@article {pmid41133969,
year = {2025},
author = {Lindenborn, P and Fabian, R and Grehl, T and Nazlican, H and Meyer, T and Bernsen, S and Weydt, P},
title = {Combination of Serum Neurofilament Light Chain and Serum Cardiac Troponin T as Biomarkers Improves Diagnostic Accuracy in Amyotrophic Lateral Sclerosis.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78066},
pmid = {41133969},
issn = {1531-8249},
abstract = {OBJECTIVE: We aimed to evaluate the clinical utility of serum neurofilament light chain (sNfL) and cardiac troponin T (cTnT) in amyotrophic lateral sclerosis (ALS) and assess whether their combination improves diagnostic accuracy.

METHODS: We retrospectively analyzed 293 ALS patients, 85 neurodegenerative disease controls, and 29 healthy controls. A validation cohort of 501 ALS patients was analyzed to confirm reproducibility of the results. Receiver operating characteristic (ROC) curve analysis was performed for sNfL, cTnT, and their combination, and the area under the curve (AUC) was compared across groups. An ALS-specific cTnT cut-off of 8.35ng/L was determined using the Youden index and applied in subgroup analyses, in which "biomarker-negative" ALS patients were compared to "biomarker-positive" patients regarding disease duration and progression.

RESULTS: sNfL showed excellent performance in discriminating ALS patients from healthy controls (AUC = 0.94), but only moderate performance in discriminating neurodegenerative disease controls (AUC = 0.82). Combining sNfL and cTnT improved diagnostic accuracy for ALS over neurodegenerative controls, with an AUC of 0.90, whereas cTnT alone showed an AUC of 0.77. The validation cohort showed similar AUCs. "Biomarker-negative" ALS patients had a longer disease duration (73.0 vs 18.0 months, p = 0.0003) and a lower progression rate (0.19 vs 0.70 points per months, p < 0.0001) than "biomarker-positive" patients.

INTERPRETATION: Although sNfL alone performs well in distinguishing ALS from healthy controls, repurposing cTnT for ALS provides additional value in discriminating ALS from disease controls. The combination of sNfL and cTnT improves diagnostic accuracy and may help identify prognostically distinct ALS subgroups. ANN NEUROL 2025.},
}

@article {pmid41133655,
year = {2025},
author = {Di Fronzo, P and Gaetti, G and Marcassa, D and Gervasi, V and Dardour, O and Pedretti, A and Gambolò, L},
title = {The Impact of ACLS Training in the Management of Cardiac Arrest: A Narrative Review.},
journal = {Epidemiologia (Basel, Switzerland)},
volume = {6},
number = {4},
pages = {},
pmid = {41133655},
issn = {2673-3986},
abstract = {BACKGROUND: Cardiac arrests can occur both in and out of hospital settings. Over the years, several protocols have been developed to standardize the behavior of healthcare professionals called upon to deal with these emergencies. Advanced Cardiac Life Support (ACLS) algorithms enable healthcare professionals to effectively manage cardiac arrest and achieve better patient outcomes, particularly at the time of discharge.

METHODS: We conducted a narrative review. Three databases (PubMed, Embase, Cochrane) were searched for relevant articles. The articles were screened and analyzed in accordance with the PRISMA guidelines.

RESULTS: A total of 1252 articles were initially identified. After screening, 11 papers were included in the review. From the selected studies, it has emerged that ACLS training had several positive effects, including an overall decrease in mortality rates. Adherence to ACLS protocols throughout an event is associated with increased Return of Spontaneous Circulation (ROSC) in the setting of In-Hospital Cardiac Arrest (IHCA). Advanced Life Support (ALS) response interval in out-of-hospital cardiac arrest was associated with decreased survival and a favorable neurological outcome. ALS response ≤ 10 min was associated with improved survival and favorable neurological outcomes.

CONCLUSIONS: This review underscores the importance of adherence to ALS/ACLS guidelines in the resuscitation of patients who suffer in-hospital and out-of-hospital cardiac arrest.},
}

@article {pmid41132886,
year = {2025},
author = {Agüera-Morales, E and Fernández-Sánchez, VE and Navarro-Mascarell, G and Cabezas-Rodríguez, JA and Peña-Toledo, MÁ and Reyes-Rodríguez, V and Postigo-Pozo, MJ and Patrignani-Ochoa, G and Geniz-Clavijo, MÁ and Márquez-Infante, C and Tallon-Aguilar, L and Tinoco-González, J and Padillo-Ruiz, J and Valladares-Sánchez, A and Caballero-Eraso, C and López-Ramírez, C and Mata Alcázar-Caballero, R and Leyva-Fernández, L and Rodríguez-Acosta, A and Maldonado-Sánchez, R and García-Martín, ML and Somoza-Ramírez, M and Quijano-Ruiz, B and Macías-Sánchez, MDM and Carmona-Sánchez, G and Fernández-López, O and Fernández-Fernández, Ó},
title = {Adipose-derived mesenchymal stem cells for the treatment of Amyotrophic Lateral Sclerosis. A phase I/II safety and efficacy clinical trial.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1655124},
pmid = {41132886},
issn = {1664-2295},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease with few treatments available. Mesenchymal stem cells have arisen as a potential treatment option for ALS due to their immune system modulation and their neuroprotective effects. This clinical trial aimed to evaluate the safety, efficacy and feasibility of three intravenous doses of autologous adipose-derived mesenchymal stem cells (AdMSC) in ALS patients.

METHODS: A multicentre, randomized, parallel group, placebo-controlled, double-blinded clinical trial (EudraCT: 2011-006254-85) was conducted in 40 patients with ALS in treatment with riluzole. Patients were randomized 1:1:1:1 into the following treatment groups: 1 × 10[6] cells/kg, 2 × 10[6] cells/kg, 4 × 10[6] cells/kg and placebo. After a 6 month follow-up, patients in the placebo group were randomized 1:1:1 to receive one of the three doses of AdMSC and they were followed up for another 6 months. Lastly, all patients were followed-up in a 36-month open-label extension. Safety was mainly assessed through the evaluation of adverse events and their relationship with the medicinal product. Several variables were measured to assess efficacy, such as ALS Functional Rating Scale, Ashworth spasticity scale, neurophysiological and neuropsychological parameters and overall survival. The feasibility of the procedure was assessed through the evaluation of the extraction and infusion of AdMSC.

RESULTS: Safety of AdMSC was observed through all follow-up periods, with similar percentages of adverse events between groups and no significant differences between groups in the rate of adverse events related to treatment. The administration procedure was feasible for all patients. Across all analyzed measures, we observed the expected progressive decline characteristic of ALS, with no statistically significant between-group differences in the rate of change.

DISCUSSION: The results obtained in this study are consistent with the ones obtained in other clinical trials using similar doses of MSC, where safety was demonstrated and efficacy results were inconclusive, due to not reaching statistical significance. Larger studies with an increased sample size, different doses and route of administration or combination of routes, repeated dosing or larger duration and comprehensive assessment of immunological effect would be needed to analyze the efficacy of AdMSC in the treatment of ALS.

CLINICAL TRIAL REGISTRATION: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2011-006254-85.},
}

@article {pmid41131916,
year = {2025},
author = {Shen, D and Liu, A and Yang, X and Liu, Q and Liu, M and Cui, L},
title = {The Impact of Bulbar and Upper Motor Neuron Involvement on Oculomotor Movement in Amyotrophic Lateral Sclerosis.},
journal = {Brain and behavior},
volume = {15},
number = {10},
pages = {e70906},
doi = {10.1002/brb3.70906},
pmid = {41131916},
issn = {2162-3279},
support = {2022-PUMCH-A-069//National High Level Hospital Clinical Research Funding/ ; UHB11982//Peking Union Medical College Hospital Talent Cultivation Program (Category D)/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/complications ; Male ; Female ; Middle Aged ; Aged ; *Motor Neurons/physiology ; Saccades/physiology ; *Eye Movements/physiology ; Adult ; Reaction Time/physiology ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the degeneration of both lower and upper motor neurons (UMN). Clinical heterogeneity manifests in subtypes such as bulbar-onset ALS (bALS) and spinal-onset ALS (sALS), with emerging evidence suggesting that oculomotor dysfunction may reflect broader multisystem involvement. This study aims to investigate oculomotor parameters across different ALS phenotypes and their associations with neuropsychological domains.

METHODS: A total of 46 patients meeting the Gold Coast Criteria for ALS were enrolled, alongside 23 age- and education-matched healthy controls (HCs). Participants were assessed for demographic variables and clinical features, and underwent cognitive and oculomotor testing using the EyeKnow system. Eye movement performance was compared between groups, and correlations between oculomotor metrics and cognitive and clinical data were examined.

RESULTS: ALS patients displayed longer reaction times in anti-saccade tasks (357.48 ± 61.28 ms vs. 316.10 ± 52.70 ms, p = 0.005) and significantly lower predictive saccade accuracy (86.77 ± 19.17% vs. 99.36 ± 2.22%, p < 0.001) compared to HCs. There is no significant difference in the eye movement parameters between sALS and bALS. Patients with bulbar involvement exhibited poorer performance in predictive saccade accuracy (77.53 ± 26.66% vs. 96.01 ± 4.92%, p < 0.001) and longer initial time in the smooth pursuit task (647.43 [402.14, 760.64] ms vs. 452.43 [131.62, 598.20] ms, U = 161.00, p = 0.037) compared to those without bulbar involvement. UMN involvement was associated with poorer performance across prosaccade, anti-saccade, and predictive saccade tasks. No significant correlation between oculomotor metrics and cognitive tests or clinical data was detected.

CONCLUSIONS: The findings highlight the impact of bulbar and UMN involvement on oculomotor dysfunction in ALS, demonstrating distinct patterns across various phenotypes. Although oculomotor metrics show sensitivity to the pathophysiology of ALS, their effectiveness as independent biomarkers needs further validation through longitudinal studies that include larger cohorts, advanced neuroimaging techniques, and multimodal assessments to capture the complex interplay between motor, cognitive, and anatomical changes in this varied disease.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/complications
Male
Female
Middle Aged
Aged
*Motor Neurons/physiology
Saccades/physiology
*Eye Movements/physiology
Adult
Reaction Time/physiology

@article {pmid41131592,
year = {2025},
author = {Theunissen, F and Flynn, L and Iacoangeli, A and Al Khleifat, A and Al-Chalabi, A and Giordano, JJ and Strømme, M and Akkari, PA},
title = {Entering the era of precision medicine to treat amyotrophic lateral sclerosis.},
journal = {Molecular neurodegeneration},
volume = {20},
number = {1},
pages = {111},
pmid = {41131592},
issn = {1750-1326},
mesh = {*Amyotrophic Lateral Sclerosis/genetics/drug therapy/therapy ; Humans ; *Precision Medicine/methods ; },
abstract = {With the disease modifying therapy Qalsody (tofersen) which targets the RNA product of the SOD1 gene, having been shown effective in amyotrophic lateral sclerosis (ALS), the present perspective seeks to explore progress towards the implementation of precision medicine principles in ALS drug development. We address the advances in our understanding of the complex genetic architecture of ALS, including the varying models of genetic contribution to disease, and the importance of understanding population genetics and genetic testing when considering patient selection for clinical studies. Additionally, we discuss the advances in long-read whole-genome sequencing technology and how this method can improve streamlined genetic testing and our understanding of the genetic heterogeneity in ALS. We highlight the recent advances in omics-data for understanding ALS patient sub-groups and how this knowledge should be applied to pre-clinical drug development in a proposed patient profiling workflow, particularly for gene targeted therapies. Finally, we summarise key ethical considerations that are pertinent to equitable care for patients, as we enter the era of precision medicine to treat ALS.},
}

*Amyotrophic Lateral Sclerosis/genetics/drug therapy/therapy
Humans
*Precision Medicine/methods

@article {pmid41131452,
year = {2025},
author = {Eager, KLM and Jolly, RD and Manning, L and Willet, CE and Snell, RG and Lehnert, K and Mckean, NE and Sneddon, NW and O'Rourke, BA and Dittmer, KE and Tammen, I and Littlejohn, M},
title = {A novel frameshift variant in ALS2 associated with segmental axonopathy in Merino sheep.},
journal = {Genetics, selection, evolution : GSE},
volume = {57},
number = {1},
pages = {60},
pmid = {41131452},
issn = {1297-9686},
mesh = {Animals ; *Frameshift Mutation ; Sheep/genetics ; *Sheep Diseases/genetics/pathology ; Axons/pathology ; *Neurodegenerative Diseases/genetics/veterinary/pathology ; Female ; Male ; },
abstract = {BACKGROUND: Segmental axonopathy is a recessively inherited neurodegenerative disorder that has affected Merino sheep since the early 1930s. Despite its long-standing recognition, the genetic basis of the condition remained unknown. This study aimed to identify the genetic cause of segmental axonopathy and confirm its pathological features to improve diagnostic accuracy and inform breeding strategies.

RESULTS: Whole genome sequencing and genotyping of affected and unaffected Merino sheep identified a novel homozygous frameshift variant in the ALS2 gene that segregated with disease. RNA sequencing of cerebellar peduncle tissue confirmed the nonsense consequence on the ALS2 transcript. Histological analysis highlighted the hallmarks of the disease as large, foamy eosinophilic axonal swellings predominantly in the trigeminal ganglia, with additional degenerative changes in both the brain and spinal cord. These findings support the value of targeted sampling of sensory roots of the trigeminal nerve, spinal cord tracts, and dorsal nerve rootlets to enhance diagnostic accuracy. The same ALS2 variant was found across multiple unrelated flocks in both Australia and New Zealand, indicating a broader presence within the fine-wool Merino sheep population.

CONCLUSIONS: This study identifies a novel ALS2 frameshift variant associated with segmental axonopathy in Merino sheep and provides both genetic and histological evidence supporting its role in disease pathology. The development of a DNA diagnostic test will enable more informed breeding decisions, reduce the prevalence of this condition, and improve animal welfare and productivity in the Merino industry. Moreover, the findings offer a potential large-animal model for exploring early-onset forms of human motor neuron diseases, including amyotrophic lateral sclerosis, in which ALS2 variants are implicated.},
}

Animals
*Frameshift Mutation
Sheep/genetics
*Sheep Diseases/genetics/pathology
Axons/pathology
*Neurodegenerative Diseases/genetics/veterinary/pathology
Female
Male

@article {pmid41131433,
year = {2025},
author = {De Luca, S and Paladugu, S and Balla, SB and Moukarzel, M and Angelakopoulos, N},
title = {Accuracy of third molar eruption for legal age estimation using the Gambier method in Lebanese subadults.},
journal = {Odontology},
volume = {},
number = {},
pages = {},
pmid = {41131433},
issn = {1618-1255},
abstract = {Assessing whether an individual has reached the legal age of 18 is a complex, multifactorial process that requires the application of reliable, standardized, and reproducible methods. Among the various approaches, the assessment of third molar eruption has recently emerged as a useful preliminary tool for estimating whether an individual has reached the age of majority. This study aims to evaluate the accuracy of the Gambier et al. scoring system for legal age estimation based on third molar eruption in a sample of Lebanese subadult individuals. A retrospective analysis was conducted on 537 orthopantomograms (OPGs), comprising 298 males and 239 females, aged between 15 and 24 years. An increase in mean chronological age was observed with the progression of third molar eruption stages (1-3) and phases (A-D) in both sexes. Only in limited cases has a strong relationship been found between phase D and the probability that an individual is 18 years of age or older. In this Lebanese sample, phase D, which corresponds to complete emergence in the occlusal plane, was not always associated with individuals being 18 years or older: the 11.9% of males and females in this phase is above the legal age threshold. This technique may serve only as a preliminary tool for estimating the probable age of alleged minors of Lebanese origin, particularly in the context of migrant populations and child marriage contexts. Its application is recommended in accordance with the minimum age principle, as minimum age thresholds have been established for each stage and phase of third molar eruption. This method, however, ought to be applied only in combination with other internationally validated dental age estimation methods, thereby safeguarding against potential ethical implications associated with legal age assessment.},
}

@article {pmid41129733,
year = {2025},
author = {Aouti, S and Kommu, P and Hegde, RP and Ali, A and Mm Srinivas, B and Padavattan, S and Padmanabhan, B},
title = {Structure and Molecular Basis for Inhibiting Human SOD1 Aggregation by a Promising Decan Derivative Modulator: A Potential Therapeutic Strategy for Treating Amyotrophic Lateral Sclerosis (ALS).},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.5c00168},
pmid = {41129733},
issn = {1948-7193},
abstract = {Misfolding and aggregation of the human superoxide dismutase (hSOD1) protein are pathological hallmarks of amyotrophic lateral sclerosis (ALS), a motor neuron disease. The structural stabilization and enzymatic activation of hSOD1 occur upon binding to Cu/Zn ions and forming an intramolecular disulfide bond. Mutations in hSOD1 result in structural changes in the electrostatic and metal-binding loops, leading to the dissociation of Cu and/or Zn ions, which in turn triggers SOD1 oligomerization in ALS. Through X-ray studies, we have identified 1,2,10-decanetriol, a solubilizing agent commonly used in drug delivery, as a modulator that binds at the electrostatic loop and dimer interface regions of SOD1. The crystal structure of hSOD1 complexed with 1,2,10-decanetriol, refined to 1.97 Å resolution, reveals that the ligand stabilizes both loop regions as well as the dimeric structure of hSOD1. Notably, this compound exhibits a low nanomolar binding affinity of 32.40 ± 0.65 nM for hSOD1 and significantly inhibits aggregation in both metalated and demetalated wild-type and disease mutant proteins. Among the various inhibitors investigated for their ability to reduce SOD1 oligomerization, our study is the first to identify a molecule that binds at the electrostatic loop, as confirmed by in vitro experiments. These findings suggest that 1,2,10-decanetriol is a promising scaffold with potential inhibitory properties for library development against SOD1's amyloidogenic behavior.},
}

@article {pmid41129425,
year = {2025},
author = {Radakovic, R and Gray, D and Trucco, AP and Mioshi, E and Copsey, H and Dick, D and Newton, J and Pal, S and Simmons, Z and Abrahams, S},
title = {Self-reported initiation apathy is related to worse quality of life in amyotrophic lateral sclerosis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-6},
doi = {10.1080/21678421.2025.2574684},
pmid = {41129425},
issn = {2167-9223},
abstract = {Objective: Apathy is the most prevalent behavioral impairment or difficulty for people with ALS (pwALS), with Initiation apathy (a lack of motivation for self-generation of thoughts and/or actions) the most common subtype. Self-rated or self-perceived quality of life (sQoL) is impacted for pwALS, but the relationship to apathy subtypes is unknown. The aim was to explore the relationship between sQoL domains and apathy in pwALS. Methods: 32 pwALS were recruited and completed self-rated measures of apathy (Dimensional Apathy Scale), depression, anxiety, and emotional lability. The ALS-specific QoL short-form instrument was used to measure QoL. Cognitive functioning and functional disability were measured. Exploratory, comparative, and predictive multiple hierarchical regression analyses were performed. Results: Initiation apathy was the most common apathy subtype at 37.5% (N = 12). PwALS with Initiation apathy had higher depressive symptoms (p <.05, d = 1.11 large effect) and lower cognitive functioning (p <.05, d = 0.76 medium effect) than those without apathy. PwALS with Initiation apathy had significantly worse sQoL in domains of interaction with people and the environment (p <.05, d = 0.92, large effect) and negative emotions (p <.05, d = 0.80, large effect) than those without apathy. Regression analysis showed Initiation apathy was a significant negative predictor of the sQoL domain of interaction with people and the environment (beta =-.20, p <.01), controlling for confounders (functional disability, depression, cognitive functioning). Conclusions: Initiation apathy was associated with QoL domains of interaction with people and the environment, from the perspective of the pwALS. This emphasizes the importance of self-rating or self-perception for clinical and researcher assessment of apathy and QoL for pwALS.},
}

@article {pmid41129353,
year = {2025},
author = {Avila-Chauvet, L and Cruz, DM and Hernández, LA and González, FC},
title = {Effect of visual range on producer responses: Insights from humans (Homo sapiens) and an agent-based model.},
journal = {Journal of comparative psychology (Washington, D.C. : 1983)},
volume = {},
number = {},
pages = {},
doi = {10.1037/com0000432},
pmid = {41129353},
issn = {1939-2087},
support = {//Secretaría de Ciencia, Humanidades, Tecnología e Innovación (SECIHTI)/ ; },
abstract = {The Producer-Scrounger game proposes that individuals in social foraging situations tend to choose one of two strategies: (a) actively invest effort in searching for resources (producing) or (b) exploit resources discovered by others (scrounging). Models have typically given scroungers an advantage. In Vickery et al.'s (1991) model, remaining food in a patch is equally shared among scroungers regardless of their position or visual range. Similarly, agent-based models assume scroungers have a comprehensive view of the habitat, enabling them to detect all opportunities to exploit resources, while producers move randomly. This study examined the effect of visual range on producer-scrounger dynamics using a computerized behavioral task where four human participants interacted in real time within a virtual habitat. Two groups, differing in food probability (λ80 and λ20), were exposed to four experimental conditions that varied visual range by manipulating the top-down camera angle (45° or 75°) and camera distance (240 or 80 px). Results showed that the producer index was higher when the probability of finding resources increased, and highest in the 75°-240 px condition, where participants had limited depth of view but could better perceive their immediate surroundings. A modified agent-based model that included visual range parameters revealed a similar pattern. These findings highlight the importance of visual range, often underestimated in theoretical models, for producer strategies. (PsycInfo Database Record (c) 2025 APA, all rights reserved).},
}

@article {pmid41127961,
year = {2025},
author = {De Marchi, F and Baj, A and Menegon, F and Caminiti, SP and Sacchetti, M and Sarnelli, MF and Corrado, L and Puricelli, C and Matheoud, R and Binaschi, L and Sacchetti, GM and D'Alfonso, S and Comi, C and Perani, D and Mazzini, L and Tondo, G},
title = {Profiling cognition and brain metabolism in amyotrophic lateral sclerosis and frontotemporal dementia.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awaf401},
pmid = {41127961},
issn = {1460-2156},
abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are described as a disease continuum, given their shared clinical, genetic, and pathological characteristics. The comparisons of clinical and biomarker features within ALS and behavioral variant FTD (bvFTD) spectrum, would be of utmost importance for diagnostic and prognostic purposes. This study investigated biomarker differences between patients with ALS cognitively-normal (ALS-cn), ALS-FTD, and bvFTD. Participants, genetically screened for known ALS- and FTD-associated mutations, underwent neuropsychological assessments, CSF analysis, and brain imaging through 18-fluorodeoxyglucose PET ([18F]FDG-PET). Neuropsychological data were analyzed by calculating, for each cognitive domain, a composite score by averaging the rank-transformed z-scores of all tests measuring the same domain. [18F]FDG-PET analysis was performed using a validated voxel-based SPM method at single-subject and group-level. To evaluate the ability of the identified markers to differentiate ALS-cn, ALS-FTD, and bvFTD, machine-learning models-including support vector machine (SVM) and random forest (RF)-were applied, offering a streamlined, data-driven approach to improve diagnostic precision across this spectrum of disorders. 20 ALS-cn, 19 ALS-FTD, and 21 bvFTD patients were included. Neuropsychological composite z-scores revealed significant differences across groups, underlining worse performance in bvFTD regarding memory, visuospatial, language and executive functions. Brain [18F]FDG-PET showed a pattern of hypometabolism increasing from ALS-cn to ALS-FTD and reaching its greatest extent in bvFTD. Specifically, brain hypometabolism was mainly confined to the sensorimotor cortices and the frontobasal regions in the ALS-cn group, whereas in the ALS-FTD group it was extended to the supplementary motor area and the dorsolateral frontal cortex, and in the bvFTD group, a widespread hypometabolism further affected the frontomesial and orbitofrontal cortices. No significant differences in CSF biomarkers were observed. SVM correctly classified 83% of patients, indicating a good level of classification performance, while RF showed perfect accuracy (100%). The two models shared eight to ten most relevant features in the classification system, namely age, disease duration from symptoms onset to diagnosis, total composite z-score, superior frontal gyrus (left), middle frontal gyrus (left), middle frontal gyrus - pars orbitalis (left and right), and anterior cingulate cortex (left). Our study identified significant differences in the biomarkers according to the neurodegenerative clinical groups within the same disease spectrum. These differences were evident in neuropsychological profiles and brain hypometabolism patterns, successfully addressing the study's aim and providing valuable insights for differential diagnosis into ALS-FTD continuum heterogeneity.},
}

@article {pmid41127439,
year = {2025},
author = {Xu, J and van Eijk, RPA and Ellis, A and Pan, T and Nelson, LM and Roes, KCB and van Dijk, M and Sarno, M and van den Berg, LH and Tian, L and Lu, Y},
title = {On the Two-Step Hybrid Design for Augmenting Randomized Trials Using Real-World Data.},
journal = {Statistics in biopharmaceutical research},
volume = {},
number = {},
pages = {},
pmid = {41127439},
issn = {1946-6315},
support = {P01 CA257907/CA/NCI NIH HHS/United States ; R01 HL089778/HL/NHLBI NIH HHS/United States ; UM1 TR004921/TR/NCATS NIH HHS/United States ; },
abstract = {Hybrid clinical trials, which borrow real-world data (RWD) from patient registries, claims databases, or electronic health records (EHRs) to augment randomized clinical trials, are of increasing interest. Hybrid clinical trials are especially relevant for rare diseases, where the recruitment of large sample sizes may be challenging. While these trials may better use available information, they assume that the RWD and randomized control arm are exchangeable. Violating this assumption can induce bias, inflate Type I error, or adversely affect statistical power. A two-step hybrid design first tests the exchangeability between randomized control arm and external data sources before incorporating RWD as a comparator for statistical inferences (Yuan et al. 2019). This approach reduces the chance of inappropriate borrowing but may simultaneously inflate the Type I error rate. We propose four different methods to control the Type I error rate under the exchangeability assumption. Approach 1 estimates the variance of the overall test statistic and rejects the null hypothesis based on a Z-test. Approach 2 uses a numerical method to determine the exact critical value for Type I error control. Approach 3 splits the Type I error rates according to the equivalence test outcome. Approach 4 adjusts the critical value only when equivalence is established. We illustrate these methods using a hypothetical scenario in the context of amyotrophic lateral sclerosis (ALS). We evaluate the Type I error and power under various clinical trial conditions in comparison with the Bayesian power prior approach (Ibrahim et al. 2015). We demonstrate that our proposed methods and Bayesian power prior control Type I error and increase power under the exchangeability assumption, whereas the method proposed by Yuan et al. (2019) results in an increased Type I error. In the scenario where the exchangeability assumption does not hold, all methods fail to control the Type I error. Our proposed methods, however, limit a maximum Type I error inflation ranging from 6% to 8%, which compares favorably to 10% for Yuan et al. (2019) and 16% for the Bayesian power prior. All methods increase statistical power under the exchangeability condition but may lead to a loss of statistical power when the exchangeability assumption is violated.},
}

@article {pmid41126461,
year = {2025},
author = {Ayton, S and Moreau, C and Devos, D and Bush, AI},
title = {Iron on trial: recasting the role of iron in neurodegeneration.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awaf398},
pmid = {41126461},
issn = {1460-2156},
abstract = {Iron is critical for numerous neurophysiological functions, while its dysregulation is potentially hazardous for neurodegeneration through oxidative stress and ferroptosis. For decades, elevated brain iron levels observed in neurodegenerative diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis was presumed to drive disease progression; a hypothesis that propelled clinical trials of strong iron chelators like deferiprone. Results from these trials, however, have challenged this paradigm, with deferiprone markedly worsening outcomes in Alzheimer's and, in certain contexts, Parkinson's patients. These findings underscore the vital role of iron for brain health and suggest functional compensatory mechanisms that could become deleterious at the extremes of iron distribution (both low and high levels). Here, we outline an evolving understanding of iron's role in neurodegeneration, and we explore pathways for therapeutic development strategies that mitigate potential iron-mediated damage, while preserving its essential functions in the brain.},
}

@article {pmid41126230,
year = {2025},
author = {Lai, YH and Lin, KH and Huang, HK and Huang, TW and Kuo, YS},
title = {The first case of diaphragm pacing system implantation in a patient with high cervical spinal cord injury in taiwan: a case report and literature review.},
journal = {Journal of cardiothoracic surgery},
volume = {20},
number = {1},
pages = {377},
pmid = {41126230},
issn = {1749-8090},
mesh = {Humans ; *Diaphragm/innervation/physiopathology ; *Spinal Cord Injuries/complications ; Taiwan ; Male ; Laparoscopy/methods ; Middle Aged ; Cervical Vertebrae/injuries ; *Electric Stimulation Therapy/methods ; *Respiratory Insufficiency/etiology/therapy ; },
abstract = {INTRODUCTION: This report presents the first case of a patient with high cervical spinal cord injury who underwent successful laparoscopic implantation of a diaphragm pacing system in Taiwan. It also compares the pros and cons of laparoscopic and thoracoscopic implantation and discusses postoperative care.

