101186939//HORIZON EUROPE Widening participation and spreading excellence/ ; DOI: 10.3030/101186939//HORIZON EUROPE Widening participation and spreading excellence/ ; },
mesh = {Humans ; *Diet, Ketogenic/methods ; *Neurodegenerative Diseases/diet therapy/metabolism ; Animals ; *Translational Research, Biomedical/methods ; Gastrointestinal Microbiome/physiology ; Oxidative Stress/physiology ; },
abstract = {The ketogenic diet (KD) is increasingly recognized as a promising therapeutic strategy for neurodegenerative disorders because of its multifaceted impacts on key pathophysiological mechanisms. This review explores the molecular pathways through which KD may protect against neurodegeneration, including the use of ketone bodies as alternative energy substrates, reduction of oxidative stress and inflammation, modulation of autophagy and protein aggregation, and impact on the gut microbiome. The potential benefits of KD are explored across neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis, based on both preclinical and clinical evidence that supports its feasibility. However, challenges in long-term safety, patient adherence, and clinical practicality limit its widespread adoption. This review underscores the potential of KD for treating neurodegeneration on the basis of current scientific evidence while highlighting the need for further research to optimize its application and address existing gaps.},
}

Humans
*Diet, Ketogenic/methods
*Neurodegenerative Diseases/diet therapy/metabolism
Animals
*Translational Research, Biomedical/methods
Gastrointestinal Microbiome/physiology
Oxidative Stress/physiology

@article {pmid42186501,
year = {2026},
author = {AlSabah, AA and Reda, H},
title = {SOD1 amyotrophic lateral sclerosis associated with Neurosarcoidosis: a case report and review of the literature.},
journal = {Oxford medical case reports},
volume = {2026},
number = {5},
pages = {omag078},
pmid = {42186501},
issn = {2053-8855},
abstract = {We describe a 37-year-old man with coexisting amyotrophic lateral sclerosis (ALS) caused by a mutation in superoxide dismutase 1 (SOD1) and probable neurosarcoid myeloradiculitis. The concurrence of the two rare conditions posed significant diagnostic and therapeutic challenges. We discuss the diagnostic timeline, therapeutic interventions, outcomes over half a decade of care, and a review of relevant literature.},
}

@article {pmid42186604,
year = {2026},
author = {Albadri, Z and Häbel, H and Thorslund, K and Grönhagen, C and Seifert, O},
title = {Associations between bullous pemphigoid and comorbidities: A Swedish nationwide cohort study of 5,738 patients.},
journal = {Journal of multimorbidity and comorbidity},
volume = {16},
number = {},
pages = {26335565261455676},
pmid = {42186604},
issn = {2633-5565},
abstract = {BACKGROUND: Bullous pemphigoid (BP) has been linked to neurological and psychiatric disorders, but no nationwide population-based study has comprehensively examined the association of various comorbidities in BP patients in Sweden.

OBJECTIVES: To investigate the associations between BP and various comorbidities, comparing these conditions before and after BP diagnosis with a matched control group.

METHODS: A nationwide cohort study was conducted in Sweden from 2005 to 2016, including 5,738 BP cases and 17,167 age, sex and county of residence matched controls. Multivariable Cox proportional hazard regression models were used to calculate hazard ratios (HR). Univariable logistic regression assessed pre-diagnosis comorbidities, generating prevalence odds ratios (POR) with 95% confidence intervals (CI).

RESULTS: BP was associated with a significantly higher overall HR for comorbidity (HR: 2.20, 95% CI: 2.08-2.33). Before BP diagnosis, the overall comorbidity was significantly increased POR 2.72 (95% CI: 2.56-2.90). Pre-diagnosis association included dementia, Parkinson's disease, epilepsy, amyotrophic lateral sclerosis, multiple sclerosis, schizophrenia, unipolar/bipolar disorders, suicide, diabetes, stroke, systemic lupus erythematosus, systemic sclerosis, psoriasis, lichen planus, alopecia areata, and vitiligo. After diagnosis, the overall hazard ratio (HR) for comorbidities was highest within the first year (HR 2.88, 95% CI: 2.68-3.10) and remained elevated beyond one year (HR 1.57, 95% CI: 1.44-1.71). Post-diagnosis associations remained elevated for dementia, Parkinson's disease, epilepsy, schizophrenia, unipolar/bipolar, diabetes, psoriasis, lichen planus and autoimmune diseases such as systemic sclerosis and Sjögren's syndrome.

CONCLUSION: BP is strongly associated with neurodegenerative, psychiatric, autoimmune, and metabolic comorbidities before and after diagnosis, highlighting their clinical significance as predisposing and prognostic factors in BP patients.},
}

@article {pmid42186910,
year = {2026},
author = {Tong, VS and Pontell, ME},
title = {Invited Commentary on: Islam et al.'s "Evaluating Appropriateness of Interfacility Transfers for Patients with Facial Trauma Including Acute Orbital Floor Fractures".},
journal = {Facial plastic surgery & aesthetic medicine},
volume = {},
number = {},
pages = {26893614261452862},
doi = {10.1177/26893614261452862},
pmid = {42186910},
issn = {2689-3622},
}

@article {pmid42187212,
year = {2026},
author = {Kibreab, F and Haraburda, A and Albaba, YAA and Yong, AC and Shah, K and Buthelezi, S and Chan, VF},
title = {A scoping review of theoretical and measurement approaches to women's empowerment in low-and middle-income countries' capacity-building interventions.},
journal = {Global health action},
volume = {19},
number = {1},
pages = {2676412},
doi = {10.1080/16549716.2026.2676412},
pmid = {42187212},
issn = {1654-9880},
mesh = {*Developing Countries ; *Empowerment ; Humans ; Female ; *Capacity Building/organization & administration ; *Women's Rights ; Entrepreneurship ; Gender Equity ; *Power, Psychological ; },
abstract = {Women's empowerment is critical for achieving gender equality and sustainable development in low-and-middle-income countries (LMICs). Capacity-building interventions, such as vocational training, microfinance, and digital literacy programmes, are frequently employed to foster empowerment. However, wide variation exists in how empowerment is defined, theorised, and measured, limiting comparability across studies. This scoping review mapped the conceptual foundations, theoretical frameworks, and measurement approaches used in capacity-building interventions for women entrepreneurs in LMICs. The review followed Arksey and O'Malley's framework and was reported in line with PRISMA-ScR guidelines. Searches were conducted in PubMed, Scopus, Web of Science, and JSTOR, complemented by grey literature from major development agencies (2010-2024). Eligible studies focused on capacity-building interventions targeting women entrepreneurs in LMICs. Two reviewers independently screened and extracted data, which were synthesised thematically. Of 11,109 records identified, 25 met inclusion criteria. Most studies were cross-sectional, conducted in sub-Saharan Africa (48%) and South Asia (32%). While 76% defined empowerment, 60% did not employ any explicit theoretical or conceptual framework. Among those that did, frameworks, such as Kabeer's, Longwe's, and Malhotra et al.'s were used inconsistently. Economic empowerment was the most frequently assessed domain, often measured through income or business performance, while social, political, and psychological dimensions were seldom examined. Indicators were heterogeneous and largely self-reported. Conceptual ambiguity and inconsistent measurement hinder progress in women's empowerment research in LMICs. Future studies should adopt theoretically grounded, multidimensional, and context-sensitive frameworks to capture empowerment as a dynamic process beyond economic gains.},
}

*Developing Countries
*Empowerment
Humans
Female
*Capacity Building/organization & administration
*Women's Rights
Entrepreneurship
Gender Equity
*Power, Psychological

@article {pmid42187452,
year = {2026},
author = {Kolukisa Birgec, B and Toprak, B and Mullen, AB},
title = {Assessment of Respiratory Rate and Simulated Apnea Utilizing the PneumoWave Biosensor: In Vitro and In Vivo Validation.},
journal = {Biosensors},
volume = {16},
number = {5},
pages = {},
doi = {10.3390/bios16050256},
pmid = {42187452},
issn = {2079-6374},
support = {YLSY2018/YLSY2020//Mi̇lli̇ Eği̇ti̇m Bakanliği/ ; },
mesh = {Humans ; *Biosensing Techniques ; *Respiratory Rate/physiology ; *Apnea/diagnosis/physiopathology ; Monitoring, Physiologic ; Male ; Adult ; Female ; Manikins ; },
abstract = {Accurate monitoring of respiratory rates is critical for early detection of a range of clinical conditions. However, standard manual counting or inadequate clinical monitoring often fails to provide reliable measurements. This study evaluated and validated the PneumoWave biosensor for respiratory rate measurement across a broad physiological range and different body postures (45°, 90°, and 180°) in both in vitro and in vivo settings. In vitro validation was performed using a SimMan ALS manikin operated at respiratory settings of 6-30 breaths per minute, with 10 s periods of simulated apnea. In vivo validation involved 20 healthy volunteers performing metronome-guided breathing while wearing bilateral PneumoWave biosensors. In vitro results demonstrated an excellent correlation between biosensors and manikin respiratory settings and captured all apnea events (r = 0.99, ICC = 0.99). In vivo findings showed good agreement with direct observational count (r = 0.99, R[2] = 0.99, ICC = 0.99), with 97% of apnea events captured by both devices in all positions. Body postures had no significant impact on biosensor accuracy. These findings demonstrate that the PneumoWave biosensor provides accurate and reliable respiratory monitoring and supports its potential as a robust, non-invasive tool for continuous clinical and remote patient monitoring.},
}

Humans
*Biosensing Techniques
*Respiratory Rate/physiology
*Apnea/diagnosis/physiopathology
Monitoring, Physiologic
Male
Adult
Female
Manikins

@article {pmid42187823,
year = {2026},
author = {Hayden, E and Kebe, A and Chen, S and Chumley, A and Xia, C and El-Zein, W and Zhong, Q and Ju, S},
title = {RNA-Binding Protein TAF15 Suppresses Toxicity in a Yeast Model of FUS Proteinopathy.},
journal = {Journal of fungi (Basel, Switzerland)},
volume = {12},
number = {5},
pages = {},
doi = {10.3390/jof12050341},
pmid = {42187823},
issn = {2309-608X},
support = {1R15NS109804-01A1/NS/NINDS NIH HHS/United States ; },
abstract = {Mutations in an RNA-binding protein FUS are known to cause familial amyotrophic lateral sclerosis (ALS). Since this discovery, mutations in several other RNA-binding proteins (RBPs) have also been linked to ALS. Some of these ALS-associated RBPs have been shown to colocalize with ribonucleoprotein (RNP) granules such as stress granules and processing bodies (p-bodies). Increasing evidence has emerged supporting a hypothesis that the impaired clearance, inappropriate assembly, and dysregulation of RNP granules play a role in ALS. Through the genome-scale overexpression screening of a yeast model of FUS toxicity, we found that TAF15, a human RBP with a similar protein domain structure and belonging to the same FET protein family as FUS, suppresses FUS toxicity in yeast. The suppression by TAF15 is specific to FUS and not found in other yeast models of neurodegenerative disease-associated proteins. We showed that the RNA recognition motif (RRM) of TAF15 is required for its suppression of FUS toxicity. Furthermore, FUS and TAF15 physically interact, and the C-terminus of TAF15 is required for both the physical protein-protein interaction and its protection against FUS toxicity. Finally, while FUS induces and colocalizes with both stress granules and p-bodies, TAF15 only induces and colocalizes with p-bodies. Importantly, the co-expression of FUS and TAF15 induces more p-bodies than individually expressing each gene alone, and FUS toxicity is exacerbated in yeast that is deficient in p-body formation. Overall, our findings suggest a role of increased p-body formation in the suppression of FUS toxicity by TAF15.},
}

@article {pmid42188341,
year = {2026},
author = {Buccarello, L and Montagna, C and Di Matteo, S and Mangione, R and Carota, G and Sibbitts, J and Jarosova, R and Lunte, SM and Lazzarino, G and Caruso, G},
title = {The Bright and Dark Sides of Nitric Oxide in Neurodegenerative Diseases.},
journal = {Journal of personalized medicine},
volume = {16},
number = {5},
pages = {},
doi = {10.3390/jpm16050246},
pmid = {42188341},
issn = {2075-4426},
abstract = {Nitric oxide (NO) plays an important role in neuronal communication, synaptic plasticity and vascular regulation. Due to its important function in neuronal homeostasis, NO imbalance is associated with neurodegeneration. Specifically, in Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and frontotemporal lobar degeneration (FTLD), an excessive amount of NO, mostly produced by inducible NO synthase (iNOS), reacts with superoxide to form peroxynitrite, driving oxidative/nitrosative stress, mitochondrial dysfunction, and aberrant protein modifications. In AD, NO dysregulation promotes amyloid-β (Aβ) accumulation, tau hyperphosphorylation and synaptic loss, creating a self-perpetuating cycle of neuronal damage. NO's dual role, protective at physiological levels but harmful if overproduced, underscores the therapeutic potential of antioxidant compounds that restore the balance of NO/NOS (especially iNOS) while preserving physiological functions. However, despite the emerging role of antioxidant-based therapeutic approaches, clinical translation is limited by the complexity of NO signaling and the absence of safe, specific NOS inhibitors. By targeting the molecular switch from protective to toxic, NO activity may offer new personalized treatment avenues for neurodegenerative diseases.},
}

@article {pmid42188687,
year = {2026},
author = {Fajkić, A and Belančić, A and Pilipović, K and Rački, V and Mežnarić, S and Janković, T and Gkrinia, EMM and Vitezić, D and Mršić-Pelčić, J},
title = {Nanotube-Assisted Motor Neuron and Neuromuscular Junction Stabilization in Spinal Muscular Atrophy: A Hypothesis for Adjunctive Therapy.},
journal = {Neurology international},
volume = {18},
number = {5},
pages = {},
doi = {10.3390/neurolint18050087},
pmid = {42188687},
issn = {2035-8385},
abstract = {Spinal muscular atrophy (SMA) therapies that restore SMN expression improve survival and motor function but often fail to fully stabilize distal motor units or sustain endurance. We propose a hypothesis-driven adjunctive approach, intended to complement SMN-restoring therapies, in which localized nanotube-enabled interfaces acting at or near the distal motor unit and neuromuscular junction enhance neuromuscular transmission reliability in surviving, remodeled motor units. The model predicts a temporal cascade: improved junctional reliability and reduced activity-dependent failure, followed by consistent motor unit output across repeated activation, and ultimately, enhanced endurance and functional reserve. Phenotype-specific responsiveness identifies patients most likely to benefit, specifically those with preserved-but-limited residual motor unit substrate accompanied by measurable neuromuscular junction instability. Drawing on shared mechanisms from ALS, spinal cord injury, and other neuromuscular disorders, we discuss mechanistic, translational, safety, regulatory, and ethical considerations. This framework links objective physiological constructs to functional outcomes, offering a mechanistically grounded path for adjunctive therapy development in SMA and related conditions.},
}

