@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).},
}

@article {pmid41182353,
year = {2025},
author = {Cai, Y and Huang, S and Dong, Y and Li, S and Jin, X},
title = {PIWI-Interacting RNAs in brain health and disease: biogenesis, mechanisms, and therapeutic horizons.},
journal = {Psychopharmacology},
volume = {},
number = {},
pages = {},
pmid = {41182353},
issn = {1432-2072},
support = {81971083//National Natural Science Foundation of China/ ; 25JCLZJC00190//Tianjin Natural Science Foundation Project/ ; },
abstract = {PIWI-interacting RNAs (piRNAs), a class of small non-coding RNAs originally identified for their role in transposon silencing in germ cells, have recently been recognized as pivotal regulators of gene expression in the central nervous system. Beyond their canonical functions in genome defense, emerging evidence highlights piRNAs as key modulators of neuronal development, synaptic plasticity, axonal regeneration, and neuroimmune interactions-processes central to brain function and dysfunction. This review provides a comprehensive overview of piRNA biogenesis, molecular mechanisms, and regulatory pathways relevant to neurobiology. We focus on the growing body of evidence implicating piRNA dysregulation in major neurological and neuropsychiatric disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke, glioma, autism spectrum disorder, and schizophrenia. Importantly, we discuss the neuropharmacological implications of piRNA pathways as novel targets for therapeutic intervention and their potential utility as biomarkers for early diagnosis and treatment stratification. By integrating mechanistic insights with emerging translational evidence, this review highlights piRNAs as promising molecular targets in the development of next-generation neurotherapeutics aimed at modifying disease progression and improving brain health.},
}

@article {pmid41181835,
year = {2025},
author = {Keritam, O and Erdler, M and Fasching, B and Zulehner, G and Rath, J and Krenn, M and Waldhör, T and Gruber, VA and Langweil, N and Kiss, C and Griedl, TA and Gold, V and Wanschitz, J and Hotter, A and Kleinveld, VEA and Horlings, CGC and Erber, A and Schernhammer, E and Troger, J and Grinzinger, S and Müller, P and Langenscheidt, D and Rappold, M and Wiesenhofer, A and Gosk-Tomek, M and Knipp, F and Mahal, S and Bernert, G and Baumann, M and Zimprich, F and Topakian, R and Eggers, C and Quasthoff, S and Löscher, W and Cetin, H},
title = {Efficacy and safety of risdiplam in adults with 5q-associated spinal muscular atrophy: a nationwide observational cohort study in Austria.},
journal = {EClinicalMedicine},
volume = {88},
number = {},
pages = {103536},
pmid = {41181835},
issn = {2589-5370},
abstract = {BACKGROUND: Spinal muscular atrophy (SMA) is a genetic motor neuron disease marked by the progressive decline of motor function. Risdiplam, an orally administered SMN2 splicing modifier, was approved for the treatment of 5q-associated SMA (5q-SMA) across all age groups. However, clinical trial data have primarily focused on paediatric populations, with limited evidence available for adult patients. This study aimed to evaluate the efficacy and safety of risdiplam in treatment-naïve adults with 5q-SMA in a real-world, multicentre setting.

METHODS: We conducted a nationwide, observational cohort study across eight neuromuscular centres in Austria. Patients aged ≥16 years at treatment initiation with genetically confirmed 5q-SMA, who were previously untreated and initiated risdiplam between December 2020 and September 2024 were eligible for inclusion if they had received risdiplam for ≥3 months and had functional motor assessments available at baseline (T0) and at least one follow-up. Functional outcomes were assessed at four predefined intervals after baseline: 3-<6 months (T1), 6-<12 months (T2), 12-<18 months (T3), and ≥18 months (T4). The primary outcome was the change from baseline in the Hammersmith Functional Motor Scale Expanded (HFMSE). Secondary outcomes included changes in the Revised Upper Limb Module (RULM), Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R), and 6-min walk test (6MWT). Adverse events were extracted from medical records.

