@article {pmid41885638,
year = {2026},
author = {Sadhukhan, A and Chauhan, A and Kumar, M and Singh, TG and Mujwar, S and Awasthi, A},
title = {Cryptoxanthin as a multitarget neuroprotective agent: mechanistic and in silico perspectives.},
journal = {The Journal of pharmacy and pharmacology},
volume = {78},
number = {3},
pages = {},
doi = {10.1093/jpp/rgag029},
pmid = {41885638},
issn = {2042-7158},
mesh = {*Neuroprotective Agents/pharmacology/therapeutic use ; Humans ; Molecular Docking Simulation ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Xanthophylls/pharmacology/therapeutic use ; Animals ; Oxidative Stress/drug effects ; Anti-Inflammatory Agents/pharmacology ; Antioxidants/pharmacology ; Computer Simulation ; },
abstract = {OBJECTIVES: Neurodegenerative diseases such as Parkinson's disease (PD), Huntington's disease (HD), Alzheimer's disease (AD), and Amyotrophic lateral sclerosis (ALS) are complex disorders driven by multiple pathological processes, including oxidative stress, mitochondrial dysfunction, protein misfolding, and neuroinflammation. Due to this multifactorial nature, there is a growing interest in identifying natural compounds with multi-targeted neuroprotective properties. This review aims to evaluate the therapeutic potential of β-cryptoxanthin, a naturally occurring xanthophyll carotenoid, as a candidate molecule for mitigating neurodegenerative diseases.

METHODS: A comprehensive literature review was conducted to examine the neuroprotective mechanisms of β-cryptoxanthin, focusing on its antioxidant, anti-inflammatory, and immunomodulatory properties. In addition, in silico molecular docking studies were performed using AutoDock Vina to investigate the binding interactions of β-cryptoxanthin with key molecular targets associated with inflammation and neurodegenerative pathways.

KEY FINDINGS: β-Cryptoxanthin demonstrated strong neuroprotective potential due to its ability to scavenge reactive oxygen species (ROS) and modulate key molecular pathways involved in neuroinflammation and oxidative damage. Structurally characterized by a hydroxylated β-carotene backbone with 11 conjugated double bonds, β-cryptoxanthin showed favorable binding affinities with several inflammation- and neurodegeneration-related targets, including COX-2 (-11.6 kcal/mol), PI3K (-9.6 kcal/mol), mTOR1 (-9.2 kcal/mol), and GSK-3β (-8.7 kcal/mol). Additionally, interactions with JAK2, MAPK1, NF-κB, NRF2, and TLR4 suggest its involvement in regulating neuroimmune signalling pathways and inflammatory mediators.

CONCLUSIONS: The findings of this review highlight β-cryptoxanthin as a promising candidate for future neurotherapeutic investigation due to its multi-targeted mechanisms of action against key pathways implicated in neurodegeneration. Molecular docking results support its potential mechanistic role in modulating inflammation- and oxidative stress-related targets. However, these findings represent mechanistic plausibility rather than confirmed clinical efficacy, and further validation through preclinical and clinical studies is required.},
}

*Neuroprotective Agents/pharmacology/therapeutic use
Humans
Molecular Docking Simulation
*Neurodegenerative Diseases/drug therapy/metabolism
*Xanthophylls/pharmacology/therapeutic use
Animals
Oxidative Stress/drug effects
Anti-Inflammatory Agents/pharmacology
Antioxidants/pharmacology
Computer Simulation

@article {pmid41885937,
year = {2026},
author = {Akiyama, T and Zeng, Y and Guo, C and Gautier, O and Koepke, L and Lyons, H and Molotsky, E and Bombosch, JS and Sianto, O and Ross, JP and Hoang, P and Zhao, L and Spencer, C and Sumner, CJ and Monje, M and Day, JW and Gitler, AD},
title = {KIF5A downregulation in spinal muscular atrophy links axonal regeneration defects with ALS.},
journal = {JCI insight},
volume = {},
number = {},
pages = {},
doi = {10.1172/jci.insight.197941},
pmid = {41885937},
issn = {2379-3708},
abstract = {Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder caused by mutations in the survival motor neuron 1 (SMN1) gene leading to decreased SMN protein levels and motor neuron dysfunction. SMN-restoring therapies offer clinical benefit, but the downstream molecular consequences of SMN reduction remain incompletely understood. SMN deficiency resulted in downregulation of kinesin heavy chain isoform 5A (KIF5A) in human neurons and in a mouse model of SMA. SMN associated with KIF5A mRNA and contributed to its stability. Reduced SMN levels impaired axon regeneration, which was rescued by KIF5A overexpression. Because KIF5A has also been connected to ALS, these findings provide evidence of a molecular link between SMA and ALS pathophysiology, highlighting KIF5A as an SMN regulated factor. Our findings suggest SMN-independent interventions targeting KIF5A could represent a complementary therapeutic approach for SMA and other motor neuron diseases.},
}

@article {pmid41888300,
year = {2026},
author = {Sanchez-Mico, MV and Calvo-Rodriguez, M and Bacskai, BJ},
title = {Role of dysregulated calcium homeostasis in astrocytes in neurodegenerative disorders.},
journal = {Nature reviews. Neuroscience},
volume = {},
number = {},
pages = {},
pmid = {41888300},
issn = {1471-0048},
abstract = {Calcium signalling in astrocytes is a fundamental mechanism for maintaining brain homeostasis, shaping neuronal activity, and coordinating vascular and immune responses. Once considered secondary to neuronal signalling, astrocytic Ca[2+] dynamics are now recognized as highly versatile, spatially compartmentalized and essential for regulating neurotransmitter uptake, ion buffering, metabolic support and mitochondrial function. Accumulating evidence shows that these Ca[2+] signalling pathways are progressively remodelled during ageing and become profoundly dysregulated in neurodegenerative diseases, including Alzheimer disease, Parkinson disease, Huntington disease and amyotrophic lateral sclerosis. Importantly, astrocyte Ca[2+] alterations are heterogeneous and context-dependent, ranging from aberrant spontaneous activity to loss of signalling in specific subcellular domains, reflecting the disease stage, brain region and molecular pathology. Disruption of astrocyte Ca[2+] homeostasis compromises core homeostatic functions and contributes to neuronal vulnerability, circuit dysfunction and impaired neurovascular regulation. By integrating current evidence across physiological, ageing and disease contexts, this Review highlights astrocytic Ca[2+] signalling as a central node in neurodegenerative pathophysiology and underscores its potential as a target for therapeutic intervention.},
}

@article {pmid41888437,
year = {2026},
author = {McLellan, C and Campos-Melo, D and Hammond, R and Strong, MJ},
title = {Preservation of miR-9-5p and miR-124-3p in ALS-resistant oculomotor neurons contrasts with their downregulation in vulnerable spinal motor neurons, irrespective of TDP-43 pathology.},
journal = {Acta neuropathologica},
volume = {151},
number = {1},
pages = {},
pmid = {41888437},
issn = {1432-0533},
support = {201806SOP-411481/CAPMC/CIHR/Canada ; },
mesh = {*MicroRNAs/metabolism/genetics ; *Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics ; *Motor Neurons/metabolism/pathology ; Humans ; Male ; Middle Aged ; Female ; Down-Regulation ; *DNA-Binding Proteins/metabolism ; Aged ; *Spinal Cord/pathology/metabolism ; Adult ; },
abstract = {Selective vulnerability of motor neurons is a defining feature of amyotrophic lateral sclerosis (ALS) and provides a valuable framework for uncovering mechanisms that distinguish resilient from vulnerable neuronal populations. We investigated whether dysregulation of neuroprotective microRNAs (miRNAs), miR-9-5p and miR-124-3p, contributes to the differential susceptibility of motor neuron subtypes. We focused on cervical spinal motor neurons (SMNs), which undergo drastic degeneration in ALS, and oculomotor neurons (OMNs), which remain functionally intact and rarely degenerate, allowing preservation of eye movement in ALS patients. Using a modified multiplexed fluorescent in situ hybridization protocol combined with immunofluorescence, we quantified the expression of miR-9-5p and miR-124-3p in cervical SMNs and OMNs from ALS and control cases. We observed significant downregulation of both miRNAs in ALS SMNs, while their expression was maintained in ALS OMNs. Stratification of ALS SMNs by TDP-43 pathological status revealed similarly reduced miRNA expression in neurons with and without cytoplasmic inclusions, suggesting that miRNA downregulation occurs independently of visible TDP-43 pathology. We assessed the localization of the Dicer cofactor TRBP and found that it colocalized with TDP-43 inclusions in ALS SMNs, suggesting that TRBP sequestration could prevent proper miRNA processing. However, TRBP remained normally localized in neurons without cytoplasmic inclusions, indicating that sequestration cannot fully account for miRNA reduction across all ALS motor neurons. These findings support a model in which early or subtle disruptions, preceding visible pathology, may also contribute to miRNA downregulation in ALS. By identifying preserved miRNA networks as correlates of oculomotor neuron resilience in ALS, this work also exposes new therapeutic targets potentially capable of reinstating miRNA expression and reprogramming vulnerable SMNs.},
}

*MicroRNAs/metabolism/genetics
*Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics
*Motor Neurons/metabolism/pathology
Humans
Male
Middle Aged
Female
Down-Regulation
*DNA-Binding Proteins/metabolism
Aged
*Spinal Cord/pathology/metabolism
Adult

@article {pmid41888964,
year = {2026},
author = {Haddouali, K and Simma, K and Bellakhdar, S and El Otmani, H and El Moutawakil, B and Rafai, MA},
title = {Multifocal motor neuropathy secondary to gluten intolerance: a case report.},
journal = {Journal of medical case reports},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13256-026-05968-2},
pmid = {41888964},
issn = {1752-1947},
abstract = {BACKGROUND: Peripheral nervous system manifestations of gluten sensitivity usually present as distal symmetric axonal polyneuropathy, small fiber neuropathy, or sensory neuropathy, often accompanied by ataxia or painful symptoms. By contrast, motor neuropathies are extremely rare, with only a few cases of multifocal motor neuropathy reported. Notably, the most recent guidelines of the European Society for the Study of Coeliac Disease do not recognize multifocal motor neuropathy as a classical neurological manifestation of gluten-related disorders. The main differential diagnoses include amyotrophic lateral sclerosis and chronic inflammatory demyelinating polyneuropathy. Currently, strict adherence to a gluten-free diet remains the only therapeutic option. Although clinical improvement is not universal, when observed, it strongly supports the causal role of gluten-related neurotoxicity.

CASE PRESENTATION: We report the case of a 50-year-old North African man with a history of dermatitis herpetiformis and persistent chronic diarrhea. Over the past 5 years, he developed progressive asymmetric motor weakness. Clinical examination revealed an asymmetric, pure motor, peripheral neurogenic syndrome, confirmed by nerve conduction studies, without evidence of proximal conduction block. Cerebrospinal fluid analysis showed elevated protein levels (0.75 g/L), and serum anti-GD3 IgM antibodies were positive. Brachial plexus magnetic resonance imaging revealed bilateral hypertrophy on T1-weighted sequences, with hyperintensity on short tau inversion recovery sequences but no contrast enhancement. The motor deficit gradually improved after the introduction of a gluten-free diet. The patient also received intravenous immunoglobulin without significant clinical benefit. On the basis of clinical, paraclinical, and follow-up findings, a diagnosis of multifocal motor neuropathy secondary to gluten intolerance was established.

CONCLUSION: This case highlights the importance of considering gluten intolerance as a potential etiology, particularly given the reversible nature of this neuropathy, which can otherwise be misdiagnosed as a more severe condition such as amyotrophic lateral sclerosis. Further studies are needed to better elucidate the pathophysiology of this rare gluten-related neurological phenotype.},
}

@article {pmid41889878,
year = {2026},
author = {Hines, TJ and Funke, JR and Pratt, SL and Rice, AD and Twiss, JL and Burgess, RW},
title = {A mouse model of autosomal dominant spastic ataxia and myopathy caused by a mutation in Tuba4a.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.03.06.710113},
pmid = {41889878},
issn = {2692-8205},
abstract = {Hereditary ataxias are a heterogeneous group of neurodegenerative disorders characterized by impaired balance and coordination, often due to cerebellar dysfunction. Despite advances in identifying genetic causes, animal models remain essential for dissecting underlying mechanisms and testing therapeutic strategies. Here we describe a mouse model of spastic ataxia and myopathy caused by a missense mutation in Tuba4a (n.A626C, p.Gln176Pro). In an ENU mutagenesis screen, a male C57BL/6J mouse exhibiting muscle wasting and an intention tremor starting at approximately 4 weeks-of-age was identified. The male was bred by in vitro fertilization to BALB/cByJ oocyte donors. Genetic mapping determined dominant inheritance and localized the mutation to Chromosome 1. Genome sequencing revealed single nucleotide polymorphisms (SNPs) in serine threonine kinase 36 (Stk36 [Y1003N]) and alpha-tubulin 4A (Tuba4a [Q176P]) in the mapping interval. These SNPs were CRISPR-engineered into C57BL/6J mice, which confirmed the Tuba4a [Q176P] variant as the causative mutation. Mutant mice are normal at 3 weeks, except for decrement in muscle response following repetitive nerve stimulation. However, by 30 days these mice have ataxia, Purkinje neuron degeneration, and extensive skeletal muscle defects, which contribute to a decreased lifespan. Dominant TUBA4A mutations in humans are associated with spastic ataxia type 11 (SPAX11), congenital myopathy type 26 (CMYO26), and frontotemporal dementia/amyotrophic lateral sclerosis type 9 (FTDALS9). Our mice exhibit hallmark features of SPAX11 and CMYO26, but do not show motor neuron degeneration. This specificity makes this model a valuable tool for studying cell-type selective effects of TUBA4A mutations in neurodegeneration and myopathy.},
}

@article {pmid41890126,
year = {2026},
author = {Spence, H and Read, FL and Waldron, FM and Gregory, JM},
title = {Metabolic signatures of ferritin and TDP-43 co-pathology provide a mechanistic basis for stratified therapeutic approaches in ALS.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.03.13.711539},
pmid = {41890126},
issn = {2692-8205},
abstract = {BACKGROUND: ALS is increasingly recognized as a biologically heterogeneous disease in which several molecular and pathological mechanisms converge on a similar clinical phenotype. One of these molecular markers is ferritin accumulation which is observed in a subset of ALS cases and has been shown to directly correlate with TDP-43 pathology in some brain regions. Additionally, TDP-43 proteinopathy is observed outside of ALS which may complicate the interpretation of case vs control approaches to target discovery. Here, we propose a pathology-stratified approach to empower targeted theranostics. We hypothesised that biologically distinct ALS subtypes may be defined by specific metabolic dysfunction linked to brain-accumulated ferritin and TDP-43 pathology.

METHODS: Post-mortem primary motor cortex tissue from 15 ALS cases and 20 age- and sex-matched controls was stratified, using immunohistochemistry, by single- or co-occurrence of ferritin accumulation, and pathological TDP-43. Untargeted metabolomics (>1,000 metabolites) was performed, and samples were stratified into dual positive (ferritin and TDP-43), single positive (either), or negative. Group-discriminating metabolites were identified using partial least squares discriminant analysis.

RESULTS: Dual ferritin and TDP-43 pathology reflected a distinct metabolomic profile, separable from single-pathology states. This dual positive metabolic signature was characterised by disruption of lysophospholipid, lysoplasmalogen, and fatty acid metabolism, consistent with impaired membrane and energy homeostasis. In contrast, pathological TDP-43 presence without ferritin, was characterised metabolically by significant depletion of secondary bile acids and increase in glycosylation markers, whilst ferritin accumulation alone reflected significant increase in oxidative stress and depletion of lipid peroxidation inhibition markers. The dual positive state suggests failure of compensatory metabolic responses present in single-pathology conditions.

CONCLUSIONS: Ferritin accumulation and TDP-43 pathology define biologically distinct subtypes associated with ALS with divergent metabolic vulnerabilities. The metabolic signature associated with dual pathology provides a mechanistic correlate to MRI-visible ferritin accumulated iron, supporting paired non-invasive biomarker and target discovery for pathology-dependent patient stratification. These findings argue for pathway-targeted, subtype-specific therapeutic strategies and highlight the necessity of precision medicine approaches in ALS.

SHORT ABSTRACT: Amyotrophic lateral sclerosis (ALS) exhibits profound molecular heterogeneity that is not captured by current clinical classifications. Additionally, TDP-43 proteinopathy is observed outside of ALS which may complicate the interpretation of case vs control approaches to target discovery. Here, we propose a pathology-stratified approach to therapeutic target discovery, identifying convergent iron dysregulation and TDP-43 pathology with specific metabolic consequences. Post-mortem primary motor cortex tissue from 15 ALS cases and 20 controls was investigated for ferritin, and pathological TDP-43 using RNA aptamer-based immunostaining. Untargeted metabolomics (>1,000 metabolites) was performed with stratification into dual positive, single positive, or negative groups, followed by partial least squares discriminant analysis. Dual ferritin and TDP-43 pathology produced a distinct metabolic state characterised by disruption of lysophospholipid, lysoplasmalogen, and fatty acid metabolism, indicating impaired membrane integrity and energy homeostasis. In contrast, single positive states engaged divergent compensatory pathways involving bile acid metabolism, glycosylation, or oxidative stress regulation. Ferritin-TDP-43 convergence defines a metabolically decompensated ALS subtype corresponding to MRI signatures, providing a mechanistic basis for imaging-guided, pathology-dependent patient stratification and targeted intervention.

KEY FINDINGS: Metabolically distinct subtypes were defined by the presence or absence of ferritin-associated iron accumulation and TDP-43 pathology in the primary motor cortex.Concurrent ferritin and TDP-43 pathology produce a unique, metabolically decompensated state characterised by disrupted lipid, membrane, and energy metabolism, distinct from either pathology alone.Single positive states engage divergent compensatory metabolic pathways, which are lost when ferritin and TDP-43 co-occur.The metabolic signature of dual positivity provides a mechanistic correlate to the MRI-visible motor band sign.These findings support the use of pathology-based stratification of ALS patients and a foundation for pathway-targeted, precision therapeutic approaches.},
}

@article {pmid41890230,
year = {2026},
author = {Aguerd, A and Nouadi, B and Ezaouine, A and Fenjar, I and Bennis, F and Chegdani, F},
title = {An in silico protocol for predicting genetic biomarkers in rare diseases: a case study in sporadic amyotrophic lateral sclerosis.},
journal = {Frontiers in genetics},
volume = {17},
number = {},
pages = {1742595},
pmid = {41890230},
issn = {1664-8021},
abstract = {Studying the genetics of rare diseases is challenging because small sample sizes limit the statistical power of standard methods like Genome-wide association studies (GWAS). We created a new machine-learning approach to find candidate Single Nucleotide Polymorphisms (SNPs) when data is scarce. Our method trains a Random Forest model to spot similarities between SNPs. We used 189 known Sporadic Amyotrophic Lateral Sclerosis (sALS)-linked SNPs as positive examples and 938,544 unrelated SNPs as negatives. The model learns from genomic location, significance levels, nearby genes, and other features. When we tested it on sALS, it performed exceptionally well, with 93.8% accuracy and near-perfect AUC scores. The method uncovered 1,890 new SNP candidates for sALS. Among these, 209 reached genome-wide significance, and 50 appeared repeatedly in our analyses, making them strong candidates. Key genes like SARM1, OPHN1, and BPTF emerged from the results, all connected to neural health and survival pathways. Our examination revealed a notable excess of SNPs on chromosome 18 compared to expectations. This non-random distribution underscores the region's particular interest. Here, our approach demonstrates its ability to extract meaningful signals from a restricted sample. The results generated by this approach enable early diagnosis of the disease under study, explanation of its mechanism, and identification of therapeutic targets.},
}

@article {pmid41890274,
year = {2026},
author = {Silva-Hucha, S and Hernández, RG and Baena-López, D and Fernández de Sevilla, ME and Paradas, C and Morcuende, S},
title = {Excitotoxicity in amyotrophic lateral sclerosis: a key pathogenic mechanism.},
journal = {Brain communications},
volume = {8},
number = {2},
pages = {fcag098},
pmid = {41890274},
issn = {2632-1297},
abstract = {Amyotrophic lateral sclerosis is a complex neurodegenerative disease affecting motor neurons, characterized by the involvement of various factors, including oxidative stress, inflammatory processes, glutamate excitotoxicity, mitochondrial dysfunction, protein aggregation, axonal transport abnormalities, and apoptosis. The complexity of amyotrophic lateral sclerosis arises from its multifactorial aetiology involving diverse genetic, protein, metabolic, and cellular alterations. Mutations of different genes, such as SOD1, C9ORF72, TARDBP, and FUS, have been identified as critical contributors to disease pathophysiology through their facilitation of aberrant protein misfolding and aggregation. All these factors disrupt glutamate homeostasis, leading to calcium-mediated neurotoxicity. Under oxidative stress, motor neurons exhibit a diminished capacity to regulate calcium influx, along with impaired functioning of the mitochondria and endoplasmic reticulum, further compromising cellular integrity. Dysregulation of glutamate signalling also triggers astrocytic stress responses, leading to reduced glutamate clearance, thus worsening neuronal damage through excitotoxic mechanisms. These factors contribute to the excessive production of reactive oxygen species, which exacerbates glutamate imbalance and establishes a detrimental cycle of neuronal damage and glial dysfunction, ultimately intensifying excitotoxicity. This review aims to highlight the role of excitotoxicity in motor neuronal degeneration and to explore the molecular mechanisms underlying the pathogenesis of amyotrophic lateral sclerosis. It also examines current therapeutic approaches, including approved treatments and ongoing clinical trials to reduce excitotoxicity, while emphasizing the urgent need for novel, targeted strategies. Given the lack of definitive diagnostic tools and curative therapies, advancing our understanding of the molecular mechanisms driving excitotoxicity and neurodegeneration is, therefore, crucial for the development of more effective, disease-modifying treatments to slow amyotrophic lateral sclerosis progression.},
}

@article {pmid41890591,
year = {2026},
author = {Gabbay, U},
title = {Axonal transport impairment as an upstream mechanism in amyotrophic lateral sclerosis pathogenesis.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1802313},
pmid = {41890591},
issn = {1662-4548},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive loss of upper and lower motor neurons. Despite marked genetic and pathological heterogeneity, a unifying pathogenic framework remains lacking. We propose that axonal transport impairment represents an early and convergent but genotype-modulated upstream vulnerability in ALS, contributing to distal synaptic failure, bioenergetic stress, protein aggregation, neuroinflammation, and neuronal death. Across many ALS models, including SOD1, TARDBP (TDP-43), FUS, and C9orf72, transport deficits are frequently detectable in presymptomatic stages, often preceding overt motor neuron loss or clinical manifestation, although temporal ordering varies by molecular subtype. Human data from induced pluripotent stem cell-derived motor neurons and neuroimaging in mutation carriers further support early transport dysfunction in both familial and sporadic ALS. We synthesize genetic, cellular, and systems-level evidence demonstrating that diverse ALS-associated mutations converge on intracellular trafficking machinery through distinct but interacting mechanisms, disrupting long-range cargo delivery and clearance in motor neurons. This framework provides a mechanistic basis for selective motor neuron vulnerability, the dying-back pattern of neuromuscular junction degeneration, and the emergence of downstream pathological hallmarks including mitochondrial dysfunction, excitotoxicity, aggregation, and inflammation. This model generates testable predictions regarding presymptomatic transport biomarkers and the timing of therapeutic intervention. We discuss implications for biomarker development and therapeutic strategy, proposing restoration of axonal transport as a central component of rational multimodal disease modification in ALS.},
}