@article {pmid42189100,
year = {2026},
author = {Lockhart, ENS},
title = {Cybernetic Feedback: an Apt Realignment of Batterham et al.'s Three-Body Problem of Suicide (2025).},
journal = {Journal of evaluation in clinical practice},
volume = {32},
number = {4},
pages = {e70487},
doi = {10.1111/jep.70487},
pmid = {42189100},
issn = {1365-2753},
}

@article {pmid42190746,
year = {2026},
author = {Zheng, P and Chen, L},
title = {Comments on Wu et al's "The efficacy and adverse reactions of 755 nm picosecond alexandrite laser on the treatment of nevus of Ota at different endpoints".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.03.126},
pmid = {42190746},
issn = {1097-6787},
}

@article {pmid42174979,
year = {2026},
author = {Faujour, C and Bouee, S and Emery, C and Jannot, AS},
title = {Evaluating the Role of Order and Time Information for Classifying Sequences of Healthcare Events Derived from Claims Data.},
journal = {Studies in health technology and informatics},
volume = {336},
number = {},
pages = {879-883},
doi = {10.3233/SHTI260305},
pmid = {42174979},
issn = {1879-8365},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology ; *Insurance Claim Review/statistics & numerical data ; },
abstract = {Sequences of healthcare events from claims data are increasingly used for predictive modeling. Despite the rise in popularity of neural networks, the benefit of modeling event order and timing remains underexplored. We simulated patient trajectories using parameters estimated from claims data including 22,000 amyotrophic lateral sclerosis (ALS) cases and 22,000 age and gender-matched controls. The simulation reproduced irregular event timing and condition-related activity that increased near an incident diagnosis. We compared three model families for population classification: frequency-based models, sequential models (long short-term memory and Transformer architectures) capturing event order, and sequential models incorporating temporal information. Performance was evaluated using the area under the ROC curve (AUC) at multiple time points before diagnosis. Sequential models outperformed frequency-based baselines by about +0.06 AUC on average, confirming the benefit of modeling event order. Adding time information provided no noticeable improvement, and results were stable across different time encoding and scaling methods. These findings suggest that, in claims-based classification tasks, event order captures most of the useful temporal signal, while explicit time encoding offers limited additional benefit under similar conditions.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/epidemiology
*Insurance Claim Review/statistics & numerical data

@article {pmid42175187,
year = {2026},
author = {Yadav, R and Pragya, P and Agastinose Ronickom, JF},
title = {Identification of Reliable Biomarkers for ALS Through Machine Learning Approach.},
journal = {Studies in health technology and informatics},
volume = {336},
number = {},
pages = {1705-1709},
doi = {10.3233/SHTI260516},
pmid = {42175187},
issn = {1879-8365},
mesh = {*Amyotrophic Lateral Sclerosis/genetics/diagnosis ; Humans ; *Machine Learning ; Biomarkers/analysis ; Gene Expression Profiling/methods ; Transcriptome ; Algorithms ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron degeneration and limited diagnostic biomarkers. Identifying robust molecular biomarkers for ALS remains a major challenge due to disease heterogeneity and high-dimensional gene expression data. In this study, we developed a machine learning (ML) based pipeline integrating transcriptome data and feature selection to identify potential ALS biomarkers. RNA-Seq data of motor neuron disease patients and healthy controls were obtained from publicly available GEO datasets, followed by preprocessing was performed. We implemented two ensembled ML models such as eXtreme gradient boosting (XGBoost) and random forest (RF) algorithms under a five-fold stratified cross-validation framework to identify the differentially expressed genes. These models were evaluated using the performance metrics. We identified top 10 genes ranked by feature importance from the XGBoost and RF models. Notably, the DCN (Decorin) gene appears consistently in the top 10 features of both models, underscoring its stability and biological relevance. Both ML models exhibited excellent classification performance, with RF achieving 98.8% accuracy and XGBoost achieving 97.6% accuracy, alongside consistently high sensitivity, specificity, precision, and F1-score values. This work highlights the utility of transcriptomic data and ML in identifying key genes as biomarkers for diagnostic and therapeutic potential in ALS.},
}

*Amyotrophic Lateral Sclerosis/genetics/diagnosis
Humans
*Machine Learning
Biomarkers/analysis
Gene Expression Profiling/methods
Transcriptome
Algorithms

@article {pmid42177450,
year = {2026},
author = {Ghasemi, F and Khoshnam Rad, N and Rashidinejad, B and Nasrollahzadeh, M},
title = {Pulmonary toxocariasis presenting as migratory pulmonary infiltrates and mediastinal lymphadenopathy: a case report and literature review.},
journal = {BMC pulmonary medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12890-026-04362-4},
pmid = {42177450},
issn = {1471-2466},
abstract = {BACKGROUND: Pulmonary toxocariasis, caused by the nematode Toxocara canis or T. cati, is an underdiagnosed cause of eosinophilic lung disease with highly variable radiological presentation that often mimics malignancy or other eosinophilic conditions.

CASE PRESENTATION: A 53-year-old female smoker presented with progressive dyspnea and cough. Initial chest CT revealed right lower lobe consolidation with mediastinal lymphadenopathy (station 4R with short-axis diameters 12 mm), raising concern for lung cancer. Bronchoscopy with EBUS-TBNA was non-diagnostic. The patient was empirically started on dexamethasone (8 mg daily, tapered over 3 months) for suspected organizing pneumonia. During steroid taper, her symptoms recurred with delayed emergence of peripheral eosinophilia (670/µL; initial absolute eosinophil count on presentation was 90/µL), elevated IgE (456 IU/mL), and serial CT scans demonstrating migratory pulmonary infiltrates involving the right lower, right middle, and left lower lobes. A history of raw beef liver consumption prompted serological testing, which confirmed Toxocara canis infection. Treatment with albendazole alone (400 mg twice daily for 14 days, without corticosteroids) resulted in complete clinical and radiological resolution.

LITERATURE REVIEW: We searched PubMed and Scopus (January 2014 - February 2026) for English- and French-language case reports of pulmonary toxocariasis. Fourteen new cases were identified and analyzed alongside the 12 cases from Ranasuriya et al.'s [1] review. These 26 cases demonstrate marked radiologic heterogeneity: multiple bilateral nodules (50%), consolidations (23%), pleural effusion (27%), and migratory infiltrates (8%). Pleural effusion has emerged as a distinct manifestation in seven recent cases. Delayed eosinophilia occurred in 12% of cases. Immunocompromised states (including primary ciliary dyskinesia, hematologic malignancies, and immunosuppressive therapy) were present in 23% of cases and may predispose to atypical presentations.

CONCLUSION: Pulmonary toxocariasis should be considered in patients with migratory infiltrates, unexplained eosinophilic pleural effusion, or lung nodules with eosinophilia. A meticulous dietary and exposure history is essential. Diagnosis is confirmed by serology, and patients respond well to albendazole therapy.},
}

@article {pmid42177561,
year = {2026},
author = {Sharma, S and Cortés-Pérez, C and Bird, S and Di Curzio, D and Vandenakker, A and Schellenberg, K and Douville, RN},
title = {ERVK activity in CD8[+] T cell immune cell compartment in patients with ALS.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-026-03871-7},
pmid = {42177561},
issn = {1742-2094},
support = {19-IIA-489//ALS Association/ ; 19-IIA-489//ALS Association/ ; },
abstract = {Endogenous retrovirus-K (ERVK) expression has been associated with Amyotrophic Lateral Sclerosis (ALS), and its viral proteins can be detected in affected brain and spinal cord tissues. Despite confirmation of ERVK load in the blood of patients with ALS, few studies have examined ERVK protein expression in immune cells. ERVK produces an enzyme called integrase (IN), which can cause DNA damage during the integration of viral DNA into the host genome. Given that genomic instability is a hallmark of ALS, we hypothesized that the ERVK IN enzyme may also be expressed in lymphoid and myeloid-derived immune cells of patients. Peripheral blood mononuclear cells (PBMC) were isolated from blood specimens using Ficoll isolation, and either flash-frozen for western blot analyses or affixed onto slides using the cytospin technique for subsequent confocal microscopy analysis. Image analysis of confocal micrographs revealed that ERVK IN expression was significantly elevated in CD3[+]CD8[+] T cells from a subset of patients with ALS as compared to controls. CD3[+]CD8[+] T cells in ALS exhibit enhanced number and size of ERVK IN puncta within the nucleus and at the plasma membrane. The DNA damage load, as measured by marker γH2AX, was strongly associated with ERVK IN levels in both controls and patients with ALS. Stratification of molecular data based on clinical parameters showed an association of elevated ERVK IN load in CD8[+] T cells from patients with ALS with lower ALSFRS-R and higher King's scores, as well as a significant decline in lung function metrics. In bulk PBMC from patients with ALS, ERVK IN was associated with expression of immune checkpoint marker PD-1, but not T cell exhaustion marker TOX. ERVK IN in CD14[+]CD11b[+] myeloid cells was also elevated, with ERVK[+] cells exhibiting notable membrane ruffling typical of immune cell activation and increased expression of HLA-DR. However, ERVK IN expression in monocytes was not correlated with clinical metrics in patients with ALS. This work points to the use of ERVK IN in CD8[+] cytotoxic T cells as a blood biomarker for ALS clinical trials, especially those focused on testing the efficacy of antivirals as a therapeutic strategy for ALS.},
}

@article {pmid42177632,
year = {2026},
author = {Schimmack, U and Soto, MD},
title = {A response to Pek et al.'s commentary on Z-curve: clarifying the assumptions of selection models.},
journal = {Cognition & emotion},
volume = {},
number = {},
pages = {1-5},
doi = {10.1080/02699931.2026.2678998},
pmid = {42177632},
issn = {1464-0600},
abstract = {Pek et al. (2026. What does a Z-curve analysis tell us? Cognition & Emotion, 1-16) comment on Soto and Schimmack (2025. Credibility of results in emotion science: A z-curve analysis of results in the journals Cognition & Emotion and Emotion. Cognition & Emotion) and raise concerns about the use of z-curve to evaluate the credibility of emotion research. Their central criticism is based on simulations showing that z-curve can overestimate the expected discovery rate when selection operates not only at the level of statistical significance but also within the set of significant results as a function of effect size. This point is correct: if researchers selectively publish larger significant effects while suppressing smaller significant ones, selection models that assume threshold-based filtering can be biased. However, this limitation is not unique to z-curve and applies equally to other selection models used in meta-analysis. More importantly, there is currently little empirical evidence for effect-size bias, while there is ample evidence of selection based on significance. Under these more realistic conditions, z-curve provides informative estimates of (a) selection bias, (b) the expected replication rate, and (c) the false positive risk. Our results also demonstrate substantial inflation of effect size estimates in traditional meta-analyses that ignore selection processes. For these reasons, we reject the recommendation to rely solely on standard meta-analytic approaches and advocate for the use of selection models to obtain more realistic estimates.},
}

@article {pmid42178739,
year = {2026},
author = {Paquet, A and Touzel-Deschênes, L and Roy, V and Saikali, S and Dupré, N and Gros-Louis, F},
title = {Proteomic Analysis of Corpora Amylacea Extracted From Post-mortem Brain of MAiD-end-of-life Sporadic ALS Patients.},
journal = {Brain and behavior},
volume = {16},
number = {5},
pages = {e71486},
doi = {10.1002/brb3.71486},
pmid = {42178739},
issn = {2162-3279},
support = {//tier-1 Canada Research Chair/ ; //CHU de Québec Foundation-Desjardins/ ; /CAPMC/CIHR/Canada ; //Canada Foundation for Innovation/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology ; Proteomics/methods ; Male ; Female ; Aged ; Middle Aged ; *Brain/metabolism/pathology ; *Inclusion Bodies/metabolism/pathology ; Biomarkers/metabolism ; Aged, 80 and over ; Autopsy ; Proteome ; },
abstract = {PURPOSE: Corpora amylacea (CA) are starch-like inclusions that accumulate in the central nervous system (CNS) with aging and are enriched in neurodegenerative conditions, including amyotrophic lateral sclerosis (ALS). Although often regarded as waste reservoirs, their cellular origins, molecular composition, and pathological significance remain poorly understood.

METHODS: Here, we performed an unbiased proteomic analysis of purified CAs isolated from post-mortem brains of sporadic ALS patients and controls.

FINDINGS: In-depth mass spectrometry identified 4,470 proteins, of which 658 were quantified, revealing distinct ALS-specific proteomic signatures. Enriched proteins included markers of cytoskeletal remodeling, mitochondrial dysfunction, and proteostasis disruption, as well as known ALS-associated proteins such as TDP-43 and neurofilament proteins. These findings demonstrate that CAs serve as reservoirs of dysfunctional, disease-relevant proteins and capture key pathological processes in ALS.

CONCLUSION: By applying an unbiased proteomic approach to purified CAs, this study provides the first comprehensive map of their protein content in ALS, supporting their potential as biomarker sources and as a source of mechanistic insights into neurodegeneration.