BACKGROUND: The diaphragm pacing system (DPS) represents a substantial advancement in respiratory support technology, particularly for patients with chronic respiratory insufficiency. It electrically stimulates the phrenic nerve, which in turn activates the diaphragm-the primary muscle involved in respiration [1]. This stimulation mimics the natural neural impulses that drive diaphragmatic contractions, thereby promoting inhalation and a more efficient lung ventilation. The DPS typically consists of implanted electrodes, an external pulse generator, and connecting leads [2]. It is mainly used in patients with high spinal cord injuries, amyotrophic lateral sclerosis, and central hypoventilation syndrome. These conditions often result in compromised neural control of the diaphragm, leading to severe respiratory insufficiency. By restoring diaphragm function, DPS can enhance the patients' quality of life, reduce dependence on mechanical ventilators, and lower the risk of ventilator-associated complications [3]. Despite its benefits, DPS is not without challenges. Patient selection and the surgical approach are critical to perform successful DPS implantation for the restoration of diaphragm function [4]. This report presents the first case of a patient with cervical spine injury who underwent successful laparoscopic implantation of DPS in Taiwan. Furthermore, it discusses postoperative ICU care and reviews the pros and cons of different surgical approaches to performing DPS implantation.},
}

Humans
*Diaphragm/innervation/physiopathology
*Spinal Cord Injuries/complications
Taiwan
Male
Laparoscopy/methods
Middle Aged
Cervical Vertebrae/injuries
*Electric Stimulation Therapy/methods
*Respiratory Insufficiency/etiology/therapy

@article {pmid41125961,
year = {2025},
author = {Jang, HS and Sodhi, CP},
title = {Segmental cholestasis drives global hepatic fibrosis: lessons from the sBDL model in weaned rats.},
journal = {Pediatric research},
volume = {},
number = {},
pages = {},
pmid = {41125961},
issn = {1530-0447},
abstract = {This commentary provides a detailed analysis of Gonçalves et al.'s research paper, "Key genes and histopathological alterations in hepatic fibrogenesis after segmental cholestasis in weaned rats.[1]" It emphasizes how segmental cholestasis caused by selective bile duct ligation in young rats leads to extensive hepatic fibrogenesis, affecting both obstructed and non-obstructed liver lobes-similar to pediatric cholangiopathies like biliary atresia and post-transplant strictures in children. It not only illustrates regional hepatic disease patterns but also offers a valid preclinical platform for testing antifibrotic treatments.},
}

@article {pmid41124800,
year = {2025},
author = {Sergeeva, OS and Neklesova, MV and Reushev, VA and Artemov, AV and Kuznetsova, IM and Turoverov, KK and Uversky, VN and Fonin, AV},
title = {On the potential roles of TDP-43 in the formation of membraneless organelles and their transformation into toxic aggregates.},
journal = {Biochemical and biophysical research communications},
volume = {788},
number = {},
pages = {152808},
doi = {10.1016/j.bbrc.2025.152808},
pmid = {41124800},
issn = {1090-2104},
abstract = {Trans-activation response (TAR) DNA-binding protein 43 (TDP-43) is an RNA-binding protein involved in the processing, transport, and regulation of mRNA translation. It is distributed in many tissues, including the brain, where it is found mainly in hippocampal neurons. Abnormal localization, hyperphosphorylation, and aggregation of TDP-43 are pathological signs of a group of neurodegenerative diseases known as TDP-43 proteinopathies. Despite the growing understanding of the physiological role of TDP-43 in ensuring neuronal plasticity and the formation of long-term memory, to date, there is no comprehensive data on the molecular and cellular mechanisms of the transformation of functional membraneless organelles (MLOs) containing TDP-43 into toxic aggregates and the pathogenesis of associated diseases, such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This review is devoted to highlighting the role of MLOs in the formation of irreversible aggregates, the role of TDP-43 in the formation of MLOs and their relationship with pathological forms of TDP-43, most often found in people suffering from neurodegenerative diseases.},
}

@article {pmid41124655,
year = {2025},
author = {Saraa, N and Mohammed Alhaqbani, H and Hasan Al-Qadri, A and Al-Khadher, MA},
title = {The Development of Emotional Intelligence Scale for Algerian Higher Education EFL Students: Validating the Modified Version of Schutte et al.'s (1998) Model.},
journal = {Psychological reports},
volume = {},
number = {},
pages = {332941251390463},
doi = {10.1177/00332941251390463},
pmid = {41124655},
issn = {1558-691X},
abstract = {Emotional intelligence (EI) has received increasing interest in recent years. The field of English as a Foreign Language (EFL) is a promising context for enhancing EI skills. Despite the potential benefits of EI measurement tools, relatively little research is conducted in EFL education. This study thus aims to validate an Emotional Intelligence Scale (EIS) specifically for Algerian EFL learners using Schutte et al.'s (1998) theoretical framework. In doing so, a panel of experts have assessed the surface validity of the EIS and provided constructive feedback to refine the content of the scale. A pilot testing was conducted to further validate these improvements. 503 Algerian EFL students aged 18 to 23 years participated in this research. Through Exploratory Factor Analysis (EFA), six distinct factors namely: Control of emotions, Appraisal of own emotions, Appraisal of others'emotions, Utilization of emotions, Social skills, and Optimism were identified. These factors were subsequently confirmed through Confirmatory Factor Analysis (CFA) using goodness of- fit-indices. The final scale consisted of 27- item indicating a good model fit and confirming its suitability as a research instrument for the target group. The study confirm that the EI construct exhibits strong construct validity, as evidenced by the factor analytic procedures and the convergent and discriminant validity measures. Additionally, the measurement invariance across distinct samples confirms the portability of the EI construct, underscoring its applicability in psychoeducational assessments across different counties. Limitations of the study and future implications were also discussed accordingly.},
}

@article {pmid41124200,
year = {2025},
author = {Wright-Brown, T and Gaid, D and Najafizada, M and Schwartz, E and Cooper, T and Newell, W and Bishop, L and Donnan, J},
title = {Insights from the ground: A qualitative investigation of retailer perspectives of the challenges and opportunities in the legal cannabis market in Newfoundland and Labrador, Canada.},
journal = {PloS one},
volume = {20},
number = {10},
pages = {e0333706},
pmid = {41124200},
issn = {1932-6203},
mesh = {Humans ; Newfoundland and Labrador ; *Cannabis ; *Commerce/legislation & jurisprudence/economics ; Qualitative Research ; },
abstract = {BACKGROUND: The legalization of recreational cannabis in Canada has resulted in varying regulatory and market environments across provinces and territories. These differences shape how retail markets develop and how retailers perceive their opportunities, challenges, and roles in advancing public health objectives. In Newfoundland and Labrador (NL), cannabis retail operates within a distinctive framework shaped by centralized distribution, licensing requirements, and pricing regulations. This qualitative study explores how licensed and prospective retailers perceived the factors influencing the cannabis retail market in NL.

METHODS: Semi-structured virtual interviews were conducted with nine licensed and nine prospective cannabis retailers in NL. A thematic analysis, using Wright-Brown et al.'s Comprehensive Cannabis Retail Framework and Ritchie and Spencer's framework analysis, was conducted. Both deductive and inductive coding were applied to identify framework-aligned and emergent themes.

RESULTS: Licensed retailers reported challenges such as restrictive advertising rules, high taxation, and supply chain inefficiencies, which they viewed as constraints on profitability and growth. At the same time, access to quality products, positive customer relationships, and informal mentorship networks were seen as enablers of success. Prospective retailers identified high licensing fees, limited access to opportunities, and financing difficulties as significant barriers to entering the legal market.

CONCLUSION: This study highlights how NL's cannabis retail system, designed to balance public health protection with market development, may inadvertently limit participation and business sustainability. The study illustrates how regulatory design can shape retailer experiences and market dynamics, underscoring the need to assess whether current regulations are achieving their intended outcomes. While focused on NL, these findings offer valuable insights for other jurisdictions with similar regulatory models, emphasizing the importance of aligning policy design with retailers' experiences to foster a more inclusive, sustainable, and public health-oriented cannabis retail sector.},
}

Humans
Newfoundland and Labrador
*Cannabis
*Commerce/legislation & jurisprudence/economics
Qualitative Research

@article {pmid41123679,
year = {2025},
author = {Rocha, DC and Omoregbee, MO and Contiliani, DF and Mandlik, R and Li, G and Mascoveto, J and Coleman, G and Culver, JN and Leal, DR and de Souza, AA and Qi, Y},
title = {Transgene-free genome editing in citrus and poplar trees using positive and negative selection markers.},
journal = {Plant cell reports},
volume = {44},
number = {11},
pages = {244},
pmid = {41123679},
issn = {1432-203X},
support = {IOS-2132693//Division of Integrative Organismal Systems/ ; 2224203//Division of Integrative Organismal Systems/ ; IOS-2428015//Division of Integrative Organismal Systems/ ; 2021-67013-34554//National Institute of Food and Agriculture/ ; 2020-33522-32274//National Institute of Food and Agriculture/ ; 2024-33522-42755//National Institute of Food and Agriculture/ ; 2020-70029- 33161//National Institute of Food and Agriculture/ ; DE-SC0023011//Department of Energy/ ; 2023/09068-9//FAPESP/ ; },
mesh = {*Populus/genetics ; *Gene Editing/methods ; Plants, Genetically Modified/genetics ; *Citrus/genetics ; Transgenes/genetics ; CRISPR-Cas Systems/genetics ; Genome, Plant ; Genetic Markers ; Herbicide Resistance/genetics ; },
abstract = {Transgene-free genome editing of the gene of interest in citrus and poplar has been achieved by co-editing the ALS gene via transient transgene expression of an efficient cytosine base editor. CRISPR-Cas genome editing systems have been widely used in plants. However, such genome-edited plants are nearly always transgenic in the first generation when Agrobacterium-mediated transformation is used. Transgene-free genome-edited plants are valuable for genetic analysis and breeding as well as simplifying regulatory approval. It can be challenging to generate transgene-free genome-edited plants in vegetatively propagated or perennial plants. To advance transgene-free genome editing in citrus and poplar, we investigated a co-editing strategy using an efficient cytosine base editor (CBE) to edit the ALS gene to confer herbicide resistance combined with transient transgene expression and potential mobile RNA-based movement of CBE transcripts to neighboring, non-transgenic cells. An FCY-UPP based cytotoxin system was used to select non-transgenic plants that survive after culturing on 5-FC containing medium. While the editing efficiency is higher in poplar than in citrus, our results show that the CBE-based co-editing strategy works in both citrus and poplar, albeit with low efficiency for biallelic edits. Unexpectedly, the addition of the TLS mobile RNA sequence reduced genome editing efficiency in both transgenic and non-transgenic plants. Although a small fraction of escaping plants is detected in both positive and negative selection processes, our data demonstrate a promising approach for generating transgene-free base-edited plants.},
}

*Populus/genetics
*Gene Editing/methods
Plants, Genetically Modified/genetics
*Citrus/genetics
Transgenes/genetics
CRISPR-Cas Systems/genetics
Genome, Plant
Genetic Markers
Herbicide Resistance/genetics

@article {pmid41122380,
year = {2025},
author = {Liu, Z and Dong, H and Yang, H and Zhou, L and Li, M and Zhang, X and Zhao, Y and Han, M and Liu, Y and Geng, Z},
title = {Glymphatic dysfunction in amyotrophic lateral sclerosis: a multimodal MRI investigation of brain-CSF functional and structural dynamics.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1666114},
pmid = {41122380},
issn = {1662-4548},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron degeneration and glial activation. The coupling of global blood oxygen level-dependent (gBOLD) signals with cerebrospinal fluid (CSF) inflow dynamics is a novel non-invasive biomarker, which is applied to assess the relationship between lymphatic function and ALS.

OBJECTIVE: The gBOLD-CSF coupling was used to assess the glymphatic system dysfunction related to ALS, and the relationship between this disease and the glymphatic system was further explored by combining the diffusion tensor imaging index of the perivascular space (DTI-ALPS) and the volume fraction of the choroid plexus (choroid plexus volume [CPV]/intracranial total volume [TIV]).

METHODS: We conducted a systematic analysis and comparative study of the imaging indicators and clinical data of 41 patients with ALS and 43 healthy controls (HC).

RESULTS: ALS patients showed significantly reduced gBOLD-CSF coupling (p < 0.001), reduced ALPS index (p < 0.001), and increased CPV fraction (p < 0.001). The area under the ROC curve (AUC) were 0.790 (gBOLD-CSF), 0.760 (ALPS index), and 0.748 (CPV fraction). A diagnostic model for ALS was developed based on gBOLD-CSF coupling, ALPS index, and CPV fraction with an AUC of 0.897 (0.830-0.964). The calibration curve demonstrates that the model exhibits strong consistency. The results of the Decision Curve Analysis (DCA) further indicate that the nomogram possesses substantial clinical utility.

CONCLUSION: This study identified that gBOLD-CSF coupling has diagnostic value for ALS and developed a diagnostic model by combining the ALPS index and CPV fraction, which has good diagnostic efficacy and clinical application value.},
}

@article {pmid41122379,
year = {2025},
author = {Takahashi, H and Kasai, T and Miyagawa-Hayashino, A and Ohara, T},
title = {Emerging roles of primary cilia in the pathogenesis of amyotrophic lateral sclerosis.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1688839},
pmid = {41122379},
issn = {1662-4548},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease primarily affecting motor neurons, for which effective disease-modifying therapies remain elusive. Primary cilia are solitary microtubule-based organelles critical for signal transduction and have recently been implicated in ALS pathogenesis. In this review, we provide a basic overview of the structure, dynamics, and functions of primary cilia, particularly in the brain. We highlight accumulating evidence from ALS models showing altered ciliary structure and function and explore how mutations in ALS-associated genes such as NEK1, C21orf2, and C9orf72 disrupt ciliogenesis and ciliary signaling. Moreover, we examine the interplays between primary cilia dysfunction and known ALS-related mechanisms, including loss of proteostasis, abnormal RNA metabolism, microtubule dysfunction, neuroinflammation, and mitochondrial dysfunction. Collectively, the evidence suggests a bidirectional relationship in which ciliary impairment and ALS pathomechanisms reinforce one another in a vicious cycle. We further discuss emerging therapeutic strategies targeting ciliary function, as well as the potential for primary cilia as novel clinical applications. Our review highlights primary cilia as a previously underappreciated yet potentially important component of ALS biology, offering novel insights into disease mechanisms and future therapeutic development.},
}

@article {pmid41121980,
year = {2025},
author = {Koide, S and Ikegami, I and Hanyu, R and Koike, YM and Yamagishi, T and Toyama, G and Washida, A and Tada, M and Kakita, A and Onodera, O and Sugai, A},
title = {Quantifying subpercent nuclear TDP-43 loss in cells and ALS cortex using junction-specific cryptic exon RT-qPCR.},
journal = {FEBS letters},
volume = {},
number = {},
pages = {},
doi = {10.1002/1873-3468.70198},
pmid = {41121980},
issn = {1873-3468},
support = {KAKENHI grant / JP24K22094//Japan Society for the Promotion of Science/ ; KAKENHI grant / JP25K02462//Japan Society for the Promotion of Science/ ; JP22ek0109603//Japan Agency for Medical Research and Development/ ; SICORP grant / JP22jm0210097//Japan Agency for Medical Research and Development/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive neurodegenerative diseases characterised by nuclear TDP-43 loss. Its hallmark, cryptic exon (CE) splicing, is often masked in bulk tissue analyses by the low abundance of affected neurons. We developed an ultrasensitive RT-qPCR assay targeting STMN2 CE using one exon-CE junction-spanning primer and the other within the CE. The design expands the dynamic range sevenfold: TDP-43 knockdown boosted STMN2 CE levels 1395-fold in differentiated SH-SY5Y neurons. Spike-in tests set detection at 0.16% deficient cells. Crucially, the assay revealed a 42-fold CE increase in ALS motor cortex, previously missed by conventional primers. This streamlined tool enables precise quantification of TDP-43 dysfunction and sensitive pharmacodynamic monitoring for future ALS-FTD therapeutic studies. Impact statement Because cryptic-exon signals are diluted in bulk tissue, we developed a junction-spanning STMN2 RT-qPCR with sub-percent sensitivity. This deployable biomarker will aid ALS/FTD researchers and drug developers by standardizing measurements and enabling sensitive pharmacodynamic monitoring of therapies targeting nuclear TDP-43 dysfunction.},
}

@article {pmid41121754,
year = {2025},
author = {Chin, ML and Choi, MMF and Tong, R and Pavlović, NM and Chan, W},
title = {Simultaneous Determination of Aristoloxazines, Aristolochic Acids, and Aristolactams Using HPLC-Fluorescence Detection with a Post-column Microreactor: Application in Identifying New Aristoloxazines.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c11092},
pmid = {41121754},
issn = {1520-5118},
abstract = {Aristoloxazines (AXs), aristolochic acids (AAs), and aristolactams (ALs) are potent genotoxins found in Asarum and Aristolochia plants, many of which are commonly used as herbal medicines. Emerging evidence indicates that these compounds contaminate arable soil during the cultivation of Aristolochiaceae herbs. Currently, no method exists for their simultaneous detection. In this study, we developed a high-performance liquid chromatography (HPLC)-based method for their determination. This method employs an iron powder-packed microreactor to convert non-fluorescent AXs and AAs into naturally fluorescent ALs, enabling fluorescence detection after HPLC separation. After being validated against LC-MS/MS analysis, the method was applied to quantify these genotoxins in herbal and soil samples, detecting AXs at concentrations as high as hundreds of μg/g in some Asarum samples. Given that Asarum plants are widely used in herbal medicine, these results reveal previously unrecognized human exposure to genotoxins that warrants the attention of both the general public and regulatory agencies.},
}

@article {pmid41120751,
year = {2025},
author = {Bryce-Smith, S and Brown, AL and Chien, MZYJ and Dattilo, D and Mehta, PR and Mattedi, F and Barattucci, S and Mikheenko, A and Zanovello, M and Pellegrini, F and El-Agamy, SE and Yome, M and Hill, SE and Qi, YA and Sun, K and Ryadnov, E and Wan, Y and , and Vargas, JNS and Birsa, N and Raj, T and Humphrey, J and Keuss, M and Wilkins, OG and Ward, M and Secrier, M and Fratta, P},
title = {TDP-43 loss induces cryptic polyadenylation in ALS/FTD.},
journal = {Nature neuroscience},
volume = {},
number = {},
pages = {},
pmid = {41120751},
issn = {1546-1726},
abstract = {Nuclear depletion and cytoplasmic aggregation of the RNA-binding protein TDP-43 are cellular hallmarks of amyotrophic lateral sclerosis (ALS). TDP-43 nuclear loss causes de-repression of cryptic exons, yet cryptic alternative polyadenylation (APA) events have been largely overlooked. In this study, we developed a bioinformatic pipeline to reliably identify alternative last exons, 3' untranslated region (3'UTR) extensions and intronic polyadenylation APA event types, and we identified cryptic APA sites induced by TDP-43 loss in induced pluripotent stem cell (iPSC)-derived neurons. TDP-43 binding sites are enriched at sites of these cryptic events, and TDP-43 can both repress and enhance APA. All categories of cryptic APA were also identified in ALS and frontotemporal dementia (FTD) postmortem brain tissue. RNA sequencing (RNA-seq), thiol(SH)-linked alkylation for the metabolic sequencing of RNA (SLAM-seq) and ribosome profiling (Ribo-seq) revealed that distinct cryptic APA categories have different downstream effects on transcript levels and that cryptic 3'UTR extensions can increase RNA stability, leading to increased translation. In summary, we demonstrate that TDP-43 nuclear depletion induces cryptic APA, expanding the palette of known consequences of TDP-43.},
}

@article {pmid41120750,
year = {2025},
author = {Zeng, Y and Lovchykova, A and Akiyama, T and Rayner, SL and Maheswari Jawahar, V and Liu, C and Sianto, O and Guo, C and Calliari, A and Prudencio, M and Dickson, DW and Petrucelli, L and Gitler, AD},
title = {TDP-43 nuclear loss in FTD/ALS causes widespread alternative polyadenylation changes.},
journal = {Nature neuroscience},
volume = {},
number = {},
pages = {},
pmid = {41120750},
issn = {1546-1726},
support = {R35NS097263//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U54NS123743//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01AG064690//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R35NS097273//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; P01NS084974//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; },
abstract = {In frontotemporal dementia and amyotrophic lateral sclerosis, the RNA-binding protein TDP-43 is depleted from the nucleus of neurons in the brain and spinal cord. A key function of TDP-43 has emerged as a repressor of cryptic exon inclusion during pre-mRNA splicing, but a role for TDP-43 in other RNA-processing events remains unresolved. Here we show that loss of TDP-43 from neuronal nuclei of human brain and disease-causing mutations in TDP-43 are associated with widespread changes in alternative polyadenylation (APA). Using high-resolution polyadenylation site mapping, we comprehensively defined TDP-43-regulated APA events in human stem cell-derived neurons and found that both the strength and position of TDP-43 binding influence polyA site usage. APA events caused by loss of TDP-43 impact expression of disease-relevant genes (for example, SFPQ, NEFL and TMEM106B). These findings provide evidence that, in addition to cryptic exon inclusion, APA changes are a new facet of TDP-43 pathology.},
}

@article {pmid41118343,
year = {2025},
author = {Cheng, YH and Ho, MS},
title = {Disease-associated microglia in neurodegenerative diseases: Friend or foe?.},
journal = {PLoS biology},
volume = {23},
number = {10},
pages = {e3003426},
pmid = {41118343},
issn = {1545-7885},
mesh = {*Microglia/metabolism/pathology ; Humans ; Animals ; *Neurodegenerative Diseases/pathology/metabolism ; Alzheimer Disease/pathology/metabolism ; Mice ; Disease Models, Animal ; Aging ; Amyotrophic Lateral Sclerosis/pathology/metabolism ; Phagocytosis/genetics ; Lipid Metabolism ; Transcriptome ; },
abstract = {Recent advances in single-cell transcriptomics have led to the identification of disease-associated microglia (DAM) as a distinct, conserved microglia state associated with mouse models of Alzheimer's disease (AD) and amyotrophic lateral sclerosis, and with aging. DAM are characterized by downregulation of homeostatic genes and upregulation of lipid metabolism and phagocytosis genes, including key risk factors for AD in humans. Although characterized in models of AD, whether DAM acts as universal sensor across all neurodegenerative diseases remains unknown. This Essay discusses the dynamics, origins, and therapeutic potential of DAM in neurodegeneration, alongside evidence supporting a protective role for them in regulating disease processes.},
}

