@article {pmid41477570,
year = {2025},
author = {Almalki, MG and Abdel-Aziem, AA},
title = {Validation and cross-cultural adaptation of an Arabic version of the chronic pain self-efficacy scale.},
journal = {Hong Kong physiotherapy journal : official publication of the Hong Kong Physiotherapy Association Limited = Wu li chih liao},
volume = {45},
number = {2},
pages = {143-155},
pmid = {41477570},
issn = {1013-7025},
abstract = {BACKGROUND: Self-efficacy in pain sufferers includes beliefs about one's capacity to tolerate pain. For usage by Arabic-speaking individuals, the Chronic Pain Self-Efficacy Scale (CPSS), which was initially developed in English, must be translated and modified into the Arabic language.

OBJECTIVE: To assess the CPSS's psychometric qualities for subjects suffering from chronic pain in Arabic.

METHODS: This was a cross-sectional survey that followed Beaton et al.'s guidelines. The CPSS underwent cross-cultural adaptation and Arabic translation in the initial phase. Then, the reliability and validity of the Arabic version of CPSS were examined. A total of 329 patients completed the questionnaire (40.7% males and 59.3% females).

RESULTS: The subscales had good internal consistency, the Cronbach's alpha was 0.870 for subscale 1 (self-efficacy for managing pain), 0.935 for subscale 2 (physical function self-efficacy), and 0.925 for subscale 3 (coping with other symptoms self-efficacy). Test-retest total scores had an acceptable intraclass correlation coefficient (ICC) of 0.743 (95% CI -0.29 to -0.196, p = 0 . 92). When performing principal component analysis with varimax rotation [exploratory factor analysis (EFA)> 0 . 4 ], the test is helpful. Regarding construct validity, the correlation between the total score of Beck depression inventory (BDI) and CPSS subscales and total score have significant moderate negative correlations (r =- 0 . 479 ; p = 0 . 001) except the pain management subscale has significantly weak negative correlations (r =- 0 . 345 ; p = 0 . 001).

CONCLUSION: The Arabic version seems to be a reliable and valid instrument for evaluating a person's self-efficacy in chronic pain among Arabic-speaking individuals making it a good and acceptable instrument.},
}

@article {pmid41477139,
year = {2025},
author = {Syamal, M},
title = {Treatment of Neurogenic Voice Disorders.},
journal = {World journal of otorhinolaryngology - head and neck surgery},
volume = {11},
number = {4},
pages = {541-547},
pmid = {41477139},
issn = {2589-1081},
abstract = {This overview serves as a foundational resource for clinicians caring for neurologically complex patients presenting with voice complaints. Neurogenic voice disorders are diverse in their clinical presentations and therapeutic approaches. A thorough medical history, including family history, detailed laryngeal examination, voice assessments, and neuroimaging, are imperative, as well as a multidisciplinary, collaborative approach with neurologists, speech language pathologists, and patient caregivers. Disorders such as amyotrophic lateral sclerosis (ALS), cerebrovascular accidents (strokes), Huntington's disease, myasthenia gravis (MG), Parkinson's disease (PD), and voice tremor should be understood by otolaryngologists. Each condition presents unique challenges and requires tailored treatment strategies ranging from supportive therapies and pharmacological interventions to surgery. Voice management techniques, including the use of botulinum toxin for hyperkinetic disorders and deep brain stimulation for refractory cases, are highlighted as promising interventions.},
}

@article {pmid41476442,
year = {2025},
author = {Kato, N and Hashida, G and Sahara, W},
title = {Short-Term Effects of Exercise Therapy on Muscle Characteristics in Patients With Mild-to-Moderate Amyotrophic Lateral Sclerosis: A Preliminary Case Series Study.},
journal = {Cureus},
volume = {17},
number = {12},
pages = {e100383},
pmid = {41476442},
issn = {2168-8184},
abstract = {BACKGROUND: Exercise therapy is recommended for patients with amyotrophic lateral sclerosis (ALS), but its effects on muscle mass and intramuscular conditions remain unclear. In recent years, ultrasonography has enabled the simple and non-invasive estimation of muscle mass and intramuscular conditions. This study aimed to investigate the short-term effects of exercise therapy on muscle characteristics in patients with mild-to-moderate ALS using ultrasonography.

METHODS:  Ambulatory patients with ALS and an ALS Functional Rating Scale-Revised (ALSFRS-R) score of ≥30 underwent moderate-intensity exercise therapy for 3-4 weeks. Primary outcome measures included muscle strength (handgrip strength (HGS) and ankle dorsiflexion strength (ADFS)), muscle thickness (MT), echo intensity (EI), and the ratio of muscle strength to muscle thickness for both the forearm muscles and the tibialis anterior muscle. The Bayesian Wilcoxon signed-rank test was used to compare outcomes before and after the intervention.

RESULTS:  Six consecutive patients with ALS (median age: 75.5 years; three males (50%) and three females (50%); four with bulbar onset (66.7%) and two with upper limb onset (33.3%)) were included. Following the intervention, the muscle thickness of the forearm muscles and the tibialis anterior muscle decreased. However, qualitative muscle characteristics were partially maintained or improved: the echo intensity of the forearm muscles was maintained, and the ratio of ankle dorsiflexion strength to muscle thickness of the tibialis anterior muscle showed a large increase.

CONCLUSION:  In patients with mild-to-moderate ALS, exercise therapy resulted in short-term qualitative changes in muscle, while a concurrent reduction in muscle mass may have attenuated these effects. The benefits of exercise therapy may have been counteracted by muscle mass loss, suggesting the need for future studies to investigate the combined effects of exercise and nutritional therapy on muscle characteristics and activities of daily living (ADL).},
}

@article {pmid41476438,
year = {2025},
author = {Oza, R},
title = {Physical Activity as an Intervention for Frailty Syndrome: A Narrative Review.},
journal = {Cureus},
volume = {17},
number = {12},
pages = {e100293},
pmid = {41476438},
issn = {2168-8184},
abstract = {Frailty is a geriatric syndrome characterised by a decline in functional reserves as the body ages, resulting in increased disability, comorbidity, and mortality. With trends towards ageing populations, frailty syndrome becomes more clinically relevant, highlighting the importance of appropriately preventing and managing the characteristics of frailty syndrome. Risk factor modification is recommended to delay or prevent the onset of frailty, including physical activity alongside other modifiable behaviours such as diet. Ageing is associated with chronic low-grade inflammation, resulting in reduced muscle protein synthesis and increased resistance to insulin, which both contribute to sarcopenia. Sarcopenia underpins key characteristics of frailty, including weakness and slow speed. Physical activity stimulates anabolic pathways and improves insulin resistance, reducing sarcopenia. Moreover, aerobic exercise is responsible for increasing the VO2 peak, whilst resistance exercise improves muscle strength, both of which are known to decrease in frail elders. This narrative review primarily explored the effectiveness of physical activity in reducing the risk of the onset of frailty syndrome through a narrative review of the relevant literature concerning this subject. A secondary focus of this narrative review is to compare the success of alternative interventions for preventing frailty, relative to physical activity. Physical activity interventions have been shown to improve components of frailty scoring and selected biological markers of frailty, with evidence suggesting physical activity is an effective single-domain intervention for frailty; however, multidomain approaches may result in a greater overall improvement in frailty prevention. Further research is required to identify the types of exercise that modify specific aspects of Fried et al.'s frailty criteria (FFC), as well as what interventions can be used alongside physical activity, to holistically treat all characteristics of frailty syndrome.},
}

@article {pmid41476266,
year = {2026},
author = {Cai, F and Xu, D and Yang, D and Huang, F and Song, X and Jiang, Q and Wan, S and Zhao, Y and Zhou, J},
title = {Multidimensional predictors of fatigue in amyotrophic lateral sclerosis: a cross-sectional study in China.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-33192-3},
pmid = {41476266},
issn = {2045-2322},
support = {Grant No. ZY2025Q006//Hubei Provincial Administration of Traditional Chinese Medicine/ ; Grant No. 82575246//National Natural Science Foundation of China/ ; GZY-KJS-2025-008 and Joint Fund, 2023AFD128//Science and Technology Special Project of State Administration of Traditional Chinese Medicine and Hubei Provincial Natural Science Foundation/ ; },
}

@article {pmid41475669,
year = {2025},
author = {Mirzalieva, O and Reed, RE and Haas, AL and Juncker, MA and Logarbo, P and Klein, JM and Worthylake, D and Desai, SD},
title = {ISG15 dysregulates endoplasmic reticulum-mitochondrial contacts and calcium homeostasis in Ataxia telangiectasia.},
journal = {Cellular signalling},
volume = {},
number = {},
pages = {112347},
doi = {10.1016/j.cellsig.2025.112347},
pmid = {41475669},
issn = {1873-3913},
abstract = {Dysregulation of endoplasmic reticulum and mitochondrial (ER:Mit) contacts and mitochondrial calcium (mitCa[2+]) homeostasis are found in several neurodegenerative disorders, including Ataxia Telangiectasia (A-T). However, the cellular basis of these defects remains unclear. Previously, we demonstrated that the aberrantly elevated Interferon-Stimulated Gene 15 (ISG15) pathway inhibits protein polyubiquitylation, its dependent protein turnover, and mitophagy pathways in A-T. Literature indicates that silencing of mitochondrial ubiquitin ligase 1 (MUL1) stabilizes mitofusin2 (MFN2) and attenuates mitCa[2+] uptake from ER to Mit (mitCa[2+]influx) in primary neurons. We have replicated these findings in apparently healthy fibroblasts. We hypothesized that elevated ISG15 may inhibit ubiquitin-dependent MUL1-mediated degradation of MFN2 and dysregulate ER:Mit contacts and mitCa[2+] homeostasis in A-T fibroblasts. Concurrently, MFN2 is stabilized in A-T, MUL1-silenced A-T, MUL1/ISG15-silenced A-T vs ISG15-silenced A-T fibroblasts. Moreover, the number of ER:Mit contacts is increased in A-T vs ISG15-silenced A-T fibroblasts. Notably, mitCa[2+]efflux is significantly attenuated in A-T vs ISG15-silenced A-T fibroblasts in which mitCa[2+]efflux is restored to levels comparable to those observed in normal fibroblasts. The mitCa[2+]efflux remains attenuated in MUL1 and MUL1/ISG15-silenced A-T fibroblasts. We conclude that ISG15 impairs MUL1/MFN2-mediated regulation of ER:Mit contacts and attenuates mitCa[2+]efflux, which may, in turn, cause Ca[2+] overload-mediated mitochondrial damage in A-T. These findings suggest that ISG15 silencers may correct mitochondrial abnormalities and improve mitochondrial health in A-T patients and in those with other neurodegenerative disorders in which ISG15 is elevated, such as ALS.},
}

@article {pmid41475349,
year = {2025},
author = {Dubey, SK and Chaubey, D and Ikenaga, C and Lin, WW and Bellen, HJ and Lloyd, TE},
title = {Aberrant nuclear pore complex degradation contributes to neurodegeneration in VCP disease.},
journal = {Neuron},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuron.2025.11.017},
pmid = {41475349},
issn = {1097-4199},
abstract = {Defective nucleocytoplasmic transport (NCT) has emerged as a contributing factor in the pathogenesis of neurodegenerative diseases and aging. Valosin-containing protein (VCP) is an AAA+ATPase required for disassembly of protein complexes, and mutations in VCP cause neurodegenerative and neuromuscular diseases. We find that VCP is required for quality control of nuclear pore complexes (NPCs) by extracting selected nucleoporins from NPCs for proteasome-mediated degradation. Pathogenic VCP variants cause a reduction in nucleoporins in Drosophila, induced pluripotent stem cell (iPSC)-derived motor neurons, and muscle biopsies from patients, indicating a dominant gain-of-function mechanism. Mechanistically, disease-associated mutations in VCP result in increased recruitment to NPCs through interactions with Ufd1-Npl4, leading to the removal of a subset of nucleoporins from NPCs and disrupting NCT. These findings show that the VCP-Ufd1-Npl4 pathway regulates NPC quality control and that disease-associated variants aberrantly activate the VCP-Ufd1-Npl4 complex to degrade NPCs and disrupt NCT.},
}

@article {pmid41475066,
year = {2025},
author = {Kaji, R and Nishi, Y and Ishida, T and Takase, T and Ueda, T and Maeda, T and Izumi, Y and , },
title = {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 = {480},
number = {},
pages = {125701},
doi = {10.1016/j.jns.2025.125701},
pmid = {41475066},
issn = {1878-5883},
abstract = {OBJECTIVE: To develop combined therapies for amyotrophic lateral sclerosis (ALS), we investigated the long-term safety of ultra-high-dose methylcobalamin (50-mg intramuscular, twice weekly) in patients with advanced ALS.

METHODS: As an open-label extension of a multicenter, randomized, double-blind, placebo-controlled phase 2/3 study, patients were enrolled and administered methylcobalamin 50 mg intramuscularly twice weekly for up to 52 weeks.

RESULTS: In total, 144 patients (mean age, 62.1 years; 61.1 % male) were included, and the overall disease duration was 53.2 ± 17.9 months, with 85.4 % of patients having an ALS severity stage ≥3. The incidence of adverse events was 94.4 %, and adverse drug reactions occurred in 3.5 % of patients, which included proteinuria (2.1 %) and single cases of supraventricular arrhythmia, increased blood urea, and hypertension (0.7 % each). None led to discontinuation or death. The survival rate at 52 weeks was 85.7 %, and as shown for the following patient subgroups: by ALS severity (stage 1-2, 100 %; 3, 85.3 %; 4, 82.8 %; 5, 82.0 %) and by presence of tracheostomy (with, 88.8 %; without, 84.1 %). The median change in the ALS functional rating scale total score from baseline to 52 weeks was -1.0.

CONCLUSION: There were no particular safety issues as reported in the phase 2/3 study and no clear deterioration in survival rate or physical function when ultra-high-dose methylcobalamin was administered intramuscularly in patients with advanced ALS. This regimen could be a candidate for initial therapy with further add-on to overcome ALS in the future.},
}

@article {pmid41474642,
year = {2026},
author = {Luo, H and Yang, Y and Cao, X and Deng, C and Chen, H},
title = {Unveiling the Genetic Association Between Hemoglobin Concentration and Amyotrophic Lateral Sclerosis.},
journal = {Brain and behavior},
volume = {16},
number = {1},
pages = {e71152},
doi = {10.1002/brb3.71152},
pmid = {41474642},
issn = {2162-3279},
support = {82171422//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/blood ; *Hemoglobins/genetics/metabolism ; Genome-Wide Association Study ; Motor Neurons/metabolism ; Mendelian Randomization Analysis ; Induced Pluripotent Stem Cells/metabolism ; Genetic Predisposition to Disease ; Polymorphism, Single Nucleotide ; },
abstract = {BACKGROUND: Although previous studies have suggested an association between hemoglobin (Hb) concentration and amyotrophic lateral sclerosis (ALS), the precise cause-and-effect relationship between them is still unclear. This study aims to investigate the causal correlation between Hb concentration and ALS, and explore the potential genes related to their association.

METHODS: We extracted summary statistical data of Hb concentration and ALS from genome-wide association studies (GWAS), performed Mendelian randomization (MR) analyses, and conducted RNA sequencing of motor neurons different from ALS patient-derived induced pluripotent stem cells (iPSCs), followed by an intersection analysis between differentially expressed genes (DEGs) in ALS motor neurons and selected instrumental variables (IVs) associated with Hb concentration.

RESULTS: As a result, Hb concentration had a negative causal relationship with the risk of ALS, established through IVW (OR = 0.854; 95% CI: 0.767-0.951; p = 0.00418) of the univariable MR analysis. A multivariable MR further confirmed that this causal link remained robust, even when accounting for confounders including systolic blood pressure, total cholesterol levels, body mass index, LDL cholesterol, diastolic blood pressure, and smoking. Importantly, genetically predicted ALS did not show a causal connection to Hb concentration. Additionally, RNA sequencing analysis and qRT-PCR results revealed that transcripts for BACH1 and FLVCR1 were upregulated, while those for TRIM58 were downregulated in SOD1[D90A] ALS motor neurons, compared to the control. In motor neurons differentiated from a sporadic ALS patient-derived iPSCs, qRT-PCR showed increased transcript levels of BACH1, and decreased transcript levels of FLVCR1 and TRIM58. These three genes were intersected with harmonized SNPs between Hb concentration and ALS.

CONCLUSION: Our study concludes that genetically predicted Hb concentration exhibited an independent inverse causal association with the risk of developing ALS, with potential involvement of genes such as BACH1, FLVCR1, and TRIM58.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/metabolism/blood
*Hemoglobins/genetics/metabolism
Genome-Wide Association Study
Motor Neurons/metabolism
Mendelian Randomization Analysis
Induced Pluripotent Stem Cells/metabolism
Genetic Predisposition to Disease
Polymorphism, Single Nucleotide

@article {pmid41472414,
year = {2025},
author = {Wu, J and Tao, Z and Cao, J and Hu, W and Jiang, M and Li, Y and Cao, H and Liao, M and Zhao, N},
title = {Cytochrome P450 and glutathione S-transferase may confer bensulfuron-methyl resistance in Cyperus iria.},
journal = {Pest management science},
volume = {},
number = {},
pages = {},
doi = {10.1002/ps.70492},
pmid = {41472414},
issn = {1526-4998},
support = {2021YFD1700100//National Key Research and Development Program of China/ ; X202510364082//College Students' Innovation Training Project in Anhui Agricultural University/ ; },
abstract = {BACKGROUND: Rice flatsedge (Cyperus iria L.) is one of the most troublesome weeds infesting rice fields across China. Bensulfuron-methyl, an acetolactate synthase (ALS)-inhibiting herbicide, has been widely used for the control of Cyperaceae weeds in rice production. However, long-term and extensive use of this herbicide has resulted in the evolution of resistant C. iria populations. In this study, a suspected bensulfuron-methyl-resistant (R) population collected from a rice field that survived field-recommended applications was investigated to elucidate its resistance level and underlying mechanism.

RESULTS: Compared with a susceptible (S) population, the R population exhibited a high level of resistance to bensulfuron-methyl [resistance index (RI) = 12.88] and cross-resistance to metazosulfuron (RI = 11.66), bispyribac-sodium (RI = 9.10) and penoxsulam (RI = 6.35). No mutations were detected in the ALS gene, and ALS expression levels did not differ significantly between the R and S plants. Pretreatment with the cytochrome P450 inhibitor malathion and the glutathione S-transferase inhibitor 4-chloro-7-nitrobenzoxadiazole effectively reversed bensulfuron-methyl resistance in R plants. Liquid chromatography tandem mass spectrometry analysis showed that the R plants metabolized bensulfuron-methyl significantly faster than the S plants. RNA sequenccing analysis revealed remarkable upregulation of CYP97A3 and GSTF1 in the R population, while molecular docking indicated strong binding affinities between both enzymes and bensulfuron-methyl at their active sites.

CONCLUSION: These results reveal that enhanced expression of CYP97A3 and GSTF1 may contribute to bensulfuron-methyl resistance in C. iria, highlighting the role of metabolic detoxification in the evolution of non-target-site resistance in this species. © 2025 Society of Chemical Industry.},
}

@article {pmid41471389,
year = {2025},
author = {Gershoni Emek, N and Tan, AM and Geva, M and Fekete, A and Abate, C and Hayden, MR},
title = {Pridopidine, a Potent and Selective Therapeutic Sigma-1 Receptor (S1R) Agonist for Treating Neurodegenerative Diseases.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {12},
pages = {},
doi = {10.3390/ph18121900},
pmid = {41471389},
issn = {1424-8247},
abstract = {Pridopidine is a highly selective sigma-1 receptor (S1R) agonist in clinical development for Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). The S1R is a ubiquitous chaperone protein enriched in the central nervous system and regulates multiple pathways critical for neuronal cell function and survival, including cellular stress responses, mitochondrial function, calcium signaling, protein folding, and autophagy. S1R has a crucial role in the ER mitochondria-associated membrane (MAM), whose dysfunction is implicated in several neurodegenerative diseases. By activating the S1R, pridopidine corrects multiple cellular pathways necessary to the cell's ability to respond to stress, which are disrupted in neurodegenerative diseases. Pridopidine restores MAM integrity; rescues Ca[2+] homeostasis and autophagy; mitigates ER stress, mitochondrial dysfunction, and oxidative damage; and enhances brain-derived neurotrophic factor (BDNF) axonal transport and secretion, synaptic plasticity, and dendritic spine density. Pridopidine demonstrates neuroprotective effects in in vivo models of neurodegenerative diseases (NDDs). Importantly, pridopidine demonstrates the biphasic dose response characteristic of S1R agonists. In clinical trials in HD and ALS, pridopidine has shown benefits across multiple endpoints. Pridopidine's mechanism of action, modulating core cellular survival pathways, positions it as a promising candidate for disease modification for different nervous system disorders. Its broad therapeutic potential includes neurodevelopmental disorders, and rare diseases including Wolfram syndrome, Rett syndrome, and Vanishing White Matter Disease. Here, we review the experimental data demonstrating pridopidine's S1R-mediated neuroprotective effects. These findings underscore the therapeutic relevance of S1R activation and support further investigation of pridopidine for the treatment of different neurodegenerative diseases including ALS and HD.},
}

@article {pmid41468784,
year = {2025},
author = {Palanivel, V and Salkar, A and Shenoy, A and Eva, TA and Perera, R and Chitranshi, N and Gupta, V and You, Y and Mirzaei, M and Graham, SL and Gupta, V and Basavarajappa, D},
title = {Neuropeptide Y at the crossroads of neurodegeneration: Mechanistic insights and emerging therapeutic strategies.},
journal = {Neuropeptides},
volume = {115},
number = {},
pages = {102583},
doi = {10.1016/j.npep.2025.102583},
pmid = {41468784},
issn = {1532-2785},
abstract = {Neuropeptide Y (NPY), a widely distributed and highly conserved neuropeptide, plays a central role in the regulation of diverse physiological processes, including stress responses, energy homeostasis, vascular tone, and immune modulation, via activation of its receptor subtypes. Beyond its physiological roles, the dysregulation of NPY expression has been documented in several neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Machado-Joseph disease, and retinal disorders such as diabetic retinopathy and glaucoma. These alterations in NPY levels and receptor activity highlight its potential not only as a biomarker for disease progression but also as a promising therapeutic target. Previous evidence revealed that NPY exerts neuroprotection by alleviating excitotoxicity, oxidative stress, mitochondrial dysfunction, and neuroinflammation while concurrently facilitating neurogenesis, synaptic plasticity, and cellular resilience. NPY activates receptor-mediated intracellular signaling cascades like PI3K/Akt, MAPK/ERK, and p38K, that control cellular survival, proteostasis, and inflammation and thereby influence disease trajectories. Understanding NPY operation with these mechanisms can unveil new avenues for targeted therapy. Current insights into the complex roles of NPY in neurodegeneration are discussed in this review, and their implications in diagnostic and treatment strategies are addressed.},
}

@article {pmid41468379,
year = {2025},
author = {Spencer, BE and Irwin, DJ and Van Deerlin, VM and Suh, E and Lee, EB and Elman, L and Quinn, CC and Amado, D and Baer, M and Grossman, M and Wolk, DA and McMillan, CT},
title = {Polygenic associations with clinical and neuropathological trait heterogeneity across TDP-43 proteinopathies.},
journal = {PloS one},
volume = {20},
number = {12},
pages = {e0338398},
doi = {10.1371/journal.pone.0338398},
pmid = {41468379},
issn = {1932-6203},
mesh = {Humans ; *Multifactorial Inheritance ; *TDP-43 Proteinopathies/genetics/pathology ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide ; Male ; Female ; *DNA-Binding Proteins/genetics ; Aged ; Phenotype ; Middle Aged ; Genetic Predisposition to Disease ; },
abstract = {TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration with TDP-43 (FTLD-TDP), and limbic-predominant age-related TDP-43 encephalopathy, encompass a spectrum of clinical and neuropathological traits. Despite mounting evidence for shared genetic risk across TDP-43 proteinopathies, the modifiers of individual-level traits are unknown. We aimed to identify polygenic contributions to trait heterogeneity across TDP-43 proteinopathies. We used weighted correlation analysis of GWAS summary statistics for ALS, FTLD-TDP, and hippocampal sclerosis of aging (HS-Aging) to identify data-driven clusters of highly correlated single nucleotide polymorphisms (SNPs). We performed gene ontology enrichment analysis for each identified cluster. We derived cluster-specific polygenic scores and evaluated their association with clinical and neuropathological traits in an independently evaluated sample of individuals who met neuropathological and/or genetic criteria for FTLD-TDP or ALS (n = 260). We identified 5 distinct data-driven clusters, including 3 GWAS phenotype-specific clusters (FTLD-TDP, ALS, HS-Aging) and 2 clusters representing the overlap between a pair of GWAS phenotypes (ALS-FTLD and FTLD-HS). Pathway analysis revealed biologically meaningful associations including distinct GWAS phenotype-specific processes within clusters. Cluster-specific ALS and FTLD-TDP polygenic risk each associated with individual-level clinical traits, even within the context of autosomal dominant mutation carriers, where higher ALS polygenic risk associated with neuromuscular impairment and higher FTLD-TDP polygenic risk associated with cognitive-behavioral impairment. Moreover, higher FTLD-TDP polygenic risk associated with higher TDP-43 burden within characteristic FTLD-TDP brain regions. We suggest that there are polygenic modifiers of clinical and neuropathological traits across TDP-43 proteinopathies that may contribute to individual-level differences, including likelihood for developing FTLD or ALS.},
}