SIGNIFICANCE: Unbiased analyses of CAs in the context of ALS have yet to be undertaken. This study provides the first proteomic profiling of purified CAs, isolated from ALS patient brains using biochemical methods, revealing that CAs harbor disease-relevant proteins implicated in sporadic ALS. By demonstrating that CAs act as reservoirs of dysfunctional proteins related to metabolism, cytoskeletal organization, and proteostasis, our findings highlight their potential as a novel source of ALS-specific mechanistic insight into disease pathology.},
}

Humans
*Amyotrophic Lateral Sclerosis/metabolism/pathology
Proteomics/methods
Male
Female
Aged
Middle Aged
*Brain/metabolism/pathology
*Inclusion Bodies/metabolism/pathology
Biomarkers/metabolism
Aged, 80 and over
Autopsy
Proteome

@article {pmid42178909,
year = {2026},
author = {Debnath, J and Leidal, AM},
title = {Membrane ATG8ylation in secretory autophagy.},
journal = {Autophagy},
volume = {},
number = {},
pages = {1-16},
doi = {10.1080/15548627.2026.2676796},
pmid = {42178909},
issn = {1554-8635},
abstract = {Mammalian Atg8-family (ATG8) proteins are crucial for macroautophagic/autophagic degradation in the lysosome and facilitate non-degradative processes including multiple distinct forms of unconventional protein secretion. These secretion pathways, collectively termed secretory autophagy, depend upon ATG8 conjugated to membranes to both specify and traffic molecules for extracellular release. Here, we review the current understanding of how membrane ATG8ylation supports secretory autophagy, and propose a cell biological framework for classifying the growing repertoire of secretory autophagy pathways based on membrane ATG8ylation at discrete intracellular vesicular intermediates. Finally, we detail the emerging roles of these pathways in physiology and disease.Abbreviations: Aβ, amyloid-β; Acb1, acyl-coA-binding 1; ALS, amyotrophic lateral sclerosis; APP, amyloid beta precursor protein; APEX2, ascorbate peroxidase; ATG, autophagy related; AWOL, autophagosome-mediated exit without lysis; BafA1, bafilomycin A1; BirA*, mutant BirA biotin ligase; BMI, body-mass index; CASM, ATG8 conjugation at single membranes; DAMPs, danger/damage-associated molecular patterns; DBI, diazepam binding inhibitor, acyl-CoA binding protein; DSS, dextran sodium sulfate; ER, endoplasmic reticulum; ERGIC, endoplasmic reticulum intermediate compartment; ESCRT, endosomal complexes required for transport; EVs, extracellular vesicles; EVPs, extracellular vesicles and particles; HMGB1, high mobility group box 1; IDE, insulin degrading enzyme; IFNB, interferon beta; ILV, intralumenal vesicles; LANDO, LC3-associated endocytosis; LAP, LC3-associated phagocytosis; LIR, LC3 interacting region; LDELS, LC3-dependent EV loading and secretion; LLOMe, L-leucyl-L-leucine methyl ester hydrobromide; M2, influenza A virus matrix 2, MAD, migratory autolysosome disposal; miRNAs, microRNAs; M-MDSC, monocytic myeloid derived suppressor cells; MVEs, multivesicular endosomes; PAMPs, pathogen-associated molecular patterns; P-bodies, processing bodies; PE, phosphatidylethanolamine; PD, Parkinson disease; PS, phosphatidylserine; RBPs, RNA binding proteins; R-EV, RAB22A-induced extracellular vesicle; SLC2A1, solute carrier family 2 member 1; TFRC, transferrin receptor; TGN, trans-Golgi network; TMED10, transmembrane p24 trafficking protein 10; THU, TMED10-channeled unconventional secretion; SALI, secretory autophagy during lysosome inhibition; SCF, SKP1-CUL1-F-box; SNAREs, soluble NSF attachment protein receptors.},
}

@article {pmid42178983,
year = {2026},
author = {Liu, JQ and Liu, H and Sun, YX and Li, Y and Liu, X and Wang, LQ and Yang, Z and Fu, Q and Xu, X and Chen, J and Zhang, Y and Zhou, J and Le, W and Cui, M and Liang, Y},
title = {Protein Disulfide Isomerase Disassembles TDP-43/G3BP1 Condensates and Antagonizes TDP-43 Pathological Aggregates.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e16846},
doi = {10.1002/advs.202516846},
pmid = {42178983},
issn = {2198-3844},
support = {U1967221//National Natural Science Foundation of China/ ; 32071212//National Natural Science Foundation of China/ ; U1967221//National Natural Science Foundation of China/ ; 22022601//National Natural Science Foundation of China/ ; 2024YFA1307300//National Key Research and Development Program of China/ ; 2023ZD0507202//National Major Science and Technology Projects of China/ ; },
abstract = {Cytoplasmic mislocalization and aggregation of transactive response DNA-binding protein-43 (TDP-43) is a common pathological feature of amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration, and Alzheimer's disease with TDP-43 pathology (AD-TDP); the exact role of protein disulfide isomerase (PDI), an enzyme with chaperone activity, in modulating the pathological behavior of TDP-43 is unknown. In this study, we report that wild-type PDI, through its specific interaction with TDP-43, markedly attenuates phase separation of TDP-43, competitively displaces G3BP1 to disassemble TDP-43/G3BP1 condensates, and further counteracts the pathological mislocalization, abnormal phosphorylation, and pathological aggregation of TDP-43 through the b' domain of the enzyme. Ultimately, this alleviates mitochondrial damage and neuronal toxicity caused by TDP-43 aggregation and suppresses UNC13A cryptic splicing in stressed cells. In the presence of abnormal forms of PDI, however, PDI loses its activity, and stress granules containing TDP-43 are assembled into amyloid fibrils, resulting in mitochondrial impairment and neuronal cell death in ALS and AD-TDP patients. These findings not only provide new insights into the pathogenic mechanisms of TDP-43 in neurodegenerative diseases such as ALS and AD-TDP, but also propose PDI as a potential therapeutic target.},
}

@article {pmid42180530,
year = {2026},
author = {Zhao, W and Lai, Y and Li, Z and Yuan, Z and Wen, Z and Zhang, L},
title = {Targeting non-apoptotic regulated cell death (RCD) to treat neurodegenerative diseases.},
journal = {Acta pharmaceutica Sinica. B},
volume = {16},
number = {5},
pages = {2601-2644},
pmid = {42180530},
issn = {2211-3835},
abstract = {Regulated cell death (RCD) is well-known as a controlled form of cell death regulated by one or more cascading signaling pathways. Over the past few decades, increasing evidence has implicated various non-apoptotic forms of RCD in neurons-including ferroptosis, parthanatos, necroptosis, pyroptosis, autophagic cell death, paraptosis, and cuproptosis-in the pathogenesis of neurodegenerative diseases (NDs) and their associated clinical manifestations. We provide an in-depth analysis of the associations between these RCDs and NDs, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), and highlight the potential of modulating non-apoptotic RCD subtypes as neuroprotective targets. Besides, we highlight the crosstalk mechanisms among different non-apoptotic RCDs in NDs and the key targets regulating the crosstalk, which hold significant promise for developing dual-functional inhibitors that precisely modulate the pathological microenvironment and overcome drug resistance. As our understanding of death signaling networks deepens, such strategies may lead to breakthrough therapies for multiple NDs. Moreover, we further discuss the emerging small molecule compounds targeting non-apoptotic RCDs and their current research progress in clinical trials for the treatment of NDs, which may provide novel directions for related drugs. This comprehensive analysis paves the way for future research and therapeutic strategies aimed at harnessing non-apoptotic RCD pathways to mitigate neurodegeneration and improve patient outcomes.},
}

@article {pmid42181829,
year = {2026},
author = {Kuru Çolak, T and Akçay, B and Weiss, HR and Nan, X and Elliott, L and Akkoyunlu, SZ and Borysov, M},
title = {Treatment outcomes across curve patterns and severities in adolescent idiopathic scoliosis treated with a pattern-specific CAD-CAM brace.},
journal = {Frontiers in rehabilitation sciences},
volume = {7},
number = {},
pages = {1826976},
pmid = {42181829},
issn = {2673-6861},
abstract = {BACKGROUND: Whether treatment outcomes differ according to curve pattern or baseline severity in adolescents with idiopathic scoliosis (AIS) remains a subject of debate. In particular, it is unclear whether pattern-specific, CAD-CAM-designed brace systems provide comparable effectiveness across different curvature types. This study aimed to evaluate the influence of curve pattern and initial curve magnitude on treatment outcomes in AIS patients treated with a pattern-specific CAD-CAM-designed brace.

METHODS: A retrospective analysis was conducted on female AIS patients aged 10-14 years (Risser 0-2) treated between 2015 and 2024. Cobb angle and angle of trunk rotation (ATR) were used as primary outcome measures. Data from four international clinics were analyzed for changes in spinal curvature and curve pattern.

RESULTS: A total of 145 patients were included (mean age 12.2 years; mean Cobb angle 38.4° ± 11.4°). Post-treatment, mean Cobb angle and ATR values decreased significantly (p < 0.001). The overall treatment success rate was 91%, with no significant differences based on apex vertebra location (p = 0.459), ALS patterns (p = 0.705), or baseline curve severity (p = 0.274).

CONCLUSION: In this multicenter cohort of skeletally immature adolescents with idiopathic scoliosis, pattern-specific brace treatment was associated with significant reductions in both radiographic curvature and trunk rotation. Improvements were observed across different curve patterns and baseline severities. However, given the retrospective design and absence of a comparison group, these findings should be interpreted with caution. Prospective controlled studies are warranted to further validate these observations.},
}

@article {pmid42182254,
year = {2026},
author = {Fonda, BD and Murray, DT},
title = {Phosphorylation Mimicking Mutations Cause TDP-43 to Adopt Different Fibril Conformations.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.05.14.725298},
pmid = {42182254},
issn = {2692-8205},
abstract = {UNLABELLED: The Tar-DNA Binding Protein-43 C-terminal region, TDP43LC, has been previously shown to form amyloid-like fibrils with distinct folds in ALS and FTD. In both diseases, proteinaceous inclusions contain TDP43 C-terminal protein fragments as well as phosphorylated TDP43. Here, we use solution NMR to show that soluble phosphomimetic TDP43LC, P-TDP43LC, is structurally similar to wild-type TDP43LC. Disperse P-TDP43LC, like wild-type protein, contains a central helical region flanked by long disordered regions. Despite this similarity, our turbidity measurements, imaging, and kinetic assays show that P-TDP43LC has different aggregation behavior than wild-type protein. Using solid state NMR measurements we find that that phosphomimetic mutations alter the wild-type fibril conformation. Electrostatic repulsion from negatively charged sidechains, despite having little effect on the soluble protein's structure, perturbs amyloid-like fibril formation and selects for a different conformation in vitro. These results shed light on the structural role of TDP43LC phosphorylation in fibril formation in disease.

SYNOPSIS: Phosphomimetic mutations at ALS and FTD neurodegeneration-associated sites in an amyloid forming protein perturbs the aggregated structure compared to wild-type protein.},
}

@article {pmid42182325,
year = {2026},
author = {Chauhan, BS and Brennan, MA and Forstmeier, PC and Yifu, H and Godfrey, RK and Van Keuren-Jensen, K and Sattler, R and Ichida, J and Zarnescu, DC},
title = {C9orf72 -associated G4C2 hexanucleotide repeat expression in Drosophila mushroom bodies causes age dependent TDP-43 pathology and dementia relevant phenotypes mediated in part by the glypican Dlp/GPC6.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.05.08.723849},
pmid = {42182325},
issn = {2692-8205},
abstract = {Hexanucleotide repeat expansions (HREs) in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), yet the age-, sex-, repeat-length-, and circuit-specific influence on the pathology of neurons remains incompletely understood. Here, we established a Drosophila model of C9orf72 -associated dementia by expressing G4C2 repeats in mushroom body neurons (MBNs), a brain region critical for memory, locomotion, and sleep. Expression of 44X G4C2 repeats ((G4C2) 44X) led to progressive axonal thinning, age-dependent accumulation of Repeat Associated Non-AUG (RAN) translated GR-GFP dipeptide repeat (DPR) puncta, premature nuclear-to-cytoplasmic mislocalization of endogenous TDP-43, increased caspase, reduced lifespan and a loss of presynaptic active zones. Behaviorally, (G4C2) 44X expression caused locomotor hyperactivity, altered spatial working memory, and fragmentation of sleep architecture in an age- and sex-dependent manner, recapitulating core features of FTD. Surprisingly, the shorter (G4C2) 12X repeat, traditionally considered a control, also produced detectable RAN translation and intermediate phenotypes in aging MBNs, suggesting that length- and tissue-associated factors modulate repeat toxicity. We further identified a repeat-length- and age-dependent reduction of the glypican Dally-like protein (Dlp) in (G4C2) 44X consistent with disrupted Wnt-related signaling linked to TDP-43 proteinopathies. Restoring Dlp expression in MBNs mitigated locomotor and working-memory alterations, and loss of presynaptic active zones. In contrast, axonal degeneration, TDP-43 mislocalization, and lifespan were not significantly improved by restoring Dlp, suggesting that multiple mechanisms contribute to G4C2-induced toxicity. Supporting our findings in Drosophila MBNs, a CRISPRi screen in TDP-43 knock-down iNeurons identified GPC6, a human ortholog of Dlp, as a significant contributor to TDP-43 dependent synaptic loss. Together, our findings reveal an aging-sensitive, circuit-specific model of C9orf72 -associated neurodegeneration and highlight roles for DPR accumulation and Dlp/GPC6 dependent synaptic loss in FTD pathomechanisms.},
}

@article {pmid42183197,
year = {2026},
author = {Dashti, M and AlAbdulghafour, F and AlMutairi, O and Mohammad, A and Malik, MZ and AlRefaie, K and Nizam, R and Jacob, S and Chalabi, A and Al Khleifat, A and Al-Mulla, F},
title = {Classical HLA class II associations with ALS in Kuwait reveal a DR7-DQ2.2 risk haplotype.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1820694},
pmid = {42183197},
issn = {1664-3224},
mesh = {Humans ; Male ; *Amyotrophic Lateral Sclerosis/genetics/immunology ; Kuwait ; Middle Aged ; Female ; *Haplotypes ; *Genetic Predisposition to Disease ; Aged ; Alleles ; Adult ; Genome-Wide Association Study ; *Histocompatibility Antigens Class II/genetics ; *HLA-DQ Antigens/genetics ; },
abstract = {BACKGROUND: Genome-wide association studies have implicated the human leukocyte antigen/major histocompatibility complex (HLA/MHC) region in amyotrophic lateral sclerosis (ALS) susceptibility, and immune dysregulation is increasingly recognised as a modifier of disease course. High-resolution HLA data for ALS remain confined to European and East Asian ancestries. We tested whether classical HLA class I and class II variation contributes to ALS susceptibility in a Kuwaiti cohort.

