@article {pmid41226260,
year = {2025},
author = {Cutter, LR and Ren, AR and Banerjee, IA},
title = {Advances in Naturally and Synthetically Derived Bioactive Sesquiterpenes and Their Derivatives: Applications in Targeting Cancer and Neurodegenerative Diseases.},
journal = {Molecules (Basel, Switzerland)},
volume = {30},
number = {21},
pages = {},
pmid = {41226260},
issn = {1420-3049},
support = {N/A//Henry Luce Foundation/ ; N/A//Fordham University/ ; },
mesh = {Humans ; *Sesquiterpenes/chemistry/pharmacology/therapeutic use/chemical synthesis ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neoplasms/drug therapy/metabolism ; Animals ; *Biological Products/chemistry/pharmacology/therapeutic use ; *Antineoplastic Agents/pharmacology/chemistry ; Antioxidants/chemistry/pharmacology ; },
abstract = {Sesquiterpenes are a diverse class of natural products that have garnered considerable interest for their potent bioactivity and structural variability. This review highlights advances in the derivatization of various sesquiterpene lactones, quinones, and alcohols, particularly in targeting cancer and neurodegenerative diseases. The structural modifications discussed include the incorporation of triazole, arylidene, or thiol moieties with eudesmane, guaiane, and germacranolide-type sesquiterpenes, among others. In addition, the conjugation with chemotherapeutics, as well as the development of nanoscale therapeutics, is also discussed. Such modifications have expanded the pharmacological potential, enabling improved specificity, cytotoxicity profiles, and sensitization toward tumor cells. Additionally, sesquiterpenes such as parthenolide (20), pterosinsade A (176), and cedrol (186) have demonstrated potential in mitigating neurodegeneration via anti-inflammatory and antioxidant signaling pathway-modulation mechanisms, with potential applications in Alzheimer's, Parkinson's, and ALS diseases. Mechanistic insights into redox signaling modulation, NF-κB inhibition, ROS regulation, and disruption of aggregation underscore their multifaceted modes of action. This review highlights the translational promise of sesquiterpene derivatives as dual-action agents for potential drug development in a plethora of diseases that are caused by inflammation and free-radical damage. It provides a framework for future rational design of multifunctional drug candidates and therapeutics.},
}

Humans
*Sesquiterpenes/chemistry/pharmacology/therapeutic use/chemical synthesis
*Neurodegenerative Diseases/drug therapy/metabolism
*Neoplasms/drug therapy/metabolism
Animals
*Biological Products/chemistry/pharmacology/therapeutic use
*Antineoplastic Agents/pharmacology/chemistry
Antioxidants/chemistry/pharmacology

@article {pmid41225259,
year = {2025},
author = {Ghayal, NB and Crook, RJ and Jain, A and Sachdeva, G and Jiang, P and Roemer, SF and Sekiya, H and DeTure, MA and Baker, MC and De Coster, W and Oskarsson, B and Josephs, KA and Rademakers, R and van Blitterswijk, MM and Dickson, DW},
title = {Expanding the spectrum of annexin A11 proteinopathy in frontotemporal lobar degeneration and motor neuron disease.},
journal = {Acta neuropathologica},
volume = {150},
number = {1},
pages = {52},
pmid = {41225259},
issn = {1432-0533},
support = {P30 AG062677/AG/NIA NIH HHS/United States ; R01-AG037491//Foundation for the National Institutes of Health/ ; UG3 NS103870/NS/NINDS NIH HHS/United States ; G064223N//Fund for Scientific Research Flanders (FWO)/ ; },
mesh = {Humans ; *Frontotemporal Lobar Degeneration/pathology/genetics/metabolism ; *Motor Neuron Disease/pathology/metabolism/genetics ; Male ; Female ; Aged ; Middle Aged ; *Annexins/metabolism/genetics ; DNA-Binding Proteins/metabolism ; Aged, 80 and over ; TDP-43 Proteinopathies/pathology ; Brain/pathology/metabolism ; Amyotrophic Lateral Sclerosis/pathology ; },
abstract = {Aggregation of TAR-DNA-binding protein 43 (TDP-43) is strongly associated with frontotemporal lobar degeneration (FTLD-TDP), motor neuron disease (MND-TDP), and overlap disorders like FTLD-MND. Three major forms of motor neuron disease are recognized and include primary lateral sclerosis (PLS), amyotrophic lateral sclerosis (ALS), and progressive muscular atrophy (PMA). Annexin A11 (ANXA11) is understood to aggregate in amyotrophic lateral sclerosis (ALS-TDP) associated with pathogenic variants in ANXA11, as well as in FTLD-TDP type C. Given these observations and recent reports of ANXA11 variants in patients with semantic variant frontotemporal dementia (svFTD) and FTD-MND presentations, we sought to characterize ANXA11 proteinopathy in an autopsy cohort of 379 cases diagnosed with a primary TDP-43 proteinopathy, including FTLD-TDP, FTLD-MND, and MND-TDP. Cases with FTLD-MND and MND-TDP were classified further into PLS, ALS, and PMA based on the relative loss of upper and lower motor neurons. ANXA11 proteinopathy was present in over 40% of FTLD-MND cases. Further, ANXA11 colocalized with TDP-43 in the pathologic inclusions of all FTLD-TDP type C cases, as well as 38 out of 40 FTLD-PLS cases (95%), of which 84% had TDP type B or an unclassifiable TDP-43 proteinopathy and 16% had TDP type C. Genetic analysis excluded pathogenic ANXA11 variants in all ANXA11-positive cases. We thus demonstrated two novel ANXA11 proteinopathies strongly associated with FTLD-PLS, but not with TDP type C or pathogenic ANXA11 variants. Given the emerging relationship between TDP-43 and ANXA11 in neurodegenerative disease, we propose that TDP-43 and ANXA11 proteinopathy (TAP) comprises a distinct group of molecular pathologies and define three TAP types based on key clinical and neuropathologic characteristics.},
}

Humans
*Frontotemporal Lobar Degeneration/pathology/genetics/metabolism
*Motor Neuron Disease/pathology/metabolism/genetics
Male
Female
Aged
Middle Aged
*Annexins/metabolism/genetics
DNA-Binding Proteins/metabolism
Aged, 80 and over
TDP-43 Proteinopathies/pathology
Brain/pathology/metabolism
Amyotrophic Lateral Sclerosis/pathology

@article {pmid41224659,
year = {2025},
author = {Moss, KR and Darvishi, FB and Badawi, Y and Fish, LA and Funke, JR and Pedersen, TH and Robitaille, R and Arnold, WD and Burgess, RW and Meriney, SD and Nishimune, H and Saxena, S},
title = {The Neuromuscular Junction: A Shared Vulnerability in Aging and Disease.},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume = {45},
number = {46},
pages = {},
doi = {10.1523/JNEUROSCI.1353-25.2025},
pmid = {41224659},
issn = {1529-2401},
mesh = {Humans ; *Neuromuscular Junction/pathology/physiopathology/physiology ; *Aging/pathology/physiology ; Animals ; *Neuromuscular Diseases/physiopathology/pathology ; Schwann Cells ; },
abstract = {The neuromuscular junction (NMJ) is a specialized synapse essential for effective motor neuron-muscle communication and is increasingly recognized as a vulnerable site in aging and neuromuscular disease. While traditionally considered a final common pathway for motor deficits, accumulating evidence demonstrates that NMJ dysfunction is an early and critical driver of disease onset and progression in conditions such as amyotrophic lateral sclerosis and Charcot-Marie-Tooth disease. This review highlights shared and disease-specific mechanisms contributing to NMJ impairment, including presynaptic, postsynaptic, and perisynaptic Schwann cell defects in these diseases. We also discuss age-related changes at the NMJ, emphasizing its role in sarcopenia and muscle weakness in older adults. Furthermore, we explore emerging molecular drivers of NMJ dysfunction uncovered through studies in congenital myasthenic syndromes, autoimmune disorders, and advanced omics approaches. By integrating insights across diseases and aging, we underscore the potential for shared therapeutic strategies aimed at stabilizing NMJ function. Promising interventions targeting presynaptic neurotransmitter release, postsynaptic excitability, and perisynaptic Schwann cells are discussed as avenues to improve neuromuscular transmission and maintain muscle strength. Finally, we discuss the challenges and opportunities in translating these mechanistic insights into clinical therapies and highlight how novel human neuromuscular organoid models and advanced molecular profiling can bridge this gap. Together, these insights establish the NMJ as a critical, modifiable target for preserving motor function across neuromuscular diseases and aging.},
}

Humans
*Neuromuscular Junction/pathology/physiopathology/physiology
*Aging/pathology/physiology
Animals
*Neuromuscular Diseases/physiopathology/pathology
Schwann Cells

@article {pmid41224274,
year = {2025},
author = {Takubo, M and Matsumoto, Y and Sasaki, C and Ikeda, K and Sugeno, N and Warita, H and Aoki, M},
title = {Spinocerebellar Ataxia Type 3 Accompanied by Amyotrophic Lateral Sclerosis: A Case Report and Comprehensive Literature Review.},
journal = {Internal medicine (Tokyo, Japan)},
volume = {},
number = {},
pages = {},
doi = {10.2169/internalmedicine.6369-25},
pmid = {41224274},
issn = {1349-7235},
abstract = {Spinocerebellar ataxia type 3 (SCA3) is a hereditary neurodegenerative disorder characterized by cerebellar ataxia, whereas amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease. We herein report a 62-year-old man with genetically confirmed SCA3 who subsequently developed rapidly progressive asymmetric muscle weakness, atrophy, and fasciculations. Clinical features, including preserved tendon reflexes and widespread denervation observed on electromyography, support the diagnosis of concomitant sporadic ALS. Our literature review revealed only a few similar cases, suggesting the under-recognition of this rare combination. This case underscores the importance of considering coexisting ALS in patients with SCA3 to enable a timely diagnosis and management.},
}

@article {pmid41224202,
year = {2025},
author = {Metelmann, M and Heyne, S and Peuker, M and Claßen, J and Mehnert-Theuerkauf, A and Esser, P},
title = {[Experiences with the Application of Short-Term Psychotherapy in Patients with Amyotrophic Lateral Sclerosis: What Can We Learn from It?].},
journal = {Psychotherapie, Psychosomatik, medizinische Psychologie},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2711-2085},
pmid = {41224202},
issn = {1439-1058},
abstract = {Amyotrophic lateral sclerosis (ALS) is associated with elevated distress, but evidence on psychosocial interventions is limited. We tested the feasibility of a psychotherapy for palliative cancer patients in ALS patients.We applied CALM (Managing Cancer and Living Meaningfully), an effective psychodynamic short-term therapy for advanced cancer patients, within a pre-post study among patients with ALS. We provided patient flow and formal treatment information. Based on the treatment protocols, the therapist reflected on the applicability of the treatment structure, specifics in the psychosocial work with ALS patients and suggestions for treatment modification.Among 15 eligible patients, five participated. Three patients completed the treatment, two patients provided complete study data. The trial was prematurely stopped due to issues in feasibility. Six (22%) sessions were conducted via telephone, 10 (37%) were attended by family caregivers. The structure showed limited applicability largely because fear-laden topics including suffering and death were extensively avoided. Compared to palliative cancer patients, ALS patients fluctuated more strongly in their psychological and physical symptom burden and were more strongly distressed by disease-related practical issues. Recommendations included a multi-professional team, booster sessions and a direct support for caregivers.A psychotherapy effective for cancer patients showed features that limit its applicability among ALS patients. Some of these limitations are treatment-inherent and thus hard to adapt. Rather than modifying the program, we suggest to develop a specific supportive psychotherapeutic intervention within a participatory approach.},
}

@article {pmid41223995,
year = {2025},
author = {Michelerio, A and Tomasini, C and Brazzelli, V},
title = {Response to Gronbeck et al.'s "Dermatologic toxicities of antibody-drug conjugates": why ado-trastuzumab emtansine-associated telangiectasias deserve clinical attention.},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.11.008},
pmid = {41223995},
issn = {1097-6787},
}

@article {pmid41223829,
year = {2025},
author = {Patil, N and Mirveis, Z and Byrne, HJ},
title = {Exploration of multivariate curve resolution- alternating least squares (MCR-ALS) for datamining kinetically evolving complex cellular spectroscopic data (Spectralomics).},
journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy},
volume = {348},
number = {Pt 2},
pages = {127156},
doi = {10.1016/j.saa.2025.127156},
pmid = {41223829},
issn = {1873-3557},
abstract = {Multivariate curve resolution- alternating least squares (MCR-ALS) approach for datamining the complex spectral fingerprints from kinetically evolving cellular Raman spectroscopy data was explored in this study. Principal components analysis and partial least squares- discriminant analysis indicated the metabolic changes were captured in individual metabolic conditions (Control, Stimulation and Inhibition) as a function of time; however, MCR-ALS could not resolve the spectral components accurately. Hence simulated datasets were generated to test the limit of resolution which revealed the significance of initial estimation of spectral components in the MCR, and the effect of equality constraints in the ALS was studied. The resolved rate constants for the time evolution of the components were not quantitatively accurate at higher cellular background overlayed on the evolving components, although they did exhibit a consistent qualitative trend across the modulated conditions. Hence, the cellular data was analysed qualitatively, and the initial estimates constraint in MCR along with a kinetic hard model constraint in ALS was deduced to be the best strategy for datamining complex cellular spectra. The spectral fingerprints of both glycolytic and non-glycolytic cellular processes were resolved in all the modulated conditions, highlighting the high-content insights from the label-free approach. The study demonstrates the potential of Raman spectroscopy coupled with a spectralomics approach for datamining of the complex spectral fingerprints as a function of time and highlights its limitations. This approach could potentially find applications in high-content drug screening, drug discovery, disease diagnostics and process analytical techniques for monitoring bioprocesses.},
}

@article {pmid41223590,
year = {2025},
author = {Elmansy, MF and Soares, P and Dos Remedios, JRD and Nowar, R and Fox, SG and Yu, A and Klein, WL and Morimoto, RI and Silverman, RB},
title = {Modifications of NU-9, a potent protein aggregation inhibitor. Properties and activity in a cellular model of amyotrophic lateral sclerosis.},
journal = {Bioorganic chemistry},
volume = {167},
number = {},
pages = {109190},
doi = {10.1016/j.bioorg.2025.109190},
pmid = {41223590},
issn = {1090-2120},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fast-progressing disease characterized by the loss of voluntary movements and death due to respiratory failure. The presence of protein aggregates is a major hallmark of the disease. Hence, targeting the pathological protein aggregation may provide more efficient therapeutics for ALS. Recently, we reported a cyclohexane-1,3-dione (NU-9) with in vitro anti-aggregation capacity and promising in vivo efficacy in ALS animal models, which validated our approach toward the development of novel and potentially more effective ALS therapeutics. Herein, we report the design and synthesis of a new series of small-molecule derivatives of NU-9 and the evaluation of their in vitro anti-aggregation activity in a PC12 cellular model containing an SOD1[G85R] familial ALS mutation. The most promising compound (20) presented an in vitro anti-aggregation potency comparable to that of NU-9. Moreover, the better in vitro BBB permeability, microsomal stability, and toxicity profile of 20 also suggests a potentially higher efficacy in vivo.},
}

@article {pmid41222918,
year = {2025},
author = {Feng, J and Jiang, H and Bi, X},
title = {Letter to the editor: re-evaluating perioperative antibiotic strategies in mild-to-moderate acute cholecystitis: addressing unresolved questions from Park et al.'s randomized trial.},
journal = {International journal of surgery (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1097/JS9.0000000000003976},
pmid = {41222918},
issn = {1743-9159},
}

@article {pmid41222589,
year = {2025},
author = {Heyming, T and Knudsen-Robbins, C and Kain, A and Morphew, T and Ta-Perez, Z and Darabpour, A and Lee, H and Brukman, S and Shelton, SK},
title = {Prehospital PAT - Real World Data; EMS Use of the Pediatric Assessment Triangle in the Prehospital Environment.},
journal = {Prehospital emergency care},
volume = {},
number = {},
pages = {1-15},
doi = {10.1080/10903127.2025.2581753},
pmid = {41222589},
issn = {1545-0066},
abstract = {OBJECTIVES: Emergency medical services (EMS) clinicians report lack of training and experience with children, leading to discomfort and uncertainty regarding assessment and treatment. The Pediatric Assessment Triangle (PAT) was designed to provide a rapid and standardized approach. Despite widespread adoption, literature examining EMS implementation of PAT remains limited. We examined EMS use of PAT and assessment of clinical stability, and the association between EMS use of PAT and prehospital interventions, EMS transport decisions (ALS versus BLS), emergency department (ED) interventions, and ED disposition.

METHODS: This was a retrospective cohort study of pediatric patients 0 to <15 years transported to a quaternary care pediatric ED via EMS between October 2022 and November 2023. Data were abstracted from EMS and ED electronic health records (EHRs) including PAT evaluation, demographics, EMS and ED interventions, and ED disposition. Data were analyzed using counts and percentages, logistic regression, chi-square and McNemar's test.

RESULTS: A total of 2,929 patients were included. Most patients, 65.9%, had a PAT score of 0; for those with non-zero PATs, abnormalities in the appearance domain were most prevalent, 50.7%. A PAT score of 1 or higher was associated with transport via Advanced Life Support (OR 67.9; 95% CI 32.0, 144.1) compared to a PAT of 0. Most patients, 62.2%, received an EMS intervention; the most common was diagnostics (blood glucose or EKG). The EMS administered medications to 22% of patients. Pediatric Assessment Triangle scores of ≥2 were associated with double the odds of admission to the floor (OR 2.09; 95% CI 1.4, 3.0) and quadruple the odds of admission to ICU level of care/direct to surgery/expired (OR 4.9; 95% CI 2.9, 8.3); PATs abnormal for work of breathing only were associated with increased odds of admission to the floor (OR 2.5; 95% CI 1.8, 3.6).

CONCLUSIONS: This study suggests that EMS PAT assessment in the field appropriately reflects patient stability and may be associated with EMS intervention en-route. The EMS PAT scores demonstrate promise as an adjunct to ED assessment, alerting clinicians to increased likelihood of admission. The PAT has potential to serve as a practical mechanism for EMS feedback and quality improvement studies.},
}

@article {pmid41222474,
year = {2025},
author = {Bagheri, S and Saboury, AA and Ahmad, O and Khan, RH and Ryszkiel, I and Stanek, A},
title = {Association of mercury exposure with neurodegenerative diseases - a reality or a misconception?.},
journal = {Neurologia i neurochirurgia polska},
volume = {},
number = {},
pages = {},
doi = {10.5603/pjnns.108158},
pmid = {41222474},
issn = {0028-3843},
abstract = {INTRODUCTION: Exposure to heavy metals has long been considered a potential risk factor for neurodegenerative diseases.

STATE OF THE ART: Most existing studies include in vitro and animal models, and research involving human subjects has yielded conflicting results, obscuring the overall understanding of this topic.

AIMS OF THE STUDY: In this article, the aim is to clarify the situation by carefully reviewing and categorizing the available body of knowledge in this field. Specifically, the focus is on research that explores the relationship between mercury exposure and common neurodegenerative diseases.

CONCLUSIONS: Despite its neurotoxic properties, results show that mercury is not associated with frequent neurodegenerative disorders.},
}

@article {pmid41221610,
year = {2025},
author = {},
title = {Platform Communications: Abstract Book 36th International Symposium on ALS/MND (Complete printable file).},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {26},
number = {sup2},
pages = {1-78},
doi = {10.1080/21678421.2025.2564539},
pmid = {41221610},
issn = {2167-9223},
}

@article {pmid41221045,
year = {2025},
author = {Zhang, D and Han, L and Zhang, W and Wang, D and Huo, D and Tan, X and Su, X and Wang, M and Xu, J and Cheng, J and Wang, J and Feng, H},
title = {Neuroprotective mechanisms of valproic acid and alpha-lipoic acid in ALS: a network pharmacology-based investigation.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1681929},
pmid = {41221045},
issn = {1663-9812},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, and its multi-mechanism pathology makes single-target therapy insufficient. Valproic acid (VPA) and alpha-lipoic acid (ALA) are known neuroprotective agents, but their combined therapeutic potential and mechanisms in ALS remain unclear.

METHODS: In this study, network pharmacology method was used to integrate the target data of VPA, ALA and ALS, and key targets and pathways were screened by function enrichment, protein-protein interaction (PPI), network analysis and molecular docking. Furthermore, Mendel randomization (MR) was used to analyze the causal relationship between targets and ALS risk. The synergistic neuroprotective effects of VPA and ALA were then validated in the hSOD1[G93A] ALS cell and mouse models.

RESULTS: In this study, four core targets-TNF, EGFR, MAPK1 and MAPK8-were identified for the first time. Genetic analysis indicated that higher TNF levels and reduced MAPK8 expression are linked to a greater risk of ALS. Molecular docking demonstrated strong binding affinities of both compounds to these targets. In vitro and in vivo experiments showed that the combined therapy significantly improved neuronal survival and motor function, inhibited inflammation and apoptosis by activating the PI3K/AKT/FoxO3a pathway, and yielded significantly better therapeutic effects compared to the single drug treatments.

DISCUSSION: VPA and ALA synergistically alleviate ALS by modulating multiple targets and activating the PI3K/AKT/FoxO3a pathway. These findings support their potential as a combinatorial therapeutic strategy for ALS.},
}

@article {pmid41220979,
year = {2025},
author = {Konopka, A},
title = {Colocalizing Telomeres With PML or γH2AX Foci by IF-FISH in Mouse Brain Neurons.},
journal = {Bio-protocol},
volume = {15},
number = {21},
pages = {e5485},
pmid = {41220979},
issn = {2331-8325},
abstract = {Telomere length maintenance is strongly linked to cellular aging, as telomeres progressively shorten with each cell division. This phenomenon is well-documented in mitotic, or dividing, cells. However, neurons are post-mitotic and do not undergo mitosis, meaning they lack the classical mechanisms through which telomere shortening occurs. Despite this, neurons retain telomeres that protect chromosomal ends. The role of telomeres in neurons has gained interest, particularly in the context of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), where aging is a major risk factor. This has sparked interest in investigating telomere maintenance mechanisms in post-mitotic neurons. Nevertheless, most existing telomere analysis techniques were developed for and optimized using mitotic cells, posing challenges for studying telomeres in non-dividing neuronal cells. Thus, this protocol adapts an already established technique, the combined immunofluorescence and telomere fluorescent in situ hybridization (IF-FISH) on mitotic cells to study the processes occurring at telomeres in cortical neurons of the mouse ALS transgenic model, TDP-43 rNLS. Specifically, it determines the occurrence of DNA damage and the alternative lengthening of telomeres (ALT) mechanism through simultaneous labeling of the DNA damage marker, γH2AX, or the ALT marker, promyelocytic leukemia (PML) protein, together with telomeres. Therefore, the protocol enables the visualization of DNA damage (γH2AX) or the ALT marker (PML) concurrently with telomeres. This technique can be successfully applied to brain tissue and enables the investigation of telomeres specifically in cortical neurons, rather than in bulk tissue, offering a significant advantage over Southern blot or qPCR-based techniques. Key features • This protocol enables the labeling of telomeres in mouse brain tissue prepared from paraffin-embedded brain sections. • This method facilitates concurrent labeling of proteins that are colocalized at telomere sites.},
}

@article {pmid41220958,
year = {2025},
author = {Highlander, M and Elbasiouny, S},
title = {Methodological and analytical limitations undermine reported outcomes of spinal DC stimulation in ALS.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1706131},
pmid = {41220958},
issn = {1664-2295},
}

@article {pmid41220229,
year = {2025},
author = {Sehgal, D and Martín-Sanz, A and Sayago, A and Perraki, A and Kaundun, SS},
title = {Prevalence of two acetolactate synthase target site resistance mutations in sunflower broomrape from Europe as determined by robust kompetitive allele-specific assays (KASP).},
journal = {Pest management science},
volume = {},
number = {},
pages = {},
doi = {10.1002/ps.70355},
pmid = {41220229},
issn = {1526-4998},
abstract = {BACKGROUND: Orobanche cumana is an important pest of sunflower crops in Europe and Asia. Recently, two highly virulent populations of sunflower broomrape from Greece were found to have evolved resistance to imazamox owing to the A205D and S653N acetolactate synthase (ALS) target-site mutations. We have developed two robust fluorophore-based kompetitive allele-specific (KASP) assays to cost-effectively genotype a large European collection of O. cumana for these two mutations.