Humans
*Multifactorial Inheritance
*TDP-43 Proteinopathies/genetics/pathology
*Amyotrophic Lateral Sclerosis/genetics/pathology
Genome-Wide Association Study
Polymorphism, Single Nucleotide
Male
Female
*DNA-Binding Proteins/genetics
Aged
Phenotype
Middle Aged
Genetic Predisposition to Disease

@article {pmid41467445,
year = {2025},
author = {Dikwella, N and Lingor, P and Tzeplaeff, L},
title = {Seeing amyotrophic lateral sclerosis in a multi-omic perspective.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-01010},
pmid = {41467445},
issn = {1673-5374},
}

@article {pmid41467443,
year = {2025},
author = {Yang, Y and Chen, M and Ding, L and Liu, J and Luo, J and Yan, R and Ning, J and Xie, S and Li, X and Ren, Z and Zhou, R and Chen, Z},
title = {Mitochondria-associated endoplasmic reticulum membranes and calcium ion exchange: A novel direction for aging and neurodegenerative diseases.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00857},
pmid = {41467443},
issn = {1673-5374},
abstract = {Mitochondria-associated endoplasmic reticulum membranes serve as crucial signaling hubs mediating communication between the endoplasmic reticulum and mitochondria, and play a central role in calcium ion exchange. This dynamic interface regulates key cellular processes including bioenergetic metabolism, apoptosis, autophagy, and stress responses. Dysregulation of calcium transport associated with mitochondria-associated endoplasmic reticulum membranes can disrupt intracellular homeostasis, leading to mitochondrial dysfunction, oxidative stress, and neuronal death, which are hallmarks of aging and neurodegenerative diseases. This review systematically examines the functions of protein complexes within mitochondria-associated endoplasmic reticulum membranes and the pathogenic mechanisms of calcium signaling regulated by these membranes in neurodegenerative disorders. It places particular emphasis on structural alterations in calcium ion transport machinery as a common mechanism underlying various neurodegenerative diseases. In Alzheimer's disease, mitochondria-associated endoplasmic reticulum membranes exhibit a hyperactive state, promoting the generation of amyloid-β and enhancing calcium ion flux from the endoplasmic reticulum to the mitochondria. In contrast, in Parkinson's disease and amyotrophic lateral sclerosis, the activity of mitochondria-associated endoplasmic reticulum membranes is reduced, leading to a decline in mitochondrial calcium ion buffering capacity and exacerbating excitotoxicity. Proteins residing in mitochondria-associated endoplasmic reticulum membranes are disrupted across various neurodegenerative diseases, resulting in abnormal communication between the endoplasmic reticulum and mitochondria. Recent studies indicate that mitochondria-associated endoplasmic reticulum membranes play a bidirectional role in disease progression, and compensatory mechanisms often exacerbate the pathological process. Therapeutic strategies aimed at preserving the integrity of mitochondria-associated endoplasmic reticulum membranes hold promise for alleviating neurodegenerative damage. Therefore, calcium ion exchange mediated by mitochondria-associated endoplasmic reticulum membranes plays a key role in aging and neurodegenerative diseases, making it a highly promising therapeutic target.},
}

@article {pmid41467440,
year = {2025},
author = {Akbergenov, R and Wolfer, DP and Gillingham, D and Shcherbakov, D},
title = {Error-prone translation as a driver of proteostasis collapse and neurodegeneration.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00795},
pmid = {41467440},
issn = {1673-5374},
abstract = {Error-prone translation, resulting in inaccuracies in protein synthesis, is increasingly recognized as a critical contributor to proteostasis disruption and the pathogenesis of age-related neurological disorders. In recent years, numerous studies have elucidated that stochastic errors during mRNA translation may act as a molecular "tipping point" initiating pathogenic protein misfolding. A detailed analysis of how translation errors lead to protein misfolding, aggregation, and subsequent neurotoxicity will facilitate the identification of promising therapeutic targets for neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This article explores the contribution of mistranslation to proteostasis decline, focusing on the unique vulnerabilities of neuronal cells. We review the sources of translation errors, effects of ribosomal ambiguity and error-restrictive mutations, role of proteostatic mechanisms (such as molecular chaperones, ubiquitin-proteasome system, and unfolded protein response), and provide a unified perspective that links age-related translational infidelity to neurodegeneration. By synthesizing the most recent data obtained with genetically modified cellular and animal model studies, we highlight how age-associated decline in translational fidelity exacerbates proteostasis failure and propose potential therapeutic interventions targeting translation accuracy to mitigate neurodegeneration.},
}

@article {pmid41467439,
year = {2025},
author = {Dong, T and Zhang, T and Wang, H and Zhang, J and Abdullah, R and Sun, B and Peng, G},
title = {Microbiota-gut-brain axis and bile acids-driven neuromodulation.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00927},
pmid = {41467439},
issn = {1673-5374},
abstract = {Bile acids emerge as multifunctional signaling molecules with dual hepatic and microbial origins, acting through farnesoid X receptor and Takeda G protein coupled receptor 5 to influence inflammation and metabolism. Their dysregulation is consistently observed across various neurodegenerative diseases. The microbiota-gut-brain axis is a pivotal conduit for bile acids-driven neuromodulation, while sex-specific bile acid profiles and signaling pathways introduce critical biological heterogeneity. Emerging translational evidence indicates the promise of bile acids as biomarkers and therapeutic targets, yet highlights the critical hurdles that need to be addressed to realize precision interventions. Our core findings are: (1) Bile acids are far more than mere metabolic byproducts. They orchestrate core pathological processes such as neuroinflammation and energy metabolism. Their functions, whether neuroprotective or neurotoxic, are highly context-dependent, varying with cell type and disease-specific pathological backgrounds, thus exhibiting a potent "double-edged sword" effect. (2) The "microbiota-bile acids-brain axis" serves as a crucial bridge linking peripheral metabolic dysregulation to central nervous system pathology. (3) Sexual dimorphism emerges as a fundamental biological variable essential for understanding the heterogeneity in bile acid profiles and disease susceptibility. The primary contribution of this work is the proposal of an integrated "microbiota-bile acids-sex" framework that systematically describes the key scientific challenge of the context-dependent, dual roles of bile acids. Ultimately, this review champions a paradigm shift from a traditional brain-centric view to a systemic, metabolic perspective, establishing the bile acid system as a promising target for future precision therapeutic interventions.},
}

@article {pmid41467438,
year = {2025},
author = {Zhao, J and Wang, J and Guo, X},
title = {Organoids: Key advances, optimization, and technological iterations in their application to neurodegenerative diseases.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00924},
pmid = {41467438},
issn = {1673-5374},
abstract = {Organoid technology, as an innovative approach, has shown great potential in disease modeling, target screening, and the development of treatment strategies. However, traditional organoids still have three major limitations in research: the absence of specific cell types, the lack of blood-brain barrier structure, and insufficient reproducibility of experimental results. In recent years, researchers have gradually overcome these limitations by introducing innovative techniques such as advanced culture methods, microfluidic systems, bioprinting, organoid transplantation, and assembloid construction. This progress has facilitated the widespread application of organoids in the study of neurodegenerative diseases. This paper aims to systematically review the technological innovations of organoids in the study of neurodegenerative diseases. By summarizing classical organoid construction strategies and their limitations, it emphasizes the value of organoids in comprehensive applications within neurodegenerative disease research. In this review, we focus on five specific neurodegenerative diseases: Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and frontotemporal dementia. Research in these diseases demonstrates that organoids improve experimental accessibility and reduce development cycles in disease modeling, target discovery, and therapeutic strategy formation. Using customized equipment and gene editing techniques, these organoids can be tailored to specific needs, providing pathophysiologically relevant disease models and enhancing our understanding of neurodegenerative diseases. Although organoid technology has demonstrated significant advantages in disease research, its potential for treating neurodegenerative diseases has not yet been fully explored, which may become an important direction for future research.},
}

@article {pmid41467429,
year = {2025},
author = {Liang, X and Qin, R and Qin, Q and Xu, W and Xu, H and Lai, X and Shao, L and Li, C and Xie, M and Xiong, X and Tang, Q and Chen, L},
title = {Therapeutic potential of astrocyte transdifferentiated neurons.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00554},
pmid = {41467429},
issn = {1673-5374},
abstract = {The permanent functional deficits resulting from the inability of adult mammalian central nervous system neurons to regenerate after injury present a significant clinical challenge. While traditional stem cell transplantation strategies continue to encounter ethical concerns and the risk of immune rejection, this impasse has shifted regenerative medicine research toward targeting endogenous astrocytes. Due to their intrinsic plasticity, widespread distribution throughout the central nervous system, and affinity for neurodevelopmental lineage, astrocytes are a unique target for in situ neuronal regeneration. This review systematically elucidates the core regulatory network governing astrocyte transdifferentiation, identifying 10 key signaling pathways, such as Wnt signaling pathway, that form a cascade regulatory system. Directed overexpression of transcription factors such as NeuroD1, Ascl1, or Neurog2 can directly initiate neuronal phenotypic conversion. Meanwhile, small molecule compounds such as valproic acid combined with CHIR99021 activate endogenous neurogenic programs by inhibiting the bone morphogenetic protein signaling axis. Notably, polypyrimidine tract binding protein 1 (PTB) gene silencing significantly enhances transdifferentiation efficiency by suppressing the microRNA 124/re1 silencing transcription factor (miR-124/REST) feedback loop. From a translational perspective, a multidimensional evaluation system based on morphological, molecular marker, and electrophysiological properties has demonstrated considerable therapeutic potential. In stroke models, NeuroD1-mediated transdifferentiation replenished approximately 30% of lost cortical neurons and improved motor coordination, evidenced by enhanced performance in food pellet retrieval, grid walking, and cylinder tests compared with controls. In spinal cord injury studies, SOX2-induced glutamatergic neurons moderately reduced glial scar density by about 25%, permitting regenerating axons to pass through while preserving the supportive structure of scar. In neurodegenerative contexts, PTB inhibition yielded functionally mature dopaminergic neurons and reconstructed nigrostriatal pathways in Parkinson's disease models. In Alzheimer's disease models, adeno-associated virus-delivered NeuroD1 induced whole-brain neural circuit remodeling, generating 500,000 new neurons widely distributed across the cortex and hippocampus, accompanied by improved cognitive performance. Current technical limitations include off-target effects of adeno-associated virus vectors, which cause nonspecific gene expression and require rigorous validation via Cre-loxP lineage tracing. Transdifferentiation efficiency is also highly influenced by regional microenvironments: gray matter astrocytes show higher conversion rates than those in white matter, and oxidative stress increases apoptosis among newly generated neurons. Clinical translation is further constrained by the safety of delivery systems and the aging tissue microenvironment, where transforming growth factor beta 1 is often elevated. Ferroptosis inhibitors have been shown to nearly double the survival rate of transdifferentiated cells, offering a novel strategy to mitigate oxidative damage. Based on current evidence, astrocyte transdifferentiation enables neural functional recovery across multiple disease models through endogenous repair mechanisms. Future advances should focus on optogenetically inducible vectors for spatiotemporal precision, non-viral delivery systems to mitigate vector-related risks, and integration of long-term safety validation in non-human primates with single-cell multi-omics technologies to facilitate the clinical translation of personalized regenerative therapies.},
}

@article {pmid41467421,
year = {2025},
author = {Huerta, TJ and Urbina-Muñoz, V and Urra-Alvarez, V and Villablanca, C and Gomez-Perez, LS and Saavedra, B and Contreras, T and Vidal, RL},
title = {Cell-based immunotherapy for neurodegenerative disease: A promising avenue.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00816},
pmid = {41467421},
issn = {1673-5374},
abstract = {Neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and Huntington's disease are characterized by progressive neuronal loss and chronic neuroinflammation, with current treatments remaining largely symptomatic. This review explores the potential of cell-based immunotherapy as a disease-modifying strategy. Advances in stem cell biology and immune engineering have facilitated the development of therapies using mesenchymal stem cells, chimeric antigen receptor T cells, macrophages, regulatory T cells, modified macrophages, and monoclonal antibodies. These approaches aim to regulate immune mechanisms implicated in neurodegeneration, such as microglial activation, systemic inflammation, and immune checkpoint dysregulation. Notably, macrophage-mediated delivery systems, such as genetically modified cells expressing neurotrophic factors or antioxidant enzymes, have demonstrated neuroprotective effects. Likewise, emerging data support T-cell modulation and monoclonal antibody development as therapeutic targets in amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and Huntington's disease. We highlight current preclinical findings, underlying mechanisms, and translational challenges, emphasizing that immunomodulatory cell therapies represent a promising avenue for precision medicine in neurodegenerative diseases.},
}

@article {pmid41467385,
year = {2025},
author = {Zhou, Z and Zhao, Y and Fan, X and Zhang, J and Niu, R and Ma, Y and Xie, F and Tang, P and Mei, X and Zhang, L and Deng, J},
title = {CD11c+ microglia: From basic research to clinical application.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00868},
pmid = {41467385},
issn = {1673-5374},
abstract = {CD11c+ microglia are a functionally specialized subpopulation of microglia that play a crucial role in the pathophysiological processes of various central nervous system diseases. This review synthesizes compelling evidence that CD11c+ microglia exhibit unique transcriptomic and phagocytic characteristics. These characteristics distinguish them from homeostatic microglia and support their specialized functions. During development, CD11c+ microglia are crucial for the maturation of oligodendrocytes and the integrity of white matter, particularly in regions such as the corpus callosum and cerebellum. In preclinical models of neurodegenerative diseases (such as Alzheimer's disease and amyotrophic lateral sclerosis) and central nervous system injuries (such as stroke and spinal cord injury), they are consistently associated with neuroprotective phenotypes. CD11c+ microglia exhibit enhanced phagocytic capacity near amyloid plaques and damaged neurons, helping to clear pathological protein aggregates and cell debris, thereby reducing neurotoxicity and promoting a repair environment. The current consensus is that specific microenvironmental cues, particularly hazard signaling molecules (DAMPs) and cytokines (such as interferon-γ), are the main drivers of the differentiation and activation of CD11c+ microglia. Among these, the TREM2-APOE signaling axis is a key and widely accepted regulatory pathway for their survival, proliferation, and functional status. The plasticity of CD11c+ microglia is regulated by multiple signaling pathways, including CSF1R, SIRPα-CD47, IFN-γ, and the complement cascade. Emerging therapeutic strategies aim to regulate their activities through gene targeting, metabolic intervention, and immune regulation using TREM2 agonists, CSF1R inhibitors, or nanopharmacological methods. However, challenges remain in defining specific CD11c+ biomarkers, understanding environment-dependent functions, and achieving targeted delivery. Future prospects depend on clearly addressing individual developmental issues, deciphering the molecular switches that control phenotypic plasticity, and developing highly specific therapeutic strategies to leverage their beneficial functions, thereby paving the way for new intervention methods for neurological diseases.},
}

@article {pmid41466523,
year = {2025},
author = {Watabe, K},
title = {Praja1 E3 ubiquitin ligase and the role it plays in neurodegeneration.},
journal = {The FEBS journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/febs.70383},
pmid = {41466523},
issn = {1742-4658},
abstract = {Protein aggregation and transmission are hallmarks of neurodegenerative diseases. Praja1 E3 ubiquitin ligase has been shown to suppress the aggregation of causative proteins in amyotrophic lateral sclerosis, frontotemporal lobar degeneration, Parkinson's disease, Huntington's disease, and spinocerebellar degeneration, which include transactivation response DNA-binding protein of 43 kDa, fused in sarcoma, superoxide dismutase 1, α-synuclein, huntingtin, and ataxin-3. Aoki et al. demonstrated that Praja1 ubiquitinates and degrades tau, a key molecule in tauopathies such as Alzheimer's disease, Pick's disease, progressive supranuclear palsy, and corticobasal syndrome, furthering our understanding of the role of Praja1 in neurodegenerative diseases and potential therapeutic approaches.},
}

@article {pmid41466416,
year = {2025},
author = {Howard, I and Simmons, Z},
title = {Does the ACT Have ImpACT for ALS?.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70117},
pmid = {41466416},
issn = {1097-4598},
}

@article {pmid41466038,
year = {2025},
author = {Cauchi, RJ and Tosolini, AP},
title = {ALS: a field in motion.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {44791},
pmid = {41466038},
issn = {2045-2322},
}

@article {pmid41465514,
year = {2025},
author = {Riku, Y and Brion, JP and Ando, K and Uchihara, T and Iwasaki, Y},
title = {The Determinant of Tau Spreading in Alzheimer's Disease: Dependent on Senile Plaque, Neural Circuits, or Spatial Proximity?.},
journal = {International journal of molecular sciences},
volume = {26},
number = {24},
pages = {},
doi = {10.3390/ijms262412088},
pmid = {41465514},
issn = {1422-0067},
support = {JPMH23FC1008//MHLW Research on rare and intractable diseases Program/ ; 23K06935, 25K22597, and 25K10781//JSPS-KAKENHI/ ; },
mesh = {Humans ; *Alzheimer Disease/metabolism/pathology ; *tau Proteins/metabolism ; *Plaque, Amyloid/metabolism/pathology ; Animals ; Neurofibrillary Tangles/metabolism/pathology ; Amyloid beta-Peptides/metabolism ; Brain/metabolism/pathology ; },
abstract = {Alzheimer's disease (AD) is neuropathologically characterized by tau-immunopositive neurofibrillary tangles (NFTs) and amyloid-β (Aβ)-immunopositive senile plaques. According to the widely accepted amyloid cascade hypothesis, Aβ pathology represents the upstream event in AD pathophysiology and induces tau aggregation. However, numerous studies have suggested that tau aggregates correlate more closely with neuronal loss and regional brain atrophy than with Aβ depositions. Tau aggregation in AD demonstrates a hierarchical spreading pattern beginning in the transentorhinal cortex, but the mechanisms underlying this spreading manner of lesions remain to be elucidated. This review aims to address current controversies regarding tau pathology in AD from the perspectives of both the 'amyloid cascade' and 'tauopathy' hypotheses. From the 'amyloid cascade' viewpoint, Aβ deposition prominently involves distal axon and axon terminals, and in some regions, there are anatomical correspondences between axonal Aβ pathology and cytoplasmic tau aggregations (e.g., a close relationship between senile plaques in the molecular layer of the hippocampal dentate gyrus and NFTs in the transentorhinal cortex). Nevertheless, this model cannot explain the whole body of hierarchical spreading of tau aggregation because notable spaciotemporal discrepancies also exist in many regions. From the 'tauopathy' perspective, the distribution of tau aggregates in AD involves key nodes within the memory circuits. Also, experimental studies have suggested that patient-derived tau exhibits seeding and neuron-to-neuron propagation properties. Interestingly, tau aggregation in AD appears to spread laterally in a proximity-dependent, cortico-cortical fashion rather than along long-range memory circuits. This contrasts with the system-selective, poly-nodal degenerations seen in four-repeat tauopathies, amyotrophic lateral sclerosis, or spinocerebellar degenerations. Moreover, the proportions of three-repeat and four-repeat isoforms shift during the maturation of NFTs in AD. Overall, spreading patterns of tau-pathology in AD cannot be fully explained by Aβ pathology and also differ from the system degeneration seen in other tauopathies.},
}

Humans
*Alzheimer Disease/metabolism/pathology
*tau Proteins/metabolism
*Plaque, Amyloid/metabolism/pathology
Animals
Neurofibrillary Tangles/metabolism/pathology
Amyloid beta-Peptides/metabolism
Brain/metabolism/pathology

@article {pmid41465496,
year = {2025},
author = {López-Royo, T and Gascón, E and Moreno-Martínez, L and Macías-Redondo, S and Zaragoza, P and Manzano, R and Osta, R},
title = {Region-Specific Expression Patterns of lncRNAs in the Central Nervous System: Cross-Species Comparison and Functional Insights.},
journal = {International journal of molecular sciences},
volume = {26},
number = {24},
pages = {},
doi = {10.3390/ijms262412069},
pmid = {41465496},
issn = {1422-0067},
support = {PI21/00372//Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER) "Una manera de hacer Europa" from the European Union/ ; CB18/05/0037//CIBERNED/ ; A19_23R//Consolidated Groups from Gobierno de Aragón/ ; PRTR-C17.I1//The Spanish Ministry of Science and Innovation with funds from the European Union NextGenerationEU, from the Recovery, Transformation and Resilience Plan/ ; FPU19/05625//Ministerio de Universidades from Gobierno de España/ ; PT20/00109//Instituto de Salud Carlos III/ ; },
mesh = {*RNA, Long Noncoding/genetics/metabolism ; Animals ; Humans ; Male ; Female ; Mice ; *Central Nervous System/metabolism ; Spinal Cord/metabolism ; Species Specificity ; Brain/metabolism ; Gene Expression Profiling ; Organ Specificity ; },
abstract = {Increasing evidence demonstrates that long noncoding RNAs (lncRNAs) are crucial for brain evolution and proper development and function of the central nervous system (CNS), exhibiting specific time-, spatial-, and sex-biassed expression patterns. This study investigated whether region-specific spatial expression patterns of brain-relevant lncRNAs are conserved between the mouse and human CNS. Demonstrating such cross-species conservation informs the translational value of mouse models for lncRNA biology. To test this, the expression of 14 lncRNAs was studied in the adult CNS of mice and humans across three different regions (spinal cord, brainstem, and frontal cortex), and age effects were assessed in mice. The results demonstrated conserved expression patterns between the two species, with region-specific changes. The frontal cortex exhibited high expression of Meg3, Miat, and Pvt1 lncRNAs, while the spinal cord showed high levels of Hotair and Gas5. Additionally, Malat1 displayed lower levels in females compared to males in the spinal cord compared to other regions. Finally, through GO functional enrichment analysis and literature review, this study emphasizes the role of lncRNAs in CNS physiology and disease, suggesting their involvement in neurological processes and conditions such as cortical development, neuronal synapsis, schizophrenia, Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. Overall, this research highlights the importance of further investigating the role of lncRNAs in brain function and their potential as key players in neurological disorders, opening the door to explaining the high region- and sex-specific effects of these disorders.},
}

*RNA, Long Noncoding/genetics/metabolism
Animals
Humans
Male
Female
Mice
*Central Nervous System/metabolism
Spinal Cord/metabolism
Species Specificity
Brain/metabolism
Gene Expression Profiling
Organ Specificity

