@article {pmid40364629,
year = {2026},
author = {Sepehrimanesh, M and Xu, W and Ding, B},
title = {Comparative analysis of chemical and lentiviral approaches in the generation of human induced pluripotent stem cell-derived motor neurons.},
journal = {Neural regeneration research},
volume = {21},
number = {7},
pages = {2968-2974},
pmid = {40364629},
issn = {1673-5374},
support = {R56 NS133252/NS/NINDS NIH HHS/United States ; },
abstract = {The generation of human induced pluripotent stem cell–derived motor neurons overcomes limited access to human tissues and offers an unprecedented approach to modeling motor neuron diseases such as dystonia and amyotrophic lateral sclerosis. Motor neurons generated through different strategies may exhibit substantial differences in purity, maturation, characterization, and even neuronal identity, leading to variable outcomes in disease modeling and drug screening. However, very few comparative studies have been conducted to determine the similarities and differences among motor neurons prepared via different protocols. In this study, we prepared human induced pluripotent stem cell–derived motor neurons via lentiviral delivery of transcription factors and chemical induction and performed a systematic comparative analysis. We found that motor neurons generated by both approaches showed typical motor neuron morphology and robustly expressed motor neuron-specific markers, such as nuclear homeobox transcription factor 9 and choline acetyltransferase. The chemical induction protocol utilizes a combination of small molecules to induce motor neuron differentiation, offering a significantly faster maturation time of 35 days compared to 46 days with lentiviral delivery of transcription factors. Additionally, while lentiviral delivery of transcription factors are suitable for downstream biochemical analysis, chemical induction are more applicable for therapeutic approaches as they avoid the use of lentiviruses. Both approaches produce motor neurons with high purity (> 95%) and yield. No significant differences were found between chemical induction and lentiviral delivery of transcription factors in terms of motor neuron markers and maturation markers. These robust methodologies offer researchers powerful tools for investigating motor neuron diseases and potential therapeutic strategies.},
}

@article {pmid42464213,
year = {2026},
author = {Özbilici, Z and Issı, ES},
title = {SYNE1-Related motor neuron disease-like phenotype with mild distal contractures and 24-month clinical stability: a case report.},
journal = {BMC neurology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12883-026-05142-7},
pmid = {42464213},
issn = {1471-2377},
abstract = {BACKGROUND: SYNE1 encodes nesprin-1, a nuclear envelope protein involved in cytoskeletal linkage, nuclear positioning, and neuromuscular integrity. Biallelic SYNE1 variants cause a broad spectrum ranging from cerebellar ataxia to arthrogryposis multiplex congenita and motor neuron disease-like phenotypes. Distinguishing these entities can be difficult when subtle distal contractures coexist with neurogenic electrophysiological findings.

CASE PRESENTATION: A 22-year-old woman born to consanguineous parents presented with bilateral intrinsic hand muscle wasting, impaired fine motor performance, and mild gait difficulty. Examination showed distal hand atrophy, mild weakness of the abductor pollicis brevis and first dorsal interosseous muscles, brisk deep tendon reflexes, preserved sensation, and mild distal finger contractures. Sensory nerve conduction studies were normal. Motor studies showed reduced compound muscle action potential amplitude in the right abductor pollicis brevis and borderline-low amplitude on the left. Needle electromyography showed widespread chronic neurogenic motor unit changes affecting the upper and lower extremities, with active denervation most evident in the bilateral abductor pollicis brevis muscles. Genioglossus examination was normal. SMN1 deletion testing and selected familial amyotrophic lateral sclerosis gene testing were negative. Whole exome sequencing identified a homozygous truncating SYNE1 variant, NM_182961.4:c.21009G > A; p.(Trp7003Ter). Segregation analysis confirmed heterozygous carrier status in both parents and two unaffected siblings. At 24-month follow-up, weakness, atrophy, contractures, reflex pattern, and functional status remained clinically stable, without bulbar, cerebellar, sensory, or clinically evident respiratory involvement.

CONCLUSIONS: This case supports classification as a SYNE1-related motor neuron disease-like phenotype with mild distal contractures rather than an isolated arthrogryposis multiplex congenita type 3 (AMC3) phenotype. The case also supports including SYNE1 in genetic testing panels for young patients with unexplained motor neuron disease-like presentations, particularly when consanguinity, normal sensory conduction, and subtle distal contractures coexist.},
}

@article {pmid42464712,
year = {2026},
author = {Gao, N and Cui, B and Yun, Y and Yu, W and Gao, X and Sun, X and Shao, K and Lin, P and Liu, F and Li, W and Zhao, Y and Yu, D and Yan, C and Liu, S and Lou, J},
title = {Corticospinal Subfiber Neurite Density Index Detects Upper Motor Neuron Degeneration in Prediagnostic Patients With Sporadic Amyotrophic Lateral Sclerosis.},
journal = {European journal of neurology},
volume = {33},
number = {7},
pages = {e70703},
pmid = {42464712},
issn = {1468-1331},
support = {82471429//National Natural Science Foundation of China/ ; ZR2024MH013//Natural Science Foundation of Shandong Province/ ; 2025CXPT133//the Key Research and Development Program of Shandong Province, China/ ; Z-2017-24-2509//the Yantu Neuroscience Specialized Research Fund Project/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/diagnostic imaging/blood/diagnosis ; Female ; Male ; *Pyramidal Tracts/diagnostic imaging/pathology ; Middle Aged ; *Neurites/pathology ; Retrospective Studies ; Aged ; Neurofilament Proteins/blood ; Diffusion Magnetic Resonance Imaging ; Diffusion Tensor Imaging ; *Motor Neurons/pathology ; *Nerve Degeneration/pathology/diagnostic imaging ; },
abstract = {BACKGROUND: Using multi-shell diffusion MRI, we aimed to identify whether corticospinal tract (CST) subfiber damage can be detected in prediagnostic amyotrophic lateral sclerosis (ALS) patients. We also explored whether the combination of serum neurofilament light chain (NfL) levels and CST subfiber abnormalities may provide better diagnostic performance in differentiating prediagnostic ALS patients from disease controls (DCs) and healthy controls (HCs) than single markers.

METHODS: In this retrospective study, prediagnostic ALS was used as an operational term for patients who presented at baseline with chronic progressive limb weakness or bulbar symptoms, had no clinically evident typical UMN signs, and were subsequently confirmed to have sporadic ALS according to the Awaji criteria during longitudinal follow-up. Patients whose final diagnosis was not ALS after follow-up were classified as disease controls. Probabilistic tractography was performed on baseline MRI data to assess CST subfiber damage in 47 ALS patients, 20 DCs, and 51 HCs.

RESULTS: Compared with Controls, ALS patients had significantly lower neurite density index (NDI) values of CST subfibers, particularly those originating from the primary and supplementary motor cortex. The diagnostic performance of the combined model incorporating serum NfL and CST subfiber NDI values in differentiating prediagnostic ALS patients from HCs and DCs was 0.925 and 0.928, respectively, which was better than that of single markers (0.634-0.886 and 0.699-0.856, respectively).

CONCLUSIONS: Our findings suggest that CST subfibers NDI values are promising neuroimaging markers for detecting in vivo UMN degeneration in prediagnostic ALS. Moreover, combining blood and neuroimaging markers may further improve early diagnostic performance.},
}

Humans
*Amyotrophic Lateral Sclerosis/pathology/diagnostic imaging/blood/diagnosis
Female
Male
*Pyramidal Tracts/diagnostic imaging/pathology
Middle Aged
*Neurites/pathology
Retrospective Studies
Aged
Neurofilament Proteins/blood
Diffusion Magnetic Resonance Imaging
Diffusion Tensor Imaging
*Motor Neurons/pathology
*Nerve Degeneration/pathology/diagnostic imaging

@article {pmid42465739,
year = {2026},
author = {You, Y and Zhu, H and Zhang, Q and Wang, J and Dong, C and Yang, Z and Zhang, J and Zhang, Y and Zhang, M and Lu, M and Du, C},
title = {Development and efficacy of ex vivo expanded autologous regulatory T cells for the treatment of amyotrophic lateral sclerosis.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1854252},
pmid = {42465739},
issn = {1664-3224},
mesh = {*Amyotrophic Lateral Sclerosis/therapy/immunology/genetics ; *T-Lymphocytes, Regulatory/immunology/transplantation/metabolism ; Animals ; Humans ; Mice ; Disease Models, Animal ; Female ; Superoxide Dismutase-1/genetics ; Mice, Transgenic ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited therapeutic options, in which neuroinflammation critically drives disease progression. Regulatory T cells (Tregs) exert potent immunosuppressive and neuroprotective effects, offering great potential for ALS treatment. However, clinical application of Treg therapy is hampered by low peripheral cell abundance and unstable expansion quality. Here, we established and optimized a GMP-grade protocol for sorting and expanding peripheral blood-derived Tregs, and validated cryopreserved apheresis products as feasikble starting materials. Although ALS patient-derived Tregs showed reduced expansion capacity compared with healthy donor counterparts, they maintained comparable purity, stable regulatory phenotypes, and robust immunosuppressive function. Transcriptomic analysis confirmed the lineage fidelity and low pro-inflammatory characteristics of expanded Tregs. Therapeutic efficacy was verified in SOD1G93A ALS and GvHD mouse models with delayed disease progression and relieved inflammation. This study provides standardized GMP manufacturing strategies and solid preclinical evidence to support the ongoing clinical trial (NCT06671236) and facilitate Treg immunotherapy translation for ALS.},
}

*Amyotrophic Lateral Sclerosis/therapy/immunology/genetics
*T-Lymphocytes, Regulatory/immunology/transplantation/metabolism
Animals
Humans
Mice
Disease Models, Animal
Female
Superoxide Dismutase-1/genetics
Mice, Transgenic

@article {pmid42466415,
year = {2026},
author = {Mei, A and Jewett, D and Jewett, A and Kaur, K and Malarkannan, S},
title = {Multi-hit genetic lesions and a stress-imprinted immune transcriptome define the inflammatory pathology in ALS patients.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {42466415},
issn = {2693-5015},
abstract = {Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative disease whose peripheral immune architecture remains incompletely defined. Here, we integrated whole-genome sequencing and single-cell RNA sequencing to define genomic and immune correlates of ALS. Genome-wide analysis of a monozygotic twin pair discordant for ALS pathology identified shared ALS-associated variants, as well as patient-enriched variants in genes linked to RNA metabolism, neurodegeneration, and immune inflammation, supporting a multilayered genetic architecture. Single-cell profiling of 40,484 peripheral blood mononuclear cells from three ALS patients and two healthy individuals, including 33,667 cells retained after quality control, resolved 13 immune clusters and revealed broad remodeling of the peripheral immune compartment, with relative enrichment of natural killer, mucosal-associated invariant T, and γδ T-cell populations. Across immune subsets, ALS samples exhibited inflammatory and stress-adapted transcriptomic programs, including TNF-α/NF-κB, IFN-γ, hypoxia, and ribosomal stress pathways. These data support a model in which multi-hit genetic susceptibility converges on a stress-induced immune transcriptome, marked uniquely by innate lymphocyte activation in ALS patients.},
}

@article {pmid42459525,
year = {2026},
author = {Majumdar, S and Samaiya, PK and Ahmed, S and Prajapati, SK},
title = {Imaging biomarkers in neurodegenerative diseases: advances and challenges.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1813588},
pmid = {42459525},
issn = {1663-4365},
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), represent a major global health burden. Imaging biomarkers have emerged as important tools for improving the diagnosis, monitoring, and biological characterization of neurodegenerative diseases. Structural MRI, diffusion tensor imaging (DTI), functional MRI (fMRI), positron emission tomography (PET), hybrid PET/MRI and molecular imaging have transformed our ability to investigate neurodegeneration in vivo non-invasively. This review highlights updated information on how each imaging modality offers a unique window into different disease pathophysiology including regional atrophy, amyloid-β, tau, dopaminergic terminal degeneration, synaptic density (SV2A), and neuroinflammation. We also focused on the translational and evidence supporting biomarkers, appropriate use criteria for amyloid and tau PET imaging, and standardized quantification methods such as the Centiloid scale. The growing role of multimodal fusion, where imaging is increasingly integrated with scalable fluid biomarkers to enable "blood-first" strategies where high-risk patients are selectively referred to advanced imaging, improving feasibility and equity. Despite tremendous progress, there are still issues with their standardization, sensitivity, specificity, and clinical translation. Moreover, the review emphasizes the frontiers of α-synuclein and glial state-specific PET ligands, advanced diffusion models, and dynamic connectivity analysis to support precision medicine and mechanism-based trial design for NDDs.},
}

@article {pmid42459857,
year = {2026},
author = {Hu, M and You, L and Zhang, X and Xuan, Z and Ma, S and Wu, X},
title = {Experimental evidence of electroacupuncture in ALS mouse models: a systematic review and meta-analysis.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1780176},
pmid = {42459857},
issn = {1664-2295},
abstract = {OBJECTIVE: This study aimed to systematically evaluate the therapeutic efficacy of electroacupuncture (EA) in amyotrophic lateral sclerosis (ALS) and to elucidate the underlying neurobiological mechanisms by synthesizing preclinical evidence.

METHODS: According to the PICOS principle, relevant studies were searched in the following databases: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and CNKI. Search terms and strategies were determined based on MeSH terms. The methodological quality of the included studies was assessed using the SYRCLE's Risk of Bias tool and the CAMARADES checklist. Meta-analysis was performed using Stata 15.0 and Rstudio software.

RESULTS: Seventeen studies involving 372 animals were included. The quality scores of the included studies ranged from 5 to 8, with an average score of 7. The meta-analysis of the primary outcome, the rotarod test score, showed a significant improvement in the EA group compared to the control group [SMD = 3.31, 95% CI (2.05, 4.57), Z = 5.151, p < 0.001], indicating that EA can enhance motor function in ALS mice. Regarding secondary outcomes, EA intervention alleviated neuroinflammation, promoted neuronal survival, improved axonal regeneration inhibition, and stabilized RNA metabolism homeostasis. Consequently, it slowed disease progression, improved motor performance, prolonged survival time, and effectively protected motor neurons at the histopathological level (p < 0.05). These findings underscore the potential of EA as a promising multimodal therapeutic strategy for ALS. For the heterogeneity observed in the rotarod test, sensitivity analysis, subgroup analysis, and meta-regression did not identify its source. However, potential publication bias was detected, which might contribute to the heterogeneity. The heterogeneity for other outcome measures might originate from differences in stimulation parameters (e.g., waveform), acupoint selection, or treatment duration.

CONCLUSION: This meta-analysis demonstrates that EA confers significant neuroprotective benefits in preclinical ALS models, primarily through multi-target modulation of key pathological processes such as neuroinflammation, aberrant cell death signaling, and RNA metabolism. These preclinical findings underscore the potential of electroacupuncture as a complementary neuroprotective strategy and warrant further investigation in rigorous clinical trials.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251229183.},
}

@article {pmid42459893,
year = {2026},
author = {Ogino, M},
title = {Single-subject auditory ERP-BCI performance enhancement in ALS via an AI coding assistant prompt.},
journal = {Frontiers in human neuroscience},
volume = {20},
number = {},
pages = {1869918},
pmid = {42459893},
issn = {1662-5161},
abstract = {INTRODUCTION: Auditory event-related potential (ERP) brain-computer interfaces (BCIs) offer communication support for individuals with amyotrophic lateral sclerosis (ALS) who eventually progress to completely locked-in states. However, individual-specific BCI pipeline optimization is technically demanding and time-consuming, leaving substantial room for performance improvement in practice. A central challenge is increasing selection speed while maintaining reliable classification accuracy, since slower selections reduce the sense of agency and undermine the motivational and feedback dynamics essential for sustained BCI use.

METHODS: We investigated whether an AI coding assistant could address this challenge for individual patients. A three-class auditory ERP-BCI was optimized for a single ALS patient using Claude Code (Anthropic, Inc.), which iteratively generated and evaluated 23 optimization scripts over approximately 24 hours with minimal human-in-the-loop oversight. The resulting AI-Designed ERP classifier (AIDE) was evaluated on 189 EEG trials spanning 3.5 years using five cross-validation strategies.

RESULTS: For the baseline models, halving the stimulus repetitions to shorten selection time degraded classification accuracy; AIDE prevented this degradation, achieving 85.03% mean cross-validation accuracy (selection time 17 s; ITR 2.92 bits/min). This doubled the information transfer rate from 1.43 to 2.92 bits/min. Accuracy exceeded 84% across four of five cross-validation strategies. Feature space visualization revealed that the AI autonomously selected and combined EEG features established in prior studies into an effective discriminative architecture, without domain-specific algorithmic guidance from the human researcher. In addition, online test confirmed 66.7% accuracy for AIDE versus 50.0% for the baseline model.

DISCUSSION: These findings provide proof of concept that single-subject BCI performance can be improved via a single prompt, offering an efficient pathway to individualized optimization in clinical and research settings.},
}

@article {pmid42460499,
year = {2026},
author = {Leichsenring, F and Heim, N and Steinert, C},
title = {Conceptual problems and questionable evidence in defining non-inferiority margins - a reply to Flückiger et al.},
journal = {Psychotherapy research : journal of the Society for Psychotherapy Research},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/10503307.2026.2701025},
pmid = {42460499},
issn = {1468-4381},
abstract = {From 19 meta-analyses comparing active bona fide treatments, Flückiger et al. (2026) recently calculated a between-group effect size (SMD) of -0.17 for primary outcomes and of -0.16 for secondary outcomes. They suggested using these effect sizes as empirically derived non-inferiority margins. However, Flückiger et al.'s approach is conceptually problematic and lacks empirical support. Without a rationale, empirically found differences between active treatments cannot per se be regarded as non-inferiority margins.},
}

@article {pmid42460524,
year = {2026},
author = {Cai, X and Bai, Y and Ma, F and Xu, R and Xie, Y and Cao, X},
title = {Mechanisms and Therapeutic Targeting of the cGAS-STING Pathway in Central Nervous System Disorders.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X472988260627201746},
pmid = {42460524},
issn = {1875-6190},
abstract = {OBJECTIVE: The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway is a core DNA-sensing axis in innate immunity and has been increasingly implicated in the pathogenesis of multiple Central Nervous System (CNS) disorders. This review summarizes current knowledge of cGAS-STING signaling in CNS disorders and evaluates its therapeutic potential.

METHODS: Relevant studies on cGAS-STING signaling in CNS disorders were collected from PubMed and Web of Science, with emphasis on disease mechanisms, neuroinflammatory regulation, and pathway-targeted therapeutic strategies.

RESULTS: In the CNS, cGAS-STING signaling exhibits marked region-, cell-, and pathology-dependent heterogeneity. Aberrant DNA sensing activates this pathway and amplifies neuroinflammation, cellular stress, and tissue injury in Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS), ataxia-telangiectasia (A-T), and ischemic and hemorrhagic stroke. Pharmacological inhibition of cGAS, cyclic GMP-AMP (cGAMP), or STING, together with emerging delivery strategies, has shown promise in preclinical models.

DISCUSSION: Clinical translation remains limited by incomplete validation of pathway specificity, limited human evidence, restricted brain delivery, and inconsistent efficacy assessment.

CONCLUSION: The cGAS-STING pathway links aberrant DNA sensing to innate immune activation and CNS pathology. Clarifying its disease-, cell-, and stage-specific roles may support future targeted therapeutic strategies for CNS disorders.},
}

@article {pmid42460525,
year = {2026},
author = {Liu, Y and Yang, J and Su, J and Hao, L},
title = {High Levels of Plasma Neurturin Partially Mediate the Protective Effect of Reduced Ruminococcus2 Abundance on Multiple Sclerosis: A Mendelian Randomization Study.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X468669260626223524},
pmid = {42460525},
issn = {1875-6190},
abstract = {BACKGROUND: Genetic evidence implicates the contribution of the gut-brain axis to neurodegenerative diseases (NDDs). Alterations in gut microbiota and inflammation are key pathophysiological contributors. Elucidating the genetic basis and the role of cytokines can provide insights into mechanisms linking gut microbial composition to neurodegeneration.

METHODS: Using aggregated statistics from five large-scale Genome-Wide Association Studies (GWAS) on Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, multiple sclerosis, and amyotrophic lateral sclerosis, bidirectional two-sample Mendelian Randomization (MR) was used to examine the associations. A two-step multivariable Mendelian randomization approach incorporates data from 91 cytokines to explore potential mediators.

RESULTS: The study reveals 18 positive and 17 negative effects between gut microbiota and NDDs, as well as 10 positive and 10 negative effects between cytokines and NDDs. Remarkably, mediation analysis identified a causal pathway, with evidence that plasma neurturin levels partially mediate the association from genus Ruminococcus2 to multiple sclerosis, with a mediation proportion of 19.19% (OR = 1.038, 95% CI = 1.001-1.086, P = 0.044). No pleiotropy or heterogeneity was detected.

DISCUSSION: These MR findings provide compelling evidence for a genetically anchored gutimmune-brain network in NDDs, with cytokines as intermediates. Bidirectional effects highlight disease-specific microbial signatures and inflammatory contexts. The Ruminococcus2-neurturin pathway in multiple sclerosis may offer mechanistic specificity, aligning with neurotrophic and anti-inflammatory signaling pathways.

CONCLUSION: This study emphasizes the importance of gut microbiota alterations in NDDs and explores inflammation's partial intermediary role. The findings suggest potential targets for personalized neurodegeneration prevention strategies.},
}

@article {pmid42460529,
year = {2026},
author = {Chen, H and Yang, Z and Meng, H and Hu, Z and Ke, Z and Ye, Q and Xu, Y and Wu, J and Liu, Z},
title = {White Matter Functional Dysregulation in Amyotrophic Lateral Sclerosis: Machine Learning-Based Biomarkers and Transcriptomic Signatures.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X465668260629073047},
pmid = {42460529},
issn = {1875-6190},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor system degeneration, yet its white matter (WM) functional pathophysiology remains underexplored.

METHODS: This study utilized resting-state functional magnetic resonance imaging to decode WM functional abnormalities in 50 ALS patients and 55 healthy controls. Next, machine learning analysis was applied to evaluate the utility of these WM functional patterns in diagnosing ALS and predicting disease progression, and their pathophysiological mechanisms were preliminary explored through neurotransmitter mapping and imaging transcriptomics.

RESULTS: ALS patients exhibited reduced activity in central WM regions (including bilateral corticospinal tracts), accompanied by elevated activity in anterior and posterior WM territories. The aberrant topological properties and disrupted functional connectivity are predominantly localized within bilateral precentral/postcentral WM networks. A support vector machine model incorporating these features achieved 75.24% classification accuracy and predicted the rate of disease progression (r = 0.56, p = 0.001). The spatial pattern of WM dysfunction in ALS was associated with both the spatial distribution of disease-related neurotransmitters and the expression profiles of specific genes.

DISCUSSION: Our findings reveal distinct WM functional dysfunction patterns in ALS and their molecular-genetic underpinnings, providing novel insights into the pathophysiological mechanisms of ALS.

CONCLUSION: ALS involves specific patterns of WM dysfunction, and these WM-centric biomarkers may facilitate the development of therapeutic monitoring frameworks for this devastating disease.},
}

@article {pmid42461162,
year = {2026},
author = {Zhang, R and Zhang, N and Li, B and Liu, Q and Xu, C and Li, B and Zhang, J},
title = {Nursing a Patient With Amyotrophic Lateral Sclerosis Stage 4B With Epilepsy: A Case Study.},
journal = {Nursing in critical care},
volume = {31},
number = {4},
pages = {e70573},
pmid = {42461162},
issn = {1478-5153},
support = {25ZZJJLW-015//Medical Research Council Foundation of the 305 Hospital of the PLA/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/nursing/complications ; *Epilepsy/nursing/complications ; Male ; Intensive Care Units ; *Critical Care Nursing/methods ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a rare motor neuron disease characterised by progressive muscle weakness, which can eventually lead to death. So far there is no effective cure for it. This case report discusses the nursing of a patient with stage 4B amyotrophic lateral sclerosis complicated with epilepsy and sudden disturbance of consciousness during his stay in an intensive care unit (ICU). After 34 days of treatment and care, the patient regained consciousness with stable vital signs before being transferred out of the ICU. This report focusses on nursing interventions adopted in terms of respiratory management, nutritional management, psychological care and exercise during both the epileptic seizure and the awake period of the patient in the hope of providing a reference for the nursing of patients with amyotrophic lateral sclerosis with epilepsy in intensive care units.},
}

Humans
*Amyotrophic Lateral Sclerosis/nursing/complications
*Epilepsy/nursing/complications
Male
Intensive Care Units
*Critical Care Nursing/methods

@article {pmid42461445,
year = {2026},
author = {Mitsumoto, H and Cheung, K and Matsumoto, T and Lanza, I and Oskarsson, B and Johnson, S and Petterson, XT and Jang, GE and Andrews, HF},
title = {Metabolomic analyses of amyotrophic lateral sclerosis, muscle cramps, and TJ-68 treatment.},
journal = {Metabolomics : Official journal of the Metabolomic Society},
volume = {22},
number = {4},
pages = {},
pmid = {42461445},
issn = {1573-3890},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy/blood ; *Muscle Cramp/drug therapy/metabolism/blood ; *Metabolomics/methods ; Female ; Male ; Middle Aged ; Aged ; Cross-Over Studies ; Medicine, Kampo ; *Drugs, Chinese Herbal/therapeutic use ; },
abstract = {INTRODUCTION: Most patients with amyotrophic lateral sclerosis (ALS), a fatal motor neuron disease, experience painful muscle cramps. Our recent pilot trial of the Japanese Kampo medicine TJ-68 suggested its efficacy in improving muscle cramps in patients with ALS.

OBJECTIVES: This study analyzed plasma metabolomic changes to identify the underlying mechanisms of muscle cramps in ALS and the effects of TJ-68.