METHODS: We analysed 38 unrelated ALS cases (mean age, 57.4 years; 63.2% male) and 150 population-matched controls (mean age, 57.0 years) from Kuwait. HLA-A, -B, -C, -DRB1, -DQA1, and -DQB1 alleles were typed at two-field resolution using HLA-HD from next-generation sequencing (NGS) data. Allele, haplotype, and amino-acid residue associations were tested in BIGDAWG with locus-specific Bonferroni correction, with additional across-locus sensitivity analysis. Significant class II residues were mapped onto AlphaFold 3 structural models and interpreted alongside published class II crystal structures.

RESULTS: No class I allele, haplotype, or residue remained significant after correction. In class II, DQA1*02:01 [odds ratio (OR) = 3.18, 95% confidence interval (CI) 1.67 to 5.95, p c = 0.0007], DRB1*07:01 (OR = 3.00, 95% CI: 1.58-5.59, p c = 0.001), and DQB1*02:02 (OR = 2.48, 95% CI: 1.28-4.69, p c = 0.03) were enriched in cases. The extended haplotype DQA1*02:01~DQB1*02:02~DRB1*07:01 (DR7-DQ2.2) conferred increased odds of ALS (OR = 3.11, 95% CI: 1.53-6.19, p c = 0.002). Amino-acid residue analysis identified convergent risk positions in DQα1 (positions 47, 52, and 54; OR = 3.18, p c = 0.006) and DRβ1 (positions 11, 13, 14, 25, and 30; OR = 2.84, p c = 0.03) that map to the peptide-binding groove and correspond to the defining motifs of DQA1*02:01 and DRB1*07:01.

CONCLUSION: Using high-resolution NGS-based HLA typing in a Kuwaiti cohort, we identified a class II risk signal for ALS centred on the DR7-DQ2.2 haplotype with convergent residue-level support in the peptide-binding domains. These findings support a contribution of class II-restricted antigen presentation to ALS susceptibility and warrant functional validation and replication in larger, independent Middle Eastern cohorts.},
}

Humans
Male
*Amyotrophic Lateral Sclerosis/genetics/immunology
Kuwait
Middle Aged
Female
*Haplotypes
*Genetic Predisposition to Disease
Aged
Alleles
Adult
Genome-Wide Association Study
*Histocompatibility Antigens Class II/genetics
*HLA-DQ Antigens/genetics

@article {pmid42174808,
year = {2026},
author = {Bosoni, P and Vazifehdan, M and Aidos, H and Alves, I and Birolo, G and Faggioli, G and González-Martínez, S and Gromicho, M and Jovanović, A and Kostić, B and Longato, E and Manera, U and Tavazzi, E and Tavazzi, E and Bellazzi, R and Bergamaschi, R and Fernanda Cabrera, M and Chiò, A and de Carvalho, M and di Camillo, B and Fariselli, P and Ferro, N and Madeira, SC and Dagliati, A},
title = {Environmental Personal Exposure Clusters to Investigate Multiple Sclerosis and Amyotrophic Lateral Sclerosis Progression.},
journal = {Studies in health technology and informatics},
volume = {336},
number = {},
pages = {173-177},
doi = {10.3233/SHTI260131},
pmid = {42174808},
issn = {1879-8365},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/physiopathology ; *Multiple Sclerosis/diagnosis/epidemiology ; *Environmental Exposure/analysis ; Disease Progression ; Male ; Female ; Middle Aged ; *Volatile Organic Compounds/analysis ; Prognosis ; Cluster Analysis ; Adult ; *Environmental Monitoring/methods ; },
abstract = {Reliable prognosis in Multiple Sclerosis (MS) and Amyotrophic Lateral Sclerosis (ALS) is hampered by data scarcity and variability. Beyond clinical variables, evidence suggests that environmental data can help capture disease trajectories. We investigated whether personal environmental measures can be organized into stable patterns that inform prognosis. In a multicenter cohort, 293 patients with MS or ALS were equipped with Atmotube air-quality sensors. We normalized volatile organic compound (VOC) time series and computed Dynamic Time Warping distances to capture temporal similarity. Hierarchical clustering yielded five daily exposure clusters, which were profiled using Atmotube variables (season, day type, humidity, temperature) and patient self-reports (work status, time outdoors), and evaluated by day-level differences between personal and fixed-station variables. These clusters can support interpolation of missing wearable intervals and generation of context-aware exposure estimates, thereby strengthening environmental inputs for prognostic modeling in MS and ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/physiopathology
*Multiple Sclerosis/diagnosis/epidemiology
*Environmental Exposure/analysis
Disease Progression
Male
Female
Middle Aged
*Volatile Organic Compounds/analysis
Prognosis
Cluster Analysis
Adult
*Environmental Monitoring/methods

@article {pmid42174849,
year = {2026},
author = {Ferraro, PM and Narteni, S and Lenatti, M and Oliveri, F and Gemelli, C and Cabona, C and Uccelli, A and Paglialonga, A and Mongelli, M and Schenone, A},
title = {A Consensus Clustering Approach to Amyotrophic Lateral Sclerosis Phenotyping.},
journal = {Studies in health technology and informatics},
volume = {336},
number = {},
pages = {338-342},
doi = {10.3233/SHTI260173},
pmid = {42174849},
issn = {1879-8365},
mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/classification ; Humans ; Phenotype ; Cluster Analysis ; Consensus ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) phenotyping is a challenging task due to its heterogeneous nature and low prevalence. In this paper, we introduce a data-driven approach to support the characterization of ALS phenotypes based on clinical data from a battery of examinations. A consensus clustering method is proposed to identify stable clusters across multiple random data sub-samples, with the objective of discovering whether the retrieved patients' groups and related features align with clinical phenotypes and medical knowledge. Results suggest consistent profiles for bulbar onset ALS patients, driven by onset characteristics, whereas spinal onset ALS patients exhibit greater within-phenotype heterogeneity.},
}

*Amyotrophic Lateral Sclerosis/diagnosis/classification
Humans
Phenotype
Cluster Analysis
Consensus

@article {pmid42174910,
year = {2026},
author = {Strube, T and Weltermann, L and Weber, J and Defosse, J},
title = {Guideline-Aligned Machine Learning for Predicting Ondansetron Administration at the End of Anaesthesia: Explainable Decision Support for PONV Prophylaxis.},
journal = {Studies in health technology and informatics},
volume = {336},
number = {},
pages = {570-574},
doi = {10.3233/SHTI260235},
pmid = {42174910},
issn = {1879-8365},
mesh = {*Ondansetron/administration & dosage ; *Machine Learning ; Humans ; *Postoperative Nausea and Vomiting/prevention & control ; *Decision Support Systems, Clinical/standards ; *Practice Guidelines as Topic ; *Antiemetics/administration & dosage ; },
abstract = {Artificial Intelligence (AI) and Clinical Practice Guidelines (CPGs) both aim to support clinical decision-making but may provide conflicting suggestions. This manuscript presents a Guideline-Aligned Machine Learning (GAML) model to predict ondansetron administration at the end of anaesthesia, based on Gan et al.'s Fourth Consensus Guidelines for the Management of Postoperative Nausea and Vomiting (PONV). n= 16,240 anaesthesia protocols were analysed for risk factors and administered PONV prophylaxes. Logistic regression, multinomial naïve Bayes, and CatBoost classifiers were trained on 80% of protocols with 12-fold cross-validation; optimal thresholds were set by the mean F1-maximising cut-off across folds. Models were evaluated on the remaining 20%, achieving high accuracy (90 ± 1%) and moderate precision and recall (60 ± 5%, 75 ± 4%) across all models. A SHAP decision plot was further computed on the test set to visualise predictor contributions and illustrate a potential interactive preoperative planning interface. Overall, GAML is a promising basis for explainable decision support in clinical care.},
}

*Ondansetron/administration & dosage
*Machine Learning
Humans
*Postoperative Nausea and Vomiting/prevention & control
*Decision Support Systems, Clinical/standards
*Practice Guidelines as Topic
*Antiemetics/administration & dosage

@article {pmid41963935,
year = {2026},
author = {Zhang, B and Shang, D},
title = {Commentary on "Intercellular TIMP-1-CD63 signaling directs the evolution of immune escape and metastasis in KRAS-mutated pancreatic cancer cells".},
journal = {Molecular cancer},
volume = {25},
number = {1},
pages = {},
pmid = {41963935},
issn = {1476-4598},
support = {2025AHGXZK40703//Anhui Provincial Department of Education Natural Science Research Youth Project/ ; 2025byjbgs064//Bengbu Medical University "Jie Bang Gua Shuai" Research Project/ ; 82374248//National Natural Science Foundation of China/ ; },
abstract = {We recently carefully read the article titled “Intercellular TIMP-1-CD63 signaling directs the evolution of immune escape and metastasis in KRAS-mutated pancreatic cancer cells” published by Chu-An Wang et al. in Molecular Cancer. While this study provides valuable insights into tumor-immune crosstalk, we raise two points for clarification to enhance its precision. First, the manuscript classifies T2N0M0 samples as stage II pancreatic ductal adenocarcinoma (PDAC), which conflicts with the eighth edition of the AJCC Cancer Staging Manual that designates T2N0M0 as stage IB. Second, the authors used pancreatic stellate cells (PSCs) as a surrogate for fibroblasts to model stromal effects, but accumulating evidence indicates that PSCs and fibroblasts are not equivalent. To address this, we integrated single-cell, spatial, and bulk transcriptomic data from multiple cohorts. Our analyses revealed substantial differences between fibroblasts and stellate cells in abundance (fibroblasts enriched in primary pancreatic cancer tumor tissues), prognostic relevance (high fibroblasts associated with poorer survival, high stellate cells with better prognosis), spatial distribution (fibroblasts localized around malignant tumor cells), and intercellular communication (fibroblasts as stronger signal senders to malignant tumor cells). These findings confirm that PSCs cannot accurately represent fibroblasts in PDAC. We emphasize that clarifying these points will not undermine the study’s significance but will strengthen its rigor and comparability. Wang et al.’s work remains a valuable contribution to understanding PDAC progression, and we anticipate these clarifications will further advance stromal-immune crosstalk research in PDAC.},
}

@article {pmid42170793,
year = {2026},
author = {Michelon, H and Lefèvre-Dognin, C and Paquereau, J and Guidoni, R and Boudy, V and Ruiz, F and Vallet, T},
title = {Acceptability of Atropine Eyedrops Administered Sublingually for Sialorrhea Treatment Related to Neurological Conditions.},
journal = {Pharmacology research & perspectives},
volume = {14},
number = {3},
pages = {e70250},
doi = {10.1002/prp2.70250},
pmid = {42170793},
issn = {2052-1707},
mesh = {Humans ; *Sialorrhea/drug therapy/etiology ; *Atropine/administration & dosage ; Male ; Middle Aged ; Cross-Sectional Studies ; Female ; Adult ; Ophthalmic Solutions/administration & dosage ; Aged ; Administration, Sublingual ; *Nervous System Diseases/complications ; France ; *Patient Acceptance of Health Care ; *Cholinergic Antagonists/administration & dosage ; },
abstract = {Off-label use of anticholinergic agents (atropine eye drops) administered sublingually are a first-line treatment in standard clinical practice in France to treat sialorrhea in patients with neurological conditions. The ability and willingness to using and administering such medication have become key factors to ensure safe and effective therapy. Given that the critical aspects for ophthalmic product development differ from those for oral medicine, the objectives of this study were to investigate patient acceptability of atropine eye drops for treating sialorrhea. A multi-centric, cross-sectional study using the CAST-ClinSearch Acceptability Score Test methodology was conducted in France between February 2021 and April 2023. In total, 31 evaluations were collected. Most patients were males (74.2%) and the mean age was 51.6 ± 20 years. Poor acceptability was reported in real-life settings. A lack of a suitable administration device combined with excessive saliva flow and patient disabilities made it difficult to ensure the required dose intake. Due to the bitter taste of the drug, poor palatability of the product appeared to be a key concern for oral administration. Designing a suitable form of atropine in accordance with the specificities of patients with neurological disabilities is needed to ensure the effective treatment of sialorrhea.},
}

Humans
*Sialorrhea/drug therapy/etiology
*Atropine/administration & dosage
Male
Middle Aged
Cross-Sectional Studies
Female
Adult
Ophthalmic Solutions/administration & dosage
Aged
Administration, Sublingual
*Nervous System Diseases/complications
France
*Patient Acceptance of Health Care
*Cholinergic Antagonists/administration & dosage