@article {pmid41892827,
year = {2026},
author = {Pérez-Bonilla, M and Mora-Ortiz, M and Díaz-Borrego, P and Muñoz-Alcaraz, MN and Mayordomo-Riera, FJ and Girela-López, E},
title = {Biomechanical Voice Parameters as Potential Biomarkers for Phenotype Differentiation in Amyotrophic Lateral Sclerosis: A Cross-Sectional Study.},
journal = {Medical sciences (Basel, Switzerland)},
volume = {14},
number = {1},
pages = {},
doi = {10.3390/medsci14010112},
pmid = {41892827},
issn = {2076-3271},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Aged ; Biomechanical Phenomena ; Phenotype ; Biomarkers ; *Voice/physiology ; *Voice Disorders/physiopathology/diagnosis/etiology ; Adult ; Phonation/physiology ; },
abstract = {Background/Objectives: Amyotrophic lateral sclerosis (ALS) is a clinically heterogeneous neurodegenerative disease in which bulbar involvement frequently affects speech and voice production. Although acoustic voice analysis can detect phonatory alterations in ALS, its ability to differentiate clinical phenotypes remains limited. This study investigated whether biomechanical voice parameters provide complementary information for characterizing bulbar involvement across bulbar-onset ALS (ALS-B) and spinal-onset ALS (ALS-S) and explored their association with clinical and functional measures. Methods: This cross-sectional observational study included 50 patients with ALS (20 ALS-B, 30 ALS-S) and 50 controls with non-neurological voice disorders. Sustained vowel phonation was analyzed using acoustic measures and biomechanical voice parameters derived from a standardized model of vocal fold vibration. Perceptual voice severity was assessed using the GRBAS scale, while functional status was evaluated with the ALS Functional Rating Scale-Revised (ALSFRS-R) and the Barthel Index. Associations with clinical measures were explored in secondary analyses. Results: Compared with controls, ALS patients showed significant differences in acoustic measures and several biomechanical parameters related to glottal closure and vibratory stability. Biomechanical analysis revealed significant differences between ALS-B and ALS-S, particularly in parameters reflecting vibratory asymmetry, glottal tension and cycle-to-cycle instability. Unexpectedly, ALS-B showed greater perceptual voice severity and higher Barthel Index scores than ALS-S, while no differences were observed in global ALSFRS-R total scores. Conclusions: Biomechanical voice analysis appears to capture physiologically meaningful alterations in vocal fold function in ALS and provides complementary information for characterizing bulbar motor involvement across clinical phenotypes, particularly ALS-B disease. When combined with acoustic and clinical assessments, this approach may enhance the evaluation of bulbar involvement and functional status in ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/diagnosis
Male
Female
Cross-Sectional Studies
Middle Aged
Aged
Biomechanical Phenomena
Phenotype
Biomarkers
*Voice/physiology
*Voice Disorders/physiopathology/diagnosis/etiology
Adult
Phonation/physiology

@article {pmid41893050,
year = {2026},
author = {Duranti, E and Villa, C},
title = {Misfolded Proteins and Cognitive Decline: Mechanistic Insights into Neurodegenerative Disorders.},
journal = {Neurology international},
volume = {18},
number = {3},
pages = {},
doi = {10.3390/neurolint18030048},
pmid = {41893050},
issn = {2035-8385},
abstract = {Cognitive decline represents one of the most common clinical manifestations of neurodegenerative diseases (NDs), substantially affecting the quality of life of both patients and their families. Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis are major NDs characterized by a progressive degeneration of the central nervous system, with functional impairments extending beyond motor symptoms to multiple cognitive domains, including memory, attention, language, and executive functions. Increasing evidence highlights misfolded protein accumulation as a key driver of neuronal dysfunction and cognitive deterioration. This narrative review examines the major cognitive deficits associated with these disorders, focusing on the underlying molecular mechanisms, particularly protein aggregation, as well as clinical manifestations and their effects on daily life. Furthermore, current diagnostic tools and emerging therapeutic options for mitigating cognitive decline will be further discussed.},
}

@article {pmid41894152,
year = {2026},
author = {Kutahyalioglu, NS and Onan, N},
title = {The Relationship Between Academic Literacy and Critical Thinking Disposition on Nursing Students.},
journal = {The Journal of nursing education},
volume = {},
number = {},
pages = {1-9},
doi = {10.3928/01484834-20260317-02},
pmid = {41894152},
issn = {1938-2421},
abstract = {BACKGROUND: Evidence-based nursing practice requires strong academic literacy (AL) and critical thinking (CT) skills, yet the link between these two competencies has not been adequately explored. This study aimed to assess nursing students' AL and CT levels and to examine the relationship between them.

METHOD: A descriptive and correlational design was used with 120 nursing students. Data was collected using a Socio-demographic Information Form, the Academic Literacy Scale (ALS), and the Critical Thinking Disposition Scale (CTDS), and analyzed through descriptive statistics and correlation analyses.

RESULTS: Students' mean ALS score was 86.54 (SD = 9.54), and the mean CTDS score was 3.85 (SD = 0.56). AL was strongly correlated with CT disposition (r = .641, p < .01). Regression analysis indicated that CT disposition explained 41% of the variance in AL (R[2] = .410).

CONCLUSION: Critical thinking significantly predicts academic literacy, underscoring the need for educational strategies that foster both skills.},
}

@article {pmid41894255,
year = {2026},
author = {Hirata, Y and Kobatake, Y and Koyama, H and Furuta, K and Takemori, H and Kamatari, YO},
title = {Destabilized Soluble SOD1 Species as Potential Determinants of Disease Severity in Familial Amyotrophic Lateral Sclerosis.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.5c00668},
pmid = {41894255},
issn = {1948-7193},
abstract = {Mutations in the Cu/Zn superoxide dismutase (SOD1) gene are linked to familial amyotrophic lateral sclerosis (ALS), yet the identity of the toxic molecular species remains unclear. We investigated the relationship between protein misfolding and pathogenicity by expressing GFP-tagged wild-type and mutant SOD1 (A4V, H46R, G93A) in mouse hippocampal HT22 cells. Western blotting under nonreducing conditions suggested that A4V, associated with rapid disease progression, was largely depleted of properly folded soluble SOD1 and instead produced highly destabilized soluble species. In contrast, H46R, associated with a milder phenotype, showed a moderate reduction in properly folded soluble SOD1 and generated partially folded/native-like conformers. G93A exhibited biochemical characteristics intermediate between those of A4V and H46R. A4V also showed a pronounced loss of GFP fluorescence, indicating severe structural destabilization; the extent of fluorescence loss in A4V, G93A, and H46R broadly correlated with clinical severity. Neither CuATSM nor ebselen─targeting metal binding and disulfide formation, respectively─rescued fluorescence, suggesting broader defects in SOD1 maturation. Nevertheless, both compounds inhibited ferroptosis, a nonapoptotic form of cell death characterized by iron-dependent lipid peroxidation, in HT22 cells, indicating alternative neuroprotective mechanisms. These findings identify destabilized soluble SOD1 species as a key toxic entity in ALS and highlight the utility of GFP-tagged constructs for evaluating folding status and screening therapeutic candidates.},
}

@article {pmid41895196,
year = {2026},
author = {Schmidlin, D and Thaysen, EM and Platikanov, S and Xu, J and Chesa, MJ and Tauler, R and Vázquez-Suñé, E and Teixidó, M},
title = {Impact of the superblock model on key components of the urban water cycle: Trace metals and dissolved organic matter dynamics across the built environment.},
journal = {Journal of hazardous materials},
volume = {508},
number = {},
pages = {141867},
doi = {10.1016/j.jhazmat.2026.141867},
pmid = {41895196},
issn = {1873-3336},
abstract = {Climate change, growing urban pollution, and increasing water scarcity are forcing cities to adopt strategies that enhance resilience to both climatic and anthropogenic pressures. The Barcelona Superblock model is a novel urban planning strategy that highly restricts vehicle traffic, converts streets into pedestrian-priority corridors, and promotes green spaces. Within this framework, green infrastructures, also called sustainable urban drainage systems (SUDS), are implemented as local, site-specific measures to capture (i.e., flood control), treat, and infiltrate treated stormwater (i.e., aquifer recharge). To evaluate the Superblock model impact on urban water quality, we conducted seven sampling campaigns across three Barcelona districts, targeting rainfall, stormwater "first-flush" from roads and pedestrianized streets, as well as SUDS influent and effluent within and in the vicinity to Superblocks, with a focus on dissolved trace metals and dissolved organic matter (DOM). Results showed that Superblocks reduced pollutant loads and mitigated ecotoxicological risks. Trace metal and DOM concentrations followed the trend: Rain < SUDS effluent < Pedestrian Street runoff < Road runoff, highlighting traffic-related impacts and SUDS treatment capacity (23-70% in best case scenario). Risk assessment indicated episodic ecotoxicological risk in stormwater, especially in road runoff due to elevated concentrations of Cu and Zn, while SUDS consistently remained below risk thresholds. SUDS also transform DOM into more stable, humic-like forms. Trace metals and DOM emerged as biogeochemical proxies for stormwater quality, enabling more effective and sustainable urban water management. These findings support the integration of Superblock-like strategies into urban planning to control and reduce contaminant urban discharges.},
}

@article {pmid41881396,
year = {2026},
author = {Zhou, R and Lin, X and Lin, J and Liao, Z and Ni, H and Lin, X and He, Q and Ning, W},
title = {Cellular senescence in neurodegenerative diseases: a bibliometric analysis and mechanistic synthesis linking translational pathways to therapeutic implications.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {103110},
doi = {10.1016/j.arr.2026.103110},
pmid = {41881396},
issn = {1872-9649},
abstract = {BACKGROUND: Cellular senescence is now recognized as a pivotal driver of neurodegenerative diseases (NDs). Despite advances in understanding senescence mechanisms, such as the p16[INK4A]/p53-p21[CIP1] pathways and the senescence-associated secretory phenotype (SASP), along with the development of therapeutic strategies like senotherapeutics, the research landscape remains fragmented.

OBJECTIVE: Systematically addresses the fragmentation characterizing current research on cellular senescence in NDs, integrating bibliometric analysis with a mechanistic synthesis of translational relevance and therapeutic implications.

METHODS: A comprehensive bibliometric analysis was performed. Literature retrieval on cellular senescence and four NDs (AD, PD, ALS, HD) was executed in Web of Science Core Collection (WoSCC) on April 30, 2025. CiteSpace V.6.4 R1 and VOSviewer 1.6.20 reconstructed networks for temporal trends, burst detection, and co-occurrence visualization. In addition to bibliometric mapping, we provide a mechanistic synthesis of emerging translational pathways.

RESULTS: Analysis included 269 relevant articles (2002-April 2025). Annual publications and cumulative citations increased markedly since 2018. The US led in output/influence, followed by China and Italy. Key collaborative institutions included Chinese Academy of Sciences, University of Texas System, and University of California System. Leading authors were Lorenz Studer, Judith Campisi, and Julie K. Andersen. Tyler J. Bussian and Peisu Zhang were highly co-cited. Top-cited journals were Nature, PNAS, and PLOS One. Research hotspots focus on abnormal tau protein in senescence and senescent microglia mediating chronic neuroinflammation, development of multi-target senomorphics targeting SASP is emerging as a promising therapeutic direction.

CONCLUSION: Cellular senescence research in NDs (notably AD, PD) shows broad promise from mechanisms to therapy. Future priorities include elucidating tau dysregulation's core role in senescence, developing specific biomarkers and targeted interventions. Senescent microglia are new therapeutic targets. Multi-target senomorphics modulating SASP offer new mechanisms for delaying ND progression. Understanding senescence mechanisms and precise interventions may provide novel ND therapies.},
}

@article {pmid41882018,
year = {2026},
author = {Lin, J and Agote-Aran, A and Liao, Y and Cloarec, M and Andronov, L and Schoch, RL and Ronchi, P and Cochard, V and Zhu, R and Grandgirard, E and Liu, X and Lemée, MV and Kleiss, C and Golzio, C and Ruff, M and Chevreux, G and Schwab, Y and Klaholz, BP and Sumara, I},
title = {RanBP2-dependent annulate lamellae drive nuclear pore assembly and nuclear expansion.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-71101-y},
pmid = {41882018},
issn = {2041-1723},
support = {ANR-22-CE13-0025//Agence Nationale de la Recherche (French National Research Agency)/ ; },
abstract = {Nuclear pore complexes (NPCs) enable nucleocytoplasmic transport. While NPCs primarily localize to the nuclear envelope (NE), they also appear in cytoplasmic endoplasmic reticulum (ER) membranes called annulate lamellae (AL). Though discovered in the mid-20th century, AL's function and biogenesis remain unclear. Previously considered exclusive to embryonic and malignant cells, we find AL in somatic mammalian cells. Under normal conditions, AL store pre-assembled AL-NPCs that integrate into the NE, producing approximately one-third of newly formed nuclear pores and supporting nuclear expansion during G1. Upon pathological stimuli, AL transfer to the NE is impaired, leading to their cytoplasmic accumulation. RanBP2 (Nup358) is essential for AL biogenesis, with its phenylalanine-glycine repeats promoting AL-NPC scaffold oligomerization. ER-associated Climp63 (CKAP4) directs AL-NPCs to ER sheets and the NE. This AL-driven nuclear pore formation is complementary to the canonical routes, constituting a distinct NPC assembly pathway. Our work uncovers the biogenesis mechanism of AL and the nuclear function of this key cellular organelle.},
}

@article {pmid41883703,
year = {2026},
author = {Nassan, M and Ayala, I and Sloan, J and Bonfitto, A and Stark, B and Song, S and Naymik, M and Geula, C and Gefen, T and Barbieri, E and Piras, I and Mesulam, MM and Huentelman, M},
title = {The Genetics of TDP-43 Type C Neurodegeneration: A Whole-Genome Sequencing Study and Literature Review.},
journal = {Neurology. Genetics},
volume = {12},
number = {2},
pages = {e200369},
pmid = {41883703},
issn = {2376-7839},
abstract = {BACKGROUND AND OBJECTIVES: Frontotemporal lobar degeneration TDP43 type C (TDP-C) is a rare and unique neurodegenerative disease that attacks the anterior temporal lobe. Recently, it was shown that Annexin-A11 and TDP-43 coaggregate specifically in TDP-C. Current literature on the genetic associations with TDP-C, reviewed here, lacks a discernible corpus of robust or replicated findings. In this study, using blood tissue, we completed whole genome sequencing to investigate ANXA11 and TARDBP genetic variants for their association with TDP-C. Then, we completed genome-wide hypothesis-free analyses using artificial intelligence to identify rare pathogenic variants associated with TDP-C.

METHODS: (1) We tested common variants in ANXA11 and TARDBP for their association with 37 TDP-C cases vs 290 controls. We attempted to replicate our findings in a different cohort of 467 TDP-C cases vs 3,153 controls and contrasted them with cohorts of TDP-A and TDP-B. (2) AI-guided analyses were completed to prioritize pathogenic rare variants associated with TDP-C in our cohort.

RESULTS: (1) Four common variants in ANXA11 (rs113772135, rs2789686, rs1079242, rs61860017) were significantly associated with TDP-C in the discovery cohort and replicated in the other cohort of TDP-C but not in TDP-A or TDP-B, providing evidence for ANXA11 specific association with TDP-C. Rs1079242-A showed the most robust replication (p = 7.35 × 10[-05]) and correlates with higher ANXA11 level in CSF (p = 4 × 10[-11]). No associations were found between TARDBP and TDP-C (p > 0.05). Using AI-guided rare variant analyses, we identified a pathogenic variant in FIG4, a gene that has been implicated in amyotrophic lateral sclerosis (ALS). Because of the observed potential genetic overlap between some ALS genes and TDP-C, we leveraged mendelian randomization and found that ALS genetic load is associated with TDP-C risk (p = 0.0046).

DISCUSSION: This study provides replicated evidence for the association between common variants in ANXA11 with TDP-C. Knowing rs1079242-A affects ANXA11 level in CSF, future studies may aim to investigate ANXA11 level as potential CSF biomarker for TDP-C. Moreover, FIG4 and ANXA11 have been implicated in the inositol pathway. Our results provide novel insights into the genetic risk of TDP-C and offer new clues about its underpinning mechanisms.},
}

@article {pmid41884057,
year = {2026},
author = {Tannoury, C and Denwood, H and Khan, RR and Kyada, RJ and Zhou, OT and Atassi, S and Saade, A and Chahine, MN and Tannoury, T},
title = {Is the antepsoas oblique lumbosacral interbody fusion safe in patients with aortoiliac calcification?.},
journal = {North American Spine Society journal},
volume = {25},
number = {},
pages = {100867},
pmid = {41884057},
issn = {2666-5484},
abstract = {BACKGROUND: The anterior approaches to lumbar arthrodesis, including direct anterior (ALIF) and antepsoas (ATP)/oblique (OLIF) fusions, require careful manipulation of the abdominal prevertebral vessels for safe and adequate spinal access. Therefore, surgeons who perform anterior lumbar fusions in patients with aortoiliac calcifications are often cautious due to concerns for perioperative vascular complications, as well as the associated risks of concomitant medical comorbidities. This study sought to compare the incidence of perioperative vascular and medical complications in patients with and without abdominal aortoiliac calcification (AAC) undergoing the minimally invasive antepsoas (MIS-ATP) lumbosacral fusion.

METHODS: This was a retrospective matched cohort study including 482 adult patients undergoing MIS-ATP lumbosacral fusions at a single institution between 2014 and 2020 (227 with AAC and 255 without AAC), matched by sex and American Society of Anesthesiologists (ASA) scores. Through preoperative standing lateral lumbar radiographs, using Kaupilla et al.'s AAC grading system, we graded anterior and posterior aortic wall calcification from L1 to L4. Electronic medical records were reviewed to identify and collect the perioperative complications.

RESULTS: While there was no occurrence of intraoperative vascular injuries in either group, patients with AAC were more likely to develop medical complication (34.8% vs. 13.3%, p < .001), with anemia (18.9% vs. 9.2%), ileus (16.3% vs. 2.7%) and acute kidney injury (6.6% vs. 5.5%) being the most common. Overall, individuals with AAC had 2.62 times increased odds of developing a postoperative medical complication. Moreover, moderate AAC was found to be a significant risk factor (OR = 3.48).

CONCLUSIONS: Presence of AAC in patients undergoing MIS-ATP fusion was not associated with increased risk of direct surgical or exposure related vascular complications. However, patients with AAC were significantly more likely to experience medical complications following MIS-ATP fusion.},
}

@article {pmid41884172,
year = {2026},
author = {Seki, S and Enomoto, A and Tanaka, S},
title = {The mesencephalic trigeminal neuron: electrophysiological insights into function and dysfunction.},
journal = {Frontiers in cellular neuroscience},
volume = {20},
number = {},
pages = {1752701},
pmid = {41884172},
issn = {1662-5102},
abstract = {Mesencephalic trigeminal neurons (MTNs) are the sole primary afferent neurons with cell bodies located within the central nervous system. MTNs convey proprioceptive inputs from masticatory muscles and periodontal ligaments, thereby contributing to the precise regulation of jaw-oral motor functions. Through ionic mechanisms such as currents generated by the voltage-dependent sodium (Nav) channel isoform Nav1.6, hyperpolarization-activated currents, and persistent inward currents, MTNs generate sustained and burst firing that regulate masticatory rhythm and jaw-jerk reflex timing. Their activity is further modulated by neurotransmitters, including serotonin and norepinephrine, which provide flexibility in sensorimotor integration. Pathological conditions such as chronic stress and sodium channel dysfunction induce MTN hyperexcitability or irregular firing, contributing to bruxism, temporomandibular disorders, and feeding impairment in amyotrophic lateral sclerosis models. In addition, aging and tooth loss lead to Piezo2 downregulation and neuronal death, potentially resulting in masticatory dysfunction and cognitive decline. Recent findings suggest that interventions targeting vesicular glutamate transporter 1 projections, melanocortin 4 receptor signaling, and nitric oxide pathways represent novel therapeutic approaches. Taken together, MTNs have emerged as promising targets for treating conditions ranging from masticatory motor disorders to neurodegenerative diseases.},
}

@article {pmid41884597,
year = {2026},
author = {Milioto, C and Carcolé, M and Zanovello, M and Ahmed, M and Nirujogi, RS and Biggs, D and Roberts, MJ and Schweers, K and Cammack, AJ and Marchi, PM and Katona, E and Glaria, I and Santos, A and Devoy, A and Fratta, P and Alessi, DR and Davies, B and Greensmith, L and Fisher, EMC and Isaacs, AM},
title = {C9orf72 poly(glycine-alanine) knock-in mice exhibit mild rotarod and proteomic changes consistent with amyotrophic lateral sclerosis/frontotemporal dementia.},
journal = {Brain communications},
volume = {8},
number = {2},
pages = {fcag087},
pmid = {41884597},
issn = {2632-1297},
abstract = {A GGGGCC repeat expansion in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The repeat expansion is translated into five different dipeptide repeat proteins: poly(glycine-alanine) (polyGA), poly(glycine-proline) (polyGP), poly(glycine-arginine) (polyGR), poly(alanine-proline) (polyAP) and poly(proline-arginine) (polyPR). To investigate the effect of polyGA, which is the most abundant dipeptide repeat protein in patient brains, we used clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR associated nuclease 9 (Cas9) to insert 400 codon-optimized polyGA repeats immediately downstream of the mouse C9orf72 start codon. This generated (GA)400 knock-in mice driven by the endogenous mouse C9orf72 promoter, coupled with heterozygous C9orf72 reduction. PolyGA remains soluble up to 18 months of age and (GA)400 mice develop subtle dysfunction characterized by impaired rotarod performance, without overt neuropathological alterations. Quantitative proteomics revealed polyGA expression caused protein alterations in the spinal cord, including changes in previously identified polyGA interactors. Our findings show that (GA)400 mice are a complementary in vivo model to better understand C9orf72 ALS/FTD pathology and determine the specific role of individual DPRs in disease.},
}

@article {pmid41884646,
year = {2026},
author = {Sudwarts, A and Thinakaran, G},
title = {Female-specific Cx3cr1-driven regulation of ALS and Alzheimer's risk genes in tauopathy.},
journal = {Molecular neurodegeneration advances},
volume = {2},
number = {1},
pages = {16},
pmid = {41884646},
issn = {3059-4944},
abstract = {UNLABELLED: By introducing haploinsufficiency of Cx3cr1 in the P301S (PS19) transgenic model of tau pathology, we report remarkable transcriptional changes, including crucial amyotrophic lateral sclerosis and Alzheimer's disease risk genes, several of which showed co-expression, suggesting gene-gene interactions among these genetic risk factors.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s44477-026-00022-3.},
}

@article {pmid41884800,
year = {2026},
author = {Nette, S and Purvis, JK and Helpard, H},
title = {Identifying Student Learning Challenges and Potential Solutions in Nursing Education Delivery in Rural Nova Scotia Using Photovoice.},
journal = {SAGE open nursing},
volume = {12},
number = {},
pages = {23779608251413674},
pmid = {41884800},
issn = {2377-9608},
abstract = {INTRODUCTION: Rural nursing programs encounter obstacles in providing nursing education opportunities relevant to the escalating needs of rural healthcare. Rural nursing programs often experience limited clinical placements, a stressed and burned-out rural nursing workforce, and difficulty finding nursing preceptors. Moreover, students studying in rural nursing programs experience increased travel, financial and social burden, and have less access to resources and support from their university. There is limited research giving voice to rural nursing students' experience and their suggestions for solutions.