METHODS: Plasma was obtained from 11 participants with ALS in the repeated crossover trial at five time points (baseline, two placebo phases, and two TJ-68 phases). Metabolites were analyzed using mass spectrometry. Linear mixed-effects models were applied to identify metabolite changes associated with muscle cramps, determine the effects of TJ-68 on metabolites, and predict which participants would respond to TJ-68.

RESULTS: Higher glutamine/glutamate, arginine, and leucine levels were associated with more severe muscle cramps. TJ-68 treatment increased tryptophan and aconitate levels but reduced serotonin and acetylcarnitine levels. Long-chain acylcarnitine levels were correlated with muscle cramp severity, and their levels tended to decrease with treatment. Uric acid, β-aminoisobutyric acid, α-aminoadipic acid, and acetylcholine emerged as predictors of the efficacy of TJ-68.

CONCLUSION: This study identified the metabolite profile of muscle cramps in ALS and the changes in metabolite levels after TJ-68 treatment. Several baseline metabolites were associated with the prediction of the response to muscle cramps following TJ-68 treatment. Uric acid might be particularly useful because of its easy measurement in standard assays. Our study affirms the value of metabolomic technology for future pharmacotherapy and studies in ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/metabolism/drug therapy/blood
*Muscle Cramp/drug therapy/metabolism/blood
*Metabolomics/methods
Female
Male
Middle Aged
Aged
Cross-Over Studies
Medicine, Kampo
*Drugs, Chinese Herbal/therapeutic use

@article {pmid42461653,
year = {2026},
author = {Kneepkens, SCM and Lingham, G and van Hemert, DJ and Loughman, J and Strang, NC and Tham, YC and Harrington, SC and Guisasola, L and French, A and He, X and Mackey, DA and Hagen, LA and Baraas, RC and Pärssinen, O and Yam, JC and Saunders, KJ and Guggenheim, JA and Saw, SM and Lan, WZ and Klaver, CCW and Flitcroft, DI and , },
title = {Global Axial Length Centile Charts.},
journal = {JAMA ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaophthalmol.2026.2539},
pmid = {42461653},
issn = {2168-6173},
abstract = {IMPORTANCE: Myopia is increasingly common worldwide and poses major public health challenges because axial elongation drives sight-threatening complications. Because axial length (AL) is the primary target for myopia management, population-specific AL reference charts are needed.

OBJECTIVE: To generate region- and sex-specific reference centile charts for AL in children and adolescents.

This was a pooled cohort analysis using individual-participant data from population- and school-based studies conducted in East Asia, Europe, and Australia contributing to the CREAM-Kids Consortium. A total of 147 404 children and adolescents contributing 559 799 AL measurements were included. Most participants were from East Asia (84%; ages 6-18 years), followed by Europe (12%; ages 6-21 years) and Australia (4%; ages 6-21 years). After assessment of comparability, European and Australian datasets were combined. Data were included from 1999 to 2024, with the analysis taking place from December 2024 to May 2026.

EXPOSURES: AL, age, sex, and geographic region.

MAIN OUTCOMES AND MEASURES: Region- and sex-specific AL centiles across age and agreement between modeled centiles and empirical values.

RESULTS: AL distributions among the 147 404 included individuals varied by sex and region. In female individuals, the 50th centile AL at age 7 years was 22.35 mm in Europe and Australia and 22.67 mm in East Asia; by age 18 years, the 50th centile ALs were 23.31 mm and 24.36 mm, respectively. Regional differences were larger at higher centiles: for female individuals at age 7 years, East Asia vs Europe and Australia differences were 0.33 mm at the 3rd centile and 0.50 mm at the 97th centile; at age 18 years, differences were 0.73 mm and 1.27 mm, respectively. Modeled centile curves closely matched empirical values (intraclass correlations >0.99) with minimal bias across sex and region subgroups (-0.08 mm to 0.04 mm).

CONCLUSIONS AND RELEVANCE: While not based solely on population-based cohorts, the region- and sex-specific AL centile charts developed in this pooled cohort study provide reference values for childhood and adolescence that may be used to support clinical and research applications, including identifying atypical axial elongation and informing targeted strategies for myopia prevention and management.},
}

@article {pmid42461927,
year = {2026},
author = {Zhong, F and Ni, C and Wang, B},
title = {Optimal pooling strategies for respiratory virus testing: A comparative cost-effectiveness analysis.},
journal = {PLOS global public health},
volume = {6},
number = {7},
pages = {e0006646},
pmid = {42461927},
issn = {2767-3375},
abstract = {Pooled testing represents a cost-efficient strategy for large-scale respiratory virus screening. However, determining the optimal pool size (OPS) across varying prevalence rates and diagnostic performance metrics remains a critical challenge in respiratory virus surveillance. We evaluated four hierarchical OPS algorithms, all employing the original solution method (OSM), and proposed a modified solution method (MSM) based on objective function optimization. Through Monte Carlo simulations and logit modeling, we generated COVID-19 infection data representative of community transmission patterns. These data were analyzed using a comparative cost-effectiveness framework to assess OSM and MSM approaches. Our analysis across various prevalence rates (0.1-30.0%), sensitivities (0.8-1.0), and specificities (0.97-1.00) revealed Hanel et al.'s algorithm consistently yielded the largest OPS values under OSM. MSM revealed minimal deviations from OSM in most scenarios, though it effectively corrected Kim et al.'s inflated OPS values at high prevalence (~30%) with low sensitivity/specificity. Three algorithms produced comparable OPS configurations, outperforming OSM. Hanel's and Regen's algorithms emerged as the most cost-effective options, with Hanel's method being optimal for low additional costs in second-stage testing and Regen's for high additional costs. MSM significantly reduced inter-algorithm cost differences compared to OSM. This study provides a comprehensive evaluation of OPS determination algorithms in pooled PCR testing for respiratory viruses, demonstrating robust OPS configurations and enhanced cost-effectiveness through MSM implementation. The proposed MSM addresses existing limitations in pooled testing strategies, facilitates efficient resource allocation, and contributes to improved respiratory virus surveillance and pandemic response.},
}

@article {pmid42462180,
year = {2026},
author = {Baskar, K and Steffke, C and Bernsen, S and Elmas, Z and Hesebeck-Brinckmann, J and Schuster, J and Meyer, T and Weydt, P and Weishaupt, J and Brenner, D and Catanese, A},
title = {Multiplex Panel Detects Glial and Inflammatory Biomarker Signatures in Sporadic and C9orf72-ALS.},
journal = {Neurology(R) neuroimmunology & neuroinflammation},
volume = {13},
number = {5},
pages = {e200618},
doi = {10.1212/NXI.0000000000200618},
pmid = {42462180},
issn = {2332-7812},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid/diagnosis/genetics ; Biomarkers/cerebrospinal fluid ; Female ; Male ; C9orf72 Protein/genetics ; Middle Aged ; Aged ; Neuroglia ; *Neuroinflammatory Diseases/cerebrospinal fluid ; Neurofilament Proteins/cerebrospinal fluid ; Adult ; *Inflammation/cerebrospinal fluid ; Chitinase-3-Like Protein 1/cerebrospinal fluid ; },
abstract = {BACKGROUND AND OBJECTIVES: CSF proteomics has emerged as a valuable strategy for identifying diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis (ALS). However, the limited availability and volumes of CSF samples restrict the broader clinical application of CSF-based biomarker panels. To address this challenge, we investigated whether the novel nucleic acid-linked immuno-sandwich assay (NULISA) multiplex platform-capable of quantifying multiple neural, glial, and inflammatory markers from minimal biofluid volumes-could validate previously proposed biomarkers and identify additional candidates relevant to ALS.

METHODS: Using this platform, we measured a targeted panel of 131 biomarkers in cohorts of patients with C9orf72-associated ALS, sporadic ALS (sALS), and matched healthy controls.

RESULTS: The 6 markers neurofilament heavy chain (NEFH) and neurofilament light chain (NEFL), chitinases-particularly chitotriosidase-1 (CHIT1) and chitinase-3-like protein-1 (CHI3L1), and chemokines CCL2 and CCL3 were significantly elevated in both ALS groups compared with controls. These biomarkers correlated with disease progression and demonstrated strong diagnostic performance when combined into aggregate scores, as reflected by a high area under the receiver operating characteristic curve for ALS. Notably, C9orf72-ALS patients exhibited higher levels of the oxidative stress-related markers PRDX6 and ENO2, compared with sALS patients, suggesting a genotype-specific molecular signature.

DISCUSSION: Overall, our findings support the use of a multiplexed panel of diverse, inflammatory, glial, and neurodegeneration-associated biomarkers as a complementary diagnostic and prognostic tool alongside established measurements of neurofilaments. This approach may enhance biomarker robustness while minimizing CSF volume requirements, thereby improving clinical feasibility in ALS research and care.},
}

Humans
*Amyotrophic Lateral Sclerosis/cerebrospinal fluid/diagnosis/genetics
Biomarkers/cerebrospinal fluid
Female
Male
C9orf72 Protein/genetics
Middle Aged
Aged
Neuroglia
*Neuroinflammatory Diseases/cerebrospinal fluid
Neurofilament Proteins/cerebrospinal fluid
Adult
*Inflammation/cerebrospinal fluid
Chitinase-3-Like Protein 1/cerebrospinal fluid

@article {pmid42463858,
year = {2026},
author = {Picchiarelli, G and Demestre, M and Zuko, A and Been, M and Higelin, J and Dieterlé, S and Goy, MA and Mallik, M and Sellier, C and Scekic-Zahirovic, J and Zhang, L and Rosenbohm, A and Sijlmans, C and Aly, A and Mersmann, S and Sanjuan-Ruiz, I and Hübers, A and Messaddeq, N and Wagner, M and van Bakel, N and Boutillier, AL and Ludolph, A and Lagier-Tourenne, C and Boeckers, TM and Dupuis, L and Storkebaum, E},
title = {Author Correction: FUS-mediated regulation of acetylcholine receptor transcription at neuromuscular junctions is compromised in amyotrophic lateral sclerosis.},
journal = {Nature neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41593-026-02396-9},
pmid = {42463858},
issn = {1546-1726},
}

@article {pmid42454381,
year = {2026},
author = {Mai, R and Zhang, X and Yu, G and Chen, Z and Zhao, W and Shi, Z and Gao, X and Liang, Z and Fu, C},
title = {Robust Covalent Organic Frameworks Comprising Accessible Catalytic Sites Enable Fast-Charging and Long-Cycling Aluminum-Sulfur Batteries.},
journal = {Advanced materials (Deerfield Beach, Fla.)},
volume = {},
number = {},
pages = {e74063},
doi = {10.1002/adma.74063},
pmid = {42454381},
issn = {1521-4095},
abstract = {Rechargeable aluminum-sulfur (Al-S) batteries are recognized as a promising option for large-scale energy storage due to high theoretical energy density and cost-effectiveness. However, the sulfur cathodes suffer from sluggish reaction kinetics and severe shuttle effect during cycling. Here we report robust two-dimensional covalent organic frameworks (COFs) as sulfur hosts that features accessible catalytic nitrogen sites and confined microporous channels. The fine regulation of different microporous sizes was achieved by controlling different-length organic ligands of various COFs, finally preparing two kinds of COFs. The sensitive comparation between both COFs demonstrates that smaller microporous channels in COFs possess higher confinement effect for polysulfides due to the stronger capillary forces, facilitating higher Coulombic efficiency and better cycling stability in Al-S batteries. Meanwhile, experimental characterizations and theoretical calculations reveal that accessible catalytic nitrogen sites in COFs promote the multistep conversion kinetics of the sulfur cathode during cycling. Consequently, the small-sized COF confined sulfur cathode exhibits a reversible capacity of 1120 mAh g[-1] at 0.2C and a 93.5% capacity retention after 100 cycles, supporting high capacity and exceptional cycling stability. This work provides a new avenue on rational design of emerging COF materials in Al-S batteries.},
}

@article {pmid42454435,
year = {2026},
author = {Walls, M and Claffey, A and Galvin, M},
title = {Moral distress in healthcare professionals working with motor neuron disease.},
journal = {Palliative & supportive care},
volume = {24},
number = {},
pages = {e196},
doi = {10.1017/S1478951526103058},
pmid = {42454435},
issn = {1478-9523},
mesh = {Humans ; *Motor Neuron Disease/psychology/complications/therapy ; *Health Personnel/psychology/statistics & numerical data ; Cross-Sectional Studies ; Female ; Male ; Adult ; Europe ; Surveys and Questionnaires ; Middle Aged ; Ethical Dilemmas ; Quality of Life/psychology ; },
abstract = {OBJECTIVES: To (1) identify clinical situations that may contribute to the experience of moral distress (MD) among professionals working with motor neuron disease (MND), (2) measure the occurrence and intensity of MD, and (3) explore associations with professional quality of life, turnover intention, and associated risk and/or protective factors.

METHODS: A cross-sectional online survey was distributed to healthcare professionals working in MND services across Europe. Data were analyzed using descriptive and inferential statistics.

RESULTS: In total, 230 responses from professionals across 17 European countries were analyzed from the international survey. And 67% of respondents indicated that MD resonated with their experience of working with MND. Those who considered leaving or changing their position due to the challenges associated with caring for this patient population were also more likely to report resonance with MD (χ[2] = 7.772, p = 0.020). The intensity of MD was associated with reduced professional quality of life (burnout [β = 0.106, p < 0.05], and secondary traumatic stress [β = 2.881, p < 0.001]). A total of 24 clinical scenarios were identified as potential contributors to experiences of MD in this population. Across all professional groups, service-/organization-level factors were the most common and distressing barriers to providing effective MND care.

SIGNIFICANCE OF RESULTS: This study demonstrates that MD is experienced by healthcare professionals working with MND across Europe. MD was associated with reduced professional quality of life and increased intentions to leave or change positions, underscoring its potential implications for workforce retention and sustainability. The findings show that system/organization, patient/condition and family-level causes are the primary drivers of MD in this population. Future research should focus on evaluating the effectiveness of interventions designed to address these key drivers and mitigate the impact of MD among healthcare professionals working with MND.},
}

Humans
*Motor Neuron Disease/psychology/complications/therapy
*Health Personnel/psychology/statistics & numerical data
Cross-Sectional Studies
Female
Male
Adult
Europe
Surveys and Questionnaires
Middle Aged
Ethical Dilemmas
Quality of Life/psychology

@article {pmid42454523,
year = {2026},
author = {Ahmed, RM and Tse, NY and Bocchetta, M and Dobson-Stone, C and Kwok, JB and Hodges, JR and Irish, M and Rohrer, JR and Piguet, O and Halliday, G},
title = {Changes in body composition in genetic C9orf72 carriers: The role of the hypothalamus and thalamus.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {7},
pages = {e71669},
doi = {10.1002/alz.71669},
pmid = {42454523},
issn = {1552-5279},
support = {//National Health and Medical Research Council/ ; },
mesh = {Humans ; *C9orf72 Protein/genetics ; *Body Composition/genetics ; Magnetic Resonance Imaging ; Female ; Male ; *Thalamus/diagnostic imaging ; *Frontotemporal Dementia/genetics ; *Hypothalamus/diagnostic imaging ; Heterozygote ; Middle Aged ; Absorptiometry, Photon ; Aged ; },
abstract = {BACKGROUND: Patients with sporadic frontotemporal dementia (FTD) display changes in metabolism and body composition. No studies have examined body composition changes in pre-symptomatic C9orf72 mutation carriers METHODS: Asymptomatic C9orf72 expansion carriers between 2017 and 2022 (n = 28 non-carriers, 16 expansion-positive), underwent dual-energy X-ray absorptiometry (measurement of changes in body composition) and brain magnetic resonance imaging (MRI).

RESULTS: Changes in body composition were identified in the C9orf72 expansion carrier group compared to non-carrier group (average 11-12 years prior to onset): lower android-to-gynoid ratio (p = 0.009), and visceral adipose tissue area (p = 0.010). Lower android-to-gynoid ratio and lean mass were associated with lower volumes across the cortex, subcortex, and thalamus.

CONCLUSIONS: The current study highlights that genetically at-risk C9orf72 patients exhibit altered body composition. These findings align with the growing recognition that changes in genetic frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) extend beyond cognitive/motor symptoms and include early alterations in broader physiological function.},
}

Humans
*C9orf72 Protein/genetics
*Body Composition/genetics
Magnetic Resonance Imaging
Female
Male
*Thalamus/diagnostic imaging
*Frontotemporal Dementia/genetics
*Hypothalamus/diagnostic imaging
Heterozygote
Middle Aged
Absorptiometry, Photon
Aged

@article {pmid42455190,
year = {2026},
author = {Lei, Y and Huang, J and Li, M and Zhang, Y and Ye, Z and He, X and Tang, Z and Wei, J},
title = {Effects of respiratory muscle training on respiratory function in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {Journal of neurology},
volume = {273},
number = {8},
pages = {},
pmid = {42455190},
issn = {1432-1459},
support = {No. EWT201947//Department of Science and Technology of Hubei Province/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/rehabilitation/complications/therapy ; *Breathing Exercises/methods ; *Respiratory Muscles/physiopathology ; },
abstract = {BACKGROUND: Respiratory decline is prognostically important in amyotrophic lateral sclerosis (ALS), but the efficacy of respiratory muscle training (RMT) remains uncertain. We synthesized randomized evidence on respiratory and related outcomes.

METHODS: We searched databases, specialized registers, and trial registries through June 19, 2025, for randomized RMT trials in ALS. Risk of bias was assessed with the Cochrane tool. Random-effects meta-analyses reported standardized mean differences (SMDs) with 95% confidence intervals (CIs), and certainty was rated with GRADE.

RESULTS: Six studies were included; five concurrently randomized trials contributed quantitative data, whereas Pinto 2013 was retained for qualitative context. RMT improved maximal expiratory pressure (MEP; SMD 0.387, 95% CI 0.192-0.581; P = 0.008) and showed small favorable effects on maximal inspiratory pressure (MIP; SMD 0.156, 95% CI 0.089-0.224; P = 0.005), sniff nasal inspiratory pressure (SNIP; SMD 0.216, 95% CI 0.039-0.392; P = 0.034), peak expiratory flow (PEF; SMD 0.205, 95% CI 0.088-0.323; P = 0.017), and ALSFRS-R (SMD 0.214, 95% CI 0.039-0.388; P = 0.030). Forced vital capacity showed a borderline favorable trend (SMD 0.129, 95% CI - 0.003 to 0.262; P = 0.053). Low heterogeneity estimates were imprecise because most endpoints included only three to four small studies. Certainty was moderate for MIP, low for MEP, FVC, and PEF, and very low for SNIP and ALSFRS-R. Exploratory analyses identified no reliable effect modifiers.

CONCLUSIONS: RMT was associated with small, directionally consistent improvements mainly in pressure- and flow-based outcomes, whereas effects on FVC and longer-term clinical outcomes remain uncertain. RMT may be considered an individualized adjunct to ALS respiratory care, not a disease-modifying therapy. Larger, longer, standardized trials with patient-important endpoints are needed.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/rehabilitation/complications/therapy
*Breathing Exercises/methods
*Respiratory Muscles/physiopathology

@article {pmid42455475,
year = {2026},
author = {Maity, D and Gowtham, A and Mishra, Y and Kaundal, RK},
title = {Exosome Biology at the Interface of Neurodegeneration and Therapeutic Innovation.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42455475},
issn = {1559-1182},
mesh = {Humans ; *Exosomes/metabolism ; Animals ; *Neurodegenerative Diseases/therapy/metabolism/pathology ; Biomarkers/metabolism ; },
abstract = {Neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are defined by progressive neuronal loss, protein misfolding, and chronic neuroinflammation, yet effective disease-modifying therapies remain absent. Exosomes have emerged as key mediators of central nervous system communication and are increasingly central to the biology of neurodegeneration. These nanoscale vesicles transport proteins, lipids, and nucleic acids across cellular and anatomical barriers, influencing synaptic function, immune signaling, and metabolic homeostasis. Under pathological conditions, exosomes facilitate the spread of misfolded proteins such as amyloid-β, p-tau, α-synuclein, and TDP-43, thereby accelerating network-level degeneration. At the same time, their cargo exhibits disease-specific molecular signatures detectable in peripheral biofluids, supporting their development as minimally invasive biomarkers for early diagnosis and longitudinal monitoring. Advances in exosome engineering further underscore their potential as therapeutic delivery vehicles capable of crossing the blood-brain barrier and targeting pathogenic pathways with RNA-based therapeutics, proteins, or gene-editing systems. Together, these findings position exosomes as pivotal contributors to both the mechanistic progression and translational targeting of neurodegenerative diseases.},
}

Humans
*Exosomes/metabolism
Animals
*Neurodegenerative Diseases/therapy/metabolism/pathology
Biomarkers/metabolism

@article {pmid42456096,
year = {2026},
author = {Soliven, REMR and Igarashi, Y and Norii, T and Nakanishi, H and Suga, R and Takiguchi, T and Okada, I and Nakae, R and Yokobori, S},
title = {Performance of termination-of-resuscitation rules in foreign body airway obstruction-related out-of-hospital cardiac arrest: a prospective multicenter registry analysis.},
journal = {Prehospital emergency care},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/10903127.2026.2703842},
pmid = {42456096},
issn = {1545-0066},
abstract = {OBJECTIVES: Termination-of-resuscitation (TOR) rules were derived mainly from cardiac-origin out-of-hospital cardiac arrest (OHCA), but their interpretation in foreign body airway obstruction (FBAO)-related OHCA remains uncertain. This condition is a potentially reversible hypoxic arrest in which standard TOR criteria may perform differently. We evaluated the 2025 American Heart Association basic life support (BLS)-TOR and advanced life support (ALS)-TOR criteria in FBAO-related OHCA.

METHODS: This secondary analysis of the prospective multicenter MOCHI registry included patients with FBAO-related OHCA transported to 25 Japanese hospitals from April 2020 to March 2023. For the primary TOR analysis, we included patients who had not achieved return of spontaneous circulation (ROSC) before emergency medical services (EMS) arrival, because TOR rules are intended for patients who remain in cardiac arrest at the time of EMS assessment. Patients were retrospectively classified according to BLS-TOR and ALS-TOR criteria. Primary measures were the specificity of TOR-positive status for predicting unfavorable neurological outcome, defined as the proportion of patients with favorable neurological outcome (Cerebral Performance Category 1-2) who were classified as TOR-negative, and the proportion of TOR-positive patients who nevertheless achieved favorable neurological outcome.

RESULTS: Of 248 patients with FBAO-related OHCA (median age, 81.5 years; 83.1% witnessed), 49 (19.8%) survived to 30 days and 9 (3.6%) achieved favorable neurological outcome. The BLS-TOR rule classified 150/229 evaluable patients as TOR-positive; 2 achieved favorable neurological outcome (1.3%; 95% CI, 0.4-4.7%; specificity, 77.8% (95% CI, 45.3-93.7%)), and 20 survived to 30 days (13.3%; 95% CI, 8.8-19.7%). The ALS-TOR rule classified 12/242 patients as TOR-positive; none achieved favorable neurological outcome, but 4 survived to 30 days (33.3%; 95% CI, 13.8-60.9%).

CONCLUSIONS: In FBAO-related OHCA, BLS-TOR would have classified two patients with favorable neurological outcome as TOR-positive. The ALS-TOR rule was restrictive, but small numbers and 30-day survival among TOR-positive patients preclude firm safety conclusions. Termination-of-resuscitation criteria warrant cautious, etiology-aware interpretation when FBAO is suspected.},
}

@article {pmid42456270,
year = {2026},
author = {Martinez, D and Georgiou, GK and Inoue, T and Parrila, R and Protopapas, A},
title = {The genesis of reading fluency in beginning readers.},
journal = {Journal of experimental child psychology},
volume = {272},
number = {},
pages = {106593},
doi = {10.1016/j.jecp.2026.106593},
pmid = {42456270},
issn = {1096-0457},
abstract = {Although reading fluency plays a crucial role in reading comprehension, little is known about its early development. In this study, we first aimed to replicate Hudson et al.'s (2009, 2012) model of reading fluency development among beginning readers and, second, to expand it by incorporating components of articulation rate, sub-lexical orthographic knowledge, and reading accuracy, all of which are theoretically linked to reading fluency development. Three hundred and thirty English-speaking Grade 1 students (51.5% female; Mage = 74.82 months; SD = 3.60) were assessed at three time points (September [T1], January [T2], and May [T3]). At T1, we administered measures of rapid automatized naming (RAN), processing speed, phonemic blending fluency, and letter-sound fluency, at T2, measures of phonogram fluency and sub-lexical orthographic knowledge, and, finally, at T3, word reading fluency, nonword reading fluency, and text reading fluency. Using path analysis, we tested three models: a baseline model based on Hudson et al.'s model and two expanded models that included the additional measures. Our results replicated the core relations proposed by Hudson et al. and further demonstrated significant contributions from sub-lexical orthographic knowledge and reading accuracy to text reading fluency through word reading fluency. These findings are consistent with theoretical frameworks such as Ehri's (2014) orthographic mapping framework and the lexical quality hypothesis (Perfetti, 2007), showing the contributions but also limitations of the components of the reading fluency model.},
}

@article {pmid42456455,
year = {2026},
author = {Jung, MJ and Oh, WO},
title = {Strategic simulation-based management of triage clinical reasoning in novice emergency nurses: A randomized block design study.},
journal = {Nurse education in practice},
volume = {95},
number = {},
pages = {104928},
doi = {10.1016/j.nepr.2026.104928},
pmid = {42456455},
issn = {1873-5223},
abstract = {AIM: To develop and evaluate the effectiveness of the Triage Clinical Reasoning Simulation Program (Triage-CRSP).

BACKGROUND: Globally, emergency department (ED) triage is largely performed by general nurses, with increasing emphasis on clinical reasoning (CR) to assess care urgency; however, novice emergency nurses have limited triage-related competencies.

