@article {pmid41728300,
year = {2026},
author = {Tsitkov, S and Raju, A and Wu, J and Li, J and Lim, RG and Wu, Z and Bistami, NA and , and Van Eyk, JE and Svendsen, CN and Rothstein, JD and Glass, JD and Finkbeiner, S and A Kaye, J and Thompson, LM and Fraenkel, E},
title = {Wild-type C9orf72 expression is a genetic modifier of C9-ALS survival.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.06.26345684},
pmid = {41728300},
abstract = {1 Amyotrophic lateral sclerosis (ALS) is highly heritable, yet the vast majority of cases lack an identifiable genetic cause and clinical progression remains largely unpredictable. To connect noncoding and rare genetic variation to disease phenotypes in a relevant cell type, we generated a multi-omic quantitative trait locus (QTL) atlas from 594 induced-pluripotent-stem-cell-derived human motor neuron lines (522 ALS patients, 72 controls). By mapping cis-QTLs for chromatin accessibility, splicing and gene expression from whole-genome sequencing, we identify common and rare variants on the wild-type C9orf72 allele that form regulatory haplotypes. These haplotypes influence C9orf72 expression levels in motor neurons and stratify C9-ALS patients into four subgroups; using clinical disease duration data and longitudinal ALSFRS-R scores, we show that these subgroups exhibit different survival trajectories, indicating that wild-type C9orf72 expression acts as a genetic modifier of disease duration. Beyond the C9orf72 locus, we detect ultra-rare intronic variants that create cryptic exons and structural and nonsense variants in established ALS genes, providing likely genetic explanations for disease in additional patients who previously lacked a molecular diagnosis. Our results show that QTL mapping in patient-derived motor neurons can reveal regulatory modifiers of progression and hidden pathogenic events in ALS, providing a framework for genetically informed risk attribution and patient stratification in complex neurological diseases.},
}

@article {pmid41728197,
year = {2026},
author = {Demaegd, KC and Koole, W and van Vugt, JJ and Dankbaar, JW and Hendrikse, J and Nazlı Başak, A and de Carvalho, M and Corcia, P and Codron, P and Bernard, E and Guissart, C and Couratier, P and Povedano Panades, M and van Doorn, PA and Warrenburg, BP and Cooper-Knock, J and , and Pasterkamp, RJ and van Rheenen, W and van Damme, P and van den Berg, LH and Veldink, JH and van Es, MA},
title = {Bi-allelic intermediate ATXN2 repeat expansions are associated with slow progressing, leg-onset familial ALS.},
journal = {BMJ neurology open},
volume = {8},
number = {1},
pages = {e001417},
pmid = {41728197},
issn = {2632-6140},
abstract = {OBJECTIVES: The identification of bi-allelic intermediate ATXN2 repeat expansions in a pedigree with amyotrophic lateral sclerosis (ALS) through clinical testing prompted us to investigate its relevance in the wider ALS population.

METHODS: ATXN2 repeat size was assessed in a large international cohort of ALS patients (n=6653 from Project MinE) and in neurologically intact control populations (n=13 515 controls from Project MinE and gnomad). For bi-allelic cases, we retrieved medical records, family history and MRI imaging. For familial cases, we obtained DNA samples from relatives for segregation analyses.

RESULTS: In total, we identified bi-allelic intermediate ATXN2 repeat expansions in five familial cases from three different pedigrees and five apparently sporadic cases. There is a relatively homogeneous phenotype characterised by lower limb onset and long survival (median 6 years) without significant cerebellar atrophy. Bi-allelic expansions were absent in controls (0 out of 13 515).

DISCUSSION: Here we report an apparently novel autosomal recessive form of familial ALS caused by bi-allelic intermediate ATXN2 repeat expansions, which is characterised by high penetrance, lower limb onset and slow progression. Although rare, testing for ATXN2 expansions should be performed in the clinical setting given its relevance to prognosis and genetic counselling.},
}

@article {pmid41727138,
year = {2026},
author = {He, Z and Zhou, J and Zhang, R and Meng, F and Nauen, DW and Troncoso, JC and Worley, PF and Zhang, W},
title = {TRIM32-UBQLN2-p62 axis promotes TDP-43 inclusion formation and amyloid aggregation through shuttle condensates.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.11.705390},
pmid = {41727138},
issn = {2692-8205},
abstract = {Aberrant protein aggregation is a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), which share overlapping genetic and pathological features. Similar aggregates are increasingly recognized in Alzheimer's disease (AD) and limbic-predominant age-related TDP-43 encephalopathy (LATE). However, it remains unclear whether a shared molecular pathway drives this pathological aggregation. Here, we report that the E3 ubiquitin ligase TRIM32, together with the shuttle factor UBQLN2 and the autophagy adaptor p62/SQSTM1, form condensates that depend on E3 ligase activity and a network of intermolecular interactions. These condensates act as scaffolds that capture UBQLN2 client proteins, including TDP-43 and ANXA11, and modulate their mobility. A unique hydrophobic loop within TRIM32's substrate-binding domain mimics low-complexity motifs in ANXA11 and TDP-43, enabling selective retention via competitive binding mediated by UBQLN2 STI1 domain. Moreover, TRIM32 condensates promote amyloid aggregation of TDP-43, an effect that is exacerbated by pathogenic UBQLN2 mutation. In brains from individuals with diverse neurodegenerative diseases, TRIM32 co-localizes with pathological phospho-TDP-43 (pTDP-43) inclusions, supporting a model in which TRIM32-driven condensates function as selective proteostasis sorting compartments that broadly contribute to TDP-43 proteinopathy.},
}

@article {pmid41727136,
year = {2026},
author = {Dubinski, A and Ferdi, A and Choughari, M and Spence, H and Adhikary, A and Fauchon, C and Touati, M and Gagné, M and Liu, M and Peyrard, S and Gregory, J and Vande Velde, C},
title = {TDP-43 pathology is linked to motor neuron loss but is independent of stress granules in vivo.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.11.705439},
pmid = {41727136},
issn = {2692-8205},
abstract = {Nuclear depletion and cytoplasmic aggregation of TDP-43 are pathological hallmarks of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease, and the recently defined limbic-predominant age-related TDP-43 encephalopathy (LATE). Chronic activation of the integrated stress response (ISR) and persistence of stress granules, phase-separated assemblies proposed to function as a protective mechanism, have been hypothesized to initiate the formation of pathological TDP-43 inclusions observed in post-mortem neurons. However, recent clinical trials targeting the ISR and stress granule dissolution failed to demonstrate clinical benefit despite robust target engagement, calling this model into question. Here, we employ a recurrent hyperthermia paradigm to directly examine the relationship between stress granules and TDP-43 pathology in vivo . We find that RNA-binding proteins classically associated with stress granules persist as phase-separated cytoplasmic structures in spinal motor neurons of both non-transgenic and mutant TDP-43 mice. Importantly, these structures are reversible and spatially distinct from TDP-43 puncta. Moreover, in a mutant TDP-43 mouse model with an impaired acute stress granule response, stress exposure induces TDP-43 nuclear export and cytoplasmic accumulation. Recurrent stress in these mice leads to a selective loss of spinal α-motor neurons. Together, our findings demonstrate that TDP-43 nuclear clearance and cytoplasmic demixing occur independently of stress granules in vivo , challenging prevailing models of TDP-43 pathogenesis and highlighting important implications for therapeutic strategies targeting the ISR.},
}

@article {pmid41727111,
year = {2026},
author = {Ding, DY and Bot, VA and Chen, KL and Groves, J and Pálovics, R and Masuda, D and Farinas, A and Oh, HS and Wagner, V and Lu, N and , and Cruchaga, C and Isakova, A and Schott, JM and Wyss-Coray, T},
title = {Cellular Aging Signatures in the Plasma Proteome Record Human Health and Disease.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.10.704909},
pmid = {41727111},
issn = {2692-8205},
abstract = {Aging is asynchronous across cells and organs, but whether plasma proteins can capture cell type-specific aging and predict disease and mortality remains unknown. We developed machine learning models to estimate the biological age of more than 40 distinct cell types-spanning neuronal, immune, glial, endocrine, epithelial, and musculoskeletal origins-using over 7,000 plasma proteins measured in 60,000 individuals across three cohorts, comprising the largest human plasma proteomics aging study to date. Individuals showed heterogeneous aging profiles, with 20-25% exhibiting accelerated aging in a single cell type and 1-3% across ten or more cell types. APOE genotype showed antagonistic aging effects in different cell types: APOE4 carriers exhibited older astrocytes but younger macrophages, while APOE2 carriers showed the inverse. Cellular aging signatures were uniquely associated with disease status and predicted incident disease and mortality over 15 years of follow-up. Amyotrophic lateral sclerosis (ALS) showed the strongest association with skeletal myocyte aging (hazard ratio = 12.7 for extreme accelerated versus youthful aging). In Alzheimer's disease (AD), prevalent cases showed accelerated aging across multiple neural and peripheral cell types, with extreme astrocyte aging conferring AD risk comparable to APOE4 carrier status. Moreover, extreme astrocyte aging increased AD risk in APOE4/4 carriers threefold, while youthful astrocytes strikingly reduced risk. Beyond neurodegeneration, respiratory cell aging identified smokers at 58% higher lung cancer risk, and myeloid aging identified normoglycemic individuals at higher diabetes risk. Both specific cellular vulnerabilities and cumulative aging burden influenced survival, wherein youthful immune or neuronal profiles were protective. A polycellular aging risk score provided robust mortality risk stratification across platforms and cohorts. These findings establish a framework for quantifying biological aging at the cellular resolution using plasma proteomics, revealing heterogeneity in aging trajectories and their impact on disease susceptibility and resilience.},
}

@article {pmid41727102,
year = {2026},
author = {Russell, KA and Shahrabi, AA and Akerman, SC and Byrne, MD and Rothstein, JD and Trotti, D and Jensen, BK and Haeusler, AR},
title = {Intrathecal (G 4 C 2) 149 delivery in C9orf72-deficient mice yields mild motor dysfunction and ALS/FTD pathological hallmarks.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.09.704060},
pmid = {41727102},
issn = {2692-8205},
abstract = {A repeat expansion in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), yet existing mouse models incompletely engage spinal regions implicated in disease. Here, an adeno-associated virus encoding (G 4 C 2) 149 repeats was delivered via neonatal intrathecal injection, achieving widespread CNS expression with robust spinal cord targeting. This approach was applied to mice with graded loss of endogenous C9orf72 to interrogate both gain- and loss-of-function mechanisms. Longitudinal motor, behavioral, and pathological analyses revealed that repeat expression primarily drives mild, progressive muscle weakness, whereas coordination deficits were largely genotype dependent. Subtle gait abnormalities and hyperactivity were also observed. Within spinal motor regions, repeat-expressing mice exhibited dipeptide repeat protein accumulation, reduced NeuN-positive area, glial activation, and sparse phosphorylated TDP-43 pathology. Cross-domain correlations further linked repeat expression, spinal pathology, and motor dysfunction. Collectively, these findings establish that CNS-wide repeat expression combined with reduced C9orf72 produces a coherent, mild ALS/FTD model.},
}

@article {pmid41692724,
year = {2026},
author = {Rönnholm, J and Weiner, S and Fuchs, J and Thorsell, A and Sihlbom, C and Dugom, L and Easton, A and Zetterberg, H and Gobom, J},
title = {Shake and bake: a robust and cost-effective proteomic sample preparation workflow for plasma and cerebrospinal fluid.},
journal = {Clinical proteomics},
volume = {23},
number = {1},
pages = {},
pmid = {41692724},
issn = {1542-6416},
abstract = {BACKGROUND: Plasma and cerebrospinal fluid are complementary sources of biomarkers for neurodegenerative diseases. The wide dynamic range of protein abundances, particularly in plasma, hampers detection of low-abundance proteins. Depletion of high-abundance proteins and efficient enzymatic digestion can improve proteome coverage but must be carefully optimized for reproducibility, throughput, and cost-efficiency for use in large-scale clinical proteomic studies.

METHODS: We developed a scalable sample preparation workflow for plasma and cerebrospinal fluid (CSF) that integrates depletion of high-abundance proteins, optimized digestion using Lys-C and trypsin, and compatibility with both label-free and tandem mass tag (TMTpro)-based quantification. Depletion was performed using a multi-affinity resin with immobilized antibodies targeting 14 high-abundance plasma proteins, which collectively constitute ≈ 95% of total plasma protein content. We systematically evaluated protein depletion and enzyme digestion conditions, and the effect of deoxycholate on digestion, monitoring the number of detectable proteins and the quantitation precision.

RESULTS: A resin-to-plasma ratio of ≥ 75 and a mixing speed of 900 rpm ensured complete and reproducible depletion. Depletion resulted in an increase in the number of identified proteins by ~ 65% in CSF, and ~ 80% in plasma, tripling the number of brain-enriched proteins, with maintained quantitative precision (median coefficient of variation (CV) for relative protein abundances < 11%). A two-step digestion protocol using Lys-C/trypsin followed by trypsin yielded the highest reproducibility and detectability in plasma. Adding the detergent deoxycholate to the samples had little effect in CSF and only marginally improved proteome coverage for plasma but decreased quantification precision and throughput. Technical replicates from a 528-sample clinical amyotrophic lateral sclerosis (ALS) cohort showed high reproducibility, with intra-sample CVs substantially lower than inter-individual variation.

CONCLUSIONS: The sample preparation workflow described here enabled deep and reproducible proteome profiling of plasma and CSF in high-throughput formats and was found to be suitable for biomarker discovery in large clinical studies.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12014-026-09589-1.},
}

@article {pmid41727032,
year = {2026},
author = {Kapsiani, S and Vora, S and Fernandez-Villegas, A and Kaminski, CF and Läubli, NF and Kaminski Schierle, GS},
title = {Discovery of TDP-43 aggregation inhibitors via a hybrid machine learning framework.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.12.705375},
pmid = {41727032},
issn = {2692-8205},
abstract = {TAR DNA-binding protein 43 (TDP-43) aggregation is a hallmark of several neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal dementia. Recent therapeutic efforts have highlighted the potential of small molecules capable of inhibiting TDP-43 aggregation; however, no effective treatments currently exist. Here, we developed a hybrid machine learning approach combining graph neural network (GNN) embeddings with traditional chemical descriptors and biological target annotations. Using XGBoost as the final classifier enabled model interpretability through SHAP analysis, allowing the identification of key chemical features and target annotations associated with TDP-43 anti-aggregation activity. Complementary Monte Carlo Tree Search analysis highlighted specific chemical substructures linked to predicted activity. By screening an external library of 3,853 small molecules, the model identified two compounds not previously evaluated against TDP-43 aggregation, namely berberrubine and PE859. Molecular docking analysis revealed that both compounds interact favourably with the TDP-43 RNA recognition motif (RRM) domain through distinct binding modes. Experimental validation showed that both compounds significantly reduced TDP-43 aggregation in HEK cells. Further testing in Caenorhabditis elegans expressing human TDP-43 demonstrated that PE859 significantly rescued locomotor defects, while berberrubine showed partial improvement. This work establishes a hybrid machine learning approach for accelerating small molecule drug discovery, yielding two promising therapeutic candidates for TDP-43 proteinopathies.},
}

@article {pmid41726972,
year = {2026},
author = {Natarajan, C and Budhwani, SM and Sreenivasamurthy, SGS and Katamoni, L and Thomson, B and Marcatti, M and Cuong, PP and Taglialatela, G and Krishnan, B},
title = {Exploring the PLD1-tau interaction in Frontotemporal Dementia.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.12.705569},
pmid = {41726972},
issn = {2692-8205},
abstract = {Frontotemporal dementia (FTD), a leading cause of young-onset dementia, is characterized by progressive behavioral and cognitive decline associated with frontotemporal cortical atrophy. Nearly 40% of cases exhibit tauopathy, yet the molecular drivers of tau aggregation leading to synaptic dysfunction remain poorly understood. Here, we investigated whether Phospholipase D1 (PLD1, a lipid signaling enzyme), implicated in Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS), contributes to tau pathology dependent synaptic deficits in FTD. Postmortem temporal (BA38) and frontal (BA9) cortices from clinically diagnosed FTD and age-matched control subjects were analyzed using fluorescence-assisted single synaptosome long-term potentiation (FASS-LTP), immunofluorescence, proximity ligation assays (PLA), and PLD1-interactome proteomics. FASS-LTP revealed markedly reduced glutamatergic potentiation in BA38 and BA9 crude synaptoneurosomes from FTD brains compared to controls. Western blotting demonstrated elevated PLD1 expression in both crude synaptoneurosomal and cytosolic fractions from FTD subjects in BA38, but not BA9. Bielschowsky staining confirmed increased Pick body burden in FTD temporal cortex. Immunofluorescence and PLA showed robust PLD1 co-localization with total tau (HT7), hyperphosphorylated tau (AT8), and acetylated tau oligomers (TOMA2), indicating a strong spatial association between PLD1 and pathological tau species. PLD1 also exhibited enhanced co-localization with astrocytic GFAP and synaptic markers (PSD95, Nrx1β), suggesting compartmentalized involvement in glial and synaptic remodeling. Proteomic profiling of PLD1-associated complexes revealed compartment-specific alterations with cytosolic fractions enriched for metabolic enzymes, stress-response proteins, and GFAP, while crude synaptoneurosomal fractions showed depletion of presynaptic scaffolds, vesicle-trafficking regulators, and proteostasis components. Cross-compartment integration indicated that over one-third of proteins were redistributed from synapses to cytosol, consistent with trafficking and degradative impairments. Gene Ontology analysis highlighted lipid metabolism, astrocyte activation, and proteasome dysfunction as dominant pathways. Collectively, these findings identify PLD1 as a critical mediator of synaptic dysfunction and tau pathology in FTD, acting through astroglial activation and disrupting synaptic proteostasis. This study provides the human clinical relevance towards PLD1 attenuation as a therapeutic target for FTD and related tauopathies to mitigate tau-driven neurodegeneration and restore synaptic integrity.},
}

@article {pmid41726966,
year = {2026},
author = {Avila, TU and Wang, J and Adams, L and Hu, E and Beltran, AA and Kozlenkov, A and Urhekar, S and Gonzalez, ABM and Lee, HG and Calabrese, JM and Dracheva, S and Beltran, AS and Mah, W and Won, H},
title = {Repeat expansions in C9orf72 rewire the 3D chromatin landscape in ALS.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.09.704902},
pmid = {41726966},
issn = {2692-8205},
abstract = {Amyotrophic lateral sclerosis (ALS) is frequently driven by GGGGCC short tandem repeat (STR) expansions in C9orf72 , yet the mechanisms by which these expansions lead to neurodegeneration remain incompletely understood. Here, we propose a novel mechanism involving higher-order chromatin architecture where C9orf72 -STR expansions induce widespread, neuron-specific gains in chromatin loops that are closely linked to transcriptomic dysregulation in ALS. These ectopic loops colocalize with the genomic binding sites of C9orf72 -STR RNAs and the architectural protein CTCF, supporting a model in which RNA-DNA interactions promote aberrant loop formation. Together, our findings demonstrate how C9orf72 -STR expansions remodel the neuronal genome and disrupt gene expression, uncovering an RNA-driven mechanism of chromatin reorganization in C9-ALS that connects altered nuclear topology to gene dysregulation in neurodegeneration.},
}

@article {pmid41726352,
year = {2026},
author = {Angurana, SK and Gupta, S and Tiwari, L and Shamarao, S and Khera, D and Sarkar, M and Dhaliwal, M and Kumar, V and Chaudhary, A and Deb, S and Samprati, M and Mehta, A and Kapoor, R and Tago, N},
title = {Development and Validation of Indian Children Length-based Tape (InChiTape) for Use in Critically Sick Children.},
journal = {Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine},
volume = {30},
number = {1},
pages = {35-39},
pmid = {41726352},
issn = {0972-5229},
abstract = {BACKGROUND AND AIM: Length-based tapes are extremely useful in critically sick children to estimate weight, emergency drug dosages, size of the equipment, and dose of defibrillation/cardioversion. The Indian Academy of Pediatrics (IAP), Advanced Life Support (ALS), and Basic Life Support (BLS) group felt the need to develop an indigenous tape for Indian children. A color-coded length-based tape [Indian Children Length-based Tape (InChiTape)] was planned to develop and later validate it.

PATIENTS AND METHODS: The population included children admitted to the emergency in the age range of 1 month-12 years and weight range of 2.5-40 kg. A color-coded length-based tape was developed using the World Health Organization (WHO) weight-for-length/height charts for boys (≤5 years) and the IAP weight-for-length/height charts for boys (>5 years). The median weights/lengths, corresponding +2SD and -2SD lengths, were marked on the charts for boys starting from 2.5 kg onward.

RESULTS: Fourteen centers from all zones of India pooled the data of 1,595 children. The majority of children were in the age range of 1-3.9 years (30%) and weight range of 5-9.9 and 10-14.9 kg (24.9 and 24.4%, respectively). The actual weight of children corresponded to the correct weight range/band on the InChiTape in 69.1% (n = 1,102) children, ranging from 56.6 to 78.4% in different age-groups and 55.5 to 76.3% in different weight ranges. There was a good correlation between actual weight and the average of respective weight range/band on the InChiTape (Pearson correlation of 0.95, p < 0.001).

CONCLUSION: The InChiTape is a rapid, reliable, and accurate method of estimating the weight of Indian children weighing 2.5-40 kg in an emergency.