OBJECTIVE: The purpose of this study was to understand the learning challenges of and potential solutions for baccalaureate nursing students attending a rural university.

METHODS: This is a descriptive qualitative study using photovoice methodology. Participants captured two pictures of things in their school surroundings or personal life that created learning challenges in rural nursing education, and two pictures of potential solutions to these challenges. Participants titled each picture and, using guided questions provided by the researcher, wrote a short reflection of what the photos represented.

RESULTS: Guided by empowerment education for critical consciousness and using Braun and Clarke's thematic analysis and Oliffe et al.'s layered photograph analysis, two overarching themes emerged: access to resources and clinical learning. Findings highlight financial, academic, and accessibility barriers in rural nursing programs as well as participant-determined solutions that could enhance learning experiences, student well-being, and retention in the rural healthcare workforce.

CONCLUSIONS: This study identified targeted resources for nursing students attending a rural nursing baccalaureate program to support their learning, wellbeing, and growth into graduate nurses. This study also identified areas for future research to explore nursing student experiences across rural and urban institutions and develop effective learning support strategies for rural nursing education.},
}

@article {pmid41885096,
year = {2026},
author = {Wolfensberger, A and Faes Hesse, M and Sax, H and Clack, L},
title = {From plan to practice: a structured report on implementation strategies for preventing non-ventilator hospital-acquired pneumonia (nvHAP).},
journal = {Infection control and hospital epidemiology},
volume = {},
number = {},
pages = {1-9},
doi = {10.1017/ice.2026.10422},
pmid = {41885096},
issn = {1559-6834},
abstract = {BACKGROUND: There is increasing evidence on the effectiveness of prevention bundles against non-ventilator hospital-acquired pneumonia (nvHAP), but detailed reports on their implementation are lacking. This study aims to describe and structure the implementation activities undertaken in a single-center multimodal intervention that achieved a 31% reduction in nvHAP incidence.

DESIGN: Longitudinal descriptive qualitative study.

SETTING: Nine medical and surgical departments of a Swiss university hospital.

PARTICIPANTS: Healthcare professionals and implementation teams in study departments.

METHODS: We collected longitudinal data on implementation activities using (1) implementation activity logs, (2) drop-in interviews and observations, (3) "action plan meetings," (4) focus groups, and (5) unstructured recall sessions among the project team. Data were deductively coded using the "Expert Recommendations for Implementing Change" taxonomy, specified using Proctor et al.'s "Recommendations for specifying and reporting implementation strategies" and mapped to the "Exploration, Preparation, Implementation, Sustainment" framework phases.

RESULTS: A total of 174 activities were undertaken. Activities varied by implementation phase, most frequently involving "evaluative and iterative strategies," "develop stakeholder interrelationship strategies" and "training and education of stakeholders" during Exploration, Preparation, and Implementation, respectively. During Implementation, 54% of activities were initiated by department nurses, and 27% were initiated by the institutional implementation team. Activities included interdisciplinary kick-off events, education in various formats, posters, informational stickers for patients, provision of new equipment (e.g., toothbrushes), and electronic medical records order sets.

CONCLUSIONS: This report offers valuable insights for future implementation efforts by providing a structured overview of the concrete implementation activities performed in a successful one-hospital multimodal nvHAP prevention project.},
}

@article {pmid41885541,
year = {2026},
author = {Chen, RF and Liu, KF and Lee, CC and Li, YT and Chen, WY and Kuo, YR},
title = {Transcriptomic Analysis of Adipose-Derived Stem Cell Therapy Modulating B Cell Immune Tolerance in Vascularized Composite Allotransplantation.},
journal = {Plastic and reconstructive surgery},
volume = {},
number = {},
pages = {},
doi = {10.1097/PRS.0000000000013074},
pmid = {41885541},
issn = {1529-4242},
abstract = {BACKGROUND: Adipose-derived stem cells (ADSCs) have been shown to prolong vascularized composite allotransplantation (VCA) survival in rodent hindlimb transplantation. However, the mechanisms by which ADSCs modulate B cell responses and induce immune tolerance remain unclear. This study used next-generation sequencing (NGS) to investigate B cell gene expression after ADSC treatment.

METHODS: A rodent orthotopic hind-limb transplantation model was established using Brown-Norway to Lewis rats. The tolerance treatment group received a combination of ADSCs, short-term cyclosporine A (CsA) and anti-lymphocyte serum (ALS), while the control rejection group received no treatment. B cells were isolated from the spleens of rejection control group at 10-14 days post-transplantation when rejection was diagnosed, or tolerance group at least ≥100 days post-transplantation without rejection. RNA sequencing (RNA-Seq) was conducted to assess transcriptomic differences. Differentially expressed genes (DEGs) were analyzed using the EBSeq bioinformatics tool and pathway enrichment analyses, with validation by qPCR.

RESULTS: RNA-Seq identified 94 DEGs (out of 13,284 mRNAs) between the tolerance and rejection groups. Gene ontology and KEGG pathway analyses revealed significant enrichment in pathways associated with cytokine secretion, B cell receptor signaling, and humoral immunity. The tolerance group exhibited upregulation of key chemokines (e.g., Cxcl1, Cxcl2, Ccl4) and downregulation of pro-inflammatory genes (e.g., Tlr3, Siglec5, C3). qPCR validation confirmed the RNA-Seq findings. These results suggest that ADSCs modulate B cell-mediated immune responses and promote a shift toward an anti-inflammatory, tolerogenic profile.

CONCLUSIONS: ADSC-based therapy combined with short-term immunosuppression promotes immune tolerance in VCA by modulating B cell-related gene expression. These findings suggest that targeting B cell-mediated pathways may provide a novel approach may offer a novel therapeutic strategy for clinical application in VCA.},
}

@article {pmid41876403,
year = {2026},
author = {Yan, K and Jiang, Y and Yong, Y and Zhang, T and Zhang, N and Zeng, Q and Gong, X and Meng, L and Bi, F and Liu, Y},
title = {ALDOA Promotes Glycolysis and NLRP3/GSDMD Pyroptosis to Accelerate ALS Progression.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.70372},
pmid = {41876403},
issn = {2328-9503},
support = {81760238//National Natural Science Foundation of China/ ; 82171433//National Natural Science Foundation of China/ ; 2022JJ30918//Natural Science Foundation of Hunan Province/ ; 2023JJ30927//Natural Science Foundation of Hunan Province/ ; TSYC202401B119//Xinjiang Uygur Autonomous Region Health Commission "Tianshan Talent" High-Level Medical and Health Personnel Project/ ; 2025D01E38//Natural Science Foundation of Xinjiang Uygur Autonomous Region/ ; },
abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron degeneration. Glycolytic dysregulation is implicated in disease progression, yet the underlying mechanisms remain unclear. This study investigates how Aldolase A (ALDOA) drives ALS progression through glycolysis-mediated motor neuron pyroptosis.

METHODS: In vivo, tamoxifen-induced TDP-43 cKO mice were assessed for motor function (rotarod/suspension tests), motor cortex L-lactic acid, and ALDOA/NLRP3/GSDMD expression. The ALDOA inhibitor Aldometanib was administered. In vitro, TDP-43 KO NSC34 cells were used to measure viability, glucose uptake, and L-lactic acid.

RESULTS: ALS model mice exhibited significant motor deficits, progressive weight loss, and reduced survival. Their motor cortex showed elevated ALDOA expression, L-lactic acid accumulation, and NLRP3/GSDMD inflammasome activation. Aldometanib treatment suppressed glycolysis, prolonged survival, and slowed disease progression by inhibiting NLRP3/GSDMD-mediated pyroptosis. In vitro, TDP-43-deficient NSC34 cells displayed increased ALDOA levels, enhanced glycolytic flux, NLRP3/GSDMD pathway activation, and impaired proliferation.

CONCLUSION: We show that ALDOA-mediated glycolytic dysregulation activates the NLRP3/GSDMD inflammasome, leading to pyroptosis in motor neurons. Pharmacological inhibition of ALDOA alleviates glycolytic dysregulation and extends survival, identifying ALDOA as a potential therapeutic target.},
}

@article {pmid41877227,
year = {2026},
author = {Estiar, MA and Yu, E and Varghaei, P and Ross, JP and Ashtiani, S and Bayne, AN and Coarelli, G and Timmann, D and Klockgether, T and Beijer, D and Mengel, D and Coutelier, M and , and Dion, PA and Suchowersky, O and Ewenczyk, C and Goizet, C and Stevanin, G and Van Damme, P and Al-Chalabi, A and Zuchner, S and Synofzik, M and Veldink, JH and Trempe, JF and Durr, A and Rouleau, GA and Gan-Or, Z},
title = {Digenic inheritance of mutations in SPG7 and AFG3L2 causes motor neuron and cerebellar disorders.},
journal = {BMC medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12916-026-04805-z},
pmid = {41877227},
issn = {1741-7015},
abstract = {BACKGROUND: Biallelic SPG7 mutations cause one of the most common forms of hereditary spastic paraplegia (HSP). Several reports have suggested that heterozygous SPG7 variants may also play a role in HSP, but also in amyotrophic lateral sclerosis (ALS). However, it remains controversial whether heterozygous SPG7 mutations are pathogenic on their own, or if other mechanisms are at play. We recently provided evidence for non-Mendelian inheritance in spastic paraplegia 7 (SPG7), as heterozygous carriers of SPG7 mutations often also carried mutations in other disease-related genes, including AFG3L2, more frequently than expected by chance. Given that SPG7 and AFG3L2 encode interacting subunits of the mitochondrial m-AAA protease complex, we hypothesized that combined heterozygous mutations in these genes may act synergistically to disrupt mitochondrial function and contribute to disease. In this study, we aimed to examine whether digenic heterozygous mutations in SPG7 and AFG3L2 can lead to a spectrum of neurodegenerative disorders.

METHODS: We first analyzed genome and exome sequencing data of 6644 unrelated individuals including 4817 motor neuron disorder (MND) and ataxia patients and 1827 controls. We next analyzed an additional 18,748 exome data from rare disease cohorts to further examine the occurrence of variants in SPG7 and AFG3L2.

RESULTS: Among the first 4817 MND and ataxia patients, we identified a total of 6 patients, 4 of whom were unrelated, who carried potentially pathogenic variants in both SPG7 and AFG3L2, in contrast to none in 1827 unrelated controls. Further analysis of the 18,748 additional patients with rare disease, as well as a comprehensive literature review, identified 6 more patients, 5 of whom were unrelated, who had digenic mutations in SPG7 and AFG3L2. In the two families we identified, digenic mutations in SPG7 and AFG3L2 perfectly segregated with the disease. The 12 patients reported here exhibited predominant signs of motor neuron and cerebellar involvement.

CONCLUSIONS: Our findings demonstrate that digenic inheritance of concurrent heterozygous mutations in SPG7 and AFG3L2 may cause motor neuron and cerebellar disorders. Screening of the entire SPG7 and AFG3L2 genes in genetically undiagnosed cases of MND and spastic ataxia may help to increase the diagnostic yield.},
}

@article {pmid41877246,
year = {2026},
author = {Shen, R and Sung, K and Ding, J and Wu, C},
title = {Axonopathy: mechanisms and potential therapeutic targets for neurodegenerative diseases.},
journal = {Translational neurodegeneration},
volume = {15},
number = {1},
pages = {},
pmid = {41877246},
issn = {2047-9158},
mesh = {Humans ; *Neurodegenerative Diseases/pathology/therapy ; *Axons/pathology ; Animals ; },
abstract = {Axons are unique structural and functional features of nerve cells, which play a critical role in regulating neuronal homeostasis. Dysfunction and degeneration of axons (axonopathy) has been established as an early and prominent contributing mechanism to the pathogenesis of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. In this review, we briefly summarize the structure and function of axons, and highlight recent advances in the understanding of the role of axons in health and disease. We argue that axons are a potential target for developing novel therapies for neurodegenerative diseases.},
}

Humans
*Neurodegenerative Diseases/pathology/therapy
*Axons/pathology
Animals

@article {pmid41879495,
year = {2026},
author = {Singh, K and Sethi, P and Jain, D and Gupta, JK and Alsaidan, OA and Alzarea, SI and Kumar, A and Tabish, M and Sharma, MC},
title = {Emerging Roles of Small-molecule Derivatives in Modulating Neurodegenerative Pathways: From Molecular Targets to Therapeutic Applications.},
journal = {Mini reviews in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0113895575429412260112060311},
pmid = {41879495},
issn = {1875-5607},
abstract = {Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease involve progressive neuronal dysfunction driven by mechanisms including protein aggregation, oxidative stress, mitochondrial impairment, and neuroinflammation. Current treatments are largely symptomatic, with limited disease-modifying options. Advances in medicinal chemistry have led to the development of small-molecule derivatives targeting specific pathological pathways, offering new therapeutic opportunities. This review summarizes recent progress in designing and optimizing such molecules to modulate amyloid-β metabolism, tau acetylation, α-synuclein aggregation, RNA-binding protein interactions, and NLRP3 inflammasome activation. Compounds acting on key signaling cascades, including PI3K/Akt, MAPK/ERK, Nrf2/ARE, and Wnt/β-catenin, are discussed, alongside drug repurposing strategies and preclinical-to-clinical translation. Special focus is given to microglial modulation, challenges in crossing the blood-brain barrier, and integration of precision medicine, metabolomics, and artificial intelligence into drug discovery. The review also highlights novel therapeutic concepts such as multi- target ligands, metal-chelation approaches, and modulation of neuroinflammatory pathways. Despite promising leads, significant challenges remain in optimizing pharmacokinetics, target selectivity, and delivery. Future directions include the identification of robust biomarkers, advanced imaging techniques, and computational tools to accelerate candidate validation. Collectively, smallmolecule therapeutics hold considerable promise in addressing unmet needs in neurodegenerative disease management, but their successful translation will require multidisciplinary approaches bridging molecular insights and clinical application.},
}

@article {pmid41880105,
year = {2026},
author = {Ng, CA and Sousa, M and Patterson, T and Mulhern, B and Luckett, T},
title = {A qualitative study of cancer clinical trial network consumers' acceptability of the modular approach to patient-reported outcome measurement: how much of it is "common sense"?.},
journal = {Journal of patient-reported outcomes},
volume = {},
number = {},
pages = {},
doi = {10.1186/s41687-026-01045-w},
pmid = {41880105},
issn = {2509-8020},
abstract = {BACKGROUND: There is growing interest in customising patient-reported outcome measures (PROMs). This involves selecting specific domains (i.e., subscales) that focus on key health-related quality of life (HRQoL) issues most relevant to a particular study's context, referred to as the modular approach. Despite available recommendations from international stakeholders and PROM developers, the modular approach has not been widely adopted in cancer clinical trials. This qualitative study explored the acceptability of the modular approach to administering PROMs from the perspectives of cancer consumers.

METHODS: Consumers (patients, family members and/or caregivers) who have experience with cancer were recruited through cancer clinical trial networks in Australian and New Zealand. Data were collected through online focus groups. Interview probes and analysis were guided by Sekhon et al.'s Theoretical Framework of Acceptability.

RESULTS: Ten consumers, all with prior experience in clinical trial design, participated across four focus groups. The acceptability of the modular approach was discussed in reference to four themes: (1) minimising respondent burden is not simply about shortening PROMs; (2) competing priorities of reducing burden, preserving PROM measurement properties and assessing breadth versus depth of issues; (3) new strategies are needed to improve PROM relevance; and (4) who should select the domains, and how? Acceptable features of the modular approach included its potential to increase the relevance of questions, minimise duplication, and allow for more in-depth assessment of priority HRQoL issues. Participants also believed that involving consumer representatives in domain selection could alleviate the burden on researchers during trial design and were supportive of giving individual clinical trial patients the option to self-select domains that are personally meaningful.

CONCLUSIONS: Consumers were generally supportive of using the modular approach in administering PROMs in clinical trials, while also identifying ways to strengthen its acceptability. These included the need for clearer consensus and guidance on what constitutes a well-justified selection of domains and further personalisation of PROM domains (e.g., through branching questions). These insights can help inform regulatory agencies and other stakeholders about consumer needs and highlight the support needed if there is to be a paradigm shift in trial design towards tailored PROM administration.},
}

@article {pmid41871620,
year = {2026},
author = {Silva, DJD and Silveira, SCD and Souza, LC and Cruzeiro, MM and Vale, TC},
title = {Clinical and Sociodemographic Profile of Familial Amyotrophic Lateral Sclerosis Type 8 Compared to the Sporadic Form.},
journal = {Arquivos de neuro-psiquiatria},
volume = {84},
number = {3},
pages = {1-8},
doi = {10.1055/s-0046-1817037},
pmid = {41871620},
issn = {1678-4227},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/diagnosis/genetics/physiopathology/classification ; Female ; Male ; Middle Aged ; Adult ; Brazil/epidemiology ; Aged ; Age of Onset ; Socioeconomic Factors ; Retrospective Studies ; Sociodemographic Factors ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a rare degenerative disease of motor neurons, predominantly sporadic, with approximately 10% of the cases showing familial inheritance.To characterize the clinical and sociodemographic profile of patients with familial ALS type 8 (fALS8) and compare it with sporadic ALS (sALS).We reviewed the medical records (1997-2022) from a specialized Brazilian center. Patients with a confirmed diagnosis of ALSs were included, and sociodemographic and clinical data were collected.The sample was composed of 89 ALS patients, with a slight female predominance (53%) and a high frequency of fALS8 cases (45%). The fALS8 patients were diagnosed at a younger age, at approximately 50 years, compared to 53 years among the sALS patients (p = 0.043). Lower limb onset predominated in the fALS8 group (87%), while the sALS group showed more heterogeneous presentations, including bulbar onset (14%). The time until the diagnosis was significantly longer in the fALS8 group compared to the sALS group, both from symptom onset (approximately 51 versus 30 months respectively; p < 0.001) and after admission to a specialized center (7 versus 4 months respectively; p = 0.002). Dysphagia and gastrostomy were more frequent in the sALS group compared to the fALS8 group (p = 0.02 and p < 0.01 respectively), and older age at diagnosis was associated with worse functional scores.The fALS8 group presented with distinct clinical and demographic features compared to the sALS group, including younger age at diagnosis, more homogeneous symptom onset, and lower frequency of dysphagia and need for gastrostomy. The diagnosis was more delayed in the fALS8 group, and older age at diagnosis was associated with worse functional status. The current study contributes to the scarce data on fALS8 in South America.},
}

Humans
*Amyotrophic Lateral Sclerosis/epidemiology/diagnosis/genetics/physiopathology/classification
Female
Male
Middle Aged
Adult
Brazil/epidemiology
Aged
Age of Onset
Socioeconomic Factors
Retrospective Studies
Sociodemographic Factors

@article {pmid41872337,
year = {2026},
author = {Croteau, E and Rousseau, E and Tremblay, S and Rousseau, JF and Espinosa-Betancourt, E and Lavallée, E and Dubreuil, S and Ait-Mohand, S and Lareau-Trudel, É and Gosselin, S and Carrier, V and Côté-Bigras, S and Allard, C and Maier, M and Salzmann, M and Tétu, A and Houde, MP and Turcotte, É and Guérin, B},
title = {A phase I study to evaluate the dosimetry and safety of [[89]Zr]Zr-DFO-AP-101, a new antibody-based radiopharmaceutical to detect misfolded SOD1 in amyotrophic lateral sclerosis.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {},
number = {},
pages = {},
pmid = {41872337},
issn = {1619-7089},
support = {Fonds d'accélération des collaborations en santé (FACS)//Ministère de la Santé et des Services sociaux/ ; },
}

@article {pmid41872984,
year = {2026},
author = {Toomey, A and Kleinerova, J and Tan, EL and Siah, WF and Bede, P},
title = {Muscle MRI and Muscle Ultrasound Applications in MND/ALS: Academic Insights and Clinical Opportunities.},
journal = {European journal of neurology},
volume = {33},
number = {3},
pages = {e70582},
doi = {10.1111/ene.70582},
pmid = {41872984},
issn = {1468-1331},
support = {HRB JPND-Cofund-2025-3/HRBI_/Health Research Board/Ireland ; JPND-2025"Qual-Bulb-MND"//EU Joint Programme - Neurodegenerative Disease Research/ ; SFI-SP20/SP/8953/SFI_/Science Foundation Ireland/Ireland ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; *Magnetic Resonance Imaging/methods ; Ultrasonography/methods ; *Muscle, Skeletal/diagnostic imaging ; },
abstract = {BACKGROUND: There is an unmet need for the clinically relevant ALS biomarkers to facilitate an accurate diagnosis in suspected cases, monitor disease progression and evaluate response to therapy in clinical trials. While the MND/ALS literature is dominated by innovative brain studies, motor disability in ALS is primarily driven by neurogenic muscle change impacting mobility, dexterity, respiratory and bulbar function.

METHODS: With the intention of raising awareness of muscle-derived imaging markers in ALS, a systematic review has been conducted. Study designs, imaging methods, data interpretation frameworks, and cohort characteristics were systematically evaluated to identify innovative approaches and barriers to clinical implementation.

RESULTS: A total of 219 studies were screened and 73 original studies selected for systematic review; 37 muscle MRI studies and 36 studies using ultrasound, PET or CT. All of the selected studies successfully captured ALS-associated muscle degeneration and their methods included the evaluation of muscle dimensions (thickness/volumes n = 34), 'acute' denervation (water content, n = 15), fasciculation counts (n = 14), 'chronic' neurogenic change (fat content, n = 21), metabolic changes (n = 4), diffusion alterations (n = 8) and echo intensity changes (n = 13).