RESULTS: The KASP assays were established using 94 tubercules from the two imazamox-resistant populations of sunflower broomrape from Orestiada (GR-ORE) and Drama (GR-DRA) regions in Greece, and two sensitive populations from Romania (RO-TUL) and Spain (SP-VIL). The genotype calls generated by the two KASP assays completely matched with those from sanger sequencing, demonstrating the reliability of the two assays developed here. Genotyping of 2114 individuals from 94 European O. cumana populations collected between 2014 and 2022 did not reveal the A205D mutation in any sample, whereas the S653N mutation, in the homozygous state, was present in a single population (OR-183) from the Drama region in Greece. Cluster analysis of ALS gene sequences suggests that resistance has evolved independently in the two geographically close populations GR-DRA and OR-183 from Drama.

CONCLUSION: The KASP assays developed here allowed high-throughput reliable genotyping of the A205D and S653N mutations in a large number of O. cumana samples from Europe. The study indicates that, so far, resistance to imazamox owing to the A205D and S653N mutations in sunflower broomrape is limited to only three populations from Greece. © 2025 Society of Chemical Industry.},
}

@article {pmid41220184,
year = {2025},
author = {Lei, J and Gong, L and Wei, S and Deng, J},
title = {Causal Relationship Between Inflammatory Bowel Disease and Neuropsychiatric Disorders: A Bidirectional Mendelian Randomization Study.},
journal = {Brain and behavior},
volume = {15},
number = {11},
pages = {e71046},
pmid = {41220184},
issn = {2162-3279},
mesh = {Humans ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; *Inflammatory Bowel Diseases/genetics/epidemiology ; *Mental Disorders/genetics/epidemiology ; Crohn Disease/genetics ; Schizophrenia/genetics ; Depressive Disorder, Major/genetics ; Colitis, Ulcerative/genetics ; Genetic Predisposition to Disease ; Bipolar Disorder/genetics ; },
abstract = {BACKGROUND: Observational studies have indicated a correlation between inflammatory bowel disease (IBD) and neuropsychiatric disorders, yet the causal relationship remains unclear.

OBJECTIVE: We aim to employ two-sample Mendelian randomization (MR) to ascertain the potential causal relationship between IBD and seven major neuropsychiatric disorders.

METHODS: We conducted a bidirectional two-sample MR analysis utilizing genome-wide association study (GWAS) summary statistics of European ancestry for IBD (31,665 cases and 33,977 controls) and its subtypes, ulcerative colitis (UC, 13,768 cases and 33,977 controls) and Crohn's disease (CD, 17,897 cases and 51,874 controls), along with seven major neuropsychiatric disorders: major depressive disorder (MDD, 135,458 cases and 344,901 controls), bipolar disorder (BD, 41,917 cases and 371,549 controls), schizophrenia (SCZ, 33,640 cases and 43,456 controls), Alzheimer's disease (AD, 39,106 cases and 46,828 controls), Parkinson's disease (PD, 33,674 cases and 449,056 controls), multiple sclerosis (MS, 14,498 cases and 24,091 controls), and amyotrophic lateral sclerosis (ALS, 27,205 cases and 110,881 controls).

RESULTS: Our analysis revealed potential positive causal effects of IBD and CD on MDD and SCZ. Similarly, SCZ was positively correlated with an increased risk of IBD and UC. There was a bidirectional positive association between IBD, UC, and MS, whereas CD showed a positive causal effect on MS. Similar to the investigation of the seven specified neuropsychiatric disorders on CD, we did not find evidence supporting causal effects of MDD, BD, AD, PD, or ALS on IBD or UC. Sensitivity analyses further reinforced the robustness of the MR estimates.

CONCLUSION: Our results support potential causal relationships between IBD (including its subtypes CD and UC) and several neuropsychiatric disorders, reinforcing the gut-brain axis concept and enhancing our understanding of extra-intestinal manifestations of IBD and neuropsychiatric manifestations in the context of IBD.},
}

Humans
Mendelian Randomization Analysis
Genome-Wide Association Study
*Inflammatory Bowel Diseases/genetics/epidemiology
*Mental Disorders/genetics/epidemiology
Crohn Disease/genetics
Schizophrenia/genetics
Depressive Disorder, Major/genetics
Colitis, Ulcerative/genetics
Genetic Predisposition to Disease
Bipolar Disorder/genetics

@article {pmid41219975,
year = {2025},
author = {Camero-Ortiz, EA and Delgado-García, SK and Bendezu-Quispe, G and Grandez-Castillo, GA},
title = {Diagnostic criteria for HPV infection classification: a comment on Wen et al.},
journal = {Virology journal},
volume = {22},
number = {1},
pages = {369},
pmid = {41219975},
issn = {1743-422X},
mesh = {Humans ; *Papillomavirus Infections/diagnosis/virology/epidemiology/classification ; *Papillomaviridae/classification/genetics/isolation & purification ; Genotype ; Male ; Prevalence ; China/epidemiology ; Coinfection/virology/epidemiology ; },
abstract = {BACKGROUND: We read with great interest Wen et al.'s article on HPV infection in Huizhou men, commending this pioneering research as the first systematic analysis of HPV epidemiology in the region. The findings, including a 30.53% positivity rate and prevalent genotypes like HPV6, HPV52, HPV11, and HPV16, offer valuable insights for developing effective prevention strategies.

MAIN BODY: We are concerned, however, about the study's HPV classification methodology. Categorizing infections into "low-risk," "high-risk," and "mixed" (which includes any combination of high and low-risk genotypes) might obscure the true incidence of high-risk HPV infections. High-risk HPV types are strongly linked to malignant transformations. Hence, a single high-risk genotype poses a significant health risk, irrespective of low-risk co-infection. Grouping high-risk infections with low-risk types in the "mixed" category could therefore underestimate the proportion of patients with high-risk HPV.

CONCLUSION: For future research, we suggest presenting high-risk HPV prevalence by distinguishing between solely low-risk, solely high-risk, and high-risk mixed infections (multiple infections that include at least one high-risk genotype). This offers a more accurate understanding of the burden, aiding public health efforts, screening, and vaccination programs.},
}

Humans
*Papillomavirus Infections/diagnosis/virology/epidemiology/classification
*Papillomaviridae/classification/genetics/isolation & purification
Genotype
Male
Prevalence
China/epidemiology
Coinfection/virology/epidemiology

@article {pmid41219399,
year = {2025},
author = {Fyfe, I},
title = {Microglia response altered by ALS mutation.},
journal = {Nature reviews. Neurology},
volume = {},
number = {},
pages = {},
pmid = {41219399},
issn = {1759-4766},
}

@article {pmid41219095,
year = {2025},
author = {Pu, S and Sawyer, A and Levinson, C and Putrino, D and Kirke, DN},
title = {Exploring Voice Banking as an Alternative Augmentative Communication Strategy for Individuals with Dysphonia, Aphonia, and Dysarthria: A Scoping Review.},
journal = {Journal of voice : official journal of the Voice Foundation},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jvoice.2025.10.018},
pmid = {41219095},
issn = {1873-4588},
abstract = {OBJECTIVES: This scoping review sought to: (i) review studies involving people diagnosed with dysphonia, aphonia, and dysarthria who have used voice banking technology in a hospital or community setting, and (ii) understand the scope of research surrounding existing voice banking technology and software in the clinical setting.

METHODS: This scoping review was conducted according to the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews. An electronic search of databases, including Ovid MEDLINE(R), Embase (Ovid), APA PsycINFO (Ovid), and CINAHL was conducted. Title, abstract, and full text screening were completed using Covidence (Veritas Health Innovation, Melbourne, Australia) by two reviewers.

RESULTS: After deduplication, 1336 studies underwent title and abstract screening. Of these, the full texts of 65 studies were reviewed, and 23 were included. Three distinct topics were identified in the search: (i) message banking, in which discrete messages or phrases are recorded for later use, without the ability to create novel phrases outside of those previously recorded; (ii) voice banking, in which all the necessary phonemes in the target language are captured, with the goal of generating a personalized synthetic voice that can generate novel phrases; (iii) and voice conversion or voice reconstruction, in which pathologic voices or speech are "converted" into a personalized synthetic voices.

DISCUSSION AND CONCLUSION: This scoping review summarized the evidence for voice banking technology use in people diagnosed with dysphonia and dysarthria and sought to understand the research landscape of existing types of voice banking technology and software use in a clinical setting. The included papers were highly heterogeneous in terms of the population and type (research vs clinical program vs review/other). There is a pressing need for the publication of clinical programs and models facilitating the adoption of voice banking, especially within populations affected by conditions such as amyotrophic lateral sclerosis and laryngectomy, to address existing gaps and foster broader implementation and accessibility.},
}

@article {pmid41218638,
year = {2025},
author = {Wasicki, B and Zawistowski, P and Jankowiak, T and de Oliveira Pires, L and Fernandes, S and Bączyk, M},
title = {Acute Invasive Dorso-Ventral DCS Applied With a Ball Electrode Does Not Alter Spinal Motoneurons' Firing Characteristics in the SOD-1 G93A Mouse Model of ALS.},
journal = {The European journal of neuroscience},
volume = {62},
number = {9},
pages = {e70314},
doi = {10.1111/ejn.70314},
pmid = {41218638},
issn = {1460-9568},
support = {2017/26/D/NZ7/00728//Narodowe Centrum Nauki/ ; 2019/35/B/NZ4/02058//Narodowe Centrum Nauki/ ; 2022/04/Y/NZ4/00117//Narodowe Centrum Nauki/ ; 2024.00602.BD//Fundação para a Ciência e a Tecnologia/ ; JPND/0003/2022//Fundação para a Ciência e a Tecnologia/ ; UID/00645/2025//Fundação para a Ciência e a Tecnologia/ ; },
abstract = {In amyotrophic lateral sclerosis (ALS), alterations of spinal motoneurons' (MNs) excitability form the hallmark of their degeneration. Trans-spinal direct current stimulation (tsDCS) is based on the delivery of low-intensity DC to the spinal column in order to alter spinal circuit excitability. Recently, this technique was applied to the management of ALS in the SOD1 G93A mice and resulted in a reduction of disease biomarkers and extended mouse survival. While indirect evidence suggests that these effects can be linked to a decrease in MNs excitability following tsDCS, this has never been directly confirmed. Therefore, in this study, we have utilized in vivo sharp intracellular recordings of spinal MN to directly investigate the impact of DC on MN intrinsic excitability in SOD1 G93A mice. Electrophysiological properties of MNs recorded before DCS were compared to the properties of MNs recorded within 1 h after DCS application using linear mixed-effect models. We have found that direct DCS application significantly increases MN peak and plateau input resistance (by 31% and 35%, respectively); however, this was not linked to any significant change to MN threshold and firing properties. Both mathematical modelling and in vivo recordings of the electric field (EF) indicate that our results may be explained by the low density of the EF at the MN recording site. While our results indicate that invasive DCS is not efficient in modifying MN excitability, it may be effective in altering the excitability of afferent fibers traversing the dorsal column close to the DCS application site.},
}

@article {pmid41218158,
year = {2025},
author = {Silva Sousa, LD and Bertuzzi, A and Rodrigues Fiuza, TE and Leite, ER and Benito, P and Ferri, D and Zanchet, D and Beale, AM},
title = {Identification of Transient Intermediates and Active Species in Atomic CZA Catalysts for CO2 Hydrogenation to Methanol.},
journal = {Journal of the American Chemical Society},
volume = {},
number = {},
pages = {},
doi = {10.1021/jacs.5c08043},
pmid = {41218158},
issn = {1520-5126},
abstract = {Direct hydrogenation of carbon dioxide to methanol is a promising strategy for carbon capture and utilization (CCU). Copper-zinc-alumina (CZA) catalysts are widely used for this transformation, yet the nature of the active Cu and Zn species and the reaction intermediates remains debated due to their sensitivity to feed composition and temperature. This challenge is compounded by the high metal loading in conventional CZA catalysts, which obscures active species signals with background contributions from spectator species. To address this, we synthesized model CuZn/Al2O3 catalysts using bimetallic coordination complexes, achieving low metal loadings that yield small Cu clusters and Cu[+] single atoms adjacent to isolated Zn[2+] sites. In situ XANES and UV-vis data were analyzed using multivariate curve resolution-alternating least-squares (MCR-ALS), revealing that Cu dispersion and reagglomeration─phenomena suspected in industrial systems─also occur at low loadings. Operando and modulation excitation with phase sensitive detection DRIFTS (ME-PSD-DRIFTS) showed: (a) Cu clusters dissociate H2 and activate CO2 via monodentate formate; (b) Al2O3 stabilizes Cu[+] under reducing conditions, with Cu content correlating with methanol productivity via CO hydrogenation; and (c) Zn in ZnAl2O4 promotes CO2 activation through reactive carbonate formation and enhances oxygenate conversion kinetics. ZnAl2O4 also acts as a structural promoter, facilitating CO2 conversion via reverse water gas shift (RWGS) and CO hydrogenation. These findings reveal new structure-activity relationships, highlighting the role of the mixed-metal interface in stabilizing transient intermediates and providing some guidance in the rational design of improved catalysts for CO2 valorization.},
}

@article {pmid41218062,
year = {2025},
author = {Takeuchi, E and Yasumizu, Y and Morita, J and Ishikawa, M and Ogawa, K and Motooka, D and Okuzaki, D and Nagata, M and Ishihara, Y and Miyashita, Y and Asano, Y and Mori, K and Morii, E and Beck, G and Saito, Y and Murayama, S and Mochizuki, H and Nagano, S},
title = {Single-nucleus multiome shows motor neuron glutamate overactivation in amyotrophic lateral sclerosis.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awaf426},
pmid = {41218062},
issn = {1460-2156},
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that causes motor neuron degeneration. However, the mechanisms underlying the selective vulnerability of motor neurons and the involvement of non-motor neuron cells in ALS remain unclear. To investigate ALS pathology at the cellular level, we performed a single-nucleus multiome analysis, including RNA sequencing and chromatin accessibility profiling, on motor cortex (75,583 nuclei) and spinal cord (62,711 nuclei) from patients with ALS (n=6) and controls (n=6). Our results revealed significant gene expression changes specifically in spinal motor neurons, including upregulation of a metabotropic glutamate receptor, GRM5, and enhanced glutamate signaling. By integrating genome-wide association study data, we identified ALS-associated SNPs in regulatory regions, suggesting cell-type-specific enrichment of risk, especially in microglia. These findings suggest that changes in spinal motor neurons and their surrounding environment, including glutamate signaling, may be involved in ALS pathology. The study also provides valuable resources for future research on the underlying mechanisms and potential therapeutic targets.},
}

@article {pmid41217159,
year = {2025},
author = {Maranges, HM and Timbs, CL},
title = {Operational and conceptual confusion in life history research necessitates the two-tiered model.},
journal = {The Behavioral and brain sciences},
volume = {48},
number = {},
pages = {e115},
doi = {10.1017/S0140525X25100940},
pmid = {41217159},
issn = {1469-1825},
abstract = {Our systematic analysis of operationalizations and conceptualizations of harshness (extrinsic mortality) and unpredictability in the (psychology) life history literature highlights that (1) employment of extremely diverse measures contributes to the confusion about the effect of harshness on life history traits and (2) few measures reflect energetic stress or ambient EM, such that Ellis et al.'s two-tiered model should motivate future research.},
}

@article {pmid41217141,
year = {2025},
author = {Sasson, I},
title = {Social inequalities as sources of extrinsic mortality: implications of the two-tiered model.},
journal = {The Behavioral and brain sciences},
volume = {48},
number = {},
pages = {e119},
doi = {10.1017/S0140525X25100861},
pmid = {41217141},
issn = {1469-1825},
mesh = {Humans ; *Mortality ; *Socioeconomic Factors ; *Bereavement ; },
abstract = {Ellis et al.'s two-tiered model compellingly integrates biological and psychosocial pathways through which extrinsic mortality shapes life history strategies. An understated, yet important, implication of their framework is the role of social inequalities in signaling mortality risk - particularly through differential exposure to bereavement - and how it may give rise to distinct life history strategies and outcomes.},
}

Humans
*Mortality
*Socioeconomic Factors
*Bereavement

@article {pmid41217139,
year = {2025},
author = {Komyaginskaya, E and Gallyamova, A and Grigoryev, D},
title = {Density slows, while pathogens and disasters accelerate life history within populations.},
journal = {The Behavioral and brain sciences},
volume = {48},
number = {},
pages = {e111},
doi = {10.1017/S0140525X25101106},
pmid = {41217139},
issn = {1469-1825},
abstract = {This commentary complements Ellis et al.'s two-tiered framework by using panel data and emphasizing the role of population density in decelerating life history (LH) strategy. We show that mortality cues and energetic constraints do not operate in isolation, demonstrating how density-dependent competition shapes LH strategies over time and underscoring the need for a dynamic, multifaceted approach to LH development.},
}

@article {pmid41217137,
year = {2025},
author = {Chen, BB},
title = {From shyness to attachment: social behaviors as adaptive responses to environmental stress.},
journal = {The Behavioral and brain sciences},
volume = {48},
number = {},
pages = {e103},
doi = {10.1017/S0140525X25101076},
pmid = {41217137},
issn = {1469-1825},
mesh = {Humans ; *Object Attachment ; *Shyness ; *Social Behavior ; *Adaptation, Psychological/physiology ; *Stress, Psychological/psychology ; },
abstract = {This commentary expands Ellis et al.'s 2-tiered life history (LH) model by integrating shyness and insecure attachment as mediators of environmental adaptation. Shyness balances survival-reproduction trade-offs with mixed LH outcomes. Avoidant attachment accelerates LH strategies under harsh conditions; anxious attachment delays reproduction under unpredictable conditions. Incorporating social behaviors, which are related to survival and safety, enhances the model's applicability across behavioral domains.},
}

Humans
*Object Attachment
*Shyness
*Social Behavior
*Adaptation, Psychological/physiology
*Stress, Psychological/psychology

@article {pmid41216790,
year = {2025},
author = {Strell, P and Waldron, MA and Johnson, ST and Shetty, A and Crane, AT and You, Y and Steer, CJ and Low, WC},
title = {Characterization of the intraspecies chimeric mouse brain at embryonic day 12.5.},
journal = {Cell transplantation},
volume = {34},
number = {},
pages = {9636897251384571},
doi = {10.1177/09636897251384571},
pmid = {41216790},
issn = {1555-3892},
abstract = {Incidence of neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis have increased dramatically as life expectancy has risen year-over-year, and can lead to neurologic changes. Neurological changes within the central nervous system, specifically the brain, include cell loss and deterioration that impact motor function, memory, executive function, and mood. Available treatments are limited and often only address symptomatic manifestations of the disease rather than disease progression. Cell transplantation therapy has shown promise for treating neurodegenerative diseases, but a source of autologous cells is required. Blastocyst complementation provides an innovative method for generating autologous neural cells. By injecting mouse induced pluripotent stem cells into a wild type mouse blastocyst, we generated a chimeric mouse brain derived of both donor and host neuronal and non-neuronal cells. At embryonic day 12.5 (E12.5), automated image analysis of mouse-mouse chimeric brains showed the presence of GFP-labeled donor-derived dopaminergic and serotonergic neuronal precursors. GFP-labeled donor-derived cholinergic precursor neurons and non-neuronal microglia-like and macrophage-like cells were also observed using more conventional imaging analysis software. This work demonstrates that the generation of mouse-mouse chimeric neural cells is possible; and that characterization of early neuronal and non-neuronal precursors provides a first step toward utilizing these cells for cell transplantation therapies for neurodegenerative diseases.},
}

@article {pmid41216506,
year = {2026},
author = {Wei, Y and Snow, BA and Stevenson, CC and Miao, H and Kaur, J and Lee, SG and Kim, NC and Kim, WJ},
title = {Surface glia for modeling ALS-FTD-associated mutant C9orf72 toxicity in the nervous system of Drosophila.},
journal = {Genes & diseases},
volume = {13},
number = {2},
pages = {101629},
pmid = {41216506},
issn = {2352-3042},
}

@article {pmid41216140,
year = {2025},
author = {Spencer, BE and Xie, SX and Ohm, DT and Elman, L and Quinn, CC and Amado, DA and Baer, M and Lee, EB and Van Deerlin, VM and Dratch, L and Massimo, L and Irwin, DJ and McMillan, CT},
title = {Cumulative incidence of motor and cognitive features in the amyotrophic lateral sclerosis-frontotemporal degeneration spectrum.},
journal = {Brain communications},
volume = {7},
number = {6},
pages = {fcaf405},
pmid = {41216140},
issn = {2632-1297},
abstract = {In frontotemporal degeneration and amyotrophic lateral sclerosis, subsequent motor or cognitive-behavioural features, respectively, are associated with shorter survival. However, factors influencing subsequent feature development remain largely unexplored. In this study, we examined whether the presence of a C9orf72 expansion or the initial clinical syndrome was associated with increased risk of subsequent feature development in individuals with amyotrophic lateral sclerosis and frontotemporal degeneration. We performed a retrospective evaluation of the entire disease course of individuals with an initial clinical syndrome of amyotrophic lateral sclerosis or frontotemporal degeneration who had neuropathological confirmation of TDP-43 proteinopathy at autopsy or a C9orf72 hexanucleotide repeat expansion. We examined the odds and hazard of subsequent feature development and assessed whether each was modified by the presence of a C9orf72 expansion or initial clinical syndrome. At autopsy, we evaluated the association between TDP-43 pathology burden in characteristic brain regions and features across this disease spectrum. For individuals with amyotrophic lateral sclerosis (n = 168) and frontotemporal degeneration (n = 73), binary logistic regression revealed increased odds (odds ratio = 3.49 [95% confidence interval 1.64-7.80], P = 0.002) and Cox proportional hazard analyses revealed an increased hazard (hazard ratio = 3.78 [95% confidence interval 1.86-7.65], P < 0.001) for developing subsequent features in those with a C9orf72 expansion compared to those without. Beyond C9orf72 expansion status, binary logistic regression revealed decreased odds (odds ratio = 0.25 [95% confidence interval 0.12-0.53], P < 0.001) and Cox proportional hazard analyses revealed a decreased hazard (hazard ratio = 0.48 [95% confidence interval 0.25-0.95], P = 0.03) for developing subsequent features in those with an initial amyotrophic lateral sclerosis clinical syndrome compared to those with an initial frontotemporal degeneration clinical syndrome. We observed a 94-month difference in the time after symptom onset of the initial clinical syndrome that a given person without a C9orf72 expansion reached the highest probability of developing subsequent features (0.12 [95% CI 0.03-0.19], 113.00 months) and a person with a C9orf72 expansion surpassed that probability (0.13 [95% CI 0.06-0.19], 19.00 months). The distribution of TDP-43 pathology across characteristic brain regions reflected both the initial clinical syndrome and subsequent features, with relatively preserved spinal cord only in frontotemporal degeneration cases without subsequent motor features (P < 0.0001) and relatively preserved neocortical regions only in amyotrophic lateral sclerosis cases without subsequent cognitive-behavioural features (P < 0.0001). These data highlight the need for clinician vigilance to detect the onset of subsequent motor and cognitive-behavioural features in patients carrying a C9orf72 expansion, regardless of initial clinical syndrome. C9orf72 clinical care can be enhanced through coordination between cognitive and neuromuscular clinics.},
}

@article {pmid41215674,
year = {2025},
author = {Adeagbo, MJ and Kahler, J and Jones, D and Reisinger, HS and Swenson, A},
title = {'I want to be generous, but I only have limited energy': a qualitative study of amyotrophic lateral sclerosis patients' preferences for clinical trials participation.},
journal = {Annals of medicine},
volume = {57},
number = {1},
pages = {2586150},
doi = {10.1080/07853890.2025.2586150},
pmid = {41215674},
issn = {1365-2060},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/therapy ; *Patient Preference/psychology ; Female ; Male ; Qualitative Research ; Middle Aged ; Aged ; *Clinical Trials as Topic/psychology ; Adult ; *Patient Participation/psychology ; Emotions ; },
abstract = {BACKGROUND AND OBJECTIVE: Research and decisions on health-related issues such as Amyotrophic Lateral Sclerosis (ALS) continue to evolve as the etiology of network degenerative disease remains indeterminate. Due to its heterogeneity, clinical trials (CTs) are continually being conducted for beneficial breakthroughs aimed at improving the lives of patients with ALS. However, there is a dearth of research on ALS patients' health-seeking decisions and preferences in CTs, particularly for patients living in rural areas. To bridge this important gap, we explored patients' subjective experiences and preferences in CT participation through their emotions.