*Microglia/metabolism/pathology
Humans
Animals
*Neurodegenerative Diseases/pathology/metabolism
Alzheimer Disease/pathology/metabolism
Mice
Disease Models, Animal
Aging
Amyotrophic Lateral Sclerosis/pathology/metabolism
Phagocytosis/genetics
Lipid Metabolism
Transcriptome

@article {pmid41117937,
year = {2025},
author = {Menge, S and Segura, I and Hartmann, M and Decker, L and Kiran, S and Danzer, KM and Iben, S and Harbauer, AB and Oeckl, P and Freischmidt, A},
title = {Comparing loss of individual fragile X proteins suggests strong links to cellular senescence and aging.},
journal = {Cellular and molecular life sciences : CMLS},
volume = {82},
number = {1},
pages = {358},
pmid = {41117937},
issn = {1420-9071},
mesh = {Humans ; *Cellular Senescence/genetics ; *Fragile X Mental Retardation Protein/genetics/metabolism ; *Aging/genetics/metabolism ; *RNA-Binding Proteins/metabolism/genetics ; CRISPR-Cas Systems ; Autophagy ; Cell Line, Tumor ; Proteomics/methods ; Mitochondria/metabolism ; Fragile X Syndrome/metabolism/genetics/pathology ; Neurodegenerative Diseases/metabolism/genetics/pathology ; },
abstract = {Members of the fragile X protein (FXP) family (FMR1, FXR1 and FXR2) are differentially expressed in most types of cancer and major neurodegenerative diseases. While increased expression of FXR1 in cancer has been linked to senescence evasion and consequently tumor initiation and progression, decreased expression of FXPs in neurodegeneration may contribute to pathogenic protein aggregation and death of vulnerable neurons. However, due the causal role in fragile x syndrome, most data are available about loss of FMR1 in neurons while functions of FXR1 and especially FXR2 remain largely unexplored. To address this knowledge gap, and to directly compare functions of the FXPs, we used proteomics of CRISPR/Cas9 edited HAP1 cells carrying knockouts of the individual FXPs for identification of cellular mechanisms associated with these proteins. Further exploration of proteomic findings suggests roles of the FXPs in ribosome biogenesis, autophagy and mitochondrial health linked to organismal aging, and cellular senescence. Validation of FXP induced defects relevant for neurodegenerative diseases in neuroblastoma cell line SH-SY5Y upon FXP knockdown revealed high cell type specificity of individual FXP functions. Overall, we provide a comprehensive overview and comparison of cellular mechanisms related to the individual FXPs, as well as starting points for further studying this protein family in respective cell types of FXP associated diseases, and in aging in general.},
}

Humans
*Cellular Senescence/genetics
*Fragile X Mental Retardation Protein/genetics/metabolism
*Aging/genetics/metabolism
*RNA-Binding Proteins/metabolism/genetics
CRISPR-Cas Systems
Autophagy
Cell Line, Tumor
Proteomics/methods
Mitochondria/metabolism
Fragile X Syndrome/metabolism/genetics/pathology
Neurodegenerative Diseases/metabolism/genetics/pathology

@article {pmid41117572,
year = {2025},
author = {Soar, J and Böttiger, BW and Carli, P and Jiménez, FC and Cimpoesu, D and Cole, G and Couper, K and D'Arrigo, S and Deakin, CD and Ek, JE and Holmberg, MJ and Magliocca, A and Nikolaou, N and Paal, P and Pocock, H and Sandroni, C and Scquizzato, T and Skrifvars, MB and Verginella, F and Yeung, J and Nolan, JP},
title = {European Resuscitation Council Guidelines 2025 Adult Advanced Life Support.},
journal = {Resuscitation},
volume = {215 Suppl 1},
number = {},
pages = {110769},
doi = {10.1016/j.resuscitation.2025.110769},
pmid = {41117572},
issn = {1873-1570},
mesh = {Humans ; *Advanced Cardiac Life Support/standards/methods ; *Cardiopulmonary Resuscitation/standards/methods ; Adult ; Europe ; *Heart Arrest/therapy ; *Out-of-Hospital Cardiac Arrest/therapy ; },
abstract = {These European Resuscitation Council (ERC) Guidelines 2025 Adult Advanced Life Support (ALS) are based on the International Liaison Committee on Resuscitation (ILCOR) Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations (CoSTR). The evidence informing the ALS Guidelines is also included. When ILCOR has not addressed a specific topic, the ERC ALS Writing Group has provided its own guidance and the evidence supporting it. This section provides recommendations for ALS for adults with in- or out-of-hospital cardiac arrest. The ERC Guidelines 2025 ALS emphasise providing early and effective ALS interventions to improve survival from cardiac arrest in adults.},
}

Humans
*Advanced Cardiac Life Support/standards/methods
*Cardiopulmonary Resuscitation/standards/methods
Adult
Europe
*Heart Arrest/therapy
*Out-of-Hospital Cardiac Arrest/therapy

@article {pmid41117436,
year = {2025},
author = {Jewett, G and Luk, C and Osman, H and Pfeffer, G},
title = {Conference proceedings from the Western Canadian Neuromuscular Conference (WCNMC) - September 27-29, 2024, Calgary, Canada.},
journal = {Journal of neuromuscular diseases},
volume = {},
number = {},
pages = {22143602251389759},
doi = {10.1177/22143602251389759},
pmid = {41117436},
issn = {2214-3602},
abstract = {The Western Canadian Neuromuscular Conference (WCNMC) is a conference focused on neuromuscular medicine that was held in Calgary, Alberta from September 27-29, 2024. Although WCNMC has a history going back to 2010 as a regional event, the most recent iteration of the conference aimed to expand this as a national meeting. A collaboration with Muscular Dystrophy Canada and the Neuromuscular Network for Canada (NMD4C) helped to achieve this goal and encourage participation from across Canada. Other goals for this event were to increase the opportunities for trainees, showcase new research, and integrate new topics into the program. The sessions included a clinicopathologic case series for the first time, which was led by neuromuscular fellows from across Canada. Sessions covering topics in neuromuscular disease focused on challenging diagnostic situations, and therapeutic developments for diseases including spinal muscular atrophy, Pompe disease, and TTR amyloidosis. A separate session covered genetic neuromuscular diseases, with a focus on conditions with genetic founder effects in western Canada. Finally, a transdisciplinary session was included, which discussed patient-focused issues in neuromuscular care, as well as preliminary results from the Burden of Inherited Neuromuscular Disease (BIND) study, on the indirect costs of living with a neuromuscular disorder. A research symposium at the conclusion of the event focused on trainee-led research but also included lectures regarding antisense therapies in neuromuscular disease and updates in research on amyotrophic lateral sclerosis.},
}

@article {pmid41117267,
year = {2025},
author = {Messina, C},
title = {Unraveling the Military Service-MND Connection: Time Frame, Exposures, and Phenotypic Considerations.},
journal = {European journal of neurology},
volume = {32},
number = {10},
pages = {e70392},
pmid = {41117267},
issn = {1468-1331},
}

@article {pmid41117139,
year = {2025},
author = {Pedro, KM and Alvi, MA and Goulart, GR and Fehlings, MG},
title = {Riluzole as a pharmacological therapy for spinal cord injury: where does this therapy stand?.},
journal = {Current opinion in neurology},
volume = {},
number = {},
pages = {},
doi = {10.1097/WCO.0000000000001434},
pmid = {41117139},
issn = {1473-6551},
abstract = {PURPOSE OF REVIEW: Spinal cord injury (SCI) remains a disabling condition associated with long term neurological impairment, functional disability, and reduced quality of life. Despite decades of research, pharmacological interventions with proven clinical efficacy remain limited. This review critically evaluates the current evidence supporting riluzole as a neuroprotective agent for acute traumatic and nontraumatic SCI. We synthesize findings from preclinical and clinical studies, assess the progress towards clinical translation, and outline key challenges and research opportunities for future implementation.

RECENT FINDINGS: Riluzole, an FDA-approved agent for amyotrophic lateral sclerosis (ALS), inhibits voltage-gated sodium channels and modulates glutaminergic transmission, two mechanisms central to the pathogenesis of secondary injury in SCI and in nerve cell degeneration in nontraumatic forms of SCI, including degenerative cervical myelopathy (DCM). Preclinical studies consistently demonstrate functional and histopathological improvements following riluzole administration. Phase I/II trials have provided evidence for its safety and tolerability in acute SCI patients, while the RISCIS and CSM-PROTECT trials, two landmark multicenter randomized controlled studies, along with their secondary analyses, revealed promising multidomain improvements in motor function, independence, and quality of life indices. Sub-studies have also established pharmacokinetic and pharmacodynamic frameworks for individualized dosing, and early biomarker analysis suggests potential for predictive stratification.

SUMMARY: Riluzole represents a promising candidate for neuroprotection in traumatic and nontraumatic SCI. The consistency of favorable trends across multiple domains and strong support from preclinical studies highlight riluzole's value in orphan diseases such as SCI. Future directions should focus on refining the therapeutic window, optimizing PK/PD modeling, and identifying patient subgroups most likely to benefit. Its implementation in a multimodal treatment paradigm for acute SCI will be crucial for optimizing management protocols in this highly disabling condition.},
}

@article {pmid41117127,
year = {2025},
author = {Kim, H and Uhm, JE and Park, J and Kim, YS and Sung, W and Lee, S and Kim, SH and Oh, KW},
title = {Monoclonal Gammopathy in Amyotrophic Lateral Sclerosis: No Impact on Clinical Progression and Immunotherapy Outcomes.},
journal = {European journal of neurology},
volume = {32},
number = {10},
pages = {e70376},
pmid = {41117127},
issn = {1468-1331},
support = {RS-2023-00265515//K-Brain Project of the National Research Foundation(NRF) Korean government (MSIT) (RS-2023-00265515)./ ; RS-2024-00348451//Korea Dementia Research Project through the Korea Dementia Research Center (KDRC), funded by the Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea (RS-2024-00348451)./ ; },
mesh = {Humans ; Male ; *Amyotrophic Lateral Sclerosis/epidemiology/therapy/complications ; Female ; Disease Progression ; Aged ; *Immunotherapy/methods ; Middle Aged ; *Paraproteinemias/epidemiology/therapy/complications ; Republic of Korea/epidemiology ; Registries ; Prevalence ; Treatment Outcome ; Adult ; Aged, 80 and over ; },
abstract = {BACKGROUND: The association between amyotrophic lateral sclerosis (ALS) and monoclonal gammopathy has been proposed, but evidence on its prevalence, clinical relevance, and treatment response remains limited, especially in Asian populations. This study aimed to investigate the prevalence of monoclonal gammopathy in Korean patients with ALS and evaluate the impact of immunotherapy.

METHODS: This registry-based study analyzed Korean patients with ALS at a tertiary referral hospital (2005-2023). All patients underwent electrophoresis and immunofixation electrophoresis to detect monoclonal gammopathy. Clinical progression was assessed using ALSFRS-R scores, disease progression rate (ΔFS), survival analysis, and electrophysiological evaluations.

RESULTS: Among 2400 patients with ALS, monoclonal gammopathy was identified in 1.0% (25/2400). Prevalence increased with age, 1.9% in patients aged ≥ 65 years and 0.7% (13/1755) aged < 65 years. Patients with ALS and monoclonal gammopathy were older (63.2 vs. 57.1; p = 0.01) and predominantly male (7.3:1 vs. 1.5:1; p < 0.01). Immunotherapy targeting monoclonal gammopathy did not significantly affect disease progression (pre-treatment ΔFS 1.00 ± 1.23 vs. post-treatment ΔFS 0.94 ± 0.86; p = 0.46) or survival outcomes (median survival 55.0 vs. 57.0 months; log-rank p = 0.93). Nerve conduction study did not correlate with clinical outcomes. IgM monoclonal gammopathy demonstrated later slower disease progression (initial ΔFS, overall ΔFS; p < 0.05) compared to IgA and IgG subtypes.

CONCLUSION: Monoclonal gammopathy in Korean patients with ALS was not more prevalent than in the general population, and immunotherapy did not impact ALS progression or survival. Clinical features may vary by immunoglobulin subtype. This collectively suggests minimal clinical significance of monoclonal gammopathy in ALS.},
}

Humans
Male
*Amyotrophic Lateral Sclerosis/epidemiology/therapy/complications
Female
Disease Progression
Aged
*Immunotherapy/methods
Middle Aged
*Paraproteinemias/epidemiology/therapy/complications
Republic of Korea/epidemiology
Registries
Prevalence
Treatment Outcome
Adult
Aged, 80 and over

@article {pmid41117105,
year = {2025},
author = {Basile, B and Cheyney, M and Vedam, S and Kennedy, HP},
title = {Narratives of Mistreatment and Coercion in Maternity Care: An Interpretive Description Qualitative Analysis.},
journal = {BJOG : an international journal of obstetrics and gynaecology},
volume = {},
number = {},
pages = {},
doi = {10.1111/1471-0528.70061},
pmid = {41117105},
issn = {1471-0528},
support = {//Association of Women's Health, Obstetric and Neonatal Nurses/ ; //March of Dimes Foundation/ ; T32NR008346/NH/NIH HHS/United States ; //Jonas Philanthropies/ ; },
abstract = {OBJECTIVE: To describe and classify mistreatment during maternity care as described by a diverse set of women across the United States.

DESIGN: Interpretive description qualitative analysis.

SETTING: Qualitative data were collected via a web-based survey (n = 1151) and in semi-structured interviews (n = 25).

SAMPLE: Adult women with a history of caesarean who had a subsequent birth (of any mode) in the United States in the 5 years preceding study participation.

METHODS: Deductive Content Analysis was employed using a priori codes based on Bohren et al.'s Typology of Mistreatment of Women during Childbirth framework.

RESULTS: Participants described all eight types of mistreatment. Marginalised participants, who are most at risk for adverse maternal and infant birth outcomes, were also the most likely to describe experiences of mistreatment during their maternity care. Consequences of mistreatment in maternity care described by participants included healthcare system distrust, reduced postpartum healthcare utilisation and maternal mental health complications.

CONCLUSIONS: Participants experienced mistreatment in their interactions with their maternity care team. Oftentimes, these same situations may have been perceived as benign or routine from the clinicians' perspectives.},
}

@article {pmid41115859,
year = {2025},
author = {Yap, K and Chung, TH and Hedges, EC and Nishimura, AL and Shaw, CE and Makeyev, EV},
title = {Enhanced hybridization-proximity labeling discovers protein interactomes of single RNA molecules.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {9257},
pmid = {41115859},
issn = {2041-1723},
support = {BB/Y009304/1//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; BB/V006258/1//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; BB/R001049/1//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; MR/Z506187/1//RCUK | Medical Research Council (MRC)/ ; Nishimura/Dec20/942-793//Motor Neurone Disease Association (MNDA)/ ; Shaw/Mar19/893-792//Motor Neurone Disease Association (MNDA)/ ; },
mesh = {Humans ; Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; C9orf72 Protein/genetics/metabolism ; *RNA/metabolism/genetics ; RNA-Binding Proteins/metabolism ; Cell Nucleus/metabolism ; RNA Precursors/metabolism/genetics ; Biotinylation ; Proteome/metabolism ; Pluripotent Stem Cells/metabolism ; },
abstract = {RNAs engage diverse protein partners and localize to specific subcellular compartments, yet dissecting proteomes associated with low-abundance or dispersed RNA molecules remains a challenge. We present an enhanced hybridization-proximity labeling (HyPro) technology for in situ proteome profiling of endogenously expressed RNA microcompartments. We re-engineer the HyPro enzyme and optimize proximity biotinylation conditions to identify proteins associated with compact RNA-containing nuclear bodies, small pre-mRNA clusters, and individual transcripts. Applying this approach to pathogenic G4C2 repeat-containing C9orf72 RNAs, retained as single-molecule foci in the nuclei of amyotrophic lateral sclerosis (ALS) patient-derived pluripotent stem cells, we reveal extensive interactions with disease-linked paraspeckle markers and a specific set of pre-mRNA splicing factors. These findings highlight early RNA processing and localization defects in ALS that may contribute to this late-onset neurodegenerative disorder. Overall, HyPro provides a broadly applicable platform for mapping RNA-protein interactions, enabling insights into RNA biology and its dysregulation in disease.},
}

Humans
Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology
C9orf72 Protein/genetics/metabolism
*RNA/metabolism/genetics
RNA-Binding Proteins/metabolism
Cell Nucleus/metabolism
RNA Precursors/metabolism/genetics
Biotinylation
Proteome/metabolism
Pluripotent Stem Cells/metabolism

@article {pmid41114109,
year = {2025},
author = {Zhou, QQ and Ren, YM and Shi, SM and Liu, TF},
title = {Microenvironmental code of pancreatic ductal adenocarcinoma: The prognostic symphony of budding, matrix and lymphocytes.},
journal = {World journal of gastrointestinal oncology},
volume = {17},
number = {10},
pages = {110523},
pmid = {41114109},
issn = {1948-5204},
abstract = {This editorial discusses Alpsoy et al's significant study of prognosis of pancreatic ductal adenocarcinoma (PDAC), which lacks histopathological markers. This study evaluated the synergistic prognolymphocytes. Peritumoral budding is significantly correlated with tumor volume, while intratumoral budding is closely related to lymph node metastasis. Peritumoral budding and intratumoral budding are confirmed as independent adverse prognostic factors, and their high levels of expression are associated with immature stromal phenotypes, suggesting the key role of epithelial-mesenchymal transition. These breakthrough findings provide a new multidimensional biomarker system for the prognostic assessment of PDAC, and promote the clinical transformation process of incorporating tumor budding indicators into the pathological reporting process. However, the complexity and spatiotemporal heterogeneity of the tumor microenvironment require us to go beyond traditional morphological analysis and move towards multiomics integration and dynamic monitoring. Through standardized pathological assessment, innovative treatment strategies and interdisciplinary collaboration, it is expected to transform tumor microenvironment-related markers into clinically applicable indicators, ultimately improving the treatment predicament of PDAC. This editorial intended to summarize relevant studies and share some of our views, in order to offer perspectives for future research.},
}

@article {pmid41114097,
year = {2025},
author = {Moyana, TN},
title = {Contrast-enhanced ultrasound as a non-invasive diagnostic modality for pancreatic ductal adenocarcinoma: The question of Ki67 for study validation.},
journal = {World journal of gastrointestinal oncology},
volume = {17},
number = {10},
pages = {110570},
pmid = {41114097},
issn = {1948-5204},
abstract = {This editorial comments on Yang et al's article that reported a correlation between dynamic contrast-enhanced ultrasound (CEUS) quantitative parameters and Ki67/tumor differentiation. The validation of CEUS as a diagnostic modality in this study deserves merit. However, it raises interesting points of discussion: (1) Since pancreatic cancer is an overarching term that includes conventional pancreatic ductal adenocarcinoma (PDAC), other subtypes, and neuroendocrine neoplasms (NENs), the inclusion/exclusion criteria require better clarification; (2) Most PDACs are grade 1-2 which contrasts with Yang et al's study where 46% were grade 3; (3) Ki67 is officially recognized for grading NENs, but not for PDAC; (4) Hotspots are selected for the Ki67 grading of NENs. However, for other tumors (e.g., breast carcinoma), the average count or hotspots are used; (5) There is no agreement for defining high-grade Ki67 cut-off for non-NENs; reports range from 10% to 50%; and (6) Ki67 reflects cellular proliferation but is not always the most important indicator for biologic aggressiveness. That notwithstanding, since the ratification of Ki67 for prognosis in NENs was based on survival outcomes, the real gold standard should be survival, instead of using Ki67 as a surrogate gold standard. In conclusion, the validation of CEUS parameters for PDAC is a work in progress. CEUS is valuable in assessing PDAC but should be viewed as augmenting other modalities such as computed tomography, magnetic resonance imaging, positron emission tomography and endoscopic ultrasound.},
}

@article {pmid41113933,
year = {2025},
author = {Wang, Z and Cao, W and Fan, D},
title = {Role of lipocalin-2 in amyotrophic lateral sclerosis.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1672903},
pmid = {41113933},
issn = {1663-4365},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized pathologically by degeneration of upper and lower motor neurons, ultimately leading to muscle weakness and respiratory failure. Lipocalin-2 (LCN2) is a secreted protein involved in lipid transport that plays a key role in inflammatory responses and the regulation of iron homeostasis. The role of LCN2 in ALS has attracted increasing attention, as significantly elevated LCN2 expression has been observed in the blood and postmortem tissues of ALS patients. Functionally, LCN2 participates in neuroinflammation, iron dysregulation, cell death, and peripheral immune immunity, proposing a central-peripheral linkage hypothesis mediated by LCN2. Clinically, LCN2 shows promise as both a biomarker and a therapeutic target, with multiple strategies demonstrating potential to mitigate ALS pathology. Moving forward, it is essential to integrate multi-omics to deeply decipher LCN2-mediated molecular networks, advance patient stratification, and accelerate its clinical translation.},
}

@article {pmid41113424,
year = {2025},
author = {Maidina, A and Wang, F},
title = {[Advances in the Structure and Function of Neurofilament Protein and Its Application in Early Diagnosis of Amyotrophic Lateral Sclerosis].},
journal = {Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition},
volume = {56},
number = {4},
pages = {1145-1151},
pmid = {41113424},
issn = {1672-173X},
mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/metabolism ; Humans ; *Neurofilament Proteins/chemistry/metabolism/physiology ; Early Diagnosis ; Biomarkers ; },
abstract = {Neurofilament proteins (NFs), defined as a type Ⅳ intermediate filaments, are important components of the neuronal cytoskeleton. They play a key physiological role in maintaining the structural integrity and plasticity of axons and in ensuring the axonal transport function. Under pathological conditions, NFs detach from axons and undergo abnormal aggregation, causing axonal transport dysfunction. In addition, some components of the detached NFs leak into the peripheral circulation system. In patients with amyotrophic lateral sclerosis (ALS), the concentration of NFs is significantly elevated in the cerebrospinal fluid and blood, and the changes in NFs concentration is significantly positively correlated with the disease progression of ALS, suggesting the potential of NFs being used as early diagnostic biomarkers for ALS. In this review, we explored the relationship between NFs structure, assembly, and physiological function, focusing on the molecular mechanisms and clinical manifestations of ALS caused by abnormal assembly of NFs. We comprehensively summarized recent advances in the application of NFs as a new humoral biomarkers for early diagnosis and therapeutic monitoring of ALS. Key challenges in biomarker development-including undefined pathological neurofilament light chain (NFL) fragments, limited antibody availability, and poor assay reproducibility-are discussed. Strategies, including ultrasensitive detection technologies such as single molecule array (Simoa), antibody optimization based on pathological fragment identification, and multi-omics biomarker panels, should be integrated. These approaches may lead to breakthroughs, pave the way for precision-based ALS diagnosis, provide theoretical support for promoting its clinical translation and application, and offer ideas for future research.},
}

*Amyotrophic Lateral Sclerosis/diagnosis/metabolism
Humans
*Neurofilament Proteins/chemistry/metabolism/physiology
Early Diagnosis
Biomarkers

@article {pmid41110100,
year = {2025},
author = {Yu, H and Chen, X and Yang, Y and Gu, M and Ren, K and Wei, Z},
title = {Decoding Glycosylation in Neurodegenerative Diseases: Mechanistic Insights and Therapeutic Opportunities.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {39},
number = {20},
pages = {e71160},
pmid = {41110100},
issn = {1530-6860},
support = {82301342//MOST | National Natural Science Foundation of China (NSFC)/ ; 82201455//MOST | National Natural Science Foundation of China (NSFC)/ ; 82470403//MOST | National Natural Science Foundation of China (NSFC)/ ; 82204389//MOST | National Natural Science Foundation of China (NSFC)/ ; },
mesh = {Humans ; Glycosylation ; *Neurodegenerative Diseases/metabolism/therapy/pathology ; *Protein Processing, Post-Translational ; Animals ; Biomarkers/metabolism ; },
abstract = {Glycosylation is a highly dynamic and complex post-translational modification that plays a pivotal role in regulating protein folding, trafficking, stability, and function. Accumulating evidence indicates that aberrant glycosylation is intimately involved in the pathogenesis of multiple neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). This review provides a comprehensive overview of the molecular mechanisms by which the two predominant forms of glycosylation, N-glycosylation and O-GlcNAcylation, contribute to protein misfolding, synaptic dysfunction, neuroinflammation, and impaired stress responses in the diseased nervous system. We further explore the diagnostic potential of glycosylation biomarkers and emerging therapeutic strategies targeting glycosylation pathways. Special emphasis has been placed on recent advances in glycomic technologies, artificial intelligence-driven analytics, and nanocarrier-based drug delivery platforms. By integrating mechanistic insights with translational applications, this review highlights glycosylation as both a pathological driver and a promising therapeutic target in neurodegenerative disorders.},
}

Humans
Glycosylation
*Neurodegenerative Diseases/metabolism/therapy/pathology
*Protein Processing, Post-Translational
Animals
Biomarkers/metabolism

@article {pmid41109388,
year = {2025},
author = {Araya-Osorio, R and Dominguez, M and Thallmair, S and Marrink, SJ and Souza, PCT and Mera-Adasme, R},
title = {Allosteric pathway connects Zn(II) loss from SOD1 to known pathogenic mechanisms.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {148349},
doi = {10.1016/j.ijbiomac.2025.148349},
pmid = {41109388},
issn = {1879-0003},
abstract = {Cu,Zn superoxide dismutase (SOD1) is one of the proteins with mutations linked to hereditary forms of the amyotrophic lateral sclerosis neurodegenerative disorder. The protein is known for its enzymatic activity, but it has been shown to also have regulatory functions, which could be related to its pathogenic potential. Seemingly unrelated to its regulatory roles, the most important hypothesis on SOD1 pathogenicity is related to misfolding of the protein, specifically centered on the region corresponding to its residues 28-38. The present work explores the structural and dynamical effect of Zn(II) removal from SOD1, which is known to influence its regulatory roles, with coarse-grained simulations of 450μs per system. In agreement with experiment, we see an increased solvent exposure of the regulatory region (residues 5-18). We also see an increased solvent exposure of the misfolding-critical 28-38 region. We unveil the mechanism and interactions connecting Zn(II) loss, and solvent exposure of both regions. The present work allows for an unified understanding of two different pathogenic mechanisms of SOD1.},
}

@article {pmid41109359,
year = {2025},
author = {Rantala, HA and Leivo-Korpela, S and Beerling, C and Helminen, M and Wijkstra, PJ and Duiverman, ML},
title = {Experienced benefits and side effects affect adherence with long-term noninvasive ventilation.},
journal = {Respiratory medicine},
volume = {249},
number = {},
pages = {108427},
doi = {10.1016/j.rmed.2025.108427},
pmid = {41109359},
issn = {1532-3064},
abstract = {BACKGROUND AND OBJECTIVE: Long-term noninvasive ventilation (LT-NIV) is widely used in different diseases causing hypoventilation. We studied factors associated with adherence to LT-NIV in two hospitals in two different countries.