@article {pmid41465278,
year = {2025},
author = {Marzetti, E and Di Lorenzo, R and Calvani, R and Coelho-Júnior, HJ and Landi, F and Pesce, V and Picca, A},
title = {Linking Cell Architecture to Mitochondrial Signaling in Neurodegeneration: The Role of Intermediate Filaments.},
journal = {International journal of molecular sciences},
volume = {26},
number = {24},
pages = {},
doi = {10.3390/ijms262411852},
pmid = {41465278},
issn = {1422-0067},
support = {D1.2024//Università Cattolica del Sacro Cuore/ ; D1.2025//Università Cattolica del Sacro Cuore/ ; Ricerca Corrente 2025//Italian Ministry of Health/ ; DM 1557 11.10.2022//European Commission/ ; 2022YNENP3//Italian Ministry of University and Research/ ; },
mesh = {Humans ; *Mitochondria/metabolism/pathology ; Animals ; *Neurodegenerative Diseases/metabolism/pathology ; *Intermediate Filaments/metabolism/pathology ; *Signal Transduction ; Neurons/metabolism/pathology ; },
abstract = {Mitochondrial dysfunction is a pivotal contributor to neurodegeneration. Neurons heavily rely on mitochondrial oxidative metabolism and therefore need highly efficient quality control mechanisms, including proteostasis, mitochondrial biogenesis, fusion-fission dynamics, and mitophagy, to sustain bioenergetics and synaptic function. With aging, deterioration of mitochondrial quality control pathways leads to impaired oxidative phosphorylation, excessive reactive oxygen species generation, calcium imbalance, and defective clearance of damaged organelles, ultimately compromising neuronal viability. Pathological protein aggregates, such as α-synuclein in Parkinson's disease, β-amyloid and tau in Alzheimer's disease, and misfolded superoxide dismutase 1 and transactive response DNA-binding protein 43 in amyotrophic lateral sclerosis, further aggravate mitochondrial stress, establishing self-perpetuating cycles of neurotoxicity. Such mitochondrial defects underscore mitochondria as a convergent pathogenic hub and a promising therapeutic target for neuroprotection. Intermediate filaments (IFs), traditionally viewed as passive structural elements, have recently gained attention for their roles in cytoplasmic organization, mitochondrial positioning, and energy regulation. Emerging evidence indicates that IF-mitochondria interactions critically influence organelle morphology and function in neurons. This review highlights the multifaceted involvement of mitochondrial dysfunction and IF dynamics in neurodegeneration, emphasizing their potential as targets for novel therapeutic strategies.},
}

Humans
*Mitochondria/metabolism/pathology
Animals
*Neurodegenerative Diseases/metabolism/pathology
*Intermediate Filaments/metabolism/pathology
*Signal Transduction
Neurons/metabolism/pathology

@article {pmid41464650,
year = {2025},
author = {Sonaglioni, A and Nicolosi, GL and Lombardo, M and Baravelli, M and Muti, P},
title = {Comparative Meta-Analysis of Left Ventricular Mechanics in Takotsubo Syndrome and Anterior STEMI Due to Left Anterior Descending Artery Occlusion.},
journal = {Journal of clinical medicine},
volume = {14},
number = {24},
pages = {},
doi = {10.3390/jcm14248748},
pmid = {41464650},
issn = {2077-0383},
support = {N/A//Ministero della Salute/ ; },
abstract = {Background: Takotsubo syndrome (TTS) often mimics anterior ST-elevation myocardial infarction (STEMI) caused by left anterior descending (LAD) occlusion, yet the two entities differ fundamentally in pathophysiology and mechanical behavior. Two-dimensional speckle-tracking echocardiography (2D-STE) enables detailed assessment of left ventricular (LV) deformation beyond conventional ejection fraction (LVEF). This meta-analysis compared global and regional LV strain patterns in TTS versus LAD-related anterior STEMI during the acute phase. Methods: A systematic search of PubMed, Embase, and Scopus through October 2025 identified observational case-control studies directly comparing TTS and angiographically confirmed anterior STEMI, with LV mechanics assessed by 2D-STE. Random-effects models were used to pool standardized mean differences (SMDs) for LVEF; global longitudinal strain (GLS); apical, mid-ventricular, and basal longitudinal strain (ALS, MLS, BLS); and global radial strain (GRS). Heterogeneity (I[2]), publication bias (funnel plots, Egger's test), meta-regression, and leave-one-out sensitivity analyses were performed. Results: Six studies comprising 221 TTS and 290 anterior STEMI patients met the inclusion criteria. TTS patients were older, predominantly female, and had fewer metabolic risk factors, while LV size was comparable. LVEF was significantly lower in TTS (SMD -1.149; 95% CI -2.20 to -0.10; p = 0.032), with stable findings across sensitivity analyses and no evidence of publication bias. GLS, ALS, MLS, and BLS showed only a non-significant trend toward greater impairment in TTS, and these comparisons were limited by marked inter-study heterogeneity. In contrast, GRS was significantly and consistently more reduced in TTS (SMD -1.284; 95% CI -1.59 to -0.98; p < 0.001), indicating more profound global radial dysfunction. Meta-regression showed no significant influence of demographic factors or vendor-specific software on LVEF or GLS differences. Conclusions: Compared with LAD-related anterior STEMI, TTS is associated with more severely depressed LVEF and markedly impaired radial strain, while longitudinal strain differences remain inconclusive and suggest only a potential trend toward greater dysfunction, reflecting the limited and heterogeneous evidence. These findings are consistent with diffuse, stress-induced myocardial stunning in TTS and suggest that 2D-STE may aid differentiation between stress cardiomyopathy and ischemic infarction in the acute setting, although longitudinal strain parameters should be interpreted cautiously and regarded as hypothesis-generating.},
}

@article {pmid41464612,
year = {2025},
author = {Klumb, S and Haley, L and Hathaway, C and Irby, J and Cheng, J and Rumley, J},
title = {Degenerative Cervical Myelopathy Diagnosis and Its Differentiation from Neurological Mimics, MS and ALS: A Literature Review.},
journal = {Journal of clinical medicine},
volume = {14},
number = {24},
pages = {},
doi = {10.3390/jcm14248711},
pmid = {41464612},
issn = {2077-0383},
abstract = {Multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and degenerative cervical myelopathy (DCM) share features that may confound diagnosis. DCM is caused by degenerative changes in the cervical spine leading to spinal cord compression and injury, resulting in significant disability. Misdiagnosis of DCM for a similar neurological condition can lead to further spinal cord damage from delayed surgical treatment. Here we review the diagnostic criteria, clinical signs and symptoms, and imaging typical for DCM, and two of its clinical mimics, MS and ALS. Shared motor symptoms of all three conditions can make diagnosis difficult, especially early in disease course. Noteworthy differences include neck and shoulder pain in DCM, visual disturbances in MS, and bulbar symptoms and the absence of sensory deficits in ALS. In DCM and MS, MRI is used to support the diagnosis, with specific findings on MRI that differentiate DCM versus MS. In ALS, MRI is used to rule out differential diagnoses. Applying the diagnostic criteria for MS and ALS, as well as understanding the typical presentation and MRI findings of DCM, is crucial. Through discussion of these conditions, this review aims to help limit misdiagnosis rates, allowing for early management, which can improve long-term patient outcomes.},
}

@article {pmid41463333,
year = {2025},
author = {Tendero-Lopez, D and Dominguez, M and Aguilar-Aragon, M},
title = {Modelling Neural Disorders with the D. melanogaster Larval Peripheral and Adult Dopaminergic Systems.},
journal = {Biomolecules},
volume = {15},
number = {12},
pages = {},
doi = {10.3390/biom15121677},
pmid = {41463333},
issn = {2218-273X},
mesh = {Animals ; *Drosophila melanogaster/metabolism ; Larva/metabolism ; *Disease Models, Animal ; Humans ; *Dopamine/metabolism ; *Dopaminergic Neurons/metabolism/pathology ; *Nervous System Diseases/metabolism ; Parkinson Disease/metabolism ; },
abstract = {The increasing prevalence of neurological disorders highlights the need for disease animal models to elucidate the underlying biomolecular and cellular mechanisms of disease and to facilitate studies aimed at developing effective treatments. The fruit fly Drosophila melanogaster, at both larval and adult stages, can serve as an effective model for different human-relevant neurological diseases. Larvae are particularly suited for studying peripheral nervous system disorders, such as Charcot-Marie-Tooth and amyotrophic lateral sclerosis, while adults enable investigations of higher-order cognitive functions and age-related conditions, including Parkinson's disease and depression-like behaviours. Combining larval and adult models offers a complementary framework to dissect the biomolecular pathways of neurological disorders and accelerate preclinical research.},
}

Animals
*Drosophila melanogaster/metabolism
Larva/metabolism
*Disease Models, Animal
Humans
*Dopamine/metabolism
*Dopaminergic Neurons/metabolism/pathology
*Nervous System Diseases/metabolism
Parkinson Disease/metabolism

@article {pmid41463293,
year = {2025},
author = {Xie, V and Franco, MC and Martin, LJ},
title = {Human Mutant Dynactin Subunit 1 Causes Profound Motor Neuron Disease Consistent with Possible Mechanisms Involving Axonopathy, Mitochondriopathy, Protein Nitration, and T-Cell-Mediated Cytolysis.},
journal = {Biomolecules},
volume = {15},
number = {12},
pages = {},
doi = {10.3390/biom15121637},
pmid = {41463293},
issn = {2218-273X},
support = {1R01NS107417-04A1/NH/NIH HHS/United States ; },
mesh = {Animals ; *Dynactin Complex/genetics/metabolism ; Humans ; Mice ; *Motor Neuron Disease/genetics/pathology/metabolism ; *Mitochondria/metabolism/pathology ; Motor Neurons/metabolism/pathology ; *T-Lymphocytes/metabolism/immunology/pathology ; Axons/pathology/metabolism ; Mutation ; Spinal Cord/pathology/metabolism ; },
abstract = {Mutations in the gene encoding the p150 subunit of the dynactin complex (DCTN1) are linked to amyotrophic lateral sclerosis, spinal and bulbar muscular atrophy, and Perry syndrome. These neurodegenerative diseases can cause muscle weakness and atrophy, parkinsonian-like symptoms, and paralysis. To examine the evolution of neuropathology caused by a mutation in DCTN1 and cellular mechanisms of disease for therapeutic discovery, we characterized mice expressing either human wildtype or mutant (G59S) DCTN1. Neuron-specific expression of mutant, but not wildtype, DCTN1 caused fatal age-related paralytic disease and motor neuron (MN) degeneration in the spinal cord with axonopathy and chromatolysis without apoptotic morphology. MNs became positive for cleaved caspase-3, cleaved caspase-8, and nitrated Hsp90. Mitochondria accumulated and appeared fragmented and dysmorphic and then were lost. This pathology was accompanied by invasion of CD95- and CD8-positive mononuclear T cells into the ventral horn and accumulation of TNFα and IL9. Administration of the mitochondrial division inhibitor-1 (Mdivi-1) protected MNs and extended the lifespan of G59S-DCTN1 mice. A mitochondrial permeability transition pore inhibitor also extended lifespan. Thus, mutant DCTN1 causes degeneration of MNs associated with axonopathy, mitochondriopathy, nitrative stress, and caspase activation. It appears as retrograde neurodegeneration and inflammatory T-cell-like cytolysis. Mitochondria are possible therapeutic targets in DCTN1-linked neurodegenerative disorders.},
}

Animals
*Dynactin Complex/genetics/metabolism
Humans
Mice
*Motor Neuron Disease/genetics/pathology/metabolism
*Mitochondria/metabolism/pathology
Motor Neurons/metabolism/pathology
*T-Lymphocytes/metabolism/immunology/pathology
Axons/pathology/metabolism
Mutation
Spinal Cord/pathology/metabolism

@article {pmid41463070,
year = {2025},
author = {Goyal, NA and Andrews, JA and Oskarsson, BE and Wiedau, MH and Kasarskis, EJ and Forrest, BD and Zhang, R and Bracci, PM and Davis, MW and Azhir, A and McGrath, MS},
title = {Quantitative Measures of Time to Loss of 15% Vital Capacity and Survival Extension in Slowly Progressive Amyotrophic Lateral Sclerosis (ALS) Patients Treated with the Immune Regulator NP001 Suggests an Immunopathogenic Subset of ALS.},
journal = {Biomedicines},
volume = {13},
number = {12},
pages = {},
doi = {10.3390/biomedicines13123060},
pmid = {41463070},
issn = {2227-9059},
support = {Neuvivo - NP001//Ari Azhir/ ; },
abstract = {Background/Objectives: Overall survival in patients with amyotrophic lateral sclerosis (ALS) is linked to the rate of predicted respiratory vital capacity (PVC) loss. The objective of this study was to test whether changes in quantitative PVC measures over time linked to survival would define an immunopathogenic subset of ALS responsive to NP001, a regulator of innate immunity. Methods: In a retrospective study, data from intent-to-treat (ITT) population of two phase 2 trials of NP001 were evaluated for over time changes in PVC, time-to-event (TTE) loss of 15% PVC and PVC change from baseline, as linked to survival outcomes in patients treated with NP001 vs placebo. Results: Treatment with NP001 was associated with a significantly lower risk compared to placebo in the loss of 15% PVC over six months (p = 0.01; HR = 0.60, 95% CI: 0.39, 0.90). Data from the two trials were subsequently divided by a disease progression rate (DPR) value of 0.50 units of ALSFRS-R score lost per month for analysis of slow vs. rapid disease. In ALS patients with slowly progressive disease (DPR < 0.50), TTE PVC changes from baseline were slowed (p < 0.0005) and overall survival extended significantly (18.5 months) in NP001-treated vs. placebo groups. The rapidly progressive ALS patients (DPR ≥ 0.50) treated with NP001 showed no significant difference in PVC change or survival from the placebo group. Conclusions: These hypothesis-generating observations suggest that inflammation might play a significant role in the loss of respiratory function in a major subset of ALS patients.},
}

@article {pmid41462986,
year = {2025},
author = {Vauti, F and Eilers, L and Kroll, A and Köster, RW},
title = {Genomic Organization, Evolutionary Conservation and Expression of Ataxin-2 and Ataxin-2-like Genes Underscore the Suitability of Zebrafish as a Model Organism for SCA2 and Related Diseases.},
journal = {Biomedicines},
volume = {13},
number = {12},
pages = {},
doi = {10.3390/biomedicines13122974},
pmid = {41462986},
issn = {2227-9059},
support = {11-76251- 2714/2024 (ZN4545)//This project was supported by the BrightBrain initiative, which is funded by zu-kunft.niedersachsen, the joint science funding program of the Lower Saxony Ministry of Science and Culture and the Volkswagen Foundation/ ; },
abstract = {Background/Objectives: The Ataxin-2 protein (ATXN2) plays an essential role in RNA metabolism and many cellular processes. Dysregulation or mutation of the Ataxin-2 gene (ATXN2) can lead to neurodegenerative diseases such as spinocerebellar ataxia type 2 (SCA2) and amyotrophic lateral sclerosis (ALS). Despite numerous efforts in this field in other animal models, little is known about Atxn2 in zebrafish. In this study, we aim to investigate the potential suitability of zebrafish as a model for Atxn2-related diseases by performing basic analyses on Atxn2. Methods: We performed a bioinformatic protein analysis of Atxn2 from zebrafish and its paralog Atxn2l in relation to human and other vertebrate homologues. Based on a structural analysis of the atxn2 and atxn2l genes, the expression of the predicted transcripts was detected by RT-PCR and the spatiotemporal expression pattern was determined by whole-mount in situ hybridization. Results: We found similarities between the protein sequences of Atxn2 and Atxn2l in zebrafish and their functional domains with those of orthologs in humans and other vertebrates. The predicted transcripts of atxn2 and atxn2l were experimentally verified and their spatiotemporal expression patterns were determined during zebrafish development. Splicing variants were detected for both genes, suggesting a different role for the isoforms in different tissues. Conclusions: These findings provide new insights into the atxn2 and atxn2l genes, suggesting the zebrafish as a suitable animal model for functional studies and research on disease modeling of SCA2 and ALS.},
}

@article {pmid41462890,
year = {2025},
author = {Fajkić, A and Belančić, A and Lam, YW and Rački, V and Pilipović, K and Janković, T and Mežnarić, S and Mršić-Pelčić, J and Vitezić, D},
title = {Novel Translational Concept: Axon-to-Muscle Exosomal Signaling as an Emerging Therapeutic Target in Spinal Muscular Atrophy.},
journal = {Biomedicines},
volume = {13},
number = {12},
pages = {},
doi = {10.3390/biomedicines13122876},
pmid = {41462890},
issn = {2227-9059},
abstract = {Spinal muscular atrophy (SMA) has transitioned from a uniformly fatal disease to a treatable condition, yet incomplete neuromuscular recovery underscores the limits of current SMN-restorative therapies. Emerging data implicate disrupted axon-to-muscle exosomal signaling as an important, overlooked driver of residual dysfunction. Exosomes, nanovesicles mediating bidirectional neuronal-muscular communication, carry synaptic organizers, trophic factors, and microRNAs essential for neuromuscular junction integrity. SMN deficiency alters exosomal biogenesis and cargo, leading to loss of agrin-MuSK signaling, impaired β-actin transport, and muscle atrophy. Comparative insights from amyotrophic lateral sclerosis and muscular dystrophy reveal that stem-cell-derived or engineered exosomes restore synaptic stability, enhance regeneration, and cross biological barriers safely. Thus, we speculate herein on a translational model integrating exosome-based therapies with existing genetic interventions to achieve durable, systems-level recovery in SMA. Exosomal profiling may further yield minimally invasive biomarkers for disease monitoring and treatment optimization, establishing vesicle-mediated communication as a novel therapeutic axis in neuromuscular medicine.},
}

@article {pmid41461594,
year = {2025},
author = {Lee, WT and Varghese, P and Gaunt, A},
title = {Post-Operative C-Reactive Protein as a Predictor of Anastomotic Leak Following Robotic Colorectal Surgery.},
journal = {World journal of surgery},
volume = {},
number = {},
pages = {},
doi = {10.1002/wjs.70217},
pmid = {41461594},
issn = {1432-2323},
abstract = {AIM: Postoperative C-reactive protein (CRP) levels are good predictors of anastomotic leak (AL) following colorectal surgery, with postoperative day-3 CRP thresholds ranging between 162 and 195 mg/L in open and laparoscopic resections. This study aims to determine a cut-off CRP value that predicts ALs following robotic colorectal surgery and identifies patients suitable for safe early discharge.

METHODS: A single-center retrospective analysis of patients who underwent an elective robotic colorectal resection, with primary anastomosis, between February 2017 and December 2024, was conducted. Primary outcome measure was clinically and radiologically confirmed AL (graded). Data were analyzed using IBM SPSS v30.0.0.

RESULTS: Seven hundred eighty-four elective robotic colorectal resections with anastomosis were performed. Median age was 69 years (IQR 60-77), 448 male, 336 female, and BMI 27.5 (IQR 24.4-31.1), indication for surgery was cancer in 681 (86.9%) patients. 51 (6.5%) patients had an AL, of which 12/51 (23.5%) had a grade ≥ 3 leak. A POD-3 CRP level of 136.0 mg/L (73% sensitivity, 79% specificity, and AUC 0.788) and POD-4 CRP level of 94.4 mg/L (84% sensitivity, 62% specificity, and AUC 0.806) were predictive of AL. At POD-5, a cut-off CRP of 243 mg/L (88% sensitivity, 73% specificity, and AUC 0.818) was predictive of ALs requiring re-operation and/or escalation to level 2-3 care. Male sex, colo-rectal anastomoses, and resections performed before 2020 were associated with higher AL rates.

CONCLUSION: Postoperative CRP levels have high predictive value in early detection and exclusion of AL, facilitating early patient discharge under the enhanced recovery after surgery (ERAS) pathways. CRP thresholds in robotic colorectal resections are lower than previously reported thresholds in open and laparoscopic surgery.},
}

@article {pmid41461417,
year = {2026},
author = {Palma-Bautista, C and Rojano-Delgado, AM and Rey, MD and Gherekhloo, J and Domínguez-Valenzuela, JA and Jorrín-Novo, JV and Plaza, G and Osuna, MD and De Prado, R},
title = {Understanding cross- and multiple-herbicide resistance in Setaria adhaerens from olive orchards with two decades of multiple herbicides use.},
journal = {Pesticide biochemistry and physiology},
volume = {217},
number = {},
pages = {106883},
doi = {10.1016/j.pestbp.2025.106883},
pmid = {41461417},
issn = {1095-9939},
mesh = {*Herbicides/pharmacology ; *Herbicide Resistance ; *Olea ; Glutathione Transferase/metabolism ; Glycine/analogs & derivatives/pharmacology ; Cytochrome P-450 Enzyme System/metabolism ; },
abstract = {Two populations of Setaria adhaerens (resistant [R] and susceptible [S]) have been identified in Spanish olive orchards. The R population shows multiple resistance to chlorotoluron (PSII inhibitor), diclofop-methyl (ACCase inhibitor), tribenuron-methyl (ALS inhibitor), glyphosate (EPSPS inhibitor), and oxyfluorfen (PPO inhibitor), along with potential natural tolerance to diflufenican (PDS inhibitor). This study evaluated herbicide efficacy at field rates, enzyme activity (ALS, ACCase, EPSPS, PPO, PSII), and the role of cytochrome P450 and glutathione-S-transferases using malathion and NBD-Cl, respectively. The S population was fully controlled by all herbicides except diflufenican, which showed only ∼45 % control in both populations, indicating possible innate tolerance. In the R population, chlorotoluron, diclofop-methyl, tribenuron-methyl, and glyphosate had no effect on enzyme activity, suggesting non-target site resistance (NTSR). In contrast, oxyfluorfen inhibited PPO activity only in the S population, indicating target-site resistance (TSR). NBD-Cl showed no activity, ruling out glutathione-S-transferases-mediated metabolism. However, malathion restored over 50 % sensitivity to chlorotoluron, diclofop-methyl, and tribenuron-methyl in the R population, suggesting enhanced metabolism likely mediated by cytochrome P450 monooxygenases. Metabolic profiling further confirmed enhanced herbicide detoxification in the R population as a key resistance mechanism. These findings highlight the complexity of resistance in S. adhaerens and underline the urgent need to incorporate metabolic resistance monitoring into weed management programs. Future studies will focus on unraveling the molecular basis of these resistance mechanisms.},
}

*Herbicides/pharmacology
*Herbicide Resistance
*Olea
Glutathione Transferase/metabolism
Glycine/analogs & derivatives/pharmacology
Cytochrome P-450 Enzyme System/metabolism

@article {pmid41460923,
year = {2025},
author = {Korada, S and Tam, OH and Greco, HC and Hammell, MG and Dubnau, J and Sher, RB},
title = {LINE-1 retrotransposition in a mouse TDP-43 model of neurodegeneration marks motor cortex neurons for cell-intrinsic and cell non-autonomous programmed cell death.},
journal = {PLoS genetics},
volume = {21},
number = {12},
pages = {e1012007},
doi = {10.1371/journal.pgen.1012007},
pmid = {41460923},
issn = {1553-7404},
abstract = {A key pathological feature of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) is the loss of nuclear localization and accumulation of cytoplasmic inclusions of TAR-DNA binding protein 43 (TDP-43). TDP-43 is a nucleic acid-binding protein involved in transcriptional repression, mRNA splicing, and the regulation of retrotransposable elements (RTEs) and endogenous retroviruses (ERVs). RTEs/ERVs are mobile virus-like genetic elements that constitute about 45% of our genome and encode the capacity to replicate through an RNA intermediate and insert cDNA copies at de novo chromosomal locations. A causal role of RTEs/ERVs has been demonstrated in Drosophila in mediating both intracellular toxicity of TDP-43 and the intercellular spread of toxicity from glia to neurons. RTEs/ERVs are inappropriately expressed in postmortem tissues from ALS, FTD, and Alzheimer's Disease (AD) patients, but the role of RTEs/ERVs has not yet been examined in a vertebrate model of TDP-43 pathology. We utilized established transgenic mouse models that overexpress moderate levels of human wild-type TDP-43 or a mutant version with a specific ALS-causal Q331K amino acid substitution, together with a LINE-1-EGFP retrotransposon indicator line. We found that TDP-43 animals exhibit broad expression of RTEs/ERVs with LINE-1 retrotransposition in glia and neurons in the motor cortex. Expression begins with onset of neurological phenotypes, earlier in hTDP-43-Q331K animals and later in hTDP-43-WT. The LINE-1-EGFP retrotransposition reporter transiently labels spatially clustered groups of neurons and glia at the time of onset of motor symptoms, while EGFP-labeled neurons undergo cell death and are therefore lost over time. Unlabeled cells also die as a function of distance from the clusters of LINE-1-EGFP labeled neurons and glial cells. Together, these findings support the hypothesis that TDP-43 pathology triggers RTE/ERV expression in the motor cortex, that such expression marks cells for programmed cell death, with cell non-autonomous effects on nearby neurons and glial cells.},
}