MATERIALS AND METHODS: Seventeen participants (10 ALS patients, 6 healthcare professionals, and an advocacy group representative associated with ALS) affiliated with the University of Iowa ALS Multidisciplinary clinic were purposively selected and interviewed for the study. Qualitative descriptive data were analyzed using thematic content analysis to understand the patients' experiences and preferences.

RESULTS: Findings indicate key emotional and logistical challenges including fatigue, travel distance and constraints, limited trial availability, which are exacerbated by the disease's rapid progression and restrictive eligibility criteria. Participants' narratives highlighted frustration, anxiety, and fear as central emotional experiences influencing their health-seeking decisions. Conversely, expressions of hope and empathy emerged as significant motivators, with patients demonstrating a willingness to participate in CTs despite the known risk of limited personal benefits, while focusing on the need to benefit future ALS research. Patients prefer and desire more compensation, broader eligibility and inclusive criteria, trial availability and publicity, and access to telemedicine.

CONCLUSION: Given the multifaceted physical, and emotional challenges faced by ALS patients, this study recommends prioritizing patient preferences in future CTs and intervention designs, while advocating for targeted grants and sustained funding that supports ALS clinical trials. This will better align with the needs and expectations of ALS patients, thereby enhancing trial participation and overall patient satisfaction.},
}

Humans
*Amyotrophic Lateral Sclerosis/psychology/therapy
*Patient Preference/psychology
Female
Male
Qualitative Research
Middle Aged
Aged
*Clinical Trials as Topic/psychology
Adult
*Patient Participation/psychology
Emotions

@article {pmid41214888,
year = {2025},
author = {Lin, H and Xie, X and Gao, R and Jing, Y and Chen, D and Zhang, J and Qiu, X and Zhang, J and Luo, L},
title = {Comparison of Ocular Biometry and Refractive Outcome between IOLMaster 700 and ZW-30.},
journal = {Journal of cataract and refractive surgery},
volume = {},
number = {},
pages = {},
doi = {10.1097/j.jcrs.0000000000001828},
pmid = {41214888},
issn = {1873-4502},
abstract = {PURPOSE: To compare the ocular biometry and refractive outcome between two optical biometers.

SETTING: Zhongshan ophthalmic center, Guangzhou, China.

DESIGN: Prospective observational study.

METHODS: A total of 953 cataract patients underwent preoperative biometry including ZW-30 sum-of-segments [SOS] method (ZWSM), ZW-30 composite method (ZWCM), and IOLMaster 700. Agreement of axial length (AL), with or without Cooke-modified AL (CMAL) adjustment, was analyzed using Bland-Altman 95% limits of agreement (LoA). Subgroup analysis were used based on ALs (Short eyes: AL<22mm; Normal eyes: 22mm≤AL<26mm; Long eyes: AL≥26mm). Refractive prediction accuracy was evaluated using Emmetropia verifying optical (EVO) 2.0 formula and its SOS-optimized version (EVO 2.0SOS).

RESULTS: In short and normal eyes, narrow 95%LoAs (<0.2mm) were identified among three ALs. However, AL obtained by ZWSM was lower compared with this obtained by ZWCM and IOLMaster 700 (95%LoA: -0.39 to 0.01mm; -0.38 to 0.04mm) in long eyes. CMAL adjustment enhanced the agreement of AL between ZWSM and ZWCM (95%LoA: -0.01mm to 0.02mm), ZWSM and IOLMaster 700 (95%LoA: -0.10mm to 0.07mm) in long eyes. Myopic prediction errors (PE) have been identified in the use of ocular biometric parameters obtained from ZWSM (Mean PE [ME]: EVO 2.0, -0.19D; EVO 2.0SOS, -0.18D). After adjusting ME to zero, no difference was observed in PE calculated using any combination of formulas based on biometric measurements from three devices.

CONCLUSIONS: This novel segmented biometer demonstrates excellent agreement with IOLMaster 700 in short and normal eyes. However, ALs obtained by IOLMaster 700 are not interchangeable with the SOS method and require CMAL adjustment in long eyes. The application of the SOS method's ocular biometric parameters in refractive prediction led to myopic errors, which suggest constant optimization.},
}

@article {pmid41214238,
year = {2025},
author = {Mushtaq, U and Ahmad, B and Khanday, FA and Ahmad, M},
title = {CHI3L1: An Emerging Player in Neuroinflammation and Neurodegeneration.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {23},
pmid = {41214238},
issn = {1559-1182},
abstract = {Neuroinflammation is now being identified as the major factor in the development of various neurological disorders. It is a vital process in neurons and the brain that maintains homeostasis under normal and healthy conditions. However, in hyperactivated states, neuroinflammation can also go awry when microglia and astrocytes enter a toxic, reactive state that can release chemicals that damage neurons. When innate immune cells encounter pathogens, infection, cell debris, or misfolded proteins, they release certain chemokines and cytokines to eliminate the intruding particles and protect the brain. However, persistent inflammatory reactions are harmful and can lead to neurodegeneration by continuously releasing toxic chemicals and proteins. Chitinase-3-like protein 1 (CHI3L1), a secretory protein, is emerging as a key inflammatory molecule that is strongly upregulated during neuroinflammation and has been implicated in the pathogenesis of many diseases. The brain's activated astrocytes are the main source of CHI3L1 and are a dependable biomarker for inflammatory pathologies affecting the central nervous system (CNS), including neurodegeneration and autoimmune diseases. The protein has been implicated in many neurological disorders, including Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis, and others, mediating neuroinflammation and neurodegeneration. CHI3L1 has contrasting functions in the CNS and other tissues. While the protein promotes cell proliferation and migration in various non-neuronal cancers, at the same time, it simultaneously promotes neurodegeneration and apoptosis in the CNS. This paper reviews the current developments in our knowledge of the pathogenic role of the CHI3L1 protein in various neurological disorders.},
}

@article {pmid41213972,
year = {2025},
author = {Chisholm, CG and Bartlett, R and Brown, ML and Proctor, EJ and Farrawell, NE and Gorman, J and Delerue, F and Ittner, LM and Vine-Perrow, KL and Ecroyd, H and Cashman, NR and Saunders, DN and McAlary, L and Lum, JS and Yerbury, JJ},
title = {Development of a targeted BioPROTAC degrader selective for misfolded SOD1.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {9713},
pmid = {41213972},
issn = {2041-1723},
mesh = {Animals ; *Superoxide Dismutase-1/metabolism/genetics/chemistry ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology/drug therapy ; Mice, Transgenic ; Mice ; Protein Folding ; Humans ; Disease Models, Animal ; Proteolysis ; Motor Neurons/metabolism/pathology ; Ubiquitin-Protein Ligases/metabolism/genetics ; CRISPR-Cas Systems ; Disease Progression ; HEK293 Cells ; },
abstract = {The accumulation of misfolded proteins underlies a broad range of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Due to their dynamic nature, these misfolded proteins have proven challenging to target therapeutically. Here, we specifically target misfolded disease variants of the ALS-associated protein superoxide dismutase 1 (SOD1), using a biological proteolysis targeting chimera (BioPROTAC) composed of a SOD1-specific intrabody and an E3 ubiquitin ligase. Screening of intrabodies and E3 ligases for optimal BioPROTAC construction reveals a candidate capable of degrading multiple disease variants of SOD1, preventing their aggregation in cells. Using CRISPR/Cas9 technology to develop a BioPROTAC transgenic mouse line, we demonstrate that the presence of the BioPROTAC delays disease progression in the SOD1[G93A] mouse model of ALS. Delayed disease progression is associated with protection of motor neurons, a reduction of insoluble SOD1 accumulation and preservation of innervated neuromuscular junctions. These findings provide proof-of-concept evidence and a platform for developing BioPROTACs as a therapeutic strategy for the targeted degradation of neurotoxic misfolded species in the context of neurodegenerative diseases.},
}

Animals
*Superoxide Dismutase-1/metabolism/genetics/chemistry
*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology/drug therapy
Mice, Transgenic
Mice
Protein Folding
Humans
Disease Models, Animal
Proteolysis
Motor Neurons/metabolism/pathology
Ubiquitin-Protein Ligases/metabolism/genetics
CRISPR-Cas Systems
Disease Progression
HEK293 Cells

@article {pmid41213652,
year = {2025},
author = {Sundar Sah, S and Kumbhalwar, A},
title = {Letter to the Editor: Comment on Kuč et al.'s "Smoking and Risk of Uveitis: A Systematic Review and Meta-Analysis".},
journal = {Ocular immunology and inflammation},
volume = {},
number = {},
pages = {1-2},
doi = {10.1080/09273948.2025.2588218},
pmid = {41213652},
issn = {1744-5078},
}

@article {pmid41213329,
year = {2025},
author = {Adachi, M and Banno, H and Inoue, H},
title = {Drug discovery research with the iPSC models of neurodegenerative diseases.},
journal = {Neuroscience research},
volume = {},
number = {},
pages = {104985},
doi = {10.1016/j.neures.2025.104985},
pmid = {41213329},
issn = {1872-8111},
abstract = {Induced pluripotent stem cells (iPSCs) are widely used in research because they can be used to create models of diseases with the same genomic background as in patients. Recently, it has become recognized that the use of iPSCs for screening can promote drug discovery research. Additionally, research is being conducted to develop high-quality models for drug discovery and to link translational research with clinical studies. The present work focuses on neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD), and broadly introduces the latest research using iPSCs, from disease mechanism studies to drug discovery research. In addition, clinical trials based on research with iPSCs have been conducted: bosutinib, ropinirole and ezogabine for ALS, WVE-004 and BIIB078 for ALS with frontotemporal dementia (ALS/FTD), and bromocriptine for familial AD. Finally, we also wish to mention screening studies utilizing artificial intelligence (AI).},
}

@article {pmid41213224,
year = {2025},
author = {Hokkoku, K and Inoue, M and Yamada, S and Namba, H and Matsukura, K and Mukai, T and Chiba, T and Hatanaka, Y and Kobayashi, S and Sonoo, M},
title = {Clinically visible but often unperceived: Low awareness of fasciculations in amyotrophic lateral sclerosis.},
journal = {Journal of the neurological sciences},
volume = {479},
number = {},
pages = {123764},
doi = {10.1016/j.jns.2025.123764},
pmid = {41213224},
issn = {1878-5883},
abstract = {BACKGROUND: Fasciculations are a key clinical sign of amyotrophic lateral sclerosis (ALS) but also occur in other conditions such as benign fasciculation syndrome. Patients often present with perceived twitching fearing ALS; however, the extent to which ALS patients themselves perceive fasciculations has not been systematically examined. We therefore aimed to clarify how often ALS patients are aware of fasciculations that are clinically visible.

METHODS: We prospectively studied 34 ALS patients. First, a structured questionnaire assessed initial symptoms, chief complaints, and awareness of twitching. Then, the frequency and concordance between objective fasciculations and subjective awareness of fasciculations (twitching) were analyzed across five body regions (bilateral upper and lower limbs and trunk) based on simultaneous visual observation and patient reports.

RESULTS: In the questionnaire, only one of the 34 patients (3 %) reported twitching as the initial symptom, and none presented with twitching as the chief complaint. More than half (19, 56 %) had never noticed twitching. In the fasciculation analysis, patients showing objective fasciculations without subjective awareness were most common (21/34, 62 %), whereas those with objective fasciculations accompanied by subjective awareness were fewer (10/34, 29 %), indicating relatively low concordance between visible fasciculations and patient awareness. No patient exhibited subjective awareness without objective fasciculations. These findings suggest that the majority of visible fasciculations in ALS are not perceived by patients.

CONCLUSION: Fasciculations in ALS are rarely the initial or presenting symptom and are often unperceived by patients despite being clinically visible.},
}

@article {pmid41213077,
year = {2025},
author = {Cai, S and Liu, Y and Liu, B and Liao, H and Li, K},
title = {Hexokinase as a Central Hub in Neurodegeneration: From Metabolic Dysfunction to Therapeutic Innovation.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2025.0891},
pmid = {41213077},
issn = {2152-5250},
abstract = {Neurodegenerative diseases represent an escalating global health crisis affecting more than 55 million people worldwide; however, underlying mechanisms remain unclear, and therapeutic breakthroughs are elusive. Emerging evidence indicates that hexokinase (HK), the rate-limiting glycolytic enzyme, functions as a master regulator orchestrating neuronal survival through metabolic‒mitochondrial coupling. This review consolidates emerging paradigms revealing that HK maintains neuronal viability through its obligate interaction with mitochondrial VDAC1, forming a metabolic checkpoint that integrates energy status with survival signaling. Disease-specific HK dysfunction patterns precede clinical manifestations and drive pathological cascades across primary neurodegenerative conditions. Pathological proteins characteristic of neurodegeneration-amyloid-β in AD, α-synuclein in PD, mutant SOD1 in ALS, and huntingtin in HD-converge to disrupt the HK-VDAC1 axis through distinct molecular mechanisms, triggering mitochondrial permeabilization, bioenergetic collapse, and inflammatory activation. This uncoupling event promotes VDAC1 oligomerization, enabling the cytosolic release of mtDNA, which in turn activates the NLRP3 inflammasome while depleting antioxidant capacity, establishing self-perpetuating neuroinflammatory cycles. The literature reveals that HK functions as a molecular rheostat, determining neuronal fate through glucose-6-phosphate-mediated feedback control, modulation of growth factor signaling, and regulation of apoptosis/survival pathways. Therapeutic targeting of HK through peptide interventions, enzymatic modulation, and gene therapy demonstrates robust neuroprotective effects across multiple disease models. Meanwhile, combination strategies addressing metabolic-inflammatory networks show synergistic efficacy. These insights position HK as a convergent therapeutic nexus offering unprecedented opportunities for precision intervention in neurodegeneration, with potential for early diagnostic applications and preventive strategies that could transform treatment paradigms for conditions affecting millions worldwide.},
}

@article {pmid41212342,
year = {2025},
author = {Zhong, R and Yang, H and Li, X and Wang, F and Zhai, L and Gao, J},
title = {Mitochondria-Mediated Mechanisms of Ferroptosis in Neurological Diseases.},
journal = {Neurochemical research},
volume = {50},
number = {6},
pages = {354},
pmid = {41212342},
issn = {1573-6903},
support = {202403070986//Health Science and Technology Project of Shandong Province/ ; RZ1900011598//post-doctoral foundation of Qingdao University/ ; },
abstract = {Ferroptosis, a regulated form of cell death driven by iron-dependent lipid peroxidation, is increasingly recognized as a critical contributor to the pathogenesis of various neurological disorders. Mitochondria, the powerhouses of cells, play dual roles as both initiators and mediators of ferroptosis by integrating lipid peroxidation cascades, oxidative stress responses, and iron homeostasis dysregulation. This review first comprehensively explores the multifaceted mechanisms by which mitochondria mediate ferroptosis in neurological diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Friedreich's ataxia (FRDA), amyotrophic lateral sclerosis (ALS), epilepsy, stroke, and brain injury, with a focus on mitochondrial lipid peroxidation and iron metabolism dysregulation. Building on these mechanistic insights, we further discuss emerging evidence suggesting that targeting mitochondrial pathways may represent a promising therapeutic strategy for mitigating ferroptosis-associated neuronal damage. By synthesizing these findings, our review establishes a conceptual foundation for developing innovative neuroprotective interventions through precise modulation of mitochondrial function within ferroptotic pathways.},
}

@article {pmid41211682,
year = {2025},
author = {},
title = {Correction to "Amyotrophic Lateral Sclerosis and Swim Training Affect Copper Metabolism in Skeletal Muscle in a Mouse Model of Disease".},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70053},
pmid = {41211682},
issn = {1097-4598},
}

@article {pmid41210976,
year = {2025},
author = {Thapa, R and Adhikari, N and Gautam, S and Sun, M and McOmie, S and Davydzenka, V and Smith, D and Syring, J and Kaligis, H and Kosmicki, JM and Chen, R and Li, Y},
title = {Single-nucleus RNA sequencing reveals GABAergic vulnerability and reactive gliosis driven by loss of TDP-43.},
journal = {iScience},
volume = {28},
number = {11},
pages = {113745},
pmid = {41210976},
issn = {2589-0042},
abstract = {TDP-43 is an RNA-binding protein important for RNA processing, whose loss of function is involved in multiple neurodegenerative disorders, including frontotemporal dementia, amyotrophic lateral sclerosis, and Alzheimer's disease (AD). We performed single-nucleus RNA-sequencing to study the convergent and divergent molecular signatures of short-term and long-term TDP-43 depletion in the medial prefrontal cortex (mPFC) using Tdp-43 [F/F] mice, compared with that of 5xFAD mice, a well-established AD mouse model with β-amyloid plaque pathology. Our results demonstrated a significant loss of GABAergic neurons in the mPFC after short-term TDP-43 depletion. This was accompanied by a remarkable reactive gliosis in the mPFC. Our results revealed a strong GABAergic and glial involvement during early stages of TDP-43 loss of function, suggesting that the GABAergic system is vulnerable to TDP-43 pathology and could be considered a potential target for developing therapeutic strategies and biomarkers for early detection in TDP-43 linked AD-related dementia.},
}

@article {pmid41210444,
year = {2025},
author = {Khan, S and Wennberg, B and Hooda, F and Witkowska, M},
title = {Delayed treatment and diagnostic challenges in differentiating multifocal acquired demyelinating sensory and motor neuropathy from lupus: a case report and literature review.},
journal = {AME case reports},
volume = {9},
number = {},
pages = {111},
pmid = {41210444},
issn = {2523-1995},
abstract = {BACKGROUND: Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) is a rare autoimmune-mediated inflammatory response with negative antibodies which causes demyelination of multiple peripheral nerves in an asymmetric distribution with both motor and sensory deficits. Diagnosis for MADSAM can be clinically challenging, relies on a combination of clinical and electrodiagnostic studies, and symptoms can overlap with other neurological conditions such as systemic lupus erythematosus (SLE). MADSAM is typically asymmetric, demyelinating, and limited to peripheral nerves, whereas SLE is systemic, more commonly axonal, and has vasculitic features. SLE is treated with steroids and immunosuppressants while MADSAM is treated with intravenous immunoglobulin (IVIG), steroids, or plasmapheresis. There is a good short-term prognosis for MADSAM with early treatment, but prognosis can worsen with delayed or inappropriate therapy.

CASE DESCRIPTION: We describe a case of a woman in her 50s who presented with progressive generalized weakness, weight loss, muscle atrophy, and numbness. She was initially diagnosed with SLE, but deteriorated despite treatment. A broad differential was considered which included SLE, paraneoplastic syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Guillain-Barré syndrome. Serological studies, neuroimaging studies, nerve conduction studies, and electromyography (EMG) were performed. She was ultimately diagnosed with Lewis-Sumner syndrome, or MADSAM, a variant of CIDP.

CONCLUSIONS: The case highlights the importance of understanding the various causes of weakness and neuropathy, particularly with an atypical presentation, to pursue the correct diagnostic tests and treatment. The case particularly focuses on the difference between MADSAM and SLE. There is significant clinical overlap between the two, and a misdiagnosis can delay effective treatment and worsen outcomes by allowing progression to more debilitating stages of the illness.},
}

@article {pmid41209626,
year = {2025},
author = {Jensen, SHJ and Frumer, M and Connelly, EDS and Østgård, R and Glerup, H and Denby, K and Egsgaard, AL and Appel, CW},
title = {Integrated Rheumatology-Gastroenterology Clinic: An Innovative Organisation for Patients with Multiple Autoimmune Diseases.},
journal = {International journal of integrated care},
volume = {25},
number = {4},
pages = {9},
pmid = {41209626},
issn = {1568-4156},
abstract = {INTRODUCTION: Patients with multiple autoimmune diseases lack continuity of care due to increasing specialisation and siloed practice in healthcare. Despite improvements in quality, this organisation has led to fragmented patient pathways, as related diseases are treated separately. Limited research has investigated approaches to integrate care for patients with co-occurrent Inflammatory Joint Disease and Inflammatory Bowel Disease, with minimal emphasis on the patient perspective. The aim was to describe the Rheumatology-Gastroenterology Clinic (ReGa), characterise its population, and investigate patient experiences.