FINDINGS: A total of 87 patients had received risdiplam, of whom 57 fulfilled the inclusion criteria and were included in this study. The median age at treatment initiation was 35.7 years (IQR 28.8-43.4), with a median disease duration of 29.6 years (IQR 24.2-36.3). Most individuals had SMA type II (40.4%) or III (47.4%). Mean HFMSE changes from baseline were +1.00 (95% CI 0.05-1.95, p = 0.0100) at T1, +0.97 (95% CI 0.22-1.72, p = 0.0132) at T2, +1.78 (0.66-2.89, p = 0.0008) at T3, and +1.73 (0.49-2.97, p = 0.0049) at T4. Clinically meaningful improvements in motor function (≥3 points in HFMSE and/or ≥2 in RULM) were observed in 63.9% of patients at T4. Improvements were more pronounced in patients with higher baseline function, ambulatory status, or without a history of spinal surgery. Risdiplam was generally well tolerated, with predominantly mild and non-specific adverse events reported in 14.0% of patients.

INTERPRETATION: In this nationwide observational study in a real-world setting, adult patients with 5q-SMA demonstrated consistent and clinically meaningful functional improvements with risdiplam over time, particularly by 18 months and beyond. These findings support the long-term use of risdiplam in adults with SMA and help close a critical evidence gap in this underrepresented population.

FUNDING: This study was financially supported by F. Hoffmann-La Roche Ltd.},
}

@article {pmid41181712,
year = {2025},
author = {Colaianni, D and Ceccato, N and Antolini, P and Conte, C and De Pittà, C and Feiguin, F and Mazzotta, GM},
title = {TDP-43-mediated amyotrophic lateral sclerosis: new/hidden insights from Drosophila.},
journal = {Frontiers in cell and developmental biology},
volume = {13},
number = {},
pages = {1677090},
pmid = {41181712},
issn = {2296-634X},
abstract = {Transactive response DNA-binding protein 43 (TDP-43) is a key factor in motor neurons and related neurodegenerative disorders, and the presence of cytoplasmic aggregates of TDP-43 is a major hallmark of diseases such amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Nevertheless, little is known about early developmental effects or the systemic nature of TDP-43-mediated pathology. Drosophila melanogaster is acknowledged as a powerful genetic model for studying the genetic inheritance and the behavioral and developmental processes associated with human neurodegenerative diseases, including ALS. To better understand the possible roles and potential pathogenic mechanisms of TDP-43 protein in the pathogenesis of ALS, we performed a transcriptomic analysis of larvae from a Drosophila model knock-out (KO) for the TBPH gene, the fly TDP-43 ortholog. Interestingly, the Gene Ontology (GO) analysis highlighted some pathways not yet associated with this pathology and this model. We identified several genes encoding for serine proteases, a class of enzymes that in the central nervous system (CNS) play important roles in neural development, synaptic plasticity, and neurodegeneration. Our work provides insights into novel pathological mechanisms underlying the disease, thereby opening new pathways for drug discovery.},
}

@article {pmid41181067,
year = {2025},
author = {Bronet, J and Borge, R},
title = {The internal democracy of the crisis parties in Western Europe: a quantitative analysis of the role of digitalization, ideology and populism.},
journal = {Open research Europe},
volume = {5},
number = {},
pages = {288},
pmid = {41181067},
issn = {2732-5121},
abstract = {BACKGROUND: Previous studies on the internal democracy of new digital parties in Western Europe suggest a plebiscitary tendency, but most focus on a limited number of cases. This paper aims to empirically analyze the intra-party democracy of electorally successful new parties in Western Europe and identify the main factors that may influence it.

METHODS: Drawing on data from the second round of the Political Parties Database (PPDB) and the first wave of the Populism and Political Parties Expert Survey (POPPA), this study covers more than 100 parties across 13 countries. Adopting a generational approach, we define a cohort of "crisis parties"-founded between the economic crisis and the pandemic-and examine their internal democracy in comparison to older parties, using Von dem Berge and Poguntke's IPD model and Böhmelt et al.,'s (2022) framework, with ideology, digitalization, and populism treated as explanatory variables.

RESULTS: Our findings show that being a crisis party-even a highly digitalized one on the left-does not entail more plebiscitary forms of intra-party democracy.