@article {pmid41459056,
year = {2025},
author = {Auclair-Ouellet, N and Kassem, O and Bronner, S and Oula, ML and Binda, S},
title = {Leveraging microbiome-based interventions to improve the management of neurodegenerative diseases: evidence for effects along the microbiota-gut-brain axis.},
journal = {Frontiers in nutrition},
volume = {12},
number = {},
pages = {1699884},
pmid = {41459056},
issn = {2296-861X},
abstract = {The microbiota-gut-brain axis (MGBA) has recently emerged as a useful model for the understanding of the onset and progression of neurodegenerative diseases (NDDs). Microbiome-based interventions using biotic supplements (probiotics, prebiotics, synbiotics, postbiotics) can modulate the MGBA and constitute relevant solutions to help reduce the risk of neurological changes associated with NDDs and manage symptoms. This narrative review provides a summary of the functioning of the MGBA and of its interactions with disease processes involved in the onset and progression of NDDs. Microbiome-based interventions and their mechanisms of action are reviewed, and important considerations for the design of interventions are discussed. Next, preclinical and clinical studies on the potential of microbiome-based interventions in Alzheimer's disease (AD), Parkinson's disease (PD), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and Huntington's disease (HD) are reviewed. Evidence related to biomarkers of pathology (e.g., beta-amyloid or alpha-synuclein protein depositions), neuroinflammation, and metabolic activity is summarized, along with emerging evidence for the improvement of clinical symptoms and disease trajectories. Overall, preclinical studies show that microbiome-based supplements have significant positive effects on mechanisms and pathways involved in the pathophysiology of NDDs. Clinical studies show that these interventions provide important benefits both in terms of biomarkers and clinical symptoms. However, evidence is limited in some key clinical areas, such as mental wellbeing in AD and cognition in PD, and for the management of clinical symptoms in ALS and HD overall. Gaps in knowledge and open questions as well as perspectives for future research are discussed.},
}

@article {pmid41458376,
year = {2025},
author = {Qian, G and Ding, L and Tan, C and Wang, L and Long, C},
title = {Mucosal immune response modulated by secreted and membrane-bound hydrolases of Candida albicans in vulvovaginal candidiasis.},
journal = {Frontiers in fungal biology},
volume = {6},
number = {},
pages = {1692795},
pmid = {41458376},
issn = {2673-6128},
abstract = {Vulvovaginal candidiasis (VVC) affects the physical and mental health of millions of women worldwide. The leading cause of VVC, Candida albicans, can induce a strong mucosal inflammatory reaction during the VVC infection, where secreted and membrane-bound adhesion and hydrolases seem to be the key virulent factors to promote the mucosal antifungal immunity and immunopathology. Several hydrolases, such as Saps, Als, candidalysin, lipases, and phospholipases, have been identified in vaginal secretions isolated from VVC patients; however, the immune impacts of some hydrolases have not been well documented. In this review, we focus on the literature that addresses the immunopathogenic roles of the Als adhesin family or proteinase, such as Sap and candidalysin, in VVC. Our goal is to expand our knowledge of VVC pathogenesis in order to provide new strategies for VVC treatment.},
}

@article {pmid41457335,
year = {2025},
author = {Nicolaou, N and Nicolaou, D and Christou, S},
title = {Letter to the Editor: Comment on Palmieri et al.'s "Uveitis Following Intravitreal Injections of Faricimab: A Case Report".},
journal = {Ocular immunology and inflammation},
volume = {},
number = {},
pages = {1-2},
doi = {10.1080/09273948.2025.2610665},
pmid = {41457335},
issn = {1744-5078},
abstract = {The article provides valuable insight on presentation and management of isolated anterior uveitis and with vitritis following intravitreal (IVT) faricimab. We highlight additional points. First sterile intraocular inflammation (IOI) onset ranges from 1-35 days; however, two patterns have been described: acute onset within 5 days and delayed onset at approximately 14 days following a mean of four IVT injections, although it may occur after the first. Sterile IOI may be recognised by delayed onset, suggestive of a type IV hypersensitivity reaction rather than infectious causes and by absence of hypopyon, although may present in severe cases. Second, faricimab's dual inhibition may alter ocular immune surveillance, potentially facilitating herpes simplex virus reactivation. Increased vigilance for dendritic ulcers is therefore warranted, and antiviral therapy should be initiated prior to corticosteroids. Finally, management should be guided by severity, with anterior or vitreous tap considered to exclude exogenous endophthalmitis. Resolution typically occurs within 15 days.},
}

@article {pmid41456636,
year = {2025},
author = {Koppali, SR and Vadia, N and Varma, P and Mishra, S and Joshi, N and Bansal, P and Al-Hasnaawei, S and Chauhan, AS and Jain, H and Nathiya, D and Devi, A and Jayasingh Chellammal, HS and Gupta, P and Wal, P and Koppula, S},
title = {Neurodevelopmental origins of neurodegeneration: a lifespan perspective on brain vulnerability.},
journal = {Brain research},
volume = {},
number = {},
pages = {150134},
doi = {10.1016/j.brainres.2025.150134},
pmid = {41456636},
issn = {1872-6240},
abstract = {Neurodegenerative disorders-including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis-are increasingly understood to have origins in early neurodevelopmental disturbances. This review examines how genetic, epigenetic, and environmental factors impact brain development during critical periods, predisposing individuals to neurodegeneration later in life. Prenatal and early-life exposures such as maternal stress, malnutrition, infection, and environmental toxins can alter key developmental processes, leading to long-term vulnerability. Mechanistic pathways linking early-life disruptions to neurodegenerative outcomes include persistent mitochondrial dysfunction, chronic neuroinflammation, increased oxidative stress, and aberrant synaptic pruning, all of which contribute to progressive neuronal damage and dysfunction. The gut-brain axis is also discussed as a key intermediary, where early microbiota dysbiosis alters neuroimmune signaling and inflammatory responses, modulating susceptibility to age-related neurological disorders. In this context, the review highlights emerging molecular and imaging biomarkers capable of detecting subtle neurodevelopmental deviations that may precede clinical symptoms by decades. The paper emphasizes the need for early-life interventions, including maternal nutritional optimization, management of prenatal stress, and microbiome-targeted strategies, as potential tools to reduce long-term neurological risk. Furthermore, it proposes the integration of precision medicine approaches aimed at individualized risk assessment and therapeutic targeting of developmental pathways. Adopting a lifespan perspective, this review argues for a paradigm shift from reactive to preventive strategies in neurology. Understanding the developmental roots of neurodegeneration opens new avenues for research and intervention, enabling resilience and reducing disease burden through early diagnostics and tailored therapeutics across the lifespan.},
}

@article {pmid41456082,
year = {2025},
author = {Erro, ME and Zelaya, MV and Eraña, H and de Gordoa, JSR and García-Amigot, F and Simonovska-Serra, A and Caballero, MC and Ferrer, I and Gelpi, E and Jericó, I and Castilla, J},
title = {Variably Protease-Sensitive Prionopathy: Two New Cases With Motor Neuron-Dementia Syndrome.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.70294},
pmid = {41456082},
issn = {2328-9503},
support = {19-2021//Health Department of Navarre Government/ ; //European Regional Development Fund/ ; //Federal Ministry Labour, Social Affairs, Health, Care and Consumer Protection/ ; PID2021-122201OB-C21//Agencia Estatal de Investigación, Ministerio de Ciencia e Innovación/ ; PID2024-160022OB-I00//Agencia Estatal de Investigación, Ministerio de Ciencia e Innovación/ ; CEX2021-001136-S//Severo Ochoa Excellence accreditation/ ; },
abstract = {We describe two patients with variably protease-sensitive prionopathy (VPSPr) who developed progressive upper motor neuron symptoms, insomnia, behavioral and cognitive decline, compatible with primary lateral sclerosis associated with frontotemporal dementia (FTD). Neuropathology revealed a spongiform encephalopathy with frontotemporal and pronounced thalamic involvement, associated with fine synaptic abnormal prion protein conformer (PrP[Sc]) deposits, microplaques, and intraneuronal aggregates. Western blot analysis revealed a characteristic VPSPr proteolytic profile, lacking the diglycosylated band. Both patients were methionine homozygous at PRNP codon 129 and carried no pathogenic mutations. These cases illustrate that VPSPr can present with a prominent motor neuron syndrome and FTD features.},
}

@article {pmid41455589,
year = {2025},
author = {Ruiz-Ortiz, M and Esteban-Pérez, J and Gómez-Grande, A and Martínez-Albero, E and Benito-León, J},
title = {Motor band sign in [18]F-FDG PET/CT studies: a biomarker of degenerative upper motor neuron disease? A study of three cases and literature review.},
journal = {Neurologia},
volume = {},
number = {},
pages = {501931},
doi = {10.1016/j.nrleng.2025.501931},
pmid = {41455589},
issn = {2173-5808},
abstract = {INTRODUCTION: Motor neuron diseases (MND) encompass conditions like amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS), marked by progressive degeneration of upper and/or lower motor neurons. The identification of specific biomarkers is crucial to reduce diagnostic delays.

METHODS: This study presents three clinical cases evaluated at the Hospital Universitario 12 de Octubre, where the motor band sign on brain 18 F-FDG PET/CT aided the diagnosis of MND. The studies were conducted using a SIEMENS Biograph True Point 6, with a review of relevant literature.

RESULTS: In all three patients, PET/CT revealed hypometabolism in the prerolandic region, indicative of the motor band sign, contributing to the diagnosis of PLS or ALS.

DISCUSSION: The motor band sign on 18 F-FDG PET/CT emerges as a potential marker of upper motor neuron involvement, though the heterogeneity of MNDs and variability across studies call for further research to establish its specificity and sensitivity.

CONCLUSION: The motor band sign on 18 F-FDG PET/CT is a promising biomarker for MNDs, although further studies are required to confirm its diagnostic validity.},
}

@article {pmid41455150,
year = {2025},
author = {Akkaya, HE and Kaya, E and Gökmen, R and Gedik, MS and Akpınar, Dİ},
title = {Global trends and collaboration networks in radiology: A bibliometric analysis of the 500 most-cited articles in web of science.},
journal = {Clinical imaging},
volume = {130},
number = {},
pages = {110700},
doi = {10.1016/j.clinimag.2025.110700},
pmid = {41455150},
issn = {1873-4499},
abstract = {OBJECTIVE: This study examined global research trends in Radiology, Nuclear Medicine, and Medical Imaging by analyzing the 500 most-cited articles in the Web of Science (WoS) Core Collection.

METHODS: A bibliometric search was conducted on June 15, 2025. Biblioshiny and VOSviewer 1.6.20 were used for network visualization, including institutional collaboration, co-authorship, keyword co-occurrence, and country-level contributions. Temporal patterns were analyzed with Python 3.13.3, and descriptive statistics summarized publication data.

RESULTS: Harvard University led institutional contributions with 54 publications, followed by Massachusetts General Hospital (n = 49), University of Oxford (n = 35), Washington University (n = 29), and University of Texas (n = 26). The United States accounted for 53.4 % of all outputs, followed by the United Kingdom (21.6 %), Germany (12 %), Canada (9 %), and France (8 %). Among authors, Stephen M. Smith contributed most (19 publications), followed by Jenkinson, M (n = 14), and Friston, KJ (n = 13). The most frequent keywords were "MRI" (n = 65), "Brain" (n = 43), "fMRI" (n = 37), "Segmentation" (n = 25), and "PET" (n = 24). In addition to leading all journals in citation impact (citations per article), Neuroimage was also identified as the most productive journal overall. Regarding the average citation impact, the top-performing entities in their respective categories were: the University of Oxford (among organizations), Germany (among countries), Smith Stephen M (among authors), and the journal Neuroimage (among journals). Emerging terms included "deep learning" and "artificial intelligence." The most-cited article was Ronneberger et al.'s U-Net (2015), cited 63,448 times.

CONCLUSION: High-impact radiology research is concentrated in North America and Western Europe, with neuroimaging and artificial intelligence representing key emerging domains. These insights provide a roadmap for research prioritization and collaboration strategies.},
}

@article {pmid41455134,
year = {2025},
author = {Du, O and Wu, YJ and Li, MY and Du, JR},
title = {The role of HMGB1 in central nervous system (CNS) diseases: mechanisms and therapeutic perspectives.},
journal = {Cytokine},
volume = {198},
number = {},
pages = {157099},
doi = {10.1016/j.cyto.2025.157099},
pmid = {41455134},
issn = {1096-0023},
abstract = {Central nervous system (CNS) diseases represent a major global health burden and are among the leading causes of disability and mortality worldwide. The pathological mechanisms underlying CNS disorders are complex and multifactorial, involving processes such as neuroinflammation, oxidative stress, neuronal damage, and synaptic dysfunction. High-mobility group box 1 (HMGB1), a member of the high-mobility group box (HMGB) protein family, is predominantly localized in the nucleus under physiological conditions, where it contributes to DNA repair, transcriptional regulation, and other cellular functions. However, in various CNS pathologies-including stroke, traumatic brain injury (TBI), Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), glioblastoma (GBM), epilepsy, depression, multiple sclerosis (MS), and schizophrenia-HMGB1 is released or secreted into the extracellular space. There, it plays a key role in regulating neuroinflammation, cell death, cell migration, and tissue damage and repair, thereby contributing to disease pathogenesis and progression. HMGB1 not only functions as a critical regulator in the progression of CNS diseases but also serves as a biomarker for predicting poor clinical outcomes. Moreover, a growing body of evidence indicates that therapeutic strategies targeting HMGB1 can significantly alleviate pathological damage in various CNS disorders, highlighting its potential as a promising therapeutic target. This review comprehensively summarizes the structure, post-translational modifications, release mechanisms, and receptor systems of HMGB1, along with its roles and mechanisms in CNS diseases. It also discusses the potential of HMGB1 as a biomarker and examines emerging HMGB1-targeted therapeutic strategies, aiming to provide a theoretical foundation for the treatment and drug development of CNS disorders.},
}

@article {pmid41454905,
year = {2025},
author = {Gómez-Tortosa, E and Agüero-Rabes, P and Roa-Escobar, J and Sainz, MJ and Viñas, J and Téllez, R and Martínez-Ulloa, P and Pérez-Pérez, J},
title = {MAPT p.V363I mutation in a patient with presenile dementia and late amyotrophic lateral sclerosis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-4},
doi = {10.1080/21678421.2025.2604238},
pmid = {41454905},
issn = {2167-9223},
abstract = {There are limited reports of motor neuron disease associated with MAPT mutations. We present a woman, carrier of the pathogenic MAPT V363I mutation, who developed a presenile dementia and, after 7 years, amyotrophic lateral sclerosis affecting both bulbar and spinal segments. This mutation has been reported in ten previous cases with various cognitive phenotypes and corticobasal syndrome, but not motor neuron disease. We also review the handful of MAPT mutations associated with motor neuron disease.},
}

@article {pmid41454699,
year = {2025},
author = {Feng, B and Xiang, W and Shan, T and Chen, X and Zheng, S and Shen, S and Wang, C},
title = {Low-Temperature Aluminum-Zinc Hydrogen-Aided Battery.},
journal = {Angewandte Chemie (International ed. in English)},
volume = {},
number = {},
pages = {e24485},
doi = {10.1002/anie.202524485},
pmid = {41454699},
issn = {1521-3773},
abstract = {The need for reliable power sources in cold environments drives the development of efficient low-temperature batteries. While zinc-air batteries (ZABs) are promising due to low cost, high safety, and environmental compatibility, their performance at low temperatures is limited by sluggish kinetics. Here, we report an aluminum-zinc hydrogen-aided battery (AZ-HAB) that overcomes this limitation through a synergistic redesign of both electrodes. At the cathode, the kinetically favorable hydrogen oxidation reaction (HOR) replaces the oxygen evolution reaction (OER), reducing the charging potential and enhancing high-rate performance at low temperatures. The anode uses a composite structure (Al@Zn) with Zn pre-deposited on Al, leveraging Al's high activity and low deposition overpotential. This design reduces the full-cell resistance to one-third that of bare Zn, promotes uniform Zn deposition, and lowers polarization by 200 mV at 150 mA cm[-] [2]. The synergistic effect of both electrodes accelerates reaction kinetics, enabling an 11-fold longer cycle life than conventional ZABs at -20 °C. This work presents a viable strategy for high-performance energy storage and electric vehicles in extremely cold environments.},
}

@article {pmid41454587,
year = {2025},
author = {Coulton, JB and He, Y and Budelier, MM and Barthélemy, N and Ireland, MD and Hu, M and Graham, D and Ferguson, T and Berry, JD and Bateman, RJ and Miller, TM and Ly, CV},
title = {Neurofilament Proteoforms in Amyotrophic Lateral Sclerosis Are Different in Cerebrospinal Fluid and Blood.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78138},
pmid = {41454587},
issn = {1531-8249},
abstract = {We used targeted immunopurification-mass spectrometry (IP-MS) to characterize human neurofilament light chain (NfL) proteoforms across various compartments to assess their alterations in amyotrophic lateral sclerosis (ALS). NfL is truncated in cerebrospinal fluid (CSF) and blood in patients with sporadic ALS (sALS) and these proteoforms differ between compartments. Mid-domain species were elevated in CSF whereas plasma NfL proteoforms were mostly comprised of the tail subdomain region. Our results suggest NfL isoforms are proteolyzed and differentially distributed between ALS biofluid compartments and that analyzing by these specific regions or in ratios between regions can provide improvements in biomarker utility. These insights enhance the understanding of NfL and its potential for disease monitoring and therapeutic targeting in ALS. ANN NEUROL 2025.},
}

@article {pmid41454317,
year = {2025},
author = {Abdi, M and Sooudi, OK and Milota, M},
title = {Professional identity formation for underrepresented groups in medicine: challenges and interventions for Dutch medical schools: a systematic scoping review.},
journal = {BMC medical education},
volume = {25},
number = {1},
pages = {1715},
pmid = {41454317},
issn = {1472-6920},
mesh = {Humans ; Netherlands ; *Schools, Medical/organization & administration ; *Students, Medical/psychology ; *Social Identification ; *Minority Groups/psychology/education ; Cultural Diversity ; *Ethnicity ; },
abstract = {BACKGROUND: The concept of intersectionality is important when considering the professional identity formation (PIF) of students who are racially and ethnically underrepresented in medicine (URiM), as they must navigate race and ethnicity within the medical landscape. Despite a growing body of studies that shed light on the challenges that URiM students face in their PIF, there remains a notable lack of practical interventions for medical schools to address these challenges. Our objective is to highlight the challenges faced by URiM students and identify interventions in the literature that would be most suitable for Dutch medical schools to address them.

METHODS: This study builds upon Teo et al.'s (2022) scoping review. We examined articles from January 1, 2000, to December 31, 2021, and conducted an extended search from January 1, 2022, to November 30, 2023. Our focus was on articles exploring the intersectionality of PIF, perspectives of minoritized groups, and diversity, equity, and inclusion (DEI) within the context of PIF in medical education. We used the Systematic Evidence-Based Approach (SEBA) guided systematic scoping review, encompassing four stages: Systematic Approach, Structured Summary and Synthesis, Jigsaw Perspective, and Literature Analysis.

RESULTS: A total of 692 abstracts were reviewed, 36 full-text articles were evaluated, and 22 articles were included. URiM students encounter multiple challenges in their PIF journeys such as a lack of role models and representation, experiences of microaggressions, and pressure to assimilate into the majority culture. The proposed interventions for medical schools included diversifying recruitment practices to create more role models, developing curricula to address these challenges, and establishing a supportive network for URiM students.

CONCLUSIONS: Our study highlights the pressing need for Dutch medical schools to address the challenges faced by URiM students in PIF. The identified interventions offer actionable strategies to cultivate a more supportive and equitable learning environment. The implementation of these interventions has the potential to enhance URiM students' educational experiences, reduce disparities, and promote diversity within the medical profession. These findings underscore the importance of ongoing efforts to prioritize inclusivity and equity in medical education.},
}

Humans
Netherlands
*Schools, Medical/organization & administration
*Students, Medical/psychology
*Social Identification
*Minority Groups/psychology/education
Cultural Diversity
*Ethnicity

@article {pmid41454086,
year = {2025},
author = {Mi, X and Shan, K and Ye, X and Cheng, R},
title = {AAD-2004 through clearing H2O2 reduces astrocyte proliferation and promotes neural regeneration after spinal cord injury.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-33322-x},
pmid = {41454086},
issn = {2045-2322},
support = {ZKKY2023003//Zhejiang Medical Association/ ; 2024KY658//Scientific Research Program of Zhejiang Medical Technology/ ; },
abstract = {To assess the effect of AAD-2004 on spinal cord injury (SCI) and to explore its mechanism, we employed an in vitro model using OGD/R-challenged astrocytes to investigate the effects of AAD-2004 against cell death (terminal deoxynucleotidyl transferase dUTP nick-end labeling, tunel), oxidative stress (H2O2 level), and the expression of the key neuroprotective factor MAP2.AAD-2004[2-hydroxy-5-[2-(4-trifluoromethylphenyl)-ethylaminobenzoic acid] is a hydrogen peroxide(H2O2) scavenger primarily used for the treatment of amyotrophic lateral sclerosis and Alzheimer disease that has demonstrated certain neuroprotective properties. In parallel, modified allen's method was adopted, further exploring the potential molecular mechanism in vivo. Based on these conditions, histological and behavioral analysis were performed by Nissl staining, basso mouse scale and footprint analysis. The level of molecules associated with glial scar formation, nerve regeneration, axonal regeneration and H2O2 level were analyzed using western blot, immunofluorescence staining and H2O2 kit. AAD-2004 significantly improved the movement function after SCI and inhibited the proliferation of astrocytes, thus preventing the formation of glial scar by inhibiting of H2O2. At the same time, AAD-2004 promoted nerve regeneration, and the effect was due to neuronal regeneration and axonal regeneration pathways. The expression levels of GFAP and vimentin were significantly downregulated in AAD-2004-treated, and the expression level of Ki67 and PH3 were downregulated. The mean fluorescence intensity of neuronal regeneration (Neun[+]and MAP2[+]) and axonal regeneration-related (NF[+] and GAP43[+]) were significantly upregulated after AAD-2004 treatment. Scavenging H2O2 level is a viable therapeutic strategy, and that AAD-2004 is prospective, and that scavenging H2O2 facilitated nerve regeneration and inhibited glial scar formation for SCI.},
}

@article {pmid41453576,
year = {2025},
author = {Viteri, JA and Kerr, NR and Brennan, CD and Paradkar, P and Suleiman, LA and Wendt, CD and Xu, C and An, H and Wang, M and Nishimune, H and Santin, JM and Arnold, WD},
title = {Reduced cortico-muscular output is associated with intrinsic hypoexcitability and reduced persistent inward currents in motor cortex neurons of TDP-43[Q331K] ALS mice.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107247},
doi = {10.1016/j.nbd.2025.107247},
pmid = {41453576},
issn = {1095-953X},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by spinal and cortical motor neuron loss and progressive neuromuscular decline. When ALS pathology involves the primary motor cortex (PMC), cortical excitability is often disrupted, yet how these alterations map onto motor deficits during symptomatic ALS remains unclear. To investigate this, we examined the neuromuscular function, cortico-muscular output, and neuronal excitability of symptomatic 4-month-old TDP-43[Q331K] mice. TDP-43 mice exhibited reduced neuromuscular excitability and impaired strength compared to WT mice. Cranial motor evoked potentials were significantly reduced in TDP-43 mice, indicating decreased cortical output to muscle. Compared to WT mice, whole-cell patch-clamp recordings from TDP-43 PMC layer V pyramidal neurons revealed intrinsic hypoexcitability, diminished persistent inward currents (PICs), and decreased excitatory synaptic activity. Corroborating PIC findings, immunohistochemical analysis showed that PMC layer V neurons exhibited reduced signal intensity of the PIC-associated proteins Nav1.6 and 5-HT2C. Bulk RNA-seq of the cortex showed distinct transcriptional profiles in TDP-43 mice, with enrichment analysis indicating altered pathways relating to ion transport, synaptic signaling, and neuronal excitability. These results suggest that cortex-wide transcriptional changes may reflect broader and additional molecular mechanisms underlying cortical hypoexcitability in ALS. Together, our results demonstrate that symptomatic TDP-43[Q331K] mice exhibit a reduction in cortico-muscular output and PMC neuron excitability, accompanied by reduced PICs and PIC-associated proteins within these neurons. These findings identify cortical hypoexcitability as a defining feature of the TDP-43[Q331k] ALS mouse model and establish multi-level associations between cortical cellular-level dysfunction and impaired motor systems output.},
}

@article {pmid41452185,
year = {2025},
author = {Wilson, J and Toriumi, DM},
title = {Invited Commentary on: Uzunoğlu et al.'s "The Effect of Subperiosteal Drain Placement on Periorbital Edema and Ecchymosis Following Ultrasonic Piezoelectric-Assisted Rhinoplasty: A Prospective Comparative Study".},
journal = {Facial plastic surgery & aesthetic medicine},
volume = {},
number = {},
pages = {},
doi = {10.1177/26893614251407595},
pmid = {41452185},
issn = {2689-3622},
}

@article {pmid41450325,
year = {2025},
author = {Gamez, J and Carmona, F and Syriani, EE and Morales-Fuciños, M and Gamez, A},
title = {Early Dropped Head Syndrome Is More Prevalent in C9orf72 and FUS/TLS ALS.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70126},
pmid = {41450325},
issn = {1097-4598},
abstract = {INTRODUCTION/AIMS: Dropped head syndrome (DHS) is common in advanced stages of amyotrophic lateral sclerosis (ALS), but infrequently reported among the early symptoms. We explored the frequency of DHS in a genetic ALS cohort harboring pathogenic variants to determine whether DHS is a prognostic factor for survival, particularly when appearing at an early stage.