METHODS: This was a retrospective study including patients with chronic obstructive pulmonary disease (COPD), obesity-hypoventilation syndrome (OHS) and amyotrophic lateral sclerosis (ALS) initiating LT-NIV from January 1, 2012, to December 31, 2015, in Finland and from January 1, 2015, to December 31, 2022, in the Netherlands and followed up for two years.

RESULTS: A total of 702 patients were included: 334 patients with COPD, 158 patients with OHS and 210 patients with ALS. Six months after initiation, 78 %, 67 % and 87 % of the patients with COPD, OHS and ALS used their ventilator ≥5 h/day, respectively. Adherent COPD and ALS patients had higher ventilatory settings compared to non-adherent patients. In OHS, female patients were more often adherent. In a multivariate model, only experienced NIV benefits, side effects and the hospital where the patient was treated were associated with better adherence to NIV. The 2-year survival was best in COPD and OHS patients (median not calculated as less than 50 % died) and worst in ALS patients being 0.9 y (IQR 0.4-1.8 y). Further, survival did not differ between adherent and non-adherent COPD, OHS and ALS patients.

CONCLUSIONS: Experienced benefits and less side effects were associated with better NIV adherence. Adherence did not affect short-time survival in patients with COPD, OHS and ALS. To improve adherence, we suggest careful follow-up from the beginning to optimize ventilation.},
}

@article {pmid41108344,
year = {2025},
author = {Freitas de Souza, G and Magalhães, RSS and Monteiro-Neto, JR and Martins, M and Follmer, C and Junqueira, M and Eleutherio, ECA},
title = {The effect of aging on post-translational modifications of wild-type human SOD1 and the A5V ALS mutant.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {41108344},
issn = {2509-2723},
support = {201.174/2022//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; E-26/010.002259/2019//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; SEI-260003/001131/2020//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; E-26/211.368/2021//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; SEI-260003/005643/202//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; 313417/2021-0//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; 88881.986154/2024-01//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 401780/2023-6//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 305146/2021-1//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; },
abstract = {Cu/Zn superoxide dismutase 1 (SOD1) is essential for maintaining neural health. Its functions include modulating metabolism, maintaining redox balance, regulating transcription, besides eliminating superoxide radicals, which are achieved through various post-translational modifications (PTMs). Consequently, unusual PTMs in SOD1 can impair its functionality and stability, leading to the accumulation of misfolded SOD1 and the increase of oxidative stress markers, hallmarks of Amyotrophic Lateral Sclerosis (ALS). Although SOD1 has been extensively studied, especially regarding its role in ALS, relatively little is known about how aging and mutations affect SOD1 PTMs. This study aimed to evaluate the effect of oxidative stress induced by chronological aging on PTMs of human SOD1: wild-type (WT) and A5V SOD1, a severe ALS-related mutant. To do this, both hSOD1 forms were expressed in Saccharomyces cerevisiae lacking the SOD1 gene, and then purified from extracts of stressed and non-stressed cells. PTMs were analyzed using mass spectrometry, observing the modification of WT and mutant human SOD1 in both conditions. We observed changes in the levels of damage, including oxidation, formylation, and carboxylation, such as oxidized tryptophan 33, associated with prion-like propagation of SOD1 misfolding. Increased levels of this PTM appeared in WT SOD1 after aging and in A5V SOD1. Acetylation and succinylation were also found on lysines. Some of these modifications already have described functions in the literature, while others still lack a defined role. Interestingly, the levels of these physiological PTMs differed between WT and mutant SOD1, providing important information for elucidating the molecular mechanisms of ALS involving SOD1.},
}

@article {pmid41108075,
year = {2025},
author = {Guida, N and Valsecchi, V and Anzilotti, S and Dubbioso, R and Cuomo, O and Ruggiero, S and Senerchia, G and Iuzzolino, VV and Kolici, X and De Iesu, N and Pignataro, G and Annunziato, L and Formisano, L},
title = {siRNA for REST ameliorates symptoms and prolongs survival in ALS mice and serum REST predicts disease prognosis and survival in patients.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2025.10.039},
pmid = {41108075},
issn = {1525-0024},
abstract = {Restrictive Element-1 Silencing Transcription factor (REST) is a key repressor of neuronal genes in stem cells and neuronal progenitor cells and its aberrant accumulation has been implicated in the pathophysiology of neurological disorders, such as Huntington's disease, epilepsy and stroke. Herein, we investigated the role of REST in Amyotrophic Lateral Sclerosis (ALS) pathophysiology and its potential as blood-based predictor of disease prognosis and survival in ALS patients. Intriguingly, REST protein levels were significantly increased in motor cortex, brainstem and spinal cord of superoxide dismutase 1 (SOD1)-G93A mice compared to wild-type mice, both during early- and late-symptomatic phases of the disease. Notably, intracerebroventricular injections of a siRNA against REST (siREST), mitigated motor neurons loss, counteracted the formation of SOD1 aggregates and reduced astrogliosis, thus improving behavioral performance and extending the survival of SOD1-G93A mice. Interestingly, ELISA assay showed that serum REST levels were significantly elevated in ALS patients compared to healthy subjects; furthermore, the higher serum REST levels have been found in patients with shorter tracheostomy-free survival. Collectively, we demonstrated that preventing REST increase in brain areas involved in ALS disorder extended the survival of SOD1-G93A mice and showed that serum REST may represent a possible prognostic biomarker in ALS patients.},
}

@article {pmid41107992,
year = {2025},
author = {Wu, S},
title = {Fixed-effect or random-effect models? A methodological reappraisal of subgroup analyses in mesenchymal stem cell therapy for knee osteoarthritis.},
journal = {Stem cell research & therapy},
volume = {16},
number = {1},
pages = {572},
pmid = {41107992},
issn = {1757-6512},
mesh = {Humans ; *Osteoarthritis, Knee/therapy ; *Mesenchymal Stem Cell Transplantation/methods ; *Mesenchymal Stem Cells/cytology ; },
abstract = {We commend Cao et al. for their systematic review demonstrating the efficacy of intra-articular mesenchymal stem cell (MSC) therapy in alleviating pain and improving function in patients with non-surgical knee osteoarthritis (OA). However, we reanalyzed their subgroup analyses to evaluate the methodological implications of statistical model selection (fixed-effect vs. random-effect models) on result reliability. In dose-stratified analyses, Cao et al. applied fixed-effect models to low-dose (I[2] = 0%) and high-dose (I[2] = 80%) MSC subgroups. Upon reanalysis using random-effect models, the high-dose group showed no statistically significant differences in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total scores compared to the control group at 6 months [MD = 8.75; 95% CI (-2.10, 19.61); P = 0.11] or 12 months [MD = 12.68; 95% CI (-4.96, 30.32); P = 0.16], contrasting with Cao et al.'s original findings. The low-dose subgroup, with no heterogeneity, yielded identical results across both models. Similarly, in cell-source stratification (adipose-derived MSCs [ADMSCs] vs. bone marrow-derived MSCs [BM-MSCs]), reanalysis of ADMSCs using random-effect models demonstrated significant 6-month WOMAC improvement [MD = 9.32; 95% CI (3.73, 14.92); P = 0.001] but non-significant 12-month differences [MD = 12.90; 95% CI (-1.76, 27.55); P = 0.08], diverging from Cao et al.'s conclusions. BM-MSCs results remained consistent due to negligible heterogeneity (I[2] = 0%). These findings underscore that fixed-effect models artificially narrow confidence intervals in heterogeneous populations, overestimating clinical significance. Our results align with Cochrane guidelines, emphasizing that random-effect models better accommodate inter-study diversity, yielding conservative and clinically generalizable estimates. This critique reinforces the necessity of transparent statistical model selection in meta-analyses, particularly when subgroup heterogeneity may influence therapeutic interpretations.},
}

Humans
*Osteoarthritis, Knee/therapy
*Mesenchymal Stem Cell Transplantation/methods
*Mesenchymal Stem Cells/cytology

@article {pmid41107100,
year = {2025},
author = {Palomeque, S and Loguercio, AD and Arrais, CAG and Sánchez, C and Pulido, C},
title = {Three-dimensionally printed and milled composite materials for definitive restorations. Part 2: Effect of surface treatment on the bond strength of light-polymerized resin cement and surface morphology.},
journal = {The Journal of prosthetic dentistry},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.prosdent.2025.09.033},
pmid = {41107100},
issn = {1097-6841},
abstract = {STATEMENT OF PROBLEM: Evidence regarding the effect of surface treatment on the bond strength and surface morphology of 3-dimensionally (3D) printed and computer-aided design and computer-aided manufacturing (CAD-CAM) composite materials is sparse. Enhancing the bond strength to these materials and their surface modifications is essential for ensuring clinical success.

PURPOSE: The purpose of this in vitro study was to evaluate the microshear bond strength (µSBS) of light-polymerized resin cement and the surface morphology of composite materials for definitive indirect restorations after different pretreatments.

MATERIAL AND METHODS: Specimens (6×7×9 mm) from composite CAD-CAM materials were fabricated: 5 by 3D printing (Varseosmile Crown Plus - BEGO (VSC), Crowntec - Saremco Print (CWT), Biocrown - Prizma (BCN), Ceramic Crown - SprintRay (CCN), and Voxel Print - FGM (VXP) and 3 by milling: Cerasmart - GC (CSM), Brilliant Crios - Coltène (BCR), and Enamic - Vita (ENA). Thirteen specimens of each material were selected: 10 for μSBS and 3 for scanning electron microscopy (SEM). Two surface pretreatment protocols were applied: Airborne-particle abrasion with aluminum oxide followed by silane (AL+S), and 5% hydrofluoric acid followed by silane (HF+S). For µSBS testing, transparent cylindrical matrices were filled with light-polymerized resin cement. After 24-hour storage, the specimens were subjected to shear testing (crosshead speed of 1.0 mm/minute). The data were analyzed by 2-way variance analysis and the Bonferroni post hoc test (α=.05).

RESULTS: Within the HF+S groups, ENA exhibited the highest µSBS values (18.47 ±1.0 MPa), although no significant differences were found with VXP (16.12 ±1.4 MPa). The highest µSBS mean value was observed on the CCN surface after AL+S (19.49 ±2.8 MPa), followed by VSC (18.74 ±2.2 MPa) and CSM (18.45 ±1.1 MPa). The surface pattern with AL+S presented more evident irregularities on both printable and machinable materials.

CONCLUSIONS: Airborne-particle abrasion with aluminum oxide was found to be appropriate for both milled and printed materials. Hydrofluoric acid etching was not recommended for all types of CAD-CAM resin ceramics, even when followed by silane application.},
}

@article {pmid41107024,
year = {2025},
author = {Bannwarth, S and Paquis-Flucklinger, V},
title = {Sporadic amyotrophic lateral sclerosis: what is the impact of the mitochondrial genome?.},
journal = {Journal of neurology, neurosurgery, and psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1136/jnnp-2025-337087},
pmid = {41107024},
issn = {1468-330X},
}

@article {pmid41106144,
year = {2025},
author = {Tamura, R and Taguchi, R and Yamada, T and Wada, H and Ayaki, T and Takahashi, R and Urushitani, M},
title = {Peripheral CD56[dim]CD16[+] NK cells correlate with serum NfL and ALS progression: An exploratory immunophenotyping analysis.},
journal = {Journal of neuroimmunology},
volume = {409},
number = {},
pages = {578779},
doi = {10.1016/j.jneuroim.2025.578779},
pmid = {41106144},
issn = {1872-8421},
abstract = {BACKGROUND: Peripheral immune dysregulation may contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS), yet, specific immunophenotypes correlated with disease progression remain unclear. We conducted an exploratory analysis to identify peripheral immune cell subsets correlated with ALS progression and serum biomarkers.

METHODS: Multicolor flow cytometry was used to evaluate 55 immune cell subsets in peripheral blood from 16 ALS patients. We assessed correlation with clinical progression (defined by monthly decline in the ALS Functional Rating Scale-Revised) and serum biomarkers: neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and estimated glomerular filtration rate (eGFR).

RESULTS: CD56[dim]CD16[+] natural killer (NK) cells were inversely correlated with both ΔALSFRS-R and serum NfL, and also showed a significant correlation with GFAP. Naive B cells positively correlated with ΔALSFRS-R. Monocyte subsets were differentially correlated with eGFR. Among all cells examined, CD56[dim]CD16[+] NK cells were the only subset significantly correlated with three clinical and biological measures.

CONCLUSIONS: CD56[dim]CD16[+] NK cells showed consistent correlations with ALS progression markers, although this exploratory study has small sample size and lacks healthy and disease controls, limiting conclusions in terms of statistical power and ALS-specificity about the observed immune alterations. These preliminary findings support the utility of immunophenotyping in ALS biomarker research and warrant validation in larger cohorts.},
}

@article {pmid41105110,
year = {2025},
author = {Wodwaski, N and Webber, E},
title = {Empowering Future Nurses: Integrating Emotional Intelligence Into Nursing Education.},
journal = {Nurse educator},
volume = {},
number = {},
pages = {},
pmid = {41105110},
issn = {1538-9855},
abstract = {BACKGROUND: Active learning strategies (ALS) focusing on the development of emotional intelligence (EI) support the growth of interpersonal and emotional competencies in nursing. These competencies are central to the development of resilience and formation of professional nursing identity.

PROBLEM: Despite the recognized importance of EI, traditional nursing education often prioritizes technical skills and clinical knowledge, with limited focus on the intentional development of emotional and interpersonal competencies.

APPROACH: This article explores the integration of reflection, emotionally focused simulations, and communication-based exercises into a BSN (Bachelor of Science in Nursing) curriculum. Incorporating Goleman's EI model and Kolb's experiential learning cycle in the implementation of ALS is a novel approach to developing EI competencies in undergraduate nursing students.

OUTCOMES: These learning methods can help students strengthen their emotional awareness, communication skills, and self-regulation. They offer practical tools to support professional identity, resilience, and the delivery of person-centered care.

CONCLUSION: Embedding EI into nursing education through active learning fosters competencies essential for delivering compassionate, safe, and effective care. This model is adaptable across diverse learning environments.},
}

@article {pmid41104192,
year = {2025},
author = {Akbar, B and Eman, R and Ali, SI and Maryum, M and Umar, M and Laique, F},
title = {Methodological and Contextual Considerations in Assessing Internet Addiction and Eating Disorder Risk Among Bangladeshi Adolescents.},
journal = {Health science reports},
volume = {8},
number = {10},
pages = {e71364},
pmid = {41104192},
issn = {2398-8835},
abstract = {BACKGROUND: Internet addiction and eating disorders are emerging public health concerns among adolescents, particularly in South Asia. A recent study by Siddik et al. explored these issues among Bangladeshi adolescents but contained several methodological and theoretical limitations.

OBJECTIVE: To critically evaluate Siddik et al.'s study on internet addiction and eating disorders among Bangladeshi adolescents, identifying methodological oversights and providing recommendations for future research.

METHODS: A critical appraisal approach was applied to review the study's design, data interpretation, and theoretical grounding. Specific focus areas included BMI classification, gender imbalance, psychosocial variables, and adherence to established behavioral models.

RESULTS: The critique revealed methodological shortcomings such as inappropriate BMI classification, lack of gender balance, omission of key psychosocial determinants, and absence of a guiding theoretical framework. These limitations may reduce the study's interpretive validity and cultural relevance.

CONCLUSION: Future research should strengthen methodological rigor, ensure inclusion of relevant psychosocial factors, and incorporate robust theoretical models to enhance understanding of adolescent digital behavior and its mental health implications.},
}

@article {pmid41104042,
year = {2025},
author = {Yassin, LK and Skrabulyte-Barbulescu, J and Alshamsi, SH and Saeed, S and Alkuwaiti, SH and Almazrouei, S and Alnuaimi, A and BaniYas, S and Aldhaheri, D and Alderei, M and Shehab, S and Hamad, MIK},
title = {The microbiota-gut-brain axis in mental and neurodegenerative disorders: opportunities for prevention and intervention.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1667448},
pmid = {41104042},
issn = {1663-4365},
abstract = {The microbiota-gut-brain axis (MGBA) is increasingly recognized as a critical regulator of brain health, influencing both neurodevelopment and age-related neurological decline. Disruptions in this axis, driven by gut dysbiosis, have been implicated in the pathogenesis of a wide range of neurodegenerative and neuropsychiatric disorders. This review synthesizes current evidence linking microbiota alterations to Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and stroke-including post-stroke cognitive impairment (PSCI), as well as major depressive disorder (MDD), bipolar disorder (BD), anxiety disorders, post-traumatic stress disorder (PTSD), and chronic fatigue syndrome (CFS). Common findings include reduced microbial diversity, depletion of short-chain fatty acid (SCFA)-producing genera, and enrichment of pro-inflammatory taxa. These changes contribute to neuroinflammation, blood-brain barrier (BBB) dysfunction, microglial activation, and neurotransmitter imbalances. The review further explores the neurotoxic effects of external factors such as radiation and xenobiotics on the MGBA. Despite disorder-specific variations, shared microbial and immunological mechanisms emerge across the spectrum of conditions. Importantly, we present current and emerging strategies aimed at restoring gut-brain communication, including dietary interventions such as fiber-rich and Mediterranean diets, SCFA supplementation, probiotics, and fecal microbiota transplantation (FMT). These approaches show promise in alleviating cognitive and emotional symptoms, modulating immune responses, and potentially slowing disease progression. By integrating mechanistic insights with therapeutic perspectives, this review underscores the gut microbiota as a modifiable factor in neuropsychiatric and neurodegenerative disease. Targeting the MGBA offers a novel, translational approach to intervention that may ultimately contribute to healthier brain aging and improved outcomes across the lifespan.},
}

@article {pmid41103971,
year = {2025},
author = {Arachchige, ASPM},
title = {Rethinking ALS: Current understanding and emerging therapeutic strategies.},
journal = {AIMS neuroscience},
volume = {12},
number = {3},
pages = {391-405},
pmid = {41103971},
issn = {2373-7972},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive degeneration of the upper and lower motor neurons, which leads to muscle atrophy, spasticity, and ultimately respiratory failure. The etiology of ALS remains unclear, though a combination of genetic and environmental factors is suspected. Advances in understanding ALS pathophysiology, including the role of RNA metabolism, mitochondrial dysfunction, and glutamate toxicity, have paved the way for new research directions. While Riluzole offers limited survival benefits, there is no cure, and treatment remains mostly supportive. This article summarizes the current understanding of ALS in terms of its pathophysiology, epidemiology, risk factors, clinical presentation, and treatment strategies.},
}

@article {pmid41103687,
year = {2025},
author = {Costa-Pallaruelo, M and García-Osuna, Á and Canyelles, M and Martínez-Bru, C and Nan, N and Ferrer-Perez, R and Blanco-Vaca, F and Guiñón, L},
title = {Refining quality control strategies in highly automated laboratories: experience in the integration of multistage statistical designs and risk management.},
journal = {Biochemia medica},
volume = {35},
number = {3},
pages = {030704},
pmid = {41103687},
issn = {1846-7482},
mesh = {*Quality Control ; Humans ; *Risk Management ; *Automation, Laboratory/standards ; *Laboratories, Clinical/standards ; *Laboratories/standards ; },
abstract = {INTRODUCTION: The ISO 15189:2022 standard considers both the robustness of analytical methods and the risk of erroneous results in the quality control plan (QCP) design. Westgard et al.'s nomogram recommends quality control (QC) rules based on sample run size to ensure that the maximum expected number of unreliable patient results remains below one. This study aimed to implement a standardized, risk-based QC strategy across multiple analyzers without integrated on board QC, ensuring practical quality assurance.

MATERIAL AND METHODS: Thirty-two biochemistry parameters on Alinity c systems and three on Cobas Pro systems were included. The analytical performance of each parameter on each analyzer was assessed using sigma metric. Workload requirements were considered to determine the desired run size. Based on the "sigma metric statistical QC run size nomogram" proposed by Westgard et al., a multistage bracketed QCP was designed for each parameter. When multiple designs were available, the simplest QC rule was prioritized.

RESULTS: Seven QCPs were initially established for 35 parameters. In the absence of automation, practical adaptations based on sigma metrics were implemented. Additionally, to streamline management, the QCP covering the greatest number of parameters per analyzer was prioritized, which ultimately resulted in the adoption of only two general QCP. Only 4 individualized QCP were required to cover 10 parameters with lower sigma values.

CONCLUSIONS: This approach demonstrates the feasibility of implementing a refined QC strategy for parameters with sigma ≥ 4 in a highly automated laboratory, ensuring consistent quality assurance and efficient resource allocation for higher-risk tests.},
}

*Quality Control
Humans
*Risk Management
*Automation, Laboratory/standards
*Laboratories, Clinical/standards
*Laboratories/standards

@article {pmid41102689,
year = {2025},
author = {Almomani, E and Tobin, J and Fernandes, S and Sullivan, J and Saadeh, O and Mustafa, E and Pattison, N and Alinier, G},
title = {A reflective learning conversation debriefing model for interprofessional simulation based education.},
journal = {BMC medical education},
volume = {25},
number = {1},
pages = {1434},
pmid = {41102689},
issn = {1472-6920},
mesh = {Humans ; *Simulation Training/methods ; Female ; Male ; Self Efficacy ; *Interprofessional Education/methods ; Clinical Competence ; Models, Educational ; Clinical Reasoning ; Adult ; *Interprofessional Relations ; Thinking ; *Health Personnel/education ; Focus Groups ; },
abstract = {BACKGROUND: Debriefing for Interprofessional Education (IPE) using Reflective Learning Conversation (RLC) methods enables learners to reflect on their actions, articulate their decisions, and benefit from peer support and the dynamics of group thinking within a team-based context. This study aims to validate a co-designed Reflective Learning Conversation (RLC) debriefing model for use in interprofessional learning groups that vary in professional seniority and clinical experience within a multicultural educational environment. The validation process focuses on enhancing clinical reasoning, clinical judgment, critical thinking skills, and self-efficacy.

METHODS: A quasi-experimental pre-test/post-test mixed method. The study sample consisted of a cohort of interprofessional healthcare providers (n = 130) who were taking part in European Resuscitation Council (ERC) Advanced Life Support (ALS) courses incorporating Simulation- Based Education (SBE) conducted at Hamad International Training Center (HITC), with the sample equally split between control and experimental groups. Data was collected through subsequent direct observations, validated questionnaires, and focus groups. Descriptive and inferential statistical analyses were performed on the quantitative data, and thematic analysis on the qualitative data.

RESULTS: The experimental group had a significantly higher level of clinical reasoning, judgment, and critical thinking skills compared to the control group at the beginning, midway, and end of simulation activities using the Clinical Reasoning Evaluation in Simulation Tool (CREST) tool, Lasater Clinical Judgment Rubric (LCJR), and Critical Thinking Rubric (CTR). The experimental group scored a significantly higher level of self-efficacy than the control group for the Self-Efficacy questionnaire subscales.