DESIGN: This study consisted of two phases: program development and effectiveness evaluation. The first phase involved developing Triage-CRSP. The second phase evaluated its effectiveness using a randomized block design, with the completion of KTAS (Korea Triage Acuracy Scale) training as the blocking factor.

METHODS: The theoretical framework of this program was based on O'Neill et al.'s clinical decision-making and novice clinical reasoning models. The simulation program was developed using a six-step approach to curriculum development. A total of 60 emergency nurses with less than three years of experience were stratified by completion of KTAS training and randomly allocated to either the intervention or control group; under a single-blind design, the intervention group received the developed Triage-CRSP, while the control group received the existing KTAS simulation.

RESULTS: The 'Triage-CR pattern' was identified as a structured multi-step clinical reasoning process. The intervention group demonstrated significantly greater improvements in triage clinical reasoning knowledge, recognition of critical clinical cues, emergency nursing performance and overall triage competence compared with the control group.

CONCLUSIONS: The simulation-based triage clinical reasoning program was effective in enhancing multiple dimensions of triage practice among novice emergency nurses.},
}

@article {pmid42456683,
year = {2026},
author = {Bouzigues, A and Grassi, M and Cantoni, V and Premi, E and Bellini, S and Binetti, G and Logroscino, G and Russell, LL and Ferry-Bolder, E and Foster, PH and van Swieten, JC and Jiskoot, LC and Seelaar, H and Sanchez-Valle, R and Laforce, R and Graff, C and Galimberti, D and Vandenberghe, R and de Mendonça, A and Di Fede, G and Santana, I and Gerhard, A and Langheinrich, T and Levin, J and Nacmias, B and Otto, M and Bertoux, M and Lebouvier, T and Ducharme, S and Butler, C and le Ber, I and Bruffaerts, R and Solje, E and Kinnunen, M and Krüger, J and Finger, E and Tartaglia, MC and Masellis, M and Rowe, JB and Synofzik, M and Moreno, F and Ghidoni, R and Migliaccio, R and Rohrer, JD and Borroni, B and , },
title = {Survival estimates and their predictors in genetic frontotemporal dementia: an international, retrospective, cohort study.},
journal = {The Lancet. Neurology},
volume = {25},
number = {8},
pages = {731-740},
doi = {10.1016/S1474-4422(26)00197-3},
pmid = {42456683},
issn = {1474-4465},
mesh = {Humans ; *Frontotemporal Dementia/genetics/mortality/diagnosis ; Retrospective Studies ; C9orf72 Protein/genetics ; tau Proteins/genetics ; Female ; Male ; Middle Aged ; Aged ; Cohort Studies ; Progranulins/genetics ; Mutation ; Kaplan-Meier Estimate ; },
abstract = {BACKGROUND: What drives the heterogeneity of survival estimates in genetic frontotemporal dementia is unknown. We sought to understand the natural history and predictors of disease trajectory, which are crucial not only for effective care but also for the design of therapeutic clinical trials and efficacy evaluation.

METHODS: In this international, cohort study, we used the Kaplan-Meier method to retrospectively assess survival estimates in patients enrolled in the GENFI cohort, which included 32 research sites located in Belgium, Canada, Finland, France, Germany, Italy, the Netherlands, Portugal, Spain, Sweden, and the UK, and comprised participants carrying a causal C9orf72 expansion or a causal mutation in GRN or MAPT genes. Survival was calculated as the time from symptom onset to time of death or censoring date; median survival estimate for all patients was the primary endpoint. Cox proportional hazards models were used to identify predictors of survival, which were subsequently externally validated in an independent cohort. We further designed a structural equation model to assess the relationships between predictors, applying a least absolute shrinkage and selection operator method.

FINDINGS: Of 278 participants of the GENFI cohort included in this study, 160 (58%) were men and 118 (42%) were women. 162 died during follow-up (58%) and 116 were still alive (42%) on June 1, 2024, the chosen censoring date. 138 participants carried a C9orf72 expansion, 94 carried a GRN mutation, and 46 a MAPT mutation. 179 participants were diagnosed with behavioural variant frontotemporal dementia, 46 with primary progressive aphasia, and 31 with frontotemporal dementia-amyotrophic lateral sclerosis. 22 participants had other diagnoses. The median survival estimate for all patients with genetic frontotemporal dementia was 6·94 years (95% CI 6·59-7·80) from symptom onset. The median survival estimate for patients with GRN mutations was 6·63 years (6·08-7·98), for patients with a C9orf72 expansion was 7·04 years (6·45-8·77), and for patients with MAPT mutations was 8·56 years (7·06-13·50). Older age at onset, shorter disease duration from onset to enrolment in the GENFI study, clinical presentation (ie, frontotemporal dementia-amyotrophic lateral sclerosis), domain of first symptom (ie, motor or language onset), and geographical area of residency (ie, central and southern Europe) were associated with poorer prognosis. Genetic group did not directly affect survival estimates; rather its effect was mediated by age at onset and clinical phenotype. We computed a genetic frontotemporal dementia survival risk index, which can be used at an individual patient level.

INTERPRETATION: Our results highlight that motor impairment in addition to cognitive and behavioural symptoms should be considered when estimating prognosis in genetic frontotemporal dementia. Individual risk scores might be of help for patient stratification in future therapeutic trials, although refinement and prospective validation are now needed.

FUNDING: Italian Ministry of Health (Ricerca Corrente), Fondation Philippe Chatrier, and Fondation Vaincre Alzheimer.},
}

Humans
*Frontotemporal Dementia/genetics/mortality/diagnosis
Retrospective Studies
C9orf72 Protein/genetics
tau Proteins/genetics
Female
Male
Middle Aged
Aged
Cohort Studies
Progranulins/genetics
Mutation
Kaplan-Meier Estimate

@article {pmid42457567,
year = {2026},
author = {Akiyama, T and Aoki, M},
title = {Cracking a New Era of Therapeutic Development in ALS.},
journal = {The Tohoku journal of experimental medicine},
volume = {},
number = {},
pages = {},
doi = {10.1620/tjem.2026.J082},
pmid = {42457567},
issn = {1349-3329},
}

@article {pmid42458007,
year = {2026},
author = {Chen, W and Jiang, L and Duan, C and Kang, M and Ye, J and Wang, L and Pan, Y and Qu, H and Liao, X and Zhou, X and Li, Y and Gan, Z and Chen, J and Schacht, I and Place, RF and Li, LC and Wang, Y},
title = {Oligonucleotide-siRNA conjugate for SOD1 amyotrophic lateral sclerosis: a phase 1 trial.},
journal = {Nature medicine},
volume = {32},
number = {7},
pages = {2619-2628},
pmid = {42458007},
issn = {1546-170X},
support = {No.Z231100004823036//Beijing Municipal Science and Technology Commission/ ; 20230484245//Beijing Nova Program/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease partly caused by gain-of-function mutations in superoxide dismutase 1 (SOD1). Here we developed RAG-17, an siRNA-targeting SOD1, using an accessory oligonucleotide conjugate platform for enhanced central nervous system (CNS) delivery. Preclinically, RAG-17 rescued motor neuron degeneration, delayed disease progression, preserved motor function and extended survival in SOD1[G93A] ALS rodents, even with advanced-stage treatment. In cynomolgus monkeys, intrathecal RAG-17 led to dose-dependent, durable reductions in SOD1 mRNA (CNS) and protein (cerebrospinal fluid (CSF)). In a first-in-human trial in patients with SOD1-ALS (n = 6), participants were assigned to two cohorts-cohort 1 (n = 3) received an initial 60 mg dose (seven doses total) and cohort 2 (n = 3) received an initial 90 mg dose (six doses total). The dose was escalated in 30 mg steps to maintenance doses of 150 mg (n = 5) or 180 mg (n = 1). Thus, the primary safety endpoint was met, showing acceptable safety and tolerability. Treatment-emergent adverse events (TEAEs) occurred in 33% of participants (two of six). All TEAEs were mild to moderate, including muscle tremor (two patients) and elevated alanine aminotransferase (one patient), all of which resolved. No serious adverse events were reported. Furthermore, no other clinically meaningful changes were observed in laboratory parameters, vital signs, the ALS Functional Rating Scale-Revised score, physical or neurological examinations or ECG. The key secondary endpoints showed CSF SOD1 reductions of 69% (cohort 1, day 240) and 56% (cohort 2, day 210), and plasma neurofilament light chain reductions of 62% (cohort 1) and 52% (cohort 2), from baseline; no patient required invasive mechanical ventilation or died by the end of the study. These results demonstrate a favorable safety outcome, supporting the continued clinical evaluation of RAG-17 for SOD1-ALS. ClinicalTrials.gov registration: NCT05903690 .},
}

@article {pmid42458453,
year = {2026},
author = {Bolsinger, MM and Vivek, N and Singh, J and Challa, A and Zhu, A and Rothell, T and Wang, S and Zhang, T and Zhu, S and Robbins, N and Fenwick, L and Ruttenberg, G and Bogoniewski, A and Taha, HB},
title = {Extracellular vesicles as a liquid biopsy for amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-08562-8},
pmid = {42458453},
issn = {1479-5876},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative syndrome diagnosed clinically using standardized criteria, with neuropathological confirmation of motor neuron loss and TDP-43 aggregates in postmortem brain tissue. Extracellular vesicles (EVs) have emerged as potential minimally invasive biomarkers for ALS, but studies vary widely in methodology and reproducibility. We conducted a systematic review and meta-analysis to evaluate the diagnostic potential of EV-associated proteins and RNAs in ALS. Following PRISMA guidelines, we searched PubMed and EMBASE from inception to May 21st, 2026. Forty-one studies met inclusion criteria. Where published summary statistics were available, these were used directly; where they were not, data were reconstructed from figures or obtained from authors and re-analyzed to derive standardized effect sizes and exploratory diagnostic accuracy estimates. Random-effects models were used for continuous outcomes, and diagnostic accuracy was assessed using hierarchical summary ROC and bivariate random-effects models. Publication bias was evaluated using Begg, Egger, and funnel plots. EV-associated TDP-43 was the most frequently studied protein. Meta-analysis of five studies showed a moderate but non-significant increase in EVs from ALS vs. controls (SMD = 1.30) with high heterogeneity (I = 97.8%). Sixteen studies assessing EV-RNA biomarkers showed minimal overlap and limited independent replication. Diagnostic accuracy meta-analysis across 11 studies yielded moderate performance (AUC = 0.839). No publication bias was found across both meta-analyses. EV biomarkers for ALS show biological promise but are limited by methodological variability and insufficient replication. This work highlights the need for standardized protocols, transparent data sharing, and independent validation.},
}

@article {pmid42458498,
year = {2026},
author = {Wang, H and Wen, R and Parker, E and Yang, L},
title = {TREM2 in neurodegenerative diseases and acute neurological injuries: mechanisms to targeted therapies.},
journal = {Cell communication and signaling : CCS},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12964-026-03083-9},
pmid = {42458498},
issn = {1478-811X},
support = {32300959//National Natural Science Foundation of China/ ; SL2024A04J00578//Guangzhou Scientific Research Grant/ ; 22KJ04//SCNU Young Faculty Development Program/ ; },
abstract = {Triggering receptor expressed on myeloid cells 2 (TREM2) is a critical myeloid receptor expressed on the surface of central nervous system microglia, capable of integrating signals from lipids, damage-associated molecular patterns, and abnormal protein aggregates to regulate phagocytosis, metabolic adaptation, inflammatory remodeling, and pathology-associated responses. Accumulating evidence indicates that TREM2 is neither uniformly protective nor uniformly pathogenic; rather, its biological effects are highly context-dependent, governed collectively by disease stage, pathological substrates, cellular compartments, and the local microenvironment. By coupling with TYROBP/DAP12 or DAP10, TREM2 actively drives the state remodeling of pathology-associated microglia. It profoundly influences the onset and progression of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), as well as acute central nervous system injuries, including ischemic stroke, spinal cord injury (SCI), and traumatic brain injury (TBI). Concurrently, soluble TREM2 (sTREM2) holds significant potential not only as a biomarker but also as a context-dependent effector molecule actively participating in pathological regulation. This review synthesizes current advancements by focusing on four core themes: the structural and signaling logic of the TREM2 axis; its regulation of disease-associated microglia (DAM) remodeling; the cross-disease significance of sTREM2; and the mechanistic basis for the divergent outcomes observed with TREM2-targeted therapies across different experimental models and disease stages. The objective is to elucidate the context-dependent roles of TREM2 by analyzing consensus mechanisms, sources of discrepancy, and translational implications, thereby providing a theoretical framework and strategic direction for more precise TREM2-targeted interventions.},
}

@article {pmid42458512,
year = {2026},
author = {Jo, M and Kim, S and Woo, J and Park, JS and Kim, SH and Nahm, M and Kim, SR and Lee, S and Kim, HJ},
title = {Targeting astrocyte-mediated neurotoxicity induced by ALS/FTD-associated RNA binding proteins.},
journal = {Cell communication and signaling : CCS},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12964-026-03082-w},
pmid = {42458512},
issn = {1478-811X},
support = {RS-2024-00454715//National Research Foundation of Korea/ ; RS-2024-00343239//National Research Foundation of Korea/ ; 26-BR-02-03//Korea Brain Research Institute/ ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders characterized by reactive astrocytes that contribute to neuronal injury through TAR DNA-binding protein 43 (TDP-43)-or fused in sarcoma (FUS)-driven neuroinflammatory signaling. Dehydrocostus lactone (DHE), a blood-brain barrier-permeable sesquiterpene lactone with established anti-inflammatory activity, represents a promising but unexplored therapeutic candidate for ALS/FTD.

METHODS: The therapeutic effects of DHE were evaluated in primary mouse and human astrocytes expressing ALS/FTD-associated RNA-binding protein pathology, ALS patient-derived fibroblasts, and primary cortical neurons exposed to astrocyte-conditioned medium. Drosophila models expressing mutant FUS or TDP-43 in glial cells were used to assess locomotor performance and survival. Molecular analyses examined nuclear factor kappa B (NF-κB) signaling, nuclear factor erythroid 2-related factor 2 (NRF2)-dependent antioxidant responses, protein aggregation, mitochondrial function, and inflammatory mediator production. Plasma concentrations of inflammatory cytokines and chemokines were measured in patients with sporadic ALS.

RESULTS: DHE exerted neuroprotective effects through a dual mechanism involving suppression of NF-κB-dependent inflammatory signaling and activation of NRF2-mediated antioxidant pathways in astrocytes exhibiting FUS or TDP-43 proteinopathy. DHE attenuated astrocyte-mediated neurotoxicity and improved neuronal mitochondrial function in conditioned-medium assays. In addition, DHE reduced pathological FUS accumulation in FUS P525L-expressing astrocytes and in stress-challenged patient-derived fibroblasts. In Drosophila models, DHE significantly improved locomotor function and extended survival. Translationally, the chemokines CXCL10, CCL3, and CCL19 were elevated in plasma from patients with ALS, were induced by FUS or TDP-43 pathology in astrocytes, and were suppressed by DHE treatment, supporting the clinical relevance of the inflammatory pathways targeted by DHE.

CONCLUSION: DHE mitigates astrocyte-driven neurotoxicity associated with ALS/FTD-related RNA-binding protein pathology by suppressing inflammatory signaling and enhancing antioxidant defense mechanisms. The consistent therapeutic effects observed across mouse and human cellular models, patient-derived samples, and in vivo Drosophila models support further investigation of DHE as a potential therapeutic strategy for ALS/FTD and highlight astrocyte-mediated signaling pathways as actionable targets in neurodegenerative disease.},
}

@article {pmid42458576,
year = {2026},
author = {Akan, T and Aishwarya, R and Bhuiyan, MS and Conrad, SA and Vanchiere, JA and Bhuiyan, MAN},
title = {From unlabeled to labeled: self-supervised deep learning in computational pathology.},
journal = {BioData mining},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13040-026-00586-6},
pmid = {42458576},
issn = {1756-0381},
support = {R01HL172970, R01HL145753, R01HL145753-01S1, and R01HL145753-03S1//Foundation for the National Institutes of Health/ ; P20GM121307//Foundation for the National Institutes of Health/ ; },
abstract = {PURPOSE: The advancement of decision support systems for pathology and their implementation in clinical practice have been limited by the necessity for extensive, manually annotated datasets. Self-supervised learning (SSL) automates the extraction and interpretation of histopathological features from unannotated images, facilitating efficient model development without dependence on expert labeling. In this study, we introduce the SSL-HistoNet model that learns disease-relevant morphological representations from histopathological images through self-supervised learning.

MATERIALS AND METHODS: We applied it to WGA-stained skeletal muscle tissues from mouse models of amyotrophic lateral sclerosis (ALS) and Type I diabetes to explore its ability to capture pathological muscle phenotypes in an annotation-free setting. Following pretraining on unlabeled data, the SSL encoder was further integrated with an attention-guided classifier to evaluate its capacity to identify pathological muscle alterations.

RESULTS: SSL-HistoNet achieved a precision of 0.98, a recall of 0.98, and an AUC of 0.98, demonstrating performance comparable to or outperforming state-of-the-art supervised models. Alongside high discriminative performance, exploratory feature analyses demonstrated consistent class-level changes in morphology-related patterns identified through representation learning.

CONCLUSION: These findings highlight the capability of SSL-HistoNet as an annotation-free framework for outlining disease-specific tissue structures, reducing manual labeling demands and mitigating inter- and intra-observer variability in histological processes.

CLINICAL TRIAL NUMBER: Not applicable.},
}

@article {pmid42441689,
year = {2026},
author = {de Vienne, D and de Vienne, DM},
title = {Age-based risk estimates for C9orf72RE-related diseases: Theoretical developments and added value for genetic counseling.},
journal = {PLoS genetics},
volume = {22},
number = {7},
pages = {e1012230},
doi = {10.1371/journal.pgen.1012230},
pmid = {42441689},
issn = {1553-7404},
abstract = {The C9orf72 hexanucleotide repeat expansion is the most common genetic cause of amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD). In genetic counseling, children of mutation carriers are often told that they have a 50% risk of carrying the mutation, but this figure does not take into account the fact that penetrance is age-related, with a unimodal distribution of disease onset around 58 years of age. Using a Bayesian approach, we developed a theory to calculate the probability of carrying the mutation for asymptomatic relatives (children/siblings and grandchildren/niblings) as well as the probability of developing ALS/FDT within a given time frame, based on their age. Using published data on age-related penetrance, we then calculated these probabilities and developed an online simulator that makes it easy to calculate them on a case-by-case basis. The conditional probabilities obtained can be very different from Mendelian values. For example, a 70-year-old asymptomatic child born to a carrier has approximately a 6% risk of being a carrier, which is far from 50%. For grandchildren, taking into account both their age and that of their parents also leads to figures that are much lower than those obtained if only their age were considered. For consultands, the decision to undergo testing is based in part on risk estimates. In this regard, the refined estimates and simulator we propose may prove to be valuable tools for genetic counseling for families affected by ALS/FTD linked to the C9orf72RE mutation. In addition, the formulas used in this study could also be used to calculate risk estimates for other diseases caused by autosomal dominant mutations with age-dependent penetrance.},
}

@article {pmid42441693,
year = {2026},
author = {Fisher, K and Ligay, A and Stratford, M and Hirani, R and Ober, DT and Al-Seykal, I and Frishman, WH and Etienne, M},
title = {Cardiac Autonomic Dysfunction and Sudden Cardiac Death in Amyotrophic Lateral Sclerosis: Clinical Implications and Considerations for Care.},
journal = {Cardiology in review},
volume = {},
number = {},
pages = {},
doi = {10.1097/CRD.0000000000001392},
pmid = {42441693},
issn = {1538-4683},
abstract = {Amyotrophic lateral sclerosis (ALS) is traditionally viewed as a motor neuron disease that progresses from muscular weakness to respiratory failure and death. Increasing evidence, however, demonstrates clinically meaningful involvement of the autonomic nervous system, particularly in cardiovascular regulation. This narrative review synthesizes current evidence on the mechanisms, clinical implications, and palliative considerations of cardiac autonomic dysfunction in ALS, with particular emphasis on its relationship to sudden cardiac death (SCD). Cardiac autonomic dysfunction is increasingly recognized as a significant contributor to disease burden in ALS, manifesting as abnormalities in heart rate variability, sympathetic overactivity, and corrected QT prolongation. These derangements may contribute to malignant arrhythmias, increasing susceptibility to SCD in combination with respiratory decline. Epidemiologic data suggest that SCD accounts for a meaningful proportion of ALS-related mortality, although it is likely underrecognized due to misclassification and lack of routine cardiac monitoring. Clinical implications include the need for improved risk stratification and earlier detection of autonomic dysfunction using accessible markers, such as electrocardiographic indices, orthostatic vital signs, and ambulatory monitoring. Emerging technologies, including wearable biosensors, may further enhance longitudinal assessment. These considerations also have direct relevance for advanced care planning, as ALS may involve unpredictable and abrupt cardiac death in addition to progressive respiratory decline. Recognizing ALS as a multisystem disorder with significant cardiac involvement supports the integration of structured cardiovascular monitoring into multidisciplinary care models and highlights the need for prospective studies to guide standardized management strategies.},
}

@article {pmid42442024,
year = {2026},
author = {Andreeva, T and Tuparev, N and Taneva, SG},
title = {Multimodal biophysical markers of neurodegeneration: Morphology, mechanics, and thermodynamics.},
journal = {Current opinion in structural biology},
volume = {100},
number = {},
pages = {103330},
doi = {10.1016/j.sbi.2026.103330},
pmid = {42442024},
issn = {1879-033X},
abstract = {The identification of novel noninvasive biomarkers remains a major challenge in the diagnosis of neurodegenerative diseases. Significant efforts focus on fluid biomarkers, including proteins, peptides, and miRNAs, detectable in blood plasma and peripheral blood cells. Here, we review recent findings on blood plasma and peripheral blood cells physical parameters in Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis emphasizing atomic force microscopy and calorimetry assay. Alterations in morphology, nanostructure, and stiffness of red blood cells and platelets, together with thermodynamic signatures of red blood cells and plasma, provide sensitive indicators of disease-related changes. These integrated biophysical parameters not only distinguish neurodegeneration from healthy states but also enable discrimination among different neurodegenerative disorders, highlighting their potential as minimally invasive diagnostic markers.},
}

@article {pmid42442469,
year = {2026},
author = {Kerner, D and Carey, L and Hughes, J},
title = {Using CoI to Address Emerging Problems in Academic Pharmacy.},
journal = {American journal of pharmaceutical education},
volume = {},
number = {},
pages = {102051},
doi = {10.1016/j.ajpe.2026.102051},
pmid = {42442469},
issn = {1553-6467},
abstract = {Pharmacy education is currently facing numerous challenges, such as concerning first-time pass rates on licensure examinations, decreasing applicant pools, new accreditation standards, progression concerns, and changing financial and regulatory landscapes. These complex and shared issues require collaborative and innovative approaches across the academy. One potential strategy is the development of Communities of Inquiry (CoI), a collaborative model grounded in Garrison et al.'s theoretical framework of social, cognitive, and teaching presence. CoI emphasize active engagement, shared problem-solving, reflective discourse, and collective responsibility for learning and innovation. This manuscript describes the theoretical foundation of the CoI model and its application within pharmacy academia. Existing applications of CoI principles in pharmacy education literature, including faculty development initiatives and webinar-based learning experiences, are also reviewed. Additionally, a real-world example of a successful CoI is presented through the development of a NAPLEX Preparation CoI. Communities of Inquiry represent an effective framework for addressing new challenges in pharmacy education. Faculty, administrators, and professional organizations are encouraged to establish and participate in CoIs. As pharmacy education continues to evolve, the CoI approach presents a promising strategy for fostering innovation, meeting accreditation standards, and enhancing student outcomes through community-driven solutions.},
}

@article {pmid42442754,
year = {2026},
author = {Sonnenberg, A and Bakis, LK and Kohen, R},
title = {Gastrointestinal Diagnoses and Symptoms in Medicare Patients With Neuropsychiatric Diseases.},
journal = {Journal of clinical gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1097/MCG.0000000000002422},
pmid = {42442754},
issn = {1539-2031},
abstract = {BACKGROUND AND AIMS: Many patients with psychiatric and neurological diseases suffer from gastrointestinal symptoms. Our study aimed to analyze the frequency of gastrointestinal disease in patients with underlying neuropsychiatric diagnoses.

METHODS: The study utilized the 2018 Inpatient Standard Analytic File of the Centers for Medicare and Medicaid Services (CMS), which contains the electronic health records of 6,462,321 unique patients. The concurrence of 2 diagnoses was assessed by calculating odds ratios (OR) with their 95% CIs, adjusted for the confounding influences of demographic characteristics (age, sex, ethnicity).

RESULTS: Dementia was most strongly associated with dysphagia (2.85, 2.83 to 2.88). Schizophrenia was associated with functional GI disorders (1.62, 1.60 to 1.64), constipation (1.67, 1.65 to 1.69), and dyspepsia (2.02, 1.88 to 2.17). Bipolar disorder was most significantly associated with irritable bowel syndrome (1.83, 1.79 to 1.87) and dyspepsia (1.88, 1.77 to 2.01). Depression was significantly associated with all types of upper and lower GI symptoms with significant ORs ranging from 1.33 to 2.14. Amyotrophic lateral sclerosis was strongly associated with complaints of functional GI disorder (2.32, 2.18 to 2.46), constipation (2.37, 2.23 to 2.51), dysphagia (11.77, 11.19 to 12.39), flatulence and bloating (2.75, 2.14 to 3.54). Parkinson disease was mostly associated with constipation (1.79, 1.77 to 1.82) and dysphagia (2.96, 2.92 to 3.00). In Alzheimer disease, only symptoms of dysphagia (2.15, 2.12 to 2.17) stood out. Multiple sclerosis was associated with most GI diagnoses (OR ranging from 1.32 to 2.06), except for abdominal pain and reflux symptoms.