CONCLUSIONS: Despite the huge impact of lower motor neuron dysfunction on the patients' independence, survival and quality of life, muscle imaging is a glaringly overlooked frontier of MND/ALS research. This is a missed opportunity, as a variety of non-invasive quantitative muscle imaging techniques have been successfully used in other neurological conditions; these protocols are easy to implement on commercial MRI and ultrasound platforms and recent studies have demonstrated their ease of use and potential clinical utility.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnostic imaging
*Magnetic Resonance Imaging/methods
Ultrasonography/methods
*Muscle, Skeletal/diagnostic imaging

@article {pmid41873182,
year = {2026},
author = {Hinten, AE and Imuta, K},
title = {Executive Function Costs of Fantastical Interference in Narrative Comprehension: A Response to Lillard's (2026) Commentary.},
journal = {Developmental science},
volume = {29},
number = {3},
pages = {e70177},
doi = {10.1111/desc.70177},
pmid = {41873182},
issn = {1467-7687},
mesh = {Humans ; *Comprehension/physiology ; *Executive Function/physiology ; Child ; *Fantasy ; *Narration ; Child, Preschool ; Cognition ; },
abstract = {Through bringing together previous findings from 16 studies involving 121 effect sizes (based on 1,297 1.5- to 6-year-olds), Hinten et al.'s (2025) meta-analysis revealed that children who viewed fantastical media in an experimental setting performed worse on inhibitory control and cognitive flexibility tasks immediately post-viewing compared to those exposed to realistic media. Lillard's (2026) commentary provided one potential explanation for our findings, revolving around the idea that processing fantastical content is cognitively taxing because it conflicts with existing schemas. In this response, we extend Lillard's (2026) perspective by drawing on Loschky et al.'s (2020) Scene Perception and Event Comprehension Theory (SPECT) to provide an additional explanation: Fantasy overloads children's executive functions because it interferes with their narrative comprehension. SUMMARY: We present a novel perspective on why fantastical media may have adverse, short-term effects on children's executive functioning. Children's executive functions may become overloaded while watching fantastical media because fantastical elements can detract from and hamper narrative comprehension processes.},
}

Humans
*Comprehension/physiology
*Executive Function/physiology
Child
*Fantasy
*Narration
Child, Preschool
Cognition

@article {pmid41874673,
year = {2026},
author = {Li, J and Gao, C and Wang, Q and Liu, J and Xie, Z and Zhao, Y and Yu, M and Zheng, Y and Lv, H and Zhang, W and Yuan, Y and Meng, L and Deng, J and Wang, Z},
title = {Aberrant SOD1 aggregates in skeletal muscle target fibers in amyotrophic lateral sclerosis.},
journal = {Acta neuropathologica},
volume = {151},
number = {1},
pages = {},
pmid = {41874673},
issn = {1432-0533},
}

@article {pmid41875078,
year = {2026},
author = {Mamede, LD and Hu, M and Vaquer-Alicea, J and Titus, AR and Passos, PM and Lantelme, E and French, RL and Kirschner, PA and Diamond, MI and Miller, TM and Ayala, YM},
title = {A quantitative cell-based reporter links TDP-43 aggregation and dysfunction to define pathogenic mechanisms.},
journal = {PLoS biology},
volume = {24},
number = {3},
pages = {e3003662},
doi = {10.1371/journal.pbio.3003662},
pmid = {41875078},
issn = {1545-7885},
mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; *Protein Aggregation, Pathological/metabolism/genetics ; Neurons/metabolism/pathology ; Exons ; Protein Aggregates ; RNA Splicing ; Amyotrophic Lateral Sclerosis/metabolism ; TDP-43 Proteinopathies/metabolism/genetics ; Genes, Reporter ; },
abstract = {TDP-43 pathology is a hallmark of fatal neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and limbic-predominant age-related TDP-43-encephalopathy (LATE). In affected patients, cytoplasmic TDP-43 aggregates are accompanied by disruption of its normal nuclear localization and function. Because TDP-43 is an RNA binding protein that controls transcript processing, including repression of cryptic exon splicing, its loss leads to dysregulation of gene expression. Despite its central significance in disease, the connection between TDP-43 aggregation and dysfunction remains poorly understood, and models to study the underlying mechanisms are limited. Here, we characterize a robust and quantitative cell-based reporter that captures both aggregation and the resulting loss of function. Using this human biosensor cell line, we show that aggregation initiated by prion-like seeding drives progressive depletion of nuclear TDP-43 and induces signature features of diminished TDP-43 activity, such as increased DNA damage and activation of cryptic exon splicing. We find that aggregate seeding also induces cryptic exon splicing in human neurons implying that this pathological link extends to disease-relevant models. The seeding model provides a platform for dissecting mechanisms that underlie TDP-43 pathology and for identifying factors that modulate the aggregation-to-dysfunction transition. Our data shows that aggregate seeding impacts TDP-43 autoregulation, initiating a toxic feed-forward mechanism that disrupts TDP-43 homeostasis. Furthermore, reducing ataxin-2 levels decreases aggregation and restores TDP-43 activity. Together, these findings reveal a molecularly guided strategy to directly impact TDP-43 activity by decreasing its misfolding and aggregation, highlighting approaches to prevent TDP-43 dysfunction and mitigate toxicity under pathological conditions.},
}

Humans
*DNA-Binding Proteins/metabolism/genetics
*Protein Aggregation, Pathological/metabolism/genetics
Neurons/metabolism/pathology
Exons
Protein Aggregates
RNA Splicing
Amyotrophic Lateral Sclerosis/metabolism
TDP-43 Proteinopathies/metabolism/genetics
Genes, Reporter

@article {pmid41875115,
year = {2026},
author = {Uversky, VN},
title = {Why is it so difficult to discover drugs for amyotrophic lateral sclerosis? A protein intrinsic disorder perspective.},
journal = {Expert opinion on drug discovery},
volume = {},
number = {},
pages = {1-21},
doi = {10.1080/17460441.2026.2648612},
pmid = {41875115},
issn = {1746-045X},
abstract = {INTRODUCTION: Amyotrophic Lateral Sclerosis (ALS) is the most common adult motor neuron disease, now viewed as a spectrum disorder rather than a single entity. Because of the significant person-to-person variability in the disease's biology, driven by both genetic and environmental interactions, finding a single "magic bullet" drug is unlikely. Despite decades of research, only a few ALS drugs have being developed. Drug discovery has a 95% failure rate due to genetic complexity, lack of sensitive biomarkers, diagnostic delays, inadequate animal models, and poor clinical trial design.

AREAS COVERED: This article considers several aspects related to the prevalence of intrinsic disorder in ALS-related proteins and highlights how these features might hinder rational structure-based drug discovery.

EXPERT OPINION: There is a common oversight in current drug discovery methodologies, which is the neglect of intrinsically disordered proteins (IDPs) playing several crucial roles in the pathology of neurodegeneration in general and ALS in particular. Therefore, it seems that the 'one-size-fits-all' approach to ALS is hitting a wall because these 'shapeshifters' of the cellular world are ignored. Consequently, to be more successful in finding drugs treating ALS, gears should be shifted from rational structure-based models to intrinsic disorder-centric approaches.},
}

@article {pmid41866066,
year = {2026},
author = {Qian, J and Li, C and Wang, Y and Tong, J},
title = {Extracorporeal sliding knot technique for simplified hysteroscopic suture fixation of levonorgestrel-releasing intrauterine device.},
journal = {Journal of minimally invasive gynecology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jmig.2026.03.020},
pmid = {41866066},
issn = {1553-4669},
abstract = {OBJECTIVE: Approximately 20% of adenomyosis cases occur in women under 40 years of age [1]. While LNG-IUD is the first-line medical therapy, its treatment failure is closely associated with uterine volume [2], with expulsion rates reported as high as 37.5% in uteri exceeding 12 gestational weeks [3]. Tong et al's hysteroscopic suture fixation technique (HCSS) reduced expulsion to 2.6% [4][5]. Although clinical studies have confirmed the safety and efficacy of this technique [5], its technical complexity and the requirement for repeated instrument exchanges have limited widespread adoption. We therefore developed an optimized extracorporeal sliding knot method to overcome these barriers.

SETTING: University hospital.

PARTICIPANTS: A 45-year-old woman diagnosed with adenomyosis and prior LNG-IUD expulsion.

INTERVENTIONS: The key modification involves three critical steps: Step 1) Construction of a secure multi-loop sliding knot using 2-0 Ethibond suture attached to the "T junction" of the LNG-IUD; Step 2) Introduction of the pre-formed knot into the uterine cavity in a single maneuver using a knot-pusher; Step 3) Adjustment of the knot position under the hysteroscopic cold-knife surgery system (HCSS), achieving secure device fixation. The complete procedure obviates repeated instrument exchanges and intracavitary knot manipulation required by the original technique.

CONCLUSION: The extracorporeal sliding knot optimization preserves therapeutic efficacy while simplifying intrauterine manipulation, significantly enhancing surgical reproducibility and accessibility for widespread clinical adoption.},
}

@article {pmid41866414,
year = {2026},
author = {Li, X and Ding, W and Xu, E},
title = {Uncoupling of apnea-hypopnea index and oxygen desaturation in als: characterization and diagnostic implications of an "AHI-SpO2 dissociation" phenotype.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {4},
pages = {},
pmid = {41866414},
issn = {1590-3478},
support = {202610452//Health Commission of Jiangxi Province/ ; },
}

@article {pmid41866449,
year = {2026},
author = {Wang, Z and He, F and Li, L and Wang, W and Zhang, L and Tang, J and Le, W},
title = {Sleep Disorders in Neurodegenerative Diseases: Pathological Correlations and Underlying Mechanisms.},
journal = {Neuroscience bulletin},
volume = {},
number = {},
pages = {},
pmid = {41866449},
issn = {1995-8218},
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), multiple system atrophy (MSA), amyotrophic lateral sclerosis (ALS), and others, represent an escalating public health burden in aging populations. NDDs are characterized by progressive neuronal loss and misfolded protein aggregation. Despite distinct clinical heterogeneity, these diseases universally present with debilitating non-motor symptoms, among which sleep-wake disorders are highly prevalent. Once considered secondary to neuronal damage, growing evidence now highlights a bidirectional interplay: sleep disruption is not only a consequence of neurodegeneration but also exacerbates its progression. This review synthesizes this complex interplay, outlining sleep phenotypes across major NDDs, dissecting key underlying mechanisms (impaired protein homeostasis, glymphatic dysfunction, chronic neuroinflammation, sleep-regulatory nucleus vulnerability, and circadian dysregulation), and summarizing current pharmacotherapeutic and non-pharmacological interventions. Attenuating sleep disorders may therefore provide symptomatic relief and disease‑modifying effects for NDDs.},
}

@article {pmid41866924,
year = {2026},
author = {Seyam, M and Morelli, KH and Waheed, W and van den Berg, LH and Tandan, R},
title = {Predicting Disease Progression and Survival in Amyotrophic Lateral Sclerosis.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70198},
pmid = {41866924},
issn = {1097-4598},
abstract = {Amyotrophic lateral sclerosis (ALS) progresses relentlessly and is characterized by a median survival of 2-5 years from symptom onset with death from respiratory failure. ALS is a complex, multi-system neurodegenerative disorder with significant phenotypic heterogeneity and markedly variable disease progression. This variability presents challenges in determining the optimal timing for therapeutic interventions, complicates clinical trial design due to lack of effective stratification methods, and makes it difficult to reliably measure the longitudinal impact of specific interventions. Accurately capturing disease progression in ALS can be challenging. We propose that early respiratory phenotyping offers a promising approach to facilitate patient stratification, improve assessments of disease progression, and predict survival.},
}

@article {pmid41867322,
year = {2026},
author = {Alabdali, A and Alharkan, M},
title = {Comparative Cost Analysis of Ambulance Utilization: Advanced Life Support (ALS) vs Basic Life Support (BLS) at King Abdulaziz Medical City, Riyadh.},
journal = {ClinicoEconomics and outcomes research : CEOR},
volume = {18},
number = {},
pages = {570790},
pmid = {41867322},
issn = {1178-6981},
abstract = {PURPOSE: Unit-hour utilization (UHU) is the most common metric for evaluating the productivity of ambulances and crews for ambulance services. Calculating UHU is essential for maximizing profitability and evaluating the number of hours of ambulance utilization during a shift. This has not been examined previously at King Abdulaziz Medical City (KAMC). KAMC is a major tertiary-care medical center in Riyadh, Saudi Arabia, with dedicated ALS (Advanced Life Support) and BLS (Basic Life Support) ambulance units. This study aimed to determine the cost of operating the emergency calls (advanced life support [ALS]) unit and non-emergency calls (basic life support [BLS]) unit and compare the costs of emergency calls (ALS) and non-emergency calls (BLS). The study used a standardized institutional checklist that itemizes expenditures across logistics, equipment, maintenance, salary, pharmacy, and fuel cost components.

METHODS: This was a retrospective cross-sectional study. Institutional Review Board approval was obtained from King Abdullah International Medical Research Center. The study examined emergency and non-emergency calls for a period of 12 months. This study was based on a checklist assessing various expenditures to calculate the cost of ambulance utilization at KAMC in 2022.

RESULTS: The total average ambulance utilization cost per year for ALS was 4,806,245.7 SR, and the average ambulance utilization cost per hour was 548.65 SR; these costs were to operate the ALS crew for 24 hours, seven days a week. Conversely, the total average ambulance utilization cost per year for BLS was 3,934,156.92 SR, and the average ambulance utilization cost per hour was 449.10 SR. The main expenses concerned salaries and overhead costs for ALS and BLS.

CONCLUSION: This study provides insights into the cost of ambulance utilization between ALS and BLS. The higher cost of ALS calls may be attributed to the higher level of training, equipment, and staffing required.},
}

@article {pmid41868461,
year = {2026},
author = {Yu, J},
title = {Postoperative acute ultra-early fish mouthing of a Surpass Evolve flow diverter leading to ischemic complication.},
journal = {Radiology case reports},
volume = {21},
number = {6},
pages = {2346-2354},
pmid = {41868461},
issn = {1930-0433},
abstract = {Currently, the Surpass Evolve flow diverter (SE FD) is widely adopted for endovascular treatment of intracranial aneurysms. Although generally safe, acute ultra-early fish mouthing remains an exceptionally rare complication. Following Torche et al.'s 2023 report of the first case, the present case represents the second documented instance. A 66-year-old woman was diagnosed with a left posterior communicating artery aneurysm and a left ophthalmic artery aneurysm. Physical examination revealed no abnormalities. The endovascular treatment (EVT) procedure was performed. After advancing a microcatheter into the left middle cerebral artery, an SE FD with appropriate size was deployed to cover both aneurysms, achieving confirmed complete expansion and optimal wall apposition. Two hours postoperatively, the patient developed aphasia and hemiparesis. Subsequent angiography at 4 hours revealed thrombosis within the SE FD and fish mouthing at the proximal segment. Successful microguidewire traversal through the affected site restored complete FD expansion and wall apposition. Postoperatively, the patient's hemiparesis improved, and her motor aphasia resolved. Magnetic resonance imaging confirmed multiple acute infarctions, while computed tomography demonstrated proper FD expansion. At 3-month follow-up, near-normal functional recovery was observed. This case indicates that SE FD deployment may be complicated by acute ultra-early fish mouthing attributable to post-deployment tension release. Preventive strategies should emphasize appropriate device sizing, adequate landing zone selection, and post-implant tension assessment.},
}

@article {pmid41868729,
year = {2026},
author = {Sethi, N and Levy, OA and Richardson, A and Harari, OA and Sellati, R},
title = {A Qualitive Investigation of Geographic Disparities in Genetic Testing and Care Access for Amyotrophic Lateral Sclerosis: Insights From Patient Journey Mapping.},
journal = {Patient preference and adherence},
volume = {20},
number = {},
pages = {566747},
pmid = {41868729},
issn = {1177-889X},
abstract = {PURPOSE: Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease that is associated with a high patient burden, reduced lifespan, and reduced quality of life. People living with ALS (PLwALS) often experience delays in diagnosis of ~1 year, and while current treatment options can slow disease progression, improve quality of life, and offer modest benefits in functional decline, they do not reverse neuronal damage. Defining and understanding the experiences of PLwALS can help identify gaps and barriers to optimal care.

PATIENTS AND METHODS: This non-interventional study was intended to obtain insights on the patient experience from the perspective of PLwALS. We sought to develop an ALS patient journey map from initial presentation through to end-of-life care for 4 regions (North America, Asia-Pacific, Latin America, and Europe/Middle East/Africa). The map was based on results from a global audit of data sources (including publications, patient narratives, society guidelines, academic reports, industry white papers [n=104]), and one-to-one, 60-minute, semi-structured interviews with PLwALS (n=12) or those caring for PLwALS (n=2). The initial patient journey map was subsequently reviewed during 2 advisory sessions with patient advocates (7 PLwALS and 2 caregivers) in September and November 2023.

RESULTS: We identified several barriers and challenges that most impact PLwALS, caregivers, and clinicians, with many similarities but also some differences across the regions.

CONCLUSION: These insights will enable targeted improvements in education, personalized care, resource allocation, care coordination, policy development, and funding, ultimately improving patient outcomes.},
}

@article {pmid41869005,
year = {2025},
author = {Lorenz, J and Hawkins, S and McCarthy, B},
title = {Griffiths et al.'s Study of Psilocybin with Religious Professionals: A Theological Response from a Christian Perspective.},
journal = {Psychedelic medicine (New Rochelle, N.Y.)},
volume = {3},
number = {4},
pages = {202-206},
pmid = {41869005},
issn = {2831-4433},
abstract = {Griffiths et al.'s recent "Effects of Psilocybin on Religious and Spiritual Attitudes and Behaviors in Clergy from Various Major World Religions" is an important study in the literature on psychedelic medicine and religious experience. In this commentary on the study, we argue: (1) The study design's implicit presupposition of perennialism in its conception of mysticism burdens it with metaphysical and theological freight it doesn't need to support its hypothesis; and (2) Psychedelic usage in pursuit of mysticism, however construed, risks two pathologies-hyper-individualism and idolatry-that religious traditions and communities are well-positioned to counter.},
}

@article {pmid41870290,
year = {2026},
author = {Narayan, A and Neupane, K and Woodside, MT},
title = {Scalable assay to identify inhibitors of prion-like propagation of protein misfolding as potential therapeutics for neurodegeneration.},
journal = {Protein science : a publication of the Protein Society},
volume = {35},
number = {4},
pages = {e70535},
doi = {10.1002/pro.70535},
pmid = {41870290},
issn = {1469-896X},
support = {PJT-185931/CAPMC/CIHR/Canada ; //NSERC Banting Postdoctoral Fellowship/ ; //Alberta Innovates Postdoctoral Fellowship/ ; },
mesh = {*Superoxide Dismutase-1/chemistry/metabolism/antagonists & inhibitors ; *Protein Folding/drug effects ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; *Prions/metabolism/chemistry/antagonists & inhibitors ; },
abstract = {Protein misfolding is linked to many neurodegenerative diseases. In some cases, misfolding can propagate through a prion-like mechanism whereby natively folded molecules are converted into more copies of the misfolded isoform. Prion-like propagation of misfolding is an attractive therapeutic target, but difficulties with assaying conversion directly and simply have severely limited efforts to find drugs targeting conversion of disease-related proteins. Here, we demonstrate a scalable enzymatic assay for testing potential inhibitors of prion-like conversion in superoxide dismutase-1 (SOD1), whose misfolding is linked to amyotrophic lateral sclerosis (ALS). We tested several small-molecule inhibitors of SOD1 aggregation to determine if they also inhibited prion-like conversion. We found that some compounds, like telbivudine and cisplatin, did indeed significantly delay conversion, but others, like baicalein and quercetin, had little effect. Surprisingly, some compounds, like two statins tested, actually accelerated conversion, suggesting that they might act to promote ALS progression. These results underline the fact that conversion and aggregation are distinct biophysical processes. The ability of the assay to identify compounds effective at delaying prion-like conversion holds out promise for applications in future drug discovery efforts that target propagated misfolding specifically.},
}

*Superoxide Dismutase-1/chemistry/metabolism/antagonists & inhibitors
*Protein Folding/drug effects
Humans
*Amyotrophic Lateral Sclerosis/drug therapy/metabolism
*Prions/metabolism/chemistry/antagonists & inhibitors

@article {pmid41870380,
year = {2026},
author = {Elhami Athar, M and Miller, JD and Lynam, DR},
title = {From controversy to confusion: A commentary on how Marcus et al.'s (2025) Psychopathic Boldness Scale further muddies the boldness construct.},
journal = {Psychological assessment},
volume = {38},
number = {4},
pages = {332-338},
doi = {10.1037/pas0001442},
pmid = {41870380},
issn = {1939-134X},
mesh = {Humans ; *Antisocial Personality Disorder/diagnosis/psychology ; *Psychometrics/standards ; *Psychiatric Status Rating Scales/standards ; Reproducibility of Results ; },
abstract = {The Psychopathic Boldness Scale (see record 2025-96918-001) is a newly developed 21-item self-report measure intended to assess boldness as it manifests within psychopathy. In this commentary, we raise concerns about the PBS's construct validity, particularly its conceptual and empirical overlap with antagonism-related traits. Drawing on theoretical analysis and results from Marcus et al., we evaluated how PBS items function relative to the Triarchic Psychopathy Measure. Intraclass correlations of overall correlational profiles revealed that the nomological network of the PBS more closely aligns with Triarchic Psychopathy Measure meanness than with boldness. Rather than clarifying the role of boldness within psychopathy, the PBS repackages maladaptive content typically captured by meanness/antagonism under the boldness label and results in a case of the jingle fallacy. We argue that this conflation undermines theoretical precision and sets the stage for a more difficult-to-integrate literature. (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}

Humans
*Antisocial Personality Disorder/diagnosis/psychology
*Psychometrics/standards
*Psychiatric Status Rating Scales/standards
Reproducibility of Results

@article {pmid41870498,
year = {2026},
author = {Strojny, A and Kiszka, P and Strojny, P},
title = {Rethinking escapism and escape: A cognitive perspective on the C-DOG model.},
journal = {Journal of behavioral addictions},
volume = {},
number = {},
pages = {},
doi = {10.1556/2006.2025.00357},
pmid = {41870498},
issn = {2063-5303},
abstract = {This commentary builds on Giardina et al.'s (2021, 2024) conceptualization of escapism and escape in the C-DOG model, highlighting unresolved definitional ambiguities. We argue that the distinction between these constructs cannot rely solely on pre-game intentions (expectation to return vs. remain) due to potential cognitive biases and self-deception, particularly among players with Gaming Disorder (GD). Drawing on goal systems theory and research on maladaptive gaming-related beliefs, we propose that the post-game outcome, successful return vs. persistent difficulty disengaging, offers a more reliable criterion. This perspective reframes escapism and escape as goal-driven processes shaped by experiential avoidance and motivational rigidity.},
}