CONCLUSION: Reflective Learning Conversation (RLC) model was found to be valid for enhancing clinical reasoning, clinical judgment, critical thinking, and self-efficacy among interprofessional healthcare providers attending advanced life support simulation-based courses in multicultural learning environments. However, further research is recommended to explore how clinical experience and professional seniority interact with debriefing approaches to influence these cognitive and affective outcomes in simulation-based education.},
}

Humans
*Simulation Training/methods
Female
Male
Self Efficacy
*Interprofessional Education/methods
Clinical Competence
Models, Educational
Clinical Reasoning
Adult
*Interprofessional Relations
Thinking
*Health Personnel/education
Focus Groups

@article {pmid41102629,
year = {2025},
author = {Masbi, M and Tavkoli, N and Payrovi, H and Dowlati, M},
title = {Special care services delivery at disaster scenes: a systematic review.},
journal = {International journal of emergency medicine},
volume = {18},
number = {1},
pages = {206},
pmid = {41102629},
issn = {1865-1372},
abstract = {BACKGROUND: Disasters create strain on health systems and require significant preparedness to reduce mortality and morbidity. Special care services; e.g. Advanced Life Support, critical care interventions (intubation; vasopressor therapy) and point of care diagnostics (ultrasound) may be provided in disaster-settings, although actual use of services is dependent on logistical, operational and contextual issues. This systematic review identifies an important gap to understand the effectiveness, feasibility and barriers to, special care services.The overall aim of this systematic review is to synthesise global evidence on the evidence-based practices and improve disaster response.

METHODS: This systematic review utilized PubMed, Scopus, Web of Science, Embase, and grey literature from the time of inception of the different databases to January 2025, from which a total of 4465 records were identified. After a thorough, organized review of the identified records based on our exclusion criteria and inclusion criteria, a total of 31 articles were retained. The systematic review followed PRISMA 2020, and searched for studies on special care services in a pre-hospital disaster setting, and included primary research and review articles that described advanced interventions, and which had no time restrictions on date of publication. Articles that were waived from the cost of in-app purchasing were excluded due to limited resources and could limit the studies that were included. Quality assessment using STROBE, SANRA and checklists, along with the categories of findings using a thematic content analysis based on the dimensions of prehospital care.

RESULTS: Thematic analysis revealed six broad themes: Patient Care and Clinical Management, Operational Efficiency and Logistics, Personnel and Training, Technology and Equipment, System Coordination and Preparedness, and Ethical and Contextual Considerations. Advanced functions like REBOA, ultrasound and AI-related diagnostics improved survival and neurological outcomes, However, they were restricted due to limited resources, lack of training, and lack of coordination, particularly in low resource contexts.

CONCLUSIONS: The reviewed literature demonstrated that critical-care services such as Advanced Life Support (ALS), intubation, and ultrasound resulted in improved morbidity and mortality outcomes in disaster settings but were limited due to resource constraints, lack of training and inadequate coordination all the more pertinent to low-resource settings.

CLINICAL TRIAL NUMBER: Not applicable.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12245-025-01041-9.},
}

@article {pmid41102382,
year = {2025},
author = {Wang, Q and Wang, Y and Jiang, YDD and Donahue, R and Cao, G and Yan, W and Guo, H and Li, Z and Liang, J and Hao, J and Lu, Y and Bei, F and Wang, Q and Tian, F},
title = {OPTN protects retinal ganglion cells and ameliorates neuroinflammation in optic neuropathies.},
journal = {Communications biology},
volume = {8},
number = {1},
pages = {1475},
pmid = {41102382},
issn = {2399-3642},
support = {EY032181//U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)/ ; },
mesh = {*Retinal Ganglion Cells/metabolism/pathology ; Animals ; *Membrane Transport Proteins/metabolism/genetics ; Mice ; *Cell Cycle Proteins/genetics/metabolism ; *Optic Nerve Diseases/metabolism/pathology/genetics ; *Neuroinflammatory Diseases/metabolism/pathology/genetics ; Mice, Knockout ; Mice, Inbred C57BL ; Disease Models, Animal ; *Transcription Factor TFIIIA/genetics/metabolism ; Glaucoma ; Humans ; Male ; },
abstract = {Optineurin (OPTN) is an adaptor protein that plays a crucial role in many cellular pathways, including NF-κB signaling, programmed cell death, and vesicular trafficking. OPTN dysfunction has been implicated in the pathogenesis of several diseases, such as primary open angle glaucoma (POAG), amyotrophic lateral sclerosis (ALS). While mutations of OPTN seem to be predominantly loss-of-function in ALS, only gain-of-function mechanisms have been reported in POAG. Here, we demonstrate that OPTN knockout in the retina contributes to short-term astrogliosis, retinal ganglion cell (RGC) loss and long-term microglial activation. Moreover, OPTN loss of function does not exacerbate RGC death induced by ocular hypertension. Integrated bioinformatics and immunofluorescence analyses reveal that OPTN dysfunction leads to neuropeptide Y (NPY) downregulation and CHOP upregulation. Overexpression of wild-type OPTN in a hypertension glaucoma model prevents the RGC loss and attenuates microglial activation. Together, our findings highlight a neuroprotective role for OPTN as a key neuroimmune modulator.},
}

*Retinal Ganglion Cells/metabolism/pathology
Animals
*Membrane Transport Proteins/metabolism/genetics
Mice
*Cell Cycle Proteins/genetics/metabolism
*Optic Nerve Diseases/metabolism/pathology/genetics
*Neuroinflammatory Diseases/metabolism/pathology/genetics
Mice, Knockout
Mice, Inbred C57BL
Disease Models, Animal
*Transcription Factor TFIIIA/genetics/metabolism
Glaucoma
Humans
Male

@article {pmid41101465,
year = {2025},
author = {Veenstra, J and Ozog, D and Stephens, A},
title = {Response to Bunick et al, "Response to Veenstra et al.'s 'Benzoyl Peroxide Acne Treatment Shows No Significant Association with Benzene-Related Cancers: A Multicenter Retrospective Analysis' on Statistical Design".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.09.104},
pmid = {41101465},
issn = {1097-6787},
}

@article {pmid41101301,
year = {2025},
author = {Sasidharan, A and Somayaji, Y and Fernandes, R},
title = {Shifting Microglial Phenotypes: Targeting Disease-Associated Microglia in Neurodegeneration.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.5c00159},
pmid = {41101301},
issn = {1948-7193},
abstract = {Neurodegenerative disorders are marked by the gradual degeneration of neurons and deterioration of cognitive function. One key underlying factor in these diseases is neuroinflammation. An essential component of this process is microglia, which are the innate immune cells that maintain homeostasis in the brain. A common outcome of microglial dysregulation in neurodegenerative diseases is chronic neuroinflammation, which exacerbates neuronal damage and impairs synaptic function. This review focuses on the dual roles that disease-associated microglia (DAMs) play in neural inflammation and neuroprotection as well as their distinct transcriptional profile in neurodegenerative diseases. DAMs engage in phagocytosis to remove debris, in addition to releasing cytokines that promote inflammation. To create an effective medicine, it is imperative to comprehend these dual functions. The roles of DAMs in Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are discussed, along with the mechanisms (such as the TREM2-APOE pathway) causing their activation. This review attempts to highlight the important aspects that could direct future investigations and treatment development by clarifying the interactions between DAMs and neurodegenerative diseases.},
}

@article {pmid41101251,
year = {2025},
author = {Westeneng, HJ and Nitert, AD and van Veenhuijzen, K and Wismans, C and Donatelli, G and Tan, HHG and van Hoek, W and van Es, MA and Klomp, DWJ and Bhogal, AA and Veldink, JH and Wijnen, JP and van den Berg, LH},
title = {Patterns of altered in vivo brain metabolism in patients with amyotrophic lateral sclerosis (ALS) and asymptomatic C9orf72 mutation carriers: a cross-sectional [1]H and [31]P magnetic resonance spectroscopic 7T imaging study.},
journal = {EBioMedicine},
volume = {121},
number = {},
pages = {105963},
doi = {10.1016/j.ebiom.2025.105963},
pmid = {41101251},
issn = {2352-3964},
abstract = {BACKGROUND: Processes leading to the onset of neurodegeneration in amyotrophic lateral sclerosis (ALS) are largely unknown. To gain insight into disease mechanisms, we measured brain metabolism in vivo in asymptomatic C9orf72 mutation carriers and patients with ALS.

METHODS: We enroled 15 asymptomatic family members with (AFM C9+) and 18 without a C9orf72 mutation (AFM C9-), 4 patients with ALS with (ALS C9+) and 35 without this mutation (ALS C9-), and 25 population-based controls (CO). Two-dimensional proton ([1]H) and whole-brain phosphorus ([31]P) magnetic resonance spectroscopic imaging (MRSI) data were obtained using a 7T MR scanner. 11 brain metabolites were compared between groups using weighted Bayesian linear multilevel models.

FINDINGS: Compared to AFM C9-, AFM C9+ showed evidence of neuronal dysfunction (decreased total N-acetyl aspartate/total creatine (tNAA/tCr)), widespread increased membrane breakdown product (glycerol phosphorylethanolamine/phosphocreatine (GPE/PCr)), glutamate excitotoxicity (increased glutamate + glutamine/tNAA (Glx/tNAA)) and, in frontoparietal regions, an increase in the glycogen precursor uridine diphosphoglucose/PCr (UDPG/PCr). Compared to AFM C9+, neuronal dysfunction and membrane breakdown are similar in ALS C9+, but glutamate excitotoxicity and increased glycogen precursor are more severe and widespread, also involving the primary motor region. Moreover, lower total adenosine triphosphate/PCr (tATP/PCr) emerged in ALS C9+, and signs of disturbed membrane synthesis, intracellular second messenger system and glial pathology (myo-inositol + glycine/tCr (mI + Gly/tCr)). ALS C9- is characterised by glutamate excitotoxicity, increased tATP/PCr, and lower phospholipid levels.

INTERPRETATION: [1]H and [31]P 7T MRSI can detect evolving patterns of altered brain metabolism in asymptomatic mutation carriers and patients with ALS. Abnormalities in patients with ALS C9+ appeared to be different from those in patients with ALS C9-. Metabolic markers, measured in vivo, can serve as biomarkers for inclusion or stratification as well as for drug-target engagement in clinical trials. This method can facilitate identification of new and personalised drug targets to prevent or treat this devastating disease.

FUNDING: ALS Foundation Netherlands.},
}

@article {pmid41101174,
year = {2025},
author = {Garry, F and MacFarlane, A and Phelan, H and Hassan, A and Salsberg, J and MacCarron, P and Papyan, A},
title = {Music and singing as arts-based methods to facilitate participatory spaces for co-production in migration health research: A mixed methods study.},
journal = {Social science & medicine (1982)},
volume = {386},
number = {},
pages = {118453},
doi = {10.1016/j.socscimed.2025.118453},
pmid = {41101174},
issn = {1873-5347},
abstract = {Opportunities for refugees and migrants to be involved in health research in re-settlement countries is not optimal. This creates a structural bias in evidence to transform health systems into diversity sensitive inclusive systems. Arts-based methods using music and singing are underexplored in migration health research even though they may have specific characteristics to facilitate participatory spaces for co-production. We report a mixed-methods analysis of an innovative participatory space using the 'Irish World Music Café' method. Twenty-five participants from community, health, and academic sectors took part in five 2 hour music cafés with the goal of co-producing a vision and action plan to improve refugee and migrant involvement in health research in Ireland. We evaluated the space using quantitative and qualitative methods. We explored the resonance of the combined findings against Palmer et al.'s theoretical model of change in co-production. Participants reported high levels of enjoyment and high motivation for new partnerships, with evidence of migrants gaining centrality in networks for such partnerships. There were multiple examples of how characteristics of music and singing resonate with mechanisms of co-production. These findings point to potential for a new area of interdisciplinary work in the field of migration health that warrants further investigation.},
}

@article {pmid41100402,
year = {2025},
author = {Fortuna Baptista, M and Gromicho, M and Alves, I and Oliveira Santos, M and De Carvalho, M},
title = {Predictors in late-stage amyotrophic lateral sclerosis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {26},
number = {7-8},
pages = {659-663},
doi = {10.1080/21678421.2025.2536647},
pmid = {41100402},
issn = {2167-9223},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/mortality/therapy ; Male ; Female ; Middle Aged ; Aged ; Disease Progression ; Prognosis ; Adult ; Retrospective Studies ; },
abstract = {Aim: Prognostic factors in amyotrophic lateral sclerosis (ALS) are defined by clinical features and progression rate at first observation or over follow-up. The prognostic factors associated with late-stage disease are uncertain. We sought to identify factors predicting survival in advanced ALS. Methods: We analyzed data collected from patients followed at our clinic who progressed to late-stage ALS, defined as ALS Functional Rating Scale Revised (ALSFRS-R) ≤ 24 (group A), patients followed for at least 6 months thereafter constituted group B. We studied demographic and clinical variables, including phenotype, sex, age, diagnostic delay (disease duration at diagnosis), noninvasive ventilation (NIV), percutaneous endoscopic gastrostomy (PEG), early (from diagnosis to ALSFRS-R ≤ 24) and thereafter late functional progression rates (ΔFS), and survival. Multivariable analysis with Cox regression was performed to ascertain predictive factors for survival in late-stage. Results: Group A included 704 patients and group B 260 patients. For group A, predictors associated with shorter survival were bulbar-onset (p = 0.03), and ΔFS at diagnosis and until late stage (p < 0.001). For group B, predictors associated with shorter survival were older age (p = 0.005), bulbar-onset (p = 0.02), shorter diagnostic delay (p < 0.001), ΔFS until late stage (p < 0.02), and late stage ΔFS (p < 0.001), but not ΔFS at diagnosis. Discussion: Similar to the general ALS population, survival in late-stage patients is predicted by age, region of onset, and diagnostic delay. Although ΔFS in later stages is prognostic, the initial ΔFS at diagnosis is not. Therefore, continuous monitoring of functional decline remains crucial for patients already in advanced stages.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/mortality/therapy
Male
Female
Middle Aged
Aged
Disease Progression
Prognosis
Adult
Retrospective Studies

@article {pmid41100401,
year = {2025},
author = {Graco, M and Carey, KA and Russo, K and Sheers, NL and Berlowitz, DJ and , and , },
title = {Understanding the uptake and use of noninvasive ventilation among Australians living with amyotrophic lateral sclerosis: results of a national survey.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {26},
number = {7-8},
pages = {649-658},
doi = {10.1080/21678421.2025.2529406},
pmid = {41100401},
issn = {2167-9223},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/epidemiology/psychology ; Male ; Female ; *Noninvasive Ventilation/statistics & numerical data ; Middle Aged ; Australia/epidemiology ; Aged ; Cross-Sectional Studies ; Surveys and Questionnaires ; Quality of Life ; *Patient Acceptance of Health Care/statistics & numerical data ; Adult ; Australasian People ; },
abstract = {Objective: Noninvasive ventilation (NIV) improves quality of life and extends survival in amyotrophic lateral sclerosis (ALS), yet NIV uptake among Australians with ALS has been estimated at 19%. This study aimed to identify demographic and disease-related factors associated with NIV uptake among people with ALS (pwALS). Methods: A national cross-sectional survey. PwALS (or their family caregivers) completed an online survey about their NIV use and healthcare experiences. Survey data were analyzed descriptively. Associations between demographic factors and three dichotomous NIV outcomes: "using NIV"; "offered and accepted NIV"; and "discussed NIV with a healthcare professional (HCP)" were investigated using multivariate logistic regression modeling. Results: A total of 224 responses were received, of which 201 completed the demographic questions. Mean (SD) age was 64 (11) years, 62% were male, and median (IQR) time since diagnosis was 2 (1-5) years. Forty-six percent were using NIV; 6% had started NIV and stopped; 4% had accepted a referral but not started; 3% had declined NIV; and 26% had never discussed NIV with a HCP. Demographic factors positively associated (p < 0.05) with at least one NIV outcome included: being male, age < 65 years, residing in a metropolitan/regional area, attending a ALS multidisciplinary clinic, and longer time since diagnosis. Conclusion: NIV uptake among Australians with ALS appears to have increased in the last decade, however this survey identified concerning disparities related to sex, age, and location of residence. Research exploring the underlying causes of these disparities is urgently required so that targeted interventions can be designed and implemented.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/epidemiology/psychology
Male
Female
*Noninvasive Ventilation/statistics & numerical data
Middle Aged
Australia/epidemiology
Aged
Cross-Sectional Studies
Surveys and Questionnaires
Quality of Life
*Patient Acceptance of Health Care/statistics & numerical data
Adult
Australasian People

@article {pmid41100025,
year = {2025},
author = {El Ansari, W and Elhag, W},
title = {Response to Borah et al's Comments on Manuscript: "From Outcomes to Long-Term Impact: Do Improvements in Individual Cardiometabolic Risk Factors After Sleeve Gastrectomy Translate to Reductions in Composite Indicators of Cardiovascular Risk".},
journal = {Obesity surgery},
volume = {},
number = {},
pages = {},
pmid = {41100025},
issn = {1708-0428},
}

@article {pmid41099730,
year = {2025},
author = {Polu, PR and Mishra, S},
title = {Genetic convergence in brain aging and neurodegeneration: from cellular mechanisms to therapeutic targets.},
journal = {Journal of neurogenetics},
volume = {},
number = {},
pages = {1-20},
doi = {10.1080/01677063.2025.2571127},
pmid = {41099730},
issn = {1563-5260},
abstract = {The distinction between normal brain aging and neurodegeneration has traditionally been viewed as a binary classification, yet emerging evidence reveals a complex continuum of shared genetic mechanisms underlying both processes. This review synthesises current understanding of conserved molecular pathways that contribute to age-related neural decline across the spectrum from healthy aging to pathological neurodegeneration. We examine how fundamental cellular processes including protein quality control, mitochondrial dysfunction, inflammation, and synaptic maintenance are genetically regulated and become progressively dysregulated during aging. Key genetic pathways, such as insulin/IGF signalling, autophagy-lysosomal networks, and stress response mechanisms demonstrate remarkable conservation from model organisms to humans, suggesting evolutionary constraints on neural aging processes. The review highlights how genetic variants in these pathways can determine individual trajectories along the aging-neurodegeneration continuum, influencing susceptibility to diseases like Alzheimer's, Parkinson's, and ALS. We discuss evidence from comparative studies in C. elegans, Drosophila, rodents, and human populations that illuminate shared vulnerability genes and protective factors. Understanding these convergent mechanisms offers unprecedented opportunities for therapeutic intervention, as strategies targeting fundamental aging processes may simultaneously address multiple neurodegenerative conditions. This integrated perspective challenges traditional disease-centric approaches and supports the development of unified therapeutic strategies for promoting healthy brain aging while preventing neurodegeneration.},
}

@article {pmid41099622,
year = {2025},
author = {Yoshida, M and Muraki, N and Tajiri, M and Hengphasatporn, K and Sue, K and Kubo, T and Akashi, S and Shigeta, Y and Kambe, T and Furukawa, Y},
title = {Oxidative denaturation of Cu/Zn-superoxide dismutase associated with neurodegenerative diseases.},
journal = {Protein science : a publication of the Protein Society},
volume = {34},
number = {11},
pages = {e70339},
pmid = {41099622},
issn = {1469-896X},
support = {19H05765//Ministry of Education, Culture, Sports, Science and Technology/ ; 22H02768//Ministry of Education, Culture, Sports, Science and Technology/ ; 22K19389//Ministry of Education, Culture, Sports, Science and Technology/ ; 24H01329//Ministry of Education, Culture, Sports, Science and Technology/ ; },
mesh = {Humans ; Oxidation-Reduction ; *Superoxide Dismutase-1/chemistry/metabolism/genetics ; Molecular Dynamics Simulation ; Protein Denaturation ; Zinc/metabolism/chemistry ; Cysteine/chemistry/metabolism ; Protein Folding ; Hydrogen Peroxide/chemistry ; *Neurodegenerative Diseases/enzymology ; Amyotrophic Lateral Sclerosis/genetics/enzymology ; },
abstract = {Misfolding of mutant Cu/Zn-superoxide dismutase (SOD1) is a well-established pathological feature of familial amyotrophic lateral sclerosis (ALS). While amino acid substitutions in mutant SOD1 destabilize its structure and promote misfolding, oxidation has also been implicated in the pathological alterations of wild-type SOD1, particularly in neurodegenerative diseases including sporadic ALS. However, the impact of oxidation on SOD1 folding remains to be fully elucidated. Here, we demonstrate that Cys111 is primarily oxidized to sulfonic acid upon exposure of apo-SOD1 to hydrogen peroxide, as confirmed by the quantitation of thiol groups and mass spectrometry. Molecular dynamics simulations showed that sulfonylation of Cys111 disrupts the dimer interface and promotes monomerization. This monomeric form then facilitates the subsequent oxidation of buried Cys6, leading to structural disruption, as evidenced by circular dichroism spectroscopy and loss of thiol groups. SOD1 denaturation triggered by Cys111 oxidation became evident when zinc binding was impaired due to pathological mutations and/or under zinc-deficient conditions. Given that increased oxidative stress is frequently associated with many neurodegenerative diseases, modulating Cys111 oxidation may offer a potential strategy for maintaining SOD1 structural stability and preventing its pathological misfolding.},
}

Humans
Oxidation-Reduction
*Superoxide Dismutase-1/chemistry/metabolism/genetics
Molecular Dynamics Simulation
Protein Denaturation
Zinc/metabolism/chemistry
Cysteine/chemistry/metabolism
Protein Folding
Hydrogen Peroxide/chemistry
*Neurodegenerative Diseases/enzymology
Amyotrophic Lateral Sclerosis/genetics/enzymology

@article {pmid41099526,
year = {2025},
author = {Lami, R},
title = {From biocides to biology: multispecies biofilms as a sustainable, self-regenerating, and effective antifouling strategy.},
journal = {Applied and environmental microbiology},
volume = {},
number = {},
pages = {e0160925},
doi = {10.1128/aem.01609-25},
pmid = {41099526},
issn = {1098-5336},
abstract = {Finding antifouling strategies that are effective and environmentally safe remains a central challenge for maritime operations and ecosystem protection. Amador et al.'s article in Applied and Environmental Microbiology (91:e01392-25, 2025, https://doi.org/10.1128/aem.01392-25) proposes a bioinspired, applied-microbial-ecology solution: deliberately shaping pioneer biofilm communities, so they form a physical barrier against macrofouler settlement, avoiding biocides and low-adhesion inert coatings. Though focused on the ocean, this paradigm could inform broader anti-biofilm interventions across microbiology, reframing control as ecological steering rather than chemical suppression or materials-based design.},
}

@article {pmid41098540,
year = {2025},
author = {Dafsari, HS and Schuler, J and Schober, E and Möller, B and Antebi, A and Fanto, M and Jungbluth, H},
title = {The space-time continuum in neurological disorders of the autophagosome-lysosome fusion machinery.},
journal = {Autophagy reports},
volume = {4},
number = {1},
pages = {2560903},
pmid = {41098540},
issn = {2769-4127},
abstract = {Autophagy is a highly conserved cellular pathway for the degradation and recycling of defective intracellular cargo and plays a vital role in the homeostasis of post-mitotic tissues, particularly the nervous system. Autophagosome-lysosome fusion represents the final critical step in macroautophagy with a tightly regulated process mediated by a complex molecular machinery of tethering vesicles for degradation. Since the first reports of human autophagy disorders, the scientific and clinical focus condensed on severe phenotypes with biallelic-truncating genotypes as monogenic models of near-complete autophagy perturbation. Recent reports suggest a much wider disease spectrum with defective autophagy, ranging from neurodevelopmental disorders to neurodegenerative phenotypes with later manifestation due to "milder" genotypes, including Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic Lateral Sclerosis-Frontotemporal Dementia (ALS-FTD). In addition, recent evidence identified molecular connections between physiological autophagy regulation during normal aging and pathophysiological hallmarks of aging-related disorders. These translational observations led to a more comprehensive understanding of autophagy at health and disease, in particular: 1) genetic location and allelism of pathogenic variants ("genomic space"); 2) protein-protein interaction in functional protein complexes ("proteomic space"); 3) metabolic autophagic flux with positive and negative regulators ("metabolomic space"); 4) age-related phenotypic progression over time. Here, we review the autophagosome-lysosome fusion machinery as a key structure both on the molecular level and with regards to the pathogenesis of the autophagy-related disease spectrum. We highlight the clinicopathological signature of disorders in the autophagosome-lysosome fusion machinery, in particular features warranting awareness from clinicians and geneticists to inform adequate diagnosis, surveillance, and patient guidance.},
}

@article {pmid41098254,
year = {2025},
author = {Marie, D and Miller, LE and Bhattacharyya, SK and Frankhauser, FM},
title = {Navigating End-of-Life Decisions With Amyotrophic Lateral Sclerosis: A Patient-Centered Perspective on the Clinical and Legal Barriers to Medical Aid in Dying.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e92254},
pmid = {41098254},
issn = {2168-8184},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and incurable neurodegenerative disease that often leads to loss of speech, swallowing restrictions, respiratory failure, paralysis, and total physical dependence, despite preserved cognitive function. For some affected individuals, the anticipated decline in autonomy associated with ALS leads to the consideration of medical aid in dying (MAiD). In the United States (US), MAiD is legally permitted in 12 jurisdictions (11 states and Washington, DC); however, most require patients to self-administer the prescribed medications. This stipulation creates an inequitable barrier for people with late-stage ALS, as the ability to swallow medication or manipulate delivery devices is often lost well before the end of life. Patients with ALS who are considering MAiD and otherwise meet all eligibility criteria must weigh the decision to end their lives earlier than desired against the risk of prolonging life and becoming physically unable to self-administer MAiD. This paper, coauthored by a patient with bulbar-onset ALS, integrates clinical literature, legal analysis, and lived experience to examine how existing MAiD statutes in the US fail to accommodate the physical disabilities of otherwise eligible patients from using this option. Overall, legislative reform in the US is urgently needed to ensure that MAiD eligibility is based on informed consent and clinical criteria without unfair exclusion based on physical disability.},
}

@article {pmid41097931,
year = {2025},
author = {Rutkove, S and Tiwari, G and Nath, AK},
title = {Performing Compound Motor Action Potential Measurement in Zebrafish: A Description of Methodology and a Comparison Between Healthy and ALS-Affected Animals.},
journal = {Muscle & nerve},
volume = {72},
number = {5},
pages = {1168-1177},
doi = {10.1002/mus.70009},
pmid = {41097931},
issn = {1097-4598},
support = {//Beth Israel Deaconess Medical Center/ ; },
mesh = {Animals ; Zebrafish ; *Amyotrophic Lateral Sclerosis/physiopathology/genetics/diagnosis ; Disease Models, Animal ; *Action Potentials/physiology ; *Motor Neurons/physiology ; Animals, Genetically Modified ; Electric Stimulation ; Superoxide Dismutase/genetics ; },
abstract = {INTRODUCTION/AIMS: The compound motor action potential (CMAP) is a very well-established output from standard motor conduction studies in patients. CMAP methods have also been developed for various animal models, including mice, rats, and dogs. Here, we describe a CMAP methodology for adult zebrafish.