@article {pmid42170807,
year = {2026},
author = {Renou, Q and Néant, N and Destere, A and Lagoutte-Renosi, J and Grégoire, M and Parant, F and Lalanne, S and Lemaitre, F and Gandia, P and Venisse, N and Bouchet, S and Lê, MP and Muret, P and Peytavin, G and Solas, C and Benaboud, S and , },
title = {External Evaluation of Population Pharmacokinetic Models of Cabotegravir, During Its Oral and Intramuscular Administration in HIV-Infected Patients.},
journal = {CPT: pharmacometrics & systems pharmacology},
volume = {15},
number = {6},
pages = {e70180},
doi = {10.1002/psp4.70180},
pmid = {42170807},
issn = {2163-8306},
support = {ANRS 0255//Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS)/Maladies Infectieuses Emergentes/ ; ANRS 0691b//Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS)/Maladies Infectieuses Emergentes/ ; },
mesh = {Humans ; *HIV Infections/drug therapy ; Injections, Intramuscular ; *Models, Biological ; Female ; Male ; *Anti-HIV Agents/pharmacokinetics/administration & dosage ; Administration, Oral ; Middle Aged ; Adult ; *Pyridones/pharmacokinetics/administration & dosage ; Prospective Studies ; Diketopiperazines ; },
abstract = {Cabotegravir (CAB), combined with rilpivirine, is the first long-acting injectable therapy approved for HIV-1 maintenance treatment. While adherence and patient satisfaction have been improved, pharmacokinetic (PK) variability remains a concern. Two population PK models have been developed: one based on data from phase I-III trials and the other on routine clinical data. However, neither model has undergone thorough external evaluation. The aim of this study was to evaluate the predictive performance of these models using an independent prospective dataset to evaluate their suitability to support model-informed precision dosing (MIPD). External validation was performed using data from the French observational and multicenter (n = 14) ANRS0255 CARLAPOP study (736 HIV-infected patients, representing 2192 concentrations). Models were implemented using MONOLIX software and evaluated using goodness-of-fit, prediction-based, and simulation-based diagnostics. For Han's model, regarding plasma concentrations following intramuscular administration, Median Prediction Error (MDPE) was -1.2% (PRED) and -4.4% (IPRED); Median Absolute Prediction Error (MDAPE) was 36.6% (PRED) and 17.9% (IPRED). For Thoueille's model, MDPE was -24.2% (PRED) and -9.2% (IPRED); MDAPE was 39.0% (PRED) and 15.3% (IPRED). However, < 70% of predictions were within a 20% error margin with both models. Graphical analyses of Thoueille's model showed systemic bias, particularly in women, nonsmokers, and patients with higher body mass index. Therefore, neither model was considered reliable enough for MIPD application in our population. Although Han et al.'s model demonstrated higher predictive performances, further improvements are required before it can be reliably applied for MIPD in daily routine.},
}

Humans
*HIV Infections/drug therapy
Injections, Intramuscular
*Models, Biological
Female
Male
*Anti-HIV Agents/pharmacokinetics/administration & dosage
Administration, Oral
Middle Aged
Adult
*Pyridones/pharmacokinetics/administration & dosage
Prospective Studies
Diketopiperazines

@article {pmid42171198,
year = {2026},
author = {Tian, J and Jin, Z and Chi, Y and Wang, P and Sun, H},
title = {Targeting lipid nanoparticle mediated co-delivery of edaravone and kaempferol for amyotrophic lateral sclerosis therapy.},
journal = {Nanoscale},
volume = {},
number = {},
pages = {},
doi = {10.1039/d6nr00300a},
pmid = {42171198},
issn = {2040-3372},
abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by a progressive and selective loss of motor neurons in the central nervous system, particularly in the brain and spinal cord. However, the main cellular mechanisms and cell death pathways leading to motor neuron degeneration have not yet been clarified. Research indicates evidence of ferroptosis in ALS, and the natural compound kaempferol has been demonstrated to inhibit neuronal ferroptosis. However, damage to the blood-brain barrier (BBB) prevents the drug from penetrating the central nervous system, which significantly reduces its therapeutic efficacy. Here, we developed a targeted delivery system named Eda/Kae@Lip-RGD (EKLR), which consisted of liposome-grafted RGD peptides for the co-delivery of the drugs kaempferol and edaravone, capable of crossing the BBB to provide co-delivery of kaempferol and edaravone for combined treatment of ALS. As expected, treatment with EKLR for one month significantly slowed down weight loss and improved athletic performance in SOD1[G93A] transgenic mice. Mechanistically, this nanomedicine suppressed ferroptosis by upregulating the antioxidant proteins GPX4 and SLC7A11, alongside the downregulation of Nrf2 and ACSL4 levels, thus collectively preserving neuronal integrity. Meanwhile, EKLR restored the normal morphology and the survival rate of neurons and maintained the mitochondrial structure and morphological integrity. Accordingly, this nanoplatform may represent a distinctive and potentially effective strategy for achieving neuroprotection in ALS as well as in other disorders of the central nervous system.},
}

@article {pmid42171508,
year = {2026},
author = {Ramos, S and Watson, MD and Lee, JC},
title = {Kinetics and Spatial Distribution of β-Sheet Development in TDP-43CTD Condensate Maturation.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.6c00226},
pmid = {42171508},
issn = {1948-7193},
abstract = {Cytosolic inclusions of aggregated TAR DNA-binding protein 43 (TDP-43) are hallmarks of neurodegenerative disorders such as amyotrophic lateral sclerosis and frontotemporal lobar dementia. A prevailing hypothesis suggests that TDP-43 condensates undergo a liquid-to-solid transition during maturation, involving the formation of β-sheet-rich, amyloid-like aggregates. To test this hypothesis, we sought to study the temporal and spatial evolution of protein secondary structure within individual condensates by Raman spectroscopy. We measured in vitro β-sheet development of the C-terminal domain of TDP-43 (TDP-43CTD) at the single-condensate level under physiological solution conditions. All condensates showed apparent single-exponential kinetics (k = 1.6 × 10[-5] s[-1]) for the disordered-to-β-sheet transformation, as indicated by increased amide-I intensity and a shift of the amide-III band to lower energy. Interestingly, the water bend-libration band exhibited a slower rate (k = 4.0 × 10[-6] s[-1]), suggesting that changes in the water environment lag behind protein conformational rearrangement. Further, Raman maps revealed that protein density is highest near the condensate center, whereas β-sheet content is mostly uniform in the interior of the condensate. The unexpected difference between the spatial distributions of β-sheet content and protein density challenges the typical concentration-dependent model of protein aggregation. Importantly, rare events were captured where condensates exhibited spatially asymmetric β-sheet development, revealing localized structural heterogeneity not detectable by ensemble measurements. Collectively, these results provide insight into the temporal and spatial dynamics of protein structure within TDP-43CTD condensates and demonstrate the utility of Raman spectral imaging for tracking condensate maturation.},
}

@article {pmid42171861,
year = {2026},
author = {Condorelli, GA and Iozzia, A and Bonifacio, D and Pelin, A},
title = {TDP-43 Acetylation at the Neuroimmune Interface: A Hypothesis-Driven Framework for Peripheral Inflammatory Stratotypes in ALS.},
journal = {Neurochemical research},
volume = {51},
number = {3},
pages = {},
pmid = {42171861},
issn = {1573-6903},
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/immunology ; Humans ; Acetylation ; *DNA-Binding Proteins/metabolism ; Animals ; *Inflammation/metabolism/immunology ; Blood-Brain Barrier/metabolism ; *Neuroimmunomodulation/physiology ; },
abstract = {Transactive Response Deoxyribonucleic Acid-Binding Protein-43 (TDP-43) acetylation may couple motor-neuron degeneration to systemic immune orchestration in Amyotrophic Lateral Sclerosis (ALS). Upon nuclear clearance and mislocalisation, TDP-43 enters the periphery; acetylation shapes its conformation, trafficking and immunogenicity. This narrative review synthesises single-cell transcriptomics, proteomic immunoprofiling and clinical inflammatory phenotyping to examine whether site-specific acetylated TDP-43 species may be associated with peripheral inflammatory signatures relevant to ALS immunopathology. By integrating separate datasets on acetylated TDP-43, monocyte phenotypes and cytokine modules, we propose two provisional endotypes characterised by monocyte reprogramming, cytokine modules and Blood-Brain Barrier (BBB) dysfunction-each representing clinically actionable pathways. Framed as a provisional neuroimmune interface, the acetylation state is considered here as a plausible molecular correlate and potential therapeutic entry point: a measurable clue to inform pharmacological targeting and, potentially, a modifiable target via p300CREB-Binding Protein (CBP)-Histone Deacetylase (HDAC) axes or sirtuin activity. Recasting TDP-43 from neuropathological hallmark to immunoactive sentinel supports a shift from descriptive nosology to stratified immunotherapy, in which treatment allocation is informed by acetylation-defined peripheral signatures.},
}

*Amyotrophic Lateral Sclerosis/metabolism/immunology
Humans
Acetylation
*DNA-Binding Proteins/metabolism
Animals
*Inflammation/metabolism/immunology
Blood-Brain Barrier/metabolism
*Neuroimmunomodulation/physiology

@article {pmid42172922,
year = {2026},
author = {Myers, S and Kraus, E and Davis, ES and Murillo, A and Ng, SC and Sachs, T and Davids, JS and Kenzik, KM},
title = {Ostomy and Anastomotic Leak Differences Among Rural and Urban Surgical Colon Cancer Patients.},
journal = {The Journal of surgical research},
volume = {324},
number = {},
pages = {59-66},
doi = {10.1016/j.jss.2026.04.017},
pmid = {42172922},
issn = {1095-8673},
abstract = {INTRODUCTION: Rural populations experience higher morbidity and mortality after resection of colon cancer (CC) than urban populations. Ostomy creation may obviate or reduce the severity of anastomotic leaks (ALs); however, this practice is surgeon-dependent. Differences in rural-urban ostomy practices and AL following CC resection are unknown.

METHODS: We identified patients who underwent CC resection between 2014 and 2019 from the Surveillance, Epidemiology, and End Results-Medicare database and characterized ostomy practices. We used multivariable logistic regression to evaluate rural-urban differences in AL and readmissions, with and without ostomies. Oaxaca-Blinder nonlinear effect decomposition was used to analyze the proportion of rural-urban difference in AL explained by age, sex, race, Charlson Comorbidity Index, stage of cancer, surgical approach, surgeon specialty, and ostomy creation.

RESULTS: Among 28,031 individuals (17.9% rural), rural patients underwent ostomy surgery less often than urban (47.6% versus 52.4%, P< 0.0001). The rate of AL was higher among rural patients with ostomies (8.6% versus 7.0%, P= 0.0069), and rural ostomy patients were discharged with postacute care services less often (43.8% versus 47.3%, P= 0.0034). Resection by a general surgeon was associated with higher odds of AL only among urban patients (versus colorectal, OR = 1.27; 95% CI = 1.13-1.42). Surgical approach explained 37.5% of the rural-urban AL disparity, surgeon specialty explained 21.5%, and ostomy surgery only explained 2.6% of the difference.

CONCLUSIONS: Ostomy surgery explained a small proportion of the rural-urban AL disparity, while surgical approach explained over a third of the higher AL risk among rural populations. Surgical approach should be prioritized in interventions to improve CC surgical outcomes among rural populations.},
}

@article {pmid42173382,
year = {2026},
author = {Braza, AJ and Viñas-Bastart, M and Sureda-Rosich, M and García-Parra, B and Guiu-Segura, JM and Modamio, P},
title = {Tofersen in SOD1-associated amyotrophic lateral sclerosis: From molecular mechanisms to regulatory milestones.},
journal = {European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences},
volume = {223},
number = {},
pages = {107563},
doi = {10.1016/j.ejps.2026.107563},
pmid = {42173382},
issn = {1879-0720},
abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a progressive and ultimately fatal neurodegenerative disorder characterized by degeneration of upper and lower motor neurons. Mutations in the superoxide dismutase 1 (SOD1) gene account for approximately 2% of ALS cases and are associated with toxic protein misfolding and aggregation. Tofersen is an antisense oligonucleotide therapy designed to reduce the synthesis of mutant SOD1 protein through targeted mRNA degradation. While this strategy represents a gene-specific therapeutic approach for a subset of ALS patients, evidence regarding its efficacy, effectiveness and long-term outcomes continues to be evaluated in clinical trials and post-marketing studies.

OBJECTIVE: First, to describe the molecular mechanisms underlying SOD1-associated ALS and second, to analyze the therapeutic development, clinical outcomes, and regulatory evolution of tofersen.

METHODS: A narrative review was conducted in PubMed on preclinical and clinical studies published from 2016 through late 2025, complemented by an analysis of public registries and regulatory documentation. Clinical trials were identified through ClinicalTrials.gov and the Clinical Trials Information System (CTIS), and official reports from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) were reviewed to contextualize their development and regulatory evaluation.

RESULTS: Fifty-three publications were identified, of which 20 met predefined inclusion criteria after screening and full-text review. Preclinical studies showed reduced mutant SOD1 expression and prolonged survival in transgenic models. Phase I-II trials demonstrated safety, favorable pharmacokinetics, and dose-dependent reductions in SOD1 in the cerebrospinal fluid and plasma neurofilament light chain (NfL) levels. Although the phase III VALOR trial did not meet the primary ALSFRS-R endpoint (a validated questionnaire-based functional rating scale-revised for determining ALS disease progression) at 28 weeks, significant reductions in the surrogate biomarker NfL indicated target engagement and supported accelerated regulatory approval. Extension data suggested potential clinical benefit with early treatment. Ongoing studies, including ATLAS in presymptomatic carriers, and real-world European data support continued evaluation, alongside accelerated regulatory approvals by FDA and EMA.

CONCLUSION: Tofersen marks a paradigm shift in ALS management, establishing the foundation for precision medicine in neurodegenerative diseases. Its ongoing evaluation in the ATLAS trial will determine whether early intervention can prevent or delay disease onset in presymptomatic SOD1 mutation carriers.},
}

@article {pmid42174751,
year = {2026},
author = {Grouls, A and Leavell, YL and Mehta, AK and Kojimoto, G and O'Riordan, DL and Maiser, S and Kluger, BM and Pantilat, SZ and Bischoff, KE},
title = {Embedding Palliative Care Clinicians in ALS Teams Improves ALS Clinicians' Confidence in Their Patient Management and Satisfaction With Palliative Care.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70291},
pmid = {42174751},
issn = {1097-4598},
support = {A142921//ALS Association/ ; },
abstract = {INTRODUCTION/AIMS: Specialty palliative care (SPC) can improve symptoms and well-being for people living with ALS. Few studies capture how ALS clinicians utilize or are impacted by SPC. We sought to understand how the presence of SPC clinicians on ALS teams impacts ALS clinicians' referrals to and satisfaction with SPC.

METHODS: We conducted a survey of interdisciplinary ALS clinicians to understand their confidence in their team's care, SPC referral patterns, and satisfaction with SPC. We compared responses from ALS clinicians with and without SPC in their team.