METHODS: We collected the following variables to investigate a phenotype/genotype correlation: pathogenic variant (PV), sex, age at clinical ALS onset, time between ALS onset and DHS onset, and between DHS onset and death. DHS appearing within 12 months of clinical onset was classified as early DHS (EDHS); otherwise, as late DHS (LDHS).

RESULTS: We observed DHS in 62 of 93 patients with genetic ALS, with a median of 26.5 months between ALS clinical onset and identification of DHS. DHS was present in 72.1% of the 43 patients with C9orf72 expansions, 52.9% of the 34 with SOD1, 100% of the 10 with FUS/TLS, and 50% of the 6 with other ALS gene PVs. EDHS appeared in 16 patients. Ten EDHS patients were C9orf72, and six were FUS/TLS. DHS was a significant factor for survival in the age-adjusted Cox regression model. The hazard ratio was 11.63 times higher for patients with DHS, with age as a concomitant variable.

DISCUSSION: Our results suggest that DHS is more prevalent in patients with C9orf72 and FUS/TLS than in those with SOD1 and other ALS-linked genes, and a risk factor for short survival, especially when appearing within 12 months of ALS onset.},
}

@article {pmid41450148,
year = {2025},
author = {Li, A and Cao, SQ and Fang, EF and Su, H},
title = {Pharmacological activation of mitophagy antagonizes motor neuron degeneration in a cross-species platform of amyotrophic lateral sclerosis.},
journal = {Autophagy},
volume = {},
number = {},
pages = {},
doi = {10.1080/15548627.2025.2610450},
pmid = {41450148},
issn = {1554-8635},
abstract = {Mitochondrial dysfunction is widely recognized as a key driver of aging and neurodegenerative diseases, with mitophagy acting as an essential cellular mechanism for the selective clearance of damaged mitochondria. While pharmacological activation of mitophagy has been reported to exert beneficial effects across multiple neurodegenerative diseases, its functional relevance in amyotrophic lateral sclerosis (ALS) remains poorly characterized. Our recent study published in EMBO Molecular Medicine demonstrates that PINK1-PRKN-dependent mitophagy is markedly impaired in ALS motor neurons. Through high-content drug screening, we identified a potent mitophagy agonist isoginkgetin (ISO), a bioflavonoid from Ginkgo biloba that stabilizes the PINK1-TOMM complex on the outer mitochondrial membrane, enhances PINK1-PRKN-dependent mitophagy, and ameliorates motor neuron degeneration in ALS-like Caenorhabditis elegans, mouse models, and induced pluripotent stem cell-derived motor neurons. Consequently, ISO is able to alleviate ALS-associated phenotypes. In this commentary, we contextualize these findings broadly to discuss whether pharmacologically induced mitophagy can act as an effective therapeutic strategy, distinct from current clinical approaches, for the development of ALS-targeted treatments.},
}

@article {pmid41449086,
year = {2025},
author = {Jankowiak, T and Cholewiński, M and Kryściak, K and Krok, E and Grycz, K and Bączyk, M},
title = {Increase in Ia Afferent Synaptic Excitation of SOD1 G93A Mouse Motoneurons by 2-Week Anodal Trans-Spinal Direct Current Stimulation Does Not Ameliorate the Cellular Burden of the Disease.},
journal = {The European journal of neuroscience},
volume = {62},
number = {12},
pages = {e70375},
pmid = {41449086},
issn = {1460-9568},
support = {2017/26/D/NZ7/00728//National Science Center/ ; 2019/35/B/NZ4/02058//National Science Center/ ; },
mesh = {Animals ; *Motor Neurons/physiology ; Male ; *Amyotrophic Lateral Sclerosis/physiopathology/therapy/genetics/pathology ; Mice ; Mice, Transgenic ; *Superoxide Dismutase/genetics ; *Excitatory Postsynaptic Potentials/physiology ; Superoxide Dismutase-1 ; Receptors, AMPA/metabolism ; *Synapses/physiology ; Spinal Cord/physiopathology ; Electric Stimulation ; },
abstract = {An imbalance between cells' intrinsic excitability and synaptic excitation levels underlies the spinal motoneuron (MN) pathophysiology in Amyotrophic Lateral Sclerosis. Recently, a transient restoration of the deficient Ia synaptic excitation of spinal MNs in the presymptomatic SOD1 G93A mice was achieved by applying a single trans-spinal direct current stimulation (tsDCS) session. Here we investigate whether two-week repeated tsDCS applied to presymptomatic SOD1 G93A animals can permanently alter spinal MN synaptic excitation levels and in this way affect intracellular metabolic pathways and cellular burden of the disease. Anodal, cathodal, or sham polarization of 100 μA was applied to P30-P35 SOD1 G93A male mice, and passive membrane properties and Ia excitatory post-synaptic potential (EPSP) characteristics were investigated by intracellular recordings of spinal MNs in vivo. A second cohort of animals was used to test the impact of our intervention on Ia synapse morphology, intracellular metabolic pathways activity, and disease markers. Anodal tsDCS evoked a strong increase in maximal Ia EPSPs amplitudes, coupled with a significant upregulation of GluR4 subunits of AMPA receptors at the Ia synapse. The cathodal polarization failed to induce any alteration to Ia synapse morphology, but increased the input resistance of MNs. However, changes in MN electrophysiological profile and Ia synapse morphology did not translate into alterations of intracellular molecular pathways activity and did not decrease the cellular burden of the disease. Our results indicate a strong polarity-dependent plasticity of spinal MNs in SOD1 G93A mice in response to tsDCS, which however does not alleviate disease burden.},
}

Animals
*Motor Neurons/physiology
Male
*Amyotrophic Lateral Sclerosis/physiopathology/therapy/genetics/pathology
Mice
Mice, Transgenic
*Superoxide Dismutase/genetics
*Excitatory Postsynaptic Potentials/physiology
Superoxide Dismutase-1
Receptors, AMPA/metabolism
*Synapses/physiology
Spinal Cord/physiopathology
Electric Stimulation

@article {pmid41446138,
year = {2025},
author = {Ozguney, B and Puterbaugh, RZ and Viswanathan, R and Shenoy, J and Mohanty, P and Mittal, J and Fawzi, NL},
title = {Site-specific methionine oxidation alters structure and phase separation of TDP-43 C-terminal domain.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2025.12.15.694486},
pmid = {41446138},
issn = {2692-8205},
abstract = {TAR DNA binding protein 43 (TDP-43), a key protein linked to ALS pathology, undergoes phase separation and forms functional assemblies via condensation within cells. The conserved region (CR) within its C-terminal domain (CTD) mediates self-assembly through helix-helix interactions, while the flanking intrinsically disordered regions (IDRs) contribute to phase separation through transient interactions involving aromatic and hydrophobic residues. The CTD contains ten methionine residues distributed equally between these regions, making it particularly susceptible to oxidative modifications. While methionine oxidation is known to impair phase separation, neither the precise mechanism nor the specific contribution of methionines in the CR compared to the IDRs has been determined. Here, we combine NMR spectroscopy and all-atom molecular dynamics (MD) simulations to reveal if and how methionine oxidation in each region differentially affects CTD structure and phase separation. We demonstrate that all methionine residues are vulnerable to oxidation, leading to distinct regional effects: oxidation of CR methionines disrupts helical structure and directly impairs intermolecular helical association, while oxidation of IDR methionines disrupts long-range contacts. Hence, oxidation of methionines in both regions contributes to impaired phase separation, albeit through different mechanisms. These findings establish methionines as critical redox-sensitive modulators of TDP-43 phase behavior and provide molecular insights into how oxidative stress may contribute to TDP-43 dysregulation in neurodegenerative diseases.},
}

@article {pmid41444821,
year = {2025},
author = {Safkhani, M and Ghorbani Fard, M},
title = {Two secure authentication protocols for mitigating vulnerabilities in IoD.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-33020-8},
pmid = {41444821},
issn = {2045-2322},
support = {1404/385773//Shahid Rajaee Teacher Training University/ ; },
abstract = {The Internet of Drones (IoD) is a network layer control system that manages the communication of Unmanned Aerial Vehicles (UAVs). Drones have emerged as a novel approach to addressing everyday human challenges and are now used in a variety of domains, such as personal activities (e.g., photography and videography), urban applications (e.g., traffic monitoring and structural inspection), commercial operations (e.g., power line and tower inspection), agriculture, and military operations. Given the rapid growth of UAVs and their expanding applications, interconnecting drones to form an IoD is a desirable trend for enhancing flight safety and quality. However, challenges related to security, privacy, and inter-drone communication remain significant obstacles. Numerous authentication protocols have been developed to address these concerns. Recently, Zhang et al. proposed a PUF-based authentication scheme that uses unique identifiers and hash functions to secure authentication in the IoD environment. However, in this paper, we demonstrate that Zhang et al.'s scheme is vulnerable to several attacks, including secret value disclosure, integrity violation, key extraction, traceability, and anonymity violation. The presented attacks are shown to have a success probability of one. We also introduce two enhanced protocols that, through both informal and formal security proofs using the Scyther tool, demonstrate that they do not suffer from the vulnerabilities found in the earlier protocol. The communication costs of the proposed protocols (a) and (b) have increased by [Formula: see text] and [Formula: see text], respectively, compared to the previous protocol. The computational costs for the proposed protocols (a) and (b) have also increased by [Formula: see text] and [Formula: see text], respectively, while the storage costs in both proposed protocols remain unchanged compared to the previous protocol. It is true that the costs in the proposed protocols have risen; however, the previous design was vulnerable to various attacks, whereas the proposed protocols have demonstrated better security and have successfully achieved all their security objectives.},
}

@article {pmid41442833,
year = {2025},
author = {Zhong, Q and Wang, X and Xu, Y and Wang, R and Zhou, M and Liu, X},
title = {Response to "Constructive appraisal of Zhong et al.'s study on Mycobacterium tuberculosis dormant antigens and PB2-DIMQ vaccine: Opportunities for translational strengthening".},
journal = {Tuberculosis (Edinburgh, Scotland)},
volume = {156},
number = {},
pages = {102723},
doi = {10.1016/j.tube.2025.102723},
pmid = {41442833},
issn = {1873-281X},
}

@article {pmid41441345,
year = {2025},
author = {Endo, K and Kubota, K and Karino, K and Sato, R and Miura, S and Ueda, Y and Iwashita, Y},
title = {Setting the Next Vital Sign Observation Interval as a Learning Objective in Simulation-Based Nursing Education: A Prospective Exploratory Observational Study.},
journal = {Nursing reports (Pavia, Italy)},
volume = {15},
number = {12},
pages = {},
pmid = {41441345},
issn = {2039-4403},
abstract = {Background/Objectives: Abnormal vital signs often precede in-hospital clinical deterioration, but little is known about how nurses decide when to recheck vital signs. We examined how nurse characteristics relate to the next vital sign observation interval after detecting abnormal values and how this decision could be used as a learning objective in simulation-based education. Methods: In this prospective exploratory observational study at a university hospital in Japan, twenty-seven nurses used a full-body patient simulator across three scenarios: normal, low-urgency, and moderate-risk (moderately abnormal vital signs according to National Early Warning Score 2 [NEWS2] risk bands). After each assessment, participants specified in hours the interval they considered appropriate for the next vital sign observation. Nurse characteristics included years of clinical experience, advanced life support (ALS) training, and prior experiences recognizing or responding to deterioration. Mann-Whitney U tests and multiple regression were used to explore univariate and adjusted associations. Results: In the low-urgency scenario, ALS training was associated with shorter intervals (median 1 h vs. 3 h; p = 0.04). In the moderate-risk scenario, univariate analyses showed shorter intervals among nurses with greater experience and among those with ALS training (both p < 0.01). In adjusted models for the moderate-risk scenario, years of experience and prior experiences of recognizing and responding to deterioration were independently associated with shorter intervals (all p < 0.05), whereas ALS training was not. Conclusions: The decision to shorten observation intervals appears to reflect experiential aspects of clinical judgment. Integrating "setting the next observation interval" as an explicit learning objective in simulation may help strengthen nurses' clinical judgment for early recognition of deterioration. As an exploratory, single-center study with a small sample and fixed scenario order, these findings should be interpreted cautiously and used to guide larger confirmatory studies and curricular design. This study was not registered.},
}

@article {pmid41440090,
year = {2025},
author = {Martucci, G and Bonilauri, SC and Canalini, A and Baraldi, M and Costantini, L and Mora, F and Vacondio, P},
title = {Integrating Neurology, Palliative Care and Emergency Services in ALS: A Community-Integrated Neuropalliative Pathway in Modena, Italy.},
journal = {Brain sciences},
volume = {15},
number = {12},
pages = {},
pmid = {41440090},
issn = {2076-3425},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that causes severe motor, respiratory and communication impairment and imposes a high psychosocial burden on patients and families. Recent evidence shows that integrated neuropalliative care-early collaboration between neurology and palliative services with community support-improves quality of life and reduces avoidable hospitalisations. Yet there are few descriptions of how such integration is operationalised.

OBJECTIVE: This study examines a Community-Integrated Neuropalliative Pathway (CINP) implemented in the province of Modena (Emilia-Romagna, Italy), analysing how neurology, palliative care and emergency services collaborate to provide continuous, person-centred care for people with ALS.

METHODS: A single, holistic case study was conducted following Yin's analytical approach. Data sources included ten semi-structured interviews with neurologists, palliative physicians, nurses, home-care professionals and emergency clinicians; ethnographic observations in the ALS outpatient clinic; relevant organisational documents (the regional Clinical Pathway on ALS); and aggregated quantitative data from the palliative care registry (January 2023-December 2024). Thematic analysis with investigator triangulation was used to explore care integration, advance care planning and emergency coordination. Quantitative data were summarised descriptively.

RESULTS: Three interrelated themes were identified: (1) Progressive and flexible integration between neurology and palliative care. Neurologists remained longitudinal reference points while palliative teams were activated in response to evolving needs and became more relevant with the progression of the disease. Regular multidisciplinary meetings and shared discharge planning facilitated coordination. (2) The shared culture of advance care planning. Professionals framed advance care planning (ACP) as a relational, iterative process anchored in therapeutic relationships. Shared care plans, once completed, triggered an electronic Emergency Warning ("warning 118") procedure that notified the emergency service of patient preferences. (3) The integration of palliative and emergency services. The warning system enabled emergency clinicians to respect care plans and avoid aggressive interventions during crises. Quantitative data on 47 ALS patients followed by territorial palliative services showed that 16 had an active Emergency Warning flag; among these, most died at home or in a hospice rather than in hospital.

CONCLUSIONS: The Modena CINP exemplifies how a public health system can operationalise early neuropalliative integration and connect hospital, community and emergency services. The qualitative findings illustrate the cultural and organisational shifts required for continuous care, while the quantitative data show that the system is correctly used and that patients with the Emergency Warning activation died mostly at home or in a hospice. Lessons from this analytical case study can inform the development of similar pathways in other regions, although further research is needed to assess outcomes in larger populations and such models need to be adapted to local contexts.},
}

@article {pmid41440030,
year = {2025},
author = {Su, J and Alaiz Noya, J and Lingappa, AF and Solas, D and Tong, J and Daughrity, L and Castanedes-Casey, M and Kurti, A and Dickson, DW and Lingappa, VR and Petrucelli, L and Zhang, Y},
title = {Preclinical Evaluation of the Assembly Modulator PAV-615 in a Mouse Model of C9orf72-Associated ALS/FTD.},
journal = {Cells},
volume = {14},
number = {24},
pages = {},
pmid = {41440030},
issn = {2073-4409},
support = {ADSF-24-1284327-C//Alzheimer's Disease Strategic Fund grant/ ; NA//Robert Packard Center for ALS Research at Johns Hopkins/ ; NA//Florida Department of Health Ed and Ethel Moore Alzheimer's Disease Research Program/ ; NA//BrightFocus Foundation/ ; NA//Target ALS Foundation/ ; U19 AG063911/AG/NIA NIH HHS/United States ; NA//Cure Alzheimer's Fund/ ; NA//Kissick Family Foundation/ ; U54NS123743, R35 NS137447, P01NS084974, R01NS132330 and R01NS117461//National Institutes of Health/National Institute of Neurological Disorders and Stroke/ ; P01 NS084974/NS/NINDS NIH HHS/United States ; P30 AG062677/AG/NIA NIH HHS/United States ; NA//Association for Frontotemporal Degeneration Biomarkers Initiative/ ; R01 NS117461/NS/NINDS NIH HHS/United States ; R01 AG089380/AG/NIA NIH HHS/United States ; R01 NS132330/NS/NINDS NIH HHS/United States ; U54 NS123743/NS/NINDS NIH HHS/United States ; 5P30AG0062677, ALLFTD U19AG063911, R01AG089380 and R01AG085307//National Institutes of Health/National Institute on Aging/ ; R01 AG085307/AG/NIA NIH HHS/United States ; R35 NS137447/NS/NINDS NIH HHS/United States ; },
mesh = {Animals ; *C9orf72 Protein/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/pathology/metabolism ; Disease Models, Animal ; *Frontotemporal Dementia/drug therapy/genetics/pathology/metabolism ; Mice ; Humans ; Male ; Mice, Transgenic ; Drug Evaluation, Preclinical ; },
abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal neurodegenerative diseases that share clinical and pathological features, as well as genetic causes. A G4C2 repeat expansion in chromosome 9 open reading frame 72 (C9orf72) is the most common genetic cause of ALS and FTD, collectively referred to as c9ALS/FTD. Assembly modulation is a new therapeutic approach which appears to target allosteric sites on aberrant forms of multi-protein complexes and restore them to the healthy state. Recent findings demonstrate that tetrahydroisoquinolone (THIQ)-based protein assembly modulators can ameliorate ALS/FTD-associated phenotypes in cellular and animal models. In the present study, we investigated the effects of PAV-615, a novel and advanced THIQ-based modulator, in a c9ALS/FTD mouse model expressing 149 G4C2 repeat expansions (referred to as 149R mouse model). Specifically, PAV-615 was administered to 5-month-old 149R mice via intraperitoneal injection for one month. Motor function was evaluated using the hang wire test, while anxiety-like behavior and hyperactivity were assessed using the open-field test. Pathological markers, including dipeptide repeat (DPR) proteins, phosphorylated TAR DNA-binding protein 43 (pTDP-43) and ataxin 2-positive stress granules, were quantified by Meso Scale Discovery and immunohistochemistry assays. Compared with vehicle-treated controls, PAV-615 significantly improved motor performance and modestly reduced anxiety-like behavior and hyperactivity in 149R mice. Moreover, PAV-615 treatment significantly decreased cortical DPR, pTDP-43 and ataxin 2-positive stress granule burdens. These results support assembly modulation as a promising therapeutic approach treatment of ALS/FTD.},
}

Animals
*C9orf72 Protein/genetics/metabolism
*Amyotrophic Lateral Sclerosis/drug therapy/genetics/pathology/metabolism
Disease Models, Animal
*Frontotemporal Dementia/drug therapy/genetics/pathology/metabolism
Mice
Humans
Male
Mice, Transgenic
Drug Evaluation, Preclinical

@article {pmid41439884,
year = {2025},
author = {Di Gregorio, R},
title = {A Novel Single-Loop Mechanism for Neck Rehabilitation.},
journal = {Biomimetics (Basel, Switzerland)},
volume = {10},
number = {12},
pages = {},
pmid = {41439884},
issn = {2313-7673},
support = {FAR 2023//University of Ferrara/ ; },
abstract = {Trauma, amyotrophic lateral sclerosis (ALS), and head and neck cancer (HNC), which cause neck pain, are only some of the possible issues requiring suitable therapy for alleviating or even healing the neck dysfunctions they cause. Static and dynamic neck braces are commonly employed in therapies for neck recovery and in the necessary measurements to quantify neck impairment or to set up a suitable therapy. Serial and parallel mechanisms, among others, have been proposed for neck braces. Here, a novel single-loop spherical mechanism is proposed for a possible neck brace. Its kinematics and mobility analyses are presented with reference to their specific applications in a neck brace. Then, dimensional synthesis with a set of neck brace's kinematic requirements is addressed to compute the geometric constants that guarantee an orientation workspace similar to that of the human neck. The presented analyses and syntheses show that the new proposal is effective and can alleviate some concerns about already-proposed mechanisms for neck braces.},
}

@article {pmid41438688,
year = {2026},
author = {Su, T and Li, Z and Yang, Y and Dai, Y and Li, Y and Zhao, H},
title = {In vitro 3D models of neuron-astrocyte interactions.},
journal = {Biochemistry and biophysics reports},
volume = {45},
number = {},
pages = {102400},
pmid = {41438688},
issn = {2405-5808},
abstract = {The pathological processes of neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis) also include relationships between neuron and glia cells. Conventional two-dimensional (2D) cell cultures have limitations to mimic the microenvironment of cells inside living organisms because of flaws in intercellular relationships investigated using 2D cell cultures. Recent advances have introduced three-dimensional (3D) cell cultures that have the capability to create 3D cellular architecture to mimic advanced platforms for scientific inquiries into neurodegenerative diseases, simulating microenvironments inside living organisms.This review provides a brief overview of the development of in vitro 3D cell culture models of astrocytes and attempts to highlight the role of astrocytes in crucial pathophysiologic events occurring in 3D cultures. Studies have shown the use of in vitro 3D cultures to better represent the dual functions of astrocytes in neurodegenerative disorders. Looking ahead to the future, novel advances in microfluidics and multi-omics analysis promise to further improve 3D cultures and push forward new insights into neurological dysfunction to spark innovative advances for treatment strategies.},
}

@article {pmid41438236,
year = {2025},
author = {Li, T and Gao, Y and Zhou, J and Chen, Y and Zhang, S and Gong, X and Liu, Y},
title = {Advancements in the application of brain-computer interfaces based on different paradigms in amyotrophic lateral sclerosis.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1658315},
pmid = {41438236},
issn = {1662-4548},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurological condition that leads to the gradual loss of movement and communicative abilities, significantly diminishing the quality of life for affected individuals. Recent advancements in neuroscience and engineering have propelled the swift evolution of brain-computer interfaces (BCIs), which are now extensively utilised in medical rehabilitation, military applications, assistive technologies, and various other domains. As a communication medium facilitating direct interaction between the brain and the external world independent of the peripheral nervous system, BCI provides ALS patients with an innovative method for communication and control, offering unparalleled prospects for improving their quality of life. Recent collaborative endeavours among several specialists have markedly enhanced the precision and velocity of diverse BCI paradigms, signifying a breakthrough in BCI applications for ALS. Nonetheless, obstacles and constraints remain. This study methodically extracted pertinent literature from the Web of Science and PubMed databases in accordance with PRISMA guidelines. Following stringent inclusion and exclusion criteria, 23 studies were identified. This data allows us to summarise the application results and current limitations of several BCI paradigms in motor control and communication, while delineating prospects in multimodal fusion and adaptive calibration. This review presents evidence-based references for the effective translation and application of BCI technology in ALS rehabilitation.},
}

@article {pmid41437944,
year = {2026},
author = {Tannemann, N and Tsarenko, O and Herbstreit, F and Gestmann, M and Brenner, T and Szalai, C},
title = {Enhancing theoretical BLS knowledge with virtual reality: a randomized controlled trial in medical students.},
journal = {Resuscitation plus},
volume = {27},
number = {},
pages = {101169},
pmid = {41437944},
issn = {2666-5204},
abstract = {BACKGROUND: High-quality cardiopulmonary resuscitation (CPR) training, including both technical and non-technical skills, is essential for medical students. Virtual reality (VR) offers immersive learning environments that may enhance traditional teaching methods. This study investigates the impact of a single VR session prior to an Advanced Life Support (ALS) course on knowledge and performance of basic life support skills among medical students.