CONCLUSIONS: Concurrence of gastrointestinal and neuropsychiatric diagnoses is common. Caring for patients with neuropsychiatric diseases, physicians need to be aware of and proactively search for the presence of concurrent gastrointestinal disease.},
}

@article {pmid42442908,
year = {2026},
author = {Dongre, S and Soni, N and Bissa, B},
title = {Role of ESCRT pathway and autophagy in neurodegenerative diseases.},
journal = {International review of neurobiology},
volume = {187},
number = {},
pages = {1-16},
doi = {10.1016/bs.irn.2026.05.022},
pmid = {42442908},
issn = {2162-5514},
mesh = {Humans ; *Endosomal Sorting Complexes Required for Transport/metabolism ; *Autophagy/physiology ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; },
abstract = {Neurodegenerative diseases are characterized by progressive neuronal dysfunction and loss resulting from impaired proteostasis and vesicular trafficking. Neurons are particularly vulnerable to these processes due to their post-mitotic nature and complex architecture. Autophagy and the endolysosomal system constitute the primary degradative pathways responsible for maintaining neuronal homeostasis. However, increasing evidence indicates that their effective function critically depends on coordination with the endosomal sorting complexes required for transport (ESCRT). Beyond their canonical role in multivesicular body biogenesis and membrane scission, ESCRT components are now recognized as essential regulators of autophagosome closure, amphisome formation, autophagosome-lysosome fusion, and endolysosomal membrane repair. Disruption of this ESCRT-autophagy interface has emerged as a common pathological feature across major neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis/frontotemporal dementia. This review synthesizes evidence from genetic, biochemical, and neuropathological studies to highlight shared molecular nodes, such as ESCRT-III components, the VPS4 ATPase, the adaptor protein ALIX, and late endosomal regulators, including Rab7, that couple membrane remodeling to autophagic flux. Failure of these regulatory checkpoints destabilizes endolysosomal integrity, arrests autophagic maturation, and promotes the accumulation of toxic protein species, thereby driving progressive neuronal degeneration. By framing neurodegeneration through the lens of ESCRT-autophagy coupling failure, this review provides a unified mechanistic perspective that links diverse pathogenic proteins to shared cellular vulnerabilities and identifies ESCRT-mediated membrane dynamics as a critical determinant of neuronal survival.},
}

Humans
*Endosomal Sorting Complexes Required for Transport/metabolism
*Autophagy/physiology
*Neurodegenerative Diseases/metabolism/pathology
Animals

@article {pmid42443201,
year = {2026},
author = {Wang, Y and Hu, W and Huang, R and Wu, F and Su, H and Zang, J and Huang, X and Liu, Y and Ren, H and Li, J and Zhang, M and Zhang, Y and Wang, G and Hao, Z},
title = {Nuclear condensates formed by truncated mutant NEK1s impede ribosomal RNA biogenesis and drive motor dysfunction.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-75500-z},
pmid = {42443201},
issn = {2041-1723},
support = {32000676//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {NIMA-related kinase 1 (NEK1), a serine/threonine kinase, is a risk variant for amyotrophic lateral sclerosis (ALS). While the full-length NEK1 is involved in diverse cellular processes, such as DNA damage response and microtubule stability, the pathogenic mechanism of NEK1 nonsense mutations in ALS remains elusive. Here, we demonstrate that three truncated forms of NEK1 derived from ALS-related NEK1 nonsense mutations translocate from the cytoplasm to the nucleus, exhibit nucleolar localization, and simultaneously form liquid-like nucleoplasmic foci. In contrast to the diffuse cytoplasmic distribution of wild-type NEK1, these nuclear-localized truncated mutants are prone to undergo liquid-liquid phase separation both in cells and in vitro. Mechanistically, the truncated NEK1s interact with the nucleolar protein FBL, thereby impairing ribosomal RNA biogenesis and translation. Transgenic flies expressing truncated mutant NEK1s display motor dysfunction and reduced survival length, and a knock-in transgenic mouse model expressing ALS-related NEK1 mutant similarly exhibits motor deficits accompanied by ribosomal RNA dysregulation. These findings suggest that ALS-related NEK1 mutants expressing truncated forms of NEK1 cause cell toxicity by interfering with ribosomal RNA metabolism and reveal a gain-of-function mechanism in ALS pathogenesis involving NEK1.},
}

@article {pmid42443387,
year = {2026},
author = {Kim, WS and Halliday, GM},
title = {Astrocytic lipid dysregulation as an early driver of neurodegeneration.},
journal = {Nature reviews. Neurology},
volume = {},
number = {},
pages = {},
pmid = {42443387},
issn = {1759-4766},
abstract = {Astrocytes have traditionally been cast as supportive glia, but they are increasingly recognized as metabolic hubs that regulate cholesterol synthesis, fatty acid detoxification, lipid droplet dynamics and redox homeostasis in the CNS. Neurons have a limited intrinsic capacity for lipid storage and detoxification and rely heavily on astrocytes to maintain a safe lipid environment. Emerging evidence indicates that dysregulation of astrocytic lipid homeostasis precedes overt neuronal degeneration in a range of neurodegenerative diseases, including Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, frontotemporal dementia and Huntington disease. Perturbations in astrocytic lipid handling can drive maladaptive reactive states, promote oxidative stress, impair lysosomal and mitochondrial function and disrupt neuron-glia lipid exchange, collectively creating an environment that leads to neurodegeneration. Therefore, lipid dysregulation within astrocytes could trigger or amplify neuronal vulnerability. In this Review, we assess evidence that astrocytic lipid metabolism is not solely protective or pathological but has instructive physiological roles and that astrocytic lipid dysregulation is an early driver of neurodegeneration. We critically evaluate disease-specific evidence, distinguishing correlative observations from causal mechanisms. We propose that targeting of astrocytic lipid homeostasis represents a promising strategy for preventing or minimizing neurodegeneration and opens new avenues for early detection and biomarker development.},
}

@article {pmid42444959,
year = {2026},
author = {Akpa, B},
title = {The role of radiologic assessment in evaluating and monitoring respiratory function in amyotrophic lateral sclerosis (ALS) patients: a narrative review.},
journal = {Journal of thoracic disease},
volume = {18},
number = {6},
pages = {672},
pmid = {42444959},
issn = {2072-1439},
abstract = {BACKGROUND AND OBJECTIVE: Respiratory failure is the primary cause of mortality in amyotrophic lateral sclerosis (ALS), usually caused by progressive neuromuscular respiratory weakness. Standard pulmonary function tests (PFTs) such as maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and both supine and upright forced vital capacity (FVC) are crucial for objective measurements of diaphragmatic weakness but have limitations, including dependence on the patient's performance and the inability to detect early, subclinical diaphragmatic impairment or be used effectively in patients with bulbar symptoms. Radiological assessments, particularly dynamic imaging, have emerged as potential objective tools for evaluating respiratory function. This review comprehensively summarizes findings on the use of diaphragmatic ultrasound (DUS), dynamic chest magnetic resonance imaging (MRI) and deep learning (DL)-based chest computed tomography (CT) for assessing lung function in ALS patients.

METHODS: Key radiological metrics include diaphragm thickness (DT), thickening fraction during inspiration, real-time diaphragmatic excursion, lung diameter changes and changes in pulmonary length and area. These measures have been compared with conventional PFTs in various studies to validate their use for diagnostic accuracy, particularly in early stages of disease.

KEY CONTENT AND FINDINGS: DUS is a non-invasive, widely available tool that strongly correlates with PFT measurements, especially FVC, MIP, and sniff nasal inspiratory pressure (SNIP). Dynamic measures, such as excursion and velocity, appear more sensitive to early dysfunction than thickness alone. Chest dynamic MRI has also shown significant correlations with spirometric parameters. Small cohort studies indicate that dynamic chest MRI is a superior, sensitive tool for detecting early respiratory impairment in asymptomatic patients with normal spirometry.

CONCLUSIONS: Radiological assessments, primarily DUS, DL-based chest CT and dynamic MRI, offer valuable, objective, and non-invasive methods for monitoring respiratory muscle strength in ALS. These techniques serve as complementary tools to traditional PFTs, particularly in selected clinical scenarios such ALS patients with early disease, bulbar involvement and unable to perform PFTs. Further longitudinal research with larger cohorts is needed to standardize protocols and validate their role as early parameters to guide the timely initiation of supportive interventions like non-invasive ventilation (NIV).},
}

@article {pmid42445484,
year = {2026},
author = {Ahmed, R and Kayande, A and Patil, R and Shelar, A and Zore, GB},
title = {Context-dependent reprogramming of ALS adhesin expression in Candida albicans: a multi-inducer analysis linking morphogenesis to virulence plasticity.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1848556},
pmid = {42445484},
issn = {1664-302X},
abstract = {Candida albicans employs the ALS (Agglutinin-Like Sequence) gene family to encode cell-surface adhesins that are central to host colonization, tissue invasion, and biofilm formation. Although individual ALS genes have been studied under specific conditions, no systematic, multi-inducer temporal analysis of the entire family has been reported to date. In this study, we present the first comprehensive temporal expression profiling of seven ALS genes (ALS1-ALS5, ALS7, and ALS9) under six host-relevant inducers, temperature (37 °C), neutral pH, serum, glucose, N-acetylglucosamine (NAG), and proline, across four time points (45 min, 90 min, 3 h, 6 h) in both yeast (30 °C) and hyphal (37 °C) growth phases. Morphological analysis confirmed that 37 °C and serum were the most potent hyphal inducers (94.13 ± 0.94% hyphae with serum at 37 °C). Quantitative PCR revealed a temporally stratified regulatory program: early-phase adhesins (ALS1, ALS2) showed transient induction during the first 90 min, whereas invasion-associated genes exhibited sustained late-phase activation. Notably, ALS3 displayed exceptional upregulation under glucose at 37 °C (25.17 ± 1.76-fold at 6 h; p < 0.001) and responded robustly to all inducers except serum. ALS7 reached 9.48-fold induction specifically under thermal stress, while ALS5 was preferentially expressed at 30 °C (6.70-fold under neutral pH), indicating niche-specific functional specialization. In silico promoter analysis linked these expression patterns to binding motifs for key transcription factors (Efg1, Cph1, Rim101, and Nrg1). Phylogenetic analysis revealed functional conservation of ALS2/ALS4 versus evolutionary divergence in ALS6/ALS7/ALS9. STRING-based protein interaction networks confirmed the central involvement of ALS proteins in adhesion and biofilm regulatory circuits. These findings establish a molecular framework for niche-specific virulence, identifying ALS3 as a prime therapeutic target for anti-adhesion strategies in invasive candidiasis. We hypothesize that C. albicans employs a temporally stratified and inducer-specific transcriptional program of the ALS family to adapt its surface architecture to diverse host microenvironments.},
}

@article {pmid42447123,
year = {2026},
author = {Wohnrade, C and Thau-Habermann, N and Gschwendtberger, T and Rückoldt, J and Huang, Z and Schreiber, S and Haastert-Talini, K and Petri, S},
title = {Neuromuscular ultrasound as a biomarker in the SOD1 mouse model of amyotrophic lateral sclerosis.},
journal = {PloS one},
volume = {21},
number = {7},
pages = {e0353397},
pmid = {42447123},
issn = {1932-6203},
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology/genetics/physiopathology ; Mice ; *Superoxide Dismutase/genetics ; Disease Models, Animal ; Superoxide Dismutase-1 ; Biomarkers/metabolism ; Ultrasonography ; Mice, Transgenic ; Humans ; Sciatic Nerve/diagnostic imaging/pathology ; Muscle, Skeletal/diagnostic imaging/pathology ; Motor Neurons/pathology ; Disease Progression ; },
abstract = {A progression marker that indicates early disease-related changes and treatment responses in the to date incurable neurodegenerative disease amyotrophic lateral sclerosis (ALS) is highly desirable. Translation of therapeutics that have been successful in in vivo models into trials in human patients has proven difficult in recent decades. This failure can be attributed, at least in part, to the lack of specific biomarkers for ALS diagnosis and progression in human ALS patients as well as in in vivo models. Neuromuscular ultrasound is an easily accessible, non-invasive tool to support diagnosis of ALS in humans. Our current study shows for the first time that the disease can be detected in an ALS mouse model with the help of neuromuscular ultrasound. We characterized disease progression regarding changes in the peripheral nerves and muscles of the hind limb in the SOD1G93A mouse model of ALS using different techniques (neuromuscular ultrasound, electroneurography, motor function tests, phenotypic assessments and histology). By neuromuscular ultrasound, we measured the cross-sectional area and diameter of the sciatic nerve and analyzed hind limb muscle texture and thickness. Our results show that motor neuron loss and muscle atrophy - analogous to ALS in humans - can be measured by ultrasound in the SOD1G93A mouse model. Changes in nerve and muscle morphology appear at the same time or even before changes in the established tests (including electroneurographic measurements) performed in vivo in this model. Correlations with histologic features of disease progression make neuromuscular ultrasound a sensitive, non-invasive outcome marker for preclinical studies.},
}

Animals
*Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology/genetics/physiopathology
Mice
*Superoxide Dismutase/genetics
Disease Models, Animal
Superoxide Dismutase-1
Biomarkers/metabolism
Ultrasonography
Mice, Transgenic
Humans
Sciatic Nerve/diagnostic imaging/pathology
Muscle, Skeletal/diagnostic imaging/pathology
Motor Neurons/pathology
Disease Progression

@article {pmid42447443,
year = {2026},
author = {Hicks-Courant, K},
title = {Taking Responsibility.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2502100},
doi = {10.1200/JCO-25-02100},
pmid = {42447443},
issn = {1527-7755},
abstract = {This essay is about how caring for my complicated father with amyotrophic lateral sclerosis (ALS) unexpectedly shaped how I approached my work as a gynecologic oncologist.},
}

@article {pmid42447895,
year = {2026},
author = {Arnolds, KB and Peinemann, F},
title = {[Infant-driven versus Practitioner-driven Feeding of Preterm Infants: A Systematic Review of Randomized Controlled Trials].},
journal = {Zeitschrift fur Geburtshilfe und Neonatologie},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2894-2931},
pmid = {42447895},
issn = {1439-1651},
abstract = {HINTERGRUND: Voraussetzung für eine erfolgreiche orale Ernährung ist die Berücksichtigung des individuellen Entwicklungsstands der Frühgeborenen. Pflegekräfte und Eltern sollten geschult sein, wie sie Verhaltenssignale des Säuglings während des Fütterns erkennen und darauf angemessen reagieren können. Diese Art der Ernährung wird in dieser Arbeit als "signalorientiertes und co-reguliertes" Füttern von Frühgeborenen bezeichnet. Im Unterschied zeichnet sich das "herkömmliche" Füttern dadurch aus, dass eine vorab festgelegte Flüssigkeitsmenge zu einer festgelegten Zeit verabreicht wird.

ZIELSETZUNG: Es soll untersucht werden, ob das "signalorientierte und co-regulierte" Füttern im Vergleich zum "herkömmlichen" Füttern zu einer früheren vollständigen oralen Ernährung führen kann.

METHODEN: Wir haben am 26. Juni 2024 in den elektronischen Datenbanken MEDLINE und Cochrane Library nach thematisch relevanten randomisierten Studien gesucht. Als primärer Endpunkt wurde die Anzahl der Tage bis zur vollständigen oralen Ernährung und als Effektmaß die mittlere Differenz gewählt. Die Metaanalyse wurde unter Verwendung der inversen Varianzmethode und des Random-Effects-Modells durchgeführt, und wir verwendeten den GRADE-Ansatz (Grading of Recommendations Assessment, Development, and Evaluation) für die Bewertung der Evidenz.

ERGEBNISSE: In der Studienauswahl fanden sich 12 randomisierte Studien, die den Einschlusskriterien entsprachen. Von diesen wurden 5 Studien in eine Metaanalyse einbezogen. Die geschätzte mittlere Differenz favorisierte die Gruppen mit signalorientiertem und co-reguliertem Füttern im Vergleich zu den Gruppen mit herkömmlicher Fütterung: -4,93 (95%-Konfidenzintervall -6,60 bis -3,26, p<0,00001, I[2] =66%). Die Qualität der Evidenz wurde als moderat eingestuft.

SCHLUSSFOLGERUNGEN: Die Daten der Studienteilnehmer sind mit einem leicht vorteilhaften Effekt für die signalorientierte und co-regulierte Ernährung von Frühgeborenen im Vergleich zur herkömmlichen Ernährung von Frühgeborenen vereinbar. Zukünftige Studien könnten weitere Daten zu unerwünschten Ereignissen während der Ernährung und Informationen zur häuslichen Nachsorge ergänzen.},
}

@article {pmid42448407,
year = {2026},
author = {Rangappa, N and Upadhyay, R and Lakshman, N and Ramasamy, S and Sevanan, M and Justin, A and Chinnathambi, S},
title = {Small molecular therapeutic targets for neurodegenerative diseases.},
journal = {Advances in protein chemistry and structural biology},
volume = {153},
number = {},
pages = {135-167},
doi = {10.1016/bs.apcsb.2025.10.012},
pmid = {42448407},
issn = {1876-1631},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology/genetics ; Animals ; *Molecular Targeted Therapy ; },
abstract = {Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis disease are characterized by progressive neuronal loss, protein aggregation, and synaptic dysfunction. These diseases share common pathological mechanisms including oxidative stress, mitochondrial impairment, chronic neuroinflammation, protein misfolding, and epigenetic dysregulation. Current therapies offer only symptomatic relief and fail to halt disease progression. Recent advances in transcriptomics and proteomics have enabled the identification of shared molecular pathways and druggable targets across multiple neurodegenerative diseases. The key targets, such as BDNF-TrkB, TREM2, SIRT1, PINK1-Parkin, GSK-3β, NLRP3, and mTOR have shown promise in preclinical models, offering opportunities for broad-spectrum therapeutic development. Importantly, blood-brain barrier disruption and neuroinflammatory crosstalk exacerbate disease pathology and hinder drug delivery. Innovative strategies involving nanocarriers, gene therapy, and epigenetic modulation are emerging to overcome these barriers. This review highlights the convergence of disease mechanisms, discusses common molecular signatures and therapeutic vulnerabilities, and explores novel small molecular interventions targeting shared pathways mainly in AD and PD. A deeper understanding of aging-associated molecular dysfunction is essential to design sustainable, disease-modifying therapeutics with cross-disease relevance.},
}

Humans
*Neurodegenerative Diseases/drug therapy/metabolism/pathology/genetics
Animals
*Molecular Targeted Therapy

@article {pmid42449472,
year = {2026},
author = {de Albuquerque Bueno, MG and Dos Santos, DF and Rossor, AM and Laura, M and Horga, A and Frezatti, RSS and de Sousa Ferreira, EV and Blake, JC and Morrow, JM and Reilly, MM and Marques Júnior, W and Tomaselli, PJ},
title = {VRK1-Related Motor Neuropathy With Upper Motor Neuron Signs and Selective Muscle Involvement.},
journal = {Journal of the peripheral nervous system : JPNS},
volume = {31},
number = {3},
pages = {e70145},
doi = {10.1111/jns.70145},
pmid = {42449472},
issn = {1529-8027},
support = {MR/S005021/1//International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD)/ ; 25000.160.096/2014-07//Programa Nacional de Apoio à Atenção da Saúde da Pessoa com Deficiência (PRONAS)/ ; 465 458/20114-9//National Institute of Sciences and Technology (INCT)-Translational Medicine/ ; 310378/2021-4//Conselho Nacional de Pesquisa (CNPq)/ ; FE-CLI-24-0005-05//Biogen/ ; },
mesh = {Humans ; Female ; Male ; *Motor Neuron Disease/genetics/physiopathology/diagnostic imaging/pathology ; *Protein Serine-Threonine Kinases/genetics ; Adult ; Middle Aged ; Magnetic Resonance Imaging ; *Intracellular Signaling Peptides and Proteins/genetics ; *Muscle, Skeletal/physiopathology/diagnostic imaging/pathology ; Nerve Conduction Studies ; Young Adult ; Electromyography ; Neural Conduction/physiology ; Adolescent ; Child ; },
abstract = {INTRODUCTION: Hereditary motor neuropathies (HMN) represent a heterogeneous group of disorders with wide clinical and genetic variability. Despite advances in molecular diagnostics, approximately 50% of cases remain genetically unresolved, particularly those where distinguishing length-dependent motor neuropathy from motor neuron disorder with disproportionate segmental involvement is a challenge. Variants in the VRK1 gene, originally described in association with pontocerebellar hypoplasia, are now known to produce a broad clinical spectrum, including amyotrophic lateral sclerosis, dHMN, and less frequently, spastic paraplegia.

OBJECTIVES: This study's aim was to characterize the clinical presentation, electrophysiological findings, and muscle MRI patterns associated with VRK1-related motor neuron disease in a cohort of nine patients from five unrelated families.

METHODS: Five unrelated families with inherited motor neuropathy were investigated using next-generation sequencing techniques, including targeted gene panels or whole-exome sequencing, with subsequent confirmation by Sanger sequencing. A total of nine affected individuals underwent detailed clinical evaluation, nerve conduction studies (NCS), electromyography (EMG), and whole-body muscle MRI (wbMRI).

RESULTS: Nine affected individuals carrying biallelic VRK1 variants were evaluated. In most cases (66%), symptom onset occurred during the first decade of life. All patients presented with gradually progressive distal muscle weakness. Mean Medical Research Council (MRC) scores were 2.8 for ankle dorsiflexion and 1.9 for plantar flexion. Sensory nerve conduction studies were normal in all individuals evaluated (8/9), although mild sensory complaints were reported in four patients. Muscle cramps were observed in two-thirds of the cohort, while fasciculations were uncommon (11%). EMG findings consistently demonstrated a neurogenic pattern with predominant distal involvement, and evidence of both acute and chronic denervation was present in four patients. Whole-body muscle MRI, available for all patients, revealed a consistent pattern of fatty infiltration predominantly affecting posterior muscle compartments, with minimal STIR signal changes. Brain and spinal imaging, performed in all individuals, showed no abnormalities.

INTERPRETATIONS: Biallelic mutations in VRK1 are associated with a recognizable form of motor neuron disease characterized by features of dHMN combined with upper motor neuron involvement, along with a distinctive posterior-predominant pattern on muscle MRI. Identifying this phenotype, a known presentation of VRK1-related disorders, highlights the importance of targeted genetic testing in unresolved cases of hereditary motor neuropathy.},
}

Humans
Female
Male
*Motor Neuron Disease/genetics/physiopathology/diagnostic imaging/pathology
*Protein Serine-Threonine Kinases/genetics
Adult
Middle Aged
Magnetic Resonance Imaging
*Intracellular Signaling Peptides and Proteins/genetics
*Muscle, Skeletal/physiopathology/diagnostic imaging/pathology
Nerve Conduction Studies
Young Adult
Electromyography
Neural Conduction/physiology
Adolescent
Child

@article {pmid42450002,
year = {2026},
author = {Kim, Y and Jung, YK},
title = {Proteasome Dysfunction and Aggregation-Prone Proteins in Neurodegenerative Diseases: From Mechanisms to Therapeutic Opportunities.},
journal = {International journal of molecular sciences},
volume = {27},
number = {13},
pages = {},
doi = {10.3390/ijms27135730},
pmid = {42450002},
issn = {1422-0067},
support = {RS-2025-00519823//National Research Foundation of Korea/ ; RS-2024-00439842//National Research Foundation of Korea/ ; },
mesh = {Humans ; *Proteasome Endopeptidase Complex/metabolism ; *Neurodegenerative Diseases/metabolism/therapy/pathology/drug therapy ; Animals ; Proteostasis ; *Protein Aggregation, Pathological/metabolism ; *Protein Aggregates ; Proteotoxic Stress ; Ubiquitin/metabolism ; Proteolysis ; Oxidative Stress ; },
abstract = {Neurodegenerative diseases are characterized by the accumulation of misfolded and aggregation-prone proteins, reflecting a failure of proteostasis. The ubiquitin-proteasome system (UPS), a major pathway for selective intracellular protein degradation, is essential for maintaining neuronal protein homeostasis. Proteasome dysfunction has been implicated in several major neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), although its extent and mechanisms vary across disease contexts. In this review, we examine current evidence for proteasome dysfunction in neurodegeneration and discuss how disease-associated proteins impair proteasome function through direct inhibition, defective substrate processing, and sequestration into protein aggregates. We also address the contribution of oxidative stress, neuroinflammation, and aging to proteasome dysregulation. Finally, we highlight emerging therapeutic strategies aimed at restoring proteasome function, including pharmacological activation, modulation of proteasome assembly and stability, and targeted protein degradation approaches. Understanding the context-dependent nature of proteasome dysfunction will be important for developing effective proteostasis-based therapies.},
}

Humans
*Proteasome Endopeptidase Complex/metabolism
*Neurodegenerative Diseases/metabolism/therapy/pathology/drug therapy
Animals
Proteostasis
*Protein Aggregation, Pathological/metabolism
*Protein Aggregates
Proteotoxic Stress
Ubiquitin/metabolism
Proteolysis
Oxidative Stress