@article {pmid41870813,
year = {2026},
author = {Upadhayay, S},
title = {Role of Pentacyclic Triterpenes in the Management of Neurological Disorders: An Insight into Molecular Mechanisms and Therapeutic Approaches.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41870813},
issn = {1559-1182},
mesh = {Humans ; Animals ; *Nervous System Diseases/drug therapy/metabolism ; *Pentacyclic Triterpenes/therapeutic use/pharmacology ; *Neuroprotective Agents/therapeutic use/pharmacology ; Signal Transduction/drug effects ; Oxidative Stress/drug effects ; },
abstract = {Neurological disorders represent major public health concerns globally, as they profoundly affect motor function, memory, and cognitive abilities, thus compromising patients' independence and quality of life. Despite extensive research, current treatment approaches predominantly offer palliative care, failing to hinder disease progression. The rising incidence of these disorders underscores an urgent necessity for more efficacious and disease-modifying therapies. According to findings, pentacyclic triterpenoids exhibit neuroprotective properties by inhibiting neuronal oxidative stress, neuroinflammation, apoptosis, and degeneration, making them promising candidates for targeting the underlying causes of neurodegeneration. Therefore, in this review, we explore natural and synthetic pentacyclic triterpenoids that exhibit neuroprotective effects by modulating signaling pathways, such as HMGB1, TLR4, NLRP3, NF-κB, Nrf2, PI3K, Akt, and CREB, which play crucial roles in regulating cell proliferation, differentiation, and neuronal plasticity. The present literature survey is performed by searching various keywords with several combinations: "pentacyclic triterpenes", "neurological disorders", Parkinson's Disease", "Huntington's Disease", "Alzheimer's Disease", "Multiple sclerosis", "Amyotrophic Lateral Sclerosis" "Epilepsy", "mitochondria dysfunction", "oxidative stress", "preclinical studies", "molecular mechanisms", and "clinical studies". Studies indicates that pentacyclic triterpenoids have a wide range of therapeutic potentials, current findings summarizes existing knowledge and examines the neuroprotective properties and potential molecular mechanisms of pentacyclic triterpenoids related with health benefits and neurological diseases. Available evidence suggests that pentacyclic triterpenoids possess the capacity to impede disease progression and may be beneficial in the treatment of neurological disorders. This review strengthens the understanding of pentacyclic triterpenoids and their molecular mechanisms, while also facilitating pharmaceutical discovery and development for neurodegenerative disorders.},
}

Humans
Animals
*Nervous System Diseases/drug therapy/metabolism
*Pentacyclic Triterpenes/therapeutic use/pharmacology
*Neuroprotective Agents/therapeutic use/pharmacology
Signal Transduction/drug effects
Oxidative Stress/drug effects

@article {pmid41870864,
year = {2026},
author = {Gomez, R and Brown, T and Zarate, D and Houghton, S and Stavropoulos, V},
title = {A Network Approach to the Association Between Emotional Regulation and ADHD Symptoms in Adults: Pathways between Difficulties in Emotional Regulation and ADHD Dimensions.},
journal = {The Psychiatric quarterly},
volume = {},
number = {},
pages = {},
pmid = {41870864},
issn = {1573-6709},
}

@article {pmid41862640,
year = {2026},
author = {Onwunma, J and Binsabaan, S and Allen, SP and Thanthirige, SR and Gaur, D and Sankaran, B and Wohlever, ML},
title = {ALS mutations disrupt self-association between the ubiquilin STI1 hydrophobic groove and internal placeholder sequences.},
journal = {The EMBO journal},
volume = {},
number = {},
pages = {},
pmid = {41862640},
issn = {1460-2075},
support = {R35 GM137904-01S2//HHS | National Institutes of Health (NIH)/ ; P30 GM124169-01//HHS | National Institutes of Health (NIH)/ ; CAREER Award 2343131//National Science Foundation (NSF)/ ; },
abstract = {Ubiquilins are molecular chaperones that play multifaceted roles in proteostasis, with point mutations in UBQLN2 leading to altered phase-separation properties and amyotrophic lateral sclerosis (ALS). Our mechanistic understanding of this essential process has been hindered by a lack of structural information on the STI1 domain, which is essential for ubiquilin chaperone activity and phase separation. Here, we present the first crystal structure of a ubiquilin-family STI1 domain bound to a transmembrane domain (TMD), and show that ALS mutations disrupt the STI1-TMD interaction. We further demonstrate that ubiquilins contain multiple conserved internal sequences that bind to the STI1 domain, including the PXX-repeat region that is a hotspot for ALS mutations. We propose that these placeholder sequences prevent solvent exposure of the STI1 hydrophobic groove and contribute to the multivalency that drives ubiquilin phase-separation. Together, this work provides a new paradigm for understanding how STI1 domains modulate ubiquilin chaperone activity and phase separation, and offers insights into the molecular basis of ALS pathogenesis.},
}

@article {pmid41863273,
year = {2026},
author = {Singh, DD},
title = {PROTAC-Based Therapeutics: From Design to Clinical Potential in Neurodegenerative Disease.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X438970260115164001},
pmid = {41863273},
issn = {1875-6190},
abstract = {Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and ALS, are characterized by a progressive loss of neuronal function and a direct correlation between their progression and proteins with misfolded and aggregated structures. Although significant efforts have been made, and various therapies are available for their treatment, they show only a modest beneficial response to their progression. The main reasons for this phenomenon can be correlated with a loss of target specificity, low permeability in crossing the BBB, and their ineffectiveness in clearing proteins from neurons. Within this therapeutic paradigm, proteolysis-targeting chimaeras, or PROTACS, have been identified as a novel therapeutic strategy. Unlike traditional smallmolecule inhibitors, PROTACS take advantage of the natural ubiquitin proteasome system to specifically degrade target proteins. At a molecular level, PROTACS consist of a ligand that specifically recognizes a target protein, a linker, and an E3 ligand-recruiting ligand that specifically recruits an E3 ligase. At a therapeutic level, this offers the advantage of catalytic protein degradation that should allow for reduced dosing. Preclinical studies carried out using neurodegenerative disease models have shown the potential for selective targeting of major pathologic proteins, such as tau, α- synuclein, TDP-43, and mHTT, which are crucial for pathogenesis. In addition, developments in the formulation of brain-permeable PROTACS, understanding of E3 ligase expression levels in the central nervous system, and application of iPSC-derived neuronal systems have contributed to rapid developments in this area. Although pharmacokinetic modification and degradation-specific approaches are still required, evidence suggests a major therapeutic potential for PROTAC-based approaches for the treatment of neurodegenerative disorders.},
}

@article {pmid41863275,
year = {2026},
author = {Singh, AK and Kush, A and Bhushan, B and Dhanawat, M and Sharma, PK},
title = {Targeting Autophagy with Bioactive Compounds: Therapeutic Potential in Neurodegenerative Disorders.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X408653251130061347},
pmid = {41863275},
issn = {1875-6190},
abstract = {Neurodegenerative disorders (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are characterized by the accumulation of misfolded proteins and impaired cellular clearance mechanisms. Autophagy, a critical lysosomedependent degradative pathway, plays a vital role in maintaining proteostasis and neuronal health. Dysregulation of autophagy has been implicated in the pathogenesis of multiple NDs, making it a promising therapeutic target. This review comprehensively examines the molecular mechanisms of autophagy and its dysfunction across major NDs. Furthermore, it highlights the potential of bioactive compounds such as flavonoids, alkaloids, polyphenols, and terpenoids to modulate autophagic flux, thereby promoting the clearance of toxic protein aggregates like amyloid-β, tau, and α- synuclein. Emerging strategies, including nanotechnology-based delivery systems, are also discussed for enhancing the bioavailability and efficacy of these compounds. The evidence suggests that pharmacological or natural induction of autophagy may alleviate neurodegenerative pathology, though context- and stage-specific modulation is essential. This work underscores the therapeutic promise of autophagy-enhancing bioactives and calls for further research into their clinical applications.},
}

@article {pmid41863659,
year = {2026},
author = {Mullick, S and Chakraborty, A and Porel, P and Nath, R and Chaudhary, P and Islam, A and Das, J and Pramanik, S and Panigrahy, UP and Sridhar, SB and Mondal, M and Debnath, B and Ashique, S},
title = {Decoding Neuroinflammatory Pathways: The Role of the CXCL12-CXCR4/CXCR7 Axis in ALS-Related Cognitive Impairment.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41863659},
issn = {1559-1182},
mesh = {Humans ; *Chemokine CXCL12/metabolism ; *Receptors, CXCR/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism/complications/pathology ; Animals ; *Receptors, CXCR4/metabolism ; *Cognitive Dysfunction/metabolism ; *Signal Transduction/physiology ; *Neuroinflammatory Diseases/metabolism/pathology ; Inflammation/metabolism/pathology ; },
abstract = {Cognitive impairment (CI) and accelerating neuronal deterioration are hallmarks of amyotrophic lateral sclerosis (ALS). Under these circumstances a crucial molecular mechanism in the pathophysiology of CI has been identified: the CXC chemokine receptor type 7 (CXCR7)/CXC chemokine receptor type 4 (CXCR4)/Cysteine-X-cysteine chemokine ligand 12 (CXCL12) region. Research on ALS shows that the CXCR7/CXCR4/CXCL12 complex plays a role in the degeneration of motor neurons and the resulting cognitive decline. JAK/STAT, PI3K/AKT, MAPK, and other signaling pathways are among the ways the axis controls neuronal inflammation, synaptic remodeling, and neuronal maintenance in each of these scenarios. The CXC motif chemokine ligand 12 (CXCL12) and CXC chemokine receptor type 4 (CXCR4) axis is crucial for the start of the inflammatory mechanism because of their function in mediating the chemotaxis of inflammatory cells. By preventing the migration of inflammatory cells via CXCL12 in the inflammatory area, the response to inflammation can be prevented or reduced. Consequently, the development of CXCR4 antagonists has emerged as a cutting-edge strategy for inflammation treatment. Recent research suggests that managing this relationship could reduce cognitive deficits and offer neuroprotective benefits. According to the current review, the CXCL12/CXCR4/CXCR7 pathway may be a promising target for treating cognitive dysfunction in neurodegenerative disorder. It also emphasizes the need for additional research to completely comprehend its function and identify efficient treatments which may result in improved clinical treatment modalities for these debilitating illnesses.},
}

Humans
*Chemokine CXCL12/metabolism
*Receptors, CXCR/metabolism
*Amyotrophic Lateral Sclerosis/metabolism/complications/pathology
Animals
*Receptors, CXCR4/metabolism
*Cognitive Dysfunction/metabolism
*Signal Transduction/physiology
*Neuroinflammatory Diseases/metabolism/pathology
Inflammation/metabolism/pathology

@article {pmid41864292,
year = {2026},
author = {Liu, H and Zhu, J and Chen, Y and Lin, X and Hua, C and Chen, H},
title = {Response to Jia et al.'s "Comment on the "genetic classification helps with precise sirolimus treatment in slow-flow vascular malformations"".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.03.041},
pmid = {41864292},
issn = {1097-6787},
}

@article {pmid41864411,
year = {2026},
author = {Davias, A and Tang, IW and Hansen, J and Knekt, P and Rantakokko, P and Weisskopf, MG},
title = {Associations between pre-disease biomarkers of persistent organic pollutants and amyotrophic lateral sclerosis risk in four European cohorts.},
journal = {Environmental research},
volume = {},
number = {},
pages = {124337},
doi = {10.1016/j.envres.2026.124337},
pmid = {41864411},
issn = {1096-0953},
abstract = {OBJECTIVES: Previous retrospective studies suggested that occupational exposures to persistent organic pollutants (POPs) may be associated with amyotrophic lateral sclerosis (ALS), but prospective studies with biomarker exposure assessment are scarce. This study aimed to prospectively investigate the relationship between POP exposures and ALS risk in the Danish Diet, Cancer and Health study (EPIC) cohort and to conduct a meta-analysis including results from the prior study of 3 small prospective Finnish cohorts in addition to the Danish EPIC cohort.

METHODS: We identified 166 incident ALS cases between 1993 and 1997 using the Danish National Patient Register and randomly selected 334 controls by individual matching on birth-year and sex. Levels of 13 polychlorinated biphenyls, 9 organochlorine pesticides and 3 polybrominated diphenyl ethers were assessed from baseline plasma samples. We employed conditional logistic regression models using exposure quartiles, and generalized additive models (GAMs), adjusting for confounders. We conducted a meta-analysis combining 3 Finnish prospective cohorts with the Danish data using a random-effects model.

RESULTS: The Danish results suggested generally inverse trends between several POPs and the predicted ALS risk; especially for chlordane-related compounds (co-pollutant quartile model, p-value<0.01). GAMs supported these trends, although most were not statistically significant. However, hexachlorobenzene was positively associated with ALS risk in co-pollutant GAM (p-value=0.02). Additionally, the GAMs suggested higher ALS odds at the highest levels of exposure of some POPs, but the data at these levels was sparse. Meta-analysis results were mostly consistent with the Danish findings.

CONCLUSION: Our study suggested elevated ALS risk among those exposed to hexachlorobenzene when adjusting for co-pollutants. Higher level of some POPs suggested a positive association with ALS occurrence, but the data was scarce at these levels.},
}

@article {pmid41864543,
year = {2026},
author = {Wu, J and Ma, H and Niu, X and Zhang, Z and Guo, R and Shen, N and Tian, Y and Zhao, H and Yang, Y and Chen, Y},
title = {The p75NTR Signaling Axis: Bridging Neurodevelopmental Homeostasis, Pathological Mechanisms, and Therapeutic Strategies in Neurodegenerative Diseases.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {103105},
doi = {10.1016/j.arr.2026.103105},
pmid = {41864543},
issn = {1872-9649},
abstract = {The neurotrophin receptor p75 (p75NTR) plays dual, context-dependent roles in the nervous system that are regulated by ligand binding, co-receptor interactions, and microenvironmental cues. During neurodevelopment, synaptic plasticity, and in neurodegenerative disorders, p75NTR orchestrates opposing cellular responses: it can support neuronal homeostasis through pro-survival pathways, while also initiating apoptotic and inflammatory cascades that exacerbate disease progression. In Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), activation of p75NTR drives pathological processes such as neuronal apoptosis and axonal degeneration, leading to impaired cognitive and motor function.Importantly, different structural domains of p75NTR have divergent effects. The extracellular domain (p75ECD) exhibits neuroprotective properties in AD models, in contrast with the pro-apoptotic activity associated with the full-length receptor. Therapeutic targeting of p75NTR with small-molecule ligands and ROCK inhibitors has shown efficacy in preclinical models, and some candidates have progressed to clinical trials. However, several challenges hinder clinical translation: (1) the mechanisms underlying p75NTR upregulation are not fully understood; (2) its downstream signaling network is highly complex; and (3) existing biomarker systems remain limited.A comprehensive understanding of p75NTR's role in neurodegeneration may clarify pathological mechanisms and reveal novel therapeutic targets. Achieving this will require multidisciplinary collaboration to bridge the gap between basic research and clinical applications.},
}

@article {pmid41865815,
year = {2026},
author = {Liu, X and Gao, Z and Xu, J},
title = {Beyond Fluorescence: A Critical Look at AI-Powered Brightfield Analysis for T-Cell Killing Assays.},
journal = {SLAS discovery : advancing life sciences R & D},
volume = {},
number = {},
pages = {100307},
doi = {10.1016/j.slasd.2026.100307},
pmid = {41865815},
issn = {2472-5560},
abstract = {This comment evaluates dela Cruz-Chuh et al.'s AI-based label-free workflow for analyzing T-cell mediated tumor killing via brightfield imaging. The study's core strengths include eliminating fluorescent labeling artifacts, achieving comparable consistency to conventional segmentation-based methods, and accommodating phenotypically diverse cancer cells without manual parameter tuning-addressing key bottlenecks in immunotherapy screening. However, critical considerations persist: the binary "killing/non-killing" classification framework may insufficiently resolve low-level or partial cytotoxicity, as evidenced by six false negatives; generalizability to non-adherent hematological malignancies or alternative effector cells remains untested; and the model lacks interpretability regarding morphological features driving cytotoxicity predictions. Additionally, performance across variable imaging platforms or culture conditions is unevaluated, limiting translational reproducibility. Despite these gaps, the workflow advances high-throughput immunotherapy screening efficiency. Future studies incorporating multi-class training, validation across diverse cancer types, and mechanistic decoding of AI-predicted features will strengthen its rigor and broader applicability in drug discovery.},
}

@article {pmid41861969,
year = {2026},
author = {Kamar, N and Congy-Jolivet, N and Salhi, S and Darres, A and Colombat, M and Milhes, J and Esposito, L and Guy, P and Hebral, AL and Prudhomme, T and Sallusto, F and Pellegrini, J and Medrano, C and Marion, O and Del Bello, A},
title = {Anti-lymphocyte globulin versus anti-thymocyte globulin in kidney transplant patients with preformed donor specific antibodies.},
journal = {Transplant immunology},
volume = {},
number = {},
pages = {102375},
doi = {10.1016/j.trim.2026.102375},
pmid = {41861969},
issn = {1878-5492},
abstract = {State-of-the-art immunosuppressant therapies recommend the use of induction therapy after kidney transplantation. Anti-interleukin-2 receptor antibody (basiliximab) is used for low-risk patients whereas polyclonal anti-lymphocyte sera (ALS) are recommended for medium/high-risk patients. There are two commercially available rabbit-derived ALS, namely anti-thymocyte globulin (RATG; Thymoglobulin®) and anti-lymphocyte globulin (RATLG; Grafalon®). We retrospectively compared the efficacy and safety of RATG or RATLG induction therapy in high-risk kidney transplant recipients with preformed donor specific antibodies (DSAs; n = 124). Forty-seven recipients received 1.25 mg/kg RATG for 2 to 3 days. Seventy-seven recipients were treated with 9 mg/kg RATLG on day 0 followed by 4 mg/kg RATLG for 2 to 3 days (n = 21) or a single dose of 9 mg/kg RATLG on day 0 (n = 56). Overall there were no significant differences observed between patients treated with RATG and RATLG. Similarly, no difference was observed between patients who had been given a single dose of RATLG and multiple doses of RATLG or RATG. At one year, patient and graft survival rates, acute rejection rate and type of rejection, kidney function, infections and malignancies did not differ between groups. Kidney transplant patients with preformed DSA showed similar clinical outcomes when treated with RATG or RATLG induction therapy. Polyclonal antibodies in high immunological risk kidney transplant patients.},
}

@article {pmid41856848,
year = {2026},
author = {Wang, R and Chen, W},
title = {Comment on: "Clinical safety of ultra-high-dose methylcobalamin in patients with amyotrophic lateral sclerosis: Open-label extension of a phase 2/3 randomized controlled study".},
journal = {Journal of the neurological sciences},
volume = {},
number = {},
pages = {125791},
doi = {10.1016/j.jns.2026.125791},
pmid = {41856848},
issn = {1878-5883},
}

@article {pmid41858070,
year = {2026},
author = {Zhang, Z and Fan, R and Jing, S and Liu, S and Liu, L and Que, W and Lu, D and Gan, Y and Xiao, F},
title = {Plasma proteomic trajectories before the onset of neurodegenerative diseases.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/17582024.2026.2646760},
pmid = {41858070},
issn = {1758-2032},
abstract = {BACKGROUND: The study aimed to identify indicative proteins associated with the occurrence and mortality of three neurodegenerative diseases (NDDs) and track the changes of proteins before the onset of NDDs.

RESEARCH DESIGN AND METHODS: We analyzed plasma proteomic data from UK Biobank. Cox regression analyses were utilized to detect the relationship between plasma proteins and the risk of development and all-cause mortality of Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Predictive models were established based on related proteins using Lasso regression.

RESULTS: We identified 14 disease-associated proteins for AD, 35 for PD, and one for ALS. The trajectory of plasma proteins before the onset of NDDs was portrayed. Neuroinflammation and the remodeling of the extracellular matrix might be common pathways for NDDs.

CONCLUSIONS: Our results highlighted that the landscape of plasma protein changes before the onset of NDDs.},
}

@article {pmid41858090,
year = {2026},
author = {Ellis, AC and Dobak, S and Pearson, K and McGuire, R and Sutton, T},
title = {Registered Dietitians' perspectives on nutrition management of persons living with amyotrophic lateral sclerosis.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/17582024.2026.2646759},
pmid = {41858090},
issn = {1758-2032},
abstract = {AIM: Persons with amyotrophic lateral sclerosis (PALS) are at high risk for malnutrition, which is a negative prognostic factor for disease progression and survival. This study explored the perspectives of Registered Dietitians (RDs) providing nutrition care to PALS, focusing on barriers and facilitators to optimal patient care.

METHODS: RDs from U.S. multidisciplinary ALS clinics participated in six virtual focus groups. Recordings were transcribed verbatim and independently coded by two researchers for deductive content analysis.

RESULTS: RDs highlighted the importance of using clinical judgment to assess nutrition status and individualizing recommendations to respect patient autonomy. The multidisciplinary team model was identified as a strong facilitator to optimal patient care, while insurance coverage for nutrition-related supplies was a common barrier. RDs reported having little prior knowledge of ALS before assuming their current roles and described the need to upskill through self-teaching and on-the-job experience.