HOW TO CITE THIS ARTICLE: Angurana SK, Gupta S, Tiwari L, Shamarao S, Khera D, Sarkar M, et al. Development and Validation of Indian Children Length-based Tape (InChiTape) for Use in Critically Sick Children. Indian J Crit Care Med 2026;30(1):35-39.},
}

@article {pmid41725371,
year = {2026},
author = {Carbó, J},
title = {Reviewer Comment on Dallaire et al. "Mortality and Complications of Percutaneous Gastrostomy in Amyotrophic Lateral Sclerosis Patients".},
journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques},
volume = {},
number = {},
pages = {1},
doi = {10.1017/cjn.2025.10512},
pmid = {41725371},
issn = {0317-1671},
}

@article {pmid41724566,
year = {2026},
author = {Caldero-Escudero, E and Romero-Sanz, S},
title = {Modeling stress-induced proteinopathies in Caenorhabditis elegans.},
journal = {Methods in cell biology},
volume = {203},
number = {},
pages = {201-231},
doi = {10.1016/bs.mcb.2025.12.007},
pmid = {41724566},
issn = {0091-679X},
mesh = {Animals ; *Caenorhabditis elegans/metabolism/genetics ; Disease Models, Animal ; Mitochondria/metabolism ; Proteostasis ; Reactive Oxygen Species/metabolism ; Endoplasmic Reticulum Stress ; *Proteostasis Deficiencies/metabolism/pathology ; *Caenorhabditis elegans Proteins/metabolism ; *Neurodegenerative Diseases/metabolism/pathology ; Humans ; *Stress, Physiological ; },
abstract = {Proteinopathies are a type of disorders characterized by the intracellular or extracellular accumulation of misfolded proteins that disrupt cellular proteostasis and exert toxic effects. These proteotoxic effects are a common hallmark of various age-related neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and polyglutamine disorders such as Huntington's disease (HD). Misfolded protein accumulation can impair numerous cellular processes, including mitochondrial function, protein degradation pathways, the endoplasmic reticulum stress response, and redox homeostasis, ultimately compromising cell viability. The nematode Caenorhabditis elegans (C. elegans) has emerged as a powerful model for studying proteotoxic stress due to its genetic tractability and the high degree of conservation of key cellular pathways when compared to mammals. These include mitochondrial dynamics and function, regulation of reactive oxygen species (ROS), and the cellular capacity to manage protein aggregates in terms of number, size, and clearance efficiency. The integration of these conserved stress response pathways together with C. elegans experimental versatility positioned this nematode as an ideal system to investigate the molecular mechanisms underlying proteinopathy-induced toxicity. In this chapter, we describe a set of complementary methodologies to evaluate proteotoxic stress in C. elegans models of protein misfolding. These include assays to measure mitochondrial reactive oxygen species (ROS) and membrane potential (Δψm), analyses of mitochondrial morphology and oxygen consumption, protein extraction protocols, and in vivo staining and semi-automated quantification of protein aggregates.},
}

Animals
*Caenorhabditis elegans/metabolism/genetics
Disease Models, Animal
Mitochondria/metabolism
Proteostasis
Reactive Oxygen Species/metabolism
Endoplasmic Reticulum Stress
*Proteostasis Deficiencies/metabolism/pathology
*Caenorhabditis elegans Proteins/metabolism
*Neurodegenerative Diseases/metabolism/pathology
Humans
*Stress, Physiological

@article {pmid41724277,
year = {2026},
author = {Zhao, X and Pu, L and Zeng, X and Nie, J},
title = {Role of nuclear import proteins in maintaining proteostasis and disease pathogenesis.},
journal = {Biochemical pharmacology},
volume = {},
number = {},
pages = {117831},
doi = {10.1016/j.bcp.2026.117831},
pmid = {41724277},
issn = {1873-2968},
abstract = {Nuclear import receptors (NIRs), particularly the importin α/β heterodimer system, function as essential gatekeepers of nucleocytoplasmic trafficking by decoding diverse nuclear localization signals (NLSs) to orchestrate cellular proteostasis. This review delineates the structural basis of NLS recognition and the coordinated mechanisms that facilitate the nuclear import of critical cargoes, including transcription factors, RNA-binding proteins, and DNA repair factors. Beyond their canonical transport role, we emphasize the emerging functions of NIRs as molecular chaperones that suppress aberrant phase separation and their co-translational regulatory roles in ensuring proper protein biogenesis and folding. The collapse of these regulatory functions underpins the pathogenesis of major human diseases. We examine in detail the pathological consequences of nuclear import dysfunction, highlighting its central role in specific neurodegenerative disorders such as Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD), oncogenic transformation, and viral pathogenesis. The discussion provides a critical appraisal of emerging therapeutic strategies that target the nuclear import machinery, including small-molecule inhibitors (e.g., importazole, ivermectin), peptide competitors, and advanced delivery platforms. We conclude by providing the associated challenges such as achieving tissue specificity, avoiding off-target effects and the significant opportunities that lie in pharmacologically modulating this fundamental pathway to restore proteostasis and develop disease modifying therapies.},
}

@article {pmid41723979,
year = {2026},
author = {Gao, Y and Lu, Y and Zhao, S and Chen, R and Liu, J and Zhang, S and Bai, X and Zhang, J},
title = {Allicin improves motor neuron survival in amyotrophic lateral sclerosis by reducing neuroinflammation and modulating gut microbiota.},
journal = {Biochemical and biophysical research communications},
volume = {809},
number = {},
pages = {153503},
doi = {10.1016/j.bbrc.2026.153503},
pmid = {41723979},
issn = {1090-2104},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons (MNs). Allicin, a defensive molecule in garlic with anti-inflammatory and gut microbiota-modulating properties, has shown therapeutic potential in animal models of various diseases including Alzheimer's disease (AD). However, its possible therapeutic role in ALS remains unclear. The purpose of this study is to investigate the therapeutic effect of allicin in ALS transgenic SOD1[G93A] mice. Starting at 60 days of age, SOD1[G93A] mice received oral gavage of allicin (10 mg/kg) on alternate days, while the control group received an equal volume of normal saline (NS) on the same schedule. Twelve mice per group were used for monitoring disease onset and survival. Nissl staining and choline acetyltransferase (ChAT) immunofluorescence were used to quantify MNs in the anterior horn. Microglial activation was analyzed by immunofluorescence staining for Iba1, ARG1, and CD86. The mRNA expression levels of IL-10, TGF-β, IL-1β, and TNF-α were examined using qPCR. Additionally, fecal samples were collected for 16S rDNA sequencing to evaluate changes in gut microbiota composition. We observed that allicin treatment failed to prolong the onset time and survival period of SOD1[G93A] mice, but it extended the disease duration. Nissl staining analysis revealed that allicin treatment delayed the loss of spinal MNs, a finding corroborated by ChAT immunofluorescence. Furthermore, allicin treatment significantly reduced neuroinflammation and improved gut microbiota. Taken together, although allicin may prolong disease duration in ALS, it did not improve overall survival or delay disease onset. Therefore, its potential disease-modifying effects require further validation.},
}

@article {pmid41723333,
year = {2026},
author = {Wang, Y and Zhang, H and Yang, T and Luo, J and Lin, T and Yan, X and Ding, J and Qiu, Y and Zhao, M and Yang, G},
title = {Imaging-derived neuromuscular ultrasound phenotypes are associated with functional status in amyotrophic lateral sclerosis.},
journal = {Journal of neurology},
volume = {273},
number = {2},
pages = {},
pmid = {41723333},
issn = {1432-1459},
support = {2025HZZD09//Construction Fund of Key Medical Disciplines of Hangzhou for Rare Disease (Motor Neuron Disease)/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology ; Male ; Female ; Middle Aged ; Ultrasonography/methods ; Aged ; *Muscle, Skeletal/diagnostic imaging/physiopathology ; Phenotype ; Adult ; *Peripheral Nerves/diagnostic imaging/physiopathology ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) presents with marked clinical heterogeneity, complicating diagnosis and management. Neuromuscular ultrasound (NMUS) provides a non-invasive means to visualize peripheral nerve and muscle integrity, but its potential to delineate ALS subtypes has not been systematically explored.

OBJECTIVE: To identify clinically meaningful ALS subgroups through unsupervised clustering of NMUS features integrated with clinical and electrophysiological data.

METHODS: A total of 454 ALS patients (August 2024-December 2025) underwent standardized NMUS assessment, including muscle thickness, echogenicity, and nerve cross-sectional area, alongside ALSFRS-R, manual muscle testing (MMT), and compound muscle action potentials (CMAPs). K-means clustering was applied to standardized NMUS variables, with cluster stability assessed using silhouette coefficients, sensitivity analyses (k = 2-5), and resampling-based adjusted Rand indices. Multivariable regression examined associations between cluster membership and ALSFRS-R.

RESULTS: Two reproducible NMUS-based subgroups were identified: a Mild cluster (n = 288, 63.4%) and a Severe cluster (n = 166, 36.6%). The Severe cluster showed reduced muscle thickness and higher echogenicity across multiple sites, together with lower ALSFRS-R scores (adjusted β = - 3.84, 95% CI - 5.41 to - 2.27, P < 0.001). Cluster membership correlated negatively with MMT and CMAP amplitudes, supporting functional and electrophysiologic validity. Stability metrics confirmed robustness of the two-cluster solution.

CONCLUSION: Integrating NMUS with clinical data enables objective, imaging-derived stratification of ALS patients into biologically and functionally distinct subgroups. This approach offers a pragmatic framework for phenotypic characterization and may inform personalized monitoring and trial design in ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology
Male
Female
Middle Aged
Ultrasonography/methods
Aged
*Muscle, Skeletal/diagnostic imaging/physiopathology
Phenotype
Adult
*Peripheral Nerves/diagnostic imaging/physiopathology

@article {pmid41723070,
year = {2026},
author = {Togawa, N and Ayaki, T and Yoshii, D and Maki, T and Sawamoto, N and Takahashi, R},
title = {Corrigendum to "TMEM119-positive microglia were increased in the brains of patients with amyotrophic lateral sclerosis" [Neurosci. Lett. 833 (2024) 137829].},
journal = {Neuroscience letters},
volume = {},
number = {},
pages = {138544},
doi = {10.1016/j.neulet.2026.138544},
pmid = {41723070},
issn = {1872-7972},
}

@article {pmid41722586,
year = {2026},
author = {Jing Jing Yeo, C},
title = {The Tuesday lessons of ALS.},
journal = {The Lancet. Neurology},
volume = {25},
number = {3},
pages = {231},
doi = {10.1016/S1474-4422(26)00048-7},
pmid = {41722586},
issn = {1474-4465},
}

@article {pmid41722440,
year = {2026},
author = {Squintani, G and Muzio, MD and Rasera, A and Paio, F and Borin, GU and Humaidan, K and Orlando, D and Refatti, N and Romito, S and Tinazzi, M and Bonetti, B and Ermani, M},
title = {Corrigendum to "Sensory and motor cortical hyperexcitability in patients with amyotrophic lateral sclerosis: are they related? A prospective pilot study". [CLINPH 183 (2026) 2111485].},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {184},
number = {},
pages = {2111703},
doi = {10.1016/j.clinph.2026.2111703},
pmid = {41722440},
issn = {1872-8952},
}

@article {pmid41722224,
year = {2026},
author = {Ye, Y and Shen, B and Jiang, MY and Jong, MS},
title = {Beyond immersion: Investigating the impact of SVVR on FLCA in a Chinese EFL speaking class.},
journal = {Acta psychologica},
volume = {264},
number = {},
pages = {106504},
doi = {10.1016/j.actpsy.2026.106504},
pmid = {41722224},
issn = {1873-6297},
abstract = {Although spherical video-based virtual reality (SVVR) has demonstrated efficacy in enhancing English-as-a-foreign-language (EFL) learning outcomes, its impact on foreign language classroom anxiety (FLCA) within speaking contexts remains underexplored. This mixed methods study implemented a 16-week experiential learning (EL)-based SVVR intervention to examine its effects on FLCA that resides in four dimensions and on the speaking performance among Chinese EFL learners. Using a pre-post control-group design with 69 sophomores, quantitative data from Horwitz et al.'s (1986) FLCAS and speaking tests were analyzed with ANCOVA, and 12 post-intervention interviews were examined using reflexive thematic analysis. Relative to the control group, the SVVR group reported significantly lower overall FLCA, with moderate to large reductions in communication apprehension (partial η[2] = 0.160) and fear of negative evaluation (partial η[2] = 0.111) but no detectable changes in test anxiety (partial η[2] = 0.037) or other general anxiety (partial η[2] = 0.037), and achieved higher post-test speaking scores (partial η[2] = 0.078). Thematic analysis identified four underlying mechanisms that helped to explain the dimension-specific FLCA levels after intervention: (1) SVVR as a psychological "safety shield", (2) displaced social judgment, (3) pedagogy-test disconnect, and (4) task-based anxiety control. Theoretically, the study demonstrates that FLCA-CA and FLCA-FNE are most responsive to EL-based SVVR and shows that this approach primarily alleviates situational, interaction-related anxiety rather than all forms of FLCA. Practically, it indicates how SVVR can be used as a supplementary tool to design low-anxiety, high-engagement speaking activities that support EFL learners' emotional regulation and oral proficiency.},
}

@article {pmid41721173,
year = {2026},
author = {Bonin, P and Méot, A and Argon, S and Boucheix, JM and Thiebaut, G},
title = {The survival processing advantage in memory using virtual reality versus traditional desktop display: Does it make a difference?.},
journal = {Memory & cognition},
volume = {},
number = {},
pages = {},
pmid = {41721173},
issn = {1532-5946},
abstract = {The survival processing advantage refers to the fact that words processed in relation to survival (e.g., finding food) are memorized better than words processed in a context that is not evocative of survival (e.g., moving to a foreign country). This effect has been extensively studied in laboratory tasks in which participants have to imagine a survival situation rather than being placed in a "supporting perceptual context." In the present study, we aimed to investigate the survival effect using virtual reality and compare it with a traditional desktop display. Using virtual reality technology, we replicated the survival processing advantage found in Wang et al.'s (Survival processing advantage demonstrated with virtual reality-based survival environment: A promising tool for survival processing research. Memory & Cognition, 51[1], 129-142, 2023) study. More importantly, the survival effect obtained with virtual reality was no greater than that obtained using more conventional means (i.e., a desktop display). The findings are discussed in relation to the issue of the optimality of the survival effect and the way proximate mechanisms are involved.},
}

@article {pmid41720774,
year = {2026},
author = {Yang, M and Wang, Q and Yan, R and Kang, D and Luo, W and Zhang, L and Liu, R and Wu, L and Gu, J and Wang, X},
title = {A neurotoxic cryptic peptide arising from TDP-43-dependent cryptic splicing of PKN1.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-68916-0},
pmid = {41720774},
issn = {2041-1723},
abstract = {Dysfunction of transactive response DNA-binding protein 43 (TDP-43) drives neurodegeneration in amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD), in part through inducing aberrant RNA splicing. However, whether such mis-splicing yields stable, pathogenic proteins remains unclear. Here, we identify a TDP-43-repressed cryptic exon in Protein kinase N1 (PKN1), designated PKN1-5a1, which is activated in ALS patient brains and introduces a premature termination codon. This aberrant transcript escapes nonsense-mediated decay and is translated into a truncated peptide, PKN1-N207 (PKN207), detectable in AD brains with TDP-43 pathology. In mice, PKN207 impairs cognition, memory, and synaptic plasticity. Our findings demonstrate that TDP-43 loss-induced cryptic splicing can generate stable neurotoxic polypeptides, revealing a peptide-mediated mechanism in TDP-43 proteinopathies.},
}

@article {pmid41720758,
year = {2026},
author = {Falahati, M and Orangi, K and Shaabanpoor Haghighi, A and Pouroushaninia, N and Niknam, N and Soltani, S and Radnia, P and Arab Bafrani, M and Shirdel, S and Aarabi, MH},
title = {Microstructural alterations of the amygdala in neurodegenerative and neuroinflammatory disorders: insights from diffusion tensor imaging.},
journal = {Reviews in the neurosciences},
volume = {},
number = {},
pages = {},
pmid = {41720758},
issn = {2191-0200},
abstract = {Diffusion tensor imaging (DTI) is a valuable method for evaluating microstructural changes in the amygdala associated with neurodegenerative and neuroinflammatory disorders. This systematic review examines amygdala microstructural alterations in Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB), and multiple sclerosis (MS) using DTI metrics. Following PRISMA 2020 guidelines, we searched PubMed, Scopus, and Web of Science databases through August 2025, identifying 4,442 records. After screening and eligibility assessment, 13 studies were included, comprising 1,412 patients and 1,146 healthy controls. Due to sample heterogeneity and lack of standardized effect size measures, meta-analysis was not performed. Across disorders, elevated mean diffusivity (MD) emerged as the most consistent finding, present in 100 % of AD patients and observed in all examined conditions. Reduced fractional anisotropy (FA) was the second most frequent alteration, with 36.6 % of AD patients showing decreased FA. In MS, increased radial diffusivity (RD) was prominent, while longitudinal DLB studies revealed progressive free water (FW) increases. These DTI-based microstructural changes often preceded volumetric atrophy and correlated with clinical severity. Our findings demonstrate that DTI metrics, particularly MD and FA, serve as sensitive markers of amygdala pathology across neurodegenerative diseases and may facilitate early diagnosis, disease monitoring, and differential diagnosis of these conditions.},
}

@article {pmid41718986,
year = {2026},
author = {Shadfar, S and Assar Kashani, S and Gautam, S and Takalloo, Z and Farzana, F and Parakh, S and Atkin, JD},
title = {The Role of the Golgi Apparatus in Neurodegeneration.},
journal = {Sub-cellular biochemistry},
volume = {111},
number = {},
pages = {413-440},
pmid = {41718986},
issn = {0306-0225},
mesh = {*Golgi Apparatus/metabolism/pathology ; Humans ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; *Neurons/metabolism/pathology ; },
abstract = {The Golgi apparatus has important, well characterised functions in the trafficking, processing, and post-translational modification of proteins and lipids. However, roles in other cellular processes are increasingly reported, including autophagy, apoptosis, DNA repair, and cytoskeletal (microtubules and actin) function. The Golgi therefore serves as a regulatory hub for multiple signalling pathways that maintain essential cellular activities. The Golgi normally consists of flattened stacks of membrane (cisternae), but during normal physiology and pathological conditions it 'fragments', resulting in altered morphology and distribution. This is well described as an early pathological feature of many neurodegenerative diseases, including Alzheimer's (AD), Parkinson's (PD), Huntington's (HD) and prion diseases, and amyotrophic lateral sclerosis (ALS). These age-related conditions are characterised by the death of neurons: highly specialised, unique cells that form the foundation of the nervous system. Interestingly, many Golgi-related functions are also dysregulated in these diseases. However, this has received relatively little attention compared to other pathogenic mechanisms. The Golgi apparatus in neurons shares features common to other eukaryotic cells but it also has unique properties, such as the presence of distinctive assemblies: Golgi outposts and satellites, which remain poorly characterised. Here we discuss the increasing evidence describing dysfunction and fragmentation of the Golgi apparatus and its possible role in the pathogenesis of neurodegenerative diseases.},
}

*Golgi Apparatus/metabolism/pathology
Humans
*Neurodegenerative Diseases/metabolism/pathology
Animals
*Neurons/metabolism/pathology

@article {pmid41659424,
year = {2026},
author = {Chen, R and Stockwell, I and Pierce, JC and Peak-Chew, SY and Huang, M and Newell, K and Ghetti, B and Cousin, MA and Greger, IH and Ryskeldi-Falcon, B},
title = {Pathological TDP-43 filaments accumulate at synapses and cause synaptic dysfunction.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41659424},
issn = {2692-8205},
support = {R01 AG080001/AG/NIA NIH HHS/United States ; R01 NS137469/NS/NINDS NIH HHS/United States ; RF1 AG071177/AG/NIA NIH HHS/United States ; U01 NS110437/NS/NINDS NIH HHS/United States ; },
abstract = {The assembly of TAR DNA-binding protein 43 (TDP-43) into amyloid filaments within neurons is a hallmark of multiple neurodegenerative diseases, including motor neuron diseases (MND), frontotemporal dementias (FTD) and limbic-predominant age-related TDP-43 encephalopathy (LATE). These diseases result from the deterioration and loss of neurons, with synaptic dysfunction and neuronal hyperexcitability being prominent early events. Pathogenic mutations in the TDP-43 gene, TARDBP, that promote filament formation have established a causal role for TDP-43 assembly in neurodegenerative diseases. However, the molecular mechanisms underlying filament accumulation and their contribution to neurodegeneration are poorly understood. TDP-43 filaments can propagate between neurons in a prion-like manner, which may underlie the progressive spread and accumulation of TDP-43 pathology in disease. Here, we studied early stages of TDP-43 filament accumulation following internalisation of patient-derived TDP-43 filaments by mouse and human cortical neurons. Using proximity labelling, we identified molecular environments and putative interactions of TDP-43 filaments. We found that TDP-43 filaments accumulated at synapses, particularly in proximity to the presynaptic active zone, which we confirmed in FTD patient brain sections. Electron cryo-tomography (cryo-ET) directly visualised abundant TDP-43 filaments spanning the presynaptic cytoplasm in situ, which contacted synaptic vesicles and the plasma membrane. Functional measurements revealed that the accumulation of TDP-43 filaments led to presynaptic dysfunction and subsequent neuronal hyperexcitability. These findings suggest that synapses are a major early site of TDP-43 filament accumulation, relevant to their propagation, and directly link TDP-43 filament gain of function to synaptic dysfunction.},
}

@article {pmid41718496,
year = {2026},
author = {Judge, S and Ballesteros, K and McDermott, CJ and Bloch, S},
title = {Timing of communication and technology control support in ALS - a systematic review.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/21678421.2026.2627899},
pmid = {41718496},
issn = {2167-9223},
abstract = {Objective: To review evidence on the optimal timing of interventions that support communication and technology control for people living with Amyotrophic Lateral sclerosis (ALS). Methods: A systematic review was conducted following a pre-registered protocol. Databases were searched for studies involving people living with ALS that addressed timing of assistive technology interventions for communication or technology control. Screening and data extraction were completed in duplicate, findings were synthesized using a thematic analysis, and relevant findings presented as a descriptive summary. Results: Twenty-eight studies met the inclusion criteria. Evidence focused overwhelmingly on communication support rather than wider assistive technology interventions. Need for a communication aid typically occurs between one and five years from diagnosis and the timing of this varies significantly according to the site of onset of ALS. There are significant variations in the timing of changes for individuals within these groupings and there are likely a larger number of groupings that would be clinically useful. A significant correlation between changes in speaking rate and intelligibility has been shown. Once changes to speech do start to occur then the time to the loss of functional speech appears relatively consistent across the types of ALS. Conclusion: Current best practice guidelines are not reflective of the findings of this review and do not support professionals in identifying how to provide timely support. Monitoring speech changes systematically may support timely intervention. There is potential for individual level predictive modeling to help support people living with ALS to be proactive and prepared for changes.},
}