@article {pmid42450899,
year = {2026},
author = {Gerymski, R},
title = {Does Life Lose Its Meaning When the Heart Fails? Illness Perception, Perceived Stress and Meaning in Life in Polish Patients with Heart Failure.},
journal = {Healthcare (Basel, Switzerland)},
volume = {14},
number = {13},
pages = {},
doi = {10.3390/healthcare14131889},
pmid = {42450899},
issn = {2227-9032},
support = {Fifty percent of the study was conducted free of charge by the author (R.G.). The other half of the study was financed by the Institute of Psychology at the Opole University (no grant number provided)//University of Opole/ ; },
abstract = {Background/Objectives: Heart failure (HF) is a highly unpredictable disease that significantly impacts patients' well-being. One of the fundamental problems faced by cardiac patients is trying to answer the question of how to lead a meaningful life. Meaning in life is a crucial predictor of well-being, ill-being and quality of life for everyone, not just cardiac patients. Therefore, identifying its predictors is crucial. Based on Leventhal et al.'s common-sense model of self-regulation of health and illness, and Lipowski's disease perception concept, this study verified the role of illness perception and perceived stress in existential meaning in Polish HF patients. Methods: This manuscript presents the results of a cross-sectional study. Overall, 336 HF patients from Poland were examined. Four questionnaires were used: the Meaning in Life Questionnaire (MLQ), the Multidimensional Existential Meaning Scale (MEMS), the Perceived Stress Scale (PSS-10) and the Disease-Related Appraisals Scale (DRAS). Results: Negative illness perception and positive cognitive assessment of the illness were shown to be significant predictors of meaning in life in patients with HF. Furthermore, this relationship was mediated by perceived stress. Additionally, the positive correlation between negative illness assessment and positive illness perception was found. Conclusions: This study demonstrates that cognitive assessment of the disease can be associated with the existential resources of heart failure patients. It also highlights the importance of working on the existential sphere of cardiac patients and accurately verified theoretical assumptions regarding the relationship between illness perception and meaning in life, providing a basis for future longitudinal studies and meaning-oriented psychological help focused on individuals with HF.},
}

@article {pmid42451086,
year = {2026},
author = {Soni, N and Debnath, N and Rekapally, E and Jabbar, A and Tyagi, SC and Bissa, B and Tyagi, N},
title = {Vitamin D Signaling in Neurodegenerative Disorders: Mechanisms, Therapeutic Potential, and Clinical Implications.},
journal = {Nutrients},
volume = {18},
number = {13},
pages = {},
doi = {10.3390/nu18132082},
pmid = {42451086},
issn = {2072-6643},
support = {971566; 24 TPA1304527 and 25 TPA1481771 to Neetu Tyagi.//American Heart Association/ ; },
mesh = {Humans ; *Vitamin D/metabolism/therapeutic use ; *Neurodegenerative Diseases/metabolism/drug therapy/etiology ; *Signal Transduction ; Vitamin D Deficiency/complications ; Animals ; Oxidative Stress/drug effects ; Receptors, Calcitriol/metabolism ; Blood-Brain Barrier/metabolism ; Neuroprotective Agents ; },
abstract = {Vitamin D has long been recognized for its role in calcium homeostasis and bone metabolism; however, it is now emerging as an important regulator of central nervous system (CNS) function. Recent evidence suggests that vitamin D signaling contributes to the pathogenesis and progression of several neurodegenerative disorders. Vitamin D exerts neuroprotective effects through multiple mechanisms, including regulation of calcium homeostasis, modulation of immune responses, reduction in oxidative stress, stimulation of neurotrophic factors, and maintenance of blood-brain barrier (BBB) integrity. Vitamin D receptors and metabolizing enzymes are widely distributed across several brain regions, highlighting their direct involvement in neuronal function. This review summarizes the biosynthesis, metabolism, and signaling pathways of vitamin D. It explores its role in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), stroke, and traumatic brain injury (TBI). Evidence from experimental and clinical studies indicates that vitamin D deficiency is associated with an increased risk and severity of these conditions, while supplementation may provide therapeutic benefits.},
}

Humans
*Vitamin D/metabolism/therapeutic use
*Neurodegenerative Diseases/metabolism/drug therapy/etiology
*Signal Transduction
Vitamin D Deficiency/complications
Animals
Oxidative Stress/drug effects
Receptors, Calcitriol/metabolism
Blood-Brain Barrier/metabolism
Neuroprotective Agents

@article {pmid42451691,
year = {2026},
author = {Singh, AA and Arukha, AP and Song, M},
title = {Indole-Derived Compounds as Redox-Modulators: Antioxidant Mechanisms in Neuronal Protection.},
journal = {Molecules (Basel, Switzerland)},
volume = {31},
number = {13},
pages = {},
doi = {10.3390/molecules31132323},
pmid = {42451691},
issn = {1420-3049},
mesh = {Humans ; *Antioxidants/pharmacology/chemistry ; *Indoles/chemistry/pharmacology ; Animals ; *Neuroprotective Agents/pharmacology/chemistry ; Oxidation-Reduction/drug effects ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neurons/drug effects/metabolism ; Oxidative Stress/drug effects ; Signal Transduction/drug effects ; Reactive Oxygen Species/metabolism ; },
abstract = {Neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Amyotrophic lateral sclerosis, are distinguished by progressive neuronal dysfunction caused primarily by oxidative stress, mitochondrial impairment, neuroinflammation, and redox imbalance. Growing evidence suggests that indole-derived compounds have significant neuroprotective potential due to their antioxidant, anti-inflammatory, and redox-modulating properties. This review summarizes the structural and biological significance of indole scaffolds, focusing on the mechanisms by which natural, endogenous, microbiota-derived, and synthetic indole compounds protect neuronal networks. Indole-3-carbinol, 3,3'-diindolylmethane, indole-3-propionic acid, and melatonin are major indole derivatives that control important neuroprotective pathways like Nrf2/ARE signaling, mitochondrial bioenergetics, neurotrophic factor expression, apoptotic regulation, and suppression of proinflammatory mediators. These compounds also maintain synaptic plasticity, reduce reactive oxygen species production, and improve neuronal survival in neurodegenerative disease models. Additionally, updated information from translational and clinical research indicates that indole-based compounds may have promising therapeutic applications; however, obstacles like low bioavailability, metabolic instability, and blood-brain barrier penetration continue to be major obstacles to clinical application. Development in nanoparticle delivery systems, microbiome-targeted interventions, and rational structural optimization may improve therapeutic efficacy and translational potential. Overall, indole-derived compounds are a versatile class of redox modulators with potential applications in the prevention and treatment of neurodegenerative diseases via integrated antioxidant and neuroprotective mechanisms.},
}

Humans
*Antioxidants/pharmacology/chemistry
*Indoles/chemistry/pharmacology
Animals
*Neuroprotective Agents/pharmacology/chemistry
Oxidation-Reduction/drug effects
*Neurodegenerative Diseases/drug therapy/metabolism
*Neurons/drug effects/metabolism
Oxidative Stress/drug effects
Signal Transduction/drug effects
Reactive Oxygen Species/metabolism

@article {pmid42453524,
year = {2026},
author = {Yang, HI and Hsueh, KW and Ding, DC and Harn, HJ and Lin, YC and Chang, CY and Tsai, ST and Lin, SZ},
title = {Therapeutic potential of adipose-derived stem cell transplantation in amyotrophic lateral sclerosis: A combined clinical case and preclinical study.},
journal = {Tzu chi medical journal},
volume = {38},
number = {3},
pages = {332-339},
pmid = {42453524},
issn = {2223-8956},
abstract = {OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is an inevitably fatal neurodegenerative disease with no adequate treatment. Transplantation of adipose-derived stem cells (ADSCs) may be an effective therapeutic strategy for delaying progression or restoring neurological function in ALS.

MATERIALS AND METHODS: We evaluated the safety and therapeutic efficacy of intravenous (i.v.) and intracerebral (i.c.) ADSC injection in a late-stage ALS patient and in a SOD1 transgenic (Tg) mouse model. Magnetic resonance imaging (MRI) and computed tomography (CT) were conducted to examine potential cerebral hemorrhage and tumor generation in the treated patient. In addition, maximal inspiratory pressure, maximal expiratory pressure, tidal volume, and respiratory rate were measured as indices of respiratory function.

RESULTS: ADSC transplantation was safe, with MRI and CT showing no hemorrhage or tumorigenesis up to 12 months. The patient's Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score improved from 7 to 9 at 3 months and remained above baseline for 6 months. Respiratory function was preserved during this period. In SOD1 Tg mice, i.c. and i.v. ADSC infusion significantly prolonged survival (165.0 ± 10.4 and 147.3 ± 4.5 days vs. 129.7 ± 3.9 days) and improved motor scores (P < 0.01).

CONCLUSION: This preliminary finding suggests potential therapeutic feasibility, but further studies with larger cohorts are needed to confirm its safety and efficacy.},
}

@article {pmid42436608,
year = {2026},
author = {Teng, Z and Bushman, BJ},
title = {Rethinking Longitudinal Studies of Media Violence and Aggression: A Rejoinder to Lacko et al.'s (2026) Comment.},
journal = {Aggressive behavior},
volume = {52},
number = {4},
pages = {e70078},
pmid = {42436608},
issn = {1098-2337},
mesh = {*Aggression/psychology ; Humans ; *Violence/psychology ; Longitudinal Studies ; Media Exposure ; },
abstract = {Lacko et al. responded to the concerns raised in our commentary, providing an opportunity to reflect on broader methodological and theoretical issues in longitudinal research on media violence and aggression. This exchange highlights five lessons for future research: (1) longitudinal studies should place greater emphasis on developmental processes; (2) analytical approaches and the interpretation of findings are important; (3) examining the longitudinal effects of media violence on aggression requires high-quality longitudinal data; (4) greater transparency and openness in both data and analytical methods strengthen the field; and (5) future research should place greater emphasis on understanding when, how, and for whom media violence influences aggression. We hope these lessons will contribute to more rigorous longitudinal research and a deeper understanding of the developmental processes linking media violence and aggression.},
}

*Aggression/psychology
Humans
*Violence/psychology
Longitudinal Studies
Media Exposure

@article {pmid42436960,
year = {2026},
author = {Gromprasit, A and Thremthakanpon, W and Siripocaratana, K and Wanitcharoenporn, W and Jitprapaikulsarn, S and Sutthapakti, B and Laoruengthana, A},
title = {Accuracy and Reliability of Magnetic Resonance Imaging Measurement of Medial Femoral Condyle for Femoral Component Sizing in Oxford Unicompartmental Knee Arthroplasty.},
journal = {Arthroplasty today},
volume = {40},
number = {},
pages = {102088},
pmid = {42436960},
issn = {2352-3441},
abstract = {BACKGROUND: Accurate femoral component sizing is critical for Oxford unicompartmental knee arthroplasty (UKA) because inappropriate sizing can lead to early implant failure. Therefore, we developed a magnetic resonance imaging (MRI) measurement of medial femoral condyle (MRMFC) technique and compare its accuracy to existing methods.

METHODS: This study included 54 Oxford UKAs. Five sizing methods were assessed: radiographic templating, intraoperative sizing spoon, anthropometric estimation (based on patient height and gender), Yang et al.'s MRI method, and the MRMFC. The MRMFC determined 3 reference points of medial femoral condyle on the sagittal plane of MRI. The primary outcome was an overhang or underhang of femoral component over posterior femoral condyle as determined on postoperative lateral radiographs which ±2 mm are considered as ideal size.

RESULTS: The MRMFC method yielded the highest accuracy (50/54; 92.6%; 95% CI: 82.1-97.9), followed by the intraoperative sizing spoon (38/54; 70.4%, 56.4-82.0), Yang et al. MRI method (32/54; 59.3%, 45.0-72.4), anthropometric estimation (30/54; 55.6%, 41.4-69.1), and radiographic templating (25/54; 46.3%, 32.6-60.4). Pairwise testing demonstrated that MRMFC was better than the sizing spoon (P = .008), radiographic templating (P < .001), Yang et al. MRI method (P < .001), and anthropometric estimation (P < .001). The sizing spoon was superior to radiographic templating (P = .029). No significant differences were observed among radiographic templating, Yang et al. MRI method, and anthropometric estimation.

CONCLUSIONS: The MRMFC demonstrated the highest accuracy and reproducibility in preoperative planning for Oxford UKA. Intraoperative spoon sizing, however, remains a simple and practical method and performed moderately well with significantly better than radiographic templating.},
}

@article {pmid42437951,
year = {2026},
author = {Williams, KJ},
title = {Anti-inflammatory agents in atherosclerosis-and a need for reform: Extraordinary claims require extraordinary evidence.},
journal = {Journal of internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.1111/joim.70128},
pmid = {42437951},
issn = {1365-2796},
support = {//Ruth and Yonatan Ben-Avraham Fund/ ; },
abstract = {Since 1858, human atherosclerotic plaques have been shown to contain immune cells. But are these cells suitable therapeutic targets? Dozens of clinical trials of anti-inflammatory agents other than colchicine have been performed in patients with clinically evident atherosclerosis. None of these trials led any regulatory body in any jurisdiction to allow a cardiovascular indication for any of these agents. This discouraging work provides a background to evaluate new data on colchicine. In 2024-2025, new clinical trials of colchicine in patients with atherosclerosis showed benefit, no benefit, or harm. In 2025-2026, over a dozen meta-analyses so far have appeared, drawing on ∼34 trials, but do not agree with each other. One of these meta-analyses, Xie et al.'s in the Journal of Internal Medicine, provides a compelling graphical display of the pre-specified primary outcomes of six long-term clinical trials as they were published over time. The pattern of early positive trials, then newer negative (null) trials, suggests regression to the truth. Jeon and Cho et al.'s population-wide study in the Journal of Internal Medicine of patients with Type 2 diabetes and gout found no benefit from colchicine over nonsteroidal anti-inflammatory drugs on major adverse cardiovascular events. This information suggests several areas for reform of research on inflammation in atherosclerosis. Fully informed consent should require that clinical trials of anti-inflammatory agents in atherosclerotic arterial disease must disclose to trial participants the failures of this approach in over 50 clinical trials to date, spanning decades. Additionally, the field might reconsider its commitment to the Big Idea that inflammation must be a definitive therapeutic target in atherosclerosis. The track record so far for inflammation inhibition in atherosclerosis is extensive and disappointing-a fact that merits wider discussion. Therapeutic successes from targeting cholesterol-rich, apolipoprotein-B-containing lipoproteins-the proven causative agents of this disease-provide extraordinary evidence. Current data for colchicine and other anti-inflammatory therapies do not.},
}

@article {pmid42438447,
year = {2026},
author = {Jewett, G and Chan, E and Jagt, K and Petrillo Ballantyne, J and Wesolosky, J and Perera, T and Karnik, V and Hahn, C and Luk, C and Mobach, T},
title = {An intrathecal therapeutics clinic for administration of tofersen in amyotrophic lateral sclerosis: A Canadian nurse practitioner and neurologist collaborative model.},
journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques},
volume = {},
number = {},
pages = {1-10},
doi = {10.1017/cjn.2026.10647},
pmid = {42438447},
issn = {0317-1671},
}

@article {pmid42439979,
year = {2026},
author = {Langreen, S and Uecker, M and Juhl, S and Dingemann, J and Kiblawi, R},
title = {Is hypoalbuminemia a risk factor for small bowel anastomotic leaks in infants? A multivariate analysis.},
journal = {Pediatric surgery international},
volume = {42},
number = {1},
pages = {},
pmid = {42439979},
issn = {1437-9813},
mesh = {Humans ; *Hypoalbuminemia/complications ; Retrospective Studies ; *Anastomotic Leak/etiology/epidemiology ; Risk Factors ; Female ; *Intestine, Small/surgery ; Male ; Infant ; Multivariate Analysis ; Anastomosis, Surgical ; Infant, Newborn ; Incidence ; Serum Albumin ; },
abstract = {PURPOSE: Anastomotic leaks (AL) are critical complications following bowel anastomosis with an incidence of up to 10.5% in infants. Previous studies in animal models and adults have suggested a link between postoperative fluid overload and hypoalbuminemia with anastomotic leaks. In infants, the role of hypoalbuminemia on anastomotic integrity after small bowel anastomosis remains unclear.

METHODS: Retrospective study of infants < 1 year, undergoing elective small-bowel anastomosis between 2015 and 2024 (Ethics No.-11362-_BO_K_202). Data on demographics, weight gain, serum albumin levels and use of diuretic medication during the first five postoperative days were collected. Univariate and multivariate analysis were performed to detect risk factors for ALs in infants.

RESULTS: 13 of 219 patients (5.9%) developed ALs. Demographics were similar comparing patients with and without leaks. In univariate analysis, serum albumin levels were significantly lower (20.3 g/l vs. 26,3 g/l, p < 0.0001) in patients with AL compared to patients without AL and multivariate analysis confirmed a significant association between low serum albumin levels and AL occurrence, CONCLUSION: In infants, small bowel anastomotic leaks are associated with low postoperative serum albumin. Whether hypoalbuminemia should be regarded as an early warning sign of an undiagnosed, developing anastomotic leak or represents a causal risk factor can only be determined with further studies.},
}

Humans
*Hypoalbuminemia/complications
Retrospective Studies
*Anastomotic Leak/etiology/epidemiology
Risk Factors
Female
*Intestine, Small/surgery
Male
Infant
Multivariate Analysis
Anastomosis, Surgical
Infant, Newborn
Incidence
Serum Albumin

@article {pmid42432671,
year = {2026},
author = {Chen, F and Wang, L and Liu, H and Khan, Q and Tang, B and Bao, N},
title = {The role of AI-assisted drug repurposing in neurological disorders: a systematic review of validation strategies, challenges and opportunities.},
journal = {Journal of nanobiotechnology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12951-026-04551-7},
pmid = {42432671},
issn = {1477-3155},
abstract = {Neurological disorders refer to a diverse group of conditions that affect the brain, peripheral nerves, and spinal cord and impair socioemotional, cognitive, motor, and sensory functions. Alzheimer's disease (AD), Multiple Sclerosis (MS), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS) are some of the well-known neurodegenerative diseases that affect millions of people worldwide. Despite the advanced technologies and nano-drug delivery systems, the success rate of developing drugs for neurological disorders is significantly low. Among several constraints, including gastrointestinal irritation, rapid metabolism, and low stability, the blood-brain barrier (BBB) emerges as one of the key challenges in the development and application of drugs against neurological disorders. These challenges necessitate innovative approaches to develop cost-effective therapeutic strategies. Drug repurposing, the discovery of new therapeutic benefits of existing drugs, is a promising drug discovery approach for discovering potential treatment options for complex neurological disorders. This review aims to explore the advanced and significant progress in drug repurposing for major neurological disorders, including MS, AD, PD, ALS, HD, stroke, and neuropsychiatric conditions. It places an explicit emphasis on discussing the potential role of artificial intelligence (AI)-assisted drug repurposing and understanding of the biological mechanisms in discovering new drugs for these neurological conditions. This also examines current challenges in drug repurposing and provides a critical review of the available opportunities and limitations in AI-assisted drug repurposing.},
}

@article {pmid42432783,
year = {2026},
author = {Choi, Y and Lee, S and Ashim, J and Yu, W and Cho, E and Lee, HW and Park, JS and Yoon, JH and Kim, HJ and Cheon, M},
title = {Cross-disease LC-MS/MS plasma proteomics identifies reproducible shared and disease-enriched biomarker signatures in neurodegenerative disorders.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-026-02377-w},
pmid = {42432783},
issn = {2051-5960},
support = {RS-2024-00454715//the National Research Foundation of Korea (NRF) grant funded by the Korean government/ ; RS-2024-00343239//the National Research Foundation of Korea (NRF) grant funded by the Korean government/ ; RS-2023-00230402//the Ministry of Environment of Korea/ ; 26-BR-04-01//the KBRI basic research program through the Korea Brain Research Institute funded by the Ministry of Science and ICT/ ; 26-BR-02-03, 26-BR-02-05, 26-BR-04-01//the KBRI basic research program through the Korea Brain Research Institute funded by the Ministry of Science and ICT/ ; 26-BR-02-03, 26-BR-02-05, 26-BR-04-01, 26-BR-06-02//the KBRI basic research program through the Korea Brain Research Institute funded by the Ministry of Science and ICT/ ; RS-2024-00512888//the Korea Technology and Information Promotion Agency for SMEs (TIPA) funded by the Ministry of SMEs and Startups/ ; },
abstract = {Neurodegenerative diseases (NDDs) exhibit considerable molecular heterogeneity, making it difficult to pinpoint robust, disease-specific biomarkers. Although proteomic studies have deepened our understanding of individual disorders, systematic cross-disease comparisons with cross-platform validation remain scarce, especially for rare conditions like spinal and bulbar muscular atrophy (SBMA). To address this gap, we conducted a comparative plasma proteomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 264 participants across major neurodegenerative and related diagnostic groups, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), SBMA, and cognitively healthy controls. This unified framework allowed us to capture both disease-specific and shared protein signatures across neurodegenerative conditions. Candidate proteins were then validated in the UK Biobank (Olink Explore) and the Global Neurodegeneration Proteomics Consortium (SomaScan). Of 23 proteins assessed in the UK Biobank, four unique proteins (yielding six disease-protein associations) showed nominally significant and directionally concordant changes; of 20 proteins represented by 27 probes tested in the Global Neurodegeneration Proteomics Consortium, seven proteins reached nominal significance, all with full directional concordance across both cohorts. Notably, IGFBP2 was consistently elevated in AD and PD across independent datasets, pointing to shared metabolic dysregulation, while ADIPOQ showed parallel increases in the same conditions, reinforcing convergent shifts in energy metabolism. By contrast, CRTAC1 and COMP were selectively reduced in motor neuron diseases, suggesting disease-enriched alterations in extracellular matrix composition. Taken together, our findings provide a cross-disease, cross-platform framework for uncovering reproducible proteomic biomarkers and shed light on both overlapping and distinct molecular pathways in neurodegeneration.},
}

@article {pmid42432887,
year = {2026},
author = {Ye, H and Wang, JL and Xu, QH and Gao, YL},
title = {Refining the link between REM sleep behavior disorder and neurodegeneration: Genetic correlation, Mendelian randomization, and colocalization evidence.},
journal = {Medicine},
volume = {105},
number = {28},
pages = {e48922},
doi = {10.1097/MD.0000000000048922},
pmid = {42432887},
issn = {1536-5964},
mesh = {Humans ; *REM Sleep Behavior Disorder/genetics/complications ; Mendelian Randomization Analysis ; *Neurodegenerative Diseases/genetics ; Linkage Disequilibrium ; Genome-Wide Association Study ; Alzheimer Disease/genetics ; Parkinson Disease/genetics ; },
abstract = {Observational studies have proposed a link between isolated rapid eye movement sleep behavior disorder (iRBD) and several neurodegenerative diseases. We employed genome-wide linkage disequilibrium score regression (LDSC), standard two-sample Mendelian randomization (MR), and colocalization analysis to assess the causal links between iRBD and these neurodegenerative conditions. iRBD demonstrated a positive causal association with Alzheimer disease (odds ratio [OR] = 1.02, 95% confidence interval [CI]: 1.00-1.03, P = 1.10E-02), Parkinson disease (OR = 1.10, 95% CI: 1.03-1.16, P = 2.96E-03), and multiple sclerosis (OR = 1.09, 95% CI: 1.02-1.17, P = 1.61E-02). A strong positive genetic correlation with dementia with Lewy bodies was observed (rg = 1.6313, P = .0002), along with a causal association (OR = 1.45, 95% CI: 1.03-2.06, P = 3.53E-02), further supported by colocalization analysis. No significant causal relationship was identified between iRBD and amyotrophic lateral sclerosis (all P > .05). Additionally, reverse Mendelian randomization analyses did not reveal any causal relationships between the neurodegenerative diseases studied and iRBD. Our findings provide robust genetic evidence supporting a causal relationship between iRBD and the risk of multiple neurodegenerative diseases, highlighting the potential for shared pathophysiological mechanisms.},
}

Humans
*REM Sleep Behavior Disorder/genetics/complications
Mendelian Randomization Analysis
*Neurodegenerative Diseases/genetics
Linkage Disequilibrium
Genome-Wide Association Study
Alzheimer Disease/genetics
Parkinson Disease/genetics

@article {pmid42432946,
year = {2026},
author = {Jeong, J and Song, KJ and Lee, JC and Shin, SD and Kim, YJ},
title = {A simulation study on optimizing stationary camera locations for physician-directed telemedical supervision of prehospital advanced life support: Single-versus dual-camera setups.},
journal = {Medicine},
volume = {105},
number = {28},
pages = {e49685},
doi = {10.1097/MD.0000000000049685},
pmid = {42432946},
issn = {1536-5964},
support = {2020R1F1A1076561//National Research Foundation of Korea/ ; },
mesh = {Humans ; *Telemedicine ; *Emergency Medical Services/methods ; Prospective Studies ; *Emergency Medical Technicians/education ; Smartphone ; *Video Recording/instrumentation/methods ; },
abstract = {Prehospital telemedicine, particularly real-time video conferencing, offers significant benefits in prehospital and disaster settings by enabling rapid data transmission. Using a smartphone mounted on a tripod as a stationary camera provides stable footage, comprehensive scene evaluation, and reduced technical complexity, thus complementing smart glasses and built-in cameras. However, the optimal camera location for visualizing key procedures remains unexplored. This study aims to compare the optimal stationary camera location and the effectiveness of single-camera versus dual-camera setups in visualizing key procedures for physician-directed telemedical supervision of prehospital advanced life support (ALS). This prospective, non-randomized simulation study involved 9 advanced emergency medical technicians performing ALS procedures in 20 simulations. Each simulation was recorded simultaneously from 4 stationary camera locations: right head, left head, right leg, and left leg. Reviewers evaluated the visibility of 6 key procedures (airway management, breathing support, chest compressions, intravenous access, electrocardiogram rhythm monitoring, and teamwork) using a 1 to 5 scale. Mixed models and generalized linear mixed models were applied to analyze the visibility scores and compare the effect sizes of the different camera setups. The median visibility scores and proportion of optimal visibility (scores of 4-5) varied significantly across the 4 camera locations for most procedures. However, the mixed model and generalized linear model analyses for overall visibility did not reveal significant differences in effect sizes between individual camera locations. Dual-camera setups showed significant improvement over single-camera setups, with an adjusted odds ratio of 4.89 (95% confidence interval: 1.92-12.4) for the right head + left head combination and 3.74 (95% confidence interval: 1.50-9.32) for the right head + left leg combination. Although no single-camera location provided optimal visualization for all procedures, dual-camera setups were more effective than single cameras in capturing field activity. These findings support the use of dual-camera setups to enhance physician-directed telemedical supervision of prehospital ALS, with potential applicability to disaster settings, and may inform the development of future protocols for prehospital telemedicine.},
}

Humans
*Telemedicine
*Emergency Medical Services/methods
Prospective Studies
*Emergency Medical Technicians/education
Smartphone
*Video Recording/instrumentation/methods

@article {pmid42434198,
year = {2026},
author = {Sleutjes, BTHM and Jacobsen, AB and Tankisi, H and Sirin, NG and Oge, AE and Henderson, RD and van Doorn, PA and van den Berg, LH and van Eijk, RPA},
title = {Quantifying motor unit loss prior to functional impairment in muscles affected by amyotrophic lateral sclerosis.},
journal = {Clinical neurophysiology practice},
volume = {11},
number = {},
pages = {538-542},
pmid = {42434198},
issn = {2467-981X},
abstract = {OBJECTIVES: The compound muscle action potential (CMAP) scan is a non-invasive method for deriving motor unit number estimates (MUNE) to track disease progression in muscles affected by amyotrophic lateral sclerosis (ALS). It remains to be established whether and how long motor unit loss precedes functional impairment.