CONCLUSIONS: Results emphasize the importance of clinical judgment with respect to patient autonomy in providing nutrition care to PALS. The barriers and facilitators identified across multiple levels provide insight for future interventions to improve patient care.},
}

@article {pmid41858403,
year = {2026},
author = {Chun, S and Woon Kim, G and Bit Kim, H},
title = {Association between on-scene cardiopulmonary resuscitation duration and outcomes in out-of-hospital cardiac arrest patients.},
journal = {World journal of emergency medicine},
volume = {17},
number = {2},
pages = {137-145},
pmid = {41858403},
issn = {1920-8642},
abstract = {BACKGROUND: Prolonged on-scene Advanced Life Support (ALS) in out-of-hospital cardiac arrest (OHCA) patients may enhance return of spontaneous circulation (ROSC), but the optimal duration of cardiopulmonary resuscitation (CPR) without initial prehospital ROSC remains unclear. We investigated the association between on-scene CPR duration and outcomes using nationwide data. METHODS: This prospective, multi-regional study (2015-2022) included medical cause OHCA patients who underwent Smart ALS (SALS). Data from emergency medical services (EMS) records, SALS logs, and hospital outcomes were analyzed. Logistic regression models were developed for prehospital ROSC, survival to discharge, and good neurological outcome (Cerebral Performance Category [CPC] 1-2). RESULTS: Among 98,569 patients, 34,989 were SALS-eligible and 16,052 received SALS. Predictors of ROSC included younger age, male sex, public arrest, witnessed arrest, bystander CPR, shockable rhythm, and shorter response/scene times. Longer on-scene CPR reduced probabilities of ROSC, survival, and neurological recovery at hospital discharge. Model AUROCs were 0.697 (95%CI 0.676-0.717) for ROSC, 0.836 (95%CI 0.810-0.861) for survival, and 0.925 (95%CI 0.904-0.946) for neurological outcome. CONCLUSION: On-scene CPR duration is a critical prognostic factor in OHCA. The proposed models highlight on-scene predictors that may inform decisions about CPR continuation and support individualized resuscitation strategies. External validation in other EMS systems is warranted.},
}

@article {pmid41858506,
year = {2026},
author = {Hier, DB and Carrithers, MD and Rodríguez-Fernández, JM and Kummer, B},
title = {Editorial: The digitalization of neurology-volume II.},
journal = {Frontiers in digital health},
volume = {8},
number = {},
pages = {1806851},
doi = {10.3389/fdgth.2026.1806851},
pmid = {41858506},
issn = {2673-253X},
}

@article {pmid41858744,
year = {2026},
author = {Jessee, S and Malhotra, N and Sen, M},
title = {Is the Supreme Court veering rightward? The ebb and flow of representation.},
journal = {PNAS nexus},
volume = {5},
number = {3},
pages = {pgag060},
pmid = {41858744},
issn = {2752-6542},
abstract = {Conducting novel surveys that allow the first direct comparisons between Supreme Court decisions and public preferences, Jessee et al. find that the Court moved sharply to the right between 2020 and 2021 and attribute this change to the replacement of Justice Ruth Bader Ginsburg with Justice Amy Coney Barrett. We extend Jessee et al.'s analysis by presenting additional data gathered between 2022 and 2025. We find that the Supreme Court maintained its conservative position in 2022 but then moderated in 2023 following the backlash to the decision in Dobbs v. Mississippi (2022), which repealed Roe v. Wade (1973). We show that despite the composition of the Court remaining stable and the identity of the median voter being unchanged between 2021 and 2025, there is an ebb and flow to the representativeness of Court decisions, with the institution sometimes further to the right of the public and then sometimes shifting closer to the average voter. However, despite these important periodic shifts, the Court has, since 2021, generally remained in a more conservative position relative to the ideological positioning of the American electorate. Our findings have important implications for the legitimacy of the Court and the stability of the rule of law.},
}

@article {pmid41858792,
year = {2026},
author = {Raber, J and Sharpton, TJ},
title = {Diet, gut microbiome, and cognition in neurodegeneration: a review and methodological framework.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1771904},
pmid = {41858792},
issn = {1663-4365},
abstract = {The gut microbiome influences brain function through the gut-brain axis via synthesis of neurotransmitters, production of metabolites affecting epithelial barrier integrity and immune modulation and signaling through the vagus nerve. In humans, microbiome diversity reflects healthy aging and predicts survival, while dysbiosis is increasingly implicated in neurodegenerative conditions including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and ALS. Fecal transplant studies in germ-free mice demonstrate that microbiome alterations are sufficient to induce cognitive and neuropathological phenotypes, supporting causality in preclinical models. Genetic risk factors and environmental exposures affect both neurodegeneration risk and microbiome composition. In this review, we synthesize evidence from human cohorts and preclinical models on the gut-brain axis in cognitive health and disease. We then present a methodological framework for diet-microbiome-cognition research, addressing causal inference through mediation analysis, supervised approaches for deriving diet scores, validation strategies, and individual heterogeneity. This framework can guide development of microbiome-targeted dietary interventions to improve cognitive outcomes.},
}

@article {pmid41859232,
year = {2026},
author = {Sharbafshaaer, M and Pirozzi, MA and Caiazzo, G and Canale, F and Silvestro, M and Russo, A and Tessitore, A and Esposito, F and Trojsi, F},
title = {Subcortical microstructural impairment in amyotrophic lateral sclerosis: clinical correlates of neurite orientation dispersion and density imaging (NODDI) changes.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1757470},
pmid = {41859232},
issn = {1662-4548},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving widespread network disruption beyond the motor cortex. Deep gray matter (DGM) nuclei, crucial for motor and cognitive integration, remain underexplored in vivo. This study applied neurite orientation dispersion and density imaging (NODDI) to evaluate DGM microstructure and its relationship with clinical disability in ALS.

METHODS: Diffusion-weighted MRI data were acquired from 23 ALS patients and 24 age- and sex-matched healthy controls. Orientation dispersion index (ODI), neurite density index (NDI), and free water fraction (FWF) were extracted from the bilateral thalamus, caudate, putamen, pallidum, hippocampus, and amygdala using the Destrieux atlas. Group comparisons and partial correlations were adjusted for age, sex, and disease duration.

RESULTS: No significant group differences in DGM volumes or NODDI-derived metrics survived correction for multiple comparisons. Within the ALS group, several nominal (uncorrected) associations were observed between DGM microstructural metrics and ALSFRS-R subscores. Reduced respiratory subscores were associated with higher ODI in the left thalamus (ρ = 0.57, p = 0.0047, uncorrected). Fine-motor subscores showed nominal positive associations with ODI in the left (ρ = 0.48, p = 0.021, uncorrected) and right amygdala (ρ = 0.51, p = 0.012, uncorrected). Gross motor subscores were nominally associated with NDI in the right thalamus (ρ = 0.58, p = 0.004, uncorrected), left thalamus (ρ = 0.42, p = 0.047, uncorrected), left caudate (ρ = 0.52, p = 0.011, uncorrected), and right caudate (ρ = 0.57, p = 0.033, uncorrected). None of these associations survived false discovery rate correction and should therefore be interpreted as exploratory.

DISCUSSION: These findings suggest subtle and predominantly exploratory associations between DGM microstructural properties and clinical measures in ALS. NODDI derived metrics, particularly ODI and NDI, may provide sensitive indices of subcortical microstructural variation, warranting further investigation in larger cohorts.},
}

@article {pmid41860162,
year = {2026},
author = {Mak, SS and McManus, P and Greer, S and Haws, K and Carlson, CJ and Chandler, HK and Osinubi, O and Ash, GI},
title = {Deployment of an Activity Monitoring Program to Complement a Clinical Intervention for Veterans With Gulf War Illness: Qualitative Study.},
journal = {JMIR human factors},
volume = {13},
number = {},
pages = {e82177},
doi = {10.2196/82177},
pmid = {41860162},
issn = {2292-9495},
mesh = {Humans ; *Veterans/statistics & numerical data/psychology ; *Persian Gulf Syndrome/therapy ; Male ; Qualitative Research ; Middle Aged ; Female ; Adult ; Feasibility Studies ; United States ; },
abstract = {BACKGROUND: Many veterans who served in the Gulf experience Gulf War Illness (GWI), a chronic multisymptom condition associated with fatigue, pain, gastrointestinal problems and respiratory issues, mood/cognitive issues, and sleep difficulties. These symptoms contribute to decreased function, increased mental health needs, and poor quality of life. The Veterans Affairs War Related Illness and Injury Study Center in New Jersey developed a 26-week virtual health coaching intervention to support symptom management for veterans with GWI. In 2023, a consumer-grade smartwatch was added as part of an activity monitoring program to complement this program.

OBJECTIVE: The purpose of this project was to assess the feasibility and acceptability of including a smartwatch-based activity monitoring component to complement a virtual health coaching program for veterans with GWI.

METHODS: Twenty-four veterans enrolled in the health coaching program were invited to participate in the activity monitoring component. Participants attended a virtual orientation to set up the smartwatch, and verbal consent to share data through a Health Insurance Portability and Accountability Act (HIPAA)-compliant platform was obtained. Program feasibility was assessed by evaluating wear-time percentage and duration of use. Acceptability was assessed using two items from a monthly survey and through a midprogram semistructured interview. Quantitative data were summarized descriptively, and qualitative data were analyzed using a coding scheme adapted from Sekhon et al's Theoretical Framework for Acceptability (TFA).

RESULTS: Twenty veterans agreed to participate in the program (mean age 49 years; 7/20, 35% female; 19/20, 94% non-Hispanic White; 11/20, 55% first-time smartwatch users). Twelve participants (60%) wore the watch for the full 26 weeks. Among participants who completed 26 weeks, median daily wear-time completeness exceeded 80% for 25 weeks. Most participants (12/20, 60%) reported that wearing the smartwatch helped them achieve their wellness goals, and the majority (16/20, 80%) said they would recommend using the smartwatch for activity monitoring to other veterans. Qualitative findings supported acceptability across TFA domains. One adverse event was reported (minor skin irritation that resolved after changing the smartwatch band to a hypoallergenic watch band).

CONCLUSIONS: Within this clinical program, pairing a smartwatch with virtual health coaching for veterans with GWI was feasible and acceptable. Activity monitoring integrated into an existing intervention may support symptom self-management and augment patient education and engagement. As no prior activity monitoring programs specific to veterans with GWI have been described, these findings could inform future program development and implementation within this population.},
}

Humans
*Veterans/statistics & numerical data/psychology
*Persian Gulf Syndrome/therapy
Male
Qualitative Research
Middle Aged
Female
Adult
Feasibility Studies
United States

@article {pmid41860208,
year = {2026},
author = {Pirdankar, OH and Nene, AS and Thakur, R and Shah, S and Shenoy, P and Badole, P},
title = {Intravitreal Anti-vascular Endothelial Growth Factor in Retinopathy of Prematurity: A Bibliometric Analysis.},
journal = {Journal of pediatric ophthalmology and strabismus},
volume = {},
number = {},
pages = {1-10},
doi = {10.3928/01913913-20251106-02},
pmid = {41860208},
issn = {1938-2405},
abstract = {Retinopathy of prematurity (ROP) is one of the leading cause of blindness in premature infants. A bibliometric analysis on intravitreal anti-vascular endothelial growth factor (VEGF) in ROP was conducted. A comprehensive search of the article on the Scopus database was conducted with the terms related to "anti-vascular endothelial growth factor and retinopathy of prematurity." Only original research and review articles published in the English language were considered. VOSviewer version 1.6.20 was used for the visualization and analysis of the data. Publication trend, productive countries, researchers' details, commonly cited documents, source and influential journals, and keyword occurrence were analyzed. A total of 329 studies were considered, of which 270 were original articles and 59 were review articles. The highest numbers of publications were seen in the year 2022. The United States, China, Turkey, India, and Taiwan were the top 5 countries that published research on the use of anti-VEGF in ROP. The most documents were published by Wei-Chi Wu (22) and Chi-Chun Lai (14), and Falavarjani et al's article had the most citations (737). A total of 2,504 keywords were identified. All keyword analysis revealed the occurrence of "retinopathy of prematurity" and "human" as a keyword was 290 and 286 times, respectively. Most articles and citations were found in Retina. The use of anti-VEGF in ROP is constantly evolving and bibliometric analysis highlights a research trend and influential authors and journals that have published significant work on it. This article can serve as a guide to conduct a literature review for future researchers.},
}

@article {pmid41860259,
year = {2026},
author = {Burt-Oberecken, N and Megat, S and Rouaux, C},
title = {[Protective effect of a CREB3 gain-offunction variant in amyotrophic lateral sclerosis].},
journal = {Medecine sciences : M/S},
volume = {42},
number = {3},
pages = {234-237},
doi = {10.1051/medsci/2026027},
pmid = {41860259},
issn = {1958-5381},
}

@article {pmid41860888,
year = {2026},
author = {Bao, S and Bajet, A and Martínez, R and Müller-Trede, J and Engeler, I and Hafenbrädl, S},
title = {Commentary: On the Equal-Opportunity Jerk "Defense": Rudeness Complicates Sexism Attributions but Comes at a Cost.},
journal = {Psychological science},
volume = {},
number = {},
pages = {9567976261418939},
doi = {10.1177/09567976261418939},
pmid = {41860888},
issn = {1467-9280},
abstract = {Sexism is a pervasive and persistent problem. In their 2022 article "The 'Equal-Opportunity Jerk' Defense: Rudeness Can Obfuscate Gender Bias" (Psychological Science, Vol. 33, pp. 397-411), Belmi et al. argued that sexism can be obfuscated and go unpunished if perpetrators also act rudely toward men: the "equal-opportunity jerk defense." We introduce a simple Bayesian model that accounts for Belmi et al.'s findings and corroborated their predictions and implications in five preregistered experiments (N = 6,968 U.S. adults recruited via Prolific). We replicated that being rude toward men decreased perceived sexism but importantly found that it came at the cost of increased punishment (Study 1). Moreover, rudeness primarily decreased actors' perceived sexism, whereas their actions were still perceived as sexist (Study 2). Sexism ratings were sensitive to prior beliefs about the prevalence of sexism and to the diagnosticity of observed sexist behavior (Supplementary Studies S1-S2), in line with a broader Bayesian perspective. Bias in sexism ratings thus need not implicate fallacious cognitive processes or an "illusion of gender blindness."},
}

@article {pmid41861112,
year = {2026},
author = {Fu, P and Zhang, X and Zhou, Y and Zheng, J and Sun, A and Zhuang, K and Bao, W and Gao, G},
title = {Embedded CRISPRi Enhances Gene-Silencing Efficiency in Drosophila.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e15849},
doi = {10.1002/advs.202515849},
pmid = {41861112},
issn = {2198-3844},
support = {32500494//National Natural Science Foundation of China/ ; 32370631//National Natural Science Foundation of China/ ; //priority academic program development of jiangsu higher education institutions/ ; },
abstract = {CRISPR interference (CRISPRi), leveraging catalytically inactive Cas9 (dCas9), has transformed transcriptional silencing. However, its application in Drosophila melanogaster has been constrained by inconsistent efficiency and limited repression amplitude. Here, we present embedded CRISPR interference (emCRISPRi), an advanced gene-silencing platform that integrates transcriptional repression domains (Mxi and TRD) into a structurally flexible region of dCas9. This design significantly enhances silencing efficiency, enabling robust repression of coding genes and cis-regulatory elements, particularly at transcription start site (TSS)-proximal regions. emCRISPRi demonstrates improved gene-silencing activity compared to RNA interference (RNAi) at several tested loci and facilitates strong phenotypic rescue via unmodified cDNA. Its versatility is demonstrated through the dissection of Hippo pathway interactions and the mitigation of TDP-43-induced neurotoxicity in an amyotrophic lateral sclerosis (ALS) model. These findings position emCRISPRi as a transformative tool for functional genomics, enhancer studies, and disease modeling in Drosophila, with significant potential for cross-species adaptation and therapeutic innovation.},
}

@article {pmid41861506,
year = {2026},
author = {Oka, S and Yamazaki, T and Takefuji, Y},
title = {Breaking the spline: Why distributed lag non-linear models miss thresholds in environmental psychiatry.},
journal = {Psychiatry research},
volume = {360},
number = {},
pages = {117104},
doi = {10.1016/j.psychres.2026.117104},
pmid = {41861506},
issn = {1872-7123},
abstract = {This critique evaluates Monti et al.'s investigation into associations between air pollution, apparent temperature, and schizophrenia severity. While their findings indicate significant short‑ and medium‑term effects of PM10 and thermal stress on PANSS scores, several methodological limitations warrant caution. Their study relies on residential exposure assignments, which may not capture individual mobility or indoor environments, potentially introducing substantial exposure misclassification. Despite appropriately modeling delayed and non-linear effects, the DLNM's reliance on predefined spline structures may oversimplify the complex, synergistic interactions among atmospheric variables. Seasonal discrepancies-such as the absence of PM10 effects in autumn-winter-may reflect unmodeled dependencies or limited pollutant data, particularly for PM2.5 and black carbon. To address these constraints, future research should incorporate flexible, data‑driven approaches, particularly those capable of uncovering latent structures within environmental mixtures. Unsupervised feature‑clustering methods can identify correlated pollutant groupings and reduce dimensional noise, while rank‑based correlation metrics provide robust assessment of non‑linear dependencies that are often obscured by parametric spline specifications. These non‑parametric techniques can complement DLNM by capturing multivariate synergies and interaction patterns that rigid basis structures may overlook. Overall, integrating such approaches is essential for advancing analytical capacity and improving risk assessment for vulnerable psychiatric populations.},
}

@article {pmid41851044,
year = {2026},
author = {Takeda, T and Ishikawa, A and Kokubun, S and Saito, Y and Isose, S and Ito, K and Arai, K and Kuwabara, S and Honda, K},
title = {Reduced nuclear TDP-43 and cytoplasmic DLK1 as markers of motor neuron degeneration in amyotrophic lateral sclerosis.},
journal = {Journal of neuropathology and experimental neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnen/nlag017},
pmid = {41851044},
issn = {1554-6578},
abstract = {Loss of upper and lower motor neurons (MNs) is a defining pathological feature underlying the clinical manifestations of amyotrophic lateral sclerosis (ALS). However, the differences in MN loss and TDP-43 pathology between these areas in ALS patients remain unclear. This study included 7 patients with ALS and 3 controls from consecutive autopsies. The cell density and regional density of TDP-43-positive inclusions in 4 upper MN areas and their anatomically corresponding lower MN areas were measured. The numbers of large cells with loss of nuclear TDP-43 and cytoplasmic delta-like-1 homolog (DLK1) were counted. The results showed severe MN loss in both upper and lower MN areas. However, TDP-43-positive inclusions differed markedly, that is they were rare in upper MNs but abundant in lower MN. In upper MN areas, TDP-43 density was not associated with the residual rate of MNs, whereas in lower MN areas, the density in MNs was associated with the cell residual rate. Significantly higher numbers of MNs lacking nuclear TDP-43 and cytoplasmic DLK1 were observed in the upper and lower MN regions in ALS vs controls. These findings suggest that these morphological changes may be closely related to motor neuron vulnerability and may be mechanistic contributors to ALS development.},
}

@article {pmid41851249,
year = {2026},
author = {Leinders, S and Aarnoutse, EJ and Branco, MP and Freudenburg, ZV and Geukes, SH and Schippers, A and Verberne, MSW and van den Boom, MA and van der Vijgh, BH and Crone, NE and Denison, T and Ramsey, NF and Vansteensel, MJ},
title = {Implanted brain-computer interface functionality during nighttime in late-stage amyotrophic lateral sclerosis.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-44228-7},
pmid = {41851249},
issn = {2045-2322},
support = {UH3NS114439/NS/NINDS NIH HHS/United States ; ADV 320708/ERC_/European Research Council/International ; UGT7685//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; U01DC016686/DC/NIDCD NIH HHS/United States ; },
abstract = {Brain-computer interfaces (BCIs) hold promise as assistive communication technology for people with severe paralysis. Although such BCIs should be available 24/7, feasibility of nocturnal BCI use has not been investigated. Here, we addressed this question using data from an electrocorticography-BCI user with amyotrophic lateral sclerosis. We investigated nocturnal dynamics of neural signal features used for BCI control. Additionally, we assessed nocturnal performance of a decoder trained on daytime data, by quantifying the number of unintentional BCI activations at night. Finally, we developed a nightmode functionality and assessed its performance. Mean and variance of low and high frequency band power were significantly higher at night than during the day. When applied to night data, daytime decoders caused unintentional BCI activations in 100% of nights (245 unintended click-commands and 13 unintended caregiver-calls per hour). The specifically developed nightmode functionality, however, functioned error-free in 79% of nights over a period of ± 1.5 years, allowing the user to reliably call the caregiver. Reliable nighttime use of a BCI requires strategies to adjust to circadian and sleep-related signal changes. This demonstration of a reliable nightmode and its long-term use by an individual with amyotrophic lateral sclerosis underscores the importance of 24/7 BCI reliability.},
}

@article {pmid41851271,
year = {2026},
author = {Hodgson, RE and Huang, WP and Lang, R and Kumar, V and An, H and Stender, EGP and Chalakova, ZP and Driver, MD and Sanchez Avila, A and Ellis, BCS and Day, E and Rayment, JA and Baeg, K and Strange, A and Moll, T and Wright, GSA and van Vugt, JJFA and , and Allen, SP and Locker, N and Pitout, I and Fletcher, S and Onck, PR and Duss, O and Cooper-Knock, J and Shelkovnikova, TA},
title = {Paraspeckle condensation is controlled via TDP-43 polymerization and linked to neuroprotection.},
journal = {Nature cell biology},
volume = {},
number = {},
pages = {},
pmid = {41851271},
issn = {1476-4679},
support = {MR/W004615/1//Research Councils UK (RCUK)/ ; MR/W028522/1//RCUK | Medical Research Council (MRC)/ ; BB/V014110/1//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; PhD studentship//Motor Neurone Disease Association (MNDA)/ ; 969-799//Motor Neurone Disease Association (MNDA)/ ; PhD studentship//MND Scotland (Motor Neuron Disease Scotland)/ ; },
abstract = {The paraspeckle is a disease-relevant biomolecular condensate assembled from long non-coding RNA (lncRNA) NEAT1_2 ribonucleoprotein particles. Paraspeckle biogenesis is suppressed in normal tissues, yet it can be rapidly upregulated under stress. Here we demonstrate that a neurodegeneration-linked RNA-binding protein TDP-43 inhibits NEAT1_2 ribonucleoprotein particle condensation into the paraspeckle, in a concentration-dependent manner, which requires its intact polymerization and RNA binding. This effect is counterbalanced by core paraspeckle proteins such as FUS. Below disruptive concentrations, TDP-43 can be recruited into paraspeckles, forming non-liquid clusters. Under stress, TDP-43 sequestration into de novo nuclear condensates alleviates paraspeckle suppression and increases their dynamism. NEAT1_2 middle-part and 3'-end UG repeats mediate paraspeckle regulation by TDP-43 cotranscriptionally and post assembly, respectively. The deletion of the 3'-end UG repeat increases paraspeckle stability and cytoprotection in stressed human neurons. Consistently, longer 3'-end UG repeats are linked to shorter survival in the neurodegenerative disease amyotrophic lateral sclerosis. Thus, TDP-43 is a critical regulator of paraspeckle condensates linked to cytoprotection.},
}

@article {pmid41851470,
year = {2026},
author = {Michaelis, T and Lindestam Arlehamn, CS and Johansson, E and Frazier, A and Williams, GP and Berry, JD and Cudkowicz, M and Goyal, NA and Fournier, C and Snyder, A and Kwan, JY and Crook, J and Phillips, EJ and Mallal, SA and Ravits, J and Marder, KS and Sidney, J and Sulzer, D and Sette, A},
title = {Author Correction: Autoimmune response to C9orf72 protein in amyotrophic lateral sclerosis.},
journal = {Nature},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41586-026-10388-9},
pmid = {41851470},
issn = {1476-4687},
}

@article {pmid41852184,
year = {2026},
author = {Gagliardi, D and Villella, C and Zanovello, M and Iacobelli, V and Corti, S and Comi, GP and Fratta, P and Houlden, H and Tucci, A and Ronchi, D},
title = {High Prevalence of SOD1 Pathogenic Variants in the UK Biobank: Implications for Early Intervention in Amyotrophic Lateral Sclerosis.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78195},
pmid = {41852184},
issn = {1531-8249},
support = {//Italian Ministry of Health/ ; MR/Z506503/1//UK Medical Research Council/ ; MR/S006753/1//UK Medical Research Council/ ; },
abstract = {OBJECTIVE: SOD1 is the second most frequently mutated gene in European patients with amyotrophic lateral sclerosis (ALS). Given the recent authorization of SOD1-targeted antisense oligonucleotides for SOD1-ALS, prompt screening for SOD1 mutations in patients with ALS patients is highly recommended. Large-scale genomic analysis could inform on the population-based prevalence of SOD1 mutation carriers, who would potentially benefit from treatment. We aim to determine the number of people with pathogenic SOD1 variants in the UK Biobank (UKB), to address a critical gap between clinical and genetic prevalence of SOD1-ALS.