METHODS: In this single blind randomized controlled trial, 126 fourth-year medical students with prior Basic Life Support (BLS) training were assigned to either an intervention group (n = 66) with an additional 3-part immersive VR session covering BLS theory and practice or a control group (n = 60) receiving standard preparation. All participants underwent a seminar based on advanced life support principles as dictated by the European Resuscitation Council (ERC) and International Liaison Committee on Resuscitation (ILCOR) guidelines. Theoretical knowledge was assessed via multiple-choice questionnaires at three time points (baseline, post-course, 12 weeks later). Practical skills were evaluated through an Objective Structured Clinical Examination (OSCE). Data were analyzed using Wilcoxon tests, repeated-measures ANOVA, and linear mixed models. Student evaluations were used to gauge subjective satisfaction with the scenario during teaching.

RESULTS: No significant differences were observed between groups at baseline. The intervention group demonstrated significantly greater gains in knowledge at both post-course (p < 0.01) and follow-up (p = 0.04). However, no significant differences were found in OSCE performance. The VR group's improvement over time was significantly higher, suggesting a positive effect of VR on knowledge retention. Students were satisfied with the addition of a VR scenario in the teaching format.

CONCLUSION: A single VR session prior to ALS training enhanced theoretical knowledge but did not significantly affect practical performance. Students were open to integration of the technology into training, so that VR may serve as a valuable adjunct in CPR education. Further research is needed to evaluate its long-term impact and the optimal integration method into curricula.},
}

@article {pmid41437896,
year = {2025},
author = {Lona-Durazo, F and Byrne, RP and Pilon, MO and Greicius, MD and Dubé, MP and Belloy, ME and McLaughlin, RL and Gagliano Taliun, SA},
title = {Sex-aware causal inference assessment of the immune system in complex neurodegenerative diseases.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awaf474},
pmid = {41437896},
issn = {1460-2156},
abstract = {Sex differences, in terms of prevalence, symptoms and disease progression, are established in the etiology of complex neurodegenerative diseases, including amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease, but the underlying biology driving these differences remains poorly understood. There is emerging evidence, through genetic and functional analyses, affirming the role of the immune system in such diseases, but a thorough assessment of sex differences linking the immune system and neurodegenerative diseases is understudied. Here, we applied a robust causal inference approach, two-sample Mendelian randomization, to evaluate the causal effect of immune-related protein levels on three neurodegenerative diseases with large-scale sex-stratified genome-wide association data available: amyotrophic lateral sclerosis (females = 10,895 cases, 57,062 controls; males = 15,547 cases, 50,145 controls), Parkinson's disease (females = 7,947 cases, 90,662 controls; males = 13,020 cases, 89,660 controls) and Alzheimer's disease (females = 18,822 cases, 281,415 controls; males = 17,293 cases, 213,339 controls). As exposures, we focused on 932 immune system-related proteins with significant protein cis-quantitative trait loci (FDR cutoff < 0.01) from a large sex-combined plasma protein dataset (N = 33,477), for which corresponding genes were included in the Immunology Database and Analysis Portal gene list. We tested for a causal relationship between genetically predicted levels of each of these proteins and each neurodegenerative disease in sex-stratified and sex-combined data, followed by colocalization and estimation of sex-differential effects. We additionally performed exploratory analyses using sex-combined CSF protein cis-quantitative trait loci (N = 971) as exposures. We observed evidence for a sex-differential causal relationship between FCGR2A and Parkinson's disease, and between CD2AP, MAMDC2, PCDH17 or CSF3 and Alzheimer's disease. We validated significant results using two independent protein cis-quantitative trait loci datasets for those plasma proteins available. After performing sensitivity analyses, we validated the potential causal relationships of OMG on Parkinson's disease and of GRN, SERPINF2 and TREM2 on Alzheimer's disease. Mendelian randomization with CSF protein cis-quantitative trait loci showed a potential causal effect of ADGRE2, GPNMB and COLEC11 on Parkinson's disease and of CD33 on Alzheimer's disease, without evidence of sex-differential effects. Finally, we substantiated our findings of protein-disease pairs using triangulation, specifically reporting independent supporting evidence from the literature and drug-related databases. Overall, our results point to potential causal effects of genetically predicted levels of immune system-related plasma and CSF proteins in Alzheimer's disease and Parkinson's disease, some of which may be considered as potential candidates for drug development.},
}

@article {pmid41437053,
year = {2025},
author = {Su, WM and Duan, QQ and He, SY and Liu, RY and Wen, XJ and Zhang, N and Chen, T and Cao, B and Chen, YP},
title = {Loss of Y chromosome and its implications in male amyotrophic lateral sclerosis: insights from the UK Biobank.},
journal = {BMC medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12916-025-04594-x},
pmid = {41437053},
issn = {1741-7015},
support = {no. 82371422 and no. 81971188//the National Natural Science Fund of China/ ; no. 2022YFC2703101//the National Key Research and Development Program of China/ ; no. 2023HXFH032//the 1·3·5 project for disciplines of excellence Clinical Research Fund, West China Hospital, Sichuan University/ ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) shows a male predominance, yet the underlying mechanism remains unclear. Although the loss of Y chromosome (LOY) in peripheral blood - a male-specific genetic alteration - has been implicated in certain neurodegenerative disorders (NDDs), its association with ALS in men remains unexplored and has not been explored.

METHODS: We focused on men in the UK Biobank to investigate whether LOY influences the risk and prognosis of ALS. Initially, the LOY level for each male participant was determined using sequencing data. Subsequently, Cox proportional hazards (Cox PH) model analysis was used to assess LOY-associated risk of ALS; thirdly, piecewise linear regression, Kaplan-Meier, and Cox PH analysis assessed LOY's associations with ALS age at onset (AAO) and survival. Fourthly, multiple analytical methods were implemented to explore the relationship between LOY and ALS indicators, including plasma GFAP (glial fibrillary acidic protein) and NfL (neurofilament light chain). Finally, sensitivity analysis was carried out.

RESULTS: Our final cohort consisted of 158,953 male participants, with a mean follow-up of 11.7 years. Among them, 297 individuals developed ALS. After adjusted multiple confounding factors, including C9orf72 hexanucleotide repeat expansion (HRE), male participants with LOY exhibited an elevated risk of developing ALS (HR [95% CI]: 1.619 [1.059-2.475], p = 0.026). LOY carrier may be more likely to be associated with a later AAO and shorter survival; however, this association did not reach statistical significance in multivariate models. Additionally, our findings revealed that LOY was significantly associated with elevated plasma NfL levels (p = 0.004). Moreover, the median Log2 R ratios of Y chromosome (mLRRY value) exhibited a modest inverse correlation with plasma GFAP levels (Pearson's r = - 0.059). Nevertheless, LOY did not exert an influence on the longitudinal trends of NfL and GFAP and was not clearly associated with C9orf72 HRE status.

CONCLUSIONS: Our results indicate that LOY makes a potential contribution to the risk of ALS and the elevation of plasma NfL levels. While LOY's impact on ALS AAO and survival requires further validation, these findings identify it as a promising sex‑specific therapeutic target and support its potential for stratifying male ALS patients toward personalized treatments.},
}

@article {pmid41436842,
year = {2025},
author = {Mao, H and Matsubara, T and Tanaka, N and Peled, N and Farzaneh, H and Melania Lon, D and Suzuki, N and Richardson, RM and Cole, AJ and Fang, X and Stufflebeam, SM},
title = {Transcriptomic decoding of regional cortical vulnerability to drug-resistant epilepsy using 7T MRI.},
journal = {Communications biology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s42003-025-09397-7},
pmid = {41436842},
issn = {2399-3642},
abstract = {The mechanism by which genetic risk leads to cortical vulnerability in drug-resistant epilepsy (DRE) remains unclear. This study used 7T structural and resting-state functional MRI to investigate cortical neural activity alterations in 105 DRE patients and 105 healthy controls (HCs), and to explore related genetic mechanisms. Vertex-wise analyses of mean amplitude of low-frequency fluctuation (mALFF) and regional homogeneity (ReHo) revealed that DRE patients primarily exhibited decreased mALFF and increased ReHo in the Cingulo-Opercular Network. Using the Allen Human Brain Atlas, we conducted spatial transcriptomic analysis via partial least squares (PLS) and gene enrichment analysis to identify gene categories associated with these functional changes. The results showed that cortical alterations were related to epilepsy-general genes (e.g., TMEM74, KCNN2, RBFOX1) and brain-relevant genes. Genes positively correlated with mALFF alterations enriched in mitochondrial inner membrane, matrix, and carboxylic acid metabolism; negatively in chromatin remodeling, binding, and postsynapse. Genes positively correlated with ReHo alterations enriched in nucleic acid-related catalytic activity, ribonucleoprotein granule, and centrosome; negatively in amyotrophic lateral sclerosis, mitochondrial membrane, and pyrophosphatase activity. These findings link spatial brain activity abnormalities in DRE to specific genetic signatures and biological pathways, suggesting new mechanistic insights and potential therapeutic targets for this difficult-to-treat condition.},
}

@article {pmid41433413,
year = {2025},
author = {Pak, V and Hong, JH and Bezgin, G and Dadar, M and Zeighami, Y and Medina, YI},
title = {Alzheimer's Imaging Consortium.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 8},
number = {Suppl 8},
pages = {e109795},
doi = {10.1002/alz70862_109795},
pmid = {41433413},
issn = {1552-5279},
mesh = {Humans ; *Brain/pathology/diagnostic imaging/metabolism ; *Neuroimaging ; *Alzheimer Disease/pathology/diagnostic imaging ; Atrophy/pathology ; Male ; Female ; *Neurodegenerative Diseases/pathology/diagnostic imaging ; Neurons/pathology/metabolism ; Aged ; },
abstract = {BACKGROUND: Disrupted interactions among neurons, glial and vascular cell types can lead to inflammation, vascular dysfunction, and neuronal death, highlighting the need to understand how functional interactions between these cells predispose the development of different neurodegenerative conditions. Here we identified cell-cell interactions across the whole human brain that explain atrophy patterns characteristic to 13 neurodegenerative conditions.

METHOD: We generated 1,050 whole-brain neuroimaging maps of ligand-receptor interactions specific to neurons, astrocytes, microglia, oligodendrocytes, oligodendrocyte precursor cells, and endothelial cells. These maps were created by inferring literature-curated ligand-receptor interaction pairs from microarray gene expression derived from post-mortem tissues of six healthy human donors, sourced from the Allen Human Brain Atlas (Figure 1a-b). Next, using Partial Least Squares Regression (PLS) analysis, we identified key LR pairs whose patterns of communication explain the spatial distribution of atrophy maps specific to 13 neurodegenerative conditions (Figure 1c). Atrophy maps were previously generated for early- and late-onset Alzheimer's disease (EOAD and LOAD), clinical and pathological subtypes of frontotemporal lobar degeneration (FTLD), Parkinson's disease (PD), dementia with Lewy bodies (DLB), and amyotrophic lateral sclerosis (ALS). Finally, we performed gene enrichment analyses to uncover underlying signaling pathways that explain future atrophy in neurodegeneration.

RESULT: The first latent variable (LV1) accounted for 84.21% of the covariance (p < 0.05), with the COL1A1-CD36 interaction and other CD36-associated pairs playing a dominant role in explaining atrophy patterns (Figure 2a). Atrophy patterns common to five FTLD-related disorders contributed the most to LV1, followed by EOAD and LOAD (Figure 2b). Among the top 10% of ligand-receptor pairs, 28 of 107 showed strong bi-directional signaling between astrocytes and neurons, along with prominent contributions from neuron-microglia and neuron-neuron signalling (Figure 2d). These top ligands and receptors were significantly enriched for pathways including Slit/Robo-mediated axon guidance, opioid prodynorphin, enkephalin release, and Alzheimer's disease presenilin pathway (Figure 2e; p < 0.001, FDR-corrected).

CONCLUSION: We identified whole-brain ligand-receptor interactions involved in neuron-astrocyte, neuron-microglia, and neuron-neuron signaling pathways that explain the observed atrophy patterns in multiple neurodegenerative conditions. These key ligands and receptors may serve as potential therapeutic targets and advance our understanding of neurodegeneration.},
}

Humans
*Brain/pathology/diagnostic imaging/metabolism
*Neuroimaging
*Alzheimer Disease/pathology/diagnostic imaging
Atrophy/pathology
Male
Female
*Neurodegenerative Diseases/pathology/diagnostic imaging
Neurons/pathology/metabolism
Aged

@article {pmid41432752,
year = {2025},
author = {Więcławski, W and Paszulewicz, J},
title = {ERP evidence of attentional selection outside of effective oculomotor range.},
journal = {Experimental brain research},
volume = {244},
number = {1},
pages = {16},
pmid = {41432752},
issn = {1432-1106},
support = {2016/21/N/HS6/02771//Narodowe Centrum Nauki/ ; },
abstract = {UNLABELLED: The close link between visual attention and the oculomotor system is well documented. Within the selection-for-action framework, two perspectives exist. According to Visual Attention Model (VAM) attention is seen as a prerequisite for successful movement execution, though it is considered a distinct cognitive and neural process. By contrast, the premotor theory of attention (PMTA) argues that the beneficial effects of attention are fully accounted for by the system’s preparation for saccadic eye movements. From this standpoint, a central prediction emerges: attentional advantages should be confined to regions within the oculomotor range, since saccadic planning is not feasible outside those limits. A common way to examine this prediction is to present cues and targets in a hemifield beyond the oculomotor range, typically achieved by occluding one eye while abducting the other. Using this method, Smith et al. showed that in a visual search task, exogenous orienting is reduced in the temporal hemifield when the eye is abducted. They concluded that exogenous attentional orienting is constrained by the range of potential saccadic movements. In our study, we sought to replicate Smith et al.’s findings while extending the paradigm with EEG recordings—an approach not yet applied in this context. PMTA predicts that, under eye abduction, stimuli appearing in the temporal hemifield would yield diminished N2pc amplitudes. An ANOVA revealed no reduction of N2pc amplitude in the temporal hemifield. Taken together, our results support the growing body of evidence suggesting that visual attention is not strictly bound to the oculomotor range.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00221-025-07219-0.},
}

@article {pmid41432316,
year = {2025},
author = {Genge, A and Rothstein, J and De Silva, S and Zinman, L and Chum, M and Chiò, A and Sobue, G and Aoki, M and Yoshino, H and Doyu, M and Selness, D and Todorovic, V and Hirai, M and Sasson, N and Takahashi, F and Cecić, M and Wamil, A and Apple, S},
title = {Phase 3b Extension Study MT-1186-A04 to Evaluate the Continued Efficacy and Safety of Edaravone Oral Suspension for Up to an Additional 48 Weeks in Patients With Amyotrophic Lateral Sclerosis.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70120},
pmid = {41432316},
issn = {1097-4598},
support = {//Tanabe Pharma America, Inc./ ; },
abstract = {INTRODUCTION/AIMS: An On/Off dosing regimen of intravenous (IV) edaravone and edaravone oral suspension is currently approved in the US for treatment of amyotrophic lateral sclerosis (ALS). Placebo-controlled clinical trials showed that IV edaravone slows physical functional decline. Study MT-1186-A04 continued to examine the efficacy and safety of investigational once daily and approved on/off dosing of edaravone oral suspension in patients with ALS.

METHODS: Study MT-1186-A04 (NCT05151471) was a phase 3b, multicenter, randomized, double-blind, parallel group extension study for up to an additional 48 weeks following 48-week Study MT-1186-A02 that randomized patients to investigational once daily or approved 105-mg on/off dosing of edaravone oral suspension. Patients who met Study MT-1186-A04 eligibility criteria, including Study MT-1186-A02 completion, continued in the same treatment regimen as Study MT-1186-A02. The primary efficacy endpoint for MT-1186-A04 was time from randomization in Study MT-1186-A02 to a ≥ 12-point decrease in ALS Functional Rating Scale-Revised (ALSFRS-R) or death, whichever happened first.

RESULTS: Over 96 weeks, including Study MT-1186-A02, daily dosing did not show a statistically significant difference vs. approved on/off dosing for the primary endpoint (p = 0.78). Edaravone oral suspension was well tolerated, and no new safety concerns were identified in either group.

DISCUSSION: Similar to Study MT-1186-A02, once daily edaravone oral suspension in extension Study MT-1186-A04 did not show superiority in terms of the primary efficacy endpoint, but had equivalent efficacy, safety, and tolerability, compared with the approved On/Off regimen. The results reinforce the appropriateness of the approved dosing regimen.},
}

@article {pmid41431415,
year = {2026},
author = {Cho, W and Lee, SY and Yoo, SH and Cho, B and Kim, KH and Hwang, IY},
title = {Home Healthcare Needs and Characteristics of Patients with Serious Illnesses Who Use Hospital-Affiliated Home-Based Medical Care in Korea.},
journal = {Yonsei medical journal},
volume = {67},
number = {1},
pages = {62-70},
doi = {10.3349/ymj.2025.0087},
pmid = {41431415},
issn = {1976-2437},
support = {RS-2021-KH120239//Patient-Centered Clinical Research Coordinating Center/Korea ; },
mesh = {Humans ; Male ; Female ; Republic of Korea ; Aged ; Retrospective Studies ; Middle Aged ; Aged, 80 and over ; Emergency Service, Hospital/statistics & numerical data ; *Home Care Services/statistics & numerical data ; *Health Services Needs and Demand ; *Home Care Services, Hospital-Based/statistics & numerical data ; Neoplasms/therapy ; },
abstract = {PURPOSE: The number of homebound adults with serious illnesses is increasing. This study aimed to examine the healthcare needs and characteristics of patients who use a hospital-affiliated physician-led home-based medical care (HBMC) program and identify factors associated with emergency department (ED) visits in Korea.

MATERIALS AND METHODS: This retrospective observational study included patients who used a HBMC program at a tertiary hospital between 2020 and 2023. Patient characteristics and home healthcare needs were analyzed by disease category: cancer, advanced neurologic disease, and others. Multivariable logistic regression analysis was used to identify factors associated with ED visits within 30 days of a physician's home visit.

RESULTS: A total of 600 patients were registered and received home visits; 58.5% had cancer and 29.7% had advanced neurologic diseases, e.g., amyotrophic lateral sclerosis. The median age was 72 years [interquartile range (IQR), 62.8-81.0], and 87.0% were dependent in daily activities. The median number of medications per patient was 6 (IQR, 3-10); 66.3% took ≥5 medications and 25.7% took ≥10 (excessive polypharmacy). Physicians provided not only physical examinations (100%) and symptom assessment (90.8%), but also home environment evaluation (86.7%), medical device management (62.0%), advanced care planning (40.7%), and acute health issue management (32.5%). Within 30 days, 19.2% of patients visited the ED. Excessive polypharmacy and cancer diagnosis were associated with increased ED visits.

CONCLUSION: Most patients who used the hospital-affiliated HBMC program had cancer, advanced neurologic disease, and polypharmacy. Targeted HBMC programs are needed for patients with serious illnesses living at home.},
}

Humans
Male
Female
Republic of Korea
Aged
Retrospective Studies
Middle Aged
Aged, 80 and over
Emergency Service, Hospital/statistics & numerical data
*Home Care Services/statistics & numerical data
*Health Services Needs and Demand
*Home Care Services, Hospital-Based/statistics & numerical data
Neoplasms/therapy

@article {pmid41431371,
year = {2025},
author = {Dobbertin, T and Schirmer, L},
title = {Spatially Resolved Profiling of Compartmentalized Muscle and Brain Inflammation.},
journal = {European journal of immunology},
volume = {55},
number = {12},
pages = {e70119},
pmid = {41431371},
issn = {1521-4141},
support = {P1180016//Gemeinnützige Hertie-Stiftung/ ; GRK2727(InCheck)//Deutsche Forschungsgemeinschaft/ ; FOR2690(SCHI1330/7-2)//Deutsche Forschungsgemeinschaft/ ; SPP2395(SCHI1330/10-1)//Deutsche Forschungsgemeinschaft/ ; FOR5705(SCHI1330/13-1)//Deutsche Forschungsgemeinschaft/ ; SCHI1330/2-1//Deutsche Forschungsgemeinschaft/ ; SCHI1330/4-1//Deutsche Forschungsgemeinschaft/ ; SCHI1330/11-1//Deutsche Forschungsgemeinschaft/ ; 950584//H2020 European Research Council/ ; },
mesh = {Humans ; Animals ; *Muscle, Skeletal/immunology/pathology/metabolism ; Proteomics/methods ; *Brain/immunology/pathology ; Inflammation/immunology ; *Neuroinflammatory Diseases/immunology ; *Encephalitis/immunology ; Transcriptome ; },
abstract = {Spatial omics technologies enable high-resolution mapping of transcriptomic, proteomic, and metabolic profiles within intact tissues, revealing how immune, stromal, and parenchymal cells interact in situ during inflammation. Chronic inflammation in skeletal muscle and the central nervous system is spatially organized within defined niches that shape disease progression and therapeutic response. In skeletal muscle, spatial analyses have uncovered fiber-type-specific vulnerability, regenerative trajectories, and immune-stromal crosstalk in disorders such as Duchenne muscular dystrophy and inclusion body myositis. In the central nervous system, these approaches have revealed compartmentalized neuroinflammation in multiple sclerosis, innate immune activation in amyotrophic lateral sclerosis, and immune evasion in glioma. Integration with single-cell gene expression enables inference of cell-cell communication networks and identification of spatial gradients of immune activation and tissue remodeling. Despite major advances, clinical translation remains limited by small cohorts, methodological variability, and insufficient functional validation. As spatial profiling becomes more accessible, standardized, and scalable, it promises to stratify inflammatory disease states, identify tissue-resident immune programs, and guide mechanism-based therapies. Hence, spatial omics provide an unprecedented opportunity to resolve the cellular architecture of inflammation, revealing not only where immune activity occurs, but how it is orchestrated within complex tissue microenvironments.},
}

Humans
Animals
*Muscle, Skeletal/immunology/pathology/metabolism
Proteomics/methods
*Brain/immunology/pathology
Inflammation/immunology
*Neuroinflammatory Diseases/immunology
*Encephalitis/immunology
Transcriptome

@article {pmid41430470,
year = {2025},
author = {Piol, D and Khalil, B and Robberechts, T and Killian, T and Georgopoulou, M and Partel, G and Wouters, D and Hecker, N and Tziortzouda, P and Verresen, Y and Corthout, N and Kint, S and Vandereyken, K and Van Damme, P and Voet, T and Davie, K and Poovathingal, S and Van Den Bosch, L and Aerts, S and Sifrim, A and Da Cruz, S},
title = {Axonal Eif5a hypusination controls local translation and mitigates defects in FUS-ALS.},
journal = {Nature neuroscience},
volume = {},
number = {},
pages = {},
pmid = {41430470},
issn = {1546-1726},
support = {962700//Muscular Dystrophy Association (Muscular Dystrophy Association Inc.)/ ; 1060285//Muscular Dystrophy Association (Muscular Dystrophy Association Inc.)/ ; },
abstract = {Local protein synthesis is vital for neuronal function, but its dysregulation in neurodegenerative diseases remains poorly defined. Here we applied spatial transcriptomics to adult mouse motor nerve axons and cell bodies to enable subcellular mapping. Among transcripts found in mature axons, the most enriched biological process is protein translation, and localization of translation machinery was confirmed using multiplexed single-molecule spatial transcriptomics combined with immunofluorescence. Amyotrophic lateral sclerosis (ALS)-associated mutations in the RNA-binding protein fused in sarcoma (FUS), which suppress local translation, disrupt the compartment-specific RNA signatures, including components of the translation machinery. In particular, eukaryotic initiation factor 5a (Eif5a), a translation factor involved in elongation and termination, is found to be locally impaired in mutant FUS axons with reduced levels of its active hypusinated form. Axon-specific treatment with polyamine spermidine restores Eif5a hypusination and ameliorates mutant FUS-dependent neuronal defects, including suppression of local protein synthesis. Finally, in vivo spermidine treatment reduces ALS-related toxicity in mutant FUS and TDP-43 Drosophila models, which may have implications for therapy development.},
}

@article {pmid41430073,
year = {2025},
author = {Fava, VM and Perico, J and Orlova, M and Dallmann-Sauer, M and Xu, YZ and Thuc, NV and Thai, VH and Belone, AF and Latini, ACP and Schurr, E},
title = {Bridging pleiotropic mechanisms in leprosy type-1 reactions and neurodegenerative diseases.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {45036},
pmid = {41430073},
issn = {2045-2322},
support = {FP 22/9//Leprosy Research Initiative/ ; },
mesh = {Humans ; *Leprosy/genetics/complications/pathology ; *Parkinson Disease/genetics ; *Neurodegenerative Diseases/genetics ; Male ; Genetic Predisposition to Disease ; Female ; Protein Kinases/genetics ; Middle Aged ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics ; Ubiquitin-Protein Ligases/genetics ; *Genetic Pleiotropy ; },
abstract = {Leprosy is an infectious disease of the skin and peripheral nervous system. Sudden episodes of hyperinflammation, known as Type 1 Reactions (T1R), are a main contributor to permanent nerve damage in leprosy. The genetic component associated with the neuro-inflammatory phenotype of T1R displays pleiotropic effects with Parkinson's disease (PD). In this study, we explored the genetic overlap between PD and T1R and expanded the evaluation of pleiotropic effects between T1R and other neurodegenerative disorders. We replicated the association of PD-linked rare variants in PRKN with T1R in Vietnamese leprosy patients. Analysis of 24 PD associated-genes revealed compound effects between rare protein-altering variants and T1R in the interacting genes PRKN/PINK1 (P = 2.7[-05]; OR = 4.0) and a combination of rare/low frequency variants in the LRRK2/GAK pair (P = 6.7[-05]; OR = 0.54). These findings validated a genetic overlap between T1R and PD with two distinct axes, one of shared risk via PRKN/PINK1 and a second of antagonistic pleiotropic via LRRK2/GAK. When testing an additional 94 genes associated with neurodegenerative diseases we identified variants in the amyotrophic lateral sclerosis disease-linked gene TBK1 associated with T1R (P = 0.004; OR = 12.9). Our results highlight shared biological processes between leprosy and neurodegenerative diseases, which may indicate candidate drugs for repurposing to improve T1R management.},
}

Humans
*Leprosy/genetics/complications/pathology
*Parkinson Disease/genetics
*Neurodegenerative Diseases/genetics
Male
Genetic Predisposition to Disease
Female
Protein Kinases/genetics
Middle Aged
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics
Ubiquitin-Protein Ligases/genetics
*Genetic Pleiotropy

@article {pmid41429969,
year = {2025},
author = {Caimi, E and Vaccari, S and Vinci, V},
title = {Comment to "Artificial Intelligence (AI)-Assisted Patient Education and Concerns Following Facelift Surgery: A Study on ChatGPT-4 and Gemini".},
journal = {Aesthetic plastic surgery},
volume = {},
number = {},
pages = {},
pmid = {41429969},
issn = {1432-5241},
abstract = {INTRODUCTION: Artificial intelligence (AI) is increasingly integrated into patient education and postoperative care. Almousa et al. recently evaluated ChatGPT-4 and Gemini for postoperative facelift counseling, reporting high accuracy and clarity. While their study represents an important step toward AI-assisted communication in aesthetic surgery, several methodological issues may limit the validity and clinical applicability of their findings.