@article {pmid41718455,
year = {2026},
author = {Wan, Y and Yu, Z and Yang, J and Zhang, W and Yu, M and Meng, L and Wang, Z and Yuan, Y and Ruan, L and Deng, J and Wang, P},
title = {The Mislocalization of TDP-43 to Mitochondria Impairs Myotube Maturation.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {40},
number = {4},
pages = {e71603},
doi = {10.1096/fj.202504624R},
pmid = {41718455},
issn = {1530-6860},
support = {2025ZD0217600//Brain Science and Brain-like Intelligence Technology/ ; 32460138//National Natural Science Foundation of China/ ; 82422025//National Natural Science Foundation of China/ ; 82401635//National Natural Science Foundation of China/ ; 82430059//National Natural Science Foundation of China/ ; 32571340//National Natural Science Foundation of China/ ; 2024YFA1803700//National Key Research and Development Program of China/ ; 2023HQ03//National High Level Hospital Clinical Research Funding/ ; PKU2025PKULCXQ016//Clinical Medicine Plus X/ ; },
mesh = {*DNA-Binding Proteins/metabolism/genetics ; Animals ; Mice ; Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology ; *Muscle Fibers, Skeletal/metabolism/pathology ; *Mitochondria/metabolism ; Cell Differentiation ; Cell Line ; Protein Transport ; Myoblasts/metabolism ; },
abstract = {Aggregation of TDP-43 in neuronal cells is a defining neuropathological hallmark of amyotrophic lateral sclerosis (ALS). Emerging evidence suggests that TDP-43 pathology also occurs in skeletal muscle fibers, but its functional significance in myocytes remains poorly understood. In this study, we utilized the C2C12 myoblast cell to investigate the subcellular localization of TDP-43 during myogenic differentiation. Our findings demonstrate that TDP-43 progressively translocates to mitochondria in parallel with myotube maturation. Notably, increased mitochondrial localization of TDP-43 was also observed in skeletal muscle tissues from patients with ALS, corroborating the clinical relevance of this phenomenon. Functional assays revealed that inhibition of TDP-43 mitochondrial translocation significantly enhances myotube maturation. Collectively, these results support a pathophysiological role for aberrant mitochondrial mislocalization of TDP-43 in regulating myogenic differentiation and contributing to muscle degeneration in TDP-43 proteinopathies.},
}

*DNA-Binding Proteins/metabolism/genetics
Animals
Mice
Humans
*Amyotrophic Lateral Sclerosis/metabolism/pathology
*Muscle Fibers, Skeletal/metabolism/pathology
*Mitochondria/metabolism
Cell Differentiation
Cell Line
Protein Transport
Myoblasts/metabolism

@article {pmid41718290,
year = {2026},
author = {Messina, C},
title = {Silent Damage, Delayed Symptoms: A Case of Breast Cancer Radiation-Induced Lumbosacral Plexopathy.},
journal = {Reports (MDPI)},
volume = {9},
number = {1},
pages = {},
pmid = {41718290},
issn = {2571-841X},
abstract = {Background and Clinical Significance: Radiation-induced lumbosacral plexopathy (RILP) is a rare but potentially debilitating complication of radiotherapy, typically affecting patients treated for pelvic malignancies. We report the first documented case of asymmetric RILP following radiotherapy for breast cancer. Case Presentation: A 64-year-old woman developed progressive left lower limb weakness, foot drop, and sensory disturbances four years after receiving locoregional radiotherapy extending to the left thoracoabdominal and lumbar areas. Electrophysiological studies revealed an asymmetric sensorimotor axonal neuropathy predominantly involving the left lower limb, without conduction block and sparing the upper limbs, whereas needle electromyography of the lower limbs showed fibrillation potentials, positive sharp waves, and fasciculations in the vastus lateralis, tibialis anterior, and medial gastrocnemius muscles on the left. Magnetic resonance imaging demonstrated edema and contrast enhancement of bilateral L2-L4 nerve roots with paraspinal muscle atrophy. Cerebrospinal fluid analysis showed albuminocytologic dissociation and elevated neurofilament levels. After exclusion of alternative diagnoses, including amyotrophic lateral sclerosis and inflammatory neuropathies, a diagnosis of radiation-induced peripheral neuropathy and RILP was made. The patient's condition stabilized with physiotherapy and symptomatic treatment. Conclusions: This case highlights the need for heightened awareness of RILP as a late complication of breast cancer radiotherapy, underscoring the importance of accurate diagnosis to avoid misclassification and unnecessary treatments. Clinicians should carefully integrate all clinical elements-including a thorough remote medical history-since radiation-related neurological damage may manifest many years after the initial insult.},
}

@article {pmid41717003,
year = {2026},
author = {Inami, S and Jenny, BP and Akpoghiran, O and Gallagher, SI and Strich, AK and Tonoki, A and Trotti, D and Haeusler, AR and Koh, K},
title = {Increased neuronal activity restores circadian function in Drosophila models of C9orf72-ALS/FTD.},
journal = {iScience},
volume = {29},
number = {2},
pages = {114798},
pmid = {41717003},
issn = {2589-0042},
abstract = {Circadian rhythm disruptions are common across neurodegenerative diseases, but their link to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) remains unclear. The C9orf72 hexanucleotide repeat expansion is the most prevalent genetic cause of ALS/FTD. Here, we used Drosophila models expressing pathogenic arginine-rich dipeptides (PR or GR) or GGGGCC hexanucleotide repeats to investigate circadian deficits in C9orf72-ALS/FTD. We found that circadian rhythmicity and period length were altered in a repeat number-, dosage-, expression pattern-, and age-dependent manner. Additionally, we observed lower levels of the neuropeptide PDF, a key regulator of free-running circadian rhythms, as well as decreased projection complexity and reduced neuronal activity in PDF-expressing neurons. Importantly, increases in neuronal activity significantly rescued mild circadian dysfunction across ages and across PR, GR, and GGGGCC repeat models when appropriately tuned. These results implicate reduced neuronal activity in C9orf72-ALS/FTD circadian deficits, underscoring the importance of calibrated, and stage-specific interventions.},
}

@article {pmid41716354,
year = {2025},
author = {Moleón, VR and Ayoubi, R and Alende, C and Fothouhi, M and Ryan, J and Bolívar, SG and Worrall, D and Durcan, TM and Brown, CM and Francis, V and McPherson, PS and Laflamme, C},
title = {A guide to selecting high-performing antibodies for Optineurin (UniProt ID: Q96CV9) for use in western blot, immunoprecipitation, and immunofluorescence.},
journal = {F1000Research},
volume = {14},
number = {},
pages = {1137},
pmid = {41716354},
issn = {2046-1402},
mesh = {Humans ; Cell Cycle Proteins ; Membrane Transport Proteins ; *Transcription Factor TFIIIA/immunology ; *Immunoprecipitation/methods ; *Blotting, Western/methods ; *Antibodies/immunology ; *Fluorescent Antibody Technique/methods ; },
abstract = {Optineurin (OPTN) is a multifunctional cytoplasmic adaptor protein implicated in maintaining neuronal homeostasis through its roles in selective autophagy, vesicle trafficking, and regulation of inflammatory signaling. Mutations in the OPTN gene are causally linked to several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and primary open-angle glaucoma. Here we have eight optineurin commercial antibodies for western blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. These studies are part of a larger, collaborative initiative seeking to address antibody reproducibility issues by characterizing commercially available antibodies for human proteins and publishing the results openly as a resource for the scientific community. While the use of antibodies and protocols vary between laboratories, we encourage readers to use this report as a guide to select the most appropriate antibodies for their specific needs.},
}

Humans
Cell Cycle Proteins
Membrane Transport Proteins
*Transcription Factor TFIIIA/immunology
*Immunoprecipitation/methods
*Blotting, Western/methods
*Antibodies/immunology
*Fluorescent Antibody Technique/methods

@article {pmid41714445,
year = {2026},
author = {Liu, X and Liu, Y and Lee, ML and Hsu, W and Liow, MHL},
title = {Reply to determining MCID threshold for Knee Society Score to assess patient satisfaction in knee arthroplasty.},
journal = {NPJ digital medicine},
volume = {9},
number = {1},
pages = {182},
pmid = {41714445},
issn = {2398-6352},
abstract = {This reply addresses Wang et al.'s comments on our prior work and clarifies that the 34.5-point Knee Society Score threshold was derived from our previously validated, anchor-based approach. We agree that future research should refine predictive models by establishing consensus, standardised minimal clinically important difference cutoffs to enhance applicability and reliability in real-world clinical settings.},
}

@article {pmid41714394,
year = {2026},
author = {Warmann, S},
title = {[Motor neuron diseases from a radiological perspective : Focus on amyotrophic lateral sclerosis].},
journal = {Radiologie (Heidelberg, Germany)},
volume = {},
number = {},
pages = {},
pmid = {41714394},
issn = {2731-7056},
abstract = {BACKGROUND: Motor neuron diseases (MND) affect the upper and/or lower motor neurons. Radiological diagnostics primarily serve to systematically exclude treatable mimics and support the clinical and electrophysiological diagnosis. The focus is on amyotrophic lateral sclerosis (ALS); supplementary progressive muscular atrophy (PMA, purely lower motor neuron, LMN disease) and spinal muscular atrophy (SMA).

OBJECTIVE: Which imaging signs support the diagnosis of ALS, how do electromyography/magnetic resonance imaging (EMG/MRI) fit into the Gold Coast criteria and which other motor neuron diseases are relevant?

MATERIAL AND METHODS: Overview of clinical criteria (Gold Coast), genetics and typical MRI findings of the brain, spinal cord and musculature.

RESULTS: Gold Coast core: progressive motor deterioration, upper motor neuron (UMN) and LMN signs in ≥ 1 region or LMN in ≥ 2 regions and exclusion of alternative causes.

IMAGING: susceptibility-weighted imaging (SWI) motor band sign as UMN marker; T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities along the corticospinal tract with low sensitivity, moderate specificity; T1 bright tongue as an indication of chronic denervation in bulbar involvement. EMG: detection of subclinical LMN involvement, sometimes limited in UMN-dominant/bulbar courses. PMA: Pure purely LMN symptoms, often continuum to ALS. SMA: Autosomal autosomal recessive (SMN1 deletion).

DISCUSSION: The diagnosis remains primarily clinical; EMG and MRI are supportive. The radiological priority is the exclusion of mimics. The UMN markers increase diagnostic certainty in the context of clinical/EMG findings but do not replace them. Clear findings facilitate classification according to Gold Coast. The PMA and SMA require careful differential diagnostics; characteristic MRI patterns support progression and treatment planning.},
}

@article {pmid41714091,
year = {2026},
author = {Howard, J and Bekker, HL and McDermott, CJ and McNeill, A},
title = {Predictive genetic testing in amyotrophic lateral sclerosis (ALS): Experiences of decision-making and engagement with UK genetic counseling services.},
journal = {Journal of genetic counseling},
volume = {35},
number = {1},
pages = {e70184},
pmid = {41714091},
issn = {1573-3599},
support = {/MNDA_/Motor Neurone Disease Association/United Kingdom ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis ; United Kingdom ; *Genetic Counseling/psychology ; *Genetic Testing/methods ; Female ; Male ; Middle Aged ; *Decision Making ; Adult ; Aged ; },
abstract = {Predictive genetic testing enables at-risk relatives of people with amyotrophic lateral sclerosis (ALS, also known as motor neuron disease or MND) to find out if they have inherited the genetic variant identified in their family member and have an increased chance of developing symptoms. As research progresses, eligibility for and interest in predictive testing is increasing. This paper explores the experiences of people making decisions about predictive testing and identifies their information needs over the process. Semi-structured interviews were carried out with 14 individuals from across the United Kingdom who had, or were considering, predictive testing for ALS. Interviews were carried out via video call or face-to-face between March and September 2023, transcribed, and analyzed using inductive framework analysis. Findings illustrate a range of experiences. Interviews suggest variation in practice in terms of the structure of the genetic counseling process and the content of information given. Some expressed positive experiences of genetic counseling, and valued feeling listened to, understood, and supported. Others perceived barriers to accessing testing, felt the information provided was directive or not sufficient to support their concerns and decision-making. Information needs varied, and whilst people felt satisfied, there were also diverse, unmet information and support needs raised throughout the decision-making process and beyond. This evidence has been used to support the development of a patient decision aid for predictive genetic testing in ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/diagnosis
United Kingdom
*Genetic Counseling/psychology
*Genetic Testing/methods
Female
Male
Middle Aged
*Decision Making
Adult
Aged

@article {pmid41621673,
year = {2026},
author = {Dev, A and Mehta, H and Vinay, K},
title = {Response to Gao et al's "Can we navigate the pitfalls of tofacitinib RCTs in vitiligo? Addressing long-term safety and generalizability for enhanced clinical translation".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.01.059},
pmid = {41621673},
issn = {1097-6787},
}

@article {pmid41713588,
year = {2026},
author = {Akaike, T and Thakuria, M and Silk, AW and Hippe, DS and Ch'en, PY and Guja, KE and Youn Park, S and Tsai, K and Yom, SS and Yu, SS and Choi, J and Chandra, S and Nghiem, PT and Zaba, LC},
title = {Response to Gao and Chen, "Comments on Akaike et al.'s 'Circulating tumor DNA level is associated with time to clinical recurrence in Merkel cell carcinoma: Implications for patient management'".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.01.094},
pmid = {41713588},
issn = {1097-6787},
}

@article {pmid41713587,
year = {2026},
author = {Gao, BY and Chen, SC},
title = {Comments on Akaike et al.'s "Circulating tumor DNA level is associated with time to clinical recurrence in Merkel cell carcinoma: Implications for patient management".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.11.110},
pmid = {41713587},
issn = {1097-6787},
}

@article {pmid41712834,
year = {2025},
author = {Finsterer, J and Mehri, S},
title = {Immobile ALS patients or those at risk of venous thromboembolism require a comprehensive examination and low-dose heparinisation.},
journal = {La Tunisie medicale},
volume = {103},
number = {3},
pages = {306},
doi = {10.62438/tunismed.v103i3.5658},
pmid = {41712834},
issn = {2724-7031},
}

@article {pmid41712833,
year = {2025},
author = {Hamad, AA},
title = {How Amyotrophic Lateral Sclerosis Contributes to Increased Venous Thromboembolism Risk.},
journal = {La Tunisie medicale},
volume = {103},
number = {3},
pages = {307-308},
doi = {10.62438/tunismed.v103i3.5734},
pmid = {41712833},
issn = {2724-7031},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/epidemiology ; *Venous Thromboembolism/etiology/epidemiology ; Risk Factors ; Female ; Male ; Middle Aged ; Aged ; },
}

Humans
*Amyotrophic Lateral Sclerosis/complications/epidemiology
*Venous Thromboembolism/etiology/epidemiology
Risk Factors
Female
Male
Middle Aged
Aged

@article {pmid41712140,
year = {2026},
author = {Li, C and Huang, L and Li, X},
title = {The effect of arousal on Chinese word segmentation.},
journal = {Psychonomic bulletin & review},
volume = {33},
number = {2},
pages = {91},
pmid = {41712140},
issn = {1531-5320},
support = {32371156//Major Research Plan/ ; },
mesh = {Humans ; *Arousal/physiology ; *Reading ; *Language ; Young Adult ; Psycholinguistics ; Adult ; *Emotions/physiology ; China ; },
abstract = {In the absence of inter-word spaces, Chinese readers rely on other available information for word segmentation. An earlier study demonstrated that the valence of words influences word segmentation (Huang et al., Psychonomic Bulletin & Review, 31 (4), 1548-1557, 2024). The current study further investigated the influence of arousal, another key dimension of emotion, on Chinese word segmentation. We first re-analyzed the segmentation results from Huang et al.'s study and found that arousal had an independent effect on Chinese word segmentation. In the experimental study, we manipulated the arousal levels of words while keeping valence at a neutral level. The results provide evidence that the arousal of words can affect Chinese word segmentation, with higher-arousal words being more likely to be segmented than low-arousal words. Moreover, our findings are also essential for understanding the impact of arousal on word processing and suggest that it impacts the early stage of activating a word's representation.},
}

Humans
*Arousal/physiology
*Reading
*Language
Young Adult
Psycholinguistics
Adult
*Emotions/physiology
China

@article {pmid41711838,
year = {2026},
author = {Duan, L and Wang, Y and Jing, H and Wang, Y and Ning, S and Yang, Z and Zhang, A},
title = {Exploring the causal relationship between plasma proteins and obstructive sleep apnea: a study using genome-wide Mendelian randomization, single-cell RNA sequencing analysis, and network pharmacology.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {41711838},
issn = {1432-1912},
abstract = {Observational studies suggest that plasma proteins play a crucial role in the development and progression of obstructive sleep apnea (OSA); however, the causal relationship between plasma proteins and OSA remains controversial. This study conducted a comprehensive evaluation of the causal relationships between 4,907 plasma proteins and OSA by employing bidirectional Mendelian randomization (MR) analysis, network pharmacology strategies, and single-cell sequencing techniques. The plasma protein data used in this study were derived from Ferkingstad et al.'s research (n = 35,559), and OSA-related data were obtained from genome-wide association studies (GWAS) conducted on European populations through Finland's biobank (FinnGen). This study utilized multi-omics integration strategies, including enrichment analysis, protein-protein interaction (PPI) network construction, drug target prediction, molecular docking simulation, and single-cell transcriptome sequencing, to investigate the biological mechanisms of identified targets and evaluate their potential applications in drug development. MR analysis identified 62 plasma proteins significantly associated with OSA risk, including NTN4 (p = 0.003, OR = 1.076, CI [1.024, 1.129]) and TFF2 (p = 0.004, OR = 1.098, CI [1.029, 1.174]). Further reverse Mendelian analysis revealed causal relationships between OSA and the CELF2, NTRK3, ANTXR2, and MYOM2 genes. PPI network analysis identified 10 core genes, including IL1β, TGFβ1, EGF, SHH, and SMAD2, which participate in critical pathological processes in OSA, such as oxidative stress, inflammatory responses, and immune regulation. Through drug prediction analysis, this study identified compounds with potential therapeutic effectiveness, including 3,4-DHB, BIM IX, and 1,9-Pyrazoloanthrone, and molecular docking studies further confirmed their high binding affinity to target proteins. Single-cell sequencing revealed high expression levels of key genes in T cells and dendritic cells, thereby confirming the critical role of these cells in the pathological progression of OSA. A total of 62 candidate therapeutic targets for OSA were identified in this study, with 10 of these targets deemed important candidates for clinical trials. These findings not only enrich the understanding of the molecular pathological mechanisms underlying OSA but also offer new perspectives for developing targeted therapeutic strategies to treat the condition. By facilitating the establishment of more precise and personalized disease management approaches, these results are expected to advance the development of therapeutic drugs for OSA and substantially reduce the economic costs associated with new drug development.},
}

@article {pmid41710977,
year = {2026},
author = {Liu, Q and Zhang, X and Wang, L and Chen, H and Wang, G and Sun, Y and He, B and Gao, J and Qiu, W and Ma, C and Sun, M and Cui, L and Zhang, X},
title = {BTK inhibition suppresses neuroinflammation and neurodegeneration in amyotrophic lateral sclerosis.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag070},
pmid = {41710977},
issn = {1460-2156},
abstract = {Amyotrophic lateral sclerosis(ALS) is a devastating neurodegenerative disorder with limited therapeutic interventions. Neuroinflammation represents a central pathogenic mechanism in ALS, yet the upstream molecular regulators that integrate multiple inflammatory cascades remain poorly understood. Here, we investigated whether Bruton's tyrosine kinase (BTK), which integrates DNA-sensing and Toll-like receptor signals upstream of the cGAS-STING-NF-κB cascade, serves as a key regulatory node in ALS pathogenesis. Public RNA-seq datasets of motor neurons and post-mortem tissues from ALS patients were utilized to identify BTK expression patterns. SOD1-mutant human induced pluripotent stem cells (hiPSC) were differentiated into motor neurons (hiPSC-MNs) and microglia (hiPSC-MGs). NF-κB dysregulation was profiled by scRNA-seq (hiPSC-MGs) and bulk RNA-seq (hiPSC-MNs). DNA damage (γH2AX), inflammatory signalling (western blot/ELISA) and phagocytosis (pH-rodo uptake) were quantified, and MG-conditioned medium was tested for MN toxicity. Monocultures and MN-MG co-cultures received zanubrutinib (3 µM, 12 h). SOD1-G93A mice were administered zanubrutinib (30 mg/kg, daily) from 2.5 months; motor performance, survival, spinal histology and PI3K-AKT-mTOR activity were assessed after 2 months of treatment. ALS spinal cord and cortex tissues of patients, as well as SOD1-mutant hiPSC-MGs and hiPSC-MNs, demonstrated elevated BTK phosphorylation with increased p-STING, p-TBK1, and nuclear NF-κB accumulation. ALS hiPSC-MGs exhibited inflammatory activation, NLRP3 induction, and impaired phagocytosis, while ALS hiPSC-MNs showed DNA damage and caspase-3-mediated apoptosis. Conditioned medium from inflammatory microglia amplified neuronal STING-NF-κB activity and apoptosis, demonstrating non-cell-autonomous toxicity. The STING inhibitor H-151 reduced neuronal p-STING/p-TBK1/NF-κB and apoptosis, confirming pathway causality. Pharmacological BTK inhibition reduced DNA damage in ALS hiPSC-MNs by 61.4% (p<0.05), restored phagocytosis in ALS hiPSC-MGs to 87.2% of control levels (p<0.01), and prevented neuronal apoptosis induced by microglial conditioned medium. In SOD1-G93A mice, BTK blockade extended median survival from 158 to 173 days (p<0.01, log-rank test), improved motor function, and attenuated neuroinflammation while moderately rebalancing PI3K-AKT-mTOR signaling without impairing autophagy-lysosome dynamics. We identify BTK as a critical upstream regulator of the dysregulated cGAS-STING-NF-κB signalling axis characteristic of ALS pathogenesis. BTK orchestrates both cell-autonomous dysfunction in motor neurons and non-cell-autonomous toxicity through microglial activation, representing a convergent regulatory node that integrates multiple pathogenic pathways. These mechanistic insights provide a molecular framework for understanding ALS neuroinflammation and establish a rational basis for BTK-targeted therapeutic intervention in neurodegeneration.},
}