METHODS: We analyzed SOD1 variants within exome sequencing data from 470,000 individuals aged over 40 years. Pathogenicity was evaluated using referenced databases and American College of Medical Genetics and Genomics (ACMG) guidelines. Leveraging the UKB carrier frequency and age at onset data, we estimated the genetic prevalence of SOD1-ALS. We examined factors that may influence penetrance.

RESULTS: We identified 122 individuals with monoallelic SOD1 coding variants, 93.4% of whom were asymptomatic. Additionally, the low-penetrance p.Asp91Ala variant was observed in heterozygosis in 535 subjects, whereas it was never found in homozygosis. Excluding this variant, the expected number of people developing SOD1-ALS is 1.04:100,000 in the UK population, 4 times higher than clinically reported figures. Symptomatic carriers had significantly increased levels of serum neurofilament at baseline. Age-related penetrance was higher in non-p.Asp91Ala carriers versus p.Asp91Ala carriers. Long-term survivor status was associated with p.Asp91Ala genotype, older age, and lower neurofilament levels.

INTERPRETATION: Incomplete and age-related penetrance, along with underascertainment due to disease heterogeneity and limitations in data collection, likely account for the reduced number of symptomatic patients identified. Our findings highlight the need to identify genetic and environmental factors, as well as biological indicators, able to influence disease penetrance and phenoconversion risk in presymptomatic carriers and to predict treatment response in patients. ANN NEUROL 2026.},
}

@article {pmid41852280,
year = {2026},
author = {Isik, FI and Pickford, R and Timmins, HC and Piguet, O and Halliday, GM and Kiernan, MC and Kim, WS},
title = {Systemic dysregulation of apolipoproteins in amyotrophic lateral sclerosis serum.},
journal = {FEBS open bio},
volume = {},
number = {},
pages = {},
doi = {10.1002/2211-5463.70232},
pmid = {41852280},
issn = {2211-5463},
support = {IM-202303-00957//FightMND/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron degeneration. Increasing evidence implicates systemic lipid perturbation in ALS pathogenesis. However, the extent and nature of apolipoprotein changes underlying lipid perturbations in ALS remain largely unknown. To address this, we performed a comprehensive analysis of major apolipoproteins involved in lipid metabolism and examined their association with lipoprotein membrane lipids in sporadic ALS (n = 32) and age-matched healthy controls (n = 32), using ELISA and liquid chromatography-mass spectrometry. Compared with controls, serum levels of apoB, apoCI, apoCII, apoCIII and apoE were significantly elevated in ALS, whereas apoAI and apoAII were unchanged. Distributional analyses demonstrated a relative decrease in apoAI and an increase in apoB in ALS, resulting in an elevated apoB/apoAI ratio, a marker of atherogenic risk, alongside a reduced apoAI/apoE ratio. Correlation analyses revealed strengthened interrelationships among apolipoproteins in ALS, suggesting altered regulatory coordination. At the lipid level, phosphatidylcholine (PC) was increased, whereas sphingomyelin (SM) was reduced in ALS serum. Notably, the strong associations of apoB to both PC and SM observed in controls were absent in ALS. Biomarker analyses identified apoE as the strongest discriminator between ALS and control groups. Collectively, these findings demonstrate a coordinated disruption of apolipoproteins and lipoprotein-associated lipids in ALS serum, with likely functional consequences for lipoprotein metabolism. This study provides new insights into lipid dysregulation in ALS pathobiology and supports the emerging view that ALS encompasses not only neurodegenerative processes but also systemic metabolic reprogramming.},
}

@article {pmid41852613,
year = {2026},
author = {Montesanti, S and Bradley, N and Demedeiros, S and McKay, R},
title = {Designing for implementation: a cognitive task analysis of intimate partner violence screening in hospital trauma care in Alberta, Canada.},
journal = {Frontiers in health services},
volume = {6},
number = {},
pages = {1743548},
pmid = {41852613},
issn = {2813-0146},
abstract = {BACKGROUND: Intimate partner violence (IPV) has serious health consequences, yet routine IPV screening remains inconsistently implemented in hospital trauma centres. Despite evidence supporting screening, implementation challenges persist. This study used Cognitive Task Analysis (CTA) to examine how trauma care providers perceive and enact IPV screening, with attention to cognitive processes, barriers, and facilitators to implementation.

METHODS: We conducted CTA group interviews with nine trauma care providers from two trauma centers in Edmonton, Alberta, Canada. Participants included trauma surgeons, nurse practitioners, social workers, and patient care managers. Using a structured interview guide and concept mapping techniques, we elicited knowledge structures, decision-making processes, and perceived constraints related to IPV screening. We applied an interpretive qualitative approach to uncover underlying themes related to cognitive work and task complexity. Grounded theory techniques, such as open and axial coding, were used in conjunction with CTA to analyze how participants reasoned through clinical scenarios. We paid close attention to how providers assessed cues, coordinated across roles, shifted priorities, and navigated organizational constraints. This hybrid approach allowed us to bridge systems-level implementation science with cognitive insights, drawing conceptually on CFIR and Proctor et al.'s implementation outcomes to generate actionable knowledge for IPV screening interventions in trauma care settings.

RESULTS: Themes were synthesized into six overarching cognitive domains: trauma care workflow, team collaboration and knowledge, critical situations and decision-making, IPV screening practices and challenges, understanding patient experiences, and institutional support. These were further illustrated through refined concept maps that visually represented participants' mental models, task sequences, and decision-making strategies.

CONCLUSION: Trauma care providers are well-positioned to identify IPV, yet screening is constrained by limited institutional support, unclear procedures, and poor integration into trauma workflows. Findings highlight the need for system-level strategies that align IPV screening with the cognitive and organizational realities of trauma care. By applying CTA, this study informs the design and implementation of context-sensitive IPV screening interventions that are more acceptable, appropriate, and feasible in hospital trauma settings. Furthermore, this study informs implementation strategies for integrating IPV screening interventions into trauma care, with particular implications for improving the acceptability, appropriateness, feasibility, and sustainability of evidence-based practices.},
}

@article {pmid41853322,
year = {2026},
author = {Elshaer, A and Thomas, L},
title = {Investigating inequality in Advanced Life Support courses: a retrospective, single-centre, survey-based pilot study.},
journal = {Resuscitation plus},
volume = {28},
number = {},
pages = {101283},
pmid = {41853322},
issn = {2666-5204},
abstract = {BACKGROUND: With more International Medical Graduates (IMGs) joining the United Kingdom's medical workforce, the demand for Advanced Life Support (ALS) courses has increased. Whilst differential attainment among IMGs is well-documented, little is understood about this phenomenon in ALS courses. This study explores the relationship between ALS course participants' background and course outcomes.

METHODS: Doctors who attended ALS courses at a UK course centre were retrospectively recruited to participate in a 28-question online survey about their language, education and clinical backgrounds, as well as their ALS course experience and outcomes. Quantitative and qualitative analyses were carried out, and recommendations were thematically summarised.

RESULTS: Of 419 invited healthcare professionals, 38 doctors (9%) completed the survey. 27 (71.1%) of the respondents graduated outside the UK, 32 (84.2%) studied medicine in English, and 15 (39.5%) were native English speakers. Passing the Cardiac Arrest Simulation Tests (CAS-Test) was statistically associated with more previous scenario-based simulation experience. Thematic analysis of responses suggested that biased treatment, language barriers, communication anxiety, inadequate undergraduate training, vulnerability, rigid professionalism and psychological insecurity were obstacles to IMGs attaining course outcomes. Suggestions for improvement focused on enhancing course accessibility, learning materials, the educational environment, assessment, and faculty development.

CONCLUSIONS: This exploratory study investigates IMGs' self-reported challenges and proposes interventions to promote the inclusivity of ALS courses. Further prospective research is required to evaluate the nature and generalisability of these findings and the applicability of the offered recommendations.},
}

@article {pmid41853978,
year = {2026},
author = {Piotrowski, SL and Allnutt, MA and Johnson, K and Tanaka, T and Ferrucci, L and Morris, H and Hardy, J and , and Ryten, M and , and Logroscino, G and Troncoso, J and Beach, TG and Serrano, GE and Cruchaga, C and Dickson, DW and Ross, OA and Chiò, A and , and , and Houlden, H and , and Dalgard, CL and Ding, J and Gibbs, JR and Traynor, BJ and Scholz, SW and Jacobson, S},
title = {Herpesvirus genome integration in whole-genome sequences of dementia and control cohorts.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71047},
doi = {10.1002/alz.71047},
pmid = {41853978},
issn = {1552-5279},
support = {1ZIAAG000935/AG/NIA NIH HHS/United States ; P30AG019610/AG/NIA NIH HHS/United States ; P30AG072980/AG/NIA NIH HHS/United States ; U24AG021886/AG/NIA NIH HHS/United States ; P50AG016574/AG/NIA NIH HHS/United States ; U19AG071754/AG/NIA NIH HHS/United States ; R01AG087165/AG/NIA NIH HHS/United States ; U24 NS072026/NS/NINDS NIH HHS/United States ; 1ZIANS003154/NS/NINDS NIH HHS/United States ; U54-NS110435/NS/NINDS NIH HHS/United States ; P50NS072187/NS/NINDS NIH HHS/United States ; 211002//Arizona Department of Health Services/ ; 4001 0011 05-901//Arizona Biomedical Research Commission/ ; //Michael J. Fox Foundation for Parkinson's Research/ ; //Ted Turner and family/ ; //Little Family Foundation/ ; //Mayo Clinic Dorothy and Harry T. Mangurian Jr. Lewy body dementia program/ ; },
mesh = {Humans ; *Dementia/virology/genetics ; *Genome, Viral/genetics ; *Herpesvirus 6, Human/genetics ; *Virus Integration/genetics ; Cohort Studies ; Whole Genome Sequencing ; Aged ; Female ; Male ; *Herpesviridae/genetics ; Alzheimer Disease/virology/genetics ; },
abstract = {INTRODUCTION: The infectious hypothesis suggests that microbes like herpesviruses may play a role in the pathogenesis of Alzheimer's disease (AD) and other related dementias through methods that may include viral genome integration. The occurrence of herpesvirus genome integration in dementia patients has not been thoroughly characterized.

METHODS: Over 7500 total whole-genome sequences from control, frontotemporal dementia/amyotrophic lateral sclerosis spectrum, Lewy body dementia (LBD), multiple system atrophy (MSA), and AD cohorts were screened for the integration of pathogen genomes using the PathSeq computational tool.

RESULTS: Low PathSeq scores for human herpesvirus 6 (HHV-6) were consistent with the suspected integration of viral genome segments. The LBD and MSA cohorts had a significantly higher prevalence of this partial HHV-6 genome integration.

DISCUSSION: This higher prevalence in both synucleinopathies was not noted in other herpesviruses, suggesting that the integration of HHV-6 may play a role in a subset of these patients.

HIGHLIGHTS: Over 7500 whole-genome sequences from controls and dementia patients were analyzed. Sequences consistent with integrated herpesviruses were identified using PathSeq. Prevalence of partial HHV-6 integration was higher in synucleinopathies. Herpesviruses genome integration may play a role in subsets of dementia patients.},
}

Humans
*Dementia/virology/genetics
*Genome, Viral/genetics
*Herpesvirus 6, Human/genetics
*Virus Integration/genetics
Cohort Studies
Whole Genome Sequencing
Aged
Female
Male
*Herpesviridae/genetics
Alzheimer Disease/virology/genetics

@article {pmid41854033,
year = {2026},
author = {Fragkoudi, A and Stern, C and Pollock, D and Barker, TH and Semendric, I and Labra, J and Vucic, S and Whitehouse, J and Munn, Z},
title = {Identifying priorities for a national motor neurone disease (amyotrophic lateral sclerosis) guideline: results from an Australian online survey.},
journal = {Disability and rehabilitation},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/09638288.2026.2643544},
pmid = {41854033},
issn = {1464-5165},
abstract = {PURPOSE: To identify the priorities of people living with motor neurone disease (MND), their carers, asymptomatic genetic carriers, and healthcare professionals (HCPs) in Australia, to inform the development of a national MND care guideline.

METHODS: An anonymous online survey was distributed via MND organisations and groups to the Australian MND community.

RESULTS: Two hundred and fourteen individuals completed the survey. Of those, 44.8% (n = 96) were HCPs, with the remaining consisting of people living with MND, genetic carriers, and carers. The following areas were rated as extremely important and should be included in the guideline: diagnosis, service delivery models, clinical care management, caregiver support, and palliative care; while views on genetic testing and cognitive assessment were mixed. Participants highlighted a need for holistic care which considered emotional/psychological and physical aspects of MND. People with MND and their carers want the Australian MND care guideline to highlight proactive and coordinated support prioritising quality of life, while maintaining independence for as long as possible.

CONCLUSIONS: Identifying priorities is a fundamental step that will shape the forthcoming Australian MND care guideline. This methodology ensures the voices of those with lived experience and interest holders are incorporated from the outset.},
}

@article {pmid41854301,
year = {2026},
author = {Walker, TB and Trowbridge, JW and McMahon, S and Marzano, NR and Rice, L and Yerbury, JJ and Ecroyd, H and McAlary, L},
title = {Small heat shock proteins HspB1 and HspB5 differentially alter the condensation and aggregation of the TDP-43 low-complexity domain.},
journal = {Protein science : a publication of the Protein Society},
volume = {35},
number = {4},
pages = {e70539},
doi = {10.1002/pro.70539},
pmid = {41854301},
issn = {1469-896X},
support = {//Motor Neurone Disease Australia/ ; //FightMND/ ; APP1194872//National Health and Medical Research Council/ ; },
mesh = {Humans ; *DNA-Binding Proteins/chemistry/metabolism/genetics ; Protein Aggregates ; *HSP27 Heat-Shock Proteins/metabolism/chemistry/genetics ; *alpha-Crystallin B Chain/metabolism/chemistry/genetics ; Molecular Chaperones/metabolism ; Protein Domains ; Phosphorylation ; Heat-Shock Proteins ; },
abstract = {TAR DNA-binding protein 43 (TDP-43) is a nucleic acid-binding protein that regulates processes of mRNA metabolism, during which it undergoes condensation mediated by its C-terminal low-complexity domain (TDP-43[LCD]). TDP-43 aggregation and condensation are associated with neurodegenerative disease. However, the proteostasis mechanisms that regulate these processes remain elusive. Some evidence has shown that the molecular chaperone small heat shock protein HspB1 binds to and regulates the cytoplasmic phase separation of TDP-43, indicating that other small heat shock proteins may have similar effects. Here, we demonstrate divergent behaviors for HspB1 and its homolog HspB5 on TDP-43[LCD] condensation and aggregation. In addition to inhibiting TDP-43[LCD] aggregation, HspB1 partitions into TDP-43[LCD] condensates and increases the dynamic exchange of TDP-43[LCD] within condensates and with the surrounding solution. Phosphorylation-mimicking mutations within HspB1 enhance these effects. HspB5 inhibits TDP-43[LCD] aggregation more effectively than HspB1 and partitions into TDP-43[LCD] condensates, where it delays the pathological transition of the condensate to a gel/solid. We identify the N- and C-terminal regions of HspB1 and HspB5 to be crucial for the chaperone effects, and highlight the role of sequence diversity within these regions in defining small heat shock protein function. These findings demonstrate that HspB1 and HspB5 are regulators of TDP-43 phase separation and aggregation and may be potential therapeutic targets in mitigating toxic TDP-43 aggregation in neurodegenerative disease.},
}

Humans
*DNA-Binding Proteins/chemistry/metabolism/genetics
Protein Aggregates
*HSP27 Heat-Shock Proteins/metabolism/chemistry/genetics
*alpha-Crystallin B Chain/metabolism/chemistry/genetics
Molecular Chaperones/metabolism
Protein Domains
Phosphorylation
Heat-Shock Proteins

@article {pmid41854370,
year = {2026},
author = {Morojele, NK and London, L and Saban, A and Myers, B and Harker, N and Mokwena, K and Zingela, Z and Nkosi, S and Ayieko, P and Kapiga, S},
title = {Implications of COVID-19 Restrictions on the Ethics and Methods of a Multi-Site Study on Alcohol and Other Drug (AOD) Use Treatment among Men in South Africa.},
journal = {Journal of empirical research on human research ethics : JERHRE},
volume = {},
number = {},
pages = {15562646261427563},
doi = {10.1177/15562646261427563},
pmid = {41854370},
issn = {1556-2654},
abstract = {Public health measures for medical emergencies generate methodological and ethical challenges for human research. Using Emanuel et al.'s framework, we assessed the ethical integrity of the research methods used in a men's alcohol and other drug (AOD) use disorder study following their revision due to COVID-19 restrictions in South Africa. Following the amendments, the study's social value, favorable risk-benefit ratio, and respect for participants increased. Collaborative partnership, scientific validity, fair participant selection, independent review, and informed consent improved in terms of successful stakeholder engagements and interviewing procedures, but were compromised due to a cellphone access eligibility criterion and complicated consenting procedures. Methodological and ethical challenges of research during health emergencies can be navigated with flexibility and innovation.},
}

@article {pmid41854409,
year = {2026},
author = {Shukla, A and Upadhyay, A and Qadeer, M and Thakur, AD and Raj, R},
title = {Eco-friendly Immersion-Coating Strategy for Scalable and Durable Superhydrophobic Aluminum Surfaces.},
journal = {Langmuir : the ACS journal of surfaces and colloids},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.langmuir.5c05945},
pmid = {41854409},
issn = {1520-5827},
abstract = {Superhydrophobic (SHPB) surfaces have strong potential to mitigate corrosion, fouling, and icing, yet conventional fabrication methods rely on fluorinated modifiers, toxic reagents, or multistep protocols that limit scalability and conformal coverage on complex geometries. Here, we report an eco-friendly, scalable, and fluorine-free immersion-coating strategy for developing SHPB aluminum (SHPB-Al) surfaces using an ionic liquid (IL, 1-ethyl-3-methylimidazolium chloride) and lauric acid (LA) as nontoxic precursors. The central novelty lies in generating the requisite hierarchical roughness via an ionic liquid adsorption-driven surface modification mechanism, rather than through conventional material-removal or etching processes, thereby minimizing substrate damage and preserving structural integrity. Specifically, the two-step protocol first forms an IL-derived adsorbed substrate layer that induces hierarchical topography and hydrophilicity, followed by lauric acid functionalization to reduce surface energy and induce superhydrophobicity. Systematic optimization of the precursor concentration and dip duration identifies an optimum condition that achieves a static contact angle (SCA) of ≈165° with contact angle hysteresis (CAH) of <5°. Microscopy and surface analyses confirm the presence of hierarchical textures and robust chemical grafting. Durability tests under harsh chemical, thermal, mechanical, and environmental conditions reveal minimal performance loss (SCA > 150° and CAH < 10°), underscoring the coating's reliability. Droplet dynamics exhibit ≥15 successive rebounds, a coefficient of restitution of ≈0.9, and contact times as short as ≈10 ms, demonstrating ultralow adhesion. Building on these insights, we introduce an improvised one-step IL-LA codeposition method that simplifies the fabrication route while retaining high performance (SCA of ≈160° and CAH of ≈5°) and prolonged durability under environmental exposure. Together, this fluorine-free immersion-coating framework offers durable, scalable, and nontoxic routes for producing SHPB-Als, enabling conformal coatings on complex geometries such as heat-exchanger fins and paving the way for industrial deployment in harsh service environments.},
}

@article {pmid41854827,
year = {2026},
author = {Calvache Anaya, JA and Urdiales Merino, A and Druetta, NN and Sanz Rigo, M and Cardona Monjo, AM},
title = {Nonlinear and Asymmetric Refractive Sensitivity to Effective Lens Position Errors in Pseudophakic Eye Models.},
journal = {Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {},
number = {},
pages = {},
pmid = {41854827},
issn = {1475-1313},
abstract = {PURPOSE: To perform a theoretical analysis of refractive sensitivity to effective lens position (ELP) errors in pseudophakic eyes using an explicit vergence-based optical model, and to quantify how this sensitivity depends on axial length (AL) and corneal power across a wide biometric range.

METHODS: A paraxial two-lens thin-lens model of the pseudophakic eye was developed, explicitly parameterised by AL, total corneal power (TCP), intraocular lens (IOL) power and effective lens position (ELP). Refraction was calculated at the corneal plane using vergence propagation. For a fixed reference ELP, the emmetropic IOL power was derived analytically for each combination of AL and TCP, and subsequently held constant while ELP was perturbed by ±1.0 mm. Simulations were performed for ALs from 19 to 31 mm and corneal powers from 38 to 50 dioptres. Refractive changes were approximated using families of quadratic regression models as functions of AL.

RESULTS: Refractive sensitivity to ELP errors was dominated by AL. Short eyes exhibited large refractive changes per millimetre of ELP error, whereas long eyes showed markedly reduced sensitivity. The relationship between refractive error and ELP displacement was nonlinear, resulting in asymmetric refractive effects for equal-magnitude anterior and posterior ELP deviations. TCP continuously modulated refractive sensitivity indirectly through its influence on the emmetropic IOL power required for a given optical configuration.