RESULTS: 141 ALS clinicians completed the survey, having primarily neurology, nursing, and therapy backgrounds. ALS clinicians who had SPC embedded in their team reported more confidence in their team's ability to address pain (63.3% v 37.4%, p < 0.001), dyspnea (88.8% v 70.8%, p = 0.05), and end-of-life needs (71.4% v 52.1%, p = 0.005). They reported fewer SPC referral barriers and referred to SPC for different reasons. ALS clinicians with SPC on their team were more satisfied with SPC's ability to help with motor symptoms (92.7% v 71.4%, p = 0.02), dyspnea (98.3% v 86.7%, p = 0.04), and care coordination (90.0% v 73.5%, p = 0.04).

DISCUSSION: The presence of SPC embedded within multidisciplinary ALS teams is associated with ALS clinicians feeling more confident in their team's ability to address certain care needs, more satisfied with the care provided by SPC, and experiencing fewer barriers to involving SPC. Additional research should explore how embedding SPC on ALS teams impacts patient outcomes.},
}

@article {pmid42166281,
year = {2026},
author = {Harden, KP},
title = {In praise of scientific open relationships: Commentary on Caspi et al. (2026).},
journal = {Journal of psychopathology and clinical science},
volume = {135},
number = {4},
pages = {505-506},
pmid = {42166281},
issn = {2769-755X},
support = {//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; /DA/NIDA NIH HHS/United States ; },
mesh = {Humans ; *Mental Disorders ; *Biomedical Research ; },
abstract = {This commentary responds to arguments presented in Caspi et al.'s (see record 2026-80066-001) viewpoint article. I endorse the authors' overall argument but note that exactly how many mental disorders one needs to study at a time will likely depend on the specific research question. I also describe how transdiagnostic research requires strong norms of data and credit sharing. (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}

Humans
*Mental Disorders
*Biomedical Research

@article {pmid42166316,
year = {2026},
author = {Meca, A and Cruz, B and Cruz, I and Hinojosa, Z and Nguyễn, M and Gonzales-Backen, M},
title = {Revisiting the two-factor model of ethnic-racial and U.S. identity exploration among Hispanic college students.},
journal = {Cultural diversity & ethnic minority psychology},
volume = {},
number = {},
pages = {},
doi = {10.1037/cdp0000810},
pmid = {42166316},
issn = {1099-9809},
abstract = {OBJECTIVE: Establishing a positive ethnic-racial identity (ERI) and U.S. identity (USI) is an important cultural asset capable of promoting positive adjustment. Although exploration has been identified as the fundamental process underlying ERI and USI development, existing research has largely utilized a unidimensional conceptualization. The present study sought to replicate Syed et al.'s (2013) findings, which differentiated between two forms of ERI exploration, search (i.e., reflection/talking to others) and participation (i.e., involvement in events/experiences), and extend to USI. Moreover, we sought to examine the unique associations between ERI and USI exploration with resolution and negative affect.

METHOD: The sample included 416 Hispanic/Latine college students (83.7% female; Mage = 20.57 years) recruited from a psychology department participant pool at a public Hispanic-serving institution in South Florida in 2017. Participants completed the online survey at their convenience in exchange for course credit.

RESULTS: Findings provided support for the differentiation between ERI and USI search and participation, which were uniquely and differentially associated with resolution and negative affect.

CONCLUSION: Our study highlights the need to move beyond unidimensional conceptualizations of exploration. (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}

@article {pmid42166520,
year = {2026},
author = {Marques Couto, C and De Melo Queiroz, E and Souza Lima, W and Camilla De Lima Santos, S and José Moreira Nascimento, O},
title = {Clinical characterization and natural history of ALS8/VAPB p.Pro56Ser: upper motor neurone signs, survival, and functional milestones in 78 patients.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/21678421.2026.2674020},
pmid = {42166520},
issn = {2167-9223},
abstract = {OBJECTIVE: Amyotrophic lateral sclerosis type 8 (ALS8), caused by the VAPB p.Pro56Ser mutation, is a rare familial motor neurone disease with an incompletely characterized profile. We aimed to characterize the clinical phenotype, upper motor neurone (UMN) sign prevalence, survival, and functional milestones.

METHODS: We retrospectively analyzed 78 patients with ALS8 confirmed via molecular testing or familial linkage analysis from 57 apparently unrelated families. UMN signs were assessed using a five-item composite of pyramidal signs. Survival and milestones were estimated using Kaplan-Meier analysis.

RESULTS: Median age at onset was 44.9 years; 51% were men. Onset was lumbar in 94%, proximally predominant. UMN signs were present in 53 patients; none exhibited clonus. At admission, 51% had spinal-onset ALS, 42% progressive muscular atrophy (PMA) and 6% flail leg; 30% of patients with PMA subsequently developed UMN signs. Survival was 21.9 years; times to wheelchair dependence and noninvasive ventilation were 7.0 and 10.0 years, respectively. Bulbar involvement occurred in 17 (21.8%) patients, predominantly as dysphonia. UMN status did not affect survival (p = 0.312). The standardized mortality ratio was 4.54 (95% CI 2.77-7.01), supporting disease-related excess mortality.

CONCLUSIONS: ALS8 is a slowly progressive motor neurone disease with lumbar onset, ascending progression, and frequent but subtle UMN signs. Survival was markedly prolonged but functional decline followed a predictable sequence. These findings expand the phenotypic characterization of ALS8 and support genetic counseling and anticipatory management.},
}

@article {pmid42167402,
year = {2026},
author = {Ballesteros, AL and Rodriguez-Cañamero, S and Martín-Conty, JL and Polonio-López, B and Pozo-Vegas, CD and López-Izquierdo, R and Martín-Rodríguez, F and Sanz-García, A},
title = {Effect of Glycemia and Diabetes on Early Warning Scores Performance in Prehospital Patients With Acute Illness: Multicenter, Prospective, Cohort Study.},
journal = {Mayo Clinic proceedings},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.mayocp.2026.05.008},
pmid = {42167402},
issn = {1942-5546},
abstract = {OBJECTIVE: To determine how glycemia and diabetes affect the performance of the NEWS and mSOFA scores to predict 30-day mortality in patients with acute illnesses requiring EMS assistance.

PARTICIPANTS AND METHODS: This prospective, multicenter cohort study evaluated 14,726 adults with acute illness attended by advanced life support (ALS) units and helicopter emergency medical services (HEMS) between January 1, 2019, and December 1, 2025. Associations between glucose levels (hypoglycemia, normoglycemia, hyperglycemia), diabetic status, and 30-day mortality were analyzed. Predictive capacity (area under the receiver operating characteristic curve, AUC-ROC) of NEWS and mSOFA stratified by metabolic groups was assessed and compared.

RESULTS: A nonlinear U-shaped relationship was observed between glycemia and mortality. mSOFA outperformed NEWS (AUC-ROC 0.877 vs 0.822). Under hyperglycemia, NEWS performance decreased (AUC-ROC 0.764), while mSOFA remained more stable (AUC-ROC 0.815). Both scores performed better in nondiabetic patients (AUC-ROC >0.82) than in diabetics with complications, suggesting stress hyperglycemia in nondiabetics reflects greater acute severity.

CONCLUSIONS: mSOFA showed greater robustness and more stable predictive performance than NEWS with glycemic variability, particularly in nondiabetic patients with stress hyperglycemia, suggesting glucose serves as a universal biomarker of acute severity across prehospital acute illness. These findings support potential value of prehospital POCT to improve critical patient identification and risk stratification where resources and infrastructure allow.},
}

@article {pmid42168009,
year = {2026},
author = {Corcia, P and Bernard, E and de la Cruz, E and Danel, V and Soriani, MH and Guy, N and Esselin, F and Bruneteau, G and Pradat, PF and Goutines, V and Catherine, J and Eyraud, N and Cheve, P and Fernandez, A and Erazo, D and Couratier, P},
title = {Primary Lateral Sclerosis French National Diagnostic and Care Protocol.},
journal = {Revue neurologique},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neurol.2026.04.006},
pmid = {42168009},
issn = {0035-3787},
abstract = {Primary lateral sclerosis (PLS) is a rare neurodegenerative motor neuron disease characterized by progressive and selective involvement of the central motor neuron within the bulbar and spinal regions. It is estimated to account for 1-5% of motor neuron diseases and typically presents in the fifth or sixth decade of life, with a slight male predominance. According to current consensus criteria, the diagnosis relies on the demonstration of progressive upper motor neuron dysfunction in the absence of lower motor neuron involvement, with persistence of isolated upper motor neuron signs for at least four years in order to exclude a slowly progressive upper motor neuron-predominant form of amyotrophic lateral sclerosis (ALS). The French Motor Neuron Disease Network (FILSLAN) developed a National Diagnostic and Care Protocol (PNDS) with the aim of standardizing diagnostic criteria, optimizing differential diagnosis, and providing evidence-based recommendations for therapeutic management and follow-up across the national territory. These recommendations were elaborated in accordance with the methodological framework of the French National Authority for Health for rare diseases. The protocol provides practical guidance for establishing PLS as a diagnosis of exclusion, distinguishing it from ALS and hereditary spastic paraplegias, and organizing appropriate clinical and paraclinical investigations. It also outlines indications for genetic testing in selected cases and defines a multidisciplinary management strategy centered on symptomatic treatment, early rehabilitation, respiratory and nutritional surveillance, and psychosocial support. Given the slower progression of PLS compared with ALS, biannual multidisciplinary follow-up is generally appropriate. This protocol aims to harmonize clinical practice and improve patient care while acknowledging the current absence of disease-modifying therapies.},
}

@article {pmid42168859,
year = {2026},
author = {Levin, AB and Joshi, Y and Vaidhya, N and Kantianis, J and Macdonald, PS},
title = {Anaesthetics considerations for organ retrieval in the voluntary assisted dying patient - case report.},
journal = {BMC anesthesiology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12871-026-03921-w},
pmid = {42168859},
issn = {1471-2253},
abstract = {BACKGROUND: Voluntary assisted dying (VAD) is now legalised in several countries. Organ donation after VAD provides unique moral and logistical challenges. This report highlights the role of the anaesthetist in such cases.

CASE PRESENTATION: A 50-year-old man with end-stage amyotrophic lateral sclerosis underwent VAD and became an organ donor. Anaesthetic and logistical considerations during procurement are described. Advances in organ retrieval after VAD and psychosocial implications are briefly outlined.

CONCLUSIONS: Organ donation after VAD presents unique opportunities and challenges. The anaesthetist plays a key role in ensuring both dignity for the patient and optimal conditions for organ retrieval.},
}

@article {pmid42169130,
year = {2026},
author = {Sarti, A and Mandrioli, J and Costanzini, S and Balbo, GX and Malagoli, C and Martini, N and Despini, F and Violi, F and Malavolti, M and Martinelli, I and Giacchino, M and Donelli, G and Canali, E and Zinno, L and Teggi, S and Vinceti, M and Filippini, T},
title = {Green space exposure and risk of amyotrophic lateral sclerosis: a population-based case-control study in Northern Italy.},
journal = {Environmental health : a global access science source},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12940-026-01311-w},
pmid = {42169130},
issn = {1476-069X},
support = {"PRIN 2022" (No. 2022MHMRPR)//Ministero dell'Università e della Ricerca/ ; "UNIMORE FAR 2023"//Università Degli Studi di Modena e Reggio Emilia/ ; },
abstract = {BACKGROUND: The contribution of environmental determinants in the etiology of amyotrophic lateral sclerosis (ALS) is still unclear. Among the various environmental factors, exposure to green spaces, also known as greenness, is attracting considerable interest as many studies have reported its beneficial associations to health outcomes, particularly to neurodegenerative diseases.

METHODS: To investigate the relation between greenness and ALS risk, we conducted a population-based case-control study in a Northern Italy population (from Modena, Reggio Emilia and Parma provinces), including 499 cases of ALS newly-diagnosed from 1998 to 2011 and 1,935 sex-, age-, and province-matched controls randomly selected from study provinces residents. We evaluated the association between greenness in the proximity of residence and ALS risk, assessing exposure through multiple satellite-based and land-use derived indices, both conventional and novel devised, for a total of six indices, each providing specific information, including annual and seasonal Normalized Difference Vegetation Index (NDVI), NDVI-weighted to green areas, green cover ratio, accessibility index, and their combined Green Exposure Index (GEI). We used conditional logistic regression models to evaluate disease risk for increasing exposure through both fixed-categories and non-linear restricted cubic splines.

RESULTS: We observed a non-linear U-shaped association between greenness and ALS risk with increased odds ratios at both low and high levels. Results were more defined when using NDVI-based indices, while the associations were smoother when considering GEI. The higher risk at low levels may be related to lower accessibility to green spaces with lower physical activity and higher exposure to outdoor air pollutants, whilst elevated greenness may reflect higher exposure to neurotoxic pesticides. These results were confirmed also after adjustment for potential confounders, namely magnetic fields and light at night. Sex stratified analysis yielded similar results, except for more distinct associations in females for GEI.

CONCLUSIONS: Despite the limitations due to possible unmeasured confounding and exposure misclassification related to the use of residential data, our results provide evidence of an inverse association between intermediate residential greenness and ALS risk, and may have public health implications including disease prevention and urban planning.},
}

@article {pmid42170697,
year = {2026},
author = {Prasun, P and Rasberry, M},
title = {Expanding Spectrum of FIG4-Related Neurological Disorders of Lysosomal Homeostasis: Case Report and Overview of the Potential Genotype-Phenotype Correlations.},
journal = {Clinical genetics},
volume = {},
number = {},
pages = {},
doi = {10.1111/cge.70185},
pmid = {42170697},
issn = {1399-0004},
abstract = {Biallelic loss-of-function variants in FIG4 are associated with Charcot-Marie-Tooth disease type 4J, a progressive peripheral sensorimotor demyelinating polyneuropathy. Biallelic null FIG4 variants cause Yunis-Varon syndrome, a severe neurological disorder characterized by global developmental delay, hypotonia, brain malformations, skeletal defects, dysmorphic facial features, and juvenile lethality. In the past few years, many individuals with combined central and peripheral nervous system disease associated with biallelic FIG4 variants have been described. In addition, certain heterozygous FIG4 variants are associated with amyotrophic lateral sclerosis. We describe an individual with global developmental delay, hypotonia, cerebral hypomyelination, peripheral hypomyelinating polyneuropathy, frequent fractures, and juvenile ossifying fibroma. The spectrum of clinical presentation of FIG4-related disorders is increasingly being recognized. Our observations expand the phenotypic spectrum of FIG4-related neurological disorders. In addition, we provide an overview of the potential genotype-phenotype correlations of this expanding group of disorders of lysosomal homeostasis.},
}

@article {pmid42160473,
year = {2026},
author = {Kim, S and Curtis, SE and Iacono, D and Mehdiyoun, NF and Mitchell, L and Genge, A and Brandt, AU and , and Mancini, M},
title = {Types and frequencies of adverse events across clinical trials for patients with amyotrophic lateral sclerosis: an analysis of the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/21678421.2026.2667290},
pmid = {42160473},
issn = {2167-9223},
abstract = {OBJECTIVE: Symptoms of amyotrophic lateral sclerosis (ALS) may present as adverse events (AEs) in ALS clinical trials. Identifying anticipated AEs independent of investigational drug is crucial for trial design and required by the FDA for safety reporting and assessment in drug development. This study describes anticipated AEs and their predicted incidence in ALS trials, leveraging data from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database.