DESCRIPTION: A Danish outpatient clinic combining rheumatology and gastroenterology.

RESULTS: During the study period, 54 patients attended the ReGa clinic. Prior to integration, these patients had an average of 29.6 outpatient visits. With most working-age patients, this frequent attendance poses individual and societal challenges. Based on Haggerty et al.'s definition of continuity of care, relational elements emerged as particularly important for patients but not independent of informational and management factors.

CONCLUSION: The integrated approach was experienced to improve continuity of care for patients with multiple autoimmune diseases. The findings highlight the potential to bridge healthcare gaps and address challenges arising from organisational structures shaped by specialisation and compartmentalisation of knowledge. This approach may also benefit other patient groups with comorbid conditions.},
}

@article {pmid41209384,
year = {2025},
author = {Han, K and Yan, SG and Liu, F and Li, L and Zhou, D and Li, L and Liu, N and Dong, J},
title = {The Alterations in the Osteoimmune Microenvironment of STZ-Induced Type 2 Diabetic Mice:A Single-Cell RNA Sequencing Analysis.},
journal = {Journal of inflammation research},
volume = {18},
number = {},
pages = {15309-15327},
pmid = {41209384},
issn = {1178-7031},
abstract = {BACKGROUND: This study aimed to delineate the single-cell transcriptome of bone marrow (BM) cells from wild-type (WT) and type 2 diabetic (T2D) mice, revealing distinct immune microenvironment features.

METHODS: Single high-throughput single-cell RNA sequencing dataset (GSE212726) from BM cells of WT and streptozotocin (STZ)-induced T2DM mice were analyzed. Uniform manifold approximation and projection (UMAP), pseudo-time analysis, gene enrichment studies, and CellphoneDB were employed to identify immune cell interactions within the osteoimmune microenvironment. Key gene expression was validated by quantitative real-time polymerase chain reaction (qRT-PCR).

RESULTS: After filtering low-quality cells and doublets, 9,360 cells (WT) and 10,885 cells (T2DM) were retained and classified into 12 clusters. Proportional analysis revealed a significant decrease in BM-neutrophils (66.56% → 54.73%) and an increase in B cells (9.16% → 19.78%) in the DM group. The DM/WT ratio for BM-neutrophils/T cells, BM-neutrophils/DCs, and monocytes/T cells increased, while the ratio for BM-neutrophils/Naïve_B decreased. KEGG pathway analysis highlighted enrichment of neurodegeneration, protein processing in the endoplasmic reticulum, and amyotrophic lateral sclerosis pathways in BM-neutrophils. Intercellular communication analysis indicated reduced incoming and outgoing interaction strength for B cells and T cells, while the T2D group showed enhanced THBS, VISFATIN, CLEC, IL4, and IL6 signaling. Notably, CLEC was specific to outgoing signaling in T cells, and THBS was specific to both outgoing and incoming signaling in monocytes, MSCs, and BM-neutrophils.

CONCLUSION: Single-cell RNA sequencing provides a comprehensive profile of bone marrow immune cells in T2D mice and has highlighted their heterogeneity, population shifts, and intercellular interactions. These findings highlight critical alterations in immune cell functions that may contribute to T2D progression and suggest possible avenues for future therapeutic investigation. Future research should continue to leverage scRNA-seq technology to refine treatment strategies and enhance patient outcomes by addressing immune dysfunction and chronic inflammation.},
}

@article {pmid41208712,
year = {2025},
author = {Godrich, D and Pasteris, J and Martin, ER and Kunkle, B and Naj, AC and Hamilton, K and Wang, H and Lee, WP and Dumitrescu, L and Hohman, TJ and Mayeux, R and Larson, EB and Crane, PK and Keene, CD and Latimer, C and Mukherjee, S and Kofler, J and Kamboh, MI and Bennett, DA and Molina-Porcel, L and Schellenberg, G and Pericak-Vance, MA and Cuccaro, M and Scott, WK and Rundek, T and Kukull, W and Montine, T and Beecham, GW and , },
title = {Genome-wide association studies of TDP-43 proteinopathy and hippocampal sclerosis reveal shared genetic associations with APOE and TMEM106B.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {11},
pages = {e70760},
pmid = {41208712},
issn = {1552-5279},
support = {R01-AG062695//Primary Funding includes (additional funding in Acknowledgements)/ ; AG074855//Primary Funding includes (additional funding in Acknowledgements)/ ; U01-AG016976//National Alzheimer's Coordinating Center (NACC)/ ; U24-AG21886//National Cell Repository for Alzheimer's Disease (NCRAD)/ ; U24-AG041689//National Institute on Aging Alzheimer's Disease Data Storage Site (NIAGADS)/ ; U01-AG032984//Alzheimer's Disease Genetics Consortium (ADGC)/ ; RC2-AG036528//Alzheimer's Disease Genetics Consortium (ADGC)/ ; U24-AG074855//ADSP Phenotype Harmonization Consortium (ADSP-PHC)/ ; U01-AG068057//ADSP Phenotype Harmonization Consortium (ADSP-PHC)/ ; R01-AG059716//ADSP Phenotype Harmonization Consortium (ADSP-PHC)/ ; AG006781//Adult Changes in Thought (ACT)/ ; AG066567//Adult Changes in Thought (ACT)/ ; AG030653//University of Pittsburg/ ; AG041718//University of Pittsburg/ ; AG064877//University of Pittsburg/ ; P30-AG066468//University of Pittsburg/ ; P30-AG010161//Rush University (ROSMAP)/ ; R01-AG019085//Rush University (ROSMAP)/ ; R01-AG15819//Rush University (ROSMAP)/ ; R01-AG17917//Rush University (ROSMAP)/ ; R01-AG3014//Rush University (ROSMAP)/ ; },
abstract = {INTRODUCTION: Transactive response DNA binding protein 43 kDa (TDP-43) proteinopathy has been linked to cognitive decline and often co-occurs with hippocampal sclerosis (HS). To identify genetic markers of TDP-43 proteinopathy and HS, we performed genome-wide association studies (GWASs) of HS and TDP-43 inclusions.

METHODS: Genetic data were obtained through the Alzheimer Disease Genetics Consortium and collaborating sites (HS: N = 9509; TDP-43: N = 4669). Statistical analyses included association analysis with HS and TDP-43 inclusions and meta-analysis, a mediation analysis, and fine mapping of the transmembrane protein 106B (TMEM106B) region.

RESULTS: Two regions achieved genome-wide significance with TDP-43: apolipoprotein E (APOE) and TMEM106B. Three loci reached genome-wide significance with HS: APOE, TMEM106B, and granulin precursor (GRN). Fine mapping of TMEM106B identified 93 variants in the credible set. Mediation analyses showed that genetic effects on HS were partially mediated through TDP-43 proteinopathy.

DISCUSSION: We identified associations with TDP-43 inclusion and HS, showing shared genetic risk across frontotemporal lobar degeneration, amyotrophic lateral sclerosis, Alzheimer's disease, and limbic-predominant age-related TDP-43 encephalopathy.

HIGHLIGHTS: HS and TDP-43 contribute to dementia and often co-occur. The etiology and relationship of HS and TDP-43 remains unclear. HS and TDP-43 share genetic risk factors in the genes APOE and TMEM106B. Genes have direct effects on HS, with additional effects mediated through TDP-43.},
}

@article {pmid41207985,
year = {2025},
author = {Mei, J and Li, L and Ma, ZS},
title = {Unraveling the Ecological Mechanisms Influencing the Structure and Composition of Lung Cancer Microbiomes.},
journal = {Microbial ecology},
volume = {88},
number = {1},
pages = {119},
pmid = {41207985},
issn = {1432-184X},
abstract = {This study investigates the ecological mechanisms governing the structure and composition of lung microbiome communities within tumor tissue from lung cancer patients. While this field has attracted increasing research attention, the ecological and etiological mechanisms driving microbial community assembly in this environment remain poorly characterized. To address this gap, we applied Sloan's near neutral model, Ning et al.'s normalized stochasticity ratio framework and Harris et al.'s multi-site neutral model to evaluate the influences of stochastic and deterministic factors at species, community and metacommunity levels, respectively. Our findings include: (i) Stochastic drift exhibited predominant influence at both species and community levels in normal adjacent tissue (NT), exceeding its effects in LUAD (lung adenocarcinoma) and LUSC (lung squamous cell carcinoma). (ii) At the metacommunity level, neutrality was not rejected at the metacommunity or local community levels, which is consistent with the previous finding (i). (iii) Elevated metacommunity biodiversity (θ) and immigration rates (m) in LUAD/LUSC compared to NT (observed in ∼50% of cases) suggest that tumor occurrence/progression may actively promote microbial recruitment to tumor microenvironments. We propose three non-exclusive mechanistic interpretations: (i) Tumor-mediated immune modulation creates permissive ecological niches; (ii) structural remodeling of tissue enhances microbial colonization potential; (iii) selective enrichment of opportunistic taxa (e.g., Streptococcus) through tumor-specific microenvironmental changes. Our results demonstrate that LUAD and LUSC microbiomes are shaped by deterministic tumor-driven selection, in contrast to the predominantly stochastic assembly observed in NT microbiomes. These findings reveal substantial reorganization of tumor-associated microbial communities, warranting further biomedical investigation and clinical validation.},
}

@article {pmid41207946,
year = {2025},
author = {Kahana, GK and Codish, S},
title = {When the hospital becomes the battlefield: patients as stakeholders in mass casualty incidents.},
journal = {Israel journal of health policy research},
volume = {14},
number = {1},
pages = {64},
pmid = {41207946},
issn = {2045-4015},
abstract = {ABSTRACT: Hospitals are uniquely positioned during disasters, functioning as first-line responders and at risk themselves. While system preparedness and staff resilience have been widely studied, the experience and preparedness of patients admitted to hospitals during mass casualty incidents (MCIs) have received little attention. This commentary was prompted by the recent study of Wolff et al., which assessed inpatients’ knowledge of how to respond during an MCI and the barriers they perceived in such situations. Their work highlights gaps in patient awareness and preparedness, raising the question of whether and how inpatients should be involved in disaster response. Drawing on the experience of Soroka Medical Center during the June 2025 Israel–Iran conflict, we reflect on these findings in the context of a real-world missile strike on a major tertiary medical center. On June 19, 2025, Soroka was directly struck by a ballistic missile that destroyed a surgical inpatient building, rendering 562 beds unusable and necessitating mass evacuation and transfers. The event revealed the complexity of patient reactions—from acute fear and uncertainty to pragmatic acceptance of crowding in compromised conditions. Hospital leadership rapidly instituted patient education on air-raid protocols, relocated vulnerable patients, and implemented staff refresher training. Despite these efforts, challenges in communication, rumor control, and logistics significantly affected inpatients’ sense of safety and continuity of care.

CONCLUSIONS: Wolff et al.’s study and Soroka’s lived experience converge on a critical insight: patients cannot be passive bystanders in disasters. Their perceptions, behaviors, and resilience have a direct impact on hospital functionality. Future research should define the scope of patient roles in preparedness, assess the psychological impact of preparedness training, and inform scalable policies for integrating patients into hospital resilience frameworks. Incorporating patient preparedness into disaster planning is crucial, especially during times of heightened alert and in regions prone to conflict or natural disasters.},
}

@article {pmid41207217,
year = {2025},
author = {Wu, Y and Huang, S and Sha, Q and Yu, J},
title = {Emerging and Re-emerging viruses as triggers of human endogenous retrovirus activation: Implications for aging and age-related pathologies.},
journal = {Molecular aspects of medicine},
volume = {106},
number = {},
pages = {101422},
doi = {10.1016/j.mam.2025.101422},
pmid = {41207217},
issn = {1872-9452},
abstract = {The human genome contains a substantial legacy of ancient retroviral infections known as Human Endogenous Retroviruses (HERVs), composing 8 % of our DNA. In healthy young individuals, these elements are kept dormant by robust epigenetic mechanisms, primarily DNA methylation and repressive H3K9me3 histone marks. However, this epigenetic silencing deteriorates with age, leading to the reactivation of HERVs, particularly the youngest HERV-K subfamily. This report posits that this HERV awakening is not a passive byproduct of aging but an active, transmissible driver of pathology. The reactivation of HERVs leads to the production of retrovirus-like particles (RVLPs) that can induce senescence in healthy neighboring cells, propagating a contagious aging phenomenon. Furthermore, the accumulation of HERV-derived dsRNA and reverse-transcribed DNA triggers chronic innate immune responses through pathways including cGAS-STING and IFIH1-MAVS, fueling the systemic, low-grade inflammation characteristic of inflammaging, catalytically accelerated by exogenous viral infections. Pathogens such as SARS-CoV-2, Epstein-Barr Virus (EBV), and Herpes Simplex Virus (HSV-1) can directly transactivate HERVs via their own viral proteins, overwhelming the already compromised epigenetic controls in an aging host. This mechanistic link between viral triggers and endogenous retroviral activity is strongly implicated in a range of age-related diseases, including neurodegenerative disorders such as Alzheimer's disease and Amyotrophic Lateral Sclerosis (ALS), where the HERV-K envelope protein is directly neurotoxic. It is also linked to autoimmune diseases like Multiple Sclerosis and various cancers. This report synthesizes these findings and identifies a novel mechanistic link between viral activity, chronic inflammation, and the onset of age-related diseases.},
}

@article {pmid41206819,
year = {2025},
author = {Buonocore, J and Fratto, E and Arcuri, F and Vescio, B and Calomino, C and Talarico, M and Cristiani, CM and Quattrone, A and Quattrone, A},
title = {Plasma NfL and GFAP in the preclinical stages of neurodegenerative diseases: insights from the UK Biobank.},
journal = {Journal of neurology},
volume = {272},
number = {12},
pages = {755},
pmid = {41206819},
issn = {1432-1459},
abstract = {BACKGROUND: Plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are promising blood-based biomarkers of neuroaxonal injury and astrocytic activation, relevant in neurodegeneration. We investigated their pre-diagnostic profiles across common neurodegenerative diseases, including Parkinson's disease (PD), atypical parkinsonian disorders (APD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS).

METHODS: Forty-eight thousand five hundred and twenty-four UK Biobank participants with baseline plasma proteomic data for NfL and GFAP were included. Incident diagnoses of PD, APD, AD, and ALS were identified through ICD-10-coded health records, after careful inclusion/exclusion procedures. Baseline plasma NfL and GFAP concentrations were standardized as z-scores adjusted for relevant covariates. The hazard ratio (HR) for incident neurodegenerative diseases was estimated using Cox regression models adjusted for demographic, clinical, socioeconomic and genetic factors.

RESULTS: The final sample included 1196 cases (505 PD, 26 APD, 476 AD, 189 ALS) and 44,107 control subjects. In Cox regression models, NfL was associated with higher risk of incident ALS (HR 1.69; 95% CI, 1.58-1.80, p < 0.001), APD (HR 1.51; 95% CI, 1.22-1.87, p < 0.001), AD (HR 1.31; 95% CI, 1.22-1.41, p < 0.001), and PD (HR 1.14; 95% CI, 1.05-1.23, p < 0.001). GFAP was independently associated with incident AD only (HR 1.72; 95% CI, 1.63-1.82, p < 0.001).

CONCLUSION: Plasma NfL and GFAP showed distinct pre-diagnostic profiles. NfL was associated with incident diagnosis of several neurodegenerative diseases, while GFAP was specific to AD, reinforcing its role in dementia. These results may help optimize the identification of target populations at risk of neurodegenerative diseases for future neuroprotective treatments.},
}

@article {pmid41206134,
year = {2025},
author = {Allel, K and Palmer, T and Abou Jaoude, GJ and Korotych, O and Yedilbayev, A and Vilc, V and Corloteanu, A and Macari, M and Evghenia, C and Laticevschi, D and Shakhimurat-Shaimovich, I and Anar-Saduakasovna, R and Gulzhan-Elbrusovna, T and Anatolievna-Ryazanet, D and Shahrizada-Yergalymovna, A and Yatskevich, N and Skrahina, A and Zhurkin, D and Avaliani, Z and Kiria, N and Lomtadze, N and Kiria, N and Avaliani, T and Khonelidze, I and Danelia, M and Maxim, C and Haghparast-Bidgoli, H and Skordis, J},
title = {Cost-effectiveness of modified fully oral 9-month treatment regimens for rifampicin-resistant tuberculosis in Belarus, Georgia, Kazakhstan and the Republic of Moldova.},
journal = {BMJ global health},
volume = {10},
number = {11},
pages = {},
doi = {10.1136/bmjgh-2024-018099},
pmid = {41206134},
issn = {2059-7908},
abstract = {INTRODUCTION: Prior to 2020, treatment options for multidrug-resistant tuberculosis (MDR-TB) were limited and typically involved long treatment durations and high financial burdens. In the eastern European and central Asian (EECA) region, traditional inpatient tuberculosis (TB) care models, alongside high MDR-TB rates, escalate nosocomial transmission risks and treatment costs. Modified, fully oral, shorter treatment regimens (mSTR) implemented in the WHO European Region under operational research conditions offered a potential reduction in the burden of MDR-TB treatment for both patients and health systems.

METHODS: We conducted the first regional evaluation of the cost-effectiveness of the novel mSTR treatment regimen compared with the standard of care (SOC) in Belarus, Georgia, Kazakhstan and Republic of Moldova. We used cohort data on mSTR efficacy and WHO data on SOC in patients with MDR-TB. We used a Markov model, with treatment costs calculated from the provider perspective. Outcomes were measured in quality-adjusted life years (QALYs), with incremental cost-effectiveness ratios (ICER) calculated per QALY gained in each country. An annual 3% discount rate was used for both costs and outcomes. We performed univariate and probabilistic sensitivity analysis (PSA) to assess the robustness of our cost-effectiveness calculations under varying assumptions. Finally, we estimated potential cost savings if mSTR was implemented nationally and we evaluated the incremental net monetary benefit (iNMB) and willingness-to-pay (WTP) thresholds based on Wood et al's country-level cost-effectiveness thresholds. All costs were reported in 2022 USD.

RESULTS: We estimated that mSTR can reduce TB treatment costs by between 23% and 47% and drug costs by 39% to 74%, compared with SOC in the countries studied. mSTR resulted in cost savings of between $3596 and $8174 per patient and offered additional health gains of between 0.56 to 2.69 QALYs per patient. mSTR remained cost-effective (iNMB>0) compared with SOC in 78%, 85%, 91% and 92% of PSA simulations in Belarus, Georgia, Kazakhstan and Republic of Moldova, respectively, when compared with their country-level WTP threshold. Implementing mSTR in up to 80% of MDR/rifampicin-resistant TB patients may result in cost savings of $20.5, 2.5, 0.7 and 0.2 million in Kazakhstan, Belarus, Republic of Moldova and Georgia; equivalent to 17%, 3%, 4% and 1% of their national TB budgets, respectively.

CONCLUSIONS: Compared with SOC, mSTR is a more cost-effective treatment option for MDR/RR-TB, which should be considered by policymakers in the EECA region. Using insights from current implementations to scale up, plan operational changes and reallocate savings from mSTR could greatly enhance TB services and patient care.},
}

@article {pmid41205880,
year = {2025},
author = {Cho, H and Lee, B and Son, C and Choi, J and Eom, S and Park, J},
title = {ERLIN1: A central regulator of protein quality control, lipid homeostasis, and cellular signaling at the endoplasmic reticulum.},
journal = {Cellular signalling},
volume = {},
number = {},
pages = {112224},
doi = {10.1016/j.cellsig.2025.112224},
pmid = {41205880},
issn = {1873-3913},
abstract = {Endoplasmic reticulum lipid raft-associated protein 1 (ERLIN1) is an endoplasmic reticulum (ER)-resident stomatin/prohibitin/flotillin/HflK/C (SPFH) family protein that assembles into oligomeric complexes within detergent-resistant membrane domains. ERLIN1 regulates multiple cellular functions, including protein quality control, calcium signaling, and lipid metabolism. Together with ERLIN2, it forms ER-associated degradation (ERAD) nanodomains through interactions with RING finger protein 170 (RNF170) and transmembrane and ubiquitin-like domain-containing 1 (TMUB1). These specialized domains facilitate the degradation of inositol 1,4,5-trisphosphate receptor type 1 (IP3R) via the ERAD pathway. ERLIN1 also controls cholesterol metabolism by inhibiting sterol regulatory element-binding protein (SREBP) activation and promoting 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) degradation. In addition, it blocks cholesterol esterification, thereby enhancing cholesterol transport to the Golgi apparatus. ERLIN1 further regulates cell fate by promoting autophagy and suppressing apoptosis; in complex with ERLIN2, it interacts with activating molecule in Beclin 1-regulated autophagy protein 1 (AMBRA1) at mitochondria-associated membranes to initiate autophagy and binds phosphatidylinositol 3-phosphate to stabilize autophagy signaling. Its overexpression enhances tumor progression, whereas silencing triggers apoptosis in colorectal cancer. Mutations in ERLIN1 are linked to neurodegenerative diseases such as hereditary spastic paraplegia type 62 and atypical amyotrophic lateral sclerosis. The ERLIN1/2 complex also influences immune responses and viral replication through cholesterol regulation. Collectively, these diverse and integrated functions highlight the potential of ERLIN1 as a therapeutic target in cancer, metabolic, neurodegenerative, and infectious diseases.},
}

@article {pmid41205804,
year = {2025},
author = {Akan, T and Alp, S and Aishwarya, R and Xing, DG and Dicharry, D and Bhuiyan, MS and Bhuiyan, MAN},
title = {PathViT: Automated disease classification from skeletal muscle histopathology.},
journal = {The American journal of pathology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajpath.2025.10.009},
pmid = {41205804},
issn = {1525-2191},
abstract = {Analyzing skeletal muscle pathology from histological images is a labor-intensive process prone to inter- and intra-user variability influencing diagnosis accuracy and consistency-conventional techniques, such as ImageJ-based tools, demand manual cell counting, segmentation, and thresholding. As a result, they are time-consuming and create different results. To address these difficulties, we developed PathViT, a transformer-based deep learning model for automated classification of pathological images. Skeletal muscle pathology is characterized by changes in myofiber cross-sectional area, increased central nuclei, and structural disruptions in sarcomeres. To investigate these changes in myofiber size, we utilized Wheat Germ Agglutinin (WGA) stained histopathological images of different skeletal muscles (quadriceps, gastrocnemius, tibialis anterior, extensor digitorum longus, and soleus) to classify amyotrophic lateral sclerosis (ALS), diabetes, and healthy controls. PathVit can automatically distinguish between healthy and diseased muscle fibers, reducing human intervention, minimizing subjectivity and variability, and significantly decreasing analysis time compared to traditional manual methods. We evaluated PathViT against state-of-the-art deep learning models using WGA-stained skeletal muscle images from wild-type and disease models (G93A*SOD1 for ALS and Akita for Type 1 diabetes). PathViT classified healthy and diseased muscle fibers with 96% accuracy, outperforming all other models. Compared to manual methods, PathVit reduces human intervention, subjectivity, variability, and analysis time. This approach enhances scalability, diagnostic accuracy, and variability, making PathViT a powerful biomedical research and clinical tool.},
}