@article {pmid41710834,
year = {2026},
author = {Chen, HW},
title = {Active Craniospinal Tensioning (ACT): Axial Spinal Traction for Glymphatic Modulation.},
journal = {Cureus},
volume = {18},
number = {1},
pages = {e101796},
pmid = {41710834},
issn = {2168-8184},
abstract = {The glymphatic system is a clearance pathway that facilitates convective exchange between cerebrospinal fluid (CSF) and interstitial fluid, and is increasingly implicated in the pathophysiology of neurodegenerative and neuroinflammatory disorders. However, translation of glymphatic physiology into intentional, noninvasive biomechanical interventions remains limited. Building on a previously introduced biomechanical framework that proposed axial spinal traction as a method to modulate CSF and glymphatic circulation, practitioner-applied pelvis-stabilized axial spinal traction (PSAST) has been characterized as a controlled prototype, although its reliance on professional administration and structured setup may constrain deployment in population-level or preventive contexts. This report introduces active craniospinal tensioning (ACT) as a translational, participant-driven extension of the established axial traction-glymphatic modulation framework, specifically designed for ambulatory populations. ACT employs a voluntary squat maneuver combined with a standardized overhead anchor system to generate controlled axial tension along the craniospinal axis, while preserving the same dural tensioning and craniospinal coupling principles described in prior axial traction models. By shifting force generation from practitioner-applied loading to participant-regulated loading, ACT presents a scalable approach for exploratory preventive application under supervised conditions. ACT is theoretically framed for individuals exhibiting reduced perivascular water diffusivity, such as those with lower diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) indices. This report provides a practical implementation framework for ACT and supports future hypothesis-driven investigation of biomechanical modulation of CSF and glymphatic circulation using advanced neuroimaging biomarkers.},
}

@article {pmid41710754,
year = {2026},
author = {Corvino, A and Caliendo, G and Fiorino, F and Frecentese, F and Valsecchi, V and Lombardi, G and Anzilotti, S and Andreozzi, G and Scognamiglio, A and Sparaco, R and Perissutti, E and Severino, B and Gargiulo, M and Santagada, V and Pignataro, G},
title = {Correction to "Newly Synthesized Indolylacetic Derivatives Reduce Tumor Necrosis Factor-Mediated Neuroinflammation and Prolong Survival in Amyotrophic Lateral Sclerosis Mice".},
journal = {ACS pharmacology & translational science},
volume = {9},
number = {2},
pages = {461},
doi = {10.1021/acsptsci.6c00037},
pmid = {41710754},
issn = {2575-9108},
abstract = {[This corrects the article DOI: 10.1021/acsptsci.4c00098.].},
}

@article {pmid41710159,
year = {2026},
author = {Pang, Y and Yang, J and Liu, J and Xie, Z and Wang, J},
title = {Metabolic interactions in the brain: the crucial roles of neurons, astrocytes, and microglia in health and disease.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1731771},
pmid = {41710159},
issn = {1662-4548},
abstract = {This review provides an in-depth exploration of the intricate energy metabolism pathways within the brain, with a particular focus on the dynamic interplay between neurons, astrocytes, and microglia. Neurons, with their high energy demands, primarily rely on oxidative phosphorylation and the tricarboxylic acid (TCA) cycle to sustain synaptic activity and neurotransmitter synthesis. In contrast, astrocytes predominantly engage in glycolysis, producing lactate and glutathione, which are essential for supporting neuronal function and protecting against oxidative stress. Additionally, microglia, the brain's resident immune cells, exhibit a metabolic flexibility that allows them to shift between oxidative phosphorylation and glycolysis, depending on their activation state, which significantly influences neuroinflammation and synaptic plasticity. The review highlights the critical role of astrocyte-neuron metabolic coupling, particularly through the lactate shuttle and glutathione metabolism, in maintaining neuronal homeostasis and facilitating synaptic function. It also delves into the metabolic underpinnings of neurodegenerative diseases such as Alzheimer's, Parkinson's, and Amyotrophic Lateral Sclerosis, illustrating how disruptions in brain energy metabolism contribute to disease progression. By synthesizing recent findings, this review not only underscores the centrality of brain energy metabolism in both normal and pathological conditions but also identifies potential therapeutic targets aimed at modulating these metabolic pathways to mitigate the effects of neurodegenerative disorders. This comprehensive analysis offers valuable insights that could propel further research and innovation in the field of neurology, making it essential reading for experts interested in the molecular mechanisms underlying brain function and disease.},
}

@article {pmid41709060,
year = {2026},
author = {Yadav, AK and Verma, P and Srivastava, A and Srivastava, P and Rai, R and Rathour, S},
title = {Molecular insights into glial neuroimmune cross reactivity with CNS antigens and its role in neuroinflammation.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {41709060},
issn = {1568-5608},
abstract = {Neuroinflammation has been increasingly considered a key player of neurodegenerative as well as psychiatric disorders. This review integrates existing knowledge on glial-neuroimmune interactions, emphasizing the roles of cytokine signaling, glial activation, and BBB modulation in neuro-pathogenesis. A systematic review was performed studying peer-reviewed literature on molecular pathways of microglia, astrocytes, endothelial cells, and peripheral immune mediators. A possible explanation of this finding could be that the model is based on the underlying pathophysiology, and this is shared across disease contexts, including multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and traumatic brain injury. Novel in vitro platforms, including the organ-on-a-chip and brain organoids, were also discussed for their translational potential. Microglia M1/M2 polarization and astrocyte reactivity appeared to be a common feature in neurotoxicity as well as excitotoxicity and chronic inflammation. Cytokine cascade of TNF-α, IL-1β, and IL-6 led to the disrupted BBB, allowing for peripheral immune cells to infiltrate. Both the NLRP3 inflammasome and mitochondrial dysfunction were identified as enhancers of neuroimmune signaling. Comparing across disease models, shared relationships emerged between glia-cytokines-BBB. Advanced in vitro systems proved to be useful to model these interactions and screen prescription drugs. This review highlights existing insights into glia-neuroimmune cross-reactivity and its critical role in CNS disease. The molecular interactions between these molecules could represent promising targets for novel therapeutic options. We suggests integrative systems platforms and AI-driven strategies to expedite clinical translation in neuroinflammation.},
}

@article {pmid41708347,
year = {2026},
author = {Gontier, G and Kim, G and Wang, C and Zhu, K and Gau, R and Zhang, N and Naphade, S and Stewart, A and Schmidt, MJ and Galemmo, R and Shook, B and Tarachandani, A and Choi, I and Raines, S and Scannevin, RH and Grievink, HW and Smits, LMG and Kremer, PHC and Cadavid, D},
title = {Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB): A Translational Pharmacodynamic Biomarker for PIKfyve Inhibition With VRG50635.},
journal = {Clinical and translational science},
volume = {19},
number = {2},
pages = {e70489},
doi = {10.1111/cts.70489},
pmid = {41708347},
issn = {1752-8062},
support = {//Verge Genomics/ ; },
mesh = {Humans ; Animals ; Mice ; *Membrane Glycoproteins/metabolism/blood/cerebrospinal fluid ; Male ; *Amyotrophic Lateral Sclerosis/drug therapy/cerebrospinal fluid/blood ; Biomarkers/blood/cerebrospinal fluid ; Female ; Adult ; Middle Aged ; *Phosphoinositide-3 Kinase Inhibitors ; Phosphatidylinositol 3-Kinases/metabolism ; Leukocytes, Mononuclear/drug effects/metabolism ; Induced Pluripotent Stem Cells/drug effects ; Healthy Volunteers ; Administration, Oral ; },
abstract = {Glycoprotein non-metastatic melanoma protein B (GPNMB) was investigated as a pharmacodynamic (PD) biomarker for PIKfyve inhibition across translational studies ex vivo, in vitro, in animals, and in the clinic, demonstrating significant response to VRG50468 in cells, in vivo in the central nervous system (CNS) and in peripheral fluids and tissues. VRG50468 is the active metabolite of VRG50635, a small molecule PIKfyve inhibitor pro-drug in development for treating amyotrophic lateral sclerosis (ALS). Peripheral pharmacology was evaluated in peripheral blood mononuclear cells (PBMCs) from healthy volunteers ex vivo and in vitro and in PBMCs from mice given oral VRG50635. Central pharmacology was evaluated in vitro using C9orf72 ALS patient-derived induced pluripotent stem cell motor neurons and mouse primary neurons, and in vivo in brains of mice given oral VRG50635. Two clinical studies in healthy adults examined plasma, PBMCs, and cerebrospinal fluid following oral VRG50635 for peripheral and central pharmacologic activity via GPNMB induction. PD GPNMB upregulation with VRG50468 was demonstrated across preclinical translational and clinical studies. A PD response to VRG50468 was observed ex vivo in rodent and human PBMCs and in primary rodent neurons and motor neurons induced from stem cells of people with ALS. Repeated administration of VRG50635 to rodents and healthy human volunteers robustly induced GPNMB peripherally and in the CNS, which was concentration and time dependent in vitro and dose and treatment duration dependent in vivo, peripherally, and in CNS. GPNMB is a robust translatable PD biomarker for clinical trials with the PIKfyve inhibitor VRG50635. TRIAL REGISTRATION: Clinical trial number: VGCS-50635-001 and VGCS-50635-003; identifier: NL81735.056.22 and NCT06286475.},
}

Humans
Animals
Mice
*Membrane Glycoproteins/metabolism/blood/cerebrospinal fluid
Male
*Amyotrophic Lateral Sclerosis/drug therapy/cerebrospinal fluid/blood
Biomarkers/blood/cerebrospinal fluid
Female
Adult
Middle Aged
*Phosphoinositide-3 Kinase Inhibitors
Phosphatidylinositol 3-Kinases/metabolism
Leukocytes, Mononuclear/drug effects/metabolism
Induced Pluripotent Stem Cells/drug effects
Healthy Volunteers
Administration, Oral

@article {pmid41708070,
year = {2026},
author = {Court, LE and Smit, J and Strauss, L and Shaw, W and Marais, A and Trauernicht, C and Joubert, N and Smith, E and Badre, S and Lazarus, GL and Khotle, T and Netherton, L and van Heerden, W and Cardenas, C and Serban, M and Seuntjens, J and Chung, CV and Govyadinov, P and Khan, M and Nair, S and Netherton, T and Zhang, L},
title = {Leveraging large language models for heuristic usability assessment of medical software: Insights with the Radiation Planning Assistant.},
journal = {Journal of applied clinical medical physics},
volume = {27},
number = {2},
pages = {e70495},
doi = {10.1002/acm2.70495},
pmid = {41708070},
issn = {1526-9914},
mesh = {Humans ; *Software/standards ; *Radiotherapy Planning, Computer-Assisted/methods ; *Heuristics ; *User-Computer Interface ; *Programming Languages ; *Neoplasms/radiotherapy ; Large Language Models ; },
abstract = {BACKGROUND: Usability engineering is essential for ensuring the safety and effectiveness of medical software, as design-related issues are a leading cause of use errors in clinical settings. Heuristic evaluation provides a practical approach to identifying usability problems, but its outcomes depend heavily on expert interpretation. Large Language Models (LLMs), such as ChatGPT, offer a potential means to augment heuristic evaluation by generating structured, context-aware usability feedback. This study explored the use of ChatGPT to support heuristic assessment of the Radiation Planning Assistant (RPA), a web-based radiotherapy planning tool designed to support clinical teams in low- and middle-income countries.

METHODS: ChatGPT was provided with the RPA user and technical guides, training videos for each functional dashboard, and Zhang et al.'s 14 usability heuristics. The model was instructed to score each dashboard according to these heuristics, using Zhang's 0-4 severity scale, and to propose concrete interface improvements. The resulting feedback was reviewed and scored independently by the RPA developer team and by 13 users during a dedicated User Meeting. Comparative analysis was performed between ChatGPT, developer, and user ratings.

RESULTS: ChatGPT identified 26 potential usability issues across six heuristic domains. The developer team considered nine of these actionable, though all were classified as minor (severity ≤ 2). User ratings showed wide variability, with nine suggestions achieving mean scores ≥ 1.5. Qualitative agreement between users and developers was limited, underscoring the importance of diverse perspectives in heuristic evaluation. Three suggestions-enhanced upload logs, reversible actions ("reopen request"), and stronger error prevention-were rated as potentially high priority by a minority of users. ChatGPT's ratings were consistent across dashboards.

CONCLUSIONS: While ChatGPT did not reveal any critical usability failures, its heuristic assessment proved valuable in prompting discussion, identifying minor refinements, and enriching both developer and user engagement with the RPA's interface design. This study demonstrates that LLMs can serve as an effective, low-cost complement to conventional heuristic evaluation, supporting early-stage usability review and stakeholder dialogue in the development of medical software.},
}

Humans
*Software/standards
*Radiotherapy Planning, Computer-Assisted/methods
*Heuristics
*User-Computer Interface
*Programming Languages
*Neoplasms/radiotherapy
Large Language Models

@article {pmid41707709,
year = {2026},
author = {He, K and Wang, H and Cao, Y},
title = {Response to Bingyang Xu et al.'s "Optimized combination: Isotretinoin in conjunction with oral tranexamic acid for the treatment of moderate to severe acne vulgaris-A randomized, double-blind, placebo-controlled trial".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.12.117},
pmid = {41707709},
issn = {1097-6787},
}

@article {pmid41707703,
year = {2026},
author = {Xu, B and Wu, J},
title = {Response to He et al.'s comments of "Optimized combination: Isotretinoin in conjunction with oral tranexamic acid for the treatment of moderate to severe acne vulgaris-A randomized, double-blind, placebo-controlled trial".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.01.092},
pmid = {41707703},
issn = {1097-6787},
}

@article {pmid41706243,
year = {2026},
author = {Ma, M and Ren, Q and Sun, X and Lin, P and Li, W and Zhao, Y and Meng, X and Yan, C and Liu, S},
title = {Fixel-based analysis to detect early fiber-specific white matter alterations in sporadic patients with amyotrophic lateral sclerosis.},
journal = {Brain imaging and behavior},
volume = {20},
number = {1},
pages = {16},
pmid = {41706243},
issn = {1931-7565},
support = {2020M672067//China postdoctoral science foundation/ ; NSFC82001354//National Natural Science Foundation of China/ ; },
}

@article {pmid41706131,
year = {2026},
author = {Brünjes, N and Brenne, N and Rupp, D and Sassen, MC and Jerrentrup, A and Wulf, H and Heuser, N and Volberg, C},
title = {[Influence of airway management on the return of spontaneous circulation in out-of-hospital cardiac arrest: secondary analysis of a prospective multidevice study].},
journal = {Medizinische Klinik, Intensivmedizin und Notfallmedizin},
volume = {},
number = {},
pages = {},
pmid = {41706131},
issn = {2193-6226},
abstract = {BACKGROUND: With an incidence of 64.9/100,000 inhabitants in Germany, out-of-hospital cardiac arrest is a frequent reason for emergency medical services (EMS) deployment. Advanced airway management is a key part of advanced life support (ALS), enabling adequate ventilation and continuous chest compressions. Video laryngoscopy (VL), which is increasingly being used, is expected to lead to better success rates and shorter interruptions in chest compressions during airway management. Thus, this article focuses on type of airway management and the devices used and how they relate to the likelihood of achieving return of spontaneous circulation (ROSC) and the resulting survival and neurological outcome.

METHODS: Between January 2020 and June 2024, EMS personnel and emergency physicians received questionnaires on airway management of out-of-hospital resuscitations in which they were involved. The data were supplemented by emergency protocols and defibrillator recordings. The analysis was conducted descriptively and statistically at a significance level of α ≤ 0.05.

RESULTS: A total of 301 questionnaires were assessed: 35% of patients who received endotracheal intubation (ETI) achieved ROSC compared with 21.1% with the use of a supraglottic airway device (SGA; p = 0.09). With the McGrath VL, the ROSC rate was 43.6%, compared to 33.3% with the C‑MAC (p = 0.24). Following 1-2 intubation attempts, ROSC was achieved in 33.8% of cases, and in 28.6% of cases after more than two attempts. The survival rate was 9.1% after ETI and 2.6% after SGA (p = 0.17). With VL, 10.9% of patients survived, 64.7% with a good neurological outcome (cerebral performance category [CPC] 1-2). With direct laryngoscopy, 6.1% survived, 57.1% with CPC 1-2 (p = 0.19/p = 0.73).

CONCLUSION: The results show a potential advantage of video laryngoscopy for endotracheal intubation, whereby > 2 intubation attempts are associated with poorer outcomes. Significant effects on ROSC, survival or an improved neurological outcome were not observed. Larger studies are necessary to verify the results. Increased use of video laryngoscopy could be beneficial regardless of the user.},
}

@article {pmid41705664,
year = {2026},
author = {De Carvalho, M},
title = {Reviewer Comment on Dallaire et al. "Mortality and Complications of Percutaneous Gastrostomy in Amyotrophic Lateral Sclerosis Patients".},
journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques},
volume = {},
number = {},
pages = {1},
doi = {10.1017/cjn.2025.10511},
pmid = {41705664},
issn = {0317-1671},
}

@article {pmid41705449,
year = {2026},
author = {Mirian, A and Kassardjian, C},
title = {Reviewer Comment on Cooper et al. "Exploring the Value of Brain T2* Weighted and FLAIR Imaging for Diagnosing Amyotrophic Lateral Sclerosis".},
journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques},
volume = {},
number = {},
pages = {1},
doi = {10.1017/cjn.2026.10528},
pmid = {41705449},
issn = {0317-1671},
}

@article {pmid41705073,
year = {2026},
author = {Sotgia, S and Zinellu, A and Zoroddu, S and Pateri, MI and Loi, E and Pisano, A and Sabalic, A and Tutedde, D and Benedetti, AFV and Floris, F and Puligheddu, M and Valera, P and Zavattari, P and Borghero, G and Madeddu, R},
title = {Elevated serum trimethylamine N-oxide (TMAO) and trimethyllysine in patients with amyotrophic lateral sclerosis (ALS): An exploratory case-control study.},
journal = {IBRO neuroscience reports},
volume = {20},
number = {},
pages = {227-231},
pmid = {41705073},
issn = {2667-2421},
abstract = {Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite implicated in protein homeostasis, inflammation, and chronic disease, but its relevance in amyotrophic lateral sclerosis (ALS) remains poorly characterized. In this exploratory pilot study, we quantified circulating TMAO and related trimethylammonium-containing compounds in a Sardinian ALS cohort using targeted LC-MS/MS. Serum samples were collected under fasting conditions from 12 ALS patients and 8 age- and sex-matched healthy controls. Median serum TMAO levels were markedly higher in ALS patients than in controls (27.9 vs. 4.0 µmol/L, P < 0.05), with substantial inter-individual variability in the ALS group (range 2.4-125.0 µmol/L). Trimethyllysine (TML) concentrations were also significantly elevated in ALS (0.43 vs. 0.34 µmol/L, P < 0.05), whereas choline, carnitine, betaine, ergothioneine, and γ-butyrobetaine levels did not differ between groups. Most ALS patients were receiving acetyl-L-carnitine (ALCAR) supplementation, suggesting that ALCAR intake may contribute to the observed metabolite profiles. Overall, these findings indicate alterations in trimethylammonium-containing compound metabolism in ALS and underscore the need for larger, well-controlled studies to determine whether such changes reflect disease-related mechanisms, treatment effects, or their interaction.},
}

@article {pmid41704326,
year = {2026},
author = {Stoian, M and Demenciuc, N and Laszlo, SS and Motataianu, A and Babă, DF and Stoian, A},
title = {Transition from ICU to home care with long-term invasive ventilation using a single-limb BiPAP circuit.},
journal = {Journal of critical care medicine (Universitatea de Medicina si Farmacie din Targu-Mures)},
volume = {12},
number = {1},
pages = {117-124},
pmid = {41704326},
issn = {2393-1809},
abstract = {BACKGROUND: Patients with chronic respiratory failure caused by severe neuromuscular impairment often require long-term respiratory support. Invasive mechanical ventilation (IMV) via tracheostomy is usually provided in intensive care units (ICUs), but in carefully selected cases, it can be safely transitioned to home care. The use of a single-limb ventilator circuit (Single BiPAP circuit with Whisper Swivel II), intended initially for non-invasive ventilation (NIV), may represent a cost-effective and practical alternative for long-term home IMV.

CASE PRESENTATION: We present a 50-year-old male with progressive neuromuscular disease and chronic respiratory failure, who required long-term IMV through a tracheostomy tube. After stabilization in the ICU, ventilation was maintained at home using a Single BiPAP circuit with Whisper Swivel II, combined with a mechanical insufflation-exsufflation (MIE) device for airway secretion clearance. The patient's family received structured training in tracheostomy care, ventilator operation, and secretion management. Over 32-month period, the patient maintained stable respiratory function, experienced a marked reduction in infectious exacerbations, and preserved an acceptable quality of life.