METHODS: We critically appraised Almousa et al.'s study design, data collection, and analytic methods. Specific attention was given to question selection, evaluation metrics, reproducibility, and statistical robustness, comparing them with established standards for AI evaluation and inter-rater reliability.

RESULTS: The study used ChatGPT-4 itself to generate the five "most common" postoperative questions, introducing circularity and potential selection bias. Responses were assessed on a dichotomous (Yes/No) scale by five surgeons, without reporting inter-rater reliability or use of scaled metrics. It was unclear whether prompts were entered sequentially or independently, raising reproducibility concerns. The limited sample size (five questions per model) provided only 25 binary data points per system, precluding meaningful statistical inference. Furthermore, AI responses lacked individualized safety guidance and escalation advice, limiting clinical safety in real-world postoperative settings.

CONCLUSION: Although the study highlights the promise of LLMs in aesthetic surgery, future studies should employ patient-derived question sets, graded and reproducible evaluation scales, transparent prompt protocols, and inclusion of complication-related queries to accurately determine the safety and educational value of AI-generated postoperative information.

LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.},
}

@article {pmid41429156,
year = {2025},
author = {Gomes, MDM and Freitas, MRG},
title = {Jean-Martin Charcot at 200: revolutionizing neurology through a multidisciplinary lens.},
journal = {Arquivos de neuro-psiquiatria},
volume = {83},
number = {11},
pages = {1-5},
doi = {10.1055/s-0045-1813236},
pmid = {41429156},
issn = {1678-4227},
mesh = {History, 19th Century ; *Neurology/history ; Humans ; },
abstract = {As we near the bicentenary of his birth, Jean-Martin Charcot (1825-1893) is remembered not only as the founder of modern neurology but also as a uomo universale. His multidisciplinary approach transcended 19[th]-century medicine, establishing neurology as a distinct discipline while integrating art, psychology, and philosophy into his study of the nervous system. His work laid foundations for neurodegenerative diseases (amyotrophic lateral sclerosis [ALS], Parkinson's disease, multiple sclerosis [MS]), functional neurological disorders (FNDs), and psychoanalysis, foreshadowing neuroplasticity and the mind-body connection. His innovative teaching at Salpêtrière-merging anatomy with artistic documentation-revolutionized medical education, inspiring figures from Freud to modern neuroscientists. Two centuries later, Charcot's legacy endures not just in eponyms but in his unifying vision of brain, mind, and art - a timeless model for interdisciplinary medicine. The present paper explores his impact on neurodegenerative research, functional disorders, medical pedagogy, and the humanities.},
}

History, 19th Century
*Neurology/history
Humans

@article {pmid41429137,
year = {2025},
author = {Li, S},
title = {Rethinking Global Trends in Pediatric Lung Transplantation Research.},
journal = {The Thoracic and cardiovascular surgeon},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2776-6215},
pmid = {41429137},
issn = {1439-1902},
abstract = {This letter discusses Yuan et al.'s bibliometric analysis of pediatric lung transplantation (PLT) research, recognizing its value in mapping global publication trends and collaborative networks. We affirm the study's contribution to understanding the evolution of PLT research but highlight several critical considerations. The current geographic imbalance, dominated by North American institutions, underscores the need for broader international collaboration and capacity building in developing regions. Moreover, while the shift from surgical to outcome-oriented research is notable, bibliometric metrics alone may not fully reflect clinical progress in perioperative management, immunotherapy, or donor ethics. We advocate for integrating bibliometric insights with systematic clinical evidence to better connect research output with improvements in graft survival, rejection control, and pediatric patient quality of life.},
}

@article {pmid41428955,
year = {2025},
author = {Jih, KY and Tsai, YS and Fang, SY and Hsu, FC and Sytwu, HP and Liao, YC and Tsai, PC and Lee, YC},
title = {SOD1 mutations in Taiwanese ALS patients: Clinical characteristics, frequency, and a p.T138R founder effect.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/21678421.2025.2604236},
pmid = {41428955},
issn = {2167-9223},
abstract = {OBJECTIVE: Mutations in SOD1 are a well-established genetic cause of amyotrophic lateral sclerosis (ALS), exerting toxic gain-of-function effects that promote protein misfolding and aggregation in motor neurons and glial cells. The emergence of SOD1-targeted antisense oligonucleotide therapy underscores the clinical importance of precise genetic diagnosis. This study aimed to determine the frequency, clinical characteristics, and potential founder effect of SOD1 mutations in a large Taiwanese ALS cohort, and to evaluate their aggregation propensity in vitro.

METHODS: All coding exons of SOD1 were analyzed by Sanger sequencing in 650 unrelated Taiwanese patients with ALS. Haplotype analysis using single nucleotide polymorphism markers flanking SOD1 was conducted to assess a potential founder effect. Protein cross-linking assays were performed to assess the aggregation propensity of 11 SOD1 variants.

RESULTS: Seventeen pathogenic SOD1 variants were identified in 26 probands and 12 affected relatives. Mean age at onset was 48.9 ± 14.9 years, and 8% had bulbar-onset ALS. The most frequent variant was p.T138R (8 probands), followed by p.G11A (3 probands). The other 15 variants each occurred in a single family. A shared ancestral haplotype was observed among p.T138R carriers. Cross-linking experiments demonstrated oligomer formation in all tested mutant SOD1 proteins compared to the wild-type protein, supporting their pathogenicity.

CONCLUSIONS: SOD1 mutations account for approximately 4% of ALS cases in Taiwan, are associated with earlier onset and predominantly spinal-onset ALS, and include a p.T138R founder variant. These findings highlight the importance of genetic screening in ALS, particularly in guiding eligibility for emerging targeted therapies.},
}

@article {pmid41428942,
year = {2025},
author = {Sannes, A and Rognli, EW and Hanssen-Bauer, K and Torp, NC and Storfossen, SK and Høstaker, MN and Aalberg, M},
title = {Barriers to and Facilitators of Implementation of Internet-Delivered Therapist-Guided Therapy in Child and Adolescent Mental Health Services: Systematic Review and Bayesian Meta-Analysis.},
journal = {Journal of medical Internet research},
volume = {27},
number = {},
pages = {e83543},
pmid = {41428942},
issn = {1438-8871},
mesh = {Adolescent ; Child ; Humans ; *Adolescent Health Services ; Bayes Theorem ; *Child Health Services ; *Internet ; *Mental Health Services ; *Psychotherapy/methods ; },
abstract = {BACKGROUND: Internet-delivered therapist-guided therapy (e-therapy) represents a promising approach for enhancing accessibility, treatment fidelity, and scalability within child and adolescent mental health services (CAMHS).

OBJECTIVE: This systematic review aimed to (1) identify and synthesize determinants of implementation, specifically barriers to and facilitators of e-therapy in CAMHS structured according to the Consolidated Framework of Implementation Research (CFIR); and (2) provide pooled benchmark estimates of key implementation outcomes for fidelity, cost-effectiveness, and acceptability.

METHODS: A PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)-compliant systematic review was performed across PsycINFO, MEDLINE, Web of Science, CINAHL, Embase, Cochrane, and ProQuest Dissertations & Thesis on June 6, 2025-to identify peer-reviewed studies assessing implementation outcomes or determinants of e-therapy in the context of outpatient CAMHS (ages 8-18 years). Barriers and facilitators were synthesized qualitatively with thematic analysis applying CFIR. A parallel quantitative synthesis of Proctor et al's taxonomy of implementation outcomes was performed using Bayesian multilevel random-effects meta-analyses to estimate pooled effect sizes and 95% credible intervals (CIs). By combining quantitative benchmarks of implementation success with qualitative insights into contextual determinants, the review provides an integrated understanding of what drives effective e-therapy implementation in CAMHS. Study quality was assessed using the CASP (Critical Appraisal Skills Programme) checklist, Cochrane Risk of Bias tool, and Risk Of Bias In Non-randomized Studies-of Interventions tool. Small study effects were evaluated using funnel plots, sensitivity analyses, and the Egger test.

RESULTS: From 50,026 screened reports, 50 studies published between 2007 and 2025 were included: 18 randomized controlled trials, 17 cohort, and 15 qualitative or mixed methods studies. Most studies originated from Western Europe (n=34), Northern America (n=11), and Oceania (n=5), targeting anxiety (n=24) and depression (n=9), through cognitive behavioral therapy-based programs (n=47), with parallel parent content (n=31). Therapist guidance was primarily asynchronous (n=43). Among the 39 studies reporting determinants, common barriers and facilitators were identified across intervention, organization, therapist, and patient domains, structured via CFIR. Pooled implementation outcomes showed modest dropout rates (~20%, CI 14%-27%), high module completion (~68%, CI 60%-75%), low therapist time (24 min per wk per patient, 95% CI 19-28), and high patient satisfaction (24/32 on Client Satisfaction Questionnaire-8, 95% CI 22-27; and 76% satisfaction rate, 95% CI 62%-87%), suggesting e-therapy is resource efficient and acceptable if implemented successfully.

CONCLUSIONS: This review provided the first integrated synthesis of pooled benchmarks for implementation outcomes of e-therapy in CAMHS and modifiable determinants to inform future service planning and scale-up. These findings highlighted service-level enablers, such as leadership anchoring, targeted use, technical stability, structured patient flow, and therapist training, that organizations could prioritize to strengthen sustainable e-therapy implementation in CAMHS.},
}

Adolescent
Child
Humans
*Adolescent Health Services
Bayes Theorem
*Child Health Services
*Internet
*Mental Health Services
*Psychotherapy/methods

@article {pmid41428861,
year = {2025},
author = {Soliman, R and Swelam, MS and Fahmy, N and Rashed, HR},
title = {Translation and validation of the Arabic version of the amyotrophic lateral sclerosis assessment questionnaire (ALSAQ40-AR).},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/21678421.2025.2603311},
pmid = {41428861},
issn = {2167-9223},
abstract = {AIM: To validate Arabic version of the ALSAQ-40, (ALSAQ40-AR) and assess the QOL in a cohort of Egyptian patients with ALS.

METHODS: This is a prospective study. One hundred consecutive ALS patients were included from the Neuromuscular Unit, Ain Shams University Hospital, in the period from February 2022 to June 2024. Functional and cognitive assessments were done using the Arabic version of ALSFRS-R and ECAS-EG questionnaires, respectively. Disease stage was identified via Kings Clinical Staging. QOL was evaluated using the Arabic WHOQOL-BREF and an Arabic version of ALSAQ-40.

RESULTS: ALSAQ40-AR showed high internal consistency using Cronbach's alpha of >0.9, Inter-rater reliability was tested, values for all variables were compared, and no statistically significant differences were found (ICC = .997). Both WHOQOL-BREF and ALSAQ40-AR domains demonstrated significant correlation with each other and with ALSFRS-R (p-value < 0.0001), denoting construct validity. Moreover, ALSAQ40-AR domains correlated significantly with time since disease onset, and showed significant increase across disease stages (p-value < 0.0001). Ceiling and floor effects were analyzed in both QOL scales, but only WHOQOL-BREF showed ceiling and floor effects.

CONCLUSION: ALSAQ40-AR and the WHOQOL-BREF were reliable and valid tools to evaluate QOL in patients with ALS; we suggest that the validated ALSAQ40-AR is more suited for ALS patients because it is a disease specific questionnaire that showed higher internal consistency with no floor or ceiling effects. QOL in ALS was correlated with time since disease onset, disease stage, functional, and cognitive disabilities.},
}

@article {pmid41428860,
year = {2025},
author = {Curtis, SE and Tatlock, S and O'Hara, L and Seçinti, E and Mehdiyoun, NF and Ayala-Nunes, L and Flynn, J and Fernelius, K and Hodson, N and Delbecque, L},
title = {Patient experience and clinical outcome assessment validity in amyotrophic lateral sclerosis: a targeted literature review.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-16},
doi = {10.1080/21678421.2025.2604233},
pmid = {41428860},
issn = {2167-9223},
abstract = {OBJECTIVE: To identify relevant concepts of measurement for people with amyotrophic lateral sclerosis (ALS) and to evaluate the face and content validity of clinical outcome assessments (COAs) that can be used to measure treatment benefits in ALS clinical trials.

METHODS: A targeted literature review was conducted to explore patient experience (stage 1) and COAs used in ALS research (stage 2). Abstracts were screened against predefined eligibility criteria; full-text articles were reviewed for eligible abstracts and relevant data were extracted. Face and content validity of the identified COAs were assessed.

RESULTS: Stage 1 searches identified 3,527 abstracts, of which 12 full-text articles, two summary reports, and one conference poster were included in this review. Twenty-five symptoms and 35 health-related quality of life (HRQoL) impacts were identified. Frequently reported symptoms included breathing and speech difficulties and muscle/limb weakness, each associated with a diverse range of impacts, including those related to emotional wellbeing, physical function, social and leisure activities, and activities of daily living. Stage 2 searches identified 119 COAs, of which 28 were reviewed. Many had acceptable face (13/28) and content validity (15/28), but 13 had not involved patients during development; only 10 were clearly worded and seven were lengthy, increasing patient burden risk.

CONCLUSIONS: This review identified wide-ranging symptoms and HRQoL impacts experienced by people with ALS, but detailed qualitative evidence is sparse. Multiple COAs were identified as potential measures in ALS clinical trials.},
}

@article {pmid41428513,
year = {2025},
author = {Román-Caballero, R},
title = {Reassessing the cognitive benefits of physical activity: A meta-analytic reanalysis of Mavilidi et al. (2025).},
journal = {Psychological bulletin},
volume = {151},
number = {11},
pages = {1382-1388},
doi = {10.1037/bul0000490},
pmid = {41428513},
issn = {1939-1455},
support = {//European Union's Horizon 2020 research and innovation program/ ; },
mesh = {Humans ; *Cognition/physiology ; *Exercise/psychology/physiology ; Meta-Analysis as Topic ; Publication Bias ; },
abstract = {Recent reviews and meta-analyses suggest the cognitive benefits of physical exercise observed in primary studies may be inflated due to multiple sources of bias, including selection bias, placebo effects, regression to the mean, and publication bias. When these biases are accounted for, the evidence for the purported enhancements has been shown to be inconclusive. The recent meta-analysis by Mavilidi et al. (2025) makes a relevant contribution by pointing out the potential role of moderating variables and therefore the possibility that, under certain conditions, the effect may be more substantive. Yet, a critical evaluation of Mavilidi et al.'s methods reveals several issues in the statistical analyses and interpretation of publication bias analyses. These appear to have led Mavilidi et al. to conclude the presence of an overall cognitive benefit of physical activities. The present commentary provides a reanalysis of the data, applying appropriate methodological corrections. After an adequate analytical strategy, the final effect was reduced and yielded inconclusive evidence of an overall cognitive benefit. Particularly, publication bias methods highlight that the overall effect of chronic physical activity on cognition is likely smaller and therefore inconclusive. Yet, as in the original meta-analysis, the cognitive benefits were significantly larger for chronic interventions with an evidence-based delivery, programs with a clear cognitive component, or high cognitive demands compared to other physical exercise interventions. These results support the possibility that motor-cognitive training/sports games and holistic movement practices/martial arts may be effective activities to improve cognitive functioning. (PsycInfo Database Record (c) 2025 APA, all rights reserved).},
}

Humans
*Cognition/physiology
*Exercise/psychology/physiology
Meta-Analysis as Topic
Publication Bias

@article {pmid41428348,
year = {2025},
author = {Elman, L and Wymer, J and Lomen-Hoerth, C},
title = {Tofersen, SOD1, and the Treatability of Amyotrophic Lateral Sclerosis.},
journal = {JAMA neurology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaneurol.2025.4927},
pmid = {41428348},
issn = {2168-6157},
}

@article {pmid41428212,
year = {2025},
author = {Grønbæk-Thygesen, M and Kampmeyer, C and Eschger, P and Tatham, MH and Arts, M and Hofmann, K and Lindorff-Larsen, K and Boomsma, W and Hartmann-Petersen, R},
title = {The Importance of UBQLN2 Ubiquitylation for Its Turnover and Localization.},
journal = {Biochemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.biochem.5c00619},
pmid = {41428212},
issn = {1520-4995},
abstract = {UBQLN2 is a member of the UBL-UBA domain protein family that functions as extrinsic substrate receptors for the 26S proteasome. UBQLN2 has been shown to undergo phase separation in vitro. In cells, UBQLN2 forms condensates that may be of importance for tuning protein degradation via the ubiquitin-proteasome system and potentially of relevance for UBQLN2-linked amyotrophic lateral sclerosis (ALS). Here we show that UBQLN2 is ubiquitylated on lysine residues in the N-terminal UBL domain. The C-terminal region of UBQLN2 is lysine-depleted, and we show that introducing lysine residues in this region leads to its E6AP-dependent degradation. The UBL domain critically stabilizes UBQLN2 and protects it from proteasomal degradation. Fusion of ubiquitin to the UBQLN2 N-terminus stabilizes UBQLN2 and increases its propensity for locating in puncta, indicating that ubiquitylation of the UBQLN2 UBL domain regulates abundance and localization.},
}

@article {pmid41428120,
year = {2025},
author = {Freri, F and Spinelli, EG and Canu, E and Basaia, S and Castelnovo, V and Müller, HP and Kassubek, J and Ludolph, AC and Krishnamurthy, SS and Roselli, F and Filippi, M and Agosta, F},
title = {Uncovering hypothalamic network disruption in ALS.},
journal = {Journal of neurology},
volume = {273},
number = {1},
pages = {37},
pmid = {41428120},
issn = {1432-1459},
support = {EU Joint Programme - Neurodegenerative Disease Research (JPND) - HiCALS project//European Commission/ ; Next Generation EU/National Recovery//European Union/ ; Resilience Plan//European Union/ ; Investment PE8-Project Age-It. Project code: PE00000015; CUP master: D43C22003100007//European Union/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology/pathology ; Female ; Male ; Middle Aged ; *Hypothalamus/diagnostic imaging/physiopathology/pathology ; Magnetic Resonance Imaging ; Aged ; Adult ; *White Matter/diagnostic imaging/pathology ; *Nerve Net/diagnostic imaging/physiopathology ; Disease Progression ; *Connectome ; },
abstract = {BACKGROUND: Structural MRI studies have shown hypothalamic atrophy and altered white matter (WM) connectivity in amyotrophic lateral sclerosis (ALS), as a possible substrate of hypermetabolism in this condition. However, hypothalamic functional connectivity and its association with clinical features in ALS remain unclear. This study explored hypothalamic resting-state functional connectivity (RS-FC) in ALS patients compared to controls and its relationship with disease severity defined by the ALS Functional Rating Scale (ALSFRS-r), body mass index (BMI), disease duration, progression rate, survival, hypothalamic volume, and WM integrity.

METHODS: Seventy-one ALS patients and 39 healthy controls underwent structural and RS functional MRI. The bilateral hypothalamus was segmented, and a seed-based RS-FC analysis was performed. Group differences in hypothalamic RS-FC and their correlations with ALSFRS-r scores, BMI, disease duration, progression rate, survival, hypothalamic volume, and WM integrity were assessed. Tract-based spatial statistics was performed to estimate the correlation between WM damage in ALS and hypothalamic RS-FC.

RESULTS: ALS patients showed increased hypothalamic RS-FC with caudate nuclei compared to controls. Additionally, greater disease severity correlated with increased hypothalamic RS-FC with the caudate nuclei and orbitofrontal cortex. Hypothalamic RS-FC mean values also associated with FA in the genu of corpus callosum and forceps minor and disease progression rate. No significant correlations were observed with other clinical features.