CONCLUSIONS: Refractive sensitivity to ELP errors in pseudophakic eye models is inherently nonlinear and asymmetric. This sensitivity is primarily governed by AL, with TCP acting as a secondary but systematic modulator through its effect on emmetropic IOL power. By explicitly separating optical sensitivity from ELP prediction, this vergence-based framework provides a physical basis for understanding ELP-related refractive variability across the biometric spectrum.},
}

@article {pmid41856038,
year = {2026},
author = {Nguyen, L},
title = {Repeat expansion RNA elicits toxicity through hybrid G-quadruplexes with promoter DNA.},
journal = {Neuron},
volume = {114},
number = {6},
pages = {969-971},
doi = {10.1016/j.neuron.2026.02.018},
pmid = {41856038},
issn = {1097-4199},
mesh = {*G-Quadruplexes ; Humans ; *Promoter Regions, Genetic/genetics ; C9orf72 Protein/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; *DNA Repeat Expansion/genetics ; *RNA/genetics ; *DNA/genetics ; *Proteins/genetics ; },
abstract = {In this Neuron issue, Liu et al.[1] show that the C9orf72 expanded G4C2 repeat RNA forms hybrid G-quadruplexes with CG-rich promoter regions, which impedes RNA polymerase II. This process causes global transcriptional dysregulation in C9orf72 amyotrophic lateral sclerosis patient-derived cells.},
}

*G-Quadruplexes
Humans
*Promoter Regions, Genetic/genetics
C9orf72 Protein/genetics
*Amyotrophic Lateral Sclerosis/genetics
*DNA Repeat Expansion/genetics
*RNA/genetics
*DNA/genetics
*Proteins/genetics

@article {pmid41856386,
year = {2026},
author = {Sadler, SM and Volker, DK and Garguilo, D and Gould, D},
title = {An Analysis of United States Olympic and Paralympic Committee National Governing Body Policies Related to Body Pressures, Body Image Concerns, and Eating Pathology.},
journal = {Psychology of sport and exercise},
volume = {},
number = {},
pages = {103124},
doi = {10.1016/j.psychsport.2026.103124},
pmid = {41856386},
issn = {1878-5476},
abstract = {Athletes are often exposed to body pressures in sport environments, which can contribute to body image concerns and eating pathology, with lasting consequences for performance and well-being. Although research has highlighted the harmful impacts of these concerns, and has called for a broader investigation into the sources of athletes' experiences of these concerns, little is known about the role of sport organizations in influencing athletes' body pressures, body image concerns, and eating pathology. Using a descriptive qualitative research design within a post-positivist paradigmatic approach, the current study explored the frequency and content of body- and eating-related policies within the United States Olympic & Paralympic Committee's (USOPC) 51 national governing bodies, examining differences in policy frequency and content by sport type. National governing body websites were searched for policy documents aligned with Viollet et al.'s (2023) definition of sport policy. Following reflexive content analysis (Nicmanis, 2024) of 156 body- and eating-related policies, five overarching categories were identified: (a) uniform requirements, (b) athlete body image and nutrition-related supports, (c) organizational strategies to prevent body- and eating-related concerns, (d) body- and eating-related maltreatment, and (e) athletes' responsibilities related to nutrition and body weight. Findings highlight the inconsistent and often vague nature of existing national governing body policies, underscoring the need for standardized and comprehensive policies. Practical recommendations include developing both proactive and reactive body- and eating-related policies, providing clear and specific guidance, and critically examining gendered appearance standards communicated through policy to create a more inclusive sport culture that reduces athletes' experiences of body pressures, body image concerns, and eating pathology.},
}

@article {pmid41845095,
year = {2026},
author = {Gurunandan, K and Greve, A and Wilmot, E and Henson, RN},
title = {Does signed prediction error drive declarative memory? Evidence from variable choice paradigms.},
journal = {Memory & cognition},
volume = {},
number = {},
pages = {},
pmid = {41845095},
issn = {1532-5946},
support = {EP/Y016815/1//Engineering and Physical Sciences Research Council/ ; SUAG/046/G101400/MRC_/Medical Research Council/United Kingdom ; POS_2023_2_0034//Eusko Jaurlaritza/ ; },
abstract = {Prediction error (PE) is the discrepancy between predictions and new information. For a binary reward outcome, PE may be signed (positive if the outcome was better than predicted and negative if the outcome was worse than predicted) or unsigned (absolute value of "surprise"). Using a "variable choice" paradigm, De Loof et al. (PLOS ONE, 131, Article e0189212, 2018) examined the role of PE in one-shot learning of unknown translations of known words and showed that associative memory for the translation was greater when (financial) reward was more unexpected and lesser when an expected reward was not received (i.e., signed PE); an effect that they replicated in several subsequent studies. However, other work on PE in declarative memory has assumed that memory is greater when an outcome is more unexpected, without any explicit reward (i.e., unsigned PE). We replicated De Loof et al.'s paradigm with and without financial reward, and found that memory was explained slightly better by unsigned PE (Experiments 1A-1B). However, we also identified a potential confound in the paradigm that could explain the results without any role of PE, as confirmed by simulations. We therefore designed a modified version of the paradigm that circumvents this confound (Experiment 2). Results were inconsistent with the PE account. We conclude that variable choice paradigms may not be well-suited to investigate the role of PE in one-shot declarative learning, and that the purported role of signed PE in declarative memory requires further investigation.},
}

@article {pmid41845971,
year = {2026},
author = {Dahlhaus, R and Braun, RJ},
title = {The role of TDP-43 fragments in regular cellular functions and homeostatic failure.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107349},
doi = {10.1016/j.nbd.2026.107349},
pmid = {41845971},
issn = {1095-953X},
abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of motor neurons, leading to severe muscle weakness, loss of voluntary movement, and respiratory failure. A widely noted feature of the disease is the presence of TDP-43 proteinopathies. Under homeostatic conditions, the RNA/DNA-binding protein TDP-43 mainly resides in the nucleus, where it functions to regulate gene expression, controlling not only RNA transcription and splicing, but also stability and transport to the cytoplasm. Upon the arrival at ribosomes, TDP-43 may further moderate translation, acting as a global repressor of protein synthesis. However, in over 95% of ALS cases, TDP-43 mislocalies from the nucleus to the cytoplasm, where it enriches in cytoplasmic inclusions that are marked by the presence of misfolded, ubiquitinated, phosphorylated and fragmented protein species of TDP-43. Although recent studies have tried to untangle the relationship between TDP fragments on the one hand, and cytotoxicity as well as neurodegeneration on the other, the results are still a matter of debate. Here, we review our current understanding of the different TDP fragments derived from proteolytic cleavage as well as alternative splicing, addressing the different N-terminal and C-terminal species and evaluating differences in rodent and primate models. We focus our analysis on the potential homeostatic functions of TDP fragments in the context of viral infections and myelination control, which are potentially pivotally interconnected. The findings illustrate several facets of fragmented TDP-43 protein species in scenarios of enhanced cellular stress. Gaining a detailed understanding could help to reveal new treatment options for ALS and other TDP-43 proteinopathies.},
}

@article {pmid41846014,
year = {2026},
author = {Yang, L and Fan, W and Wang, Z and Wu, M and Chen, Y and Cheng, J and Zhou, F and Guo, Z},
title = {The role of IRF5 in Microglia-Mediated neuroinflammation in ALS.},
journal = {Neuroscience letters},
volume = {},
number = {},
pages = {138580},
doi = {10.1016/j.neulet.2026.138580},
pmid = {41846014},
issn = {1872-7972},
abstract = {The occurrence and development of amyotrophic lateral sclerosis (ALS) involve neuroinflammatory responses, in which microglial activation plays a critical role. IRF5, a key regulator of inflammatory responses, is implicated in the disease mechanisms of various conditions. However, its mechanism in ALS remains unclear. This study found that IRF5 expression was significantly increased in hSOD1-G93A transgenic ALS mice and cell models, primarily localized in activated microglia. Silencing IRF5 altered microglial polarization, suppressed the release of inflammatory factors, enhanced phagocytic function, and reduced motor neuron apoptosis in a co-culture system. Mechanistic studies suggested that IRF5 may regulate microglial function through the NF-κB signaling pathway. This study reveals the key role of IRF5 in microglia-mediated neuroinflammation and neuronal damage in ALS, indicating that targeting IRF5 could represent a promising treatment strategy for this disease.},
}

@article {pmid41846418,
year = {2026},
author = {Ahire, C and Yadav, R and Bhamare, UU and Kaur, G and Palkar, MB},
title = {From Refractory Epilepsy to Neurodegeneration: Emerging Mechanistic and Clinical Insights Into the Ketogenic Diet.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {40},
number = {6},
pages = {e71609},
doi = {10.1096/fj.202503317R},
pmid = {41846418},
issn = {1530-6860},
mesh = {*Diet, Ketogenic/methods ; Humans ; Animals ; *Neurodegenerative Diseases/diet therapy/metabolism ; *Drug Resistant Epilepsy/diet therapy/metabolism ; },
abstract = {The ketogenic diet (KD), a high-fat, low-carbohydrate intervention, is well established for drug-resistant epilepsy and is increasingly explored in neurodegenerative disorders. KD reduces neuronal hyperexcitability through enhanced γ-aminobutyric acid (GABA)ergic transmission and modulation of neurotransmitter balance, underlying its efficacy in refractory epilepsy. Beyond seizure control, emerging evidence suggests KD may influence disease processes in conditions such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and Huntington's disease. Preclinical studies indicate that KD can modulate mitochondrial bioenergetics, oxidative stress, neuroinflammation, neurotransmitter signaling, and gut-brain interactions, though these effects are highly context-dependent and primarily derived from cellular and animal models. Clinical data remain limited, heterogeneous, and short-term, with small cohorts and variable outcome measures. Sustaining adherence and assessing long-term safety remain significant challenges in patient populations. This review summarizes recent experimental and clinical findings, highlighting the molecular and cellular mechanisms through which KD exerts neuroprotective effects. We also evaluate translational evidence and discuss the potential utility of KD as an adjunctive intervention in neurological disease management.},
}

*Diet, Ketogenic/methods
Humans
Animals
*Neurodegenerative Diseases/diet therapy/metabolism
*Drug Resistant Epilepsy/diet therapy/metabolism

@article {pmid41846510,
year = {2026},
author = {Raby, KL},
title = {Synthesizing five decades of research on sensitive caregiving: A commentary on Nivison et al. (2026).},
journal = {Journal of child psychology and psychiatry, and allied disciplines},
volume = {},
number = {},
pages = {},
doi = {10.1111/jcpp.70146},
pmid = {41846510},
issn = {1469-7610},
abstract = {This commentary highlights the contributions of Nivison et al.'s (2026) umbrella meta-analysis synthesizing five decades of research on sensitive caregiving and child development. Integrating findings from numerous meta-analyses, the authors demonstrate that caregiver sensitivity is meaningfully associated with multiple domains of child development. Notably, associations with cognitive and language development are at least as large as those with attachment security and behavior problems, expanding traditional conceptualizations of sensitivity's developmental significance. The findings further indicate substantial consistency across child, parent, and family demographic characteristics, while suggesting amplified benefits in socioeconomically disadvantaged contexts. This commentary underscores key gaps in the literature, including the need for meta-analytic investigations of children's peer competence, self-regulation, and physical health outcomes, as well as the need for refined measurement of caregiving dimensions. Although causal inferences require randomized intervention evidence, the synthesis provides compelling support for sensitive caregiving as a central determinant of healthy development and offers a roadmap for future research and policy.},
}

@article {pmid41846565,
year = {2026},
author = {Denby, K and Connelly, EDS and Glerup, H and Østgård, R and Egsgaard, AL and Vedsted, P and Appel, CW},
title = {Translation and cross-cultural adaptation of the Identification of Spondyloarthritis Questionnaire (IBIS-Q) into Danish for patients with inflammatory bowel disease.},
journal = {Scandinavian journal of gastroenterology},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/00365521.2026.2645081},
pmid = {41846565},
issn = {1502-7708},
abstract = {OBJECTIVES OF THE ARTICLE: Spondyloarthritis (SpA) affects 10-30% of patients with inflammatory bowel disease (IBD). An early diagnosis is essential as a delayed diagnosis of SpA increases the risk of disability and reduces quality of life. However, few screening tools for patients with IBD exist and none are available in Danish. To support early identification of spondyloarthritis symptoms in Danish patients with IBD, this study aimed to translate and cross-culturally adapt the Identification of Spondyloarthritis Questionnaire (IBIS-Q) into Danish and to assess face validity of the Danish version.

MATERIALS AND METHODS: Following Beaton et al.'s six step forward-backward translation guideline, the IBIS-Q was translated and cross-culturally adapted into Danish. This was done through an iterative process with an expert committee of translators, clinicians, methodologists and with inclusion of the IBIS-Q developers. Face validity was assessed through semi-structured interviews with 24 adults with and without arthritis-related symptoms.

RESULTS: Participants generally found the questionnaire easy to understand, and face validity was confirmed. The semantic equivalence of painful and sore in a Danish context was a central topic of discussion within the expert committee. However, only minor modifications were made, including the addition of an introductory paragraph and changing the questionnaire's title.

CONCLUSIONS: Following an international, standardised guideline, the IBIS-Q was successfully translated and cross-culturally adapted into Danish, and face validity was confirmed. The IBIS-Q is the first available questionnaire to assess Danish patients with IBD for SpA symptoms. Psychometric validation of the measurement properties of IBIS-Q is recommended prior to implementation.},
}

@article {pmid41847237,
year = {2026},
author = {Zarco-Martín, MT and Andreo-López, MC and Yagui-Beltrán, MS and Fernández-Soto, ML},
title = {Sarcopenia in amyotrophic lateral sclerosis: a key predictor of respiratory dysfunction and disease progression.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1713253},
pmid = {41847237},
issn = {2296-861X},
abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterized by progressive muscle weakness and respiratory decline. Sarcopenia remains underexplored in terms of prevalence and their relationship with disease progression. We aimed to determine the prevalence of sarcopenia in ALS patients, assess the predictive value of morphofunctional assessment tools for sarcopenia, and explore their relationship with respiratory function and disease progression.

METHODS: A cross-sectional study was conducted with 40 ALS patients at the ALS Multidisciplinary Unit, San Cecilio University Hospital in Granada. Sarcopenia was defined based on the European Working Group of Sarcopenia in Older People 2(EWGSOP2) and malnutrition was diagnosed using GLIM criteria. Morphofunctional status was assessed using: Phase Angle (PA) and body composition by Bioelectrical Impedance Vector Analysis, muscle strength through Handgrip Strength (HGS). Respiratory function was evaluated using Forced Vital Capacity (FVC). Associations between sarcopenia, body composition, respiratory function, and disease severity were analyzed using logistic regression models. Receiver operating characteristic analyses were performed to identify optimal predictive cut-off values.

RESULTS: Sarcopenia was identified in 25% of ALS patients. Compared with non-sarcopenic individuals, sarcopenic patients exhibited significantly lower muscle mass indices, PA, and HGS, along with higher extracellular water percentage (%ECW). Malnutrition was more frequent in sarcopenia group (90% vs. 25%, p < 0.001). Respiratory impairment was more pronounced in sarcopenic patients, with reduced FVC and elevated pCO₂ (p = 0.02), and a greater need for non-invasive mechanical ventilation (NIMV) (70% vs. 10%, p = 0.001). VC correlated positively with body cell mass index (BCMI) (r = 0.450), skeletal muscle mass index (SMI) (r = 0.413), and ALSFRS-R score (r = 0.731; all p < 0.05). Lower PA, BCMI, and ALSFRS-R scores, together with higher %ECW and partial pressure of carbon dioxide (pCO₂), predicted sarcopenia risk. Reduced BCMI, HGS, Short Physical Performance Battery (SPPB) and sarcopenia were associated with the need of NIMV. BCMI (cut-off:8.05 kg/m[2]; AUC:0.889) and ALSFRS-R (cut-off:33 points; AUC:0.884) were the most accurate predictors of sarcopenia and ventilatory support, respectively.

CONCLUSION: This study is the first to assess sarcopenia prevalence in ALS patients using standardized diagnostic criteria. The findings highlight the relationship between sarcopenia, malnutrition, and respiratory decline. PA, BCMI, and respiratory parameters emerge as potential tools for sarcopenia and NIMV risk stratification.},
}

@article {pmid41847382,
year = {2026},
author = {Talbot, SR and Scorrano, F and Gaburro, S and Lainee, P and van Gaalen, MM},
title = {From observation to optimization: behavioral metrics that matter in KPI based home cage monitoring.},
journal = {Frontiers in behavioral neuroscience},
volume = {20},
number = {},
pages = {1694689},
pmid = {41847382},
issn = {1662-5153},
abstract = {Most in vivo scientists would agree that digital biomarkers collected via home-cage monitoring generate valuable data. However, few can tell precisely how valuable. The gap between enthusiasm and evidence has slowed the adoption of digital biomarkers in preclinical research. This framework paper addresses that gap by providing explicit key performance indicators (KPIs), organized into scientific, operational, welfare, and financial categories. We show how return-on-investment calculations differ across pharmaceutical companies, contract research organizations (CROs), and academic institutions. Furthermore, we demonstrate the approach through a worked example in an Amyotrophic Lateral Sclerosis (ALS) mouse model that reduces full-time equivalent (FTE) requirements by half. When successfully integrated, digital biomarkers can generate richer datasets, reduce the number of animals, improve welfare, and enhance translational value. However, successful implementation requires clear performance metrics to justify investment and measure success. We also discuss what these technologies cannot do, because understanding limitations matters as much as understanding benefits.},
}

@article {pmid41850140,
year = {2026},
author = {Gao, Y and Sun, Z and Wei, Q and She, C and Wang, Y and Chen, J and Wang, M and Gui, X and Xia, X and Liu, Y and Wang, X},
title = {Employing an integrated computational simulation strategy to identify high-affinity ligands for TDP-43 amyloid proteins.},
journal = {Bioorganic & medicinal chemistry},
volume = {137},
number = {},
pages = {118634},
doi = {10.1016/j.bmc.2026.118634},
pmid = {41850140},
issn = {1464-3391},
abstract = {Developing high-affinity ligands targeting TDP-43 amyloid species is a potential therapeutic approach for amyotrophic lateral sclerosis (ALS). Here, we propose an integrated computational simulation strategy, which integrates multiple virtual screening methods, molecular dynamics simulations and binding free energy evaluations. Using this strategy, we successfully identified TDPL1, a high-affinity ligand for TDP-43 amyloid proteins. In vitro affinity assays confirmed the computational predictions. Based on the MD simulation results, we further investigated the binding mode between TDPL1 and TDP-43 amyloid proteins. Additionally, steered molecular dynamics simulations were employed to assess the impact of TDPL1 on the stability of β-sheet interactions within the TDP-43 amyloid structure. Our data demonstrate that TDPL1 not only binds effectively to TDP-43 amyloid proteins but also possesses the potential to disrupt the stability of amyloid aggregates. These findings provide a molecular foundation for the future development of diagnostic agents or targeted therapeutics for ALS and related diseases.},
}

@article {pmid41850233,
year = {2026},
author = {Guise, AJ and Ferber, KL and Young, D and Edwards, AL and Sabouri, S and Fraser, KB and Milliman, E and Plowey, ED and Zoghbi, J and Fradette, SM and Graham, DL},
title = {Identification of tofersen PD-response biomarkers in VALOR clinical trial CSF via multiplexed quantitative proteomics.},
journal = {Cell reports. Medicine},
volume = {7},
number = {3},
pages = {102648},
doi = {10.1016/j.xcrm.2026.102648},
pmid = {41850233},
issn = {2666-3791},
mesh = {Humans ; *Proteomics/methods ; *Biomarkers/cerebrospinal fluid ; *Amyotrophic Lateral Sclerosis/drug therapy/cerebrospinal fluid/genetics ; Superoxide Dismutase-1/genetics ; Male ; Female ; Middle Aged ; Adult ; Membrane Glycoproteins/cerebrospinal fluid ; Aged ; },
abstract = {Tofersen, the first approved genetically targeted therapy for amyotrophic lateral sclerosis (ALS), demonstrates significant lowering of plasma neurofilament in adults carrying mutations in the superoxide dismutase 1 (SOD1) gene; however, additional biomarkers of treatment response in ALS are lacking. Here, we analyze longitudinally collected cerebrospinal fluid (CSF) samples from the phase 3 VALOR clinical trial to identify candidate tofersen treatment-response biomarkers in SOD1-ALS via quantitative proteomics. We observe significant modulation from baseline abundance for 56 proteins in tofersen-treated participants relative to placebo, including CSF GPNMB, which is significantly and continuously elevated across all post-baseline timepoints. We orthogonally confirm this observation by GPNMB immunoassay in independent tofersen-treated cohorts. Taken together, these data identify pharmacodynamic-response biomarkers of tofersen treatment that can be measured as early as 4 weeks post-treatment in SOD1-ALS patients and demonstrate the utility of leveraging unbiased proteomic screening integrated with targeted validation methods to identify pharmacodynamic-response biomarkers in clinical trial patient samples.},
}

Humans
*Proteomics/methods
*Biomarkers/cerebrospinal fluid
*Amyotrophic Lateral Sclerosis/drug therapy/cerebrospinal fluid/genetics
Superoxide Dismutase-1/genetics
Male
Female
Middle Aged
Adult
Membrane Glycoproteins/cerebrospinal fluid
Aged

@article {pmid41850301,
year = {2026},
author = {Glaubitz, R and Harst, L and Ehm, F and Tesch, F and Barlinn, J and Krause, F and Schwarz, R and Malzahn, J and Werblow, A and Sinz, C and Randig, I and Riedel, T and Kutschker, C and Fiebig, S and Kubitza, J and Cording, M and Wolff, J and Schmitt, J},
title = {Testing a model-based approach for planning and regional coordination of hospital service group offerings: A model project in the East Saxony healthcare cluster.},
journal = {Gesundheitswesen (Bundesverband der Arzte des Offentlichen Gesundheitsdienstes (Germany))},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2771-8616},
pmid = {41850301},
issn = {1439-4421},
abstract = {The hospital reform passed in 2024 will lead to regional and nationwide changes in the German hospital landscape. A joint project to examine the effects of the hospital reform on health care structures in the East Saxony region was initiated by the Center for Evidence-Based Health Care (ZEGV) at Dresden University Hospital, the regional health care coordinators of the four districts in the East Saxony care cluster and the city of Dresden, a statutory health insurance provider (AOK PLUS), and other regional stakeholders. In addition, the aim was to promote cooperation between the stakeholders for the purpose of future regionally coordinated planning for inpatient care. The project involved the application and validation of a model displaying a hospital's relevance for stationary care provision (care relevance model), which was developed in cooperation with the GKV-Spitzenverband (National Association of Statutory Health Insurance Funds) and is based on the performance data of German hospitals in accordance with § 21 KHEntgG (Hospital Remuneration Act). Thirty of the 36 hospital locations in the project region agreed to participate in the project. Both in a questionnaire-based self-assessment provided by the clinics and during a joint cluster conference, the tension between the need for cooperation and individual interests became clear. At this point, the care relevance model developed can scientifically support the dialogue between the stakeholders and thus support inpatient planning.Im Zuge der im Jahr 2024 verabschiedeten Krankenhausreform wird es zu regionalen und deutschlandweiten Veränderungen der Krankenhauslandschaft kommen. Vor diesem Hintergrund wurde ein gemeinsames Projekt des Zentrums für Evidenzbasierte Gesundheitsversorgung (ZEGV) der Hochschulmedizin Dresden mit den Regionalkoordinator:innen für Gesundheit der vier Landkreise im Versorgungscluster Ostsachsen und der Stadt Dresden, der AOK PLUS und weiteren regionalen Akteuren initiiert, um die Auswirkungen der Krankenhausreform auf die Versorgungsstrukturen in der Region Ostsachsen zu untersuchen. Zudem sollte die Kooperation zwischen den Akteuren zum Zweck einer zukünftigen regional abgestimmten Planung für die stationäre Versorgung gefördert werden. Im Projekt erfolgte die Anwendung und Validierung eines Versorgungsrelevanzmodells, welches in Kooperation mit dem GKV-Spitzenverband entwickelt wurde und auf den Leistungsdaten deutscher Krankenhäuser nach § 21 KHEntgG basiert. Dreißig von 36 Krankenhausstandorten in der Projektregion konnten für eine Teilnahme am Projekt gewonnen werden. Sowohl in einer fragebogengestützten Selbstauskunft der Kliniken als auch im Rahmen der zusammenführenden Clusterkonferenz wurde das Spannungsfeld zwischen Kooperationsnotwendigkeiten und Partikularinteressen deutlich. An dieser Stelle kann das entwickelte Versorgungsrelevanzmodell den Dialog zwischen den Akteuren wissenschaftlich begleiten und so die stationäre Planung unterstützen.},
}