METHODS: In 56 patients with ALS, we compared the longitudinal trajectories of MUNE derived from thenar CMAP scans, and fine motor function (FMF) using a functional rating scale. Linear and sigmoidal disease trajectories were modelled from which time differences were estimated between these measures to reach their half-maximum scores.

RESULTS: The normalized linear decline per month was 0.02 (95% CI 0.01 to 0.03) for FMF and 0.03 (95% CI 0.03 to 0.04) for MUNE. Half-maximum of FMF was reached after 26.3 months (95% CI 18.9 to 35.1) for the linear model, while MUNE had a shorter time required to reach 50% of its maximum with 13.0 months (95% CI 10.3 to 16.4). The head-to-head comparison between FMF and MUNE showed that MUNE values reached 50% of its maximum 13.1 months (95% CI 7.0-20.8) earlier. Results were similar for sigmoidal disease trajectories.

CONCLUSIONS: Simulated disease trajectories of MUNE values derived from CMAP scans in muscles affected by ALS indicated that MUNE may reach 50% of its maximum in approximately 60% of the time compared to functional impairment.

SIGNIFICANCE: These explorative findings underscore how neurophysiological measures may be of use for early disease monitoring, with relevance for both care and research settings.},
}

@article {pmid42434808,
year = {2026},
author = {Baker, B and Emerson, S and Tran, T and Mohapatra, N and Wang, D and Zaw, T and Doshi, A and Lopez, JM and Hassan, D and Kumar, P and Farmer, D and Wang, A},
title = {Brain targeting and trafficking of extracellular vesicles in central nervous system diseases: a therapeutic roadmap.},
journal = {Nanomedicine (London, England)},
volume = {},
number = {},
pages = {1-19},
doi = {10.1080/17435889.2026.2698782},
pmid = {42434808},
issn = {1748-6963},
abstract = {Extracellular vesicles (EVs) mediate intercellular signaling in the central nervous system (CNS) by transferring lipids, proteins, and nucleic acids among neurons, glia, endothelium, and immune cells. Brain targeting depends on a linked sequence: EV ligands and adsorbed protein coronas engage receptor modules, select endocytic routes, determine intracellular fate, and define the therapeutic readouts. These fates include lysosomal degradation, recycling, rare cytosolic delivery, or transport across the blood-brain barrier (BBB). In disease, the same pathways can disseminate proteopathic seeds and amplify neuroinflammation. Heparan sulfate proteoglycans (HSPGs) and LDL receptor family members, including low-density lipoprotein receptor-related protein 1 (LRP1), regulate tau, α-synuclein, and amyloid-β handling. Phosphatidylserine readers and complement shape myeloid sink capture and inflammatory output. Integrin, tetraspanin, and ICAM-1 nanoclusters influence avidity, organotropism, and immune suppression. At the BBB, endothelial HSPGs, LRP1, and transferrin receptor (TfR) support receptor-mediated uptake, motivating engineered ligands such as rabies virus glycoprotein-derived peptides, Angiopep-2, and TfR binders. However, endosomal escape remains a major kinetic barrier to nucleic acid delivery. We synthesize these principles across Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, glioblastoma, and demyelinating disease, and outline design and assay standards needed to translate EV biology into safe, manufacturable CNS therapeutics.},
}

@article {pmid42435104,
year = {2026},
author = {Qiao, Y and Ma, ZS},
title = {Deterministic selection and compositional turnover in Parkinson's disease-associated gut dysbiosis.},
journal = {Antonie van Leeuwenhoek},
volume = {119},
number = {8},
pages = {},
pmid = {42435104},
issn = {1572-9699},
support = {NSFC Grant# 72274192//National Natural Science Foundation of China/ ; },
mesh = {*Parkinson Disease/microbiology/complications ; *Dysbiosis/microbiology ; Humans ; *Gastrointestinal Microbiome ; *Bacteria/classification/genetics/isolation & purification ; },
abstract = {The scientific understanding of links between Parkinson's disease (PD) and gut microbiome dysbiosis has advanced significantly, yet the ecological mechanisms driving these microbial changes remain poorly understood. To address this gap, we postulated that PD-associated gut dysbiosis arises as harmful microbes outcompete beneficial bacteria, and consequently any therapeutic strategies must both suppress opportunistic pathogens and restore protective, fiber-degrading microbes to effectively rebalance the gut microbiome in PD. To evaluate ecological patterns consistent with this hypothesis, we apply Sloan's near-neutral model (SNM), Ning et al.'s stochasticity framework, and ecological network analysis to reanalyze six published gut microbiome datasets (1957 samples total: 804 healthy controls, 1153 PD cases). We first applied SNM to categorize bacterial species as neutral, positively selected, or negatively selected. While the overall proportions of these categories were similar between groups (neutral: ~ 40%, positively selected: ~ 47%, negatively selected: ~ 13%), stochasticity framework analysis revealed significantly stronger deterministic selection in PD microbiomes. Shared species analysis (SSA) resolved this apparent paradox by demonstrating substantial compositional shifts within each species category, indicating that while classification frequencies remained stable, the specific microbes occupying these ecological niches changed significantly in PD. This divergence between SNM category proportions and NSR values highlights a subtle yet critical aspect of community assembly dynamics. Ecological network analysis further revealed that neutral species had fewer antagonistic co-occurrence links, consistent with their ecological equivalence, while negatively selected species maintained higher relative abundances in both groups. Together, these findings indicate that PD-associated gut microbiomes are characterized by stronger deterministic assembly signatures and substantial compositional turnover within near-neutral ecological categories. These patterns are consistent with altered ecological assembly signatures in PD-associated dysbiosis.},
}

*Parkinson Disease/microbiology/complications
*Dysbiosis/microbiology
Humans
*Gastrointestinal Microbiome
*Bacteria/classification/genetics/isolation & purification

@article {pmid42435587,
year = {2026},
author = {Domínguez-García, A and Delgado-Uriarte, JC and Cervantes-Arriaga, A},
title = {Precision therapeutics and innovative clinical trial design in neurodegenerative diseases.},
journal = {Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion},
volume = {78},
number = {4},
pages = {100050},
doi = {10.1016/j.ric.2026.100050},
pmid = {42435587},
issn = {2564-8896},
abstract = {Neurodegenerative diseases are biologically heterogeneous disorders characterized by progressive neuronal dysfunction, overlapping molecular pathologies, and limited disease-modifying therapies. Advances in biomarker development, molecular staging, and precision medicine are reshaping therapeutic strategies and clinical trial design across Parkinson's disease, Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, Huntington's disease, and related disorders. This review summarizes emerging therapeutic approaches, including monoclonal antibodies targeting protein aggregation, immune-modulating and metabolic interventions, antisense oligonucleotides, gene replacement and genome-editing strategies, stem cell-based therapies, and neurosurgical delivery platforms and neuromodulation technologies. It also examines evolving clinical trial methodologies such as biomarker-enriched recruitment, adaptive and delayed-start designs, platform trials, decentralized models, and master protocols. Additional emphasis is placed on diagnostic biomarkers, multimodal artificial-intelligence pipelines, systems-biology perspectives, network-based therapeutic strategies, and the reproducibility and interpretability requirements for computational tools. Despite recent progress, major challenges remain, including biological heterogeneity, limited translatability of preclinical models, delivery barriers, long-term safety concerns, and inequities in access to biomarker-based care and trial participation. Future directions will require combination therapies, integrated biomarker pipelines, preventive strategies, and pragmatic trial systems capable of translating biological advances into durable and equitable clinical benefit.},
}

@article {pmid42436372,
year = {2026},
author = {Roy, T and Ramesh, M and Nizam, NAA and Tandiono, S and Al-Jamal, KT and Al-Chalabi, A and Iacoangeli, A and Al Khleifat, A},
title = {Plasma exosomal HERV-K transcripts are increased in amyotrophic lateral sclerosis.},
journal = {BMC neuroscience},
volume = {27},
number = {1},
pages = {},
pmid = {42436372},
issn = {1471-2202},
support = {303476//National Institute for Health and Care Research/ ; MRC (MR/Z505705/1)//South London and Maudsley NHS Foundation Trust/ ; LS Association Milton Safenowitz Research Fellowship (RE19765)//NIHR Maudsley Biomedical Research Centre/ ; RE23378//LifeArc/ ; 1819242//Dementia Consortium/ ; 1122462/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/Z505705/1/MRC_/Medical Research Council/United Kingdom ; },
abstract = {Human endogenous retrovirus-K (HERV-K) reactivation is increasingly implicated in amyotrophic lateral sclerosis (ALS), with ongoing clinical trials investigating antiretroviral therapies. However, there is limited understanding of how HERV-K is trafficked in peripheral biofluids, and the role of exosomes, nano-sized extracellular vesicles, in this process remains largely unexplored. Exosomes offer a stable and cell-specific cargo reservoir that may reflect central pathogenic processes and serve as a minimally invasive biomarker source. In this study, we isolated plasma-derived exosomes from ALS patients (n = 21) and healthy controls (n = 16), and quantified exosomal HERV-K gag, env, and pol transcript levels using SYBR Green qPCR with RNase treatment and normalization to both traditional and exosome-enriched reference genes. HERV-K pol expression was significantly elevated in ALS, with fold-changes ranging from 1.59 to 1.85 (P = 0.037-0.051). env and gag also showed increased expression, though with greater variability. Normalization to the exosome-specific gene SOD2 provided the most consistent signal. These findings suggest that exosomal HERV-K transcripts, particularly pol, could serve as accessible biomarkers for patient stratification and treatment monitoring in HERV-K-targeted ALS trials. This work establishes proof-of-concept for using exosomal cargo to track endogenous retroviral activity in neurodegeneration and supports further investigation of liquid biopsy approaches in ALS precision medicine.},
}

@article {pmid42436431,
year = {2026},
author = {Parks, ASE and Conn, LG and Abrahao, A and Zinman, L and Sale, JEM},
title = {"Straddling two worlds": complexities of spousal caregiving in amyotrophic lateral sclerosis during younger middle age.},
journal = {BMC palliative care},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12904-026-02230-w},
pmid = {42436431},
issn = {1472-684X},
abstract = {BACKGROUND: Family support is central to amyotrophic lateral sclerosis (ALS) care. Spouses often assume the role of primary caregiver, facing daily challenges as their partner's needs progressively increase. Younger ALS caregivers appear to have distinct experiences and needs, yet age- or life-stage variations and processes of caregiving are seldom considered in studies of ALS family caregiver experience.

METHODS: We undertook a qualitative study, guided by constructivist grounded theory methodology, to explore the dynamics of family caregiving following an ALS diagnosis in a younger middle-aged family member (≤55 years). Data were coded to identify psychosocial processes, including how family caregivers engage in caregiving.

RESULTS: In-depth interviews were conducted with ten spousal caregivers between August 2023 and August 2025. Overall, our theoretical understanding of spousal caregiving for younger middle-aged adults with ALS (YMAs) was captured by the core category 'straddling two worlds,' reflecting how caregivers navigated multiple interconnected dichotomies: present and future, familiar and new norms, current and anticipated losses, and the worlds of the living and the dying. To contend with an uncertain future, caregivers anchored themselves in the present as they navigated a shifting sense of normalcy. Middle age expectations and social norms shaped how caregivers engaged in caregiving and experienced losses that were often unending and ambiguous.

CONCLUSIONS: Caregiving for a spouse with ALS in younger middle age involves temporal, practical, emotional, and existential processes. Caregivers of YMAs may benefit from interventions that help them tolerate uncertainty, stay grounded in the present, maintain normalcy, and grieve losses throughout the caregiving trajectory.},
}

@article {pmid42436563,
year = {2026},
author = {Gregory, JM},
title = {Context of use matters: interpreting extracellular vesicle TDP-43 as a biomarker in ALS.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-026-02376-x},
pmid = {42436563},
issn = {2051-5960},
}

@article {pmid42432003,
year = {2026},
author = {Chen, J and Xu, P and Chen, M and Lu, Z and Li, X and Stampas, A and Zong, Y and Zhou, P},
title = {Compound muscle action potential scan dataset in adults with spinal cord injury and healthy controls.},
journal = {Scientific data},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41597-026-07864-2},
pmid = {42432003},
issn = {2052-4463},
support = {ZR2024QH582//Natural Science Foundation of Shandong Province/ ; ZR2024YQ077//Natural Science Foundation of Shandong Province/ ; tsqn202211226//Taishan Scholar of Shandong Province/ ; tstp20221144//Taishan Scholar of Shandong Province/ ; 25S11907200//Science and Technology Commission of Shanghai Municipality/ ; KFKT-2024-KF-013//Chinese Association of Rehabilitation Medicine/ ; 82572355//National Natural Science Foundation of China/ ; },
abstract = {Certain neurological conditions, such as amyotrophic lateral sclerosis (ALS) and spinal cord injury (SCI), result in motor unit loss in muscles. The stimulus-evoked compound muscle action potential (CMAP) scan captures comprehensive information on motor unit recruitment that enables rapid and non-invasive assessment of motor unit status. However, few publicly available CMAP scan datasets exist to support research on motor unit number estimation (MUNE). To address this gap, we collected CMAP scan data from the first dorsal interosseous (FDI) muscle of 13 individuals with SCI and 13 healthy participants, and established a dedicated CMAP scan dataset. The dataset includes CMAP waveforms evoked by each nerve stimulus from which CMAP scan curve and typical parameters were extracted for direct use. All SCI participants underwent multiple clinical assessments and exhibited a spectrum of impairment severity from mild to severe, resulting in diverse CMAP features. We anticipate that this dataset will facilitate the development of advanced CMAP scan-based assessment techniques and aid in the investigation of neuromuscular impairment.},
}

@article {pmid42432423,
year = {2026},
author = {Sugisawa, R and Sekiguchi, K and Noda, Y and Matoba, S and Suehiro, H and Kozuki, J and Tanaka, T and Chihara, N},
title = {Quantitative Spatiotemporal Analysis of Ultrasound Images of Fasciculations in ALS.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70338},
pmid = {42432423},
issn = {1097-4598},
support = {JP256f0137011//Japan Agency for Medical Research and Development/ ; 25K14534//Japan Society for the Promotion of Science/ ; 24K14297//Japan Society for the Promotion of Science/ ; },
abstract = {INTRODUCTION/AIMS: Fasciculations are a hallmark of amyotrophic lateral sclerosis (ALS), yet quantitative description of individual events on muscle ultrasound (MUS) is limited. We characterized the spatiotemporal kinematics of individual fasciculations to determine whether they differ between ALS and other neurogenic conditions.

METHODS: We retrospectively analyzed biceps brachii MUS recordings from 680 examinations (January 2020-June 2025), identifying 74 ALS and 40 non-ALS neurogenic recordings with fasciculations (167 and 62 segments). After propensity score matching for age and muscle strength, 62 matched pairs were analyzed. The Lucas-Kanade optical flow algorithm, which estimates frame-to-frame displacement vectors from local intensity gradients, was applied at 1-pixel intervals (57,600 points per 240 × 240 region; ≈60 μm) to quantify twitch durations, peak displacement velocity, and directional anisotropy as a measure of spatial movement coherence.

RESULTS: ALS fasciculations showed prolonged total duration (582.8 ± 112.8 ms vs. 489.2 ± 128.7 ms, p < 0.001), reduced directional anisotropy (0.534 ± 0.245 vs. 0.627 ± 0.215, p = 0.028), and lower peak displacement velocity (6.55 ± 6.56 vs. 9.53 ± 9.07 μm/ms, p = 0.039). MANOVA showed significant multivariate differences (Pillai's trace = 0.317 ± 0.030, p < 0.001) with moderate group separation (Mahalanobis distance = 1.10 ± 0.05).

DISCUSSION: ALS fasciculations showed spatially heterogeneous and temporally prolonged contraction patterns, suggesting motor units in a transitional state of incomplete reinnervation, distinct from the more stable architecture of chronic neurogenic disorders. This framework may complement existing ultrasound assessment and aid the study of motor unit pathology in ALS.},
}

@article {pmid42432439,
year = {2026},
author = {Kavale-Henderson, LA and Buckberry, J and Buckley, H and Cameron, C and King, C and Koon, H and Petchey, P and Snoddy, AME and Loch, C},
title = {"An Injurious and Utterly Unfit Environment": A Case Study Comparing Dental Evidence of Childhood Stress in Nineteenth Century Working-Class Peoples From British and Colonial New Zealand Contexts.},
journal = {American journal of biological anthropology},
volume = {190},
number = {3},
pages = {e70315},
pmid = {42432439},
issn = {2692-7691},
support = {21-UOO-01//Ministry of Business, Innovation and Employment/ ; //University of Otago/ ; },
mesh = {Humans ; New Zealand ; History, 19th Century ; United Kingdom ; Child ; Adult ; Male ; *Tooth/pathology ; *Stress, Psychological/pathology/history ; Female ; Child, Preschool ; Young Adult ; Infant ; Adolescent ; Transients and Migrants/history ; },
abstract = {OBJECTIVES: During the nineteenth century, the health and living conditions of many working-class European peoples declined in association with growing industrialization and urbanization. Emigration to British colonies grew as people sought to escape such hardships. This research presents the first direct comparison of dental markers of stress in a case study of migrants to a British colony (Otago, New Zealand) alongside a contemporaneous assemblage representing an origin population (London, United Kingdom).

MATERIALS AND METHODS: Dental markers of childhood stress, accentuated lines, were observed in thin-sections of archeological teeth from adults (n = 9) and children (n = 16) interred in London, United Kingdom (UK), and adult European migrants interred in Otago, New Zealand (NZ) (n = 24) using standard histological techniques.

RESULTS: All individuals interred in London, and 92% (22/24) of those in New Zealand exhibited evidence of accentuated line formation within the first 2.5 years of life. There was no difference in median accentuated line occurrence between adults and children interred in the UK. However, NZ adults had a lower median occurrence of accentuated lines over the first 2.5 years since birth (5 ALs/individual) than UK adults (13 ALs/individual). Accentuated lines most frequently occurred in infancy for all three groups examined. However, temporal trends in accentuated line occurrence differed between groups in association with age.

DISCUSSION: These results highlight the impact of childhood stresses on working-class people growing up during the nineteenth century, underlining potential differences in the childhood experiences of hardship in individuals that remained in Britain and those that departed for foreign soils.},
}

Humans
New Zealand
History, 19th Century
United Kingdom
Child
Adult
Male
*Tooth/pathology
*Stress, Psychological/pathology/history
Female
Child, Preschool
Young Adult
Infant
Adolescent
Transients and Migrants/history

@article {pmid42427320,
year = {2026},
author = {Uchino, A and Kanemaru, K and Tarutani, A and Hasegawa, M and Naruse, H and Ishiura, H and Murayama, S and Saito, Y},
title = {Frontotemporal Lobar Degeneration-TDP Type C With Striatal Glial Cytoplasmic Inclusions and Motor Neuron Degeneration.},
journal = {Neuropathology and applied neurobiology},
volume = {52},
number = {4},
pages = {e70090},
pmid = {42427320},
issn = {1365-2990},
support = {JP21wm0425019//Japan Agency for Medical Research and Development/ ; JP25wm0625126//Japan Agency for Medical Research and Development/ ; JP24dk0207074h0001//Japan Agency for Medical Research and Development/ ; JP22H04923//MEXT/JSPS KAKENHI/ ; JPMH23FC1008//Research on rare and intractable diseases Program/ ; },
mesh = {Humans ; *Inclusion Bodies/pathology ; *Frontotemporal Lobar Degeneration/pathology ; *Neuroglia/pathology ; *DNA-Binding Proteins/metabolism ; *Motor Neurons/pathology ; *Corpus Striatum/pathology ; Male ; *Motor Neuron Disease/pathology ; Female ; Aged ; },
abstract = {We report an autopsy case of frontotemporal lobar degeneration (FTLD)-TDP type C with severe striatal involvement and annexin A11- and phosphorylated TDP-43-positive glial cytoplasmic inclusions. The patient developed progressive asymmetric rigidity accompanied by marked striatal atrophy and showed both upper and lower motor neuron involvement. These findings expand the clinicopathological spectrum of FTLD-TDP type C and may support the concept of an annexin A11-associated pathogenic continuum linking FTLD and amyotrophic lateral sclerosis.},
}

Humans
*Inclusion Bodies/pathology
*Frontotemporal Lobar Degeneration/pathology
*Neuroglia/pathology
*DNA-Binding Proteins/metabolism
*Motor Neurons/pathology
*Corpus Striatum/pathology
Male
*Motor Neuron Disease/pathology
Female
Aged

@article {pmid42427517,
year = {2026},
author = {Chen, Y and Zhang, S},
title = {AART enables fast and accurate cross-platform proteomic translation.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.06.29.735313},
pmid = {42427517},
issn = {2692-8205},
abstract = {Plasma proteomic profiling has been widely used for biomarker discovery, disease prediction and diagnosis, and patient stratification. However, technical differences across assay platforms often result in low-to-moderate agreement, limiting study reproducibility, data integration, and model transferability. Here we present AART, a cross-platform proteomic translation framework that integrates matched-protein ridge regression with proteome-wide residual learning. We benchmarked AART spanning three independent cohorts profiled using three major platforms, including Olink, SomaScan, and mass spectrometry. Across all six translation directions, AART achieved the best performance compared with baseline methods for both overlapping and non-overlapping protein translations, with a relative improvement of 92.0% on average over direct mapping and by up to 31.6% over cpiVAE, the strongest baseline. Proteins that were accurately translated and improved by AART were enriched for extracellular, vesicle-associated, and tissue-restricted plasma biology. In downstream applications, AART improved the reproducibility of proteomic association analyses relative to direct cross-platform comparison by 75.5% for type 2 diabetes and 370.6% for Alzheimer's disease. AART-enabled cohort integration enhanced diagnostic accuracy for amyotrophic lateral sclerosis by 92.6% compared with non-integration analysis. AART was overall one to three orders of magnitude faster than cpiVAE, facilitating biobank-scale applications. Together, these results establish AART as a fast, accurate, and scalable framework for cross-platform proteomic translation, enabling more reproducible, transferable, and integrated proteomic research.},
}

@article {pmid42427576,
year = {2026},
author = {Wang, H and Sun, S and Mathé, EA and Zhu, Q},
title = {RD-OMICS: An Integrative Multi-Omics Data Inventory in Rare Diseases.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.06.29.735296},
pmid = {42427576},
issn = {2692-8205},
abstract = {Rare diseases (RD) impact over 30 million individuals in the United States, yet fewer than 5% of the identified conditions have FDA-approved treatments. Progress in RD research is hindered by small patient cohorts, biological heterogeneity, and the fragmented, inconsistently annotated publicly available omics data, which limits integrative analysis and translational discovery. Here, we present RD-OMICS, a data inventory with integrated and structured RD omics data from Gene Expression Omnibus (GEO), in the form of a knowledge graph. We developed a metadata harmonization pipeline that combines rule-based mapping and large language model (LLM)-assisted semantic categorization. The graph-based data model was defined to integrate different types of data including disease conditions, experiments, samples, platforms, projects, and publications into a centralized inventory graph. In this preliminary study, 11,049 GEO series for 126 rare diseases were processed and integrated into RD-OMICS, which includes 375,930 individual biospecimen samples, 1,578 sequencing and array platforms, 10,938 biological projects. Case studies demonstrate the use of RD-OMICS in supporting rare disease research, omics cohort construction, and transcriptome-based drug repurposing for amyotrophic lateral sclerosis (ALS). RD-OMICS provides a scalable foundation for transforming fragmented omics data into a structured, harmonized and interoperable resource, facilitating therapeutic development and other translational discoveries in rare diseases.},
}

@article {pmid42427672,
year = {2026},
author = {Dixon, E and Azimian, F and Joby Chacko, A and Tatum, R and Boykin, C and Chen, YH and Lu, Q},
title = {Small molecules targeting ARF1 interaction with C9orf72:SMCR8:WDR41 complexes suppress its overactivation implicated in ALS/FTD.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.01.24.701325},
pmid = {42427672},
issn = {2692-8205},
abstract = {The hexanucleotide repeat expansion in C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). The C9orf72 protein forms a complex with SMCR8 and WDR41 (CSW), which functions as a GTPase-activating protein (GAP) regulating ARF1 and RAB small GTPases. While these findings implicated ARF1-GAP dysregulation in ALS/FTD and supported ARF1 suppression as potential intervention, small molecules that modulate ARF1-CSW interactions are lacking. In this study, we demonstrated upregulation of tyrosine-phosphorylated (Tyr-782) ASAP1 (also known as AMAP1, DDEF1, or Centaurin β4), an ARF-GAP, in human motor cortex of both sporadic ALS and ALS with C9orf72 mutations. Ectopic C9orf72 expression partially mimicked the effects of a known ARF1 inhibitor brefeldin A to disperse Golgi apparatus. Computer-aided rational drug design with high-throughput in-silico screening identified MCULE-5095997944 (Named as SCC944) as a ARF1-CSW modulator. SCC944 binds directly to ARF1 and reduced GTP-bound ARF1 levels upon ARF1 activation. SCC944 demonstrated brefeldin A-like ARF1-dependent alteration of organelle organization including Golgi, microtubules, and mitochondria, but also a protein trafficking pattern that is distinct from brefeldin A mechanism. These studies identified the first small molecule targeting ARF1-CSW interaction and further support ARF1 modulation as a potential therapeutic approach for ALS/FTD.},
}

@article {pmid42428129,
year = {2026},
author = {Raemaekers, M and Geukes, SH and Aarnoutse, EJ and Branco, MP and Freudenburg, ZV and Schippers, A and Crone, NE and Leinders, S and Berezutskaya, J and Ramsey, NF and Vansteensel, MJ},
title = {Association between motor cortex grey matter loss and inability to control an ECoG-based implanted Brain-Computer Interface in ALS.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.06.23.26355654},
pmid = {42428129},
abstract = {BACKGROUND: The field of implantable Brain-Computer Interfaces (iBCIs) is rapidly advancing, with individuals with amyotrophic lateral sclerosis (ALS) as key beneficiaries. However, ALS-related cortical degeneration may impair iBCI effectiveness. This study investigated whether structural magnetic resonance imaging (MRI) and functional MRI (fMRI) metrics are associated with the quality of electrocorticography (ECoG) signals critical for iBCI use.