CONCLUSION: In selected patients, long-term home IMV using a single-limb ventilator combined with an MIE device can be a safe, effective, and cost-efficient alternative to conventional ICU-based ventilation. Successful outcomes require structured patient and caregiver training, close follow-up, and coordinated multidisciplinary support.},
}

@article {pmid41703036,
year = {2026},
author = {Kremeike, K and Golla, H and Albrecht, R and Montag, T and Mollidor, A and Pusch, L and Schmidtke, J and Welling, U and Voltz, R},
title = {[Care-related questions for specialized outpatient palliative care teams when faced with requests for assisted suicide: A case series].},
journal = {Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz},
volume = {},
number = {},
pages = {},
pmid = {41703036},
issn = {1437-1588},
abstract = {INTRODUCTION: Following the repeal of § 217 of the German Criminal Code in early 2020, new related challenges have also emerged in specialized outpatient palliative care (SAPV) regarding how to address requests for assisted suicide that have so far received little systematic investigation. The aim of this study is to describe and analyze cases involving requests for assisted suicide within SAPV. On this basis, key challenges in care are identified and potential strategies for dealing with such requests are developed.

METHODS: A retrospective case analysis was conducted of all patients who were cared for by the SAPV team at the University Hospital Cologne between February 2020 and August 2025 and explicitly expressed a wish for assisted suicide. Data were extracted from the electronic documentation system (PalliDoc®). Practical and ethical issues related to care were derived within the multiprofessional team.

RESULTS: A total of six patients were included. Five patients suffered from amyotrophic lateral sclerosis and one patient had advanced oncological disease. Three patients made use of external assisted suicide services.

DISCUSSION: Central challenges in care concerned clarification of the role of SAPV, communication about assisted suicide, support of relatives, and the conclusion of care. A clear internal organizational position, as well as defined communication pathways within the team towards patients and their relatives, proved to be supportive. This study formulates practice-relevant questions for the conceptual further development of approaches to requests for assisted suicides.},
}

@article {pmid41702846,
year = {2026},
author = {Xu, G and Lopez, A and Brkic, S and Fromholt, S and Chakrabarty, P and Borchelt, DR},
title = {Efficient induction of motor neuron disease in transgenic G93A SOD1 mice by prion-like seeding.},
journal = {Prion},
volume = {20},
number = {1},
pages = {1-17},
doi = {10.1080/19336896.2026.2630484},
pmid = {41702846},
issn = {1933-690X},
mesh = {Animals ; Mice, Transgenic ; *Superoxide Dismutase-1/genetics/metabolism ; Mice ; *Superoxide Dismutase/genetics/metabolism ; *Prions/metabolism ; *Motor Neuron Disease/pathology/genetics/metabolism ; Disease Models, Animal ; Humans ; Amyotrophic Lateral Sclerosis/genetics/pathology ; },
abstract = {Mutations in superoxide dismutase 1 (SOD1) cause paralysis in familial amyotrophic lateral sclerosis and promote its misfolding into neurotoxic aggregates. Previous studies have shown that mice expressing the ALS-causing G85R variant of SOD1 develop paralysis much faster after intraspinal injection of spinal homogenates from paralysed G85R SOD1 mice. These findings, and other studies in cell models, established the prionoid templating properties of misfolded mutant SOD1. Previously, however, we noted that the widely used Gur1-G93A SOD1 mice, which express at high levels and develop paralysis by 6 months of age, were resistant to seeding by homogenates from paralysed G93A mice. A line of G93A mice that expresses at very low levels (VLE-G93A) was responsive to seeding but at low efficiency. The poor susceptibility of G93A-SOD1 mice to seeding was not what we expected if prion-like propagation is essential to SOD1 ALS pathogenesis. In our prior studies, seeding homogenates from paralysed G93A-SOD1 mice were injected into the spine of newborn mice, leading us to question whether older G93A SOD1 mice might be more susceptible to seeding. Here, we establish that adult VLE G93A SOD1 mice (up to 12 months of age) injected intrathecally with seeding homogenates containing misfolded G93A or G85R SOD1 developed accelerated motor neuron disease efficiently. Thus, we demonstrate that both the route and age of inoculation can influence the efficiency of SOD1 seeding to induce motor neuron disease in VLE G93A-SOD1 mice. These data, together with our earlier reports, suggest that prion-like templating contributes to disease progression in SOD1-ALS.},
}

Animals
Mice, Transgenic
*Superoxide Dismutase-1/genetics/metabolism
Mice
*Superoxide Dismutase/genetics/metabolism
*Prions/metabolism
*Motor Neuron Disease/pathology/genetics/metabolism
Disease Models, Animal
Humans
Amyotrophic Lateral Sclerosis/genetics/pathology

@article {pmid41702277,
year = {2026},
author = {Copat, C and Cicero, CE and Grasso, A and Ligato, F and Sica, C and Fiore, M and Patti, F and Lo Fermo, S and Zappia, M and Giammanco, S and Ferrante, M and Nicoletti, A},
title = {Trace metal signatures in cerebrospinal fluid (CSF): Insights from an amyotrophic lateral sclerosis (ALS) hotspot on Mount Etna (Sicily, Italy).},
journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)},
volume = {94},
number = {},
pages = {127844},
doi = {10.1016/j.jtemb.2026.127844},
pmid = {41702277},
issn = {1878-3252},
abstract = {Chronic exposure to trace metals has been increasingly recognized as a possible factor influencing the risk of amyotrophic lateral sclerosis (ALS). In the province of Catania, on the eastern slopes of Mount Etna, epidemiological investigations have highlighted the presence of a high-incidence cluster of the disease. Against this backdrop, the present study was designed to explore whether the concentrations of trace elements in cerebrospinal fluid (CSF) differ between ALS patients residing in this high-incidence area (In-Cluster) and those living in regions with lower incidence (Out-Cluster). For trace element analysis, CSF was analyzed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Fourteen metals (Al, V, Mn, Co, Ni, Cu, Zn, As, Cd, Hg, Pb, Fe, Se, Mg) were quantified in standard and KED modes. No single metal concentration differed significantly between In-Cluster and Out-Cluster groups. However, In-Cluster patients frequently showed higher upper quartiles for Al, Mn, As, Hg, and Se, suggesting broader variability. Ratio analysis highlighted significant differences between groups, with higher Al/Cu ratios observed in In-Cluster patients. Sex-stratified analysis further revealed increased Mn-based ratios in females, with a significantly elevated Mn/Pb ratio. These patterns indicate possible dysregulation of trace metal homeostasis linked to environmental exposure. In conclusion, although statistical significance was limited, our findings suggest that chronic volcanic ash exposure may contribute to subtle imbalances between neurotoxic and neuroprotective elements in CSF, potentially influencing ALS susceptibility. Further studies integrating environmental monitoring, speciation analysis, and larger cohorts are needed to clarify the role of trace metals in ALS pathogenesis.},
}

@article {pmid41702096,
year = {2026},
author = {Llacuna, FDG and Ong, AKS and Young, MN},
title = {Factors influencing behavioral intention to use adaptive learning systems: Integrating self-determination theory and the unified model of technology acceptance.},
journal = {Acta psychologica},
volume = {264},
number = {},
pages = {106471},
doi = {10.1016/j.actpsy.2026.106471},
pmid = {41702096},
issn = {1873-6297},
abstract = {Adaptive Learning System (ALS) is one of the useful learning tools that has emerged in the technological innovation of the educational sector. Many schools and universities have adopted it for academic use since the prompt of online learning. However, the relative evaluation of ALS has been undermined in the current generation - especially among developing countries. The purpose of this study was to analyze the variables affecting the actual academic use of online ALS among students. A total of 638 students from the Philippines answered an online survey of 50-item questions derived from the eleven constructs used in this study, which were analyzed simultaneously using Structural Equation Modeling. This study utilized two important theories, integrating both the Self-Determination Theory and the Unified Theory of Acceptance and Use of Technology Use in ALS acceptance. The findings showed that autonomy, competence, price value, and facilitating conditions were the significant factors in student's behavioral intention to use the ALS. Since developing countries are trying to adapt to the current trends among developed countries, it was suggested that developers may need to make their ALS accessible through other gadgets like smartphones and tablets. The findings of this study can contribute to the educational context of digital learning to meet the needs of the students by increasing their behavioral intentions to use ALS. Further, the results provided insights and suggestions to universities and ALS developers to collaborate on improving the ALS for the student's welfare in learning.},
}

@article {pmid41701375,
year = {2026},
author = {Zhao, Z and Xu, F and Wan, H},
title = {Comment on Shi et al.'s "Vaginal and cervical tumors in children and adolescents: a SEER population‑based study".},
journal = {Pediatric surgery international},
volume = {42},
number = {1},
pages = {97},
pmid = {41701375},
issn = {1437-9813},
}

@article {pmid41699931,
year = {2026},
author = {Avdimiretz, N and Jacobi, E and Landau, EE and McIntyre, K and Midyat, L and Benden, C},
title = {Quality of Life Measures in Pediatric Lung Transplantation.},
journal = {Pediatric pulmonology},
volume = {61},
number = {2},
pages = {e71512},
doi = {10.1002/ppul.71512},
pmid = {41699931},
issn = {1099-0496},
mesh = {Humans ; *Lung Transplantation/psychology ; *Quality of Life ; Child ; Surveys and Questionnaires ; },
abstract = {Quality of life (QOL) measures are understudied outcomes in the pediatric transplant population, specifically in pediatric lung transplant recipients. Dr. Martin and colleagues from the Medical University of Vienna have recently published on post-transplant outcomes in children who have undergone lung transplant using the EuroQol questionnaire, a unique study in this population. While lung transplantation in children has been shown to improve functional status based on international data and other small volume QOL studies, pediatric data remains sparse and often relies on extrapolation from adult measures that have not been validated in children. In this editorial, we are pleased to highlight Dr. Martin et al.'s study, present a broader view of QOL measures in pediatric lung transplant, and compare and contrast various QOL outcomes that have been proposed for use in this population. This includes a review of the PedsQL Transplant Module, KIDSCREEN-52, CHIP, KINDL, PROMIS/PSC, and others that use pediatric-specific, transplant-focused tools. There is a need for multicenter collaboration in this population, and we encourage the international community to view this as a global initiative moving forward.},
}

Humans
*Lung Transplantation/psychology
*Quality of Life
Child
Surveys and Questionnaires

@article {pmid41699714,
year = {2026},
author = {Al Kamaly, O and Al-Khateeb, LA and Halim, MK and Magdy, G and Abbas, AEF},
title = {Environmentally sustainable UV spectrophotometric-chemometric approach for simultaneous determination of budesonide, glycopyrrolate, and formoterol.},
journal = {BMC chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13065-026-01729-w},
pmid = {41699714},
issn = {2661-801X},
support = {PNURSP2025R917//Princess Nourah Bint Abdulrahman University/ ; },
abstract = {This study introduces a sustainable UV-spectrophotometric platform for the simultaneous and individual determination of budesonide (BUD), glycopyrrolate (GLY), and formoterol fumarate (FOM) in pharmaceutical inhalers. Current chromatographic approaches for this triple therapy rely on toxic solvents and complex procedures, limiting their suitability for routine pharmaceutical analysis. The proposed method replaces hazardous solvents with an ethanol-water system, reducing organic solvent use by 95% and energy demand by ~ 80%. To further enhance efficiency, a grid-based experimental design was integrated with chemometric modeling, reducing experimental runs by 60% while maintaining analytical rigor. Calibration was linear over 10-50 µg/mL (BUD), 2-10 µg/mL (GLY), and 1-5 µg/mL (FOM), with correlation coefficients (r[2]) between 0.9998 and 0.9999. Among the evaluated models, Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) provided the highest predictive accuracy (RMSEP = 0.23-0.39, recoveries = 99.8-100.5%, RSD < 1.5%). It was successfully applied to both multi-component (Breztri Aerosphere[®]) and single-component inhalers (Budecort[®], Seebri Breezhaler[®], and Metrohaler[®]), confirming selectivity, accuracy, and robustness across pharmaceutical matrices. Beyond analytical performance, the method demonstrates outstanding sustainability credentials, including minimal carbon footprint, compliance with green chemistry principles, and alignment with 11 United Nations Sustainable Development Goals. Its simplicity, affordability, and eco-friendly profile make it readily transferable to both industrial and regulatory laboratories. This validated protocol establishes a cost-effective and environmentally responsible alternative to chromatography, offering a practical solution for routine Chronic obstructive pulmonary disease drugs monitoring and pharmaceutical quality assurance.},
}

@article {pmid41699331,
year = {2026},
author = {Ercin, N and Besli, N and Beker, M and Celik, U},
title = {Non-canonical cell death in neurodegeneration: emerging mechanisms and therapeutic Frontiers.},
journal = {Apoptosis : an international journal on programmed cell death},
volume = {31},
number = {3},
pages = {72},
pmid = {41699331},
issn = {1573-675X},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/pathology/metabolism/genetics ; *Cell Death/drug effects ; Animals ; Necroptosis/drug effects ; Ferroptosis/drug effects ; Neuroprotective Agents/therapeutic use/pharmacology ; Pyroptosis/drug effects ; Oxidative Stress ; },
abstract = {Neurodegenerative diseases, specifically Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS) are defined by progressively increased neuronal loss that lacks curative therapies. Increasing evidence supports that non-canonical regulated cell death pathways including ferroptosis, necroptosis, pyroptosis, and parthanatos, are implicated in pathological mechanisms of neuroinflammation, and oxidative stress, and mitochondrial dysfunction, likely impacting neurodegenerative pathologies. In this review, we summarize the existing literature on the molecular pathways and potential pathogenic implications of these cell death pathways in neurodegenerative diseases, highlighting their upstream triggers, regulatory proteins, and downstream effectors. We also briefly describe representative pharmacological agents, including ferrostatin-1, necrostatin-1, MCC950 and PARP-inhibitors, that have shown neuroprotective effects in experimental studies. Experimental studies provide valuable information, but translation to clinical treatments presents barriers including overlapping regulated cell death mechanisms, constraints of bloodbrain barrier penetrance and concern for safety. Future development may come through concepts such as biomarker-based patient stratification strategies, multivalent interventions, and improved translational models. Identifying these new regulated cell death pathways may eventually provide new avenues to slow the progression of neurodegeneration and develop more targeted therapies.},
}

Humans
*Neurodegenerative Diseases/drug therapy/pathology/metabolism/genetics
*Cell Death/drug effects
Animals
Necroptosis/drug effects
Ferroptosis/drug effects
Neuroprotective Agents/therapeutic use/pharmacology
Pyroptosis/drug effects
Oxidative Stress

@article {pmid41698629,
year = {2026},
author = {Patwekar, F and Patwekar, M and Wei, LS and Rather, GA and Mohammed, A and Hussain, MS and Gupta, G and Fuloria, S and Fuloria, NK},
title = {Marine-Derived bioactive compounds from Aquaculture: Receptor-Mediated neuroprotection in neurodegenerative disorders.},
journal = {Brain research},
volume = {1879},
number = {},
pages = {150208},
doi = {10.1016/j.brainres.2026.150208},
pmid = {41698629},
issn = {1872-6240},
abstract = {Neurodegenerative diseases, like Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and ischemic stroke (IS), are a major global health challenge because of their complex, multifactorial pathology, and the lack of effective disease-modifying therapies. In recent years, aquaculture-derived marine bioactive molecules like fucoidan, phlorotannins, fucoxanthin, laminarin, alginate oligosaccharides, and C-phycocyanin have developed as promising agents for neuroprotection with their structural diversity and multi-target biological activity. This review showcase predominantly preclinical evidence, including in silico molecular docking analyses, in vitro functional assays, and in vivo animal models, to critically understand the receptor-mediated mechanisms with the neuroprotective actions of marine bioactives originated from aquaculture systems. Available studies shows these compounds can modulate large neuro-receptor systems, like cholinergic, dopaminergic, GABAergic, glutamatergic, toll-like, and nuclear receptors, leading in attenuation of oxidative stress, lowering of neuro-inflammation, regulation of neurotransmission, and conservation of mitochondrial and synaptic function. However, the positive approach of mechanistic evidence varies across compounds and receptor classes, with large interactions assisted by functional outcomes instead of direct receptor-binding validation. The review even discusses emerging and enabling technologies like brain organoids, multi-electrode array platforms, omics-based profiling, and artificial intelligence assisted drug discovery, which are increasingly utilized to refine mechanistic understanding and optimize marine-derived products. Importantly, current evidence stay largely preclinical, with little human studies and a lack of validated receptor-specific biomarkers. Overall, this review provides a well-balanced, evidence-based assessment of aquaculture-derived marine bioactive as potential neurotherapeutic agents.},
}

@article {pmid41697761,
year = {2026},
author = {Wilson, M and Al-Jumeily, D and Birkett, J and Khan, I and Abbas, I and Harper, M and Assi, S},
title = {Exploring the feasibility of near-infrared spectroscopy and machine learning for detecting cardiovascular diseases and diabetes mellitus in fingernails.},
journal = {The Analyst},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5an01061f},
pmid = {41697761},
issn = {1364-5528},
abstract = {Cardiovascular diseases (CVDs) and diabetes mellitus (DM) are significant conditions that impact lives around the globe. Frequently employed methods for detecting CVDs and/or DM such as blood work and cardiac catheterisation are often invasive, intrusive and can cause the patient additional physical and psychological harm. Vibrational spectroscopic methods including near-infrared (NIR) spectroscopy have emerged as novel methods for detecting medical conditions and diseases including amyotrophic lateral sclerosis, cancer, DM and periodontitis. NIR spectroscopy's ability to perform rapid and cost-effective analysis saves diagnostic waiting times, providing relief for strained healthcare systems. Moreover, their non-invasive, non-intrusive and non-destructive nature allow application to alternative biological matrices such as hair, fingernails and saliva. Therefore, this work explored the feasibility of NIR spectroscopy paired with machine learning (ML) for detecting CVDs and/or DM in fingernails. NIR spectroscopy successful characterised disease-related spectral features including key NIR regions related to the presence of advanced glycated end-products (AGEs), glycated proteins and DM. To further assess the detective capabilities of NIR spectroscopy, classification models were trained. Cubic and quadratic support vector machine (SVM) models demonstrated accuracy in terms of the classification of healthy, CVD and diabetic fingernails. Accuracy was further improved through binary classification models, which allowed the independent classification of CVD and DM spectra against healthy spectra. In summary, NIR spectroscopy combined with ML provided accurate detection for CVDs and DM in fingernails.},
}

@article {pmid41697630,
year = {2026},
author = {Allen, D and Sable, MR and Bennett, T},
title = {Response to McLemore et al.'s Letter to the Editor.},
journal = {Maternal and child health journal},
volume = {},
number = {},
pages = {},
doi = {10.1007/s10995-026-04223-w},
pmid = {41697630},
issn = {1573-6628},
}

@article {pmid41696691,
year = {2025},
author = {Matabuena, M and Straczkiewicz, M and Calcagno, N and Burke, KM and Royse, TB and Iyer, A and Carney, KT and Hall, S and Berry, JD and Onnela, JP},
title = {Exploratory analysis of smartphone-based step counts as a digital biomarker for survival in ALS patients.},
journal = {Frontiers in digital health},
volume = {7},
number = {},
pages = {1705368},
pmid = {41696691},
issn = {2673-253X},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and debilitating neurodegenerative disease. Digital biomarkers derived from smartphone data can enable scalable, low-cost, remote, unobtrusive, and quantitative measurement of physical activity (PA). These biomarkers offer opportunities for quasi-continuous assessment of PA levels, which may provide new methods for monitoring ALS disease progression in real time. In this exploratory study, we analyzed data from 31 individuals with ALS (including 16 deaths) with up to 9 years of follow-up (median 3 years) to assess the impact of incorporating smartphone-derived PA measures into survival prediction models. We examine whether the strength of the statistical association with survival differs when PA is summarized as (i) a simple metric, such as the mean daily step count, vs. (ii) distributional representations of PA. The exploratory results suggest that the addition of PA variables defined via distributional representations improves the performance of the model, as reflected by higher C-score values (0.68 vs. 0.55 , estimated as the median over bootstrap replicas B = 1 , 000). A bootstrap-based hypothesis test shows statistically significant differences between the two models at the confidence level of 90%. These exploratory results indicate that the use of more advanced metrics to summarize PA time series can produce more accurate digital biomarkers to monitor the progression of ALS, although larger studies with larger sample sizes are required to confirm these findings.},
}

@article {pmid41695269,
year = {2026},
author = {Zhang, J and Zhao, Z and Xiang, T and Teng, D and Wan, H and Zhang, Q and Liu, X},
title = {From knowledge landscapes to network mechanisms: charting regulated cell death pathways in ALS.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1742805},
pmid = {41695269},
issn = {1663-4365},
abstract = {OBJECTIVE: To map the research landscape linking amyotrophic lateral sclerosis (ALS) with regulated cell death (RCD) and to integrate bibliometric trends with bioinformatics evidence to identify convergent mechanisms and actionable targets.

METHODS: Web of Science Core Collection, PubMed, and Scopus were searched for 2005-2024 (English; Article/Review). After merging and de-duplication, 6,272 records were analyzed using CiteSpace, VOSviewer, and bibliometrix to evaluate publication trends, collaboration, co-citation structure, and keyword evolution. In parallel, ALS-related genes were intersected with apoptosis-, ferroptosis-, and pyroptosis-associated gene sets. Shared targets were used to construct PPI networks, identify core modules and hub genes, and perform GO/KEGG enrichment analyses.

RESULTS: Publications and citations increased steadily with a clear rise after 2015. The field is anchored by the USA and shows rapidly growing contributions from Asia and Europe. Keyword evolution indicates a shift from "oxidative stress/apoptosis" toward multi-pathway RCD, with prominent recent bursts in ferroptosis, pyroptosis, necroptosis, and autophagy/mitophagy, alongside persistent themes in motor-neuron degeneration, mitochondria, and neuro-inflammation. Bio-informatics results showed substantial genetic overlap between ALS and RCD modalities. Hub-gene analysis highlighted TP53, AKT1, STAT3, MYC, RELA, EP300, CREBBP, JUN, HSP90AA1, and MAPK3 as central nodes. Enrichment analyses implicated FoxO, HIF-1, and lipid-related pathways, and GO terms related to chemical/oxidative stress responses and autophagy regulation.