METHODS: Placebo-treated people living with ALS (age ≥18 years, disease duration ≤36 months, ≥50% of predicted vital capacity at screening) were included. A confirmed diagnosis per the El Escorial criteria was required for a sensitivity analysis. Reported AEs were grouped based on pathophysiology and implications in clinical management and safety monitoring. AEs were further consolidated, with seven anticipated groups pre-specified for analysis. AE incidence proportions (IPs) and rates in person-years were estimated.

RESULTS: The analysis included 1,388 participants (mean [SD] age: 56.8 [11.3] years; mean [SD] disease duration: 1.4 [0.6] years). IP was ≥5% for 24 AE groups, highest for falls and injuries (18.8%), headaches (13.5%), muscle weakness (13.1%), and gastrointestinal signs and symptoms (13.1%). Of seven pre-specified AE groups, falls, injuries, and fractures were the most frequent (23.0%), followed by severe respiratory failure and disorders including dyspnea (19.1%) and dysphagia (10.5%). Sensitivity analysis results were comparable (n = 931), although IPs were generally lower.

CONCLUSIONS: These new findings will facilitate a systematic approach for safety monitoring and reporting in ALS trials, enable detection of true safety signals that may be obscured by these events, and support clinical development.},
}

@article {pmid42160478,
year = {2026},
author = {Cosijn, FS and van Unnik, JWJ and Exalto, LG and de Groot, LN and Weemering, DN and van Rijssen, RC and Vink, RG and van den Berg, LH and van Eijk, RPA},
title = {Clinical drug development in amyotrophic lateral sclerosis: industry-reported challenges and opportunities.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/21678421.2026.2671167},
pmid = {42160478},
issn = {2167-9223},
abstract = {OBJECTIVE: The pharmaceutical industry plays a pivotal role in amyotrophic lateral sclerosis (ALS) drug development, yet the challenges and priorities remain largely unexplored. This study aims to identify industry-perceived opportunities for ALS and examine industry perspectives on trial design.

METHODS: A survey study was conducted among pharmaceutical companies involved in ALS drug development. The survey was based on literature review and interviews with industry experts. Final survey topics included scientific and operational challenges as well as preferred design settings for phase 2 and 3 clinical trials. Respondents were asked to rank trial-related topics using Likert scales.

RESULTS: In total, 53 industry professionals responded, representing 42 international companies. Respondents identified three major scientific challenges: heterogeneity in disease progression, lack of reliable biomarkers, and insensitive efficacy measures. Insufficient funding, high dropout rates, and staffing shortages emerged as main operational barriers. For phase 2 trials, neurofilament light chain was most often prioritized as primary outcome, whereas the ALS Functional Rating Scale-Revised was prioritized for phase 3, although priority rankings varied considerably among respondents. Expected median sample sizes were 100 patients (range 20-300) for phase 2 and 300 patients (range 60-800) for phase 3. Overall, 58% of the respondents indicated that standardizing aspects of trial design could enhance trial quality and success rates.

CONCLUSIONS: This study provides an overview of the industry-perceived challenges, exposing strategic knowledge gaps related to disease and clinical heterogeneity. Standardization of key trial design elements may help mitigate these challenges and better align ALS drug development efforts.},
}

@article {pmid42160479,
year = {2026},
author = {Catley, CS and Hoedt, EC and Pockney, P and Keely, S and Hedley, KE},
title = {Unravelling Anastomotic Leak: Biological Mechanisms Underlying Intestinal Healing After Resection.},
journal = {American journal of physiology. Gastrointestinal and liver physiology},
volume = {},
number = {},
pages = {},
doi = {10.1152/ajpgi.00071.2026},
pmid = {42160479},
issn = {1522-1547},
support = {//University of Newcastle Australia (UON)/ ; //Australian Government (Federal Government)/ ; G2300020//nswgov | NSW Health (The NSW Health)/ ; },
abstract = {Understanding intestinal healing following resection and anastomosis is a challenging topic due to the complexity of underlying mechanisms. Anastomotic healing follows the fundamental phases of normal wound repair; however, the intestinal anastomosis represents a unique biological environment in which factors such as the structure of the intestines as well as the microbiome, may modify the healing process. Disruptions in any of the healing phases such as the inflammatory, proliferative and remodelling phase may result in severe complications, characterised by the intraluminal contents leaking out into the extraluminal space, termed an anastomotic leak (AL). Despite decades of surgical advancements, we are still no closer in understanding the underlying AL aetiology. It is clear that ALs are multifactorial in nature and contributed to by patient, technical and biological-related factors, however, emerging evidence suggests that biological mechanisms may play a more significant role in AL pathology than originally believed. Evidence points to an interplay between epithelial healing, tissue oxygenation and the resident microbiome in influencing mucosal healing at the anastomotic site. However, the precise contribution of these factors in failed anastomotic healing and AL aetiology remains unclear. In this review, we examine the phases of healing, discuss the existing literature on biological factors affecting anastomotic healing and the advancements made to improve AL rates by targeting the healing response.},
}

@article {pmid42160515,
year = {2026},
author = {Zhang, M and Yang, W and Wang, J and Zou, B and Zheng, JC and Wu, Q and Gao, G},
title = {Immunotherapeutic landscape of amyotrophic lateral sclerosis: A bibliometric analysis of research trends, translational priorities, and collaboration networks (2006-2025).},
journal = {Human vaccines & immunotherapeutics},
volume = {22},
number = {1},
pages = {2664985},
doi = {10.1080/21645515.2026.2664985},
pmid = {42160515},
issn = {2164-554X},
mesh = {*Amyotrophic Lateral Sclerosis/therapy/immunology ; Humans ; *Bibliometrics ; *Immunotherapy/methods/trends ; *Translational Research, Biomedical/trends ; Animals ; },
abstract = {Amyotrophic lateral sclerosis (ALS) remains a major therapeutic challenge, with immune dysregulation increasingly recognized as a critical driver of disease progression. Despite extensive mechanistic research, no immunotherapeutic approach has achieved consistent disease-modifying effects, raising questions about whether this translational gap reflects biological complexity or structural misalignment within the research ecosystem. To characterize the intellectual evolution of ALS immunotherapeutics research, identify immune targets with translational potential, and evaluate collaboration patterns that may influence translational efficiency, we performed a bibliometric analysis of 2,256 publications indexed in Web of Science and Scopus using network-based approaches including co-citation clustering, keyword co-occurrence, and citation burst detection implemented in CiteSpace, VOSviewer, and R-Bibliometrix. Publication output increased 8.4-fold over the study period, delineating three developmental phases. Thematic analyses revealed a shift from early emphasis on microglial biology and SOD1-based models toward recent focus areas including the gut-brain axis, C9orf72-associated immune dysregulation, and advanced immunomodulatory strategies. Collaboration networks remain predominantly regional despite strong contributions from the United States, Europe, and Asia, with limited integration between mechanistic research groups and clinical trial consortia. Among immune-directed therapeutic strategies, regulatory T cell modulation and microglial-targeted approaches exhibit the highest translational readiness. These findings suggest that the lack of effective ALS immunotherapeutics reflects not only biological complexity but also structural and strategic misalignment within the research ecosystem. This bibliometric analysis provides a systems-level framework to guide more integrated translational strategies in ALS immunotherapeutics development.},
}

*Amyotrophic Lateral Sclerosis/therapy/immunology
Humans
*Bibliometrics
*Immunotherapy/methods/trends
*Translational Research, Biomedical/trends
Animals

@article {pmid42161327,
year = {2026},
author = {Vallikivi, JK and Kooyman, M and , and Kirby, J and Nigel Leigh, P and Iacoangeli, A and Al-Chalabi, A and Al Khleifat, A},
title = {CYP2D6 variants in amyotrophic lateral sclerosis: an association study of risk and survival.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag178},
pmid = {42161327},
issn = {1460-2156},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with limited therapeutic options. Riluzole remains the only widely available disease-modifying treatment for ALS, yet its survival benefit is modest and likely to vary substantially between patients. Cytochrome P450 2D6 (CYP2D6), is a highly polymorphic enzyme that contributes to interindividual variability in the metabolism of many drugs. CYP2D6 is also expressed in the brain, and experimental and translational studies indicate that brain CYP2D activity can influence local metabolism of neuroactive compounds. Accordingly, CYP2D6 poor function variants have been examined as susceptibility modifiers in the development of other neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease, with heterogenous evidence; however, the role of CYP2D6 in ALS has not been established.},
}

@article {pmid42161687,
year = {2026},
author = {Carter, TE and Gunarathna, I},
title = {Reassessing malaria-transmitting mosquito evolution with a neotropical lens.},
journal = {Trends in parasitology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.pt.2026.05.006},
pmid = {42161687},
issn = {1471-5007},
abstract = {Tennessen et al.'s study addresses longstanding knowledge gaps regarding the evolutionary drivers of a major Neotropical malaria vector, Anopheles darlingi. Through extensive whole-genome analysis, they revealed geographically structured An. darlingi populations with no evidence of sympatric species and strong signals of widespread insecticide resistance through convergent evolution.},
}

@article {pmid42161891,
year = {2026},
author = {Liu, Y and Shi, K and Zhang, M and Wei, J and Feng, M and Dayan, FE and Tao, X and Feng, Z},
title = {Establishment of a versatile virus-based system for elucidating herbicide resistance in Galium aparine.},
journal = {Plant physiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/plphys/kiag285},
pmid = {42161891},
issn = {1532-2548},
abstract = {Herbicide resistance challenges sustainable weed management in crop fields. However, the lack of gene manipulation tools for weeds hinders studies of herbicide resistance evolution and regulation. Here, we identified that tobacco mosaic virus (TMV) can systemically infect Galium aparine, a noxious broadleaf weed common in wheat and rapeseed fields, among thirteen broadleaf weeds. The TMV-based expression system can be used to elucidate herbicide resistance in G. aparine. We demonstrated that virus-based expression of BAR, ALS and its site-directed mutagenized form in G. aparine plants can impart herbicide resistance. To expand the application of this system in metabolic resistance studies, ten upregulated P450 genes in the tribenuron-methyl-resistant G. aparine population plants were identified. Expression of these P450 genes in G. aparine via this system enhanced tribenuron-methyl resistance in G. aparine plants. Additionally, we confirmed Eleusine indica CYP81A104 functions in herbicide resistance through heterologous expression in G. aparine plants, suggesting that this system can be used to investigate the roles of genes from other weed species. The TMV vector-based assay system enabled the functional validation of weed genes within two months, which is shorter than the time required in other heterologous expression systems (i.e., stable expression of weed genes in rice or Arabidopsis). Thus, this virus-based system provides insights into target-site and/or metabolic-based resistance mechanisms to herbicides in G. aparine and possibly in other weed species.},
}

@article {pmid42162572,
year = {2026},
author = {Mehta, AK and Steele, SU and Shah, I and Wang, K and Booth, A and Swain, C and Desai, A and Popli, KA and Maragakis, NJ and Wright, R},
title = {Improving ALS Clinic Care Through Experience-Based Co-Design: A Participatory Action Research Study.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70279},
pmid = {42162572},
issn = {1097-4598},
support = {//Harold Young Scholarship/ ; },
abstract = {INTRODUCTION/AIMS: Multidisciplinary clinics (MDCs) are the standard of care for amyotrophic lateral sclerosis (ALS), yet little is known about how well they meet patient and care partner needs, or how stakeholder engagement can be used to strengthen these services. The aim of this study was to explore the experiences of people living with ALS (pALS), care partners (cALS), and staff in an ALS MDC to identify care gaps and collaboratively develop improvement strategies.

METHODS: We conducted a six-stage experience-based co-design (EBCD) study comprising narrative interviews with pALS, cALS, and ALS clinic staff, followed by validation events and co-design workshops. Data were analyzed using reflexive thematic analysis. Priority areas for improvement were identified through collaborative ranking and translated into actionable interventions through iterative working groups.

RESULTS: A total of 11 pALS, eight cALS, and 10 clinic staff participated. Two shared priority domains were identified: (1) communication and relationships across the care continuum, and (2) navigational and supportive resources. Stakeholders unanimously identified communication and relationships between cALS and staff as the highest priority for improving MDC care delivery. Key strategies included pre-visit orientation materials, pacing information delivery aligned with patient readiness, and incorporating digital tools to enhance flexible access to resources.