METHODS: Using needle stimulating electrodes placed in proximity to the caudal spinal column and a fixed two-electrode surface array placed near the dorsal fin for recording, we obtained CMAPs in wildtype (WT) and symptomatic amyotrophic lateral sclerosis (ALS) SOD1[G93A] zebrafish, assessing repeatability and the potential for identifying differences between the groups.

RESULTS: In WT animals, CMAP amplitude exhibited robust performance with a test-retest intra-class coefficient of 0.97 (95% confidence interval 0.947-0.988; p < 0.0001, n = 30). SOD1[G93A] zebrafish exhibited a 36% lower supramaximal CMAP amplitude as compared to WT (mean ± standard deviation: 7.7 ± 1.7 mV versus 12.2 ± 1.8 mV, respectively, p < 0.0001) and an 11% longer latency (1.30 ± 0.15 ms versus 1.17 ± 0.11 ms, p = 0.002). A classifier, incorporating amplitude and latency together, provided perfect discrimination between the two cohorts.

DISCUSSION: CMAP recording is a reliable technique in zebrafish and can successfully differentiate healthy WT fish from ALS-affected animals. Since CMAP is a quantitative metric that is highly sensitive to motor neuron loss or dysfunction, it will allow the zebrafish to be more effectively harnessed for physiological and clinical therapeutic studies in ALS and other neuromuscular diseases for which adult zebrafish models are available.},
}

Animals
Zebrafish
*Amyotrophic Lateral Sclerosis/physiopathology/genetics/diagnosis
Disease Models, Animal
*Action Potentials/physiology
*Motor Neurons/physiology
Animals, Genetically Modified
Electric Stimulation
Superoxide Dismutase/genetics

@article {pmid41097145,
year = {2025},
author = {Tuigunov, D and Sinyavskiy, Y and Nurgozhin, T and Zholdassova, Z and Smagul, G and Omarov, Y and Dolmatova, O and Yeshmanova, A and Omarova, I},
title = {Precision Nutrition and Gut-Brain Axis Modulation in the Prevention of Neurodegenerative Diseases.},
journal = {Nutrients},
volume = {17},
number = {19},
pages = {},
doi = {10.3390/nu17193068},
pmid = {41097145},
issn = {2072-6643},
support = {Grant No. AP23489983//This research is funded by the Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/prevention & control/microbiology ; *Gastrointestinal Microbiome/physiology ; *Brain ; *Precision Medicine/methods ; *Brain-Gut Axis/physiology ; Prebiotics/administration & dosage ; Probiotics/administration & dosage ; },
abstract = {In the recent years, the accelerating global demographic shift toward population aging has been accompanied by a marked increase in the prevalence of neurodegenerative disorders, notably Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Among emerging approaches, dietary interventions targeting the gut-brain axis have garnered considerable attention, owing to their potential to modulate key pathogenic pathways underlying neurodegenerative processes. This review synthesizes current concepts in precision nutrition and elucidates neurohumoral, immune, and metabolic regulatory mechanisms mediated by the gut microbiota, including the roles of the vagus nerve, cytokines, short-chain fatty acids, vitamins, polyphenols, and microbial metabolites. Emerging evidence underscores that dysbiotic alterations contribute to compromised barrier integrity, the initiation and perpetuation of neuroinflammatory responses, pathological protein aggregations, and the progressive course of neurodegenerative diseases. Collectively, these insights highlight the gut microbiota as a pivotal target for the development of precision-based dietary strategies in the prevention and mitigation of neurodegenerative disorders. Particular attention is devoted to key bioactive components such as prebiotics, probiotics, psychobiotics, dietary fiber, omega-3 fatty acids, and polyphenols that critically participate in regulating the gut-brain axis. Contemporary evidence on the contribution of the gut microbiota to the pathogenesis of Alzheimer's disease, Parkinson's disease, and multiple sclerosis is systematically summarized. The review further discusses the prospects of applying nutrigenomics, chrononutrition, and metagenomic analysis to the development of personalized dietary strategies. The presented findings underscore the potential of integrating precision nutrition with targeted modulation of the gut-brain axis as a multifaceted approach to reducing the risk of neurodegenerative diseases and preserving cognitive health.},
}

Humans
*Neurodegenerative Diseases/prevention & control/microbiology
*Gastrointestinal Microbiome/physiology
*Brain
*Precision Medicine/methods
*Brain-Gut Axis/physiology
Prebiotics/administration & dosage
Probiotics/administration & dosage

@article {pmid41097004,
year = {2025},
author = {Daponte, A and Koros, C and Skarlis, C and Siozios, D and Rentzos, M and Papageorgiou, SG and Anagnostouli, M},
title = {Neurofilament Biomarkers in Neurology: From Neuroinflammation to Neurodegeneration, Bridging Established and Novel Analytical Advances with Clinical Practice.},
journal = {International journal of molecular sciences},
volume = {26},
number = {19},
pages = {},
doi = {10.3390/ijms26199739},
pmid = {41097004},
issn = {1422-0067},
mesh = {Humans ; *Biomarkers/metabolism/blood ; *Neurofilament Proteins/metabolism/blood ; *Neurodegenerative Diseases/metabolism/diagnosis ; *Neuroinflammatory Diseases/metabolism/diagnosis ; Animals ; },
abstract = {Neuroaxonal damage underlies permanent disability in various neurological conditions, both neuroautoimmune and neurodegenerative. It is crucial to accurately quantify and monitor axonal injury using biomarkers to evaluate disease progression and treatment effectiveness and offer prognostic insights. Neurofilaments (NFs), and especially neurofilament light chain (NfL), show promise for this purpose, as their levels increase with neuroaxonal damage in both cerebrospinal fluid and blood, independent of specific causal pathways. Recent advances in ultrasensitive immunoassays enable the reliable detection of NFs in blood, transforming them from research tools into clinically applicable measures. In multiple sclerosis (MS), serum NfL correlates with disease activity, treatment response, and long-term disability, and may complement MRI in monitoring subclinical progression. In MS, NfL is primarily emerging as a marker of disease activity and treatment response; in amyotrophic lateral sclerosis (ALS), it has progressed further, being integrated into clinical trials as a pharmacodynamic endpoint and considered by regulatory agencies as a drug development tool. Additionally, NFs are increasingly being investigated in Alzheimer's disease, frontotemporal dementia, and other neurodegenerative disorders, though their disease specificity is limited. Ongoing challenges include older and novel assay harmonization, normative range interpretation, biological and analytical variability, and integration with other molecular and imaging biomarkers. This critical narrative review synthesizes the existing literature on NFs as diagnostic, prognostic, predictive, and pharmacodynamic biomarkers and discusses their role in therapeutic development and precision medicine in neuroautoimmune and neurodegenerative diseases.},
}

Humans
*Biomarkers/metabolism/blood
*Neurofilament Proteins/metabolism/blood
*Neurodegenerative Diseases/metabolism/diagnosis
*Neuroinflammatory Diseases/metabolism/diagnosis
Animals

@article {pmid41096741,
year = {2025},
author = {Lee, BC and Kuo, YC and Cheng, LF and Tsai, YC and Huang, JZ and Tsai, HH and Lin, JS and Huang, PY and Ting, CH and Yang, CC and Lai, HJ and Chao, CC and Tsai, LK},
title = {The Significance and Mechanism of Cerebral Enlarged Perivascular Space in Amyotrophic Lateral Sclerosis.},
journal = {International journal of molecular sciences},
volume = {26},
number = {19},
pages = {},
doi = {10.3390/ijms26199474},
pmid = {41096741},
issn = {1422-0067},
support = {NHRI-112-B02)//National Health Research Institutes/ ; MS484//National Taiwan University Hospital/ ; 113-2314-B-002-100-MY3//National Science and Technology Council/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/pathology/diagnostic imaging/metabolism ; Humans ; Male ; Female ; Animals ; Middle Aged ; *Glymphatic System/pathology/diagnostic imaging/metabolism ; Mice ; Magnetic Resonance Imaging ; Aged ; Superoxide Dismutase-1/metabolism/genetics ; Mice, Transgenic ; Adult ; Motor Neurons/metabolism/pathology ; Disease Models, Animal ; },
abstract = {Enlarged perivascular spaces (EPVS) are MRI markers of impaired glymphatic clearance and have been associated with neurodegenerative diseases. However, their clinical significance in amyotrophic lateral sclerosis (ALS) and underlying mechanisms remain poorly understood. This study investigated the prevalence, clinical relevance, and pathophysiological basis of EPVS in ALS. MRI data from 114 ALS patients and 119 matched controls were analyzed, with high-degree EPVS defined as more than 20 visible spaces. High-degree EPVS in the centrum semiovale (CSO) was more prevalent in ALS patients (49.1%) than in controls (15.1%, p < 0.001). Age, male sex, and ALS diagnosis were independent predictors, while disease severity and aggressiveness were not associated. ALS patients with high-degree CSO-EPVS were older at disease onset and MRI but showed similar clinical progression. In SOD1/G93A ALS mice, cerebral perivascular spaces were significantly enlarged at 5 months compared to wild-type and younger ALS mice. Cervical lymphatic ligation promoted misfolded SOD1 accumulation in motor neurons and cerebral vessels, further increasing perivascular space width without altering motor function. These findings suggest that about half of ALS patients exhibit high-degree CSO-EPVS, reflecting impaired protein clearance rather than disease aggressiveness.},
}

*Amyotrophic Lateral Sclerosis/pathology/diagnostic imaging/metabolism
Humans
Male
Female
Animals
Middle Aged
*Glymphatic System/pathology/diagnostic imaging/metabolism
Mice
Magnetic Resonance Imaging
Aged
Superoxide Dismutase-1/metabolism/genetics
Mice, Transgenic
Adult
Motor Neurons/metabolism/pathology
Disease Models, Animal

@article {pmid41096667,
year = {2025},
author = {Skarlis, C and Angelopoulou, E and Rentzos, M and Papageorgiou, SG and Anagnostouli, M},
title = {Monoclonal Antibodies as Therapeutic Agents in Autoimmune and Neurodegenerative Diseases of the Central Nervous System: Current Evidence on Molecular Mechanisms and Future Directions.},
journal = {International journal of molecular sciences},
volume = {26},
number = {19},
pages = {},
doi = {10.3390/ijms26199398},
pmid = {41096667},
issn = {1422-0067},
mesh = {Humans ; *Antibodies, Monoclonal/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy/immunology ; Animals ; *Central Nervous System Diseases/drug therapy/immunology ; Neuromyelitis Optica/drug therapy ; Central Nervous System/drug effects/immunology ; Multiple Sclerosis/drug therapy ; },
abstract = {Monoclonal antibodies (mAbs) have revolutionized the treatment landscape for neurological diseases, providing targeted, mechanism-based therapies for conditions ranging from autoimmune demyelinating disorders to neurodegenerative diseases. In multiple sclerosis (MS), mAbs against CD20, CD52, and α4-integrins offer disease-modifying efficacy by altering immune responses, depleting B cells, or blocking leukocyte migration into the central nervous system (CNS). Similarly, novel agents under investigation, such as frexalimab and foralumab, modulate T and B cell interactions and regulatory immunity. In neuromyelitis optica spectrum disorder (NMOSD), mAbs targeting IL-6, the complement cascade, and B cell lineage have demonstrated significant clinical benefit in preventing relapses and disability. In Alzheimer's disease (AD), several anti-amyloid mAbs have gained regulatory approval. Anti-tau and anti-α-synuclein antibodies, though promising, have shown limited efficacy to date in AD and parkinson's disease (PD), respectively. The evolving armamentarium of mAbs reflects a paradigm shift toward personalized neuroimmunology and neurodegeneration-targeted treatments, based on ongoing clarification of molecular and neuroinflammatory mechanisms. In this context, the present review summarizes current evidence on mAbs used in CNS disorders, with an emphasis on their pathophysiological targets, molecular mechanisms, clinical efficacy, and safety.},
}

Humans
*Antibodies, Monoclonal/therapeutic use/pharmacology
*Neurodegenerative Diseases/drug therapy/immunology
Animals
*Central Nervous System Diseases/drug therapy/immunology
Neuromyelitis Optica/drug therapy
Central Nervous System/drug effects/immunology
Multiple Sclerosis/drug therapy

@article {pmid41096646,
year = {2025},
author = {García-Criado, F and Hurtado-García, L and Rojano, E and Esteban-Martos, Á and Pérez-García, J and Seoane, P and Ranea, JAG},
title = {Integrative Transcriptomic and Network-Based Analysis of Neuromuscular Diseases.},
journal = {International journal of molecular sciences},
volume = {26},
number = {19},
pages = {},
doi = {10.3390/ijms26199376},
pmid = {41096646},
issn = {1422-0067},
support = {PID2019-108096RB-C21, PID2022-140047OB-C21, CPP2022-010108//Ministerio de Ciencia, Innovación y Universidades/ ; IMP/00019, ACCI-05-703, ACCI-02-770//Instituto de Salud Carlos III/ ; HORIZON-HLTH-2022-DISEASE-06, 101080580//European Union/ ; RH-0079-2021//Fundación Progreso y Salud/ ; PI RARE 24-03//Instituto de Investigación Biomédica de Málaga/ ; FPU21/01449, PRE2022/000510//Ministerio de Ciencia, Innovación y Universidades/ ; },
mesh = {Humans ; *Transcriptome ; *Neuromuscular Diseases/genetics/metabolism ; *Gene Regulatory Networks ; Protein Interaction Maps/genetics ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Gene Expression Profiling ; Muscular Dystrophy, Duchenne/genetics/metabolism ; Muscular Dystrophies, Limb-Girdle/genetics/metabolism ; Computational Biology/methods ; },
abstract = {Neuromuscular diseases (NMDs) like Duchenne muscular dystrophy (DMD), limb-girdle muscular dystrophy (LGMD), and amyotrophic lateral sclerosis (ALS) are rare, progressive disorders with complex molecular mechanisms. Traditional transcriptomic analyses often struggle to capture systems-level dysregulation, especially given the small sample sizes typical of rare disease studies. Our differential expression analysis of eight public RNA-seq datasets from various cell types in DMD, LGMD, and ALS revealed not only disease-relevant pathways but also unexpected enrichments, such as renal development, suggesting systemic impacts beyond muscle tissue. To address limitations in capturing broader molecular mechanisms, we applied an integrative systems biology approach combining differential expression data, protein-protein interaction (PPI) networks, and network embedding techniques. Comparative functional enrichment revealed shared pathways, including glycosaminoglycan binding in both DMD and FUS-related ALS, implicating extracellular matrix-protein interactions in FUS mutation effects. Mapping DEGs onto the human PPI network and assessing their proximity to causal genes uncovered dysregulated non-coding RNAs, such as PAX8-AS1, SBF2-AS1, and NEAT1, potentially indicating common regulatory roles. We also found candidate genes within disease-proximal clusters, like HS3ST3A1, which may contribute to pathogenesis. Overall, this integrative approach reveals shared transcriptional programs and novel targets, advancing our understanding and potential treatment strategies for NMDs.},
}

Humans
*Transcriptome
*Neuromuscular Diseases/genetics/metabolism
*Gene Regulatory Networks
Protein Interaction Maps/genetics
*Amyotrophic Lateral Sclerosis/genetics/metabolism
Gene Expression Profiling
Muscular Dystrophy, Duchenne/genetics/metabolism
Muscular Dystrophies, Limb-Girdle/genetics/metabolism
Computational Biology/methods

@article {pmid41096235,
year = {2025},
author = {Savov, V and Antov, P and Kostadinova-Slaveva, A and Yusein, J and Dudeva, V and Todorova, E and Petrin, S},
title = {Development and Characterization of Sustainable Biocomposites from Wood Fibers, Spent Coffee Grounds, and Ammonium Lignosulfonate.},
journal = {Polymers},
volume = {17},
number = {19},
pages = {},
pmid = {41096235},
issn = {2073-4360},
support = {project BG05SFPR001-3.004-0010 "Development of project doctoral studies at the University of Forestry"//Programme 'Education' 2021-2027, co-funded by the European Union through the ESF+. ./ ; },
abstract = {Coffee processing generates large volumes of spent coffee grounds (SCGs), which contain 30-40% hemicellulose, 8.6-13.3% cellulose, and 25-33% lignin, making them a promising lignin-rich filler for biocomposites. Conventional wood composites rely on urea-formaldehyde (UF), melamine-urea-formaldehyde (MUF), and phenol-formaldehyde resins (PF), which dominate 95% of the market. Although formaldehyde emissions from these resins can be mitigated through strict hygiene standards and technological measures, concerns remain due to their classification as category 1B carcinogens under EU regulations. In this study, fiber-based biocomposites were fabricated from thermomechanical wood fibers, SCGs, and ammonium lignosulfonate (ALS). SCGs and ALS were mixed in a 1:1 ratio and incorporated at 40-75% of the oven-dry fiber mass. Hot pressing was performed at 150 °C under 1.1-1.8 MPa to produce panels with a nominal density of 750 kg m[-3], and we subsequently tested them for their physical properties (density, water absorption (WA), and thickness swelling (TS)), mechanical properties (modulus of elasticity (MOE), modulus of rupture (MOR), and internal bond (IB) strength), and thermal behavior and biodegradation performance. A binder content of 50% yielded MOE ≈ 2707 N mm[-2] and MOR ≈ 22.6 N mm[-2], comparable to UF-bonded medium-density fiberboards (MDFs) for dry-use applications. Higher binder contents resulted in reduced strength and increased WA values. Thermogravimetric analysis (TGA/DTG) revealed an inorganic residue of 2.9-8.5% and slower burning compared to the UF-bonded panels. These results demonstrate that SCGs and ALS can be co-utilized as a renewable, formaldehyde-free adhesive system for manufacturing wood fiber composites, achieving adequate performance for value-added practical applications while advancing sustainable material development.},
}

@article {pmid41095782,
year = {2025},
author = {Maciel, ACMG and Resqueti, VR and Costa, LMD and Silva, AAMD and Fonseca, JDMD and Vieira, RGDS and Pondofe, KM and Otto-Yáñez, M and Vilaró, J and Torres-Castro, R and Vera-Uribe, R and Ribeiro-Samora, GA and Nagem, D and Valentim, RA and Dourado Júnior, MET and Fregonezi, G},
title = {The Impact of Respiratory Function on Functionality and Mortality in ALS Patients.},
journal = {Journal of clinical medicine},
volume = {14},
number = {19},
pages = {},
doi = {10.3390/jcm14196702},
pmid = {41095782},
issn = {2077-0383},
support = {88887.692599/2022-00 (JMDF)//Coordenação de Aperfeicoamento de Pessoal de Nível Superior - CAPES/ ; 316937/2021-5 (GF)//Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPQ/ ; 305960/2021-0 (VR)//Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPQ/ ; Funding Code 001 (RGSV, LMC, AAMS)//Coordenação de Aperfeiçoamento Pessoal de Nível Superior-Brazil (CAPES)/ ; TED 132/2018//Mininstério da Saúde/ ; },
abstract = {Objective: To investigate the relationship between respiratory function, functionality, and mortality in amyotrophic lateral sclerosis (ALS) patients and to determine which respiratory parameters show the strongest correlation with functionality and mortality. Methods: The study was conducted in Rio Grande do Norte, Northeast Brazil, between January 2018 and December 2023. This was a retrospective cohort, following individuals with ALS who were evaluated at the University Laboratory. Results: A total of 74 ALS patients were included in the analysis, with a mean age of 55.7 ± 13.5 years. Most were male (66.2%) and predominantly presented with spinal-onset ALS (51.3%). Respiratory variables (except peak expiratory flow (PEF)) showed a weak but significant inverse correlation with mortality (FVC% predicted (rpb = -0.260; p < 0.001), SNIP (rpb = -0.235; p = 0.001), MEP (rpb = -0.207; p = 0.007), MIP (rpb = -0.198; p = 0.009), and PEF% predicted (rpb = -0.156; p = 0.013)). When analyzing their correlation with ALSFRS-R, all variables showed a significant positive correlation (ranging from weak to moderate) with functionality. A reduction of one unit in the respiratory variables PEF% of predicted, maximal inspiratory pressure (MIP), and sniff nasal inspiratory pressure (SNIP) increased the risk of death by an average of 300% (OR = 2.99; 95% CI: 2.05-4.35), 2% (OR = 1.02; 95% CI: 1.01-1.03), and 1% (OR = 1.01; 95% CI: 1.00-1.02), respectively. Conclusions: Our findings suggest that direct measurements of respiratory function and muscle strength, particularly PEF and SNIP, may serve as more useful markers to guide early interventions such as non-invasive ventilation, thereby improving quality of life and potentially prolonging survival.},
}

@article {pmid41095781,
year = {2025},
author = {Ferreira Laurentino, EK and Maldaner da Silva, VZ and Costa Meneses, WR and da Costa, LM and Otto-Yañez, M and Vera-Uribe, R and Torres-Castro, R and Carneiro de Sousa, BR and de Abreu Freitas, RP and Menezes Mateus, SR and Vasconcellos, IF and Fernandes Franco, HC and Pinto Nagem, DA and Medeiros Valentim, RA and Dourado Júnior, ME and Rodrigues Lindquist, AR and Santos Andrade, SMMD and Medeiros Fonseca, JD and Resqueti, VR and Freitas Fregonezi, G},
title = {High-Definition Transcranial Direct Current Stimulation (HD-tDCS) Therapy in Amyotrophic Lateral Sclerosis: Study Protocol for a Multicenter Randomized Controlled Clinical Trial.},
journal = {Journal of clinical medicine},
volume = {14},
number = {19},
pages = {},
doi = {10.3390/jcm14196701},
pmid = {41095781},
issn = {2077-0383},
support = {1748/22//Financiadora de Estudos e Projetos/ ; 88887.692599/2022-00 (JDMF)//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; 305960/2021-0 (VRR)//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; 316937/2021-5 (GF)//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; 001 (EKFL)//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; 001 (WRCM)//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; 001 (LMC)//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; 001 (BRCS)//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; },
abstract = {Background/Objectives: Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disease characterized by motor neuron loss, muscle weakness, and respiratory dysfunction, often culminating in ventilatory failure. Evidence suggests that High-Definition Transcranial Direct Current Stimulation (HD-tDCS) may modulate motor cortical excitability and potentially influence motor and respiratory function in ALS. This study aims to evaluate the effects of home-based HD-tDCS applied over the primary diaphragmatic motor cortex on respiratory parameters and disease progression in individuals with ALS. Methods: This is a multicenter, randomized, controlled clinical trial. Eligible participants (aged 18-80, both sexes, diagnosed with ALS) will be randomized into an active HD-tDCS group (gTDCS) or a sham group (gSham). The intervention consists of 30 min daily HD-tDCS sessions (3 mA) applied for two weeks (5 days/week), using a 4 × 1 ring configuration targeting the diaphragmatic motor cortex. Sham stimulation includes an identical setup but only delivers ramp currents (30 s) with a minimal ongoing current (0.1 mA). Results: Pre-, intra-, and post-intervention evaluations will include measures of cortical excitability, cerebral and tissue perfusion, surface electromyography, respiratory and pulmonary function, fatigue, sleep quality, pain, motor performance, dyspnea, quality of life, and adverse effects. All procedures will be conducted at participants' homes with appropriate safety monitoring. Conclusions: This study will investigate the effects of HD-tDCS on respiratory and motor function in ALS and explore the feasibility of a home-based neuromodulation intervention. The outcomes may provide insight into non-pharmacological strategies for respiratory management in ALS.},
}

@article {pmid41095520,
year = {2025},
author = {Whelan, BM and Aldridge, D and Ruhle, J and Whitelock, P and Taubert, S and Collins, A and Kearney, E and Charania, S and Henderson, RD and Wallace, SJ and Mitchell, C and Stipancic, KL and Kuruvilla-Dugdale, M and Vogel, AP},
title = {To Treat or Not to Treat: A Scoping Review of Speech Treatment for Dysarthria in Amyotrophic Lateral Sclerosis (ALS).},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {19},
pages = {},
doi = {10.3390/healthcare13192434},
pmid = {41095520},
issn = {2227-9032},
support = {N/A//University of Queensland, School of Health and Rehabilitation Sciences, New Staff Research Start-Up Fund/ ; },
abstract = {BACKGROUND: Speech loss is recognised as one of the most devastating outcomes for individuals with ALS, yet active speech intervention is rarely targeted in this population. Clinicians face significant challenges in managing dysarthria associated with ALS due to the rapidly progressive nature of the disease, historical concerns around intensive exercise accelerating decline, and an absence of direction on restorative and compensatory intervention strategies in current clinical care guidelines. This review evaluates the scope and quality of evidence for speech treatments in ALS to identify knowledge gaps and establish research priorities to guide clinical care.