METHODS: Six late-stage ALS participants and 76 controls underwent T1-weighted structural MRI and task-based fMRI during right-hand movement or attempts thereof. ECoG data of ALS participants was benchmarked using ECoG data acquired in epilepsy patients. Grey matter thickness in the sensorimotor cortex and fMRI activation in the motor-hand area were measured.

RESULTS: Four ALS participants showed >0.4 mm thinning in the precentral gyrus, while the postcentral gyrus was spared. ECoG signal quality was significantly associated with precentral grey matter thickness, but not with fMRI activity.

CONCLUSIONS: These findings suggest that presurgical assessment of precentral grey matter thickness could potentially prove useful for iBCI candidate selection in advanced ALS.

PLAIN LANGUAGE SUMMARY: People with amyotrophic lateral sclerosis (ALS) can lose the ability to move and speak, but their thinking often remains intact. Implantable brain-computer interfaces (iBCIs) can help by translating brain signals into commands for communication devices. However, ALS damages the motor cortex, which may reduce the quality of these signals. In this study, we examined brain scans and electrical recordings from six people with advanced ALS. We found that thinning of the motor cortex was linked to weaker brain signals needed for iBCI control, while functional MRI activity was less predictive. This suggests that measuring motor cortex thickness before surgery could help identify who will benefit most from an iBCI, improving treatment decisions and future clinical trials.

TWO SENTENCE SUMMARY: We examine presurgical MRI/fMRI and ECoG recordings from people with advanced ALS receiving implanted brain-computer interfaces. Motor cortex thinning is associated with poorer ECoG signal quality, suggesting cortical thickness may help identify candidates likely to benefit.},
}

@article {pmid42428455,
year = {2026},
author = {Cheng, P and Liu, S and Shen, Q},
title = {Laparoscopic temporary uterine artery occlusion combined with en bloc lesion resection for type III cesarean scar pregnancy: surgical technique.},
journal = {Gynecology and pelvic medicine},
volume = {9},
number = {},
pages = {16},
pmid = {42428455},
issn = {2617-4499},
abstract = {This article presents a refined laparoscopic surgical technique for the management of type IIIb cesarean scar pregnancy (CSP), as classified by Ban et al.'s 2023 criteria [residual myometrial thickness <3 mm, maximum sac diameter (MSD) ≥3 cm, bladder protrusion], in a 35-year-old female with vaginal bleeding and a history of two cesarean sections. The core protocol integrates temporary bilateral uterine artery occlusion (simple ligation of the main trunk with No. 1 absorbable Vicryl suture at 2 cm from the uterine wall) immediately before resection, adhesiolysis, en bloc excision of the ectopic mass with a 0.3 cm safe margin, and multilayer anatomical uterine repair. This technique addresses the key clinical challenge of massive intraoperative bleeding in highly vascular type IIIb CSP, with innovations in precise timing of occlusion and reversible minimally invasive ligation. Perioperative outcomes demonstrated excellent hemostasis (total blood loss 100 mL), complete lesion removal confirmed by frozen section, and intact uterine anatomy post-surgery. The study emphasizes the technique's value in hemorrhage control, anatomical restoration, and fertility preservation for patients with large type IIIb CSP (66 mm in this case). We provide a detailed step-by-step surgical guide, clarify patient selection criteria and contraindications, and discuss the technique's advantages, limitations, and potential to revise the standard of care for type III CSP. Postoperative 18-month follow-up showed successful natural conception and uncomplicated second-trimester pregnancy, validating its long-term fertility benefits.},
}

@article {pmid42428795,
year = {2026},
author = {Craig, EJ and Ryan, VH},
title = {Dysregulated neuronal mRNA transport and translation in FTD/ALS.},
journal = {NPJ dementia},
volume = {2},
number = {1},
pages = {56},
pmid = {42428795},
issn = {3005-1940},
abstract = {Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are fatal, co-occurring neurodegenerative disorders. Dysregulation of mRNA metabolism, transport, and local translation is a significant mechanism contributing to FTD/ALS. Here, we review the processes of neuronal RNA transport and translation, their disruption in FTD/ALS, and mechanistic interplay between the two. Finally, we discuss current progress targeting transport and translation defects and identify potential future directions for therapeutic development.},
}

@article {pmid42428879,
year = {2026},
author = {Hermosillo-Abundis, C and Arias-Carrion, O and Contreras-Ibáñez, C and Mendez-Rojas, MA},
title = {From Air to Brain: Environmental Nanoparticles as Modifiable Risk Factors for Neurodevelopmental, Neurodegenerative, and Mental Disorders.},
journal = {ACS omega},
volume = {11},
number = {26},
pages = {38267-38287},
pmid = {42428879},
issn = {2470-1343},
abstract = {Ultrafine particles (≤100 nm) and other environmental nanoparticles have emerged as biologically active pollutants that can cross biological barriers, including the blood-brain barrier and the placenta. Growing evidence implicates ultrafine particles in a wide range of neuropsychiatric conditions, yet their effects remain poorly integrated into clinical and public health frameworks. In this review, we distinguish between size-defined ultrafine particles (UFPs, ≤100 nm), composition-defined environmental nanoparticles originating from combustion and secondary formation processes, and engineered nanomaterials (ENPs), which differ in physicochemical properties, exposure scenarios, and regulatory status. This narrative systematic review synthesizes findings from human and experimental studies on the neuropsychiatric and neurodevelopmental effects of environmental nanopollutants. A structured search was conducted in PubMed, Web of Science, Scopus, and Google Scholar up to November 2025, following explicit inclusion and exclusion criteria. Eligible studies included peer-reviewed human and animal research assessing mental health or neurological outcomes of nanopollutant exposure. Epidemiological studies(?)primarily involving traffic-related air pollution and mixed combustion-derived ultrafine particle exposures(?)suggest associations with increased risk of cognitive impairment, autism spectrum disorder, depression, schizophrenia, and neurodegenerative diseases, including Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. Prenatal and early life exposures were linked to cortical thinning, altered neurodevelopmental trajectories, and early proteinopathies. Underlying mechanisms include neuroinflammation, oxidative stress, and protein aggregation. Despite methodological heterogeneity, the evidence supports the urgent need for regulation and prevention. Environmental nanopollutants constitute an under-recognized, modifiable risk factor for neuropsychiatric and neurodegenerative conditions. A paradigm shift is needed to incorporate environmental exposure history into mental health research, risk assessment, and prevention strategies. Regulatory action targeting nanopollutant emission and exposure, particularly in vulnerable populations, is critical to mitigating long-term neurological consequences.},
}

@article {pmid42429266,
year = {2026},
author = {Macpherson, CE and Muccini, J and Blacutt, ME and Bjalme-Evans, M and Lough, ME and Quinn, L},
title = {Gait speed and future ambulatory status in amyotrophic lateral sclerosis: a retrospective observational study with implications for power wheelchair referral.},
journal = {Physiotherapy theory and practice},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/09593985.2026.2700400},
pmid = {42429266},
issn = {1532-5040},
abstract = {BACKGROUND OR INTRODUCTION: Amyotrophic lateral sclerosis (ALS) causes rapid and progressive loss of ambulation resulting in immobility. A power wheelchair (PWC) increases safety, independence, and quality of life, however, the PWC referral process is lengthy and complex. When the PWC is delayed, immobility complications can occur. One barrier is the lack of a universal predictive "gait speed threshold" to help clinicians determine when to initiate the PWC referral process.

OBJECTIVE OR PURPOSE: Identify a clinically relevant gait speed threshold associated with future loss of ambulation in people with ALS.

METHODS: This was a retrospective chart review of a single multidisciplinary ALS Center of Excellence from July 1, 2016 - July 1, 2019 (36-months). Participants were included in this study if they were adults (age >18 years) with clinically definite ALS who were ambulatory at baseline. The primary outcome was gait speed on the 10-meter walk test. Secondary outcomes included the ALS Functional Rating Scale-Revised, forced vital capacity, falls, and ambulation status.

RESULTS: Of N = 180 people with ALS identified during the study period, n = 72 met inclusion for analysis with a mean age 66.1 ± 11.9 years, 64% male, 76% with an ALS phenotype of spinal onset, and 24% bulbar onset. A gait speed threshold of 0.79 m/s maximized the combined sensitivity and specificity for classifying ambulatory status at the subsequent 6-month visit. Faster gait speeds (>1.2-1.4 m/s) were associated with greater odds of remaining ambulatory at 6-months based on Bayesian logistic regression.

CONCLUSION: A gait speed threshold of 0.79 m/s was associated with increased likelihood of subsequent loss of ambulation, though modest predictive accuracy limits its use as a stand-alone indicator. Gait speed may serve as one component of clinical decision-making regarding PWC planning and referral in people with ALS. Larger multicenter studies are needed to confirm and generalize results across ALS phenotypes.},
}

@article {pmid42429841,
year = {2026},
author = {Li, D and Ye, Q},
title = {Re: Effects of resistance training with/without photobiomodulation on muscle and respiratory function in difficult-to-control asthma: a randomized trial.},
journal = {Lasers in medical science},
volume = {41},
number = {1},
pages = {},
pmid = {42429841},
issn = {1435-604X},
support = {2022KY1159, 2025KY1423, 2025KY1417 and 2025HY1019//Zhejiang Provincial Medical and Health Plan/ ; 2022020405//Ningbo High-Level Medical and Health Team Major Tackling Project and the Talent Development Program/ ; 2026-A36//Ningbo Municipal Key Modern Medical Discipline Development Project/ ; No.2024Z222//Key Technology Breakthrough Program of 'Ningbo Sci-Tech Innovation Yongjiang 2035'/ ; Yongweifa 2024-102-77//Ningbo Municipal Specialized Training Program for Young Technical Backbone Talents in Health/ ; },
mesh = {Humans ; *Resistance Training ; *Asthma/therapy/physiopathology/radiotherapy ; *Low-Level Light Therapy/methods ; Muscle Strength/radiation effects ; },
abstract = {This letter discusses Costa et al.'s randomized trial of resistance training (RT) combined with photobiomodulation therapy (PBMT) for difficult-to-control asthma (DTCA). The triple-blind study shows RT+PBMT safely improves peripheral muscle strength and exercise capacity better than RT alone. PBMT has dose-dependent effects, but optimal parameters for chronic respiratory patients remain unclear. Some clinicians have proposed standalone PBMT for DTCA patients unable to complete resistance training, but this approach has not been validated in clinical trials. The absence of a PBMT-only group limits assessment for patients unable to tolerate RT. The intervention did not improve lung function or asthma control, acting only peripherally. RT+PBMT is a useful adjuvant therapy; future studies should optimize PBMT dosing, test standalone PBMT, and examine long-term outcomes, and compare different PBMT wavelengths, energy settings and irradiation sites to refine real-world treatment protocols.},
}

Humans
*Resistance Training
*Asthma/therapy/physiopathology/radiotherapy
*Low-Level Light Therapy/methods
Muscle Strength/radiation effects

@article {pmid42429860,
year = {2026},
author = {D'Andrea, T and Benedetti, MC and Mochi, M and De Turris, V and Rosa, A and Fucile, S},
title = {Human iPSC-Derived Spinal Neurons Carrying the ALS FUS (P525L) Mutation Exhibit Lower Response to Inhibitory Neurotransmitters.},
journal = {Cellular and molecular neurobiology},
volume = {},
number = {},
pages = {},
doi = {10.1007/s10571-026-01773-z},
pmid = {42429860},
issn = {1573-6830},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disorder characterized by motoneurons degeneration. Functional studies have linked ALS to hyperexcitability and excitotoxicity, but the cause of the disease is unknown, though familial ALS cases are linked to pathogenic variants in several genes, including SOD1, TARDBP and FUS. Here we focused on the effect of the severe FUS (P525L) mutation on the functional properties of human spinal neurons derived from induced pluripotent stem cells (hiPSCs). This mutation delayed functional maturation, as revealed by the observation that mutated neurons showed alterations of membrane potential, reduced spontaneous synaptic activity, and altered action potentials at early differentiation stages. FUS (P525L) mutation was associated with a significant alteration of inhibitory signalling transmission: mutated neurons showed a significantly lower current response to GABA and glycine compared to control isogenic WT neurons of the same age. Also, glutamatergic currents exhibited a different temporal evolution in control and mutated neurons, but at a lower extent in comparison to inhibitory neurotransmitters. The decrease in the glycine-evoked currents was confirmed by the reduction of the expression of the α1 subunit of glycine receptor, measured by immunofluorescence assay. Similar functional alterations were measured in spinal neurons differentiated form a second hiPSC line, confirming the causative role of the FUS (P525L) mutation. Our data indicate that the FUS (P525L) mutation reduces the maturation rates and the function of hiPSC-derived spinal neurons, with a strong decrease of inhibitory transmission, which may affect the excitatory/inhibitory balance, possibly predisposing to excitotoxicity and neurodegeneration.},
}

@article {pmid42430091,
year = {2026},
author = {You, Y and Duan, D and Xiang, Q},
title = {The Role of PGC-1α in Neurodegenerative Diseases: Molecular Mechanisms, Translational Challenges, and Therapeutic Potential.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42430091},
issn = {1559-1182},
mesh = {Humans ; *Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism ; *Neurodegenerative Diseases/metabolism/therapy ; Animals ; Mitochondria/metabolism ; *Translational Research, Biomedical ; *Translational Science, Biomedical ; },
abstract = {Neurodegenerative diseases (NDDs) are progressive disorders in which mitochondrial dysfunction, oxidative stress, proteostasis failure, neuroinflammation, and synaptic damage progressively interact to drive neuronal vulnerability. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) links metabolic adaptation to stress-response pathways that are repeatedly disrupted in Alzheimer's disease, Parkinson's disease, Huntington's disease, polyglutamine (PolyQ) disorders, and amyotrophic lateral sclerosis. Rather than providing only an updated catalogue of studies, this review organizes the evidence into a cross-disease rheostat framework that explains why PGC-1α modulation is protective in some settings but incomplete or maladaptive in others. Current findings indicate that PGC-1α supports mitochondrial biogenesis, oxidative phosphorylation, antioxidant defense, mitophagy, autophagy, protein quality control, and inflammatory balance. However, its effects are highly context dependent. In several models, restoration of PGC-1α-related signaling improves mitochondrial function and reduces neuronal injury, whereas broad, sustained, or cell-inappropriate activation may produce limited benefit or undesirable outcomes. These observations suggest that PGC-1α is not a simple neuroprotective switch, but a flexible regulatory hub whose therapeutic value depends on cell type, isoform profile, disease stage, and activation level. Emerging strategies, including small-molecule modulators, gene delivery, antisense-based approaches, nanoparticle systems, and exercise-related interventions, remain largely preclinical and face major barriers related to CNS delivery, pathway selectivity, dose and cell-type control, peripheral safety, and validated target-engagement biomarkers. Nevertheless, clinical translation requires stronger causal validation, reliable target-engagement biomarkers, selective delivery methods, and long-term safety assessment. Future research should focus on precision-based modulation of PGC-1α to determine when and how this pathway can be safely used for disease modification. Such a careful approach may help transform PGC-1α from a broad experimental target into a clinically relevant strategy for well-defined neurodegenerative phenotypes.},
}

Humans
*Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism
*Neurodegenerative Diseases/metabolism/therapy
Animals
Mitochondria/metabolism
*Translational Research, Biomedical
*Translational Science, Biomedical

@article {pmid42430317,
year = {2026},
author = {Buczak, MK and Brignone, J and Caden Hamrick, W and Cole, KM and Bromberg, MB and Zhang, H and George, JA},
title = {Preliminary Investigation of Myoelectric Control of an Assistive Neck Exoskeleton by Individuals with Amyotrophic Lateral Sclerosis.},
journal = {IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/TNSRE.2026.3712219},
pmid = {42430317},
issn = {1558-0210},
abstract = {Neck weakness limits head control and quality of life for individuals with Amyotrophic Lateral Sclerosis (ALS). The Utah Neck Exoskeleton can restore neck motion, but current control methods-joystick and gaze tracking-have limited accessibility and reliability. These preliminary offline analyses investigate neck electromyography (EMG) as an alternative control modality from ALS patients. EMG signals were recorded from four male participants with ALS while performing neck flexion/extension, axial rotation, and lateral deviation. The resulting dataset was used to train convolutional neural networks (CNNs) per patient to classify either head position or movement direction from EMG features offline. Position classification significantly outperformed direction classification, with a mean accuracy of 82.5% ± 0.010 across participants. Performance was consistent when controlling one, two, or all three neck degrees of freedom. A subset of participants with sufficient residual motor function also completed neck movements while talking or chewing. Classification accuracy decreased during talking and chewing, although these effects were not statistically significant. Importantly however, training CNNs with diverse data that included periods of talking and chewing improved algorithm robustness across all conditions. These findings suggest that neck EMG signals can reliably predict intended head movements in ALS, even in the presence of weak and often confounding muscle activity. Offline accuracy and real-time computational speed suggest the approach is feasible for future online user-in-the-loop studies. Altogether, this pilot work advances EMG-based assistive technology for individuals with severe motor impairments, laying the groundwork for clinically viable, intuitive control systems.},
}

@article {pmid42430680,
year = {2026},
author = {Chang, CY and Price, TR and Jia, A and Cragg, JJ},
title = {Neurology® Journal Club: Duration of Current Statin Use and Amyotrophic Lateral Sclerosis Risk.},
journal = {Neurology},
volume = {107},
number = {3},
pages = {e218358},
doi = {10.1212/WNL.0000000000218358},
pmid = {42430680},
issn = {1526-632X},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/chemically induced ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects/therapeutic use ; Time Factors ; Cohort Studies ; Risk Factors ; Norway/epidemiology ; },
abstract = {This article critically appraises the study by Nakken et al., "Duration of Current Statin Use and Amyotrophic Lateral Sclerosis (ALS) Risk." Previous observational studies and Mendelian randomization studies examining statin use and ALS risk have reported mixed results. Millions of adults receive statins for cardiovascular prevention and may be concerned when neuromuscular symptoms suggestive of ALS appear. Using linked nationwide health survey and prescription data, this Norwegian population-based cohort study applied time-dependent models to evaluate statin use and subsequent ALS risk. Short-term statin use was associated with increased ALS risk, whereas long-term use was associated with lower risk. The authors interpreted this as evidence of reverse causation rather than a causal or protective effect of statins. Key strengths of the study include its large population-based design, the use of a negative control, and time-dependent Cox modeling. However, limitations inherent to observational study designs and potential residual confounding should be considered. In this article, we summarize the findings, highlight key statistical concepts, and discuss the study's major strengths and limitations.},
}

Humans
*Amyotrophic Lateral Sclerosis/epidemiology/chemically induced
*Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects/therapeutic use
Time Factors
Cohort Studies
Risk Factors
Norway/epidemiology

@article {pmid42431020,
year = {2026},
author = {Romano, C and Johar, L and Hundhausen, K and Kimonis, V},
title = {Clinical studies in 82 individuals with valosin-containing protein (VCP) associated multisystem proteinopathy and literature review.},
journal = {Neuromuscular disorders : NMD},
volume = {65},
number = {},
pages = {106469},
doi = {10.1016/j.nmd.2026.106469},
pmid = {42431020},
issn = {1873-2364},
abstract = {Valosin-containing protein (VCP) pathogenic variants cause a multisystem proteinopathy characterized by myopathy, Paget disease of bone, frontotemporal dementia, and amyotrophic lateral sclerosis (ALS). We evaluated 82 affected individuals, 14 presymptomatic carriers, and 36 unaffected first-degree relatives from 48 families to identify sensitive measures for disease monitoring. Mean age of onset was ∼42 years for myopathy, Paget disease, or ALS, and 53 years for dementia. Functional assessments included the Inclusion Body Myositis Functional Rating Scale (IBMFRS), ALSFRS-R, Fatigue Severity Scale (FSS), and six-minute walk test (6MWT). Affected individuals demonstrated progressive functional decline, with IBMFRS decreasing 1.9% annually, FSS increasing 4.4%, and 6MWT decreasing 6% annually when modeled against disease duration. Women declined more rapidly on IBMFRS but showed slower ambulatory and fatigue progression. Potential genotype-specific effects were observed, with earlier onset and shorter survival in p.Arg155Cys compared to later onset in p.Arg155His. Strong correlations among IBMFRS, FSS, and 6MWT indicate these as accessible endpoints for longitudinal monitoring and clinical trials. Rapid decline with ALS and dementia necessitates multidisciplinary support, while longer survival after myopathy or Paget onset offers a window for preventive and supportive interventions.},
}

@article {pmid42431556,
year = {2026},
author = {Singh, N and Gomes, J},
title = {Fisetin prevents deterioration of cellular functions in amyotrophic lateral sclerosis variants G262R and P438L of SQSTM1 in SH-SY5Y cells.},
journal = {Toxicology and applied pharmacology},
volume = {},
number = {},
pages = {117943},
doi = {10.1016/j.taap.2026.117943},
pmid = {42431556},
issn = {1096-0333},
abstract = {Oxidative stress is widely accepted as one of the important factors contributing to neurodegeneration, leading to fatal neurodegenerative diseases (NDD) such as Amyotrophic Lateral Sclerosis. Since flavonoids possess antioxidant properties, we investigated whether Fisetin (FS) and Quercetin (QR) protected cells from oxidative stress arising from pathogenic mutations G262R (G > A) and P438L (C > T) of SQSTM1 found in Indian ALS patients. SQSTM1 codes for p62 protein and is involved in multiple signaling pathways through its various domains. We studied changes in cell viability and cellular functions using immunoblotting, confocal microscopy, immunoprecipitation and FACS analysis in the presence and absence of FS and QR. Supplementation with FS and QR in SH-SY5Y cells expressing SQS-wild type and mutants increased cell viability and decreased ROS formation. Also, Nrf2 protein levels increased to offset oxidative stress response. In addition, we studied the effect of FS on the nuclear-cytoplasmic distribution of TDP-43 protein, which serves as a hallmark for ALS. FS corrected the nuclear-cytoplasm translocation of TDP-43 protein and decreased late apoptosis in mutants. Our study illustrates that both FS and QR shield cells from oxidative stress, and that FS imparted better protection against the pathogenic effect of SQSTM1 mutants in SH-SY5Y neuronal cells.},
}

@article {pmid42236288,
year = {2026},
author = {Chinoy, A and Soo, A},
title = {Effectiveness of Surgical Sealants in Reducing Prolonged Air Leaks After Pulmonary Resection: A Systematic Review.},
journal = {Interdisciplinary cardiovascular and thoracic surgery},
volume = {41},
number = {7},
pages = {},
doi = {10.1093/icvts/ivag164},
pmid = {42236288},
issn = {2753-670X},
mesh = {Humans ; *Pneumonectomy/adverse effects ; *Tissue Adhesives/therapeutic use/adverse effects ; *Surgical Stapling/adverse effects ; Treatment Outcome ; *Fibrin Tissue Adhesive/therapeutic use ; *Anastomotic Leak/prevention & control/etiology ; Time Factors ; Female ; },
abstract = {OBJECTIVES: Prolonged air leak (PAL) is the most common complication following pulmonary resection, leading to increased morbidity, hospital stay, and healthcare costs. Although staplers are currently the standard for lung parenchymal closure, ALs remain frequent. Surgical sealants have been introduced as adjuncts to staplers to reduce PAL, but evidence remains inconsistent. Prior systematic reviews frequently pooled together stapled and sutured resections, limiting applicability to contemporary practice. This review specifically evaluates whether surgical sealants reduce the incidence and duration of PAL when used with staplers in adult patients.

METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (CRD420251064592). A literature search was conducted in PubMed, Ovid MEDLINE, and Cochrane Library for studies published between 2005 and June 2025. Eligible studies included adult patients undergoing stapler-based pulmonary resection comparing sealants plus staplers versus staplers alone. Risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials (RoB2) and risk of bias in non-randomized studies of interventions (ROBINS-I) tools.

RESULTS: Eight studies were included. Surgical sealants studied included fibrin-based (autologous fibrin sealant (FS), FS patch, human FS) and synthetic polymers (polyethylene glycol hydrogel sealant, cyanoacrylate-based sealant). Most studies reported a statistically significant reduction in PAL incidence and/or duration with sealant use. Some also showed reduced chest tube duration and hospital stay, though not always statistically significant. One study showed worse outcomes in the sealant group. No study reported increased complications. Subgroup analyses were limited.