DISCUSSION: Curated, iterative education is essential for pALS and cALS across the disease trajectory. Improvement strategies developed through equitable stakeholder partnership may yield different, and potentially more patient-centered priorities for ALS MDC care delivery than strategies developed by any single stakeholder group alone.},
}

@article {pmid42162905,
year = {2026},
author = {Alamri, MA and Afzal, M and Pandey, SN and Afzal, O and Akela, MA and Rekha, A},
title = {Exosomal miRNA in cerebrospinal fluid as biomarkers for neurodegenerative disease.},
journal = {Clinica chimica acta; international journal of clinical chemistry},
volume = {},
number = {},
pages = {121094},
doi = {10.1016/j.cca.2026.121094},
pmid = {42162905},
issn = {1873-3492},
abstract = {Cerebrospinal fluid protein biomarkers, such as the Aβ42/Aβ40 ratio, phosphorylated tau, and neurofilament light chain, have significantly advanced the diagnostic process for Alzheimer's disease. Nonetheless, these biomarkers face challenges in effectively distinguishing Alzheimer's disease from frontotemporal dementia or Parkinson's disease from dementia with Lewy bodies. This limitation arises from overlapping protein profiles and the variability inherent in immunoassay techniques. A complementary class of analytes is exosomal microRNAs in cerebrospinal fluid, where these non-coding RNAs are secreted by neurons, astrocytes, and microglia, are resistant to RNase degradation, and have a disease-specific expression pattern. This review critically evaluates the existing evidence of cerebrospinal fluid exosomal miRNAs as diagnostic biomarkers in Alzheimer's disease, frontotemporal dementia, Parkinson's disease, dementia with Lewy bodies, and amyotrophic lateral sclerosis. Exosome isolation techniques and detection platform characteristics were compared using RT-qPCR, droplet digital PCR, and small RNA sequencing. Pre-analytical factors, such as collection protocols, hemolysis contamination, freeze-thaw cycling, and circadian sampling variation, were assessed. miRNA profiling data based on disease stratification, receiver operating characteristic performance of the combinatorial panel, and strategies combining exosomal miRNAs with core cerebrospinal fluid proteins were synthesized. This article brings together disease-specific miRNA signatures, pre-analytical standardization needs, and diagnostic accuracy analyses in a translational model to fill the literature gap and form the basis for developing exosomal miRNA panels for rigorously validated clinical laboratory practice.},
}

@article {pmid42163674,
year = {2026},
author = {Qi, M and Fei, L and Cui, W and Ho, PW and Lee, SM and Li, J and Zhang, Z},
title = {Unraveling the Pathological Mechanisms and Biomarkers of Amyotrophic Lateral Sclerosis: A Comprehensive Review.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X431460260227095109},
pmid = {42163674},
issn = {1875-6190},
abstract = {Amyotrophic lateral sclerosis (ALS) is an devastating neurodegenerative disorder with a very fast course and a very high fatality rate. The review discusses the intricate pathophysiology of ALS, such as the alterations caused by the genetic mutations of the C9orf72 and SOD1 genes, the misfolding and aggregation of proteins, oxidative stress, the excitotoxicity of glutamate, neuroinflammation, malfunctions in mitochondria, and axonal transport. Heterogeneity of the disease makes the development of biomarkers in ALS challenging; however, some promising candidates have been identified. Protein aggregation markers, including TDP-43 and SOD1, oxidative stress markers, such as 8-oxodG, neuroinflammatory markers, such as CRP and MCP-1, and neurological injury markers, such as NfL and pNfH, have potential in diagnosis, monitoring, and prediction. The miRNAs and particular metabolites can also provide clues to the molecular basis of ALS. The creation of biomarkers is challenged by the presence of a significant amount of disease heterogeneity and the lack of animal model reliability. The review highlights the importance of further research on biomarkers aimed at improving the diagnosis, treatment, and development of drugs for ALS. It supports the concept of a systematic biomarker development process, including genetic testing and molecular subgroup analysis, to enhance diagnostic accuracy and prognostic prediction capabilities. Exploring the interrelationship between the pathological process of ALS and the treatment based on multi-biomarker strategies is crucial for achieving effective management of this disease. As our understanding of ALS deepens, we expect to discover more new biomarkers in the future. This will significantly improve the diagnosis, treatment, and overall management of this devastating diseas.},
}

@article {pmid42163677,
year = {2026},
author = {Tiwari, D and Mukherjee, A and Singh, S},
title = {Interplay of NMDAR and AMPAR in the Pathophysiology of Alzheimer's, Parkinson, ALS, Huntington's, and Epilepsy: An Update in Therapeutic Perspective.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X466249260418090832},
pmid = {42163677},
issn = {1875-6190},
abstract = {Glutamate-mediated excitotoxicity is a central driver of neurodegeneration and represents a shared pathogenic mechanism across neurodegenerative diseases and epilepsy, with N-methyl-D-aspartate receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid recep-tors (AMPARs) occupying central roles in synaptic plasticity, Ca[2+] signalling, and neuronal survival. Dysregulation of these receptors disrupts the balance between pro-survival and pro-death pathways, accelerating neuronal loss in Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lat-eral sclerosis (ALS), Huntington's disease (HD), and epilepsy. Disease-specific triggers converge on common patterns of receptor dysregulation, including a shift toward extrasynaptic NMDAR signal-ling and the pathological emergence of Ca[2+]-permeable AMPARs (CP-AMPAR), ultimately driving synaptic failure and neuronal loss. Although numerous NMDAR and AMPAR-directed modulators have demonstrated neuroprotective efficacy in preclinical models, clinical translation has been lim-ited by inadequate spatial, kinetic, and subunit selectivity, as well as adverse effects arising from the disruption of physiological glutamatergic transmission. In this review, we synthesize the literature published between June 1990 and March 2025 to develop an integrative framework that links recep-tor localization, downstream Ca[2+]-dependent signalling, astrocytic regulation, mitochondrial dys-function, and disease progression across these disorders. By critically evaluating both successful and failed therapeutic strategies, we provide insight into evident research gaps in the field and the neces-sity of addressing them to develop precise multi-target approaches at both the genetic and cellular levels as next-generation therapeutics. Such an approach would be essential to move beyond indis-criminate receptor blockade strategies, which have repeatedly proven ineffective over the decades, and towards a future of durable neuroprotection.},
}

@article {pmid42164014,
year = {2026},
author = {Cheung, N},
title = {Symptom-Level Precision Neurology in Amyotrophic Lateral Sclerosis (ALS): Linking Microglial Pruning, Mitochondrial Nicotinamide Adenine Dinucleotide (NAD+) Compensation, and Autophagy Failure Across the Aging Spectrum.},
journal = {Cureus},
volume = {18},
number = {5},
pages = {e109147},
pmid = {42164014},
issn = {2168-8184},
abstract = {Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurological disease with limited disease-modifying treatment options and, for many patients, a short survival window. The clinical course varies widely. Limb weakness, bulbar impairment, respiratory decline, fine-motor dysfunction, cognitive change, mood symptoms, and fatigue may each appear at different times and progress at different rates. This variability suggests that motor neuron loss alone may not fully explain the patient-level pattern of symptoms. This article is a narrative hypothesis framework, not a clinical guideline or a validated stratification tool. Established ALS biology, associative genomic findings, preclinical observations, computational predictions, and author-derived hypotheses are therefore separated throughout the article. This review brings together four interlinked studies by the current author as a primary hypothesis-generating corpus, which proposes that synaptic plasticity fragility may initiate a microglial pruning continuum shared by major depressive disorder and ALS, while ALS-specific progression may depend on mitochondrial stress, oxidized nicotinamide adenine dinucleotide (NAD+) compensation failure, and collapse of autophagy under aging-related limits. The model presented here maps symptom domains to vulnerable circuit compartments and separates three broad biological states: compensated plasticity, fragile plasticity, and network collapse. A compact mechanistic formulation is used to describe the balance between pruning pressure, glutamatergic burden, and aging stress on one side, and oxidative phosphorylation capacity, NAD+ reserve, and autophagic clearance on the other. The framework also incorporates opposing phosphoinositide 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α) pathway patterns that may distinguish ALS from frontotemporal dementia (FTD) within an aging context. The result is a falsifiable, biomarker-oriented hypothesis model for future studies, not an evidence-based diagnostic or therapeutic algorithm.},
}

@article {pmid42164185,
year = {2026},
author = {Albesher, AA and Muflehi, NA and Hakami, YA and Barnawi, JA and Softah, RE and Al Ghalib, LH and Bukhari, MA and Almotiri, RA and Algethami, MS and Mahboob, SW and Hakami, RK and Alsaad, A},
title = {Top 50 Cited Articles on the Treatment of Major Depressive Disorder.},
journal = {Cureus},
volume = {18},
number = {4},
pages = {e107337},
pmid = {42164185},
issn = {2168-8184},
abstract = {Major depressive disorder (MDD) is a common mental health disorder and is one of the leading causes of disability. Numerous treatment modalities have been studied for MDD, from interventions to psychotherapies. However, no exhaustive investigation has yet provided an overview of influential research on MDD treatments. Studies do not cover influential efforts occurring in the form of a comprehensive bibliometric review. This bibliometric study aims to fill this gap by thoroughly examining the characteristics of the 50 most cited articles on MDD treatment and providing an essential understanding of the intellectual structure and historical development over time. To guarantee a comprehensive research collection of trends in the treatment of MDD, we reviewed 50 pertinent papers without limiting the search by publication year, and the data collection was performed in a neutral manner. The search focuses on extensive citations from other publications and categorizes them according to their frequencies. Between 1989 and 2018, the top 50 MDD treatment publications received 96-1,837 citations (median 210, IQR 121-299). The 2000s and 2010s had a high level of publication activity (21 articles each, 42% per decade). Geographically, the United States (24, 48%), Canada (12, 24%), and the United Kingdom (5, 10%) dominated the journals. The majority of study types were randomized controlled trials (RCTs) (32, 64%), followed by systematic reviews/meta-analyses (16, 32%) and prospective cohorts (2, 4%). The publications covered a range of treatment modalities, including pharmacological, psychotherapeutic, neurostimulation, and lifestyle/complementary approaches. Elkin et al.'s NIMH Treatment of Depression Collaborative Research Program report (1,738 citations) and Unützer et al.'s IMPACT collaborative care RCT (1,837 citations) were the most referenced publications. Our results shed light on the conceptual framework of MDD treatment research, as current guidelines are shaped by significant randomized trials and systematic reviews. Precision-based and new treatments are growing the field, while traditional therapies continue to play a major role. Global applicability is limited by the geographic concentration of research, underscoring the need for diverse populations, assessment of new treatments, and incorporation of individual patient data to bolster the body of evidence.},
}

@article {pmid42164629,
year = {2026},
author = {Akan, T and Aishwarya, R and Bhuiyan, MS and Conrad, SA and Vanchiere, JA and Bhuiyan, MAN},
title = {Computational pathology with dynamic convolutional and adaptive kernels.},
journal = {Journal of pathology informatics},
volume = {21},
number = {},
pages = {100662},
pmid = {42164629},
issn = {2229-5089},
abstract = {Data processing and learning have become essential to the advancement of medicine, with pathology and lab medicine being no exception. Integrating scientific research with clinical informatics into clinical practice facilitates novel methodologies for patient care. Computational pathology is a burgeoning subspecialty in pathology that promises a better-integrated solution to histopathological images and clinical informatics. Deep-learning methods in computational pathology have demonstrated considerable advances in automated histopathological image analysis. However, convolutional neural networks (CNNs) face fundamental limitations when dealing with the significant morphological heterogeneity present in disease tissues. Conventional CNNs use fixed convolutional kernels, which restrict their effectiveness in adaptively extracting features from histopathological images that exhibit diverse pathological patterns, staining intensities, and tissue architecture. To address this substantial limitation, we present an optimized variant of Omni-Dimensional Dynamic Convolution (ODConv) networks for distinguishing diseased tissue from healthy tissue. Compared with prior dynamic convolution methods that attend to a single kernel dimension, ODConv applies multi-dimensional attention across spatial positions, input channels, output channels, and kernel candidates, enabling more flexible and adaptive feature extraction. We evaluated our approach on wheat-germ agglutinin-stained and hematoxylin and eosin-stained skeletal muscle images from multiple disease models, including G93A*SOD1 transgenic mice (amyotrophic lateral sclerosis) and Akita mice (Type I diabetes). ODConv, trained entirely from scratch without ImageNet pretraining, achieved competitive classification performance relative to seven fine-tuned pretrained architectures across both staining modalities, demonstrating the effectiveness of omni-dimensional dynamic kernels in learning discriminative morphological representations directly from domain data. The study reports strong statistical agreement metrics, proving effective class balance handling and stable decision boundaries. These findings confirm ODConv as a strong computational pathology framework that advances automated diagnosis of neurodegenerative and metabolic skeletal muscle disorders.},
}

@article {pmid42165374,
year = {2026},
author = {Fernández-Gómez, P and Tosat-Bitrián, C and Marugán, T and Fernández-Hernández, L and Cano, A and Martinez-Mulero, JA and López-Carbonero, JI and Pignatelli, J and Corrochano, S and Palomo, V},
title = {Lighting Up Mislocalized Proteins: Quantum Dot Probes for Multiplexed Cytoplasm-Selective Cell Profiling in Neurodegeneration.},
journal = {ACS sensors},
volume = {},
number = {},
pages = {},
doi = {10.1021/acssensors.5c01941},
pmid = {42165374},
issn = {2379-3694},
abstract = {Semiconductor quantum dots (QDs) provide unique stability, brightness, and multiplexed capacity for biomarker detection in complex diseases; however, their distinctive intracellular distribution has rarely been leveraged for spatially resolved diagnostics. Here, we show how QD-based sensors enable selective detection of cytoplasmic proteins and can quantify nucleo-cytoplasm protein mislocalization in patient-derived samples. We validated this approach labeling TAR DNA-binding protein 43 (TDP-43), a key mislocalized protein in amyotrophic lateral sclerosis (ALS). Spatial resolution is achieved in several patient-derived models and mouse brain tissue, underscoring the nanosensor's versatility across biological systems. Multiplexed QD-based immunolabeling, combined with confocal imaging and high-throughput flow cytometry, enables the detection of distinct cytoplasmic biomarker signatures that discriminate ALS patients from healthy controls. These signatures include variations in TDP-43 mislocalization and protein coexpression patterns, which were further modulated by pharmacological treatment. This work establishes QDs as spatially selective, multiplexable nanosensors capable of resolving subtle yet disease-relevant intracellular phenotypes in patient-derived samples. Compared to organic fluorophores, QDs enhance sensitivity, improve signal stability, and enable simultaneous spatially resolved biomarker quantification, broadening their potential for clinical diagnostics and personalized medicine. These findings establish QDs as powerful tools for neurodegeneration research, disease monitoring, and early biomarker discovery, with potential applications in translational neuroscience and precision medicine.},
}