@article {pmid41205733,
year = {2025},
author = {Hendricus Maes, KJ and Briedé, JJ},
title = {Repurposing immunomodulatory drugs targeting microglia for amyotrophic lateral sclerosis.},
journal = {Brain research},
volume = {},
number = {},
pages = {150032},
doi = {10.1016/j.brainres.2025.150032},
pmid = {41205733},
issn = {1872-6240},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that progressively affects upper and lower motor neurons, leading to symptoms including dysarthria, muscle weakness, and paralysis. The disease is multifactorial, with a variety of contributing pathways, including excitotoxicity, oxidative stress, and neuroinflammation. Current treatments target only two of these pathways with limited efficacy, highlighting the need for alternative approaches. Increasing evidence highlights the involvement of immune dysregulation, particularly microglial-mediated neuroinflammation, in ALS pathology. Fortunately, many immunomodulatory drugs acting on microglia are already available for other diseases, indicating promising opportunities for drug repurposing. This literature review provides an overview of existing drugs under investigation for ALS, including those that have failed, and highlights new microglia-targeting candidates with repurposing potential. Compounds such as ibudilast, fingolimod, and modafinil have shown encouraging initial clinical results, whereas others were well-tolerated but underpowered or failed to demonstrate efficacy. New candidates, such as azithromycin, naltrexone, montelukast, doxycycline, tofacitinib, quercetin, belinostat, and several kinase inhibitors, have demonstrated positive preclinical results, supporting their advancement toward clinical evaluation. Overall, these findings emphasize the potential of microglia-targeting therapies for ALS. To realize this potential, future studies must include larger cohorts, assess effects across disease stages and patient subgroups, and examine sex differences. This is essential to address patient heterogeneity and improve personalized treatment in ALS.},
}

@article {pmid41204694,
year = {2025},
author = {Scirocco, E and Luppino, SD and Allen, MD and Giacomelli, E and Gelevski, D and Higgins, M and Scalia, JL and McCaffrey, AC and Sanders, DL and Ho, DT and Quarles, B and Dalamagas, H and Heintzman, S and Paganoni, S},
title = {Amyotrophic Lateral Sclerosis Clinical Research Site Operations: Emerging Challenges and Potential Solutions From Multiple Sites in the US.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70054},
pmid = {41204694},
issn = {1097-4598},
abstract = {As the amyotrophic lateral sclerosis (ALS) clinical trial landscape continues to grow and evolve, optimization of research site efficiency is essential. Herein, we outline results from a formal discussion among multiple ALS research sites in the US to help establish and maintain efficient research site infrastructure. Ten ALS site managers collaborated over a 6-month period to develop a framework of operational strategies to support ALS clinical research sites. To address the evolving ALS research landscape, it was agreed that the traditional site operational model requires continuous evaluation and adaptation. Challenges, particularly affecting staff recruitment and retention (such as salary, burnout, and limited opportunities for professional growth for certain positions), were discussed. The group identified challenges related to increased burden to maintain staff training, evolving outcome measures, and limitations in available space. Sites agreed on the importance of well-trained and experienced site personnel, and the emergence of site research nurses and nurse practitioners as trial leaders. Successful strategies to address staffing barriers were discussed, recognizing the need for ongoing improvements and increased funding to support the research team. A centralized organizational approach, consisting of multiple specialized study teams supported by an overarching site operations infrastructure, was identified as a key driver to optimize staff performance, accelerate trial conduct, and streamline workflow. Future initiatives should include refining strategies to continuously enhance site operations, identify key metrics to quantify efficiency and ensure financial sustainability.},
}

@article {pmid41204026,
year = {2025},
author = {Seemikeri, C and Menon, D and Nashi, S and Arshad, F and Srijithesh, PR and Alladi, S},
title = {Facial onset sensory and motor neuronopathy: a diagnostic challenge.},
journal = {Acta neurologica Belgica},
volume = {},
number = {},
pages = {},
pmid = {41204026},
issn = {2240-2993},
abstract = {Facial onset sensory and motor neuronopathy (FOSMN) is a rare neurological disorder that combines features of both sensory neuropathy and motor neuron disease. Its clinical resemblance to trigeminal neuralgia and amyotrophic lateral sclerosis (ALS) often leads to delayed or incorrect diagnosis. Recent evidence suggests that FOSMN may represent a sensory-onset variant within the ALS spectrum, characterised by the addition of cranial and limb sensory involvement. The present report highlights this diagnostic challenge and emphasises that FOSMN can occur with prominent sensory symptoms and cranial nerve dysfunction even in the absence of significant bulbar features. Recognising this pattern broadens the classical understanding of motor neuron diseases, which are traditionally viewed as purely motor disorders. Awareness of such presentations and the use of targeted neurophysiological tests, particularly blink reflex studies, are essential for accurate diagnosis and better characterisation of this rare and evolving disease spectrum.},
}

@article {pmid41203507,
year = {2025},
author = {Zhang, YP and Kedia, S and Klenerman, D},
title = {Rethinking neurodegeneration through a co-proteinopathy lens.},
journal = {Trends in neurosciences},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tins.2025.10.006},
pmid = {41203507},
issn = {1878-108X},
abstract = {Neurodegenerative diseases have long been considered distinct proteinopathies: amyloid-β and tau in Alzheimer's disease, α-synuclein in Parkinson's disease, and TDP-43 in amyotrophic lateral sclerosis. This single-protein paradigm has guided therapeutic development for decades; yet clinical outcomes remain modest. Mounting evidence, however, reveals that protein aggregates rarely occur in isolation; instead, they coexist, colocalise, and modulate each other's pathogenicity. Here, we propose a co-proteinopathy framework that views neurodegeneration as an interactive network of misfolded proteins rather than as isolated disorders. Adopting this framework demands multiplexed quantification of protein aggregates and disease models that better reflect the biological complexity of human neurodegeneration. The co-proteinopathy perspective offers a more realistic foundation for next-generation approaches to neurodegeneration research and treatment.},
}

@article {pmid41202295,
year = {2025},
author = {Sales de Campos, P and Smith-Hublou, M and Olsen, WL and Souza Leite, W and Wymer, JP and Napoli, NJ and Vose, AK and Pulley, MT and Mitchell, GS and Smith, BK},
title = {Acute Adenosine Receptor Antagonism in Combination With Acute Intermittent Hypoxia to Promote Breathing Plasticity in Amyotrophic Lateral Sclerosis: Protocol for a Randomized, Double-Blinded, Placebo-Controlled Trial.},
journal = {JMIR research protocols},
volume = {14},
number = {},
pages = {e76105},
doi = {10.2196/76105},
pmid = {41202295},
issn = {1929-0748},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/drug therapy/therapy ; Double-Blind Method ; *Hypoxia/physiopathology ; Purines/therapeutic use/pharmacology ; *Respiration/drug effects ; *Neuronal Plasticity/drug effects ; *Purinergic P1 Receptor Antagonists/therapeutic use ; Randomized Controlled Trials as Topic ; Male ; Adult ; Middle Aged ; Female ; },
abstract = {BACKGROUND: Respiratory impairment is a major concern in amyotrophic lateral sclerosis (ALS), shortening survival and lowering quality of life. One therapy with promise to delay respiratory decline in ALS is acute intermittent hypoxia (AIH), consisting of alternating periods of breathing mildly hypoxic (9%-12% O2) and normoxic (21% O2) gas. AIH stimulates spinal, serotonin-dependent neuroplasticity in rodent models, conferring functional benefits in diverse physiological systems without detectable pathology. However, in rodent models, AIH-induced neuroplasticity is constrained by distinct signaling cascades initiated by spinal adenosine.

OBJECTIVE: We propose to investigate a therapeutic strategy to delay breathing compromise in those living with ALS by combining a selective adenosine 2A (A2A) receptor inhibitor (istradefylline) with AIH. The fundamental hypothesis guiding this proposal is that a single AIH trial after pretreatment with istradefylline enhances respiratory neuroplasticity versus AIH or sham intervention.

METHODS: We propose to evaluate resting breathing, respiratory strength, and participant-reported symptoms in adults living with ALS after combined istradefylline plus AIH. A mixed within- and between-participant study design incorporates 4 test sessions, separated by approximately 2 weeks (±5 days). Testing conditions include single sessions of AIH + istradefylline, AIH + placebo, sham AIH (ie, normoxia) + placebo, and sham AIH + istradefylline. Safety and feasibility will be characterized using the rate of adverse events, changes in vital signs, and participant-reported breathing sensations (Aim 1). Neuroplasticity of breathing and motor function will be evaluated as changes in resting breathing, voluntary respiratory strength, respiratory control, and maximal pinch force (Aim 2).

RESULTS: As of January 2025, with a target sample of 16 participants in each group, 10 participants with ALS and 5 control participants completed study procedures. Recruiting is ongoing, and the final participant will complete the study by December 2025. Publication of results is expected by the end of 2026.

CONCLUSIONS: These aims will provide crucial data regarding the preliminary safety and feasibility of this paired intervention and help optimize therapeutic AIH as a rehabilitation strategy, thereby guiding further research concerning this novel treatment for ALS.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05377424; https://clinicaltrials.gov/study/NCT05377424.

DERR1-10.2196/76105.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/drug therapy/therapy
Double-Blind Method
*Hypoxia/physiopathology
Purines/therapeutic use/pharmacology
*Respiration/drug effects
*Neuronal Plasticity/drug effects
*Purinergic P1 Receptor Antagonists/therapeutic use
Randomized Controlled Trials as Topic
Male
Adult
Middle Aged
Female

@article {pmid41202020,
year = {2025},
author = {Senior, E and Clarke, A and Wilson-Menzfeld, G},
title = {Living with a loved one's mental health issue: Recognizing the Lived Experiences of Military Spouses.},
journal = {PloS one},
volume = {20},
number = {11},
pages = {e0336295},
pmid = {41202020},
issn = {1932-6203},
mesh = {Humans ; *Spouses/psychology ; Female ; Male ; *Military Personnel/psychology ; *Mental Health ; Adult ; Middle Aged ; Qualitative Research ; *Mental Disorders/psychology ; },
abstract = {Limited evidence surrounds the lived experiences of military spouses whose partner has mental health issues. This lack of evidence may be due to factors such as global austerity, underfunding of armed forces, and inadequate healthcare systems. As a result, family members-especially spouses-often end up being the primary caregivers for their military partners with mental health issues. The study used a qualitative, biographical methodology, collecting data through life stories. Two face-to-face semi-structured interviews took place with nine military spouse recruited through military spouse networks and snowballing. Lieblich et al.'s (1998) framework provided analytical pluralism, which allowed for both narrative and thematic analysis. Stories are presented in the stages 'in the beginning', changing times' and 'this is me'. Thematic analysis identified six overarching categories; Living with disruption, living in the midst of it all, It isn't enough, seeking support, Diagnosis and treatment, Living alongside. Whilst the first of its kind in the UK, this biographical study advances both national and global understanding of military spouse experiences in the context of mental health. Both the stories and the categories indicate that living with a serving partner who has mental health issues is a complex journey marked by both struggle and growth. A uniqueness arising from this study highlights the period leading up to a mental health diagnosis, emphasising the prolonged emotional and psychological strain experienced by military spouses before any formal recognition of mental illness in their serving partner. The study adds a new dimension to understanding the emotional toll on military spouses and underscores the importance of early recognition and support. While participants faced emotional detachment and feelings of invisibility, they also identified gains in resilience and strengthened relationships. Through the convergence of the narrative and thematic analysis the participants experience throughout their partners mental health issue is conceptualised in a Relationship Trajectory model. It illustrates the positive, early relational strength, superseded by relationship decline followed with relationship reinvention.},
}

Humans
*Spouses/psychology
Female
Male
*Military Personnel/psychology
*Mental Health
Adult
Middle Aged
Qualitative Research
*Mental Disorders/psychology

@article {pmid41201719,
year = {2025},
author = {Gautam, P and Vishwakarma, RK and Nath, M and Nath, G and Pathak, A},
title = {Microbiota Dysbiosis in Amyotrophic Lateral Sclerosis: A Systematic Review of Human Studies.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {10},
pmid = {41201719},
issn = {1559-1182},
mesh = {*Amyotrophic Lateral Sclerosis/microbiology/complications ; Humans ; *Dysbiosis/microbiology/complications ; *Gastrointestinal Microbiome/physiology ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron degeneration. Despite intensive research, its pathogenesis remains poorly understood. Recent insights suggest a pivotal role of the gut microbiota in modulating neuroinflammation and neurodegeneration via the gut-brain axis. This systematic review aims to synthesize clinical evidence on gut microbiota dysbiosis in ALS, exploring microbial and metabolic alterations and their associations with disease progression and severity. A comprehensive literature search was conducted across PubMed, Embase, Scopus, Web of Science, and other databases up to May 10, 2024, adhering to PRISMA 2020 guidelines. Eighteen eligible human studies were selected based on predefined inclusion criteria. Data on microbial diversity, taxonomic shifts, metabolite profiles, and clinical correlations were extracted and assessed using a modified Newcastle-Ottawa Scale. Most studies reported altered microbial diversity, reduced butyrate-producing bacteria (e.g., Faecalibacterium, Roseburia), and increased pro-inflammatory taxa (e.g., Escherichia coli, Bacteroides) in ALS. Integrated microbiome-metabolome analyses revealed disruptions in SCFAs, bile acids, and lipid metabolism, some correlating with ALSFRS-R scores and cognitive impairment. Although some studies showed minimal or no differences, the overall evidence supports a link between dysbiosis and ALS pathophysiology. Probiotic trials demonstrated limited efficacy, highlighting the need for targeted, patient-specific interventions. Gut microbiota dysbiosis is increasingly recognized as a contributor to ALS progression. However, methodological variability, small sample sizes, and limited longitudinal data restrict definitive conclusions. Future research should employ standardized, multi-omics approaches and larger cohorts to clarify causal links and develop microbiome-informed diagnostics and therapies for ALS.},
}

*Amyotrophic Lateral Sclerosis/microbiology/complications
Humans
*Dysbiosis/microbiology/complications
*Gastrointestinal Microbiome/physiology

@article {pmid41201375,
year = {2025},
author = {Tomlinson, J and Roberson, E and Klee, V and Ma, J and Roggenbuck, J},
title = {A study of patient recall and comprehension of genetic testing results in amyotrophic lateral sclerosis (ALS).},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/21678421.2025.2582829},
pmid = {41201375},
issn = {2167-9223},
abstract = {Objective: Assess the accuracy of ALS patient recall of genetic testing results and evaluate comprehension of key implications of results. Methods: Participants were recruited from the Center for Disease Control's National ALS Registry. A survey collected participant demographics, their recollection of their genetic test result, and their understanding of the implications of their result. Comprehension was scored based on responses to key questions. Whenever possible, patient-reported test results were confirmed by review of their test report. Results: Most participants (n = 246) were white (n = 238, 96.7%) with high health literacy. Among participants whose self-reported result could be validated, most 93/98 (94.9%) accurately recalled whether they received a positive, negative, or uncertain result. Among participants who reported positive results, 32/50 (64.0%) demonstrated understanding that their genetic testing results explained their ALS, while 38/50 (76.0%) accurately characterized the risk that first degree relatives carried the same variant. Among participants who reported negative results, 100/142 (70.4%) incorrectly indicated that their result ruled out a genetic cause. When asked about the risk for family members to develop ALS, 98/142 (69.0%) correctly characterized this residual risk. However, only 12/142 (8.5%), answered both questions correctly. Overall, participants who saw a genetic counselor were more likely to demonstrate high comprehension (p = 0.022). Conclusions: The majority of participants demonstrated accurate recall of their ALS genetic testing result. However, deficits in understanding of key implications were identified, particularly among those with negative results. Participants who saw a genetic counselor had significantly better comprehension of their test results than those who did not.},
}

@article {pmid41201205,
year = {2025},
author = {Canosa, A and Callegaro, S and Manera, U and Vasta, R and Cabras, S and Di Pede, F and De Mattei, F and Palumbo, F and Iazzolino, B and Giudici, AD and Matteoni, E and Zocco, G and Minerva, E and Maccabeo, A and Pellegrino, G and Pascariu, D and Grassano, M and Ciresi, F and Testa, M and Polverari, G and Salamone, P and De Marco, G and Paolantonio, C and Marchese, G and Moglia, C and Calvo, A and Chiò, A and Pagani, M},
title = {Cognitive Reserve in Amyotrophic Lateral Sclerosis: A 2-[[18]F]FDG-PET Study on Sex-Related Differences.},
journal = {European journal of neurology},
volume = {32},
number = {11},
pages = {e70412},
pmid = {41201205},
issn = {1468-1331},
support = {PRIN 2017SNW5MB//Ministero dell'Università e della Ricerca/ ; //Fondation Thierry Latran/ ; RF-2016-02362405//Ministero della Salute/ ; 259867//Seventh Framework Programme/ ; GA101017598//Horizon 2020 Framework Programme/ ; 101137074//Horizon 2020 Framework Programme/ ; //A.S.D. Polisportiva U.I.C.I Torino Onlus/ ; //Ministry of Education, University and Research of Italy/ ; //Ministry of Health/ ; },
mesh = {Humans ; *Cognitive Reserve/physiology ; Male ; Female ; Positron-Emission Tomography ; Fluorodeoxyglucose F18 ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/metabolism/psychology/complications ; Middle Aged ; Aged ; *Brain/diagnostic imaging/metabolism ; *Sex Characteristics ; Radiopharmaceuticals ; },
abstract = {BACKGROUND: Cognitive reserve (CR) applies to ALS-related cognitive impairment and education is a CR proxy. The influence of sex on CR in ALS is unclear.

METHODS: We compared brain 2-[[18]F]FDG-PET metabolism of male (m-ALS, n = 95) and female (f-ALS, n = 95) patients, matched for age, education, onset, and King's stage, with no significant difference in ECAS scores. In each group, clusters showing a negative/positive correlation with education were used as seed regions in an interregional correlation analysis (IRCA) to evaluate connectivity. We identified the seed regions including age, onset, King's stage and ECAS as covariates.

RESULTS: M-ALS showed a relative hypometabolism compared to f-ALS in bilateral frontotemporal regions. In f-ALS brain metabolism positively correlated with education in the left fusiform gyrus, cerebellum and pons. The IRCA showed a positive correlation of the seed region with the cerebellum, pons, right fusiform gyrus and cuneus, and the left precuneus, and a negative correlation with the frontal lobes and caudate nuclei. In m-ALS brain metabolism negatively correlated with education in the left frontotemporal and insular cortices. The IRCA showed a positive correlation of the seed region with bilateral frontotemporal and cingulate cortices, and the right parietal cortex, and a negative correlation with bilateral cerebellum and motor cortex, and the left lingual gyrus.

CONCLUSIONS: M-ALS showed relative frontotemporal hypometabolism compared to f-ALS, suggesting a male prevalence of CR. In m-ALS the negative correlation of education with left frontotemporal and insular metabolism supports the CR hypothesis. In f-ALS the positive correlation of cerebellar metabolism with education suggests compensatory mechanisms, also supported by the IRCA.},
}

Humans
*Cognitive Reserve/physiology
Male
Female
Positron-Emission Tomography
Fluorodeoxyglucose F18
*Amyotrophic Lateral Sclerosis/diagnostic imaging/metabolism/psychology/complications
Middle Aged
Aged
*Brain/diagnostic imaging/metabolism
*Sex Characteristics
Radiopharmaceuticals

@article {pmid41201192,
year = {2025},
author = {Kumar, S and Kumar, A and Sufiyan, M and Shashi, },
title = {Factor Structure and Measurement Invariance of SDO7 Scale in India.},
journal = {Journal of personality assessment},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/00223891.2025.2583443},
pmid = {41201192},
issn = {1532-7752},
abstract = {Social dominance orientation (SDO) is the generalized preference for hierarchy across groups. It is currently measured through the two-dimensional (i.e., physical dominance and anti-egalitarianism) SDO7 scale. However, a complete testing of its factor structure across varied populations is highly required. A caste-based society perhaps reflects a stronger socio-cultural expression of social dominance theory. In the present study, we examined the factor structure of the SDO7 scale in such a society, using exploratory and confirmatory factor analyses on a sample of 1,020 participants (age: M = 19.5, SD = 2.07 years). The results reported that Ho et al.'s two-factor model was one of the best good-fit models. The SDO7 scale was strongly invariant across gender, caste, religion, and region. Moreover, men and higher caste had higher SDO. The present study shows that the asymmetrical expression of the method effect across dimensions is a possible problem in the SDO conceptualizations. It supports the cross-cultural validity of SDO, suggests new ideas on its factor structure, and partially establishes a reliable and valid Hindi version of the SDO7 scale. Relevance to social dominance theory and interventions has been discussed.},
}

@article {pmid41200140,
year = {2025},
author = {Bourke, CA},
title = {Decreased purine ingestion, increased molybdenum ingestion, and the decline in amyotrophic lateral sclerosis on Guam.},
journal = {Frontiers in nutrition},
volume = {12},
number = {},
pages = {1618834},
pmid = {41200140},
issn = {2296-861X},
}

@article {pmid39505721,
year = {2025},
author = {Lu, GN},
title = {Invited Commentary on: Gossett et al.'s "Lower Lip Fascia Lata Repositioning in Flaccid Facial Paralysis".},
journal = {Facial plastic surgery & aesthetic medicine},
volume = {27},
number = {6},
pages = {504-505},
doi = {10.1089/fpsam.2024.0256},
pmid = {39505721},
issn = {2689-3622},
}

@article {pmid41199620,
year = {2025},
author = {Zelikovich, AS and Ackrivo, J},
title = {Acoustic Features in ALS: Taking a Pause to Appreciate a Novel Remote Respiratory Monitoring Strategy.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70056},
pmid = {41199620},
issn = {1097-4598},
support = {HT9425-25-1-0154//Department of Defense ALS research program/ ; K23 HL-151879/HL/NHLBI NIH HHS/United States ; },
}

@article {pmid41199372,
year = {2025},
author = {Xu, L and Huang, B and Zhou, Y and Liao, X and Chen, T and He, H},
title = {Multi-omics-based decoding of circulating biomarkers in amyotrophic lateral sclerosis and risks in environmental toxins.},
journal = {BMC pharmacology & toxicology},
volume = {26},
number = {1},
pages = {186},
pmid = {41199372},
issn = {2050-6511},
support = {2024Y389//Scientific Research Foundation of Yunnan Provincial Education Department/ ; 2024Y392//Scientific Research Foundation of Yunnan Provincial Education Department/ ; 2024JJ7319//Natural Science Foundation of Hunan Province/ ; 2025JJ70442//Natural Science Foundation of Hunan Province/ ; 2025JJ70465//Natural Science Foundation of Hunan Province/ ; 202412//Doctoral research project initiation fund at Hunan University of Medicine/ ; 202401001789//Reform Project of Hunan Provincial Education Department/ ; 2541STC72898//International Cooperative Project of Traditional Chinese Medicine/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/blood/genetics/diagnosis ; Humans ; Biomarkers/blood ; Proteomics ; Genome-Wide Association Study ; Transcriptome ; *Environmental Pollutants/toxicity ; Machine Learning ; Mendelian Randomization Analysis ; Multiomics ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the interplay of genetic and environmental factors, and currently, there there is a lack of effective diagnostic or therapeutic strategies available. This study aims to identify circulating biomarkers for ALS and investigate their interactions with environmental toxins.