CONCLUSION: ALS-cell death research is consolidating around interconnected RCD programs. Integrated bibliometric and bioinformatics evidence supports an immunometabolic convergence involving ferroptosis-inflammation-autophagy signaling, providing a focused set of candidate pathways and hub targets for mechanistic validation and translation.},
}

@article {pmid41693708,
year = {2025},
author = {Mudda, NS and Zhang, L and Sampelli, P},
title = {Targeting gut-brain-immune axis in amyotrophic lateral sclerosis.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1637976},
pmid = {41693708},
issn = {1664-3224},
mesh = {*Amyotrophic Lateral Sclerosis/immunology/microbiology/therapy/metabolism ; Humans ; *Gastrointestinal Microbiome/immunology ; Animals ; *Brain/immunology/metabolism ; Dysbiosis/immunology ; *Brain-Gut Axis/immunology ; Cytokines/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron neurodegenerative disorder with a median survival of only 3-5 years. The heterogeneity of the disease and lack of effective therapies highlight the importance of identifying novel pathogenic mechanisms. We hypothesize that dysbiosis of gut microbiota enhances ALS by disrupting intestinal barrier function and altering metabolite profiles to drive systemic inflammation and neuronal stress. Precisely, the decrease in health-promoting bacteria (e.g., Akkermansia muciniphila, Bifidobacterium and Lactobacillus spp.) in ALS can reduce neuroprotective metabolite production (short-chain fatty acids, nicotinamide, GABA, precursors of serotonin) and increase gut permeability, enabling lipopolysaccharide (LPS) and pro-inflammatory cytokines into the circulation. Such changes would activate microglia and impair motor neuron homeostasis by glutamate excitotoxicity and mitochondrial dysfunction. The gut-brain axis operates through immune-mediated mechanisms, where ALS-associated microbiota changes compromise mucosal immunity and trigger peripheral Th1/Th17-biased responses with impaired Treg regulation. Elevated endotoxin levels correlate with TLR4-driven inflammation, promoting pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) that cross into the CNS and prime microglia toward a neurotoxic M1 phenotype, creating a milieu where IL-17A and other mediators directly injure motor neurons. Our hypothesis relies on establishing human and animal evidence of microbiome derangements, barrier dysfunction, and immune deregulation with ALS. We hypothesize that restoration of an "ALS-protective" microbiota consortium or its metabolic by-products can potentially slow disease progression. Testable hypotheses include improvement of ALS model motor deficits by probiotic or fecal-microbiota therapies, and normalization of inflammatory biomarkers. This paradigm recontextualizes ALS as a gut-brain disease and suggests new directions for translational research into this unmet medical indication.},
}

*Amyotrophic Lateral Sclerosis/immunology/microbiology/therapy/metabolism
Humans
*Gastrointestinal Microbiome/immunology
Animals
*Brain/immunology/metabolism
Dysbiosis/immunology
*Brain-Gut Axis/immunology
Cytokines/metabolism

@article {pmid41692371,
year = {2026},
author = {Love, TMT and Chrysilla, E and Maddipati, KR and Falsetta, ML},
title = {Response letter to Oka et al.'s letter to the editor.},
journal = {The journal of pain},
volume = {},
number = {},
pages = {106215},
doi = {10.1016/j.jpain.2026.106215},
pmid = {41692371},
issn = {1528-8447},
}

@article {pmid41692368,
year = {2026},
author = {Dehury, S and Tiwari, S and Los Rios, P},
title = {Refolding-assisted purification of native full-length TDP-43 compatible with BSL-2 safety regulations.},
journal = {Methods (San Diego, Calif.)},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymeth.2026.02.009},
pmid = {41692368},
issn = {1095-9130},
abstract = {TAR DNA-binding protein 43 (TDP-43) is a prion-like RNA-binding protein that plays a key role in amyotrophic lateral sclerosis and frontotemporal dementia. Producing full-length TDP-43 consistently is thus relevant for its in vitro studies and yet it remains challenging, especially with the current requirement to work under biosafety level-2 (BSL-2) containment due to new safety regulations for Prion-like and amyloidogenic proteins. Here we describe a refolding-assisted purification protocol for TDP-43 from soluble fraction that can be implemented with basic equipment in standard BSL-2 laboratories. Expression in Escherichia coli is followed by IMAC-capture on an EDTA/DTT-tolerant Ni[2+]-NTA resin under 4 M urea, then on-column refolding via a gradient urea wash using resin-limiting conditions that favour the binding to high-affinity His-tagged protein. After removal of the SUMO solubility tag, the preparation is monitored by a robust quality-control pipeline: SDS-PAGE and immunoblotting for integrity and purity, mass photometry for oligomeric state, far-UV circular dichroism for secondary structure, fluorescence anisotropy for native functional assays, and light-scattering for stability and aggregation propensity measurements. A concise BSL-2 standard operating procedure specifies containment, decontamination, and waste handling for prion-like proteins. This protocol enables safe, cost-effective, and reproducible access to native-like full-length TDP-43 and is readily adaptable to other prion-like aggregation-prone proteins.},
}

@article {pmid41692171,
year = {2026},
author = {Wang, SM and Chan, JC and Supapatarnun, E and Tsai, CY and Lan, PTN and Weng, EF},
title = {C9orf72-derived dipeptide repeat proteins poly-PR disrupt membrane excitability and synaptic function in cortical neurons.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107320},
doi = {10.1016/j.nbd.2026.107320},
pmid = {41692171},
issn = {1095-953X},
abstract = {Amyotrophic lateral sclerosis (ALS) is one of the most fatal neurodegenerative disease, with the most common genetic form of the ALS is associated with hexanucleotide GGGGCC repeat expansions in the first intron of C9orf72 gene. Cortical hyperexcitability is one of the symptoms reported in several forms of ALS and implicated as a cause of neuronal death, however, the underlying mechanisms are still unclear. The dipeptide repeat (DPR) proteins produced from hexanucleotide repeat expansion have been shown toxic to neurons and induce cellular damages. In this study, we explore relationships between the membrane excitability of cortical neurons and the expression of one of the DPR proteins poly-proline-arginine (poly-PR). We found that expression of poly-PR in primary cultured cortical neurons induced an elevation of intrinsic membrane excitability and decreases in dendritic arborization and excitatory synaptic activity. The increased membrane excitability can be restored by Nav channel inhibitor riluzole and Kv7 channel activator retigabine. Our results suggest a rescuable ion channel-mediated hyperexcitability induced by poly-PR expression in cortical neurons, providing a foundation for developing targeted therapies for C9orf72 ALS.},
}

@article {pmid41691953,
year = {2026},
author = {Sandoval-Diez, N and Loizeau, N and Huss, A and Röösli, M and Vienneau, D},
title = {Long-term residential magnetic field exposure and neurodegenerative disease mortality: An 18-year nationwide cohort study in Switzerland.},
journal = {Environment international},
volume = {208},
number = {},
pages = {110145},
doi = {10.1016/j.envint.2026.110145},
pmid = {41691953},
issn = {1873-6750},
abstract = {BACKGROUND: Epidemiological evidence on the association between extremely low-frequency magnetic fields (ELF-MF) exposure and neurodegenerative diseases (NDD) remains inconsistent. Few population-based studies using exposure from high-voltage power lines (HVPL) have found mixed findings, and none have yet considered exposure from railway lines.

METHODS: We followed 3,555,064 adults from the Swiss National Cohort (2001-2018), contributing 55.4 million person-years. Long-term ELF-MF exposure from HVPL (50 Hz) and railway lines (16.7 Hz) was modelled using validated proximity models and updated over four intervals (2001-2005, 2006-2010, 2011-2015, 2016-2018). Long-term ELF-MF exposure was calculated as a time-weighted average exposure over 10-year windows preceding each interval. Cox proportional hazards models estimated hazard ratios (HRs) for mortality from Alzheimer's disease (AD), other types of dementia (OTD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and multiple sclerosis (MS), adjusting for sociodemographic and environmental co-exposures.

RESULTS: During follow-up, 146,655 NDD deaths occurred. Less than 1% of the population was exposed to long-term ELF-MF ≥ 0.3 µT from HVPL and 2.4% from railway lines. HVPL exposure was positively associated with mortality from AD (HR per 1 µT increase in exposure = 1.54; 95% CI: 1.23-1.92) and OTD (HR = 1.31; 95% CI: 1.13-1.52). Associations for railway exposure were weaker and attenuated after adjusting for environmental co-exposures. No associations were observed for ALS, PD, or MS.

CONCLUSIONS: Long-term ELF-MF exposure was associated with higher dementia mortality risk in the general population, but not with ALS, PD, or MS. Causal inference remains limited by the absence of established biological mechanisms.},
}

@article {pmid41691309,
year = {2026},
author = {Argueti-Ostrovsky, S and Lim, SM and Arogundade, OA and Diaz-Garcia, S and Yunisova, G and Meng, A and Hermann, A and Ong, K and Eremenko, E and Bravo-Hernandez, M and Driscoll, SP and Lee, CZ and Jiang, X and Stavsky, A and Barel, S and Shani, T and Kahn, J and Pfaff, SL and Monsonego, A and Marsala, M and Ravits, J and Lagier-Tourenne, C and Israelson, A},
title = {Impaired nucleocytoplasmic transport in SOD1-mediated ALS.},
journal = {Molecular neurodegeneration},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13024-026-00930-8},
pmid = {41691309},
issn = {1750-1326},
}

@article {pmid41690969,
year = {2026},
author = {Lorincz-Comi, N and Song, W and Chen, X and Paz, IR and Hou, Y and Zhou, Y and Xu, J and Martin, W and Barnard, J and Pieper, AA and Haines, JL and Chung, MK and Cheng, F},
title = {Combining xQTL and genome-wide association studies from diverse populations improves druggable gene discovery.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-69236-z},
pmid = {41690969},
issn = {2041-1723},
support = {R01AG066707//U.S. Department of Health Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01AG084250//U.S. Department of Health Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01AG076448//U.S. Department of Health Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01AG082118//U.S. Department of Health Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01AG092462//U.S. Department of Health Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01AG092591//U.S. Department of Health Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; RF1AG082211//U.S. Department of Health Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R33AG083003//U.S. Department of Health Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; P01HL158501//U.S. Department of Health Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; },
abstract = {Repurposing existing medicines to target disease-associated genes represents a promising strategy for developing effective treatments for complex diseases. However, progress has been hindered by a lack of viable candidate drug targets identified through genome-wide association studies. Gene-based association tests provide a more powerful alternative to traditional SNP-based methods, yet current approaches often fail to leverage shared heritability across populations and to effectively integrate functional genomic data. To address these challenges, we develop GenT and its various extensions, comprising a framework of gene-based tests utilizing summary-level data from genome-wide association studies. Using GenT, we identify 16, 15, 35, and 83 candidate genes linked to Alzheimer's disease, amyotrophic lateral sclerosis, major depression, and schizophrenia, respectively, not detected by Genome-Wide Association Studies (GWAS). Additionally, we use our multi-ancestry gene-based test (MuGenT) to identify 28 candidate genes associated with type 2 diabetes. By integrating brain expression and protein quantitative trait loci into our analysis, we identify 43 candidate genes associated with Alzheimer's disease that have supporting xQTL evidence. We also perform experimental assays to demonstrate that the NTRK1 inhibitor GW441756 significantly reduces tau hyper-phosphorylation (including p-tau181 and p-tau217) in Alzheimer's disease patient-derived iPSC neurons, providing mechanistic support for our predictions.},
}

@article {pmid41690802,
year = {2026},
author = {Okour, A and Bakas, T and Miller, EL},
title = {Factors Associated With Health-Related Quality of Life of Stroke Survivors: An Integrative Review.},
journal = {Research and theory for nursing practice},
volume = {},
number = {},
pages = {},
doi = {10.1891/RTNP-2025-0099},
pmid = {41690802},
issn = {1541-6577},
abstract = {Background: Stroke significantly impacts neurological and functional abilities, reducing health-related quality of life (HRQOL) within the first year poststroke. Aim: The review aimed to identify key factors influencing HRQOL among stroke survivors during their first year of stroke. Methods: Guided by Ferrans et al.'s HRQOL model and using Whittemore and Knafl's integrative review methodological strategy, PubMed, Cumulative Index to Nursing and Allied Health Literature, and PsycINFO were searched to examine the available literature from January 2013 to December 2024. Study selection followed the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses; methodological quality was appraised using the Johns Hopkins Nursing Evidence-Based Practice. Results: Twenty-two studies met the inclusion criteria, predominantly level III observational designs (cross-sectional and prospective cohorts). The most salient factors influencing HRQOL during the first year poststroke were symptom severity (depression, anxiety, insomnia, fatigue, stroke severity), functional disability (mobility, extremity function), and individual factors (older age, female sex, lower education, lower resilience), which predicted poorer HRQOL, while environmental factors (social/community support, rehabilitation access) appeared to buffer the impact of disability. Evidence suggests the presence of mediated pathways in which symptoms affect functional status, which in turn shapes health perceptions and overall health-related quality of life (HRQOL), while individual and environmental characteristics function as moderating factors. Conclusion: Stroke survivors are at risk of poor quality of life during the first year after stroke. HRQOL is strongly driven by symptom severity and functional limitations, influenced by individual and environmental contexts. The conceptual model of HRQOL provided a better understanding of stroke survivors' experiences. Findings support targeted interventions focused on symptom management, functional rehabilitation, and individualized support.},
}

@article {pmid41690299,
year = {2026},
author = {Naas, A and Kober, J and Trittler, T and Nauber, R and Dorausch, EMG and Kampfrath, N and Brinkmann, F and Arsova, M and Husman, J and Langanke, R and Sulk, S and Matthes, K and Gabriel, T and Teufel, A and Behrendt, P and Markova, A and Franck, M and Jenssen, C and Merkel, D and Blank, V and Karlas, T and Seeger, M and Eckart, MA and Poralla, L and Lehmann, M and Staudacher, J and Ziesch, M and Aland, J and Herzog, L and Herzog, A and Jürgensen, C and Fettweis, GP and Hampe, J and Herzog, M},
title = {Evaluation of image quality in five different handheld ultrasound devices and analysis of various impact factors.},
journal = {Ultraschall in der Medizin (Stuttgart, Germany : 1980)},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2809-7627},
pmid = {41690299},
issn = {1438-8782},
abstract = {PURPOSE: Handheld ultrasound (HHUS) devices are increasingly used in clinical practice due to their portability and cost-effectiveness. However, HHUS image quality remains variable, and a standardized expert-based evaluation protocol is lacking. This study compares the image quality of B-mode recordings of five HHUS models with a high-end reference system (HEUS) using a blinded assessment to identify differences, covariates, offering a standardized evaluation framework.

MATERIALS AND METHODS: In this blinded, multi-center study, video sequences of the liver, pancreas, and sigmoid colon were recorded in ten volunteers using five HHUS devices - Vscan Air, Butterfly iQ+, Philips Lumify, Clarius C3, and Clarius C3 HD3 - and one HEUS (GE Logiq E10). 22 physicians with many years of abdominal ultrasound experience rated blinded clips for five image quality parameters.

RESULTS: The HEUS consistently received the highest ratings. Image quality differed significantly between HHUS devices. Clarius systems showed the smallest deviation from the reference, followed by Vscan Air and Philips Lumify. All image parameters significantly correlated with the overall impression, without a single dominant factor. The patients´ BMI had no relevant influence. Examiner experience was less impactful than device familiarity and personal preference.

CONCLUSION: The image quality of HEUS remained superior to all tested HHUS devices. Further subdivision of image quality aspects did not provide additional information. Furthermore, we could not identify significant covariates in our setup. These findings could justify simplified setups with reduced questionnaires and requirements for examiners. Zielsetzung: Portable Ultraschallsysteme (HHUS) finden aufgrund ihrer Mobilität und Kosteneffizienz zunehmend Anwendung in der Praxis. Ihre Bildqualität ist jedoch variabel und ein standardisiertes, expertenbasiertes Bewertungsprotokoll fehlt bislang. Ziel dieser Studie ist der Vergleich von fünf HHUS-Modellen gegenüber einem High-End-Referenzsystem (HEUS) in einem verblindeten Design sowie die Analyse relevanter Kovariablen, die zur Entwicklung eines standardisierten Bewertungsverfahrens beitragen können.

MATERIAL UND METHODEN: In dieser multizentrischen, verblindeten Studie wurden Videos von Leber, Pankreas und Sigma bei 10 Probanden mit fünf HHUS-Geräten (Vscan Air, Butterfly iQ+, Philips Lumify, Clarius C3 und C3 HD3) sowie einem HEUS (Ge Logiq E10) aufgezeichnet. 22 Experten mit langjähriger Ultraschallerfahrung bewerteten die verblindeten Videos nach verschiedenen Kriterien zur Bildqualität. Ergebnisse: Das HEUS erzielte die besten Bewertungen, die HHUS unterschieden sich signifikant. Clarius-Systeme wichen am wenigsten vom HEUS ab, gefolgt von Vscan Air und Philips Lumify. Alle Bildparameter korrelierten signifikant mit dem Gesamteindruck, ohne dass ein dominanter Parameter identifizierbar war. Der BMI hatte keinen relevanten Einfluss. Die Erfahrung der Gutachter war weniger entscheidend als Gerätevertrautheit und persönliche Präferenz. Schlussfolgerung: Die Bildqualität des HEUS war allen getesteten HHUS überlegen. Eine weitere Unterteilung in einzelne Aspekte der Bildqualität lieferte keine zusätzlichen Informationen. Es wurden keine relevanten Kovariablen identifiziert, was für die Etablierung vereinfachter Bewertungsprotokolle mit reduzierten Fragebögen spricht.},
}

@article {pmid41690071,
year = {2026},
author = {El-Moaty, HIA and Sameh, A and Saber, S and Hamad, RS and Elmorsy, EA and Alsoqih, NS and Farrag, AA and Eissa, H and El-Kott, AF and Negm, S and AlShehri, MA and Ali, MAM and Hasan, WA and Gaafar, A and Khalifa, HS and Ibrahim, EH and Morsy, K and Elnaghy, F},
title = {Adenosine A2A receptor as a dual-acting molecular switch: Glial morphological changes and neurovascular tissue remodeling in neuroinflammation and neurodegeneration.},
journal = {Tissue & cell},
volume = {100},
number = {},
pages = {103389},
doi = {10.1016/j.tice.2026.103389},
pmid = {41690071},
issn = {1532-3072},
abstract = {Neuroinflammation appears in a variety of neurological disorders, including multiple sclerosis (MS), Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis. The adenosine A2A receptor (A2AR), a Gs protein-coupled receptor that affects cAMP signaling and downstream kinases like PKA, CREB, and NF-κB, is one of the primary regulators of this process. Context-dependent effects of A2AR activation include lowering acute inflammation and promoting neuronal survival when stimulated moderately, but increasing glial activation and cytokine production when overexpressed over an extended period of time. In microglia and astrocytes, A2AR signaling regulates inflammatory pathways mediated by NF-κB and MAPK, affecting oxidative stress, blood-brain barrier (BBB) stability, and excitotoxicity. Acute or transient (short-term) A2AR activation, on the other hand, increases the production of anti-inflammatory cytokines like IL-10 and enhances neurotrophic support through BDNF. A2AR antagonists, including istradefylline and SCH58261, may reduce microglial triggering and have neuroprotective benefits, according to clinical and experimental data. The context-dependent activity of the receptor is shown by the fact that total receptor blockage interferes with adaptive immune control. Therefore, the therapeutic challenge is to carefully modify A2AR signaling in particular cell populations, specifically targeting astrocytic or microglial receptors while maintaining the peripheral immunoregulatory activities. The dual regulatory role of A2AR in neuroinflammation is summarized in this review along with its molecular mechanisms, disease-specific actions, and therapeutic significance. Developing next-generation neuroprotective strategies that reduce A2AR signaling's pro-inflammatory and neurotoxic effects while preserving its beneficial homeostatic effects will require an understanding of the temporal and cell-specific dynamics of this signaling.},
}

@article {pmid41689968,
year = {2026},
author = {Qaisar, R and Deepa, SS},
title = {A Narrative Review of Necroptosis in Neuromuscular Junction Disorders: Pathogenesis and Therapeutic Strategies.},
journal = {Archives of medical research},
volume = {57},
number = {5},
pages = {103401},
doi = {10.1016/j.arcmed.2026.103401},
pmid = {41689968},
issn = {1873-5487},
abstract = {Necroptosis is a regulated and inflammatory form of cell death that has emerged as a key contributor to neuromuscular junction (NMJ) dysfunction. This narrative review aims to synthesize current evidence on the role of necroptosis in NMJ pathology and its potential therapeutic implications. First, we present the conceptual framework linking necroptosis to NMJ degradation, focusing on core mediators such as receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like pseudokinase (MLKL). Second, we summarize the available evidence across NMJ compartments, including motor neurons, Schwann cells, and skeletal muscle. We also describe how necroptosis activation correlates with structural and functional deficits in conditions such as spinal muscular atrophy, amyotrophic lateral sclerosis, and Duchenne muscular dystrophy. Third, we examine the translational potential of targeting necroptosis, highlighting preclinical studies on RIPK1, RIPK3, and MLKL inhibitors. Although these findings suggest therapeutic value, current evidence is predominantly derived from animal models, and clinical applicability remains uncertain. Rigorous trials are needed to confirm the safety and efficacy of these treatments. Understanding necroptosis as a shared mechanism across NMJ components may inform future strategies to preserve neuromuscular function.},
}