METHODS: Studies were retrieved from six electronic databases (PubMed, CINAHL, Embase, Cochrane library, Web of Science, and PsycINFO).

RESULTS: Four studies met inclusion criteria. Treatment approaches included: music-based speech therapy; multisubsystem speech rehabilitation program, tongue strengthening and articulation training; and Lee Silverman Voice Treatment-LOUD[®] combined with additional voice and articulation therapy. Sample sizes were small, with all studies demonstrating notable methodological weaknesses. The limited evidence base, marked by conflicting results and methodological flaws, prevents any reliable conclusions about treatment effectiveness.

CONCLUSIONS: Despite the prevalence and impact of dysarthria in this population, evidence for speech treatment remains sparse, of generally low quality, and provides limited guidance for clinical practice. The changing perspective on exercise in ALS warrants rigorous investigation of tailored dysarthria interventions for this population that are minimally fatiguing and enhance speech by making use of residual physiologic support.},
}

@article {pmid41095229,
year = {2025},
author = {Ren, J and Song, M and Bimpong, D and Wang, F and Chen, W and Ma, D and Du, L},
title = {Genomic and Functional Characterization of Acetolactate Synthase (ALS) Genes in Stress Adaptation of the Noxious Weed Amaranthus palmeri.},
journal = {Plants (Basel, Switzerland)},
volume = {14},
number = {19},
pages = {},
doi = {10.3390/plants14193088},
pmid = {41095229},
issn = {2223-7747},
support = {2024YFC2607600//National Key R&D Program of China/ ; 2023ZTSJJ2//Open Project Program of Key Laboratory of Integrated Pest Management on Crop in Central China, Ministry of Agriculture/Hubei Province Key Laboratory for Control of Crop Diseases, Pest and Weeds/ ; },
abstract = {Acetolactate synthase (ALS) is an important enzyme in plant branched-chain amino acid biosynthesis and the target of several major herbicide classes. Despite its agronomic importance, the role of ALS genes in stress adaptation in the invasive weed Amaranthus palmeri remains unstudied. In this study, four ApALS genes with high motif conservation were identified and analyzed in A. palmeri. Phylogenetic analysis classified ApALS and other plant ALS proteins into two distinct clades, and the ApALS proteins were predicted to localize to the chloroplast. Gene expression analysis demonstrated that ApALS genes are responsive to multiple stresses, including salt, heat, osmotic stress, glufosinate ammonium, and the ALS-inhibiting herbicide imazethapyr, suggesting roles in both early and late stress responses. Herbicide response analysis using an Arabidopsis thaliana ALS mutant (AT3G48560) revealed enhanced imazethapyr resistance, associated with higher chlorophyll retention. Furthermore, high sequence homology between AT3G48560 and ApALS1 suggests a conserved role in protecting photosynthetic function during herbicide stress. This study provides the first comprehensive analysis of the ALS gene family in A. palmeri and offers important insights into its contribution to stress resilience. These findings establish a vital foundation for developing novel strategies to control this pervasive agricultural weed and present potential genetic targets for engineering herbicide tolerance in crops.},
}

@article {pmid41094691,
year = {2025},
author = {Caggiano, C and Morselli, M and Qian, X and Celona, B and Thompson, MJ and Wani, S and Tosevska, A and Taraszka, K and Heuer, G and Ngo, ST and Steyn, FJ and Nestor, PJ and Wallace, L and McCombe, P and Heggie, S and Thorpe, K and McElligott, C and English, G and Henders, A and Henderson, R and Lomen-Hoerth, C and Wray, NR and McRae, AF and Pellegrini, M and Garton, FC and Zaitlen, N},
title = {Epigenetic profiles of tissue informative CpGs inform ALS disease status and progression.},
journal = {Genome medicine},
volume = {17},
number = {1},
pages = {115},
pmid = {41094691},
issn = {1756-994X},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/diagnosis ; *DNA Methylation ; Disease Progression ; *Epigenesis, Genetic ; Female ; Male ; *CpG Islands ; Middle Aged ; Cell-Free Nucleic Acids/genetics ; C9orf72 Protein/genetics ; Aged ; Adult ; Organ Specificity ; },
abstract = {BACKGROUND: Cell-free DNA (cfDNA), derived from dying cells, has demonstrated utility across multiple clinical applications. However, its potential in neurodegenerative diseases remains underexplored, with most existing cfDNA technologies tailored to specific disease contexts like cancer or non-invasive prenatal screening.

METHODS: To address this gap, we developed a novel approach to characterize epigenetic cfDNA profiles by identifying key regions of DNA methylation that reveal the tissues origins undergoing apoptosis or necrosis. We evaluated this method in the largest cfDNA study of amyotrophic lateral sclerosis (ALS) and other neurological diseases (OND) to date, encompassing two independent cohorts (n = 192) from Australia (UQ Ncases = 48, Ncontrols = 32, NOND = 15) and the USA, (UCSF Ncases = 50, Ncontrols = 45)).

RESULTS: Our approach accurately distinguished ALS patients from controls (UQ AUC = 0.82, UCSF AUC = 0.99) and from individuals with other neurological diseases (AUC = 0.91). It also identified an asymptomatic carrier of a pathogenic C9orf72 variant, and strongly correlated with ALS disease progression measures (Pearson's R = 0.66, p = 3.71 × 10⁻⁹).

CONCLUSIONS: We identified DNA methylation signals from multiple tissue types in ALS cfDNA, highlighting diverse tissue involvement in ALS pathology. These findings promote epigenetic cfDNA analysis as a powerful tool for advancing our understanding of neurodegenerative disease.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/pathology/diagnosis
*DNA Methylation
Disease Progression
*Epigenesis, Genetic
Female
Male
*CpG Islands
Middle Aged
Cell-Free Nucleic Acids/genetics
C9orf72 Protein/genetics
Aged
Adult
Organ Specificity

@article {pmid41094045,
year = {2025},
author = {Li, A and Huang, S and Cao, SQ and Lin, J and Zhao, L and Yu, F and Huang, M and Yang, L and Xin, J and Wen, J and Yan, L and Zhang, K and Jiang, M and Le, W and Li, P and Liu, YU and Qin, D and Lu, J and Lu, G and Shen, H and Yao, X and Fang, EF and Su, H},
title = {Isoginkgetin antagonizes ALS pathologies in its animal and patient iPSC models via PINK1-Parkin-dependent mitophagy.},
journal = {EMBO molecular medicine},
volume = {},
number = {},
pages = {},
pmid = {41094045},
issn = {1757-4684},
support = {0093/2024/AFJ//Macau University of Science and Technology (MUST)/ ; #81971327//MOST | National Natural Science Foundation of China (NSFC)/ ; #82271448//MOST | National Natural Science Foundation of China (NSFC)/ ; MYRGGRG2023-00152-ICMS-UMDF//MOST | National Natural Science Foundation of China (NSFC)/ ; #282952; #284930//Cure Alzheimer's Fund (CAF)/ ; #262175,#334361//research council of Norway/ ; 2020001,#2021021,#2023093//HELSE SOR-OST/ ; #282942//Molecule AG/VITADAO/ ; #119986//NordForsk/ ; 269901,#261973,#262960//Høgskolen i Oslo og Akershus (HiOA)/ ; #281931//civitan norges forskningsfond for Alzheimer skydom/ ; TO01000215//Ministerstvo Práce a Sociálních Věcí České Republiky (Ministry of Labour and Social Affairs of the Czech Republic)/ ; #101073251//horizon-TMA-MSCA-DN/ ; #104617//Burroughs Wellcome Fund (BWF)/ ; SKL-QRCM(UM)-2023-2025//Science and Technology Development Fund, MAR/ ; 001/2023/ALC//Science and Technology Development Fund, MAR/ ; },
abstract = {Damaged mitochondria initiate mitochondrial dysfunction-associated senescence, which is considered to be a critical cause for amyotrophic lateral sclerosis (ALS). Thus, mitophagic elimination of damaged mitochondria provides a promising strategy in ALS treatment. Here, through screening of a large natural compound library (n = 9555), we have identified isoginkgetin (ISO), a bioflavonoid from Ginkgo biloba, as a robust and specific mitophagy inducer. ISO enhances PINK1-Parkin-dependent mitophagy via stabilization of the PINK1/TOM complex. In a translational perspective, ISO antagonizes ALS pathology in C. elegans and mouse models; intriguingly, ISO improves mitochondrial function and antagonizes motor neuron pathologies in three ALS patient-derived induced pluripotent stem cell systems (C9, SOD1, and TDP-43), highlighting a potential broad application to ALS patients of different genetic background. At the molecular level, ISO inhibits ALS pathologies in a PINK1-Parkin-dependent manner, as depletion or inhibition of PINK1 or Parkin blunts its benefits. These results support the hypothesis that mitochondrial dysfunction is a driver of ALS pathology and that defective mitophagy is a druggable therapeutic target for ALS.},
}

@article {pmid41093908,
year = {2025},
author = {Wilson, E and Turner, N and Palmer, J and Davidson, S and Turner, MR and Faull, C},
title = {Living with tracheostomy ventilation for motor neurone disease: a qualitative study of family member perspectives.},
journal = {Disability and rehabilitation},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/09638288.2025.2574536},
pmid = {41093908},
issn = {1464-5165},
abstract = {PURPOSE: To examine the experiences of family members caring for people with motor neurone disease (MND) who use tracheostomy ventilation.

METHODS: Drawing on a constructivist interpretivist approach, qualitative interviews with family members from England, Scotland, and Northern Ireland were conducted. Data were thematically analysed to interpret meaning and identify key themes.

RESULTS: Sixteen family members took part. Four themes are presented: (1) Decision-making and implementation: The decision about undergoing tracheostomy was driven by the person with MND. Tracheostomy ventilation was often initiated in an emergency, leaving families unprepared and distressed. (2) Impact on quality of life for family members: Responsibilities intensified once tracheostomy ventilation was in place, leading to a gradual erosion of personal autonomy for family caregivers. (3) Redefining family place and space: The continuous presence of paid carers and the medicalisation of the home impacted family dynamics. (4) Support for family members: Family members took on many roles with little support yet found meaning in the extended life of the person with MND.

CONCLUSION: Enhanced psychological, social, and practical support is urgently needed for families caring for someone with tracheostomy ventilation for MND. Greater awareness of its long-term impact, realistic home assessments, and structured support networks are essential.},
}

@article {pmid41093062,
year = {2025},
author = {Bunick, CG and Yang, K and Jafarian, F and Barbieri, JS},
title = {Response to Veenstra et al's "Benzoyl Peroxide Acne Treatment Shows No Significant Association with Benzene-Related Cancers: A Multicenter Retrospective Analysis" on Statistical Design.},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.10.042},
pmid = {41093062},
issn = {1097-6787},
}

@article {pmid41092967,
year = {2025},
author = {Dourado Junior, MET and Dourado, LC and Santana, GC and Vale, SHL and Leite-Lais, L},
title = {Impact of weight loss and disease progression on survival in ALS: insights from a multidisciplinary care center.},
journal = {Arquivos de neuro-psiquiatria},
volume = {83},
number = {10},
pages = {1-9},
doi = {10.1055/s-0045-1812029},
pmid = {41092967},
issn = {1678-4227},
mesh = {Humans ; Male ; *Weight Loss/physiology ; Female ; Disease Progression ; Middle Aged ; *Amyotrophic Lateral Sclerosis/mortality/physiopathology/complications ; Retrospective Studies ; Aged ; Adult ; Brazil/epidemiology ; Prognosis ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a multifaceted neurodegenerative disorder with a poor prognosis. Weight loss and malnutrition emerge as significant clinical features during disease progression.To explore how demographic and clinical characteristics relate to survival in ALS patients, emphasizing the role of weight loss percentage at the time of diagnosis.We conducted a retrospective study that used the database of a multidisciplinary ALS care center in the city of Natal, Brazil.A total of 132 patients were included in the study. The mean age of the participants at symptom onset was of 56.9 years, and most of them were male (59.8%). Older age, bulbar onset, and faster disease progression were associated with weight loss ≥ 10% at diagnosis. Among 132 patients, 72% experienced death or tracheostomy, with a median survival of 34 months. Survival was notably reduced in patients aged ≥ 60 years, those with significant weight loss, rapid disease progression, or those submitted to gastrostomy. Weight loss and the rate of disease progression were the strongest predictors of reduced survival. Potential factors relating gastrostomy with reduced survival are discussed.The present study highlights the critical impact of weight loss and disease progression on survival in ALS patients, emphasizing the importance of early nutritional and clinical interventions. These findings underscore the need for comprehensive, multidisciplinary care strategies to address key prognostic factors and improve outcomes in ALS patients.},
}

Humans
Male
*Weight Loss/physiology
Female
Disease Progression
Middle Aged
*Amyotrophic Lateral Sclerosis/mortality/physiopathology/complications
Retrospective Studies
Aged
Adult
Brazil/epidemiology
Prognosis

@article {pmid41092899,
year = {2025},
author = {Ruiz de Almodovar, C and Dupraz, S and Bonanomi, D},
title = {Neurovascular dynamics in the spinal cord from development to pathophysiology.},
journal = {Neuron},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuron.2025.09.017},
pmid = {41092899},
issn = {1097-4199},
abstract = {The vasculature is increasingly recognized as an active regulator of homeostasis and repair, beyond conventional roles in nutrient delivery. In the central nervous system, vascular cells adopt region-specific traits tailored to the distinct demands of the brain, retina, and spinal cord. Despite long-standing interest in the spinal cord as a model for neural development and injury, its vascular organization and properties remain understudied. The assumption that spinal cord and brain neurovascular systems are built and function in the same way has limited progress. Here, we challenge this view by examining specific properties underlying spinal cord vascular development, physiology, and pathology. We highlight unique angioarchitecture and homeostatic mechanisms, and discuss how neurovascular disruption contributes to spinal disorders and regenerative failure after injury. Identifying critical knowledge gaps, we aim to stimulate new research in spinal cord neurovascular biology, redefining its importance for health and disease.},
}

@article {pmid41092810,
year = {2025},
author = {Lopez-Mateos, D and Harris, BJ and Hernández-González, A and Yarov-Yarovoy, V and Wulff, H},
title = {Recent advances in the pharmacology of voltage-gated ion channels.},
journal = {Pharmacological reviews},
volume = {77},
number = {6},
pages = {100090},
doi = {10.1016/j.pharmr.2025.100090},
pmid = {41092810},
issn = {1521-0081},
abstract = {Voltage-gated ion channels (VGICs) are critical regulators of membrane potential, cellular excitability, and calcium signaling in both excitable and nonexcitable tissues and constitute important drug targets for neurological, cardiovascular, and immunological diseases. This review describes recent progress in the pharmacology of voltage-gated Na[+], voltage-gated Ca[2+], and voltage-gated K[+] channels, highlighting clinical-stage compounds, emerging therapeutic modalities, and new strategies in VGIC drug discovery, emphasizing the increasingly central role of protein structures and artificial intelligence. Several compounds targeting VGICs have progressed to clinical trials for epilepsy, atrial fibrillation, psoriasis, and difficult-to-treat disorders, such as chronic pain, schizophrenia, major depression, and amyotrophic lateral sclerosis. The therapeutic landscape for VGIC-related disorders is expanding beyond traditional small molecules and antisense oligonucleotides and gene therapies targeting VGICs at the mRNA or gene level are currently in both early and late clinical trial stages for Dravet syndrome and developmental epileptic encephalopathy. The progression of such varied modalities suggests that the extensive efforts dedicated to elucidating VGIC biophysics and structure, coupled with rigorous target validation, are beginning to translate into therapeutic advancements. Furthermore, we discuss emerging discovery strategies, including the growing impact of VGIC structures, computational structural modeling, virtual screening of focused and ultralarge libraries, and artificial intelligence-driven redesign and de novo design of biologics. Although these approaches are poised to substantially accelerate the early stages of ion channel drug discovery, the clinical stages will continue to require careful selection of indications and thoughtful clinical trial design to fully realize the long-held potential of VGICs as drug targets. SIGNIFICANCE STATEMENT: Drug development for voltage-gated ion channels is widely considered to be challenging. This article reviews recent advances in the pharmacology of voltage-gated Na[+], voltage-gated Ca[2+], and voltage-gated K[+] channels by examining compounds currently in clinical trials, including emerging new therapeutic approaches such as antisense oligonucleotides and gene therapy. We then discuss noteworthy recent developments, including the increasing availability and impact of ion channel structures, structural modeling, virtual screening, and artificial intelligence-assisted protein design, which are likely to accelerate the early stages of ion channel drug discovery. Success of the later stages will continue to rely on rigorous target validation, and proper choices of clinical candidates and clinical trial design.},
}

@article {pmid41090760,
year = {2025},
author = {Key, J and Almaguer-Mederos, LE and Kandi, AR and Fellenz, M and Gispert, S and Köpf, G and Meierhofer, D and Deller, T and Auburger, G},
title = {Conditional ATXN2L-Null in Adult Frontal Cortex CamK2a+ Neurons Does Not Cause Cell Death but Restricts Spontaneous Mobility and Affects the Alternative Splicing Pathway.},
journal = {Cells},
volume = {14},
number = {19},
pages = {},
pmid = {41090760},
issn = {2073-4409},
support = {DFG AU96/21-1//Deutsche Forschungsgemeinschaft/ ; },
mesh = {Animals ; *Alternative Splicing/genetics ; Mice ; *Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism ; *Neurons/metabolism ; *Ataxin-2/metabolism/genetics ; Cell Death ; Mice, Knockout ; },
abstract = {The Ataxin-2-like (ATXN2L) protein is required to survive embryonic development, as documented in mice with the constitutive absence of the ATXN2L Lsm, LsmAD, and PAM2 domains due to knock-out (KO) of exons 5-8 with a frameshift. Its less abundant paralog, Ataxin-2 (ATXN2), has an extended N-terminus, where a polyglutamine domain is prone to expansions, mediating vulnerability to the polygenic adult motor neuron disease ALS (Amyotrophic Lateral Sclerosis) or causing the monogenic neurodegenerative processes of Spinocerebellar Ataxia Type 2 (SCA2), depending on larger mutation sizes. Here, we elucidated the physiological function of ATXN2L by deleting the LsmAD and PAM2 motifs via loxP-mediated KO of exons 10-17 with a frameshift. Crossing heterozygous floxed mice with constitutive Cre-deleter animals confirmed embryonic lethality among offspring. Crossing with CamK2a-CreERT2 mice and injecting tamoxifen for conditional deletion achieved chimeric ATXN2L absence in CamK2a-positive frontal cortex neurons and reduced spontaneous horizontal movement. Global proteome profiling of frontal cortex homogenate showed ATXN2L levels decreased to 75% and dysregulations enriched in the alternative splicing pathway. Nuclear proteins with Sm domains are critical to performing splicing; therefore, our data suggest that the Like-Sm (Lsm, LsmAD) domains in ATXN2L serve a role in splice regulation, despite their perinuclear location.},
}

Animals
*Alternative Splicing/genetics
Mice
*Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism
*Neurons/metabolism
*Ataxin-2/metabolism/genetics
Cell Death
Mice, Knockout

@article {pmid41090732,
year = {2025},
author = {Brocard, F and Dingu, N},
title = {Calpains at the Crossroads of Spinal Cord Physiology, Plasticity, and Pathology.},
journal = {Cells},
volume = {14},
number = {19},
pages = {},
pmid = {41090732},
issn = {2073-4409},
support = {ANR-24-CE16-1548//Agence National de la recherche/ ; ANR-21-CE17-0060//Agence National de la Recherche/ ; },
mesh = {*Calpain/metabolism ; Humans ; Animals ; *Spinal Cord/pathology/physiopathology/physiology/metabolism ; *Neuronal Plasticity/physiology ; },
abstract = {Calcium-dependent cysteine proteases, known as calpains, emerge as important regulators of spinal cord physiology, plasticity, and pathology. First characterized in the brain, they influence a wide range of processes in the spinal cord, maintaining neuronal homeostasis, shaping both synaptic and intrinsic plasticity, and modulating glial responses. When dysregulated, calpains contribute to the pathophysiology of traumatic and neurodegenerative spinal cord disorders, as well as to their associated motor and sensory complications, including spasticity and neuropathic pain. A recurring feature of these conditions is calpain-mediated proteolysis of ion channels, transporters, and cytoskeletal proteins, which promotes disinhibition and neuronal hyperexcitability. The resultant protein fragments are examined as prospective biomarkers for damage and disease progression. Meanwhile, promising strategies for neuroprotection and functional recovery in the clinic emerge as a result of innovative pharmacological and genetic approaches to modulate calpain activity. In this review, we present the current state of knowledge regarding the functions and regulation of calpains in the spinal cord and assess their translational potential as both therapeutic targets and effectors in spinal cord disorders.},
}

*Calpain/metabolism
Humans
Animals
*Spinal Cord/pathology/physiopathology/physiology/metabolism
*Neuronal Plasticity/physiology

@article {pmid41090725,
year = {2025},
author = {Vishnumukkala, T and Che Mohd Nassir, CMN and Hein, ZM and Kalerammana Gopalakrishna, P and Karikalan, B and Alkatiri, A and Jagadeesan, S and Naik, VR and Thomas, W and Mohd Moklas, MA and Kamaruzzaman, MA},
title = {Glial Cells as Emerging Therapeutic Targets in Neurodegenerative Diseases: Mechanistic Insights and Translational Perspectives.},
journal = {Cells},
volume = {14},
number = {19},
pages = {},
pmid = {41090725},
issn = {2073-4409},
mesh = {Humans ; *Neurodegenerative Diseases/therapy/pathology ; *Neuroglia/metabolism/pathology/drug effects ; Animals ; *Translational Research, Biomedical ; Biomarkers/metabolism ; },
abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis share converging mechanisms of neuronal dysfunction, including protein aggregation, oxidative stress, and chronic neuroinflammation. Glial cells, once considered passive supporters, are now recognized as central drivers of these processes, offering both pathogenic triggers and therapeutic opportunities. Yet, despite compelling preclinical evidence, the translation of glial-targeted therapies into clinical success has been limited. This review provides a critical synthesis of current knowledge by examining therapeutic strategies through the lens of their translational challenges and failures. This narrative review highlights how interspecies variability of glial phenotypes, shifting neuroprotective versus neurotoxic states, limited biomarker stratification, and delivery barriers have constrained trials, such as anti-triggering receptor expressed on myeloid cells 2 (anti-TREM2) antibodies in AD and glial cell line-derived neurotrophic factor (GDNF) in PD. By analyzing these obstacles across major neurodegenerative disorders, this review argue that the next stage of glial medicine requires precision approaches that integrate stage-specific phenotyping, biomarker-guided patient selection, and innovative delivery platforms. Understanding not only what has been tried but why translation has stalled is essential to chart a roadmap for effective, disease-modifying glial therapies in the aging brain.},
}

Humans
*Neurodegenerative Diseases/therapy/pathology
*Neuroglia/metabolism/pathology/drug effects
Animals
*Translational Research, Biomedical
Biomarkers/metabolism

@article {pmid41090678,
year = {2025},
author = {Jing, W and Shan, Y and Wu, H and Li, T and Tang, H and Sun, Y and Napattharin, V and Loong, S and Qin, B and Pan, W},
title = {Integrative treatment of the motor neuron disease amyotrophic lateral sclerosis, efficacy of pharmacotherapy, traditional Chinese medicine and importance of respiratory support, life-style, and gastrostomy-assisted nutrition: A review.},
journal = {International journal of clinical pharmacology and therapeutics},
volume = {63 (Suppl. 1)},
number = {},
pages = {S14-S25},
pmid = {41090678},
issn = {0946-1965},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/etiology/physiopathology ; *Gastrostomy ; *Medicine, Chinese Traditional ; *Life Style ; *Integrative Medicine/methods ; Treatment Outcome ; },
abstract = {Currently, there are no effective treatments for amyotrophic lateral sclerosis (ALS), a chronic progressive neurodegenerative disease. Although the etiology of ALS is unknown, it is thought that factors such as diet, the environment, and lifestyle habits play a role. The pathogenesis of ALS includes alterations in glutamate neurotransmission, oxidative stress, mitochondrial dysfunction. Drugs such as riluzole, edaravone, dextromethorphan/quinidine combinations, and the administration of tofersen by injection are approved treatment options for ALS although a number of other agents are being examined in clinical trials. Despite these developments, the availability of effective treatment options is limited. This review summarizes the etiology and pathogenesis of ALS and describes treatments in detail as an integrative medicine approach and including traditional Chinese medicine together with the importance of the timing for interventions, precautions necessary for noninvasive ventilator and gastrostomy surgery, and precautions for dealing with respiratory issues with the overall aim of providing state-of-the-art clinical recommendations for the care and therapy of ALS patients.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/etiology/physiopathology
*Gastrostomy
*Medicine, Chinese Traditional
*Life Style
*Integrative Medicine/methods
Treatment Outcome

@article {pmid41089020,
year = {2025},
author = {Ma, G and You, S},
title = {Predictive Validity and Cutoff Scores of the Revised Suicide Crisis Inventory in Korean Adults: A One-Year Follow-Up Study.},
journal = {Psychiatry investigation},
volume = {},
number = {},
pages = {},
doi = {10.30773/pi.2025.0109},
pmid = {41089020},
issn = {1738-3684},
abstract = {OBJECTIVE: This study aimed to examine the predictive validity of the revised Suicide Crisis Inventory (SCI-2) and determine its optimal cutoff score.