METHODS: This research utilizes plasma proteomic genome-wide association study (GWAS) data and whole blood transcriptomic data from ALS patients to screen for potential circulating biomarkers through Mendelian randomization (MR). Subsequently, functional enrichment analysis and immune infiltration analysis were performed. An integrated machine learning approach will be used to construct a diagnostic model, with hub genes selected based on SHAP values. The model's performance will be validated using receiver operating characteristic (ROC) curves, nomogram, and decision curve analysis (DCA). Finally, reverse network toxicology will be used to explore the interaction mechanisms between hub genes and environmental toxins.

RESULTS: Based on a MR analysis of plasma proteomics, we identified 68 plasma proteins significantly associated with the risk of ALS. By integrating differentially expressed genes (DEGs) from whole blood transcriptomics (1,116 DEGs), we selected four potential circulating biomarkers: FCRL3, HTATIP2, RNASE6, and SF3B4. Functional enrichment analysis indicated that the pathogenesis of ALS is closely related to autophagy, apoptosis, the endoplasmic reticulum unfolded protein response, and the NF-κB signaling pathway. Immune infiltration analysis revealed a disruption of the immune microenvironment mediated by T cells/myeloid cells in ALS patients. Validation through 113 machine learning algorithms showed that the random forest model exhibited the best diagnostic performance (AUC = 0.786), while SHAP analysis confirmed the contribution ranking of hub biomarkers: RNASE6 > FCRL3 > HTATIP2 > SF3B4. Further validation of their diagnostic value was performed using ROC curves, nomograms, and DCA. Environmental toxins analysis revealed that substances such as benzo(a)pyrene exhibit significant neurotoxicity, and molecular docking confirmed that they can interfere with the function of hub biomarkers through strong binding (∆G < -5 kcal·mol⁻¹), suggesting potential environmental pathogenic mechanisms in ALS.

CONCLUSIONS: This study not only highlights the value of FCRL3, HTATIP2, RNASE6, and SF3B4 as potential diagnostic biomarkers and therapeutic targets for ALS but also provides new evidence for the involvement of environmental toxins, particularly benzo(a)pyrene, in the pathogenesis of ALS through gene-environment interactions.},
}

*Amyotrophic Lateral Sclerosis/blood/genetics/diagnosis
Humans
Biomarkers/blood
Proteomics
Genome-Wide Association Study
Transcriptome
*Environmental Pollutants/toxicity
Machine Learning
Mendelian Randomization Analysis
Multiomics

@article {pmid41198658,
year = {2025},
author = {Volik, PI and Kopeina, GS and Zhivotovsky, B and Zamaraev, AV},
title = {p62-dependent caspase-2 activation governs TDP-43 clearance and neuronal fate in ALS.},
journal = {Cell death & disease},
volume = {16},
number = {1},
pages = {801},
pmid = {41198658},
issn = {2041-4889},
support = {222013//Cancerfonden (Swedish Cancer Society)/ ; 181301//Radiumhemmets Forskningsfonder (Cancer Research Foundations of Radiumhemmet)/ ; 23-74-30006//Russian Science Foundation (RSF)/ ; },
}

@article {pmid41198497,
year = {2025},
author = {Xue, Y and Tao, L},
title = {Letter to the Editor: Exploring venous thromboembolism (VTE) risk in patients with acute spinal cord injury (SCI).},
journal = {Injury},
volume = {},
number = {},
pages = {112868},
doi = {10.1016/j.injury.2025.112868},
pmid = {41198497},
issn = {1879-0267},
abstract = {We commend Bassa et al.'s study on VTE risk in acute SCI patients. We propose further exploring rehabilitation strategies, genetic polymorphisms (e.g., factor V Leiden), and inflammatory markers (e.g., CRP, IL-6) to refine personalized VTE prophylaxis and management in this population.},
}

@article {pmid41196652,
year = {2025},
author = {Lang, C and Guillot, SJ and Lule, D and Balz, LT and Knehr, A and Weydt, P and Dorst, J and Kandler, K and Müller, HP and Kassubek, J and Wassermann, L and Da Cruz, S and Roselli, F and Ludolph, AC and Bolborea, M and Dupuis, L},
title = {Early brain-wide disruption of sleep microarchitecture in Amyotrophic Lateral Sclerosis.},
journal = {The Journal of clinical investigation},
volume = {},
number = {},
pages = {},
doi = {10.1172/JCI194555},
pmid = {41196652},
issn = {1558-8238},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS), the major adult-onset motor neuron disease, is preceded by an early period unrelated to motor symptoms, including altered sleep, with increased wakefulness and decreased deep NREM. Whether these alterations in sleep macroarchitecture are associated with, or even precede abnormalities in sleep-related EEG features remains unknown.

METHODS: Here, we characterised sleep microarchitecture using polysomnography in patients with ALS (n=33) and controls (n=32), and in asymptomatic carriers of SOD1 or C9ORF72 mutations (n=57) and non-carrier controls (n=30). Patients and controls with factors that could confound sleep structure, including respiratory insufficiency, were prospectively excluded. Results were complemented in three ALS mouse models (Sod1G86R , Fus∆NLS/+ and TDP-43Q331K).

RESULTS: We observed a brain-wide reduction in the density of sleep spindles, slow oscillations and K-complexes in both early-stage ALS patients and presymptomatic gene carriers. These defects in sleep spindles and slow oscillations correlate with cognitive performance in both cohorts, particularly with scores on memory, verbal fluency and language function. Alterations in sleep microarchitecture were replicated in three mouse models and decreases in sleep spindles were rescued following intracerebroventricular supplementation of MCH or by the oral administration of a dual orexin receptor antagonist.

CONCLUSION: Sleep microarchitecture is associated with cognitive deficits and is causally linked to aberrant MCH and orexin signalling in ALS.

FUNDING: This work was funded by Agence Nationale de la Recherche (ANR-24-CE37-4064, ANR-10-IDEX-0002, ANR-20-SFRI-0012), Fondation Thierry Latran, Association Francaise de Recherche sur la sclérose latérale amyotrophique, Association Française contre les Myopathies (#28944), TargetALS and JPND.},
}

@article {pmid41196279,
year = {2025},
author = {Han, J and Xu, X and Zhao, Y and Xiao, Y and Huang, F and Zhou, J and Huang, H and Wang, G},
title = {Tui Na Acupressure Modulates Treg Immunosuppression via FoxP3/mTORC1 Signalling in ALS Mice.},
journal = {Immunology},
volume = {},
number = {},
pages = {},
doi = {10.1111/imm.70052},
pmid = {41196279},
issn = {1365-2567},
support = {//Hubei Provincial Natural Science Foundation's Innovation/ ; 2023AFD171//Development Joint Fund Project/ ; 2023AFD128//Development Joint Fund Project/ ; 2023AFD170//Development Joint Fund Project/ ; 2025AFD535//Development Joint Fund Project/ ; GZY-KJS-2025-008//Science and Technology Special Project of the State Administration of Traditional Chinese Medicine/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease driven by neuroinflammation, where regulatory T cell (Treg) dysfunction exacerbates immune imbalance. This study explores whether Tui Na acupressure, a traditional Chinese therapy, can restore Treg immunosuppressive function through the FoxP3/mTORC1 signalling pathway to mitigate ALS pathology. In SOD1G93A ALS mice, Tui Na was applied at the Shenshu acupoint, with motor and cognitive functions assessed via rotarod, tail suspension, novel object recognition, and Y-maze tests. Multi-omics (transcriptomics, proteomics), flow cytometry, ELISA, and Western blot analysed Treg proportions, cytokine profiles, and pathway activation. In vitro assays evaluated Treg proliferation and immunosuppression. Tui Na significantly enhanced motor and cognitive performance, increased Treg proportions in spleen, lymph nodes, and blood, and elevated anti-inflammatory cytokines (IL-10, TGF-β) while reducing pro-inflammatory markers (IL-6, TNF-α). Transcriptomic and proteomic analyses revealed upregulated FoxP3, Mtor, and Raptor, with enhanced Treg proliferation and immunosuppression confirmed in vitro. Pathway inhibitors (GSK126, rapamycin) reversed these effects, confirming FoxP3/mTORC1 dependency. Tui Na also reduced apoptosis and oxidative stress, supporting immune regulation. These findings highlight Tui Na's potential to restore Treg-mediated immune balance in ALS, offering a non-pharmacological therapeutic strategy. This study provides novel immunological insights into Tui Na's mechanisms, advocating its clinical evaluation for ALS and related immune-driven disorders.},
}

@article {pmid41196223,
year = {2025},
author = {Beck, J and O'Hara, K and van der Schaaf, M and O'Brien, BC},
title = {How supervisors leverage stress to facilitate trainee learning in clinical settings: A six-element model.},
journal = {Medical education},
volume = {},
number = {},
pages = {},
doi = {10.1111/medu.70084},
pmid = {41196223},
issn = {1365-2923},
support = {//WGEA mini-grant proposal/ ; },
abstract = {BACKGROUND: Excessive stress can hinder learning, whereas moderate stress may enhance it by boosting motivation, memory and cognitive processing. Rudland et al. proposed a theoretical stress-learning pathway in which supervisors play a central role in shaping how stress influences learning. While this pathway offers a valuable high-level framework, the specific ways supervisors enact this role in clinical settings remain underexplored. Our study addresses this gap by examining how supervisors leverage stress to enhance trainee learning in clinical settings.

METHODS: In this constructivist grounded theory study, we interviewed supervisors (senior residents and attending physicians) whom paediatric residents identified as effectively leveraging stress to facilitate learning. We recorded and transcribed semi-structured interviews, which we analysed iteratively throughout the data collection period using constant comparative techniques. We created a model that extends Rudland et al.'s pathway by detailing specific ways that supervisors harness stress to facilitate learning.

RESULTS: We interviewed 23 supervisors (10 senior paediatric residents and 13 attending physicians), all of whom conceptualised stress as a dynamic, individualised experience that can promote learning and prepare trainees for unsupervised practice. Supervisors both introduced stressors and modulated naturally occurring stressors (e.g. delivering difficult news or managing a decompensating patient) as they supported trainees in challenging situations. Attending physicians, more than senior residents, reported difficulty gauging trainee stress, citing power dynamics as a barrier. Our analysis produced a six-element model explaining how supervisors use stress to support learning: setting the stage, assessing baseline stress, introducing or modulating stressors, re-assessing, and debriefing.

CONCLUSIONS: Our findings suggest supervisors leverage stress to enhance learning in inpatient clinical environments but do so cautiously to ensure stress does not reach a level that impedes learning. Through a proactive approach, supervisors introduce and modulate stressors-thereby creating individualised learning experiences that they expect to prepare trainees for the demands of independent practice.},
}

@article {pmid41196070,
year = {2025},
author = {Kartanou, C and Kontogeorgiou, Z and Loupis, T and Vrachnos, DM and Ragazos, N and Spyropoulou, I and Petraki, M and Koniari, C and Aristeidou, S and Koropouli, E and Daponte, A and Rentzos, M and Kapaki, E and Panas, M and Makrythanasis, P and Stefanis, L and Koutsis, G and Karadima, G},
title = {Unraveling the genetic landscape of ALS in Greece: identification of known and novel causative variants in a 353-patient cohort.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/21678421.2025.2582828},
pmid = {41196070},
issn = {2167-9223},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is an adult-onset, progressive, fatal neurodegenerative disorder characterized by progressive loss of motor neurons. Approximately 15% of individuals diagnosed with ALS have a known genetic variant that contributes to disease. Herein, we present clinical and genetic data of a large Greek ALS cohort.

PATIENTS AND METHODS: The cohort consisted of 353 Greek consecutive index patients with ALS, including 16 patients with related motor neuron disease (MND) subtypes (nine with PLS, four with PBP, and three with PMA). Next generation sequencing raw data (obtained from the NYGC ALS Consortium) were further analyzed and used to screen for causative variants in known implicated genes. Repeat expansions in C9ORF72 and ATXN2 were investigated using ExpansionHunter software, repeat-primed PCR and fragment analysis.

RESULTS: Pathogenic repeat expansions in C9ORF72 were detected in 41 patients (11.6%). In addition, 30 patients (8.5%) carried a causative variant in one of the genes studied. Known causative variants were identified in 27 cases (nine in SQSTM1, seven in TARDBP, five in SOD1, three in NEK1 and one each in SETX, VCP, FUS), whereas novel causative variants were identified in three cases (SOD1, FIG4, TBK1). In total, 71 cases received a molecular genetic diagnosis (20.1%). Additionally, seven cases (2.0%) carried an intermediate repeat expansion (30-33 CAG) in ATXN2.

CONCLUSION: Our results reveal the distinct genetic profile of Greek ALS patients. These findings will have an impact on genetic counseling, the design of diagnostic gene panels for the Greek population and on genotype-specific therapeutic interventions. Understanding the genetic causes of ALS in different populations is becoming increasingly important, especially with the advent of personalized medicine.},
}

@article {pmid41196032,
year = {2025},
author = {Mansoor, N and Heiman-Patterson, T and Feldman, EL and Wicks, P and Benatar, M and Vieira, F and Glass, J and Levine, T and Bertorini, T and Barkhaus, P and Mascias Cadavid, J and Jackson, C and Jhooty, S and Brown, A and Pattee, G and Sane, H and Mcdermott, CJ and Carter, G and Beauchamp, M and Wang, O and Ratner, D and Bedlack, R and Li, X},
title = {ALSUntangled #81: Pyridostigmine (mestinon[®]).},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-5},
doi = {10.1080/21678421.2025.2582830},
pmid = {41196032},
issn = {2167-9223},
abstract = {Pyridostigmine (Mestinon[®], Bausch Health, Canada Inc.) increases acetylcholine availability at the neuromuscular junction, enhancing transmission. Preclinical studies suggest that neuromuscular junction dysfunction develops early in ALS, and pyridostigmine may temporarily improve neuromuscular transmission. However, altered neuromuscular junction transmission has uncertain benefits in ALS progression. Pyridostigmine does not have other plausible mechanisms that truly modify ALS pathophysiology. People with ALS (PALS) who have positive acetylcholine receptor autoantibodies and no myasthenia symptoms are unlikely to respond to pyridostigmine treatment. Clinical trials on pyridostigmine in PALS are lacking, but two clinical trials of other similar anticholinesterase agents did not effectively slow ALS progression. Muscarinic cholinergic side effects, including gastrointestinal symptoms, are common. Given the lack of mechanistic plausibility and efficacy, we do not support the use of pyridostigmine for slowing ALS progression.},
}

@article {pmid41196018,
year = {2025},
author = {Magara, J and Suzuki, T and Yoshihara, M and Onuki, W and Sasa, A and Tsujimura, T and Inoue, M},
title = {Lingual pressure as a physiological indicator for dysphagia in amyotrophic lateral sclerosis and multiple system atrophy.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/17582024.2025.2580876},
pmid = {41196018},
issn = {1758-2032},
abstract = {BACKGROUND: This study aimed to characterize lingual pressure (LP) and clarify its association with dysphagia in patients with amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA).

METHODS: We examined 52 patients with ALS (Spinal-onset, 39; bulbar-onset, 13) and 36 patients with MSA (MSA-C, 26; MSA-P, 10). LP was measured using a balloon-type instrument during isometric contractions. Maximum LP (MLP) and 80% endurance of LP (ELP; duration above 80% of MLP during 7 seconds) were analyzed against videofluoroscopic findings of dysphagia.

RESULTS: Both parameters significantly correlated with food intake scales, especially in ALS. Liquid aspiration was predicted in ALS with 80.8% accuracy (AUC = 0.794, p < 0.001) using MLP cutoff of 20.5 kPa, and in MSA with 75.0% accuracy (AUC = 0.786, p < 0.01) using an ELP cutoff of 1.68 second. Predictive accuracy improved in spinal-onset ALS and MSA-C.

CONCLUSION: LP thus may represent a physiological indicator for dysphagia detection and management.},
}

@article {pmid41195301,
year = {2025},
author = {Dijkstra, JIR and Hulsman, M and Waterink, L and Holstege, H and Teunissen, CE and Christiaansen, WFL and de Jong, BA and Kochunov, P and Donohue, B and Zwan, MD and den Braber, A and Vermunt, L and van der Lee, SJ},
title = {Heritability and shared environmental effects of brain diseases in 12,040 extended families.},
journal = {NPJ dementia},
volume = {1},
number = {1},
pages = {34},
pmid = {41195301},
issn = {3005-1940},
abstract = {Brain diseases have complex patterns of genetic and environmental risk factors, and better understanding of these risks is required for more effective prevention strategies. Participants of the Dutch Brain Research Registry provided detailed information on family structure and occurrence of brain diseases. A total of 12,040 participants (73% female, aged 64.9 ± 11 years) provided information on 101,379 family members (53% female, aged 62 ± 25 years). We estimated heritability (h [2]) of the nine most common brain diseases using polygenic modeling in SOLAR and assessed variations in h [2] through bootstrapping; Alzheimer's disease (AD) (h [2] = 73, range 53-86, P fdr < 0.001), ALS (h [2] = 72, range 10-98, P fdr = 0.030), frontotemporal dementia (FTD) (h [2] = 48, range 0-97, P fdr = 0.132), vascular dementia (VaD) (h [2] = 41, range 7-64, P = 0.003), Lewy Body dementia (h [2] = 34, range 0-58, P = 0.132), iCVA (h [2] = 27, 6-59, P fdr = 0.013), hCVA (h [2] = 29, 8-57, P fdr = 0.007), Parkinson's disease (PD) (h [2] = 38, 6-66, P fdr = 0.013), and multiple sclerosis (h [2] = 10, 10-97, P fdr < 0.001). Shared environmental effects could be estimated for AD (c [2] = 5.8%, P fdr = 0.011), VaD (c [2] = 9.0%, P fdr = 0.021), FTD (c [2] = 9.7%, P fdr = 0.33), iCVA (c [2] = 15.9%, P fdr < 0.001), hCVA (c [2] = 14.9%, P fdr = 0.005), and PD (c [2] = 7.5%, P fdr = 0.25). These findings underscore the significance of genetic contribution to most brain diseases and the important role of shared environments in AD and vascular-related conditions, highlighting initiatives to mitigate modifiable risk factors.},
}

@article {pmid41195023,
year = {2025},
author = {Furuya, K and Itoh, N},
title = {Red urine in a 68-year-old man with amyotrophic lateral sclerosis.},
journal = {Journal of general and family medicine},
volume = {26},
number = {6},
pages = {659-660},
pmid = {41195023},
issn = {2189-7948},
}

@article {pmid41194800,
year = {2025},
author = {Su, Z and Xiang, L},
title = {Targeting ER stress in skeletal muscle through physical activity: a strategy for combating neurodegeneration-associated muscle decline.},
journal = {Frontiers in molecular neuroscience},
volume = {18},
number = {},
pages = {1639114},
pmid = {41194800},
issn = {1662-5099},
abstract = {The pathophysiology of neurodegenerative diseases is largely driven by ER stress, contributing to cellular dysfunction and inflammation. Chronic ER stress in skeletal muscle is associated with a deterioration in muscle function, particularly in diseases such as ALS, PD, and AD, which are often accompanied by muscle wasting and weakness. ER stress triggers the UPR, a cellular process designed to restore protein homeostasis, but prolonged or unresolved stress can lead to muscle degeneration. Recent studies indicate that exercise may modulate ER stress, thereby improving muscle health through the enhancement of the adaptive UPR, reducing protein misfolding, and promoting cellular repair mechanisms. This review examines the influence of exercise on the modulation of ER stress in muscle cells, with a particular focus on how physical activity influences key pathways contributed to mitochondrial function, protein folding, and quality control. We discuss how exercise-induced adaptations, including the activation of stress-resilience pathways, antioxidant responses, and autophagy, can help mitigate the negative effects of ER stress in muscle cells. Moreover, we examine the potential therapeutic implications of exercise in neurodegenerative diseases, where it may improve muscle function, reduce muscle wasting, and alleviate symptoms associated with ER stress. By integrating findings from neurobiology, muscle physiology, and cellular stress responses, this article highlights the therapeutic potential of exercise as a strategy to modulate ER stress and improve muscle function in neurodegenerative diseases.},
}

@article {pmid41194593,
year = {2025},
author = {Levine, MP and Chung, SY and Quigg, KH and Carey, J and Babu, S and Paganoni, S and Berry, JD},
title = {Participation in U.S.-Based ALS Clinical Trials by Sex and Race.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70050},
pmid = {41194593},
issn = {1097-4598},
support = {1OT2NS136938-01/NS/NINDS NIH HHS/United States ; 1OT2NS136939-01/NS/NINDS NIH HHS/United States ; /NH/NIH HHS/United States ; },
abstract = {INTRODUCTION/AIMS: In global amyotrophic lateral sclerosis (ALS) trials, women and men appear to be proportionately enrolled, but quantification of enrollment by sex and race in U.S.-based ALS trials is limited. The objective of this study was to evaluate the sex and race of participants enrolled in U.S.-based ALS clinical trials.

METHODS: Participant demographics were extracted from recent U.S.-based Phase 2 and 3 ALS trials identified in literature and on ClinicalTrials.gov. The Centers for Disease Control and Prevention (CDC) National ALS Registry and a 2014 State Surveillance Project were used as proxies for prevalence. Participation-to-prevalence (PPR) ratios were calculated for sex and race. A modified time-trend analysis was performed for race for participants enrolled before and after 2020.

RESULTS: A total of 11 trials met criteria for inclusion with a total of 1153 patients enrolled. Compared to the CDC Registry, the PPR was 0.76 (95% CI: 0.63-0.90) for women, 1.26 (95% CI: 1.23-1.29) for White participants, 0.34 (95% CI: 0.17-0.51) for Black participants, and 0.35 (95% CI: 0.14-0.56) for all other races/multiracial. The modified time trend analysis showed no significant difference in the PPRs before and after 2020 (White: t = 1.44, p = 0.22; Black: t = -0.99, p = 0.37; Other races/multiracial: t = -1.50, p = 0.21). The comparison to the 2014 State Surveillance Project yielded similar findings.