@article {pmid41689566,
year = {2026},
author = {Joubert, N and Mels, CMC and Louw, R and Chung, ST and Wentzel, A},
title = {An allostatic load domain-specific metabolic profile in young adults: The African-PREDICT study.},
journal = {The Journal of physiology},
volume = {},
number = {},
pages = {},
doi = {10.1113/JP289807},
pmid = {41689566},
issn = {1469-7793},
support = {//South African Medical Research Council/ ; //Department of Science and Technology/ ; //National Research Foundation/ ; /DK/NIDDK NIH HHS/United States ; },
abstract = {Allostatic load scores (ALSs) quantify the cumulative physiological burden of sustained stress across neuro-endocrine, metabolic, cardiovascular and inflammatory domains; however ALS is heterogeneous in nature. Using domain-specific urinary metabolomic signatures may improve evaluation accuracy, provide an innovative alternative to stress characterization, identify early domain-specific perturbations and allow comparative investigations. We designed and evaluated a novel, multilayered perceptron neural network (MLP-NN) method to investigate metabolic perturbations reflecting domain-specific alterations in low and high sustained stress, measured by ALS, and described ALS domain-specific metabolomic profiles. Data from 955 South Africans were used. ALS was calculated from dehydroepiandrosterone (DHEA), adrenocorticotropic hormone (ACTH), cortisol, interleukin-6 (IL-6), C-reactive protein (CRP), waist circumference (WC), glycated haemoglobin (HbA1c), blood-pressure and high-density lipoprotein cholesterol. Urinary amino acids and acylcarnitines (N = 32 metabolites) were analysed using liquid chromatography-tandem-mass-spectrometry. MLP-NN assessed metabolite contribution to the allostatic load (AL) domains, controlling for confounders, identifying the main metabolites, per AL domain. The median ALS was 3, with high stress (ALS ≥ 4) observed in 30% of participants. Significant differences were observed across all 32 metabolites between high and low ALS groups (all P < 0.05). MLP-NN revealed distinct domain-specific metabolomic patterns in low and high ALS. In low ALS the neuro-endocrine, cardiovascular and metabolic domains showed metabolomic signatures reflective of normal physiology. However in high ALS, metabolomic profiles reflected compensatory mechanisms linking neurotransmitter synthesis, redox balance and energy metabolism, mainly in the neuroendocrine, inflammatory and metabolic domains. This novel MLP-NN-based approach identified unique urinary profiles reflective of higher AL, independent of traditional confounders. This non-invasive approach may serve as an alternative for assessing AL, retaining domain-specificity, yet allowing comparative studies without the heterogeneity of traditional ALS. KEY POINTS: Allostatic load scores (ALSs) are heterogenous, complicating cross-study comparisons and clinical inferences. Determining allostatic load domain-specific metabolomic profiles using neural networks may identify early changes in specific domains. This study designed and evaluated a novel neural network-based model determining allostatic-load-domain-specific metabolomic signatures in high and low sustained stress. This novel neural-network-based approach, combinedly analysing metabolomic data and ALS domain-specific patterns, identified unique urinary profiles, independent of traditional confounders. This non-invasive approach may serve as an alternative for assessing AL, retaining the domain-specificity, identifying early domain-related perturbations related to sustained stress and allowing comparative studies.},
}

@article {pmid41689476,
year = {2026},
author = {Howe, SL and Holdom, CJ and McCombe, PA and Henderson, RD and Steyn, FJ and Ngo, ST},
title = {Systemic immune-metabolic interactions in patients with amyotrophic lateral sclerosis: correlations of plasma cytokines with metabolic status.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/21678421.2026.2627902},
pmid = {41689476},
issn = {2167-9223},
abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a clinically heterogeneous disease influenced by multiple biological processes. Altered energy metabolism, particularly hypermetabolism, is observed in some people living with ALS (plwALS) and is associated with faster progression. The mechanisms underlying this metabolic phenotype remain unclear. Inflammation has been proposed as a contributing factor. We examined whether plasma cytokines, as markers of systemic inflammation, are associated with energy expenditure in plwALS.

METHODS: Plasma samples from 77 plwALS and 90 non-neurodegenerative controls were analyzed using a multiplex immunoassay quantifying 14 cytokines. Cytokine concentrations were compared between groups and examined in relation to body composition, resting energy expenditure, and functional capacity as inferred by the ALSFRS-R.

RESULTS: Interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) concentrations were higher in plwALS than in controls prior to correction for multiple comparisons (p = 0.006; p.adj = 0.083, and p = 0.035; p.adj = 0.237, respectively). Hypermetabolism was more prevalent in the ALS cohort (36% compared to 11.5%, p < 0.001); however, cytokine concentrations were not significantly different across metabolic subgroups and showed no statistically significant association with metabolic index, energy expenditure, or functional measures.

CONCLUSIONS: Findings confirm modest elevations in plasma levels of IL-6 and MCP-1 in ALS but provide no evidence that circulating cytokines correlate with hypermetabolism. Further studies integrating longitudinal and tissue-specific analyses are needed to clarify immune-metabolic mechanisms contributing to disease heterogeneity in ALS.},
}

@article {pmid41688669,
year = {2026},
author = {Ishiguro, A},
title = {Impact of G-quadruplex RNA oxidation on its conformational dynamics and interaction with ALS-associated TDP-43.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-39767-y},
pmid = {41688669},
issn = {2045-2322},
support = {22K07032//Japan Society for the Promotion of Science/ ; },
}

@article {pmid41687010,
year = {2026},
author = {Torrella, P and Martínez, M and Riera, J and Argudo, E},
title = {A Homemade Low-Cost Agar-Agar Extracorporeal Membrane Oxygenation Cannulation Model for Extracorporeal Resuscitation Simulation.},
journal = {ASAIO journal (American Society for Artificial Internal Organs : 1992)},
volume = {},
number = {},
pages = {},
doi = {10.1097/MAT.0000000000002664},
pmid = {41687010},
issn = {1538-943X},
abstract = {Extracorporeal cardiopulmonary resuscitation (ECPR) using venoarterial extracorporeal membrane oxygenation (VA ECMO) is a life-saving intervention for selected patients in refractory cardiac arrest. Given the procedure's technical complexity and time-critical nature, simulation-based training has become essential to ensure both technical proficiency and effective team coordination. However, current commercial simulators are often prohibitively expensive and lack the capacity to integrate ECMO cannulation into standard advanced life support (ALS) scenarios, limiting their real-world applicability and dissemination. To address this gap, we developed a low-cost, customizable phantom using agar-agar, basic household materials, and repurposed medical components. Our model enables ultrasound-guided vascular access, cannula insertion, and initiation of extracorporeal blood flow. It can be easily embedded within ALS mannequins, allowing seamless integration into high-fidelity ECPR simulations. The phantom realistically reproduces key procedural steps and supports training under the high-stress, time-sensitive conditions typical of ECPR. Its adaptability allows use in both technical workshops and in situ simulations involving multidisciplinary teams. This accessible, eco-friendly solution provides a practical alternative to commercial models, promoting broader implementation of ECPR training programs. It represents a step forward in bridging the gap between theoretical knowledge and hands-on practice in critical care education.},
}

@article {pmid41686369,
year = {2026},
author = {Qaisar, R},
title = {Extracellular vesicles at the neuromuscular junction: messengers of synaptic health and disease.},
journal = {Cell and tissue research},
volume = {403},
number = {2},
pages = {20},
pmid = {41686369},
issn = {1432-0878},
mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Neuromuscular Junction/metabolism/pathology ; Animals ; *Synapses/metabolism ; },
abstract = {Extracellular vesicles (EVs) have emerged as pivotal modulators of neuromuscular junction (NMJ) biology, reshaping our understanding of synaptic communication, maintenance, and degeneration. This review consolidates current insights into the roles of EVs derived from motor neurons, muscle fibers, and Schwann cells in regulating NMJ integrity. In healthy states, EVs deliver trophic factors, structural proteins, and regulatory RNAs that promote the clustering of acetylcholine receptors, presynaptic stability, and axonal growth. Motor neuron EVs carry Wnt7a, synaptophysin, and PGC-1α, while muscle-derived EVs deliver miR-206, agrin, and caveolin-3. Schwann cell EVs contribute neurotrophic support via NRG1 and GDNF. In contrast, diseased or aged NMJs exhibit EV cargo dysregulation, marked by the presence of misfolded proteins (e.g., SOD1, TDP-43), pro-inflammatory cytokines, and reduced regenerative miRNAs. These changes contribute to synaptic dismantling, neuroinflammation, and impaired repair in conditions such as ALS, SMA, MG, and sarcopenia. The review highlights the bidirectional nature of EV signalling and its dynamic regulation by neuronal activity and stress. Emerging therapeutic strategies include engineering EVs to deliver protective cargo, targeting them to NMJ components, and designing biomaterial-based depots for sustained release. Furthermore, EV signatures in blood and muscle hold promise as non-invasive biomarkers for early detection of NMJ decline in ALS, SMA, MG, and sarcopenia. Despite promising preclinical data, challenges remain in EV characterization, targeting specificity, and clinical translation. This review underscores a paradigm shift: EVs are not passive byproducts but active messengers of neuromuscular health and disease, with realistic applications in diagnostics, regenerative therapy, and personalized medicine.},
}

Humans
*Extracellular Vesicles/metabolism
*Neuromuscular Junction/metabolism/pathology
Animals
*Synapses/metabolism

@article {pmid41686235,
year = {2026},
author = {},
title = {Intime Mitbewohner - Das Mikrobiom als unterschätzter Faktor in Klinik und Praxis.},
journal = {Wiener klinische Wochenschrift},
volume = {138},
number = {3-4},
pages = {127},
doi = {10.1007/s00508-026-02714-y},
pmid = {41686235},
issn = {1613-7671},
}

@article {pmid41685660,
year = {2026},
author = {Pérez-Fuentes, MDC and Molero Jurado, MDM and Romanos-Rodríguez, A and Martos Martínez, Á and Gómez-Gómez, FJ and Aguado-Campos, J},
title = {Self-efficacy and Communication in Health Personnel After Simulation Training in Cardiopulmonary Resuscitation: A Quasi-experimental Study.},
journal = {Inquiry : a journal of medical care organization, provision and financing},
volume = {63},
number = {},
pages = {469580251411471},
doi = {10.1177/00469580251411471},
pmid = {41685660},
issn = {1945-7243},
mesh = {Humans ; *Self Efficacy ; Male ; *Cardiopulmonary Resuscitation/education ; Female ; Middle Aged ; Adult ; *Communication ; *Simulation Training ; Spain ; *Health Personnel/education/psychology ; Aged ; Surveys and Questionnaires ; Young Adult ; },
abstract = {This study aimed to evaluate the impact of a simulation-based Advanced Life Support (ALS) training programme on the self-efficacy and communication of health personnel. The research focussed on whether such training could enhance both technical and non-technical skills, particularly in managing cardiopulmonary resuscitation (CPR) situations. A quasi-experimental pre- and post-intervention study was conducted in primary care centres across Andalusia, Spain. A total of 106 health personnel (doctors and nurses), aged 21 to 65 years, participated in the study. Participants completed questionnaires measuring self-efficacy and communication styles before and after a 27-hour blended ALS training programme, which incorporated high-fidelity simulation exercises. Communication was assessed across several dimensions, including expressiveness, preciseness, impression manipulativeness, and emotionality. Post-intervention analysis revealed significant changes in communication styles. Specifically, doctors exhibited a reduction in "impression manipulativeness," while nurses showed an increase in "expressiveness." Although self-efficacy scores improved slightly after the training, the changes were not statistically significant. Correlational analyses indicated that higher self-efficacy was positively associated with "expressiveness" and "preciseness," and negatively associated with "emotionality." In conclusion, simulation-based ALS training led to improved communication among health personnel, with distinct patterns emerging between doctors and nurses. While the simulation training did not significantly increase self-efficacy, the trends observed suggest potential benefits. These findings support the inclusion of simulation in continuing professional development programmes to strengthen non-technical skills essential for effective CPR performance.},
}

Humans
*Self Efficacy
Male
*Cardiopulmonary Resuscitation/education
Female
Middle Aged
Adult
*Communication
*Simulation Training
Spain
*Health Personnel/education/psychology
Aged
Surveys and Questionnaires
Young Adult

@article {pmid41685589,
year = {2026},
author = {de Jesus, H and Alves, I and Lopes, D and Simão, S and Leitão, AC and Pronto-Laborinho, AC and Conceição, V and Oliveira Santos, M and de Carvalho, M},
title = {Cognitive Dysfunction Is Associated With an Underestimation of Respiratory Function in ALS.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70180},
pmid = {41685589},
issn = {1097-4598},
abstract = {INTRODUCTION/AIMS: The association between low forced vital capacity (FVC) and cognitive impairment in ALS is ambiguous; it could be due to respiratory dysfunction and/or poor effort from cognitive deficits. We used the objective, non-volitional phrenic nerve motor response amplitude (PAmp) to clarify how cognitive status affects the relationship between diaphragmatic strength and FVC.

METHODS: This retrospective study included 73 patients with ALS followed in our clinic. FVC and PAmp were measured, and cognitive status was assessed with the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Regression models tested for associations between FVC and distinct ECAS domains and whether these domains influenced the PAmp-FVC relationship.

RESULTS: PAmp (β = 0.58, p = 0.001) and its interaction with an abnormal ECAS's Executive score (β = -0.20, p < 0.045) were significant predictors of FVC. The latter indicated that patients with abnormal executive function had lower FVC than cognitively normal patients at similar PAmp values. Moreover, in patients with abnormal executive function, a reduction in PAmp was associated with a shallower decline in FVC. Severe bulbar dysfunction was also negatively associated with FVC (β = -0.22, p = 0.024).

DISCUSSION: FVC may underestimate respiratory capacity in cognitively impaired patients; therefore, we recommend non-volitional measures when evaluating ALS patients with executive dysfunction.},
}

@article {pmid41684936,
year = {2026},
author = {Cotto, BA and Zhang, L and Fait, B and Peralta, C and Kilic, E and Molina, H and Heintz, N and Schmidt, EF},
title = {Divergent mitochondrial and metabolic adaptations shape selective vulnerability in ALS.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.01.30.702552},
pmid = {41684936},
issn = {2692-8205},
abstract = {Neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) exhibit striking cell-type selectivity, yet the basis for this vulnerability remains elusive. Here, we uncover that even closely related neurons can harbor distinct mitochondrial properties that shape their response to disease. Using TOM-Tag, a circuit-based AAV-based strategy for cell type-specific mitochondrial immunopurification from projection neurons, we performed integrative proteomic, metabolomic, transcriptomic, and functional analyses of mitochondria from ALS-vulnerable corticospinal projection neurons (CSPNs) and resilient corticothalamic projection neurons (CTPNs) in vivo. We discovered that CSPNs and CTPNs exhibit divergent mitochondrial profiles at baseline, despite sharing cortical layer and developmental origin. CTPNs were primed for antioxidant buffering and fatty acid metabolism, whereas CSPNs were enriched for oxidative phosphorylation components. In ALS, CTPNs employed mitochondrial flexibility and redox defense, whereas CSPNs exhibited respiratory failure and metabolic stress. These findings reveal that intrinsic mitochondrial programs vary even between similar neurons, and that this hidden layer of diversity may critically shape susceptibility to neurodegeneration. By enabling high-resolution access to mitochondria in defined neuronal circuits, TOM-Tag offers a powerful new lens for dissecting disease mechanisms and identifying cell-specific therapeutic targets.},
}

@article {pmid41684905,
year = {2026},
author = {Goutman, SA and Guo, K and Park, J and Jang, DG and Teener, SJ and Webber-Davis, IF and Famie, JP and Piecuch, CE and Hur, J and Murdock, BJ},
title = {Natural Killer Cell Dysregulation During ALS Disease Progression: A Gene Expression Analysis.},
journal = {Neurology open access},
volume = {2},
number = {1},
pages = {},
pmid = {41684905},
issn = {2998-7601},
support = {R01 NS120926/NS/NINDS NIH HHS/United States ; R01 NS127188/NS/NINDS NIH HHS/United States ; R01 TS000327/TS/ATSDR CDC HHS/United States ; R01 TS000344/TS/ATSDR CDC HHS/United States ; },
abstract = {BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative motor neuron disease with a pathophysiology that features dysregulated natural killer (NK) cells that are capable of damaging neurons. Although NK cells are associated with ALS progression and survival, their specific characteristics and how these characteristics change over the course of disease is unknown. The current study examines NK cell gene expression during ALS with the goal of identifying dysregulated genes and pathways in NK cells over the course of disease in order to identify potential new therapeutic targets.

METHODS: ALS participants with an El Escorial ALS diagnosis were recruited from the University of Michigan Pranger ALS Clinic, and control participants were recruited via internet-based notifications. Blood was collected from participants and NK cells were isolated from participants with ALS at two timepoints (baseline and longitudinal) and age- and sex-matched healthy controls at one timepoint. RNA was extracted from the NK cells and quantified using a transcript-counting technology for 578 immune-related genes. Differential gene expression analysis was used to identify individual genes that were dysregulated in ALS at baseline and longitudinally, While GO and KEGG pathway analyses were performed to identify dysregulated pathways at both timepoints.

RESULTS: NK cells from participants with ALS (n=36, median age 62.6 years (54.5-69.4), 50% female) showed a 2-fold or greater reduced expression of four pro-inflammatory genes at baseline relative to control participants (N=35, median age 64.3 years (55.2-71.8), 51% female) including IFNG, FCGR1A/B, and FAS; in ALS participants over 130 genes showed a 2-fold change in expression. Dysregulated genes and pathways at the later timepoint were related to cell polarization, activation, signaling, and cell-cell adhesion. In particular, genes associated with classical Type 1 inflammation decreased while Type 2 genes increased.

DISCUSSION: NK cells grow more dysregulated with ALS progression, shifting from a classical Type 1 phenotype to a Type 2 phenotype, though a larger study will be needed to confirm these initial findings. The findings also suggest NK cells contribute to early, but not late, ALS progression. Targeting specific NK cell pathways during early ALS may be a viable therapeutic strategy.},
}

@article {pmid41684011,
year = {2026},
author = {Chico, L and Schirinzi, E and Balestrini, L and Polzella, M and Siciliano, G},
title = {Nrf2-Activating Natural Compounds in Neurodegenerative Diseases: Targeting Oxidative Stress and Protein Aggregation.},
journal = {International journal of molecular sciences},
volume = {27},
number = {3},
pages = {},
pmid = {41684011},
issn = {1422-0067},
mesh = {Humans ; *NF-E2-Related Factor 2/metabolism ; *Oxidative Stress/drug effects ; *Neurodegenerative Diseases/metabolism/drug therapy ; *Biological Products/pharmacology/therapeutic use ; Animals ; *Protein Aggregates/drug effects ; *Protein Aggregation, Pathological/drug therapy/metabolism ; Neuroprotective Agents/pharmacology/therapeutic use ; Antioxidants/pharmacology/therapeutic use ; Signal Transduction/drug effects ; },
abstract = {Neurodegenerative diseases (NDs) are among the leading causes of disability and mortality worldwide and are characterized by multifactorial pathogenesis involving interconnected mechanisms, such as oxidative stress, protein misfolding and aggregation, neuroinflammation, and mitochondrial dysfunction. Dysregulation of transcription factors, governing cellular defense responses, particularly nuclear factor erythroid 2-related factor 2 (Nrf2), a key regulator of antioxidant and proteostatic pathways, plays a critical role in neurodegenerative processes. Currently, available pharmacological treatments for NDs are largely symptomatic, as no disease-modifying therapies exist. Natural bioactive compounds have emerged as promising multi-target agents, demonstrating antioxidant, anti-aggregative, and anti-apoptotic properties, frequently mediated through activation of the Nrf2 signaling pathways. These compounds may represent valuable supportive strategies alongside conventional drug treatments, potentially contributing to the modulation of multiple pathogenic mechanisms. This review summarizes key oxidative stress- and protein aggregation-driven mechanisms underlying Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. It further examines the neuroprotective potential of plant-, fungi-, and marine-derived natural compounds, with particular emphasis on Nrf2 activation. Beyond redox regulation, the broader role of Nrf2 in maintaining proteostasis is discussed. Overall, the review highlights Nrf2-inducing nutraceuticals as promising complementary, multi-target approaches for neuroprotection in NDs.},
}

Humans
*NF-E2-Related Factor 2/metabolism
*Oxidative Stress/drug effects
*Neurodegenerative Diseases/metabolism/drug therapy
*Biological Products/pharmacology/therapeutic use
Animals
*Protein Aggregates/drug effects
*Protein Aggregation, Pathological/drug therapy/metabolism
Neuroprotective Agents/pharmacology/therapeutic use
Antioxidants/pharmacology/therapeutic use
Signal Transduction/drug effects

@article {pmid41683920,
year = {2026},
author = {Auburger, GWJ and Key, J and Gispert, S and Lastres-Becker, I and Almaguer-Mederos, LE and Bassa, C and Auburger, A and Auburger, G and Arsovic, A and Deller, T and Sen, NE},
title = {Bioinformatic Analyses of the Ataxin-2 Family Since Algae Emphasize Its Small Isoforms, Large Chimerisms, and the Importance of Human Exon 1B as Target of Therapies to Prevent Neurodegeneration.},
journal = {International journal of molecular sciences},
volume = {27},
number = {3},
pages = {},
pmid = {41683920},
issn = {1422-0067},
support = {AU96/21-1//Deutsche Forschungsgemeinschaft/ ; },
mesh = {Humans ; *Ataxin-2/genetics/metabolism/chemistry ; *Computational Biology/methods ; *Exons ; Protein Isoforms/genetics/metabolism ; Peptides/genetics/metabolism ; Animals ; *Neurodegenerative Diseases/genetics/prevention & control ; Phylogeny ; },
abstract = {Polyglutamine expansion in Ataxin-2 (ATXN2) is responsible for rare, dominantly inherited Spinocerebellar Ataxia type 2 (SCA2). Together with its paralog Ataxin-2-like (ATXN2L), both proteins have received much interest, since the deletion of their yeast and fly orthologs alleviates TDP-43-triggered neurotoxicity in Amyotrophic Lateral Sclerosis models. Their typical structure across evolution combines LSm with LSm-Associated Domains and a PAM2 motif. To understand the physiological regulation and functions of Ataxin-2 homologs, the phylogenesis of sequences was analyzed. Human ATXN2 harbors multiple alternative start codons, e.g., from an intrinsically disordered sequence (IDR) present since armadillo, or from the polyQ sequence that arose since amphibians, or from the LSm domain since primitive eukaryotes. Multiple smaller isoforms also exist across the C-terminus. Therapeutic knockdown of polyQ expansions in human ATXN2 should selectively target exon 1B. PolyQ repeats developed repeatedly, usually framed and often interrupted by (poly)Pro, originally near PAM2. The LSmAD sequence appeared in algae as the characteristic Ataxin-2 feature with strong conservation. Frequently, Ataxin-2 has added domains, likely due to transcriptional readthrough of neighbor genes during cell stress. These chimerisms show enrichment of rRNA processing; nutrient store mobilization; membrane strengthening via lipid, protein, and glycosylated components; and cell protrusions. Thus, any mutation of Ataxin-2 has complex effects, also affecting membrane resilience.},
}