CONCLUSIONS: Sealants used with staplers may reduce PAL incidence and duration, particularly in high-risk patients, without increased complications. However, variability in study design and limited subgroup data weaken current evidence. Larger, standardized randomized controlled trials are needed to confirm clinical benefit and inform routine use.},
}

Humans
*Pneumonectomy/adverse effects
*Tissue Adhesives/therapeutic use/adverse effects
*Surgical Stapling/adverse effects
Treatment Outcome
*Fibrin Tissue Adhesive/therapeutic use
*Anastomotic Leak/prevention & control/etiology
Time Factors
Female

@article {pmid42421808,
year = {2026},
author = {Ang, NKJ and Lim, JQ and Lye, TJY and Tan, DMY and Lim, CH},
title = {Endoscopic salvage for afferent loop syndrome: the antegrade lumen-apposing metal stent technique.},
journal = {VideoGIE : an official video journal of the American Society for Gastrointestinal Endoscopy},
volume = {11},
number = {7},
pages = {298-303},
pmid = {42421808},
issn = {2468-4481},
abstract = {BACKGROUND AND AIMS: Afferent loop syndrome (ALS) is a rare postgastrectomy condition with biliopancreatic limb obstruction. Revision surgery carries high morbidity in patients with hostile anatomy. We aimed to demonstrate the feasibility of a double-scope, antegrade EUS-guided lumen-apposing metal stent (LAMS) enteroenterostomy as an endoscopic alternative in the management of complex ALS.

METHODS: A patient with extensive prior gastric surgery presented with ALS. With a double-scope antegrade technique, a pediatric gastroscope (GIF-XP190 N; Olympus, Tokyo, Japan) was used to cannulate the afferent limb to place a guidewire, and a linear echoendoscope (GF-UCT180; Fujifilm, Tokyo, Japan) was advanced into the blind loop. The pediatric gastroscope was reintroduced into the efferent limb, which was water-distended to approximately 3 cm in diameter to achieve sonographic apposition. Under combined EUS and fluoroscopic guidance, a 15- × 15-mm electrocautery-enhanced LAMS (Boston Scientific, Marlborough, Mass, USA) was deployed to create an enteroenterostomy.

RESULTS: Postdeployment contrast confirmed optimal position and immediate patency without leak. Symptoms resolved rapidly; the patient resumed a diet within days and gained weight. Abdominal radiography showed progressive LAMS expansion without adverse events.

CONCLUSIONS: Double-scope antegrade EUS-guided LAMS placement safely decompressed the afferent limb in our patient, restoring enteral flow and avoiding high-morbidity reoperation. This technique merits consideration within multidisciplinary care and warrants larger comparative studies to define long-term outcomes.},
}

@article {pmid42422319,
year = {2026},
author = {Nie, J and Peters, S and Ge, CB and Portengen, L and Rothman, N and Hu, W and Ou, R and Wei, Q and Zhang, L and Hou, Y and Lan, Q and Shang, HF and Vermeulen, R},
title = {Smoking and the risk of neurodegenerative diseases in a Chinese case-control study.},
journal = {BMJ neurology open},
volume = {8},
number = {2},
pages = {e001728},
pmid = {42422319},
issn = {2632-6140},
abstract = {BACKGROUND: While smoking is inversely associated with Parkinson's disease (PD) risk, its relationship with amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA) remains unclear, particularly in Asian populations. We investigated these associations in a Chinese case-control study.

METHODS: We recruited newly diagnosed ALS (n=430), MSA (n=271), PD (n=523) cases and hospital-based controls (n=1033) in Sichuan, China. Logistic regression models were used to evaluate associations between smoking and disease risks, adjusting for demographic, lifestyle and occupational factors.

RESULTS: Compared with never-smokers, the adjusted ORs and 95% CIs of ALS for current and former smokers were 1.00 (0.61 to 1.65) and 1.79 (1.01 to 3.17), respectively. For MSA, ORs were 1.27 (0.73 to 2.23) for current smokers and 2.54 (1.41 to 4.60) for former smokers. Individuals who quit within 4 years before diagnosis showed the highest risk of ALS (OR=1.93, 95% CI 0.96 to 3.88) and MSA (OR=2.09, 95% CI 1.11 to 3.93). For both ALS and MSA, no consistent trend was found with increasing smoking duration or pack-years. In contrast, ever-smokers had a significantly lower PD risk (OR=0.49, 95% CI 0.33 to 0.71), particularly current smokers (OR=0.30, 95% CI 0.19 to 0.48). Longer smoking duration and higher cumulative smoking were also linked to PD risk with clear negative exposure-response patterns (P trend=0.039 and 0.029, respectively).

CONCLUSIONS: Consistent with findings in non-Asian populations, smoking was inversely associated with PD risks in the Chinese population. For ALS and MSA, we found evidence suggestive of positive relationships with cigarette smoking, but no clear exposure-response relationships were observed.},
}

@article {pmid42422504,
year = {2026},
author = {Tomikawa, E and Takahashi, K and Hattori, H and Arai, T and Kawai, M and Nishimura, K and Goto, Y and Yagi, R and Miyamoto, Y and Miyoshi, T},
title = {Multinucleation and cytotoxicity induced by multikinase inhibition in highly proliferative cells.},
journal = {Journal of toxicologic pathology},
volume = {39},
number = {3},
pages = {93-101},
pmid = {42422504},
issn = {0914-9198},
abstract = {Phenotypic screening using motor neurons derived from the induced pluripotent stem (iPS) cell of a patient with amyotrophic lateral sclerosis led to the identification of Compound X, a novel agent with potent neuroprotective activity that is hypothesized to act by inhibiting hematopoietic progenitor kinase/germinal center kinase-like kinase (HGK). Unlike known HGK inhibitors, including Prostetin and GNE-495, Compound X and related Compounds Y and Z exhibited broader multi-kinase-inhibition profiles, including the strong inhibition of Aurora B kinase and strong-to-moderate inhibition of Src-family kinases in kinase panel screening. Owing to their roles in cytokinesis, we performed in vitro micronucleus tests to assess their genotoxicity. Compounds X, Y, and Z induced the multinucleation of cells at rates of 88.8, 71.5, and 91.8%, respectively, whereas Prostetin and GNE-495 resulted in rates of 0.5 and 1.3%, respectively, which were comparable to the control. A 5-day repeated-dose oral toxicity study of Compound X using mice, at doses of 125, 250, and 500 mg/kg/day, revealed decreased locomotor activity, hypothermia, and mortality at 500 mg/kg/day. Histopathology showed necrosis/hemorrhage in bone marrow cells; single-cell necrosis in the thymus, spleen, and mesenteric lymph nodes; nuclear pleomorphism and single-cell necrosis/necrosis in the gastrointestinal mucosa; and karyomegaly and a reduction in testicular germ cells. These toxicopathological findings suggest that Compound X induces nuclear pleomorphism and necrosis in highly proliferative cells. Although Compound X strongly suppressed HGK, its toxicity may be associated with broader multikinase inhibition, which is consistent with the finding that Prostetin and GNE-495 do not induce multinucleation in vitro.},
}

@article {pmid42422879,
year = {2026},
author = {Grassmann, G and Amadei, M and Lardieri, A and Montemiglio, LC and Passeri, AA and Mattarelli, M and Di Rienzo, L and Miotto, M and Ruocco, G and Milanetti, E},
title = {Investigating the effect of progressive truncations at the ALS-linked protein TDP-43 RRM2 on its aggregation mechanism.},
journal = {Frontiers in molecular biosciences},
volume = {13},
number = {},
pages = {1849627},
pmid = {42422879},
issn = {2296-889X},
abstract = {Amyotrophic lateral sclerosis is a neurodegenerative disease characterized by inclusions of TDP-43 protein. C-terminal fragments (CTFs) of TDP-43, generated by cleavage within its second RNA recognition motif (RRM2), have been found forming aggregates in patients. Aggregation has often been attributed to the C-terminal domain, but increasing evidence indicates that RRM2 fragments contribute to pathological inclusions. We performed extensive molecular dynamics simulations to investigate the changes resulting from the truncation that could lead to aggregation. We analyzed the full RRM2 domain (fRRM2, residues 192-261) and two fragments commonly observed in CTFs (tRRM2A, residues 220-261, and tRRM2B, residues 209-261). We found that truncation results in distinct aggregation-prone states. tRRM2B appears to rely on β -sheet elements associated with amyloid-like aggregation, whereas tRRM2A exhibits higher structural variability and a reduced β -content, suggesting a phase separation-like aggregation mechanism. We further simulated an extended fragment of tRRM2A, tRRM2A-l (residues 220-269). Although its predicted aggregation propensity remains largely unchanged, tRRM2A-l exhibits increased structural flexibility, and a stronger exposure of Nuclear Export Signal residues. Our results indicate that subtle differences in RRM2 fragment length influence potential misfolding pathways. Future studies and therapeutic strategies to prevent TDP-43 aggregation should carefully consider the specific domain adopted.},
}

@article {pmid42422903,
year = {2026},
author = {Singh, T and Khare, SK and Siddhanta, S},
title = {Spectroscopic discrimination of bacterial species of variable pathogenicity through explainable machine learning.},
journal = {Nanoscale},
volume = {},
number = {},
pages = {},
doi = {10.1039/d6nr00689b},
pmid = {42422903},
issn = {2040-3372},
abstract = {Rapid and accurate identification of bacterial pathogens and their degree of pathogenicity is essential for guiding antimicrobial therapy. Current culture-based methods require a timeframe of at least 24-48 h for species-level identification alone, which often leads to substantial disease progression and increases the propensity of antimicrobial resistance (AMR). Surface-Enhanced Raman Spectroscopy (SERS) shows promise in mitigating these drawbacks by providing a fast, non-invasive, label-free method to capture the biochemical fingerprints of bacteria achievable under clinical settings. However, the molecular complexity of SERS spectra, which has been an impediment for conventional data analysis, demands robust computational frameworks for reliable species-level identification. Here, we employ a comprehensive SERS analysis scheme with supervised machine learning and explainable artificial intelligence (XAI) to discriminate five clinically relevant pathogens, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and Enterococcus faecalis, and to probe their degree of pathogenicity from a biomarker perspective. Among the tested models - Support Vector Machine (SVM), k-Nearest Neighbour (kNN), Random Forest (RF), and a 1D Convolutional Neural Network (CNN) - CNN achieved near-perfect classification accuracy, capturing subtle and spectrally relevant variations often inaccessible to traditional algorithms. Notably, the 1D-CNN also achieved 100% discrimination between MRSA and methicillin-sensitive S. aureus - two strains of the same species differing only in resistance phenotype. To ensure transparent decision-making and eliminate the black-box nature of machine learning models, SHapley Additive exPlanations (SHAP) analysis was applied to both RF and CNN models, which facilitated the convergence of both frameworks on the same discriminatory Raman regions, revealing conserved biochemical determinants of species identity. Complementary MCR-ALS decomposition further resolved the spectra into interpretable biochemical components and provided the rubric for biochemical differentiation. Together, this study aims to demonstrate an end-to-end explainable workflow that couples SERS with interpretable AI, offering a rapid, transparent approach for pathogenic disease diagnosis.},
}

@article {pmid42423631,
year = {2026},
author = {Chu, HS and Oh, J},
title = {Identifying Gastrostomy Care and Home Gastrostomy Tube Feeding-Related Educational Content for Patients With Amyotrophic Lateral Sclerosis and Their Family Caregivers: A Delphi Panel With Professional Stakeholders.},
journal = {Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates},
volume = {},
number = {},
pages = {},
pmid = {42423631},
issn = {1538-9766},
abstract = {Enteral nutrition is delivered through a gastrostomy tube to provide nutritional support to patients with amyotrophic lateral sclerosis (ALS) who have developed severe dysphagia at home. Complications may arise from gastrostomy and enteral nutrition when family caregivers do not provide adequate care. This study identifies key areas of educational content that can improve the care of patients with ALS requiring gastrostomy and home enteral nutrition. We conducted a modified three-round e-Delphi survey with health care experts to clarify their perspectives on the educational content regarding gastrostomy and home enteral nutrition disseminated among patients with ALS and their family caregivers. The experts provided their opinions on specific educational content areas, and their responses were analyzed to identify areas of consensus and divergence. Accordingly, in Rounds 1-3 of the survey, 16 experts, including registered nurses (n = 6), advanced practice registered nurses (n = 3), clinical neurologists (n = 3), and dieticians (n = 4), participated. In Round 3, four categories and 39 educational components reached consensus. The results provide a framework for developing educational nursing interventions for family caregivers of patients with ALS receiving home enteral nutrition through gastrostomy tubes and for defining the essential elements of the educational content of such interventions.},
}

@article {pmid42423712,
year = {2026},
author = {Lu, J and Wang, XTX},
title = {Tackling challenges in large language model-based data extraction via context engineering: A commentary on Jansen et al. (2025).},
journal = {Psychological bulletin},
volume = {152},
number = {4},
pages = {404-419},
doi = {10.1037/bul0000520},
pmid = {42423712},
issn = {1939-1455},
support = {//National Natural Science Foundation of China/ ; },
mesh = {*Large Language Models ; Humans ; },
abstract = {Systematic reviews, particularly meta-analyses, involve crucial yet labor-intensive and error-prone stages of data extraction. Recent advances in large language models (LLMs) have unlocked new avenues for automating this process, potentially enhancing both efficiency and reliability. Recently, Jansen et al. (2025) systematically evaluated the accuracy and error patterns of LLM-assisted data extraction across 22 reviews published in Psychological Bulletin. Their findings indicated that while achieving acceptable-to-good accuracy for some variables describing study characteristics, LLMs struggled with numerical variables, especially those related to effect sizes. In this commentary, we discuss the current challenges of automated data extraction and potential pathways to improve the work reported in Jansen et al.'s study. We situate our discussion within the framework of context engineering, aiming to refine the information provided to LLMs through dynamic optimization strategies tailored to specific tasks. We identify five key challenges that reflect either LLMs' unique patterns or standard practices in research synthesis: parsing semistructured data, understanding long contexts, performing arithmetic induction, engaging in complex reasoning, and ensuring the reproducibility of coding protocols. We then outline potential solutions inspired by context engineering implementations such as retrieval-augmented generation and tool-integrated reasoning. For illustration, we present four examples: extracting semistructured data via optical character recognition, reliably computing effect sizes through function calls, performing adaptive retrieval with LLM-based agents, and iteratively improving outputs through self-refinement. We conclude by calling for future research in automated data extraction to advance beyond simple instruction-following paradigms toward more reliable forms of context engineering. (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}

*Large Language Models
Humans

@article {pmid42423935,
year = {2026},
author = {Elvish, TM and Trowell, D and Bonacci, J and Turner, KJ and Kremer, P and Millett, EL and Pickering, C and Saunders, N},
title = {Biological and Race Strategy Characteristics Investigated in Elite Endurance Track Running: A Systematic Review.},
journal = {Sports medicine (Auckland, N.Z.)},
volume = {},
number = {},
pages = {},
pmid = {42423935},
issn = {1179-2035},
abstract = {BACKGROUND: Understanding biological and race strategy characteristics of endurance track runners competing at benchmark events provides high-performance athletics programmes and coaches with valuable insight into what is required to succeed.

OBJECTIVES: The aim of this systematic review was to identify biological and race strategy characteristics investigated in elite able-bodied endurance track runners (Aim 1) and, where examined, highlight whether these characteristics could differentiate performance success within this elite cohort (Aim 2).

METHODS: For this systematic review, searches across EBSCOhost (Academic Search Complete, CINAHL Complete, MEDLINE Complete and SPORTDiscus), Scopus, PubMed and Web of Science were completed until May 2023. Searches also involved World Athletics Research Centre, New Studies in Athletics, handsearching and scanning of reference lists of included studies. Eligible studies were required to be published in English and have investigated performance-related biological or race strategy characteristics among senior able-bodied endurance track runners (800-10,000 m) capable of competing at benchmark events. Risk of bias of included studies was evaluated based on Sarmento et al.'s 16-item checklist. The review separated middle-distance runners (MDR) and long-distance runners (LDR), to account for the differing performance demands of these event groups. Studies were considered to address Aim 2 if they assessed for statistical associations between athlete characteristics and overall performance (e.g. race time) or compared characteristics between athletes with different competitive results (e.g. medallists and non-medallists).

RESULTS: Thirty-nine articles were included in this review, with 23 and 21 of these articles relevant to MDR and LDR, respectively. The most commonly reported characteristics were related to anthropometry (7 studies for MDR and LDR), biomechanics (7 studies for LDR), pacing (9 and 10 studies for MDR and LDR, respectively), qualification pattern (6 studies for MDR) and benchmark performance relative to athlete history (9 and 7 studies for MDR and LDR, respectively). However, the diversity of biological characteristics investigated and the generally small sample sizes makes it difficult to define an optimal biological profile for elite endurance runners. In contrast, race strategy characteristics investigated often included larger sample sizes providing a better understanding, especially in relation to pacing and for middle-distance events qualification patterns. Further, studies investigating whether characteristics differentiate performance among elite endurance track runners indicate that the most successful runners consistently demonstrate superior finishing ability. This is reflected in faster speeds during at least one 100-m segment of the final 400 m of the race and the ability to complete the final segments of the race at a pace close to, or faster than, their season best or 32-month best performance. In long distance events, better performance was associated with faster personal best times across the previous 32 months, indicating that having a high-ranking recent best time may be a prerequisite for succeeding at benchmark events. Faster 10,000-m runners had lower body mass and smaller arm and calf circumferences, suggesting a potential advantage of having lower non-functional mass. In middle distance events, success was associated with achieving superior qualification positions in the heats and semi-final, highlighting the importance of tactical positioning and efficient progression through qualification rounds. Faster male 800-m runners had a technique characterised by longer contact times and more compliant spring mechanics which may allow athletes to maintain or elevate speed during the sprint finish.

CONCLUSION: Biological and race strategy characteristics that profile elite endurance track runners and that, in several studies, showed association with performance success were discussed. These findings may assist high-performance athletics programmes and coaches in informing athlete development and investment. However, further research is required to establish a more holistic understanding of the biological profile of elite endurance track athletes and to determine which biological and race strategy characteristics may differentiate performance reliably among these elite runners.},
}

@article {pmid42424231,
year = {2026},
author = {Szyłak, E and Czarnowska, A and Kulczyńska-Przybik, A and Kopitelow, J and Mroczko, B and Kochanowicz, J and Kułakowska, A},
title = {Neurofilament Light Chain as a Biomarker in Neurology.},
journal = {European neurology},
volume = {},
number = {},
pages = {1-18},
doi = {10.1159/000552933},
pmid = {42424231},
issn = {1421-9913},
abstract = {Neurofilament light chain (NfL) has emerged as a highly sensitive biomarker of neuroaxonal injury across diverse neurological disorders. This review synthesizes current evidence regarding its diagnostic, prognostic, and therapeutic-monitoring utility, while outlining major clinical limitations and emphasizing the complementary role of glial fibrillary acidic protein (GFAP). NfL concentrations increase following axonal damage and correlate with inflammatory activity, lesion burden, and long-term disability progression in multiple sclerosis. Elevated levels also reflect neurodegeneration in Alzheimer's disease, predict disease severity and survival in amyotrophic lateral sclerosis, and are associated with motor and cognitive decline in Parkinson's disease and multiple system atrophy. In acute neurological conditions, including traumatic brain injury and stroke, NfL serves as a robust indicator of the extent of neuronal injury. Interpretation is constrained, however, by substantial physiological variability related to age, renal function, body mass index, and comorbidities, limiting the utility of absolute cut-off values. GFAP provides complementary information by capturing astrocytic damage, and the GFAP/NfL ratio may aid in differentiating multiple sclerosis from neuromyelitis optica spectrum disorder. Integration of NfL with multimodal biomarkers- such as GFAP, tau proteins, proteomic and metabolomic signatures, and advanced neuroimaging-may enhance diagnostic specificity and prognostic accuracy. Future research priorities include establishing age-adjusted reference intervals, validating longitudinal thresholds, and incorporating NfL into therapeutic monitoring frameworks. Advances in these areas are expected to improve diagnostic precision and support broader clinical implementation of NfL.},
}

@article {pmid42425084,
year = {2026},
author = {Hosokawa, M and Kawakami, R and Imami, K and Kurosawa, R and Yoshizawa, T and Ishihama, Y and Imamura, T and Hagiwara, M and Takeuchi, A},
title = {RNA-dependent SFPQ condensates coordinate multidimensional regulation of extra-long neuronal genes.},
journal = {Cell chemical biology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.chembiol.2026.06.004},
pmid = {42425084},
issn = {2451-9448},
abstract = {The mammalian brain uniquely expresses a large repertoire of extra-long genes critical for neuronal development and function, yet these transcripts are particularly vulnerable to dysregulation linked to neurological disorders, such as autism spectrum disorder and amyotrophic lateral sclerosis. The molecular mechanisms that ensure their stable expression remain poorly understood. Here, we show that the RNA-binding protein SFPQ forms meshwork-like biomolecular condensates that scaffold a multidimensional gene regulatory complex essential for long-gene expression. Super-resolution microscopy and functional perturbation assays demonstrate that disruption of SFPQ condensates impairs both extra-long gene expression and splicing. Proximity-dependent biotin labeling combined with mass spectrometry (BioID-MS) reveals that SFPQ condensates recruit transcriptional elongation factors, splicing regulators, and chromatin remodelers. Notably, many of these interactors overlap with autism-associated genes, suggesting direct disease relevance. These findings define a higher-order nuclear architecture organized by SFPQ and provide mechanistic insight into long-gene transcriptopathies underlying neurological disorders.},
}

@article {pmid42425146,
year = {2026},
author = {Hoppe, JM and Deniz, S and Czihal, M and Lottspeich, C},
title = {Contrast-Enhanced Ultrasound versus Contrast-Enhanced Computed Tomography in the Detection of Renal and Splenic Infarctions.},
journal = {Ultraschall in der Medizin (Stuttgart, Germany : 1980)},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2908-8526},
pmid = {42425146},
issn = {1438-8782},
abstract = {PURPOSE: Intra-abdominal organ infarctions require prompt imaging for diagnosis. Contrast-enhanced computed tomography (CECT) is considered the gold standard but involves radiation, iodinated contrast, and logistical challenges in critically ill patients. Contrast-enhanced ultrasound (CEUS) enables real-time assessment of microvascular perfusion without ionizing radiation. The aim of this study was to evaluate the diagnostic performance of CEUS compared to CECT for detecting intra-abdominal organ infarctions.

MATERIALS AND METHODS: This retrospective observational study included patients treated at a tertiary care center (2010-2024) who underwent both CEUS and CECT for suspected intra-abdominal organ infarction. With CECT as reference standard, diagnostic performance parameters and agreement (Cohen's kappa) were calculated.

RESULTS: 24 patients (median age 60 years; 12 female) were included. CECT confirmed organ infarction in 16/24 patients (66.7%). CEUS correctly identified 15 of these cases (Sensitivity 93.8%; 95% confidence interval [CI]: 71.7-98.9%). Specificity was 75.0% (95% CI: 40.9-92.9%), with two false-positive CEUS findings. Positive and negative predictive values were 88.2% (95% CI: 65.7- 96.7%) and 85.7% (95% CI: 48.7-97.4%), respectively. Agreement of CECT and CEUS was substantial (Cohen's κ = 0.71). Wedge-shaped perfusion defects were identified in 93.8% of CT-confirmed infarctions on both modalities.

CONCLUSION: CEUS demonstrates high sensitivity and good agreement with CECT for the detection of intra-abdominal organ infarctions. CEUS represents a valuable imaging modality, particularly when CECT is contraindicated or not available. Prospective studies are warranted to further define its role in clinical practice. Zielsetzung: Intraabdominelle Organinfarkte erfordern eine rasche bildgebende Diagnostik. Die kontrastmittelverstärkte Computertomographie (CECT) gilt als Goldstandard, ist jedoch mit Strahlenexposition, jodhaltigen Kontrastmitteln sowie logistischen Herausforderungen bei kritisch kranken Patienten verbunden. Der kontrastmittelverstärkte Ultraschall (CEUS) ermöglicht eine Echtzeitbeurteilung der Perfusion ohne ionisierende Strahlung. Ziel dieser Studie war die Evaluation der diagnostischen Leistungsfähigkeit der CEUS zur Detektion intraabdomineller Organinfarkte im Vergleich zur CECT.

MATERIAL UND METHODEN: In diese retrospektive Beobachtungsstudie (2010-2024) wurden Patientinnen und Patienten an einem tertiären Versorgungszentrum eingeschlossen, bei denen sowohl eine CEUS- als auch eine CECT-Untersuchung bei Verdacht auf intraabdominelle Organinfarkte durchgeführt wurde. Mit der CECT als Referenzstandard wurden die diagnostischen Testparameter und Übereinstimmung (Cohen's kappa) berechnet. Ergebnisse: 24 Patientinnen und Patienten wurden eingeschlossen (Medianalter 60 Jahre; 12 weiblich). Die CECT bestätigte in 16/24 Fällen (66,7%) einen Organinfarkt. Der CEUS identifizierte 15 Fälle korrekt (Sensitivität 93,8%, 95% Konfidenzintervall [KI]: 71,7-98,9%). Die Spezifität betrug 75,0% (95% KI: 40,9-92,9%) bei zwei falsch-positiven CEUS-Befunden. Der positive und negative prädiktive Wert betrugen 88,2% (95% KI: 65,7- 96,7%) respektive 85,7% (95% CI: 48,7-97,4%). Die Übereinstimmung zwischen CECT und CEUS war substantiell (Cohen's κ = 0,71). Keilförmige Perfusionsdefekte wurden in 93,8% der bestätigten Infarkte in beiden Modalitäten identifiziert. Schlussfolgerung: Der CEUS zeigt eine hohe Sensitivität und eine gute Übereinstimmung mit der CECT bei der Detektion intraabdomineller Organinfarkte. Der CEUS stellt für diese Fragestellung eine wertvolle Bildgebungsmodalität dar, insbesondere wenn CECT kontraindiziert oder nicht verfügbar ist. Prospektive Studien sind erforderlich, um seine Rolle in der klinischen Praxis weiter zu definieren.},
}