DISCUSSION: U.S.-based ALS trials significantly under-enroll non-White participants, and there are trends toward slight underrepresentation of women. Efforts to broaden trial enrollment amongst people with ALS will help with the generalizability of trial results and hasten trial completion.},
}

@article {pmid41194479,
year = {2025},
author = {Das, S and Patel, M and Khandelwal, S and Rawat, R and Shukla, S and Kumari, AP and Singh, K and Kumar, A},
title = {From Mutations to Microbes: Investigating the Impact of the Gut Microbiome on Repeat Expansion Disorders.},
journal = {Journal of neurochemistry},
volume = {169},
number = {11},
pages = {e70278},
doi = {10.1111/jnc.70278},
pmid = {41194479},
issn = {1471-4159},
mesh = {*Gastrointestinal Microbiome/physiology/genetics ; Humans ; Animals ; *Mutation/genetics ; Dysbiosis/genetics ; *DNA Repeat Expansion/genetics ; },
abstract = {Repeat expansion disorders (REDs) are a diverse array of genetic disorders characterized by the expansion of specific DNA sequences. These expansions are frequently dynamic and are susceptible to further expansion across generations. They contribute to disease progression by leading symptoms to become more severe and manifest earlier in subsequent generations. Despite a substantial understanding of their molecular mechanisms, the exact etiology of REDs remains tricky. Emerging evidence indicates that gut microbiome dysbiosis significantly impacts REDs by regulating various biochemical pathways. Alterations in microbial diversity and composition have been observed across multiple REDs; however, a comprehensive understanding of the complete scenario remains a significant challenge. To elucidate these dynamic interactions, future research should utilize multifaceted approaches. This review focuses on the key modifications in the gut microbiome that contribute to the pathogenesis of REDs and discusses potential gut microbiome-targeted therapeutic strategies that could be effectively employed to treat these disorders.},
}

*Gastrointestinal Microbiome/physiology/genetics
Humans
Animals
*Mutation/genetics
Dysbiosis/genetics
*DNA Repeat Expansion/genetics

@article {pmid41192771,
year = {2025},
author = {Shima, S and Kondo, T and Inoue, H},
title = {iPSC-derived neural organoids in dementia research: recent advances and future directions.},
journal = {Neuroscience research},
volume = {},
number = {},
pages = {104980},
doi = {10.1016/j.neures.2025.104980},
pmid = {41192771},
issn = {1872-8111},
abstract = {Neural organoids are self-assembled three-dimensionally shaped aggregates generated from pluripotent stem cells for the purpose of generating brain-like structures. Organoids derived from patient induced pluripotent stem cells (iPSCs) can recapitulate the features of the disease from molecular to functional levels, which are not fully reproduced by other culture systems or in vivo models. Neural organoids have been applied to model dementia including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis/frontotemporal dementia, and they have recapitulated aspects of their complex pathophysiology, including neuronal network dysfunction and accumulation of pathogenic proteins. Although there are some challenges for the research using neural organoids, including their heterogeneity and the lack of cells of non-neural lineage, researchers have tried to overcome these limitations and have demonstrated their utility in conjugation with gene editing technologies and the assembly system of organoids and specific types of cells. This article reviews current research on iPSC-derived organoids for dementia, discussing both the technical hurdles and the potential for translational applications.},
}

@article {pmid41191764,
year = {2025},
author = {Qian, Y and Liu, C and Yu, P and Ran, X and Li, S and Yang, Q and Liu, Y and Xia, L and Wang, Y and Qi, J and Zhou, E and Lu, J and Li, Y and Tao, TH and Zhou, Z and Wu, J},
title = {Real-time decoding of full-spectrum Chinese using brain-computer interface.},
journal = {Science advances},
volume = {11},
number = {45},
pages = {eadz9968},
pmid = {41191764},
issn = {2375-2548},
mesh = {*Brain-Computer Interfaces ; Humans ; Language ; Male ; *Speech/physiology ; Female ; Adult ; Electroencephalography ; China ; East Asian People ; },
abstract = {Speech brain-computer interfaces (BCIs) offer a promising means to provide functional communication capacity for patients with anarthria caused by neurological conditions such as amyotrophic lateral sclerosis (ALS) or brainstem stroke. Current speech decoding research has predominantly focused on English using phoneme-driven architectures, whereas real-time decoding of tonal monosyllabic languages such as Mandarin Chinese remains a major challenge. This study demonstrates a real-time Mandarin speech BCI that decodes monosyllabic units directly from neural signals. Using the 256-channel microelectrocorticographic BCI, we achieved robust decoding of a comprehensive set of 394 distinct syllables based purely on neural signals, yielding median syllable identification accuracy of 71.2% in a single-character reading task. Leveraging this high-performing syllable decoder, we further demonstrated real-time sentence decoding. Our findings demonstrate the efficacy of a tonally integrated, direct syllable neural decoding approach for Mandarin Chinese, paving the way for full-coverage systems in tonal monosyllabic languages.},
}

*Brain-Computer Interfaces
Humans
Language
Male
*Speech/physiology
Female
Adult
Electroencephalography
China
East Asian People

@article {pmid41191168,
year = {2025},
author = {Bhore, N and Sarkar, A and Yao, Z and Herbst, S and Lewis, PA},
title = {Glutamic Acid at Position 168 Is a Constitutive Activator of Tank Binding Kinase 1 Catalytic Function.},
journal = {Neuromolecular medicine},
volume = {27},
number = {1},
pages = {73},
pmid = {41191168},
issn = {1559-1174},
support = {MN5DF/CAAu23/100008//My name'5 doddie foundation/ ; MN5DF/CAAu23/100008//My name'5 doddie foundation/ ; MN5DF/CAAu23/100008//My name'5 doddie foundation/ ; MN5DF/CAAu23/100008//My name'5 doddie foundation/ ; IF\R2\222002//Royal Society/ ; IF\R2\222002//Royal Society/ ; },
mesh = {*Protein Serine-Threonine Kinases/genetics/chemistry/metabolism/physiology ; Humans ; *Glutamic Acid/physiology/chemistry/genetics ; Catalytic Domain/genetics ; HEK293 Cells ; Enzyme Activation/genetics ; Codon ; Amyotrophic Lateral Sclerosis/genetics ; Amino Acid Substitution ; Biocatalysis ; },
abstract = {TANK binding kinase 1 (TBK1) is serine/threonine protein kinase member of the inhibitor of nuclear factor-kB kinase family, with links to the etiology of familial as well as idiopathic Amyotrophic Lateral Sclerosis. It contributes to several regulatory cellular processes such as autophagy, inflammation and apoptosis. Reduction or loss of TBK1 kinase activity is associated with increased risk of ALS, and so understanding the molecular basis of this activity is an important research priority. In this current study, the role of the E168 residue, located adjacent to the active site of TBK1, has been assessed using a combination of artificial and naturally occurring variants found at this codon - evaluated using multiple readouts for TBK1 kinase activity. The results suggest that the negative charge resulting from the presence of a glutamic acid at this codon is a constitutive activator of TBK1 activity.},
}

*Protein Serine-Threonine Kinases/genetics/chemistry/metabolism/physiology
Humans
*Glutamic Acid/physiology/chemistry/genetics
Catalytic Domain/genetics
HEK293 Cells
Enzyme Activation/genetics
Codon
Amyotrophic Lateral Sclerosis/genetics
Amino Acid Substitution
Biocatalysis

@article {pmid41191158,
year = {2025},
author = {Pal, B and Panda, S and Bashir, B and Vishwas, S and Chaitanya, M and Hussain, MS and Gupta, G and Kumbhar, P and Gupta, S and Singh, SK},
title = {Nanomedicine-enabled neuroprotection: therapeutic role of berberine in neurodegenerative diseases.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {49},
pmid = {41191158},
issn = {1573-4978},
mesh = {Humans ; *Berberine/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neuroprotective Agents/therapeutic use/pharmacology ; *Nanomedicine/methods ; Animals ; *Neuroprotection/drug effects ; Nanoparticles/chemistry ; Oxidative Stress/drug effects ; Blood-Brain Barrier/metabolism/drug effects ; },
abstract = {Neurodegenerative diseases (NDs), including Alzheimer's, Amyotrophic lateral sclerosis, Huntington's, and Parkinson's, present an increasingly widespread health burden globally with limited curative or treatment modalities, mostly having symptomatic attenuation. Berberine (BBR) is an isoquinoline alkaloid that occurs naturally and has been proposed as a potential neuroprotectant, since it has been found to exert multiple effects to modulate most of the pathological hallmarks of NDs, including neuroinflammation, oxidative stress, mitochondrial dysfunction, and protein aggregation. Although it shows promise, the practical utilization of BBR is marred by low oral bioavailability, high rate of oxidation, and low blood-brain barrier permeability. To combat these issues, recent developments in nanotechnology, especially in the use and creation of lipidic, inorganic, and polymeric nano-particles, have dramatically altered the pharmacokinetics and pharmacodynamics of BBR. This article summarizes recent advances in BBR-based nanoformulations and emphasizes the translational potential of BBR-based nanopreparations to improve treatment response in NDs. It also describes the molecular foundation of the neuroprotective effects of BBR and its possible place in clinical practice. Future nanocarrier development and investigation of BBR mechanisms will be essential to the development of the next generations of therapeutics in NDs.},
}

Humans
*Berberine/therapeutic use/pharmacology
*Neurodegenerative Diseases/drug therapy/metabolism
*Neuroprotective Agents/therapeutic use/pharmacology
*Nanomedicine/methods
Animals
*Neuroprotection/drug effects
Nanoparticles/chemistry
Oxidative Stress/drug effects
Blood-Brain Barrier/metabolism/drug effects

@article {pmid41191137,
year = {2025},
author = {Vencato, M and Zorzi, M and Bonato, M},
title = {Temporal momentum: an online replication and beyond.},
journal = {Psychological research},
volume = {89},
number = {6},
pages = {164},
pmid = {41191137},
issn = {1430-2772},
mesh = {Humans ; *Time Perception/physiology ; Young Adult ; Male ; Adult ; Female ; *Mathematical Concepts ; Adolescent ; Reaction Time ; Reproducibility of Results ; },
abstract = {Performing mental arithmetic on brief temporal durations has been recently shown to induce operation-specific distortions. In a time reproduction task, addition resulted in longer responses while subtraction induced shorter responses, despite their identical arithmetic outcome (Bonato et al., Cognition, 206, 2021). This effect has been named temporal momentum, in analogy with the representational momentum found when representing the position of moving objects, and it mirrors the operational momentum characterizing mental arithmetic with numerical quantities. In Experiment 1, we assessed the reliability of the temporal momentum effect in the first direct replication of Bonato et al.'s temporal arithmetic task by using an online procedure for data collection. In Experiment 2, we also tested whether under-estimation in subtraction could be attributed to the longer operand being always presented first in the original study. The results showed a reliable temporal momentum effect that was virtually indistinguishable from previous, laboratory-based experiments. Moreover, in Experiment 2, under-estimation in subtraction was still present when participants had to compute the difference between two operands regardless of their order, thereby excluding that the temporal momentum in subtraction is due to the specific ordering of the stimuli. This pre-registered study further demonstrates that the temporal momentum effect is a robust and reliable marker indexing the mental manipulation of time durations, consistent with the hypothesis that time processing includes some features resembling those involved in spatial processing.},
}

Humans
*Time Perception/physiology
Young Adult
Male
Adult
Female
*Mathematical Concepts
Adolescent
Reaction Time
Reproducibility of Results

@article {pmid41190025,
year = {2025},
author = {Alhassan, HH and Janiyani, K and Surti, M and Adnan, M and Patel, M},
title = {The dual role of glycogen synthase kinase-3 beta (GSK3β) in neurodegenerative pathologies: interplay between autophagy and disease progression.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1693805},
pmid = {41190025},
issn = {1663-9812},
abstract = {Glycogen Synthase Kinase-3 Beta (GSK3β), a multifunctional serine/threonine kinase, plays a central role in cellular signaling pathways and autophagy regulation, processes critical to neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic Lateral Sclerosis (ALS). Dysregulation of autophagy leads to the toxic accumulation of misfolded proteins and damaged organelles, contributing to neuronal loss in these disorders. This review explores the mechanistic interplay between GSK3β and autophagy, highlighting its modulation through key pathways, including mTOR, AMPK and Bcl-2 and its direct impact on autophagy-related proteins such as Beclin-1 and LC3. This review systematically discusses the disease-specific roles of GSK3β in autophagy dysregulation and protein aggregation, providing evidence from recent studies on neurodegenerative models. Additionally, therapeutic approaches targeting GSK3β are evaluated, including preclinical and clinical trials of GSK3β inhibitors and combination therapies with autophagy modulators, emphasizing their potential for improving neuroprotection and cellular homeostasis. Despite its promise, challenges such as off-target effects and pathway complexity remain significant. This review highlights the importance of GSK3β as both a therapeutic target and a biomarker, offering avenues for future research into selective GSK3β modulators that enhance autophagy and mitigate ND progression.},
}

@article {pmid41189652,
year = {2025},
author = {Guo, H and Yang, Z and Zhang, G and Lv, L and Zhao, X},
title = {Meta analysis of the diagnostic efficacy of transformer-based multimodal fusion deep learning models in early Alzheimer's disease.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1641548},
pmid = {41189652},
issn = {1664-2295},
abstract = {INTRODUCTION: This study aims to systematically evaluate the diagnostic efficacy of Transformer-based multimodal fusion deep learning models in early Alzheimer's disease (AD) through a Meta-analysis, providing a scientific basis for clinical applications.

METHODS: Following PRISMA guidelines, databases such as PubMed and Web of Science were searched, and 20 eligible clinical studies (2022-2025) involving 12,897 participants were included. Study quality was assessed using the modified QUADAS-2 tool, statistical analyses were performed with Stata 16.0, effect sizes were pooled via random-effects models, and subgroup analyses, sensitivity analyses, and publication bias tests were conducted.

RESULTS: Results showed that Transformer-based multimodal fusion models exhibited excellent overall diagnostic performance, with a pooled AUC of 0.924 (95% CI: 0.912-0.936), sensitivity of 0.887 (0.865-0.904), specificity of 0.892 (0.871-0.910), and accuracy of 0.879 (0.858-0.897), significantly outperforming traditional single-modality methods. Subgroup analyses revealed that: Three or more modalities achieved a higher AUC (0.935 vs. 0.908 for two modalities, p =0.012). Intermediate fusion strategies (feature-level, AUC=0.931) significantly outperformed early (0.905) and late (0.912) fusion (p <0.05 for both). Multicenter data improved AUC (0.930 vs. 0.918 for single-center, p =0.046), while sample size stratification (<200 vs. ≥200 cases) showed no significant difference (p =0.113). Hybrid Transformer models (Transformer +CNN) trended toward higher AUC (0.928 vs. pure Transformer 0.917, p =0.068) but did not reach statistical significance.

DISCUSSION: Notable studies included Khan et al.'s (2024) Dual-3DM[3]AD model (AUC=0.945 for AD vs. MCI) and Gao et al.'s (2023) generative network (AUC=0.912 under data loss), validating model robustness and feature complementarity. Sensitivity analysis confirmed stable results (AUC range: 0.920-0.928), and Egger's test (p =0.217) and funnel plot symmetry indicated no significant publication bias. Limitations included a high proportion of single-center data and insufficient model interpretability. Future research should focus on multicenter data integration, interpretable module development, and lightweight design to facilitate clinical translation. Transformer-based multimodal fusion models demonstrate exceptional efficacy in early AD diagnosis, with multimodal integration, feature-level fusion, and multicenter data application as key advantages. They hold promise as core tools for AD "early diagnosis and treatment" but require further optimization for cross-cohort generalization and clinical interpretability.},
}

@article {pmid41188870,
year = {2025},
author = {Keerie, AF and Martins, RR and Allen, CF and Bowden, K and Al Mashhadi, S and Marlow, T and Myszczynska, M and Thakur, N and Beal, SN and Shaw, A and Suresh, S and McKinnon, SN and Cooper-Knock, J and West, RJH and Bonsall, S and Daniel, A and Wells, T and Kumar, V and Ellis, BCS and Higgins, M and Dinkova-Kostova, AT and Shelkovnikova, TA and Kalfus, IN and Shan, N and Shaw, PJ and Ferraiuolo, L and Mead, RJ},
title = {M102 activates both NRF2 and HSF1 transcription factor pathways and is neuroprotective in cell and animal models of amyotrophic lateral sclerosis.},
journal = {Molecular neurodegeneration},
volume = {20},
number = {1},
pages = {118},
pmid = {41188870},
issn = {1750-1326},
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy ; *NF-E2-Related Factor 2/metabolism ; Mice, Transgenic ; Disease Models, Animal ; Mice ; Motor Neurons/drug effects/metabolism ; *Neuroprotective Agents/pharmacology ; *Heat Shock Transcription Factors/metabolism ; Humans ; Signal Transduction/drug effects ; },
abstract = {M102 is a central nervous system (CNS) penetrant small molecule electrophile which activates in vivo the NF-E2 p45-related factor 2-antioxidant response element (NRF2-ARE) pathway, as well as transcription of heat-shock element (HSE) associated genes. In the TDP-43[Q331K] transgenic mouse model of ALS dosed subcutaneously at 5 mg/kg OD or 2.5 mg/kg BD with M102, significant improvements in compound muscle action potential (CMAP) amplitude of hind limb muscles and gait parameters were observed at 6 months of age, with associated target engagement. An oral dose response study of M102 in SOD1[G93A] transgenic mice showed a dose-dependent improvement in CMAP of hindlimb muscles which correlated with preservation of lumbar spinal motor neurons at the same time point. These data enabled prediction of human efficacious exposures and doses, which were well within the safety margin predicted from Good Laboratory Practice (GLP) toxicology studies. A parallel program of work in vitro showed that M102 rescued motor neuron survival in co-culture with patient-derived astrocytes from sporadic, C9orf72 and SOD1 ALS cases. Markers of oxidative stress, as well as indices of TDP-43 proteinopathy were also reduced by exposure to M102 in these in vitro models. This comprehensive package of preclinical efficacy data across two mouse models as well as patient-derived astrocyte toxicity assays, provides a strong rationale for clinical evaluation of M102 in ALS patients. Combined with the development of target engagement biomarkers and the completed preclinical toxicology package, a clear translational pathway to testing in ALS patients has been developed.},
}

Animals
*Amyotrophic Lateral Sclerosis/metabolism/drug therapy
*NF-E2-Related Factor 2/metabolism
Mice, Transgenic
Disease Models, Animal
Mice
Motor Neurons/drug effects/metabolism
*Neuroprotective Agents/pharmacology
*Heat Shock Transcription Factors/metabolism
Humans
Signal Transduction/drug effects

@article {pmid41188584,
year = {2025},
author = {Wang, S and Li, Y and Xing, X and Man, X and Chen, Y and Wang, G},
title = {DTI changes of brachial plexus nerve roots in amyotrophic lateral sclerosis and their correlation with electrophysiology.},
journal = {European radiology experimental},
volume = {9},
number = {1},
pages = {107},
pmid = {41188584},
issn = {2509-9280},
support = {2024FY135//Scientific Research Incubation Fund of Shandong Provincial Hospital/ ; 201912004//Jinan Clinical Research Center for Neurological Disease Imaging Monitoring/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnostic imaging ; Male ; Female ; *Diffusion Tensor Imaging/methods ; Middle Aged ; *Brachial Plexus/diagnostic imaging/physiopathology ; Anisotropy ; Aged ; Adult ; Case-Control Studies ; Neural Conduction ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease with peripheral nerve involvement, but current diagnostics are limited. Diffusion tensor imaging (DTI) may improve microstructural assessment and correlate with clinical markers. We investigated the diffusion properties of the brachial plexus in ALS and examined their relationships with electrophysiological parameters of upper limb nerves.

MATERIALS AND METHODS: We enrolled 25 ALS patients and 22 age- and sex-matched healthy controls. DTI of the brachial plexus was conducted to measure fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Differences in DTI parameters between the two groups were analyzed. Correlations between DTI parameters and ALS Functional Rating Scale-Revised (ALSFRS-R) scores, along with electrophysiological measurements, were assessed.

RESULTS: In ALS patients compared to controls, FA and AD values were significantly lower (p ≤ 0.002), while the RD value was significantly higher (p = 0.002). There were no statistically significant differences in MD (p = 0.540). Both FA and AD showed a positive correlation with ALSFRS-R score, ALSFRS-upper limb score, and compound muscle action potential amplitude of median, ulnar, and radial nerves (r ≥ 0.480; p ≤ 0.015). The RD values showed a negative correlation with ALSFRS-upper limb score and motor nerve conduction velocity of median, ulnar, and radial nerves (r ≤ -0.415; p ≤ 0.039).

CONCLUSION: FA, AD, and RD values of DTI showed the potential to identify microstructural changes in the brachial plexus nerve roots of ALS patients and may serve as potential indicators of nerve conduction function in the upper extremities.

RELEVANCE STATEMENT: DTI may reveal microstructural changes in ALS brachial plexus, correlating with nerve dysfunction, offering novel biomarkers for evaluation of upper limb neurodegeneration.