Humans
*Ataxin-2/genetics/metabolism/chemistry
*Computational Biology/methods
*Exons
Protein Isoforms/genetics/metabolism
Peptides/genetics/metabolism
Animals
*Neurodegenerative Diseases/genetics/prevention & control
Phylogeny

@article {pmid41683564,
year = {2026},
author = {Jamerlan, A and Hulme, J},
title = {From Evasion to Collapse: The Kinetic Cascade of TDP-43 and the Failure of Proteostasis.},
journal = {International journal of molecular sciences},
volume = {27},
number = {3},
pages = {},
pmid = {41683564},
issn = {1422-0067},
support = {RS-2025-02292973//Ministry of Oceans and Fisheries/ ; RS-2021-NR060117//Ministry of Education/ ; },
mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics/chemistry ; *Proteostasis ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Autophagy ; Animals ; *Frontotemporal Dementia/metabolism/genetics/pathology ; Protein Folding ; Kinetics ; },
abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurodegenerative diseases that, despite the availability of symptomatic and modestly beneficial treatments, still lack therapies capable of halting disease progression. A histopathological hallmark of both diseases is the cytoplasmic deposition of TDP-43 in neurons, which is attributed to both intrinsic (e.g., mutations, aberrant cleavage) and extrinsic factors (e.g., prolonged oxidative stress, impaired clearance pathways). Mutations and certain PTMs (e.g., cysteine oxidation) destabilize RNA binding, promoting monomer misfolding and increasing its half-life. Disruptions to core ubiquitin-proteasome system (UPS) subunits impede efficient processing, contributing to the clearance failure of misfolded TDP-43 monomers. The accumulation of monomers drives phase separation within stress granules, creating nucleation hotspots that eventually bypass the thermodynamic barrier, resulting in exponential growth. This rapid growth then culminates in the failure of the autophagy-lysosome pathway (ALP) to contain the aggregation, resulting in a self-sustaining feed-forward loop. Here, we organize these factors into a conceptual kinetic cascade that links TDP-43 misfolding, phase separation, and clearance failure. Therapeutic strategies must therefore move beyond simple clearance and focus on targeting these kinetic inflection points (e.g., oligomer seeding, PTM modulation).},
}

Humans
*DNA-Binding Proteins/metabolism/genetics/chemistry
*Proteostasis
*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology
Autophagy
Animals
*Frontotemporal Dementia/metabolism/genetics/pathology
Protein Folding
Kinetics

@article {pmid41683467,
year = {2026},
author = {Czaj, PV and Szewczyk-Golec, K and Nuszkiewicz, J and Woźniak, A},
title = {Gut Dysbiosis and Microbiota-Derived Metabolites in Neurodegenerative Diseases: Molecular and Biochemical Mechanisms Along the Gut-Brain Axis.},
journal = {Molecules (Basel, Switzerland)},
volume = {31},
number = {3},
pages = {},
pmid = {41683467},
issn = {1420-3049},
mesh = {Humans ; *Gastrointestinal Microbiome ; *Dysbiosis/metabolism/microbiology ; *Neurodegenerative Diseases/metabolism/microbiology ; Animals ; *Brain/metabolism ; Oxidative Stress ; Signal Transduction ; Parkinson Disease/metabolism/microbiology ; },
abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) share key molecular features, including neuroinflammation, oxidative stress, mitochondrial dysfunction, and progressive neuronal loss. Increasing evidence indicates that gut dysbiosis and alterations in microbiota-derived metabolites are involved in these processes through multiple pathways along the gut-brain axis. However, while broad compositional changes are well-documented, a critical knowledge gap remains regarding the specific biochemical signal transduction pathways translating dysbiosis into pathology. This narrative review addresses this gap by synthesizing current human and experimental studies addressing gut microbiota alterations in AD, PD, and ALS, with particular emphasis on the biochemical and molecular mechanisms mediated by gut-derived metabolites. Dysbiosis in neurodegenerative diseases is frequently associated with reduced abundance of short-chain fatty acid (SCFA)-producing bacteria and altered metabolism of SCFAs, bile acids, tryptophan-derived indoles, trimethylamine-N-oxide (TMAO), and lipopolysaccharides (LPS). These microbial metabolites have been shown to modulate intestinal and blood-brain barrier integrity, influence Toll-like receptor- and G protein-coupled receptor-dependent signaling, regulate microglial activation, and affect molecular pathways related to protein aggregation in experimental models. In addition, emerging evidence highlights the involvement of oxidative and nitrosative stress, immune-metabolic crosstalk, and altered xenobiotic metabolism in microbiota-host interactions during neurodegeneration. By integrating microbiological, metabolic, and molecular perspectives, this review underscores the important and emerging role of microbiota-derived molecules in neurodegenerative disorders and outlines key chemical and metabolic pathways that may represent targets for future mechanistic studies and therapeutic strategies.},
}

Humans
*Gastrointestinal Microbiome
*Dysbiosis/metabolism/microbiology
*Neurodegenerative Diseases/metabolism/microbiology
Animals
*Brain/metabolism
Oxidative Stress
Signal Transduction
Parkinson Disease/metabolism/microbiology

@article {pmid41612292,
year = {2026},
author = {Maritim, B and Mbau, R and Musiega, A and Musuva, A and Amboko, B and Tsofa, B and Mazzilli, C and Vilcu, I and Wong, E and Murira, F and Nzinga, J and Boxshall, M and Mugo, P and Muthuri, RNDK and Ng'ang'a, W and Ravishankar, N and Barasa, E},
title = {"Poverty is a social issue, not a mathematical problem": examining the lessons for beneficiary identification from implementation of the UHC indigent program in Kenya.},
journal = {International journal for equity in health},
volume = {25},
number = {1},
pages = {40},
pmid = {41612292},
issn = {1475-9276},
support = {INV-049230/GATES/Gates Foundation/United States ; INV-049230/GATES/Gates Foundation/United States ; },
abstract = {BACKGROUND: Kenya rolled out a UHC indigent program aimed to expand financial protection and health service access for poor households through subsidized health insurance under the national insurer, National Health Insurance Fund (NHIF). As Kenya transitions to a new social health insurance framework under the Social Health Authority (SHA), understanding the implementation experience of the UHC indigent program is critical for informing the roll out of SHA’s indigent program.

METHODS: We conducted a qualitative process evaluation of the UHC indigent program using document reviews, semi-structured interviews with 23 key informants from national and county health authorities, development partners, and implementing actors, complemented by a validation workshop with 57 stakeholders. Our analysis was guided by Moore et al.‘s process evaluation framework and Wu et al.‘s policy capacity lens, examining implementation fidelity and capacities at multiple levels.

RESULTS: The program’s implementation deviated from its original centralized design, with counties exerting control over beneficiary identification due to national data gaps, incomplete rollout of the Harmonized Testing Tool, and political and operational constraints. Variations in targeting methods, reliance on under-resourced community health actors, and delays in biometric registration contributed to partial enrolment, limited access, exclusion errors, and mistrust. Although some counties reported increased service utilization, this was limited by unregistered dependents and lack of beneficiary awareness. Stakeholders expressed concern over SHA’s use of proxy means testing for identifying the poor, citing risks of exclusion, manipulation, and failure to capture locally constructed definitions of poverty.

CONCLUSION: Kenya’s experience demostrates the need to align national targeting frameworks with local realities, invest in policy capacity across stakeholders, and prioritize community validation and communication in subsidy programs. As SHA rolls out a new indigent program, these lessons offer critical guidance for enhancing fidelity, equity, and accountability.},
}

@article {pmid41682164,
year = {2026},
author = {Jeong, Y and Yoon, HJ},
title = {Factors Influencing Retention at Their First Hospital Among New Graduate Nurses in South Korea.},
journal = {Healthcare (Basel, Switzerland)},
volume = {14},
number = {3},
pages = {},
doi = {10.3390/healthcare14030314},
pmid = {41682164},
issn = {2227-9032},
support = {2024//Yeungnam University College Research Grants/ ; },
abstract = {Background/Objectives: Early turnover among new graduate nurses remains challenging in South Korea. This study examined how socialisation factors-based on Scott et al.'s transition model and Herzberg's motivation-hygiene theory-are associated with early retention at the first hospital of employment among new graduate nurses. Methods: This retrospective cross-sectional study analysed secondary data from the Graduate Occupational Mobility Survey (GOMS), a nationally representative dataset of college and university graduates in Korea, collected using a stratified multi-stage sampling method. The study included 602 new graduate nurses from the 2017-2019 datasets who had worked as nurses at their first hospital of employment. Anticipatory socialisation factors included personal and educational characteristics. Organisational socialisation factors referred to workplace-related characteristics of the first hospital, including motivational factors and hygiene factors. The outcome variable was early retention. Multiple logistic regression analyses were performed to identify factors associated with early retention. Results: A total of 68.6% of nurses remained in their first hospital employment. Retention was more likely among nurses whose high school, nursing school, and first hospital were in the same region (p = 0.019), those employed in Seoul (p < 0.001), and those working in larger hospitals (p < 0.001). Retention was also associated with satisfaction with autonomy and authority (p = 0.013). Conversely, lower retention was observed among nurses who were dissatisfied with interpersonal relationships (p < 0.001) and those who reported satisfaction with growth opportunities (p < 0.001). Conclusions: Targeted strategies that support new graduate nurses during their transition are essential. Aligning education-to-employment regions and strengthening workplace conditions may enhance early retention.},
}

@article {pmid41681063,
year = {2026},
author = {Kim, MS and Nam, Y and Kim, KT},
title = {Ultrasonographic Measurements of Tongue Thickness and Swallowing Dysfunction in Amyotrophic Lateral Sclerosis: A Feasibility Study.},
journal = {Annals of rehabilitation medicine},
volume = {},
number = {},
pages = {},
doi = {10.5535/arm.250135},
pmid = {41681063},
issn = {2234-0645},
abstract = {OBJECTIVE: To explore whether ultrasonographic measurements of tongue thickness are associated with swallowing function and related clinical domains in patients with amyotrophic lateral sclerosis (ALS), this feasibility study was conducted. Few studies have examined the usefulness of ultrasonographic tongue thickness measurement in patients with ALS, but its association with physiological measures remains unclear.

METHODS: Ten patients with ALS underwent tongue thickness measurement using ultrasonography. Clinical assessments including the Korean version of the ALS Functional Rating Scale-Revised (K-ALSFRS-R), Functional Oral Intake Scale (FOIS), Eating Assessment Tool-10 (EAT-10), Dysphagia Handicap Index, Korean version of the Swallowing Quality of Life Questionnaire, Mini Nutritional Assessment-Short Form (MNA-SF), handgrip strength, and bioelectrical impedance analysis for skeletal muscle index (SMI) were performed. Swallowing physiology was evaluated using the Modified Barium Swallow Impairment Profile (MBSImP), Penetration-Aspiration Scale. Simple and partial Pearson's correlation analyses as well as univariate regression were performed with adjustments for age, sex, and body mass index (BMI).

RESULTS: Tongue thickness showed significant associations with multiple functional and systemic measures in the unadjusted analyses, including FOIS, EAT-10, MNA-SF, BMI, SMI, K-ALSFRS-R. After adjustment, the most consistent associations were observed with the MBSImP oral, pharyngeal, and combined phase scores.

CONCLUSION: Tongue ultrasonography may serve as a radiation-free method to preliminarily assess bulbar involvement in ALS. Tongue thickness was most specifically associated with dysphagia outcomes, particularly MBSImP. Given the feasibility design and small sample size, larger longitudinal studies are warranted to confirm its clinical utility in monitoring the progression of dysphagia in patients with ALS.},
}

@article {pmid41679263,
year = {2026},
author = {Martínez-Hernáez, Á and Insunza, A and Vidal, F},
title = {"Those eyes that look at you:" somatic modes of care in professional encounters with amyotrophic lateral sclerosis patients.},
journal = {Social science & medicine (1982)},
volume = {395},
number = {},
pages = {119065},
doi = {10.1016/j.socscimed.2026.119065},
pmid = {41679263},
issn = {1873-5347},
abstract = {In the advanced stages of amyotrophic lateral sclerosis (ALS), individuals experience a gradual and irreversible loss of speech and voluntary movement, while cognitive and emotional capacities often remain largely preserved. ALS frequently culminates in the locked-in state (LIS), where subjectivity endures despite an almost complete breakdown of expressive capacity. This article examines how professional caregivers sustain relational engagement and recognition under such conditions. The analysis draws on eleven qualitative interviews with social workers, psychologists, occupational therapists, nurses, and a neurologist working in Catalonia (Spain) in long-term home-based and community care for people with ALS. A hermeneutic phenomenological approach was used to explore how professionals perceive, interpret, and respond to patients whose expressive capacities have largely disappeared. Findings show that communication does not cease but is reconfigured into embodied forms such as gaze, muscle tone, breathing patterns, tears, and silence. Caregivers describe these signs as requiring perceptual attunement and temporal continuity. Building on Thomas Csordas's idea of somatic modes of attention, we conceptualize "somatic modes of care" as the embodied, affective, and ethical practices through which relation and subjectivity are sustained when language fails, a dimension inherent to all care, but rendered especially visible and indispensable in ALS and LIS. For professionals, personhood emerges as a fragile relational achievement upheld through recognition, memory, and sustained presence. Somatic modes of care thus offer an analytic lens for understanding how subjectivity is maintained under radical communicative constraints, with implications for clinical practice and for broader debates on care, embodiment, and relational ethics.},
}

@article {pmid41678537,
year = {2026},
author = {Helal, MM and Almosilhy, NA and Abo-Elnour, DE and Jaffal, RSY and Allam, EG and Almosilhy, MA and Batarseh, SF and Meshref, M},
title = {Targeting metabolic dysfunction in amyotrophic lateral sclerosis: therapeutic potential of GLP-1 receptor agonists.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-27},
doi = {10.1080/21678421.2026.2627901},
pmid = {41678537},
issn = {2167-9223},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron loss and profound systemic metabolic dysfunction, including hypermetabolism, weight loss, insulin resistance, and altered glucose and lipid homeostasis. Increasing recognition of these metabolic abnormalities has driven interest in repurposing antidiabetic therapies, particularly glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonists (GLP-1RAs), for ALS. Beyond their established metabolic actions, GLP-1RAs exert pleiotropic effects relevant to neurodegeneration, including modulation of neuroinflammation, mitochondrial function, oxidative stress, excitotoxicity, and cell-survival signaling, with selected agents demonstrating central nervous system penetration. This narrative review summarizes current knowledge on metabolic impairment in ALS and critically evaluates the mechanistic rationale, preclinical evidence, and emerging clinical data supporting or opposing the use of GLP-1-based therapies in this disease. Preclinical studies suggest that GLP-1 signaling can provide neuroprotective and neurotrophic effects in ALS models, although findings are heterogeneous and highly dependent on compound selection, delivery strategy, and experimental design. In contrast, available clinical evidence is limited and does not demonstrate therapeutic benefit in ALS, while raising important safety concerns, particularly related to weight loss, lean mass reduction, and altered glucose regulation, factors associated with a worse prognosis in ALS. Collectively, current data indicate that although GLP-1-based therapies may have compelling biological plausibility and beneficial effects in other neurodegenerative disorders (NDGs), their role in ALS remains uncertain and potentially harmful. Well-designed, ALS-specific clinical studies are required to clarify safety, efficacy, and patient selection before GLP-1RAs can be considered for therapeutic use in this vulnerable population.},
}

@article {pmid41678358,
year = {2026},
author = {Johari, M and Folland, C and Saito, Y and Oud, MM and Parmar, JM and Töpf, A and Kurbatov, S and Ampleeva, M and Zakharova, EY and Chekmareva, IA and Shirokova, KS and Atiakshin, D and van Beek, R and Gardeitchik, T and Kamsteeg, EJ and Medici, E and Donker Kaat, L and Nemoto, J and Komaki, H and Okabe, T and Kimoto, Y and Tokito, T and Nakanowatari, M and Oya, Y and Bruels, CC and Stafki, SA and Estrella, EA and Littel, HR and Kunkel, LM and Kang, PB and Osei-Owusu, I and Pais, L and O'Leary, M and Austin-Tse, C and O'Donnell-Luria, A and Mangilog, B and Genetti, CA and Valivullah, ZM and Radio, FC and D'Amico, A and Ciolfi, A and Tartaglia, M and Perrin, A and Van Goethem, C and Sole, G and Martin-Négrier, ML and Cossée, M and Milic Rasic, V and Kovacevic, G and Kosac, A and Moreno, CAM and Gontijo Camelo, C and Zanoteli, E and Habib, C and Fahey, MC and Beggs, AH and Poulsen, NS and Vissing, J and Straub, V and Savarese, M and Tasca, G and Voermans, NC and Laing, NG and Udd, B and Nishino, I and Ravenscroft, G},
title = {Missense variants in TUBA4A cause myo-tubulinopathies.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag059},
pmid = {41678358},
issn = {1460-2156},
abstract = {Tubulinopathies encompass a spectrum of disorders resulting from variants in genes encoding α- and β-tubulins, the key components of microtubules. While previous studies have linked de novo or dominantly inherited TUBA4A missense variants to neurodegenerative phenotypes, including amyotrophic lateral sclerosis, frontotemporal dementia, spastic ataxia, and recently, an isolated congenital myopathy, the full phenotypic and genotypic spectrum of TUBA4A-related disorders remains incompletely characterised. In this multi-centre study, we identified one previously reported and 12 novel TUBA4A missense variants in 31 individuals from 19 unrelated families. Remarkably, individuals in 17 families presented with a myopathy without any CNS involvement or history of such disease. In the remaining two families, we observed probands with cerebellar ataxia and epilepsy accompanying proximal and axial muscle weakness along with protein aggregation. The coexistence of neuromuscular and neurodegenerative features with protein aggregation defines a multisystem proteinopathy. These two families thus establish the first association between TUBA4A and multisystem proteinopathy. Our cohort exhibited diverse genotypes and inheritance patterns: four families demonstrated autosomal dominant transmission through heterozygous variants in TUBA4A, three probands had recessive inheritance due to homozygous variants, while the respective heterozygous carriers were asymptomatic; five probands carried de novo variants, and nine probands with heterozygous variants were classified as sporadic cases. Clinical phenotypes ranged from mild to severe myopathy, predominantly affecting the axial and paraspinal muscles. We observed a range of disease onset, from congenital to late adulthood. Creatine kinase levels were variable, ranging from normal to highly elevated. Cardiac function remained preserved across the cohort. Muscle biopsies showed heterogenous myopathic changes, including myofibre size variation, nemaline bodies, core-like regions, and internal nuclei. Immunohistochemical analysis revealed protein accumulations positive for TDP-43 (n=2), p62 (n=5), and TUBA4A (n=6). Complementary in silico and in vitro investigations suggested that the identified TUBA4A variants cause significant protein abnormalities and may differentially impact microtubule dynamics. Correlation analyses integrating clinical severity, variant location, and mechanistic readouts further demonstrated that domain specificity within TUBA4A influences both the pattern of muscle involvement and the extent of microtubule disruption. Our findings establish myo-tubulinopathies as distinct clinical entities, encompassing both primary myopathies and multisystem proteinopathies with muscle involvement. This study broadens the phenotypic and genotypic spectrum of TUBA4A-related disorders beyond autosomal dominant or de novo mechanisms and neurodegenerative presentations. These results underscore the importance of considering TUBA4A variants in the differential diagnosis of axial myopathies and multisystem proteinopathies, regardless of central nervous system (CNS) involvement.},
}

@article {pmid41678221,
year = {2026},
author = {Sinclair, SJ and Haggerty, G and Cowie, KD and Shea, KE and Shea, KL},
title = {Proclaiming a psychological assessment tool is "reliable, valid, and ethical" doth not make it so: A reply to Stein et al. (2026) and Jenkins (2026).},
journal = {Psychological assessment},
volume = {38},
number = {3},
pages = {253-265},
doi = {10.1037/pas0001451},
pmid = {41678221},
issn = {1939-134X},
mesh = {Humans ; *Psychological Tests/standards ; Reproducibility of Results ; *Social Cognition ; },
abstract = {We thank Stein et al. (2026) and Jenkins (2026) for their commentaries on our critical review of the Social Cognition and Object Relations Scale-Global system as applied to the Thematic Apperception Test (Sinclair et al., 2023) and appreciate the opportunity to respond in kind. Although we acknowledge the considerable effort put into these response articles (analytically and conceptually), both fall short in addressing the myriad serious methodological and procedural concerns we raised in 2023 and do little to move the needle in support of this assessment technique. This article will review the many ways these responses misinterpret and misrepresent our original review and the voluminous methodological problems with the "meta-analyses" that are presented by Stein et al.-and the various ways they are statistically confounded, confusing, and scientifically unsound. Further, this article will highlight the considerable number of logical inconsistencies that are inherent within Stein et al.'s core arguments, as well as the numerous contradictions between Stein et al. and Jenkins-all of which seriously undermine the methodology itself. Given the many ethical ambiguities that arise as a result, we conclude with a repeat calling for a moratorium on this methodology until these issues are sufficiently resolved. (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}

Humans
*Psychological Tests/standards
Reproducibility of Results
*Social Cognition