CONCLUSIONS: These findings support hypothalamic alterations in ALS. Early detection of hypothalamic changes could be useful in prognostic stratification and evaluating intervention effects.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology/pathology
Female
Male
Middle Aged
*Hypothalamus/diagnostic imaging/physiopathology/pathology
Magnetic Resonance Imaging
Aged
Adult
*White Matter/diagnostic imaging/pathology
*Nerve Net/diagnostic imaging/physiopathology
Disease Progression
*Connectome

@article {pmid41427945,
year = {2026},
author = {Gruda, D and Hanges, P and McCleskey, JA},
title = {Decomposing Spatial Effects of State-Level Health Outcomes: A Methodological Demonstration and Re-Analysis.},
journal = {International journal of psychology : Journal international de psychologie},
volume = {61},
number = {1},
pages = {e70152},
doi = {10.1002/ijop.70152},
pmid = {41427945},
issn = {1464-066X},
mesh = {Humans ; *Narcissism ; Hypertension/mortality/epidemiology ; United States/epidemiology ; Machiavellianism ; Neoplasms/epidemiology ; Depression/epidemiology ; Antisocial Personality Disorder/epidemiology ; Male ; Female ; },
abstract = {While spatial autoregressive (SAR) models are increasingly used in population-level psychological studies, researchers often overlook the crucial step of parsing effects into direct, indirect and total impacts, a standard practice in spatial econometrics. In this paper, we demonstrate the necessity of this practice by re-analyzing Gruda et al.'s (2024) U.S. Dark-Triad and health dataset with heteroskedasticity-robust SAR models and full impact decomposition, revealing significant changes. The previously observed direct protective effect of state-level narcissism on hypertension mortality disappeared when accounting for interstate spillovers. Conversely, the association with lower cancer prevalence and depression strengthened. Several health-behaviour findings reversed direction, indicating naïve regressions conflated within- and between-state effects. Machiavellianism and psychopathy coefficients also shifted. These results demonstrate that spatial spillovers can dilute, negate or reverse local effects, cautioning against policy inferences based solely on direct estimates.},
}

Humans
*Narcissism
Hypertension/mortality/epidemiology
United States/epidemiology
Machiavellianism
Neoplasms/epidemiology
Depression/epidemiology
Antisocial Personality Disorder/epidemiology
Male
Female

@article {pmid41427267,
year = {2025},
author = {Finney, CA and An, L and Winchester, LM and Vogel, J and Wilkins, HM and Burns, JM and Swerdlow, RH and Slawson, C and Rothstein, JD and , and Lutz, MW and Saloner, R and Shvetcov, A},
title = {Mapping the circulating proteome across neurodegeneration: A harmonized, consortium-scale framework for uncovering molecular pathophysiology.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41427267},
issn = {2692-8205},
abstract = {Large-scale plasma proteomics offers unprecedented opportunities to investigate the systemic biology of neurodegeneration, yet technical heterogeneity, site-specific artifacts, and clinical confounding remain major barriers to reproducible discovery. Leveraging data from 13,733 individuals with Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), Parkinson's disease dementia (PDD), amyotrophic lateral sclerosis (ALS), and non-impaired controls in the Global Neurodegeneration Proteomics Consortium (GNPC), we present a scalable and generalizable analytical framework for harmonizing and interpreting consortium-scale proteomic datasets. Using a high-dimensional perturbation framework, we systematically benchmark five commonly used batch correction methods across a range of realistic confounding structures, including site-disease imbalance, nonlinear effects, and heteroskedasticity. Empirical Bayes modelling via limma consistently emerged as the most robust method, optimally balancing removal of site-related technical variance with retention of disease-relevant biological signal. On this harmonized foundation, we resolve neurodegenerative disease plasma signatures, including a shared immune-metabolic axis in AD and PD, neuromuscular disruption in ALS, and proteostatic imbalance in PD. Tissue and cell-type enrichment highlight widespread immune-endocrine involvement in AD and hematopoietic activation in PD. Demographically matched analyses nominate distinct, candidate biomarkers across diseases, including lipid, redox, and complement factors in AD, lysosomal and cytoskeletal proteins in PD, and muscle-derived markers in ALS. This study establishes a scalable analytical framework for integrating real-world proteomic data and provides a disease-resolved catalogue of circulating signatures to inform biomarker development and targeted intervention across neurodegenerative diseases.},
}

@article {pmid41426554,
year = {2025},
author = {Liang, L and Zhang, Y and Zhang, X and Guo, X and Yan, Y},
title = {Historical evolution, research hotspots and emerging trends of pediatric hand, foot, and mouth disease: a bibliometric worldview since the 21st century.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1722750},
pmid = {41426554},
issn = {2296-858X},
abstract = {BACKGROUND: Hand, foot, and mouth disease (HFMD) poses a significant challenge to global public health. Primarily caused by enterovirus and coxsackievirus infections, the disease has a particularly pronounced impact in the Asia-Pacific region. However, systematic analysis and discussion regarding the developmental trajectory, core research entities, current status, key research directions, and future prospects of pediatric HFMD research remain lacking.

METHODS: This study collected and analyzed papers and reviews on pediatric HFMD published between January 1, 2000, and February 1, 2025, from the Web of Science Core Collection and PubMed. Key research indicators were analyzed through bibliometric visualization, using tools including Excel, CiteSpace, VOSviewer, and BibliomeTools (an R-based tool in R-Studio).

RESULTS: Since the start of the 21 st century, academic publications in pediatric HFMD have steadily increased, with a cumulative total of 2,034 papers published by February 1, 2025. Global research distribution exhibits uneven patterns, with China emerging as core contributors. Specifically, Lin, Tzou-Yien from China, has published the largest number of papers, while Chang, Luan-Yin is the co-cited author with the highest citation rate. Solomon T et al.'s "Virology," Epidemiology, Pathogenesis, and Control of Enterovirus 71" being the most cited study in the field. Research on pediatric HFMD is closely integrated with disciplines such as virology and epidemiology, forming core research themes around "HFMD," "enterovirus 71," and "enteroviruses." Recent research has focused on the pathogenesis, epidemiology, novel therapeutic discoveries and vaccine development for pediatric HFMD. Looking ahead, it is essential to delve deeper into the molecular mechanisms underlying the interaction between the human HFMD virus and its host, and to develop multivalent vaccines targeting multiple serotypes.

CONCLUSION: This study employs bibliometric methods to visualize research in the field of pediatric hand, foot, and mouth disease, revealing trends and frontiers in this area. It will provide valuable reference for scholars seeking key research questions and potential collaborators.},
}

@article {pmid41426430,
year = {2025},
author = {van Vugt, JJFA and Zwamborn, RAJ and Dolzhenko, E and Eberle, MA and Weisburd, B and Bekema, E and Kooyman, M and Wang, BN and , and Kamsteeg, EJ and Losekoot, M and Baas, F and Novy, C and Høyer, H and van Eijk, RPA and van Es, MA and van Rheenen, W and Al-Chalabi, A and van den Berg, LH and Veldink, JH},
title = {The role of disease-associated short tandem repeats in amyotrophic lateral sclerosis.},
journal = {Brain communications},
volume = {7},
number = {6},
pages = {fcaf482},
pmid = {41426430},
issn = {2632-1297},
abstract = {Short tandem repeats (STRs) are recognized contributors to various neurodegenerative disorders, with evidence supporting genetic pleiotropy among these STRs. Multiple STRs have been associated with amyotrophic lateral sclerosis (ALS), although the strength of evidence supporting each association varies. To establish the role of disease-associated repeat expansions as pleiotropic risk factors in ALS susceptibility and progression, we genotyped a panel of 39 STRs, known to cause neurological diseases, within Project MinE in 6519 patients and 2412 controls, utilizing 100 and 150 bp short-read sequencing technology. Pathogenic allele frequencies were compared to those in a control cohort comprising 4930 Genome Aggregation Database (gnomAD) genomes. Repeat sizes and motif changes were detected using ExpansionHunter and ExpansionHunter Denovo. We developed a model to predict genotyping failures in STRs and established a best-practice protocol for assessing the accuracy of STR genotyping in short-read sequencing data. Following our genotyping assessment, 11 out of the 39 STRs exhibited insufficient genotyping accuracy, warranting caution in studying these STRs using these tools in combination with short-read sequencing. Furthermore, the observed differences in STR genotyping accuracy across studies applying different sequencing technologies and genotyping tools in control cohorts highlight the importance of a carefully designed experimental setup when interpreting potential disease-associated STR findings. Pathogenic C9orf72 and premutated ATXN2 expansions were confirmed to be significantly associated with ALS susceptibility. Additionally, pathogenic C9orf72 expansions were significantly associated with reduced mean ALS survival by 11.5 months and an earlier mean age at onset by 2.4 years. Premutation expansions in ATXN1 showed a nominally significant association with ALS susceptibility, while pathogenic expansions in NIPA1 displayed a nominally significant association with ALS survival. Previously reported ALS-associated pleiotropy in HTT and STMN2 could not be confirmed. Motif changes were identified in BEAN1, RFC1, ATXN8, C9orf72, DAB1, FXN and SAMD12; however, none of the motif changes were linked to ALS. Re-evaluation of clinical data from patients with ALS and a repeat expansion typically associated with another disease revealed that 7% of these patients' diagnoses had to be reclassified to the disease associated with the repeat expansion (e.g. Kennedy's disease or spinocerebellar ataxia). This underscores the value of broad STR screening in neurodegenerative cases. Pathogenic and premutation STRs were also found in controls in unexpected high frequencies, suggesting reduced penetrance or underdiagnosis, and highlighting the need for caution when interpreting genetic associations with disease without a proper control cohort.},
}

@article {pmid41423699,
year = {2025},
author = {Luan, W and San Gil, R and Madrid San Martin, L and Cao, MC and Vassallu, F and Venturato, J and West, PK and Brown-Wright, H and Bademosi, AT and Chye, YJ and Wu, HY and Harutyunyan, A and Robinson, KJ and Chang, MS and Blizzard, CA and Scotter, EL and Igaz, LM and Walker, AK},
title = {Synaptic changes contribute to persistent extra-motor behaviour deficits in amyotrophic lateral sclerosis.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-025-02150-5},
pmid = {41423699},
issn = {2051-5960},
support = {IG2422//Motor Neurone Disease Australia/ ; Discovery grant//FightMND/ ; Bill Guest Mid-Career Research Fellowship//FightMND/ ; },
}

@article {pmid41423553,
year = {2025},
author = {Tang, C and Foucher, J and Öijerstedt, L and Ombelet, F and Ingre, C and Van Damme, P and Van Laere, K and De Vocht, J and Koole, M},
title = {Support vector machine classification of [18]F-FDG PET scans across subtypes of amyotrophic lateral sclerosis.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {},
number = {},
pages = {},
pmid = {41423553},
issn = {1619-7089},
support = {12AQF24N//FWO/ ; fundamental clinical investigatorship//KU Leuven/ ; Een Hart voor ALS//KU Leuven/ ; Laeversfonds voor ALS Onderzoek//KU Leuven/ ; E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders//E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders/ ; ALS Liga België//ALS Liga België/ ; },
abstract = {PURPOSE: While [18]F-FDG PET imaging has demonstrated diagnostic value in people with Amyotrophic Lateral Sclerosis (PwALS) and group-level differences were identified between different disease subtypes (e.g., genetic and clinical variants), refining and validating a machine-learning-based subject-level diagnostic algorithm may improve the general applicability and reliability of [18]F-FDG PET as a diagnostic tool in ALS. In this study, we employed support vector machines (SVM) to further explore the diagnostic potential of [18]F-FDG PET in ALS, alongside its ability to classify between different genetic subtypes or clinical phenotypes.

METHODS: [18]F-FDG PET data of 36 healthy volunteers (HV), 25 people with ALS-mimicking diseases (Mimics), and 167 PwALS, grouped by genetic status (e.g., sporadic (sALS) or carrying a C9orf72 hexanucleotide repeat expansion (ALS[C9orf72RE]) and onset (bulbar or spinal) type, acquired with Biograph 'TruePoint' PET/CT scanner, were included in the study (Dataset 1). A second dataset of 183 PwALS and 31 Mimics acquired with Biograph 'HiRez' scanner was included as an independent cross-validation set (Dataset 2). PET images were spatially normalised to MNI space to fit linear SVMs with cross-validation. Only age-matched groups were considered to eliminate age-related effects.

RESULTS: For Dataset 1, the linear SVM resulted in an average accuracy of 0.86 for the classification of ALS vs. HV, 0.53 for ALS vs. Mimics, 0.83 for ALS[C9orf72RE] vs. sALS, and 0.58 for bulbar vs. spinal onset. These findings were corroborated with Dataset2, with an accuracy of up to 0.76 for ALS[C9orf72RE] vs. sALS, and 0.59 for bulbar vs. spinal.

CONCLUSION: [18]F-FDG brain PET imaging, combined with SVM and age-matching, can distinguish between ALS[C9orf72RE] and sALS with good accuracy, but lacks sufficient discriminative power to differentiate between ALS and Mimics and between different sites of onset.},
}

@article {pmid41422089,
year = {2025},
author = {Jun, YW and Lee, S and Almeida, S and Freude, KK and Ichida, JK and Gao, FB},
title = {The Ku80-p53-SIRT1 axis in DNA damage response contributes to sporadic and familial ALS and FTD.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-67749-7},
pmid = {41422089},
issn = {2041-1723},
support = {R37NS057553//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01NS101986//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; NA/ALZ/Alzheimer's Association/United States ; NRF-2019R1A6A3A03034014//National Research Foundation of Korea (NRF)/ ; },
abstract = {Although TDP-43 pathology is found in most sporadic and familial ALS and FTD cases, other shared pathogenic mechanisms remain largely unknown. Here we show that SIRT1 levels are decreased and acetylated p53 levels are increased in iPSC-derived neurons from sALS patients and with the FTD3-causing CHMP2B mutation. Ectopic expression of SIRT1 in these patient neurons rescues neurodegeneration and reduces acetylated p53 levels. DNA damage is elevated in both sALS and FTD3 neurons, leading to increased phosphorylation of p53 at Serine 15 and elevated levels of Ku80. Knockdown of either p53 or Ku80 rescues neurodegeneration and increases SIRT1 levels in these neurons. Moreover, ectopic expression of SIRT1 or genetic knockdown of either p53 or Ku80 suppresses retinal neurodegeneration caused by FTD3-associated mutant CHMP2B protein in an in vivo Drosophila model. These findings identify a dysregulated SIRT1-p53 feedback loop as a common pathogenic mechanism and promising therapeutic target in both sporadic and familial ALS/FTD.},
}

@article {pmid41420983,
year = {2025},
author = {Garcia-Delgado, AB and Bega, S and Campos-Cuerva, R and Martín-Banderas, L and Paradas, C and Fernandez-Muñoz, B},
title = {Generation of the human iPSC line ESi148-A from a patient with sporadic amyotrophic lateral sclerosis.},
journal = {Stem cell research},
volume = {90},
number = {},
pages = {103889},
doi = {10.1016/j.scr.2025.103889},
pmid = {41420983},
issn = {1876-7753},
abstract = {Nearly 90% of patients with amyotrophic lateral sclerosis (ALS) do not carry mutations in genes previously associated with the disease and are classified as sporadic cases with no identified genetic cause. In this study, peripheral blood mononuclear cells from a patient with sporadic ALS were reprogrammed to generate the human induced pluripotent stem cell (iPSC) line ESi148-A. The line was thoroughly characterized for pluripotency and genomic stability. These cells provide a valuable resource for generating 3D biomodels, such as cortical or spinal cord organoids, to investigate disease mechanisms and develop novel therapeutic approaches for sporadic ALS.},
}

@article {pmid41420832,
year = {2025},
author = {Wang, X and Wei, M and Qiao, Y},
title = {Modulation of Liquid-to-Solid Phase Transition in Coacervates for Neurodegenerative Disease Treatments.},
journal = {Chembiochem : a European journal of chemical biology},
volume = {},
number = {},
pages = {e202500795},
doi = {10.1002/cbic.202500795},
pmid = {41420832},
issn = {1439-7633},
support = {2023YFC2507000//National Key R&D Program of China/ ; 22272183//National Natural Science Foundation of China/ ; T2425001//National Natural Science Foundation of China/ ; },
abstract = {Coacervates formed through liquid-liquid phase separation represent a fundamental model for protocell and serve as a membraneless organelle in living cells, modulating various biological processes. During aging or under stress, protein misfolding and oligomerization trigger aberrant liquid-to-solid phase transition (LSPT), a process driven by multivalent interactions. These phase transitions disrupt cellular equilibrium, leading to neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The regulatory strategies is summarize to enhance molecular interactions in coacervate LSPT into three categories, including physical stimulation, molecular modulation, and sequence regulation. This review aims to establish a conceptual framework for modulating coacervate LSPT and further explores potential clinical treatments for neurodegenerative diseases.},
}

@article {pmid41420107,
year = {2025},
author = {Campos-Ribeiro, MA and Donnarumma, E and Nolte, H and Cobine, P and Vimont, E and Milenkovic, D and Hernandez-Camacho, JD and Langa-Vives, F and Kornobis, E and Pénard, E and Yde, S and Langer, T and Paquis-Flucklinger, V and Wai, T},
title = {Mutant CHCHD10 disrupts cytochrome c oxidation and activates mitochondrial retrograde signaling.},
journal = {EMBO molecular medicine},
volume = {},
number = {},
pages = {},
pmid = {41420107},
issn = {1757-4684},
support = {ANR-21-CE14 0052-02//Agence Nationale de la Recherche (ANR)/ ; ANR-23-CE13-0043-01//Agence Nationale de la Recherche (ANR)/ ; ANR-10-INSB-04-01//Agence Nationale de la Recherche (ANR)/ ; ANR-10-LABX-62-IBEID//Agence Nationale de la Recherche (ANR)/ ; INNOV 164-2022//Institut Pasteur (Pasteur Institute)/ ; },
abstract = {Mutations in CHCHD10, a mitochondrial intermembrane space (IMS) protein implicated in proteostasis and cristae maintenance, cause mitochondrial disease. Knock-in mice modeling the human CHCHD10[S59L] variant associated with ALS-FTD develop a mitochondrial cardiomyopathy driven by CHCHD10 aggregation and activation of the mitochondrial integrated stress response (mtISR). We show that cardiac dysfunction is associated with dual defects originating at the onset of disease: (1) bioenergetic failure linked to impaired mitochondrial copper homeostasis and cytochrome c oxidation, and (2) maladaptive mtISR signaling via the OMA1-DELE1-HRI axis. Using protease-inactive Oma1[E324Q/E324Q] knock-in mice, we show that blunting mtISR in Chchd10[S55L/+] mice delays cardiomyopathy onset without rescuing CHCHD10 insolubility, cristae defects or OXPHOS impairment. Proteomic profiling of insoluble mitochondrial proteins in Chchd10[S55L/+] mice reveals widespread disruptions of mitochondrial proteostasis, including IMS proteins involved in cytochrome c biogenesis. Defective respiration in mutant mitochondria is rescued by the addition of cytochrome c, pinpointing IMS proteostasis disruption as a key pathogenic mechanism. Thus, mutant CHCHD10 insolubility compromises metabolic resilience by impairing bioenergetics and stress adaptation, offering new perspectives for the development of therapeutic targets.},
}

@article {pmid41419928,
year = {2025},
author = {An, J and Hendricks, N and Wheeler, J and Hincks, J and Benitez, JAR and Snyder, JM and Kraemer, BC and Liachko, NF and Elkon, KB},
title = {Neuronal TDP-43 pathology drives astrocytic interferon response in a mouse model of ALS.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-025-03658-2},
pmid = {41419928},
issn = {1742-2094},
support = {IK6BX006467//The United States Department of Veterans Affairs/ ; I01BX004044//The United States Department of Veterans Affairs/ ; RF1AG055474/NH/NIH HHS/United States ; R01AG066729/NH/NIH HHS/United States ; },
abstract = {Neuroinflammation is implicated in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS). Amongst potential innate immune mediators of disease, Type I interferon (IFN-I) could play an important role due to its ability to inhibit protein synthesis and affect neuronal synapses and metabolism. These effects could be cell intrinsic or non-cell autonomous mediated by glia or immune cells. We examined IFN-I in rNLS8 mice that have been engineered to express doxycycline suppressible human Transactive response DNA binding protein 43 kDa (hTDP-43) with a defective nuclear localization signal (hTDP-43ΔNLS) regulated by the neurofilament heavy chain (NEFH) promoter. Following induction of hTDP-43ΔNLS in rNLS8 mice, we observed upregulation of IFN-I stimulated genes (ISG) and, specifically, activation of the DNA sensor, cyclic GMP-AMP synthase (cGAS), as determined by mass spectrometry identification of the cyclic dinucleotide, cGAMP, in whole brain. To determine the cellular source of IFN-I, we performed single nucleus RNA sequencing of whole brain. We observed that ISG were most highly upregulated in astrocytes suggesting that astrocytes themselves were largely responsible for IFN-I production and / or response in rNLS8 mice. This observation was confirmed by immunohistochemical and immunofluorescence staining of IFN-I stimulated proteins in astrocytes in the cerebrum, especially in the hippocampus. These results point to a pivotal role of astrocytes in responding to cell damage at a relatively early phase of disease which prior studies have shown is partially reversible.},
}

@article {pmid41419800,
year = {2025},
author = {Sun, Y and Zhong, Q and Chu, X and Wan, D and Peng, Y},
title = {Total intravenous anesthesia without neuromuscular blockers for ureteral lithotripsy in an ALS patient with orthopnea: a case report.},
journal = {BMC anesthesiology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12871-025-03561-6},
pmid = {41419800},
issn = {1471-2253},
}

@article {pmid41419286,
year = {2025},
author = {Phillips, G and Sharma, D and O'Reilly, G and Romero, L and Cameron, P},
title = {Developing emergency care systems in low-income and middle-income countries: a scoping review to examine the role of leadership and governance.},
journal = {BMJ open},
volume = {15},
number = {12},
pages = {e102624},
pmid = {41419286},
issn = {2044-6055},
mesh = {Humans ; *Developing Countries ; *Leadership ; *Emergency Medical Services/organization & administration ; },
abstract = {BACKGROUND: More knowledge and resources are required to strengthen 'leadership and governance' (L+G) as a central building block to further develop emergency care (EC) systems in low-income and middle-income countries (LMICs).

OBJECTIVES: This scoping review aimed to examine and map the impact of individual, collective or institutional L+G on the development of EC systems (prehospital and facility-based) in LMICs.

ELIGIBILITY CRITERIA: English language publications from January 2005 to April 2024 that linked any L+G action with the development and capacity of everyday EC in LMICs, specifically excluding disaster responses.

SOURCES OF EVIDENCE: Medline (Ovid), Embase (Ovid), CINAHL, Web of Science (Clarivate), Central (Cochrane Central Register of Controlled Trials), Global Health (Ovid) and select grey literature.

CHARTING METHODS: Data from all eligible papers were jointly extracted using a piloted tool developed from the literature and WHO's EC Systems Framework. L+G descriptors included level (from clinical to national) and components (informed by Siddiqi et al's LMIC health system 'good governance' framework and a synthesis of EC policy documents). Impact of L+G on EC systems and key lessons were extracted from each publication.

RESULTS: From an initial 9713 items, 129 papers were included for final analysis and divided by EC component: prehospital (n=35), facility-based (n=53) and 'whole of EC system' (n=41). Qualitative and descriptive papers were most common, and 72 out of a possible 131 LMICs were represented. Findings were heterogeneous across all building blocks of EC systems and for different components of leadership and/or governance. Cross-cutting L+G themes were identified that demonstrated consistent impact across all EC systems development: government recognition, vision and human rights framing; coalition-building for effective partnerships and trained, empowered EC clinicians demonstrating emotionally intelligent, transformational leadership.

CONCLUSIONS: Applying new models such as Theories of Change and Social Network Analysis concepts may assist to illuminate how effective L+G is attained, what are the essential components and how these influence EC systems for better patient-centred outcomes. Further understanding the role of L+G for EC systems has utility for future EC clinician leadership training and policy-maker awareness, to strengthen resilience of overall health systems against likely future shocks.},
}

Humans
*Developing Countries
*Leadership
*Emergency Medical Services/organization & administration

@article {pmid41419037,
year = {2025},
author = {Henriksson, S and Bäckström, M and Westberg, H and Hagberg, J},
title = {PCDD/Fs in food products produced near a contaminated former sawmill - concentrations, congener profiles and risk assessment.},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {390},
number = {},
pages = {127529},
doi = {10.1016/j.envpol.2025.127529},
pmid = {41419037},
issn = {1873-6424},
abstract = {Hillringsberg, a former sawmill site in Sweden, is severely contaminated with polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). This study collected site-specific data to assess the human health risks associated with locally produced food. To evaluate potential exposure, samples of salmon, perch, cow's milk, cattle, and sheep were collected near the site and analyzed for PCDD/Fs. The findings reveal that the most frequently detected congeners in the food samples corresponded with the most abundant congeners in the soil, underscoring the impact of contaminated sites on PCDD/F concentrations in locally produced food. Particularly concerning is the level of PCDD/Fs in sheep meat, which was found to be 11 times higher than the Tolerable Weekly Intake (TWI) for adults and 26 times higher for children. Comparing food samples from the sawmill site to those from the National Swedish Control Programme revealed that all food samples from Hillringsberg exhibited some level of contamination, even though the concentrations of PCDD/Fs remained below the European Maximum Limits (MLs) and Action Limits (ALs). The concentrations and patterns of contaminants in nearly all samples, particularly those from sheep, cattle and perch, were influenced by local contamination from the historical use of pentachlorophenol (PCP) at the old sawmill site. PCA showed that sheep and soil samples from the storage area exhibited strong covariance. Perch and sediment samples from the sawmill pond were also grouped together. These findings highlight the necessity of evaluating food production activities near contaminated sites during the initial stages of site-specific risk assessments. Ensuring food safety in these areas is crucial, and if necessary, relocating grazing lands, fish farms, and similar operations can help mitigate health risks associated with contaminated food.},
}