KEY POINTS: Lower Fractional anisotropy (FA) and axial diffusivity (AD), and higher radial diffusivity (RD) were shown in amyotrophic lateral sclerosis (ALS) brachial plexus. Diffusion tensor imaging (DTI) parameters correlated with clinical and electrophysiological parameters. FA, AD, and RD detected ALS nerve microstructural changes, indicating abnormal conduction function.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/diagnostic imaging
Male
Female
*Diffusion Tensor Imaging/methods
Middle Aged
*Brachial Plexus/diagnostic imaging/physiopathology
Anisotropy
Aged
Adult
Case-Control Studies
Neural Conduction

@article {pmid41188562,
year = {2025},
author = {Wright, R},
title = {Autoimmune target in ALS.},
journal = {Nature neuroscience},
volume = {28},
number = {11},
pages = {2175},
doi = {10.1038/s41593-025-02122-x},
pmid = {41188562},
issn = {1546-1726},
}

@article {pmid41188020,
year = {2026},
author = {Parra-Torres, M and Dissanayake, K and Gray, JA and Langlands, AJ and Kucuk, R and Gierlinski, M and Troakes, C and King, A and McGurk, L},
title = {Aberrant NSUN1 activity connects m[5]C-RNA modification to TDP-43 neurotoxicity in ALS/FTD.},
journal = {Life science alliance},
volume = {9},
number = {1},
pages = {},
pmid = {41188020},
issn = {2575-1077},
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Humans ; Animals ; *DNA-Binding Proteins/metabolism/genetics ; *Frontotemporal Dementia/metabolism/genetics/pathology ; *Methyltransferases/metabolism/genetics ; *5-Methylcytosine/metabolism ; *RNA/metabolism/genetics ; Disease Models, Animal ; Cell Line, Tumor ; Drosophila melanogaster ; Methylation ; Drosophila Proteins/metabolism/genetics ; Drosophila ; },
abstract = {In amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), the nuclear RNA-binding protein TDP-43 mislocalises to the cytoplasm and forms insoluble aggregates, but the mechanisms controlling this remain unclear. We define a native TDP-43 interactome in human SH-SY5Y cells and identify proteins linked to the 5-methylcytosine (m[5]C) RNA modification as highly enriched. Using a Drosophila model of TDP-43 pathology, we show that aberrant activity of m[5]C-RNA methyltransferases Nsun1 drives TDP-43-induced m[5]C-RNA hypermethylation, whereas Nsun1 down-regulation alleviates TDP-43-induced degeneration, lifespan deficits, and cytoplasmic accumulation. In human cells, TDP-43 selectively interacts with NSUN1 isoform 3 independently of RNA. Furthermore, NSUN1 is nucleolar and TDP-43 is largely nucleoplasmic, yet they interact in both compartments, suggesting functional roles beyond their predominant localisations. In ALS/FTD postmortem frontal cortex, NSUN1 isoform 3 persists, whereas the shorter isoform is reduced, suggesting that a pool of NSUN1 capable of contributing to pathological TDP-43 interactions remains in disease. These findings suggest that TDP-43 neurotoxicity is coupled to NSUN1 activation and m[5]C-RNA methylation, revealing a potential therapeutic axis in ALS/FTD.},
}

*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology
Humans
Animals
*DNA-Binding Proteins/metabolism/genetics
*Frontotemporal Dementia/metabolism/genetics/pathology
*Methyltransferases/metabolism/genetics
*5-Methylcytosine/metabolism
*RNA/metabolism/genetics
Disease Models, Animal
Cell Line, Tumor
Drosophila melanogaster
Methylation
Drosophila Proteins/metabolism/genetics
Drosophila

@article {pmid41187939,
year = {2025},
author = {Reis, AHO and Magno, GPO and Costa, BGF and Figalo, LB and Orsini, M},
title = {Genetic and clinical insights into ALS8: exploring the impact of VAPB pathogenic variants in familial amyotrophic lateral sclerosis.},
journal = {Arquivos de neuro-psiquiatria},
volume = {83},
number = {11},
pages = {1-5},
doi = {10.1055/s-0045-1812470},
pmid = {41187939},
issn = {1678-4227},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Male ; Female ; Middle Aged ; Adult ; Pedigree ; *Vesicular Transport Proteins/genetics ; Brazil ; Disease Progression ; Aged ; Mutation/genetics ; Genetic Predisposition to Disease ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease leading to progressive muscle weakness and paralysis. Approximately 10% of ALS cases are familial (FALS), with the VAPB gene's P56S pathogenic variant being notably prevalent in Brazilian families, contributing to the rare ALS8. This variant progresses more slowly than typical ALS, with distinct clinical features.To identify VAPB gene pathogenic variants in Brazilian FALS patients, particularly the P56S pathogenic variant associated with ALS8 and explore its clinical presentation and progression.Twelve FALS patients from 12 unrelated families in Rio de Janeiro were included in the study between 2023 and 2024. Clinical, laboratory, and electrophysiological data were reviewed. Collection of DNA samples happened via oral swabs, and VAPB gene sequencing was performed to identify pathogenic variants, specifically the P56S variant linked to ALS8.There were 3 cases of the P56S pathogenic variant, all presenting ALS8 with symptom onset in the lower limbs and slower disease progression. A family with 11 affected members across four generations showed an autosomal dominant inheritance pattern, with varying survival rates, highlighting its clinical variability.The present study underscores the importance of genetic screening for ALS subtypes, particularly ALS8, in Brazil. Identifying the P56S pathogenic variant enhances our understanding of ALS's genetic diversity and clinical presentation, offering a foundation for improved diagnostic practices and personalized care.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics
Male
Female
Middle Aged
Adult
Pedigree
*Vesicular Transport Proteins/genetics
Brazil
Disease Progression
Aged
Mutation/genetics
Genetic Predisposition to Disease

@article {pmid41187881,
year = {2025},
author = {Ge, TQ and Wang, P and Guan, PP},
title = {Targeting the C5-C5aR1 axis: A promising therapeutic strategy for Alzheimer's disease and amyotrophic lateral sclerosis by unlocking neuroprotection.},
journal = {Biochemical pharmacology},
volume = {243},
number = {Pt 1},
pages = {117518},
doi = {10.1016/j.bcp.2025.117518},
pmid = {41187881},
issn = {1873-2968},
abstract = {C5aR1 is a G protein-coupled receptor (GPCR) which is involved in exacerbating neurodegenerative diseases, including Alzheimer's disease (AD) and Amyotrophic Lateral Sclerosis (ALS). This review highlights the critical role of the C5-C5aR1 axis, in the pathogenesis of neurodegenerative diseases such as AD and ALS. In AD and ALS, abnormal protein aggregates activate the complement system (CS), leading to increased production of C5a. C5a activates C5aR1 on microglia, triggering the release of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) that induce synaptic loss. Concurrently, the C5-C5aR1 axis impairs microglial phagocytic capacity, promoting damage-associated molecular patterns (DAMPs) accumulation and forming a vicious cycle of inflammation and complement activation. Additionally, excessive complement molecule assembles into the terminal complement complex (TCC), which exerts direct neurotoxic effects and drives neuronal apoptosis. Preclinical studies show that C5aR1 antagonists, such as PMX205, mitigate disease progression in AD and ALS animal models by reducing neuroinflammation and preserving synaptic function. These findings underscore the C5-C5aR1 axis as a promising target for neurodegenerative disease therapy and highlight the need for further development of potential antagonists of C5aR1.},
}

@article {pmid41186720,
year = {2025},
author = {Aijaz, M and Ahmad, M and Ahmad, S and Afzal, M and Kothiyal, P},
title = {The gut-brain axis: role of gut microbiota in neurological disease pathogenesis and pharmacotherapeutics.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {41186720},
issn = {1432-1912},
abstract = {The gut-brain axis is a highly complex, bidirectional communication link between the gut and the central nervous system (CNS), mainly through neural, endocrine, immunological, and metabolic pathways. This review outlines the growing contribution of gut microbiota in the remediation of neurological health and also emphasizes the controlling role of gut microbiota on the synthesis of neurotransmitters. Emerging evidence indicates that dysbiosis of the gut is related to a variety of neurodegenerative and neuropsychiatric diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), autism spectrum disorders (ASD), depression, and glioblastoma. Mechanistic understandings show that gut microbes critically contribute to neuroimmune and blood-brain barrier (BBB) signaling. The peripheral association of gut microflora, networked with inflammasome activation, nuclear factor kappa B (NF-κB), and type-I IFN pathways highlights their role in CNS inflammation. Microbiota-targeted interventions with probiotics, prebiotics, synbiotics, antibiotics, dietary modifications, and fecal microbiota transplantation are examined for their therapeutic potential. These strategies appear to be promising to reinstate microbial balance, enhance neuroplastic responses, and ameliorate the disease symptoms. The review highlights personalized microbiome-based algorithms, underpinned by integrated multi-omics technologies and machine-learning-driven diagnostics. Future research should address underlying microbial mechanisms and perform large, randomized controlled trials in order to establish microbiota-based therapies for neurological disorders.},
}

@article {pmid41186253,
year = {2025},
author = {Situmorang, DDB and Hafina, A and Ilfiandra, },
title = {Expanding the Perspective of Suicide Prevention for Young Persons: The Role of Mental Health Professionals in Higher Education Settings.},
journal = {Journal of psychiatric and mental health nursing},
volume = {},
number = {},
pages = {},
doi = {10.1111/jpm.70052},
pmid = {41186253},
issn = {1365-2850},
abstract = {BACKGROUND: The purpose of this letter is to encourage the observation of Sun et al., the stages of suicide more broadly and discussing overlooked factors, most notably that as stressors for college students (e.g., academic pressures, relationship terminations, etc.). The place of mental health workers in institutions of higher education is highlighted. Furthermore, preventive and remedial measures are discussed.

OBJECTIVE: Sun et al. offered important phenomenological perspectives about how suicidal young persons at risk for suicide perceive suicide and prevention of suicidality. Their results emphasised external pressure, internal negative self-thoughts, positive self-cognitions, external support, and intrapersonal regulation as the main themes. Such findings have significant implications to mental health interventions for youth and adolescents.

CONTENT: We agree with the need to tackle both external and internal pressures as part of suicide prevention. Yet, we do observe that Sun et al.'s subjects were recruited from hospitals and clinics in Taiwan. Students at colleges experience specific forms of difficulties: too much work, graduation delayed, or emotional pain caused by a breakup. These are situational stressors that tend to precipitate suicidal thoughts yet have not been fully explored. University-employed mental health professionals (counsellors and psychologists) will be integral in providing prevention (e.g., resilience training, peer support, etc.) and intervention services (crisis counselling, referral systems, etc.). Furthermore, the potential for provision of brief or single-session interventions may help increase access to and timely delivery of intervention.

IMPLICATIONS: Future suicide prevention interventions should include contexts of higher education, ensuring that colleges and universities construct preemptive frameworks to identify and intervene with disaffected students. Guidance for policy must focus on these three areas: (a) integration of mental health services within college health systems; (b) provision of training to faculty and staff to identify early warning signs in students; and (c) application of student-centric, culturally sensitive approaches.

CONCLUSION: The phenomenological estimate of Sun et al. is a significant contribution. Through the indigenisation of this understanding within universities, and by focussing on the assertive role of mental health workers, there can be a shift towards a more responsive, holistic form of suicide prevention.},
}

@article {pmid41185046,
year = {2025},
author = {Zhou, Y and Huang, J and Xu, L and Zhang, F and Bai, C and Fan, F and Wang, Y and Fang, B and Wang, T and Mu, X and Li, J},
title = {Genomic structural equation modeling decodes skeletal aging: novel loci discovery and multisystem genetic crosstalk.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {1206},
pmid = {41185046},
issn = {1479-5876},
support = {82222076//Excellent Young Scientists Fund of the National Natural Science Foundation of China (NSFC)/ ; DZMG-LJRC0013//Talent Development Program of Dongzhimen Hospital, Beijing University of Chinese Medicine/ ; C2015//Clinical Research Funding for Central Government-Supported High-Level Traditional Chinese Medicine (TCM) Hospitals/ ; },
mesh = {Humans ; Genome-Wide Association Study ; *Aging/genetics ; Polymorphism, Single Nucleotide/genetics ; *Bone and Bones/physiology ; *Models, Genetic ; *Genomics ; *Genetic Loci ; Quantitative Trait Loci/genetics ; },
abstract = {OBJECTIVE: Skeletal aging, a core determinant of systemic aging, poses a global public health challenge due to its association with chronic diseases and functional decline. This study aimed to decode the genetic architecture of skeletal aging by identifying novel loci and multi-system crosstalk using genomic structural equation modeling (Genomic SEM).

METHODS: We integrated genome-wide association study (GWAS) data from five musculoskeletal-related traits (osteoporosis [OP], osteoarthritis [OA], lumbar spinal stenosis [LSS], telomere length [TL], and low back pain [LBP]) across 462,933 to 472,174 European individuals. Genomic SEM, FUMA, FUSION, and fine-mapping tools (SuSIE/FINEMAP) were applied to model latent skeletal aging ("mvSAge") and identify causal variants, enriched pathways, and tissue-specific gene expression.

RESULTS: The latent factor model (CFI = 0.993, SRMR = 0.065) revealed shared genetic architecture among OP, OA, LSS, TL, and LBP. We identified 514 lead SNPs (P < 5 × 10⁻[12]), including 136 novel loci enriched in regulatory regions (e.g., brain putamen, frontal cortex). Fine-mapping prioritized causal variants (posterior probability > 0.95) near MTPAP, GRAMD4, and DPP8, implicating mitochondrial function and immune regulation. Transcriptome-wide analyses highlighted PPP6R3 (bone mineral density) and SLC33A1 (anticancer target) as key genes. Enrichment analyses linked mvSAge to Wnt signaling, ER stress, and Mendelian disorders (e.g., ALS). Chromosomes 1, 2, and 4 showed elevated heritability contributions, driven by conserved regulatory elements (RUNX2, SP7) and chromatin accessibility hotspots.

CONCLUSION: This study establishes mvSAge as a genetically cohesive construct and uncovers novel loci, pathways, and multi-system interactions underlying skeletal aging. These findings advance precision medicine strategies for aging-related musculoskeletal disorders.},
}

Humans
Genome-Wide Association Study
*Aging/genetics
Polymorphism, Single Nucleotide/genetics
*Bone and Bones/physiology
*Models, Genetic
*Genomics
*Genetic Loci
Quantitative Trait Loci/genetics

@article {pmid41184709,
year = {2025},
author = {Kiecka, A and Szczepanik, M},
title = {Dietary modulation of the gut microbiome as a supportive strategy in the treatment of amyotrophic lateral sclerosis - a narrative review.},
journal = {Pharmacological reports : PR},
volume = {},
number = {},
pages = {},
pmid = {41184709},
issn = {2299-5684},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease leading to permanent damage to the central and peripheral motor neurons. Currently, there is no effective treatment for ALS, and therapy focuses solely on slowing the progression of the disease. Recent studies show that gut microbiota plays an important role in the development of neurodegenerative diseases. Altered gut microbiota has also been found in ALS. These changes have prompted the search for alternative forms of ALS treatment, focusing on changing the microbial composition of the gut. It has been noted that diet, probiotics, prebiotics and vitamins can all influence the course of ALS. Another interesting issue is fecal microbiota transplantation, which is already used in the treatment of certain intestinal diseases and could potentially be useful in the treatment of ALS. This review summarizes current knowledge on the impact of gut microbiota on the neurodegenerative process in ALS, with particular emphasis on the role of diet and probiotics. It also discusses potential mechanisms and highlights future research directions in this emerging field.},
}

@article {pmid41135587,
year = {2025},
author = {Patel, S and Cagino, KA and Roberts, AW and Wiley, RL and Cortes, C and Zullo, F and Mendez-Figueroa, H and Chauhan, SP},
title = {Fetal Heart Rate Tracings and Adverse Outcomes among Term Small versus Appropriate for Gestational Age.},
journal = {American journal of perinatology},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2729-1189},
pmid = {41135587},
issn = {1098-8785},
abstract = {This study aimed to compare the patterns of fetal heart rate tracings (FHRTs), and outcomes among individuals with small (birth weight [BW] <10% for gestational age [GA]; SGA) versus appropriate (BW at 10-89% for GA; AGA) newborns at term (≥37.0 weeks).Our retrospective cohort study included consecutive deliveries over 15 months at a level IV center. FHRTs were reviewed by obstetricians blinded to maternal and neonatal outcomes. The inclusion criteria were non-anomalous singletons, cataloged as SGA or AGA birth weight using Alexander et al's nomogram. In 20-minute segments, the last 120 minutes of tracing were characterized. Rates of cesarean delivery (CD) and composite neonatal adverse outcomes (CNAOs) were compared.Of 5,160 deliveries, 3,029 (58.7%) met the inclusion criteria, and among them, 422 (13.9%) were SGA and 2,607 (86.1%) AGA. There were no differences in FHRT baseline, variability, or accelerations. Compared to AGA, SGA was more likely to have prolonged decelerations (11.8 vs. 8.4%, p = 0.021), and recurrent decelerations with ≥50% of contractions (21.3 vs. 16.5%, p = 0.014). Overall, the presence of category II FHRT or not was similar between the SGA (91.2%) and AGA (88.5%; p = 0.097). Persistent category II FHRT was significantly more common among SGA (37.4%) than AGA (28.1%; aOR = 1.47; 95% CI: 1.47-1.82) newborns. The rate of CD for non-reassuring FHRT was similar among the two groups. CNAO occurred in 1.4% in both SGA and AGA neonates (p = 0.95).In our cohort of those with fetal monitoring prior to delivery at ≥37 weeks, persistent category II FHRT at the end of labor was significantly more common in SGA compared to AGA neonates; however, composite neonatal morbidity did not differ between the two groups. Our analysis provides data for shared decision-making that among SGA newborns, abnormalities of FHRT are not linked with adverse outcomes. · There were no differences in FHRT baseline, variability, or accelerations between AGA and SGA.. · SGA was more likely to have prolonged decelerations and recurrent decelerations with ≥50% of contractions.. · Persistent category II FHRT before delivery is significantly more common with SGA than AGA.. · FHRT abnormalities, however, were not associated with CD for non-reassuring FHRT, or adverse outcomes..},
}

@article {pmid41183928,
year = {2025},
author = {Hanada, K and Haji, S and Fukushima, K and Yamazaki, H and Osaki, Y and Takamatsu, N and Fujita, K and Izumi, Y},
title = {Increase in the amyotrophic lateral sclerosis age of onset:Analysis of cases originating in 2011-2020.},
journal = {The journal of medical investigation : JMI},
volume = {72},
number = {3.4},
pages = {286-289},
doi = {10.2152/jmi.72.286},
pmid = {41183928},
issn = {1349-6867},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology ; Age of Onset ; Male ; Female ; Aged, 80 and over ; Aged ; Japan/epidemiology ; Middle Aged ; Adult ; },
abstract = {The onset age of amyotrophic lateral sclerosis (ALS) has been increasing, but recent trends remain unclear. This study examined changes in ALS onset age over the past decade. We analyzed 233 ALS patients diagnosed from 2011 to 2020 at Tokushima University Hospital. The Jonckheere-Terpstra test assessed the trend in onset age. We compared onset age between 2011-2015 (Group A) and 2016-2020 (Group B) using the Mann-Whitney U test. We also analyzed the annual proportion of patients with onset age ≥80 using Spearman's rank correlation. In Tokushima Prefecture, we evaluated annual increase rates of individuals aged ≥80 and ALS patients with onset age ≥80, using 2011 as baseline. Regression slopes were compared using a t test. Onset age showed a significant positive trend (p=0.04), and Group B had older onset age than Group A (p=0.048). The proportion of patients with onset age ≥80 increased significantly (ρ=0.69, p=0.03). No significant difference was found between regression slopes for the general elderly population and ALS patients with onset age ≥80 (p=0.49). These findings suggest that the onset age of ALS at Tokushima University Hospital has increased over the past decade. J. Med. Invest. 72 : 286-289, August, 2025.},
}

Humans
*Amyotrophic Lateral Sclerosis/epidemiology
Age of Onset
Male
Female
Aged, 80 and over
Aged
Japan/epidemiology
Middle Aged
Adult

@article {pmid41183377,
year = {2025},
author = {Morris, AC and Seker, A and Telesia, L and Wickersham, A and Ching, BC and Roy, R and Epstein, S and Matcham, F and Sonuga-Barke, E and Downs, J},
title = {Adherence to Actigraphic Devices in Elementary School-Aged Children: Systematic Review and Meta-Analysis.},
journal = {Journal of medical Internet research},
volume = {27},
number = {},
pages = {e79718},
pmid = {41183377},
issn = {1438-8871},
mesh = {Humans ; Child ; *Actigraphy/instrumentation ; *Patient Compliance/statistics & numerical data ; Child, Preschool ; Female ; Schools ; Male ; },
abstract = {BACKGROUND: Consistent wear is essential for valid and reliable actigraphy data. Adherence to actigraphy may be challenging in primary school children due to developmental and design considerations, yet no quantitative synthesis of adherence in this age group exists.

OBJECTIVE: The aim of this study was to provide the first pooled estimate of actigraphy adherence in primary school-aged children and examine the impact of individual, device, and study-specific factors on adherence.

METHODS: We searched seven electronic databases for studies reporting adherence to actigraphy in primary school-aged children. Searches were conducted in Embase, MEDLINE, PsycINFO, Social Policy and Practice via OVID, Education Resources Information Center, British Education Index, and CINAHL via EBSCO using database-specific search strategies conducted between January 2018 and January 24, 2023. Forward and backward citation searches were completed on the Web of Science Core Collection and Google Scholar. Gray literature searches were undertaken in PsycEXTRA and Healthcare Management Information Consortium. Empirical studies reporting quantitative data on adherence to community-based actigraphy in children aged 5-11 years (or if ≥50% of the average age fell within this range) were included. Eligible studies were written in English and could be published or unpublished. Risk of bias was assessed using an 8-item checklist adapted from Berger et al's actigraphy reporting standards. All included studies were narratively synthesized, and adherence data were pooled in a proportional meta-analysis. Adherence was calculated as the proportion of children meeting wear-time criteria to be included in the analysis compared to the number of children invited to use the device at baseline. Meta-regression was used to examine the impact of individual, device, and study-specific factors on adherence. Prediction intervals were calculated to estimate the range of adherence expected across future studies.

RESULTS: Data were extracted from 235 studies (N=148,161); of these, 135 studies (n=64,541) provided adherence data for proportional meta-analysis. Pooled adherence, measured across 1-140 days, was 81.6% (95% CI 78.7%-84.4%; I2=98.8%). The prediction intervals (42.8%-100%) indicated substantial variability in adherence estimates across studies. Meta-regression suggested that individual characteristics contributed to observed heterogeneity as children with a physical health diagnosis (b=0.236, 95% CI 0.009-0.464; P=.04) and those with neurodevelopmental or mental health diagnosis (b=0.395, 95% CI 0.125-0.665; P=.004) demonstrated higher adherence than undiagnosed children, though these effects were of modest magnitude. No significant effects were found for age, placement, protocol length, protocol deviation, or incentivization. Reporting quality was poor, with only 3.4% of studies satisfying all criteria.

CONCLUSIONS: This review demonstrates generally high actigraphy adherence in primary school-aged children, particularly those with health conditions. However, observed variability indicates that adherence was much lower in some contexts, underscoring that the reported pooled adherence cannot be assumed across future actigraphy applications within this age group. Future research should use standardized adherence reporting and should plan for adherence variability.},
}

Humans
Child
*Actigraphy/instrumentation
*Patient Compliance/statistics & numerical data
Child, Preschool
Female
Schools
Male

@article {pmid41182774,
year = {2025},
author = {Heragu, P and Dieujuste, N and Mekawi, Y and Oltmanns, JR},
title = {Longitudinal measurement invariance of the Personality Inventory for ICD-11 across Black and White American older adults.},
journal = {Psychological assessment},
volume = {},
number = {},
pages = {},
doi = {10.1037/pas0001421},
pmid = {41182774},
issn = {1939-134X},
support = {//National Institutes of Health; National Institute on Aging/ ; },
abstract = {The Personality Inventory for ICD-11 (PiCD) assesses five maladaptive trait domains from the International Classification of Diseases-11th edition's dimensional model of personality disorder. Validity evidence of PiCD scores has relied primarily on White samples and there have been no evaluations of measurement invariance (MI). Research examining use of PiCD scores with diverse populations is needed. The present study investigated MI of PiCD scores across race and time in sample of White and Black American older adults (n = 843, ∼20% Black). Cross-sectionally, Marsh et al.'s (2009) 13-step exploratory structural equation modeling was used to determine MI of the five domains across Black and White participants at two waves of data collection about 2 years apart. Findings revealed partial strong invariance across race at both waves. At Wave 1, intercepts for two Anankastia items and two negative affectivity items (only one negative affectivity item at Wave 2) were noninvariant across race. Longitudinal exploratory structural equation modeling suggested strict invariance across time for the entire sample. Domain-level longitudinal confirmatory factor analysis indicated strict invariance across time for Black participants in each PiCD domain. Findings suggest four item means demonstrated noninvariance and require further examination, but the PiCD scores showed a high level of invariance (factor structure, factor loadings, 56 of 60 item intercepts). Reasons for the four noninvariant item intercepts are probed by examining scale score differences with and without the items and external correlates. Findings indicate partial strong invariance for PiCD scores, but the four item mean scores need further exploration across race, and potential revision. (PsycInfo Database Record (c) 2025 APA, all rights reserved).},
}