METHODS: Data from 662 community adults participating in a one-year follow-up study were analyzed. Receiver operating characteristic analysis was conducted to examine whether the SCI-2 could predict suicide attempts and ideation with intent at the follow-up and to determine the optimal cutoff score for identifying individuals at high risk for suicide.

RESULTS: The SCI-2 demonstrated adequate predictive validity for suicide attempts and ideation with intent at the one-year follow-up. Based on Youden's index and Runeson et al.'s criteria, a cutoff score of 102 was proposed as the threshold for high-risk groups.

CONCLUSION: The SCI-2, a measure of Suicide Crisis Syndrome, demonstrated predictive validity using longitudinal data. It is effective in identifying high-risk individuals in a community population. These findings highlight the SCI-2 as a valuable tool for early suicide risk detection and prevention.},
}

@article {pmid41088992,
year = {2025},
author = {Essa, SM and Khosa, NA and Kakar, A and Öztürk, B and Ibrahim, IA and Haq, N},
title = {Unraveling the Potential of Stem Cell Therapy in Motor Neuron Disease: A Narrative Review.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273382519250918103218},
pmid = {41088992},
issn = {1996-3181},
abstract = {Motor neuron disorders (MNDs), including ALS, are deadly neurodegenerative conditions that cause progressive motor neuron degeneration. With neuroprotection and the potential for neuron regeneration employing MSCs, ESCs, iPSCs, and NSCs, stem cell treatment presents a viable alternative to current medicines, which only control a limited number of symptoms. Following PRISMA criteria, this narrative review methodically screened 1248 records from the Cochrane, Web of Science, PubMed, and Scopus databases. Following a thorough screening process, 22 studies, including preclinical models and 19 clinical trials, were analysed to assess the therapeutic mechanisms, safety, and efficacy of stem cell therapies for MNDs. Mesenchymal stem cell (MSC) therapy has shown a promising safety profile and possible therapeutic efficacy in ALS, with no substantial transplant-related toxicity noted. ALS functional rating scale-revised (ALSFRS-R) scores and forced vital capacity (FVC) assessments from clinical trials, such as those evaluating autologous bone marrow-derived MSCs, demonstrated stabilisation in ALS development. Studies have also emphasised as to how immunomodulation and neurotrophic factors play a part in MSC-based therapies. Recent data indicate that repeated intrathecal MSC injection could extend the duration of therapeutic advantages. Clinical trials have shown safety and early efficacy signals for motor neurons produced from embryonic stem cells (ESCs), especially using AstroRx®. This suggests that ESCs could be a viable option for regenerative medicine. Nonetheless, issues, like host integration and differentiation optimisation, still exist. Although clinical translation is still in its early stages, induced pluripotent stem cells (iPSCs) and their derivatives provide disease modelling and patient-specific therapeutic applications. Stem cell therapy holds promise for treating MND, with MSCs leading the way in current trials. It is necessary to enhance ESC- and iPSC-based techniques to tackle integration issues. To ensure long-term safety and efficacy, therapies must be developed using standardised protocols, patient stratification, optimised delivery, and large-scale studies.},
}

@article {pmid41088409,
year = {2025},
author = {Ward, EL and Benowitz, L and Brunner, TM and Bu, G and Cayouette, M and Canto-Soler, V and Dá Mesquita, S and Di Polo, A and DiAntonio, A and Duan, X and Goldberg, JL and He, Z and Hu, Y and Liddelow, SA and La Torre, A and Margeta, M and Quintana, F and Shekhar, K and Stevens, B and Temple, S and Venkatesh, H and Welsbie, D and Flanagan, JG},
title = {Modeling neurodegeneration in the retina and strategies for developing pan-neurodegenerative therapies.},
journal = {Molecular neurodegeneration},
volume = {20},
number = {1},
pages = {108},
pmid = {41088409},
issn = {1750-1326},
mesh = {Humans ; *Neurodegenerative Diseases/therapy/pathology ; Animals ; *Glaucoma/therapy ; Disease Models, Animal ; *Retina/pathology ; },
abstract = {BACKGROUND: Glaucoma Research Foundation's third Catalyst for a Cure team (CFC3) was established in 2019 to uncover new therapies for glaucoma, a leading cause of blindness. In the 2021 meeting "Solving Neurodegeneration," (detailed in Mol Neurodegeneration 17(1), 2022) the team examined the failures of investigational monotherapies, issues with translatability, and other significant challenges faced when working with neurodegenerative disease models. They emphasized the need for novel, humanized models and proposed identifying commonalities across neurodegenerative diseases to support the creation of pan-neurodegenerative disease therapies. Since then, the fourth Catalyst for a Cure team (CFC4) was formed to explore commonalities between glaucoma and other neurodegenerative diseases. This review summarizes outcomes from the 2023 "Solving Neurodegeneration 2" meeting, a forum for CFC3 and CFC4 to share updates, problem solve, plan future research collaborations, and identify areas of unmet need or opportunity in glaucoma and the broader field of neurodegenerative disease research.

MAIN BODY: We summarize the recent progress in the field of neurodegenerative disease research and present the newest challenges and opportunities moving forward. While translatability and disease complexity continue to pose major challenges, important progress has been made in identifying neuroprotective targets and understanding neuron-glia-vascular cell interactions. New challenges involve improving our understanding of the disease microenvironment and timeline, identifying the optimal approach(es) to neuronal replacement, and finding the best drug combinations and synergies for neuroprotection. We propose solutions to common research questions, provide prescriptive recommendations for future studies, and detail methodologies, strategies, and approaches for addressing major challenges at the forefront of neurodegenerative disease research.

CONCLUSIONS: This review is intended to serve as a research framework, offering recommendations and approaches to validating neuroprotective targets, investigating rare cell types, performing cell-specific functional characterizations, leveraging novel adaptations of scRNAseq, and performing single-cell sorting and sequencing across neurodegenerative diseases and disease models. We focus on modeling neurodegeneration using glaucoma and other neurodegenerative pathologies to investigate the temporal and spatial dynamics of neurodegenerative disease pathogenesis, suggesting researchers aim to identify pan-neurodegenerative drug targets and drug combinations leverageable across neurodegenerative diseases.},
}

Humans
*Neurodegenerative Diseases/therapy/pathology
Animals
*Glaucoma/therapy
Disease Models, Animal
*Retina/pathology

@article {pmid41087751,
year = {2025},
author = {Masrori, P and Bijnens, B and Fumagalli, L and Davie, K and Poovathingal, SK and Meese, T and Storm, A and Hersmus, N and Fazal, R and van den Biggelaar, D and Asselbergh, B and Gruel, R and Van Den Daele, J and Denton, H and Miquel, PP and Manzella, S and De Vos, WH and Chandran, S and Van Den Bosch, L and Thal, DR and Mancuso, R and Van Damme, P},
title = {C9orf72 hexanucleotide repeat expansions impair microglial response in ALS.},
journal = {Nature neuroscience},
volume = {},
number = {},
pages = {},
pmid = {41087751},
issn = {1546-1726},
support = {11PD824N//Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)/ ; G0F8516N; G065721N//Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)/ ; 20240019//Internationale Stichting Alzheimer Onderzoek (ISAO)/ ; ADP0144//Universiteit Antwerpen (University of Antwerp)/ ; },
abstract = {Microglia and neuroinflammation are involved in amyotrophic lateral sclerosis (ALS), but the precise underlying molecular mechanisms remain elusive. We generated single-nuclei transcriptomes from the spinal cord and motor cortex of patients with sporadic ALS (sALS) and C9orf72 ALS (C9-ALS). Here we confirmed that C9orf72 is highly expressed in microglia and observed that the hexanucleotide repeat expansion (HRE) results in haploinsufficiency. Whereas sALS microglia transitioned toward disease-associated cell states, C9orf72 HRE microglia exhibited a diminished response, with alterations in endolysosomal pathways. We confirmed these observations using a human microglia xenograft model, in which C9orf72 mutations led to a reduced activation. We also confirmed the endolysosomal alterations in C9orf72 HRE and C9orf72-deficient induced pluripotent stem cell (iPSC)-derived microglia. We also found a diminished response of C9orf72 HRE astrocytes and provided a map of dysregulated ligand-receptor pairs in microglia and astrocytes. Our data highlight variations in the cellular substrate of sporadic and inherited forms of ALS, which have implications for patient stratification and selection of appropriate treatments.},
}

@article {pmid41087573,
year = {2025},
author = {Rutkove, SB and Shah, P and Hevenor, L and Tiwari, G and Patil, D and Mourey, T and Nagy, JA and Nath, AK},
title = {Surface electrical impedance myography detects disease in an adult-onset SOD1-G93A zebrafish model of amyotrophic lateral sclerosis.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {35810},
pmid = {41087573},
issn = {2045-2322},
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/physiopathology/pathology ; Zebrafish ; Disease Models, Animal ; Electric Impedance ; *Superoxide Dismutase-1/genetics ; Motor Neurons/pathology/metabolism ; *Myography/methods ; Muscle, Skeletal/pathology/physiopathology ; Humans ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that is characterized by loss of motor neurons and atrophy of skeletal muscle. Current FDA-approved drugs to treat ALS are only modestly effective at slowing the progression of the disease. Rodents have been the standard preclinical animal model for testing candidate ALS drugs; however, alternative animal models, including zebrafish, are being studied to accelerate therapeutic discovery. Here, we sought to advance a model of ALS in zebrafish with associated tools to serve as biomarkers of neuromuscular deterioration. Thus, we applied noninvasive, surface electrical impedance myography (EIM) methodology to SOD1[G93A] zebrafish and control animals to evaluate its ability to serve as an electrophysiological biomarker of disease in ALS zebrafish. Measurements were acquired from the caudal musculature of animals at 2 time points by applying an alternating current at 41 frequencies (1 kHz-1 MHz) and measuring the resulting voltages. At the first time point, SOD1[G93A] animals still exhibited normal body morphometrics, spinal cord motor neuron numbers, and skeletal muscle mass, while at the second time point, these SOD1[G93A] animals exhibited reduced weight, loss of motor neurons, type 1 and 2 myofiber atrophy, and decreased capacity for endurance swimming. We found that non-invasive surface EIM detected the alterations observed in diseased ALS zebrafish at the second time point. Specifically, EIM measurements (phase angle, reactance, and resistance) at 2 and 50 kHz were robust metrics that distinguished between healthy and diseased zebrafish. To assess the reliability of our EIM technique in healthy and ALS zebrafish, we calculated the intraclass correlation coefficient and conducted Bland-Altman analyses. The EIM methodology exhibited excellent reproducibility in both healthy and ALS zebrafish. In sum, these findings demonstrate that EIM is an effective tool to detect neuromuscular disease in symptomatic adult ALS zebrafish, and the approach described here offers a fast, noninvasive, and reliable platform that holds the potential to test candidate drug therapeutic efficacy.},
}

Animals
*Amyotrophic Lateral Sclerosis/diagnosis/genetics/physiopathology/pathology
Zebrafish
Disease Models, Animal
Electric Impedance
*Superoxide Dismutase-1/genetics
Motor Neurons/pathology/metabolism
*Myography/methods
Muscle, Skeletal/pathology/physiopathology
Humans

@article {pmid41087397,
year = {2025},
author = {Schilling, MA},
title = {The geographic association of multiple sclerosis and amyotrophic lateral sclerosis.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {34665},
pmid = {41087397},
issn = {2045-2322},
mesh = {*Amyotrophic Lateral Sclerosis/epidemiology/mortality ; Humans ; *Multiple Sclerosis/epidemiology/mortality ; Male ; Female ; Geography ; Middle Aged ; },
abstract = {Amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) are both devastating, incurable, neurodegenerative diseases that are largely considered to be of unknown etiology. While the diseases have some similarities, they are not typically considered to be closely related. They have different pathological markers and different prognoses. Additionally, MS (but not ALS) is considered an autoimmune disease. Furthermore, MS has long been noted to have a strong north-south gradient in its distribution whereas only recently has awareness grown of such a gradient in ALS. The study here will show, however, that if the distribution of ALS and MS are analyzed using mortality data, they are extremely correlated even after controlling for gender, race and latitude. This relationship was not previously identified in part because of a Simpson's paradox in the data: strong correlations that are obvious in the data when they are separated by gender are obscured when the data are pooled across gender. The presence of a strong association in the distributions of ALS and MS suggests there is a connection between the two diseases that is not yet understood. That connection may prove valuable in helping to illuminate what causes the diseases, and whether and how they can be prevented and treated.},
}

*Amyotrophic Lateral Sclerosis/epidemiology/mortality
Humans
*Multiple Sclerosis/epidemiology/mortality
Male
Female
Geography
Middle Aged

@article {pmid41086149,
year = {2025},
author = {Clackson, O and Hamid, MR and Wijesekera, A and Kulick, D and O'Neil, AL},
title = {Exposure to the organochlorine pesticide cis-chlordane induces ALS-like mitochondrial perturbations in stem cell-derived motor neurons.},
journal = {PloS one},
volume = {20},
number = {10},
pages = {e0332422},
pmid = {41086149},
issn = {1932-6203},
mesh = {*Motor Neurons/drug effects/metabolism/pathology ; *Amyotrophic Lateral Sclerosis/pathology/metabolism/chemically induced ; *Mitochondria/drug effects/metabolism/pathology ; Humans ; Reactive Oxygen Species/metabolism ; *Pesticides/toxicity ; *Chlordan/toxicity ; Membrane Potential, Mitochondrial/drug effects ; Animals ; Adenosine Triphosphate/metabolism ; Oxygen Consumption/drug effects ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a debilitating and incurable neurodegenerative disease with unsolved etiology. Due to the large proportion of patients lacking direct disease inheritance, understanding the environmental factors that contribute to ALS development is of high priority. Epidemiological studies have implicated pesticides and other environmental exposures as possible contributors to ALS pathogenesis. Recently, our group determined that the organochlorine pesticide cis-chlordane is toxic to human motor neurons in a dose-dependent manner, causing an ALS-like phenotype in culture and animals with a mode of action independent of its known GABAA antagonism. Here, we aimed to characterize downstream motor neuron phenotypes associated with cis-chlordane treatment. We performed bulk RNA sequencing, live imaging, immunofluorescent labeling, and real-time metabolic assays on stem cell-derived motor neurons to assess chlordane-associated phenotypes in vitro. We demonstrate that cis-chlordane treatment causes a highly altered mitochondrial phenotype in motor neurons, including increased production of reactive oxygen species, decreased oxygen consumption rate and ATP production, and loss of mitochondrial membrane potential. We further implicate cis-chlordane as a possible mediator of potent motor neuron damage, with exposure to the pesticide inducing mitochondrial phenotypes akin to those seen in ALS. Our findings contribute to the growing body of evidence that future studies of investigating the role of pesticides in ALS development should focus on organochlorine molecules.},
}

*Motor Neurons/drug effects/metabolism/pathology
*Amyotrophic Lateral Sclerosis/pathology/metabolism/chemically induced
*Mitochondria/drug effects/metabolism/pathology
Humans
Reactive Oxygen Species/metabolism
*Pesticides/toxicity
*Chlordan/toxicity
Membrane Potential, Mitochondrial/drug effects
Animals
Adenosine Triphosphate/metabolism
Oxygen Consumption/drug effects

@article {pmid41085218,
year = {2025},
author = {Anzilotti, S and De Iesu, N and Gargiulo, S and Di Muraglia, N and Cicatiello, AG and Dentice, M and Panico, M and Albanese, S and Annunziato, L and Salvatore, M and Pignataro, G and Pappatà, S},
title = {TSPO Expression and [18F]DPA-714 PET/CT Imaging as Pathogenetic and Diagnostic Biomarkers in Symptomatic Stages of Skeletal Muscle Fiber Degeneration in SOD1-G93A ALS Mice.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {39},
number = {20},
pages = {e71129},
pmid = {41085218},
issn = {1530-6860},
support = {CUPE63C22002170007//PNRR, Spoke 3, MNESYS, PE00000006, M4 C2 I 1.3, finanziato dall'Unione Europea-NextGenerationEU, (to G.P.)/ ; CUPB63D22000600006//PNRR, Spoke 7, MNESYS, PE00000006, M4 C2 I 1.3, finanziato dall'Unione Europea-NextGenerationEU, (to L.A. and N.D.I.)/ ; HEALTHF22011278850FP7/2007-2013//European Union's Seventh Framework Program INMiND, (to S.P.)/ ; //Italian Ministry of Health (Ricerca Corrente Project)/ ; },
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/diagnostic imaging/pathology/genetics ; Mice ; *Positron Emission Tomography Computed Tomography/methods ; *Receptors, GABA/metabolism/genetics ; Mice, Transgenic ; *Pyrazoles ; *Pyrimidines ; Biomarkers/metabolism ; *Superoxide Dismutase-1/genetics/metabolism ; *Muscle Fibers, Skeletal/metabolism/pathology ; Fluorine Radioisotopes ; Muscle, Skeletal/metabolism/pathology ; Male ; Humans ; },
abstract = {Emerging evidence highlights the involvement of skeletal muscle in the pathogenesis of amyotrophic lateral sclerosis (ALS), through mechanisms involving inflammation and mitochondrial dysfunction in skeletal muscle fibers. The 18 kDa translocator protein (TSPO) is primarily expressed on the outer mitochondrial membrane, is implicated in inflammation, and serves as both a biomarker and a therapeutic target for neuroinflammation. This study investigated whether PET imaging targeting the TSPO, immunohistochemistry, and confocal microscopy can characterize skeletal muscle inflammation and muscular fiber damage in SOD1-G93A ALS transgenic mice. High-resolution PET/CT imaging with [18F]DPA-714 was employed to assess TSPO expression in the triceps brachii of SOD1-G93A mice at mild (age range: 98-112 days; Clinical Score (CS) range:1-1.5) and moderate-severe (age range: 120-137 days; CS range: 2-4) symptomatic stages. To support PET data, TSPO was analyzed by immunohistochemistry and confocal microscopy in the triceps skeletal muscle obtained from mild and moderate-severe SOD1-G93A mice. Inflammatory and anti-inflammatory macrophage cells in skeletal muscle tissues were detected by immunofluorescence. PET/CT revealed a progressive, significant increase of [18F]DPA-714 uptake in SOD1-G93A triceps brachii in mild and moderate-severe stages. Immunohistochemistry and confocal microscopy confirmed increased TSPO expression in the degenerating muscle fibers and in infiltrating macrophage cells. In vivo studies of TSPO expression in ALS-affected skeletal muscles may provide valuable insights into muscle inflammation and mitochondrial involvement during disease progression. In addition, TSPO and PET/CT imaging with [18F]DPA-714 might represent a noninvasive and promising diagnostic biomarker for detecting early muscle pathology in ALS.},
}

Animals
*Amyotrophic Lateral Sclerosis/metabolism/diagnostic imaging/pathology/genetics
Mice
*Positron Emission Tomography Computed Tomography/methods
*Receptors, GABA/metabolism/genetics
Mice, Transgenic
*Pyrazoles
*Pyrimidines
Biomarkers/metabolism
*Superoxide Dismutase-1/genetics/metabolism
*Muscle Fibers, Skeletal/metabolism/pathology
Fluorine Radioisotopes
Muscle, Skeletal/metabolism/pathology
Male
Humans

@article {pmid41085196,
year = {2025},
author = {Lee, J and Kwon, I},
title = {Phase Separation of TAF15 C-Terminal LC Domain Enables RNA-Binding Protein-Mediated Transcriptional Regulation.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {39},
number = {20},
pages = {e71126},
pmid = {41085196},
issn = {1530-6860},
support = {RS-2022-NR075088//National Research Foundation of Korea (NRF)/ ; RS-2024-00336294//National Research Foundation of Korea (NRF)/ ; },
mesh = {*TATA-Binding Protein Associated Factors/metabolism/genetics/chemistry ; Humans ; RNA-Binding Protein FUS/metabolism/genetics ; Protein Domains ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; *RNA-Binding Proteins/metabolism/genetics ; *Transcription, Genetic ; Mutation ; HEK293 Cells ; *Gene Expression Regulation ; Transcriptional Activation ; Protein Binding ; Phase Separation ; },
abstract = {TAF15 is an RNA/ssDNA-binding protein and transcriptional activator implicated in diseases such as cancer and ALS. Its C-terminal low-complexity (LC) domain harbors most ALS-associated mutations, suggesting a crucial role in disease mechanisms. Here, we demonstrate that this LC domain mediates dynamic interactions with the RNA-binding protein hnRNPA0, which enhances the transcriptional activity of TAF15. Domain-swapping experiments with the related protein FUS show that the C-terminal LC domain of TAF15 is both necessary and sufficient for hnRNPA0 responsiveness. Phosphomimic mutations in the C-terminal LC domain disrupt this interaction and diminish hnRNPA0-mediated transcriptional activation. hnRNPA0 contains the RNA recognition motif and LC domain, both of which are required for hnRNPA0 to promote transcription. Furthermore, ALS-linked mutations in TAF15 impair its ability to undergo phase separation, reduce binding to hnRNPA0, and eliminate transcriptional enhancement. These findings suggest that TAF15's C-terminal LC domain connects hnRNPA0 to transcriptional regulation, and that this mechanism is disrupted in ALS-associated mutations.},
}

*TATA-Binding Protein Associated Factors/metabolism/genetics/chemistry
Humans
RNA-Binding Protein FUS/metabolism/genetics
Protein Domains
Amyotrophic Lateral Sclerosis/genetics/metabolism
*RNA-Binding Proteins/metabolism/genetics
*Transcription, Genetic
Mutation
HEK293 Cells
*Gene Expression Regulation
Transcriptional Activation
Protein Binding
Phase Separation

@article {pmid41084991,
year = {2025},
author = {Vasta, R and Callegaro, S and Canosa, A and Manera, U and Grassano, M and Palumbo, F and Cabras, S and Matteoni, E and Di Pede, F and De Mattei, F and Tafaro, S and Thakur, NM and Grosenick, R and De Marchi, F and Mazzini, L and Moglia, C and Calvo, A and Dave, KD and Chiò, A},
title = {Amyotrophic Lateral Sclerosis Prevalence Projection in 2040: A Less Rare Disease.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.70226},
pmid = {41084991},
issn = {2328-9503},
support = {24-SI-684//ALS Association/ ; },
abstract = {OBJECTIVE: To project ALS prevalence across multiple countries through 2040, accounting for both population aging and increased survival.

METHODS: Data from the Piemonte and Valle d'Aosta ALS register (PARALS) was used to estimate the trends in incidence and prevalence from 2005 to 2019. Survival trends over this period were also assessed. The observed annual increase was then projected into future years up to 2040. Concurrently, the incidence for each future year was calculated using population projections. Finally, the prevalence rate for each year was estimated as the product of the projected incidence and the projected survival. We also estimated survival for fifteen countries by dividing prevalence by incidence, based on available data, and applied the same increase observed in PARALS to project prevalence in these countries up to 2040.

RESULTS: Using data from 3294 patients, we determined that ALS survival increased by 0.06 years annually from 2005 to 2019 in Piemonte and Valle d'Aosta. Considering changes in incidence due to population aging, the prevalence is projected to reach 15.72 per 100,000 population by 2040 in this area, while rising by a median of 24.9% across multiple countries worldwide. If a new drug could provide a 6-month increase in survival starting in 2025, disease prevalence would rise by 37.8% by 2040. We provided a web interface so users can model different data and assumptions.

INTERPRETATION: ALS prevalence is projected to increase significantly over the next decades. This underscores the need for careful planning and allocation of public health resources.},
}

@article {pmid41084041,
year = {2025},
author = {Hassan, YM and Wanas, A and Ali, AA and El-Sayed, WM},
title = {Integrating artificial intelligence with nanodiagnostics for early detection and precision management of neurodegenerative diseases.},
journal = {Journal of nanobiotechnology},
volume = {23},
number = {1},
pages = {668},
pmid = {41084041},
issn = {1477-3155},
abstract = {BACKGROUND: Neurodegenerative diseases—including Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis (ALS)—as well as autoimmune disorders with neurodegenerative features such as multiple sclerosis (MS), present an escalating global challenge. Current diagnostics often detect pathology too late, and most treatments focus on symptom relief rather than disease modification. There is an urgent need for tools that enable early detection and precision-targeted intervention.

MAIN BODY: Nanotechnology offers unique advantages in this space, enabling early molecular detection, targeted drug delivery, and theranostic systems. Engineered nanocarriers, biosensors, and responsive nanodevices are being tailored to disease-specific features such as oxidative stress in AD or neuroinflammation in MS. Yet, issues like biocompatibility, clinical scalability, and long-term safety remain barriers to translation. Artificial intelligence (AI) enhances nanomedicine by improving biomarker sensitivity, stratifying patients, and enabling predictive disease modeling. From AI-guided nanoparticle design to closed-loop delivery systems and digital twin models, these technologies work synergistically to support real-time, personalized care. Still, critical challenges—including algorithmic bias, lack of explainability, heterogeneous datasets, and limited regulatory clarity—impede clinical integration. Additionally, high system complexity and cost risk excluding low-resource settings unless inclusive, scalable alternatives are pursued.

CONCLUSION: The convergence of AI and nanotechnology is reshaping neurodegenerative disease care, moving from reactive to proactive, personalized neurology. Realizing this promise requires cross-sector collaboration, ethical foresight, and translational rigor to ensure these innovations are safe, equitable, and accessible to all patients.

GRAPHICAL ABSTRACT: [Image: see text]},
}