CONCLUSIONS: Digitalization emerges as the most consistent predictor shaping intra-party democracy, while the cohort effect matters only insofar as crisis parties are more populist than older parties, which ultimately reduces their internal democracy.},
}

@article {pmid41180593,
year = {2025},
author = {Civita, E and Nicolella, V and Fiorenza, M and Cosimato, V and Castaldo, G and Morra, VB and Moccia, M and Terracciano, D},
title = {Advancing Clinical Use of Neurofilament Light Chain: Translational Insights From Research to Routine Practice.},
journal = {Biomarker insights},
volume = {20},
number = {},
pages = {11772719251364018},
pmid = {41180593},
issn = {1177-2719},
abstract = {Neurofilament Light Chain (NfL) has emerged as a promising biomarker for neurological diseases. NfL, a structural component of axons, is released into cerebrospinal fluid (CSF) and blood following neuro-axonal damage. Highly sensitive immunometric assays have enabled its reliable quantification in blood, facilitating non-invasive monitoring. Several studies demonstrated strong correlations between NfL levels and the risk of developing different neurological diseases and, in individuals already living with a neurological disease, with the risk of worsening. However, interpretation is affected by factors like age, BMI, renal function, and comorbidities. NfL is already utilized as a diagnostic and prognostic biomarker in clinical practice, particularly in specialized centers and research settings, although no FDA-cleared assay is currently available for routine use. Recent research has highlighted that NfL may represent the first of a new generation of neurological biomarkers, with many more ready to come, such as glial fibrillary acidic protein (GFAP), further improving diagnostic and prognostic accuracy. Despite its promising role in the landscape of biomarkers, challenges remain to implement NfL in daily clinical practice, including standardization of assays, defining reference values, and ensuring methodological consistency. Addressing these limitations will be essential for integrating NfL into routine clinical practice, ultimately advancing precision medicine in neurology.},
}

@article {pmid41180498,
year = {2025},
author = {Shamsi, A and Alrouji, M and AlOmeir, O and Tasqeruddin, S and Dinislam, K and Zuberi, A},
title = {CRISPR-Cas9: bridging the gap between aging mechanisms and therapeutic advances in neurodegenerative disorders.},
journal = {Frontiers in cellular neuroscience},
volume = {19},
number = {},
pages = {1681891},
pmid = {41180498},
issn = {1662-5102},
abstract = {Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, ALS, and spinocerebellar ataxia are becoming more prevalent as populations age, posing major global health challenges. Despite decades of research, effective treatments that halt or reverse these conditions remain elusive. Aging is the most significant risk factor in the development of these diseases, intertwining with molecular processes like DNA damage, mitochondrial dysfunction, and protein aggregation. Recent advances in gene-editing technologies, particularly CRISPR-Cas9, are beginning to shift the therapeutic landscape. This revolutionary tool allows for precise correction of genetic mutations associated with neurodegeneration, offering the potential for disease modification rather than symptom management alone. In this review, we explore how CRISPR-Cas9 is being leveraged to target key genes implicated in various neurodegenerative conditions and how it may overcome barriers posed by aging biology. We also examine the delivery systems and safety challenges that must be addressed before clinical application. With continued progress, CRISPR-Cas9 could mark a turning point in our ability to treat or even prevent age-related neurological decline.},
}

@article {pmid41180289,
year = {2025},
author = {},
title = {Corrigendum to "Predicting Factors Affecting the Behavior of Healthcare Employees in the Use of Personal Protective Equipment During Epidemics Based on Godin et al's Model: A Study in Iran".},
journal = {Health services insights},
volume = {18},
number = {},
pages = {11786329251395188},
doi = {10.1177/11786329251395188},
pmid = {41180289},
issn = {1178-6329},
abstract = {[This corrects the article DOI: 10.1177/11786329251316668.].},
}

@article {pmid41179113,
year = {2025},
author = {Luo, Y and Xu, Z and Li, Z},
title = {Advances in Induced Pluripotent Stem Cell Reprogramming and Its Application in Amyotrophic Lateral Sclerosis: A Review.},
journal = {FASEB bioAdvances},
volume = {7},
number = {11},
pages = {e70065},
pmid = {41179113},
issn = {2573-9832},
abstract = {Since Yamanaka's landmark achievement in reprogramming somatic cells into induced pluripotent stem cells (iPSCs) using the four key transcription factors-OCT4, SOX2, KLF4, and c-Myc (OSKM)-iPSC technology has made significant strides. Notable advancements include refining reprogramming factors, delivery systems, somatic cell selection, and optimization of reprogramming conditions, along with developing chemical reprogramming methods. With their unparalleled proliferative capacity and near-pluripotent differentiation potential, iPSCs have become invaluable tools for investigating neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Neuronal models derived from ALS patient-specific iPSCs, particularly iPSC-derived motor neurons (iPSC-MNs), offer a robust platform to recapitulate disease-specific pathology and investigate the molecular mechanisms underpinning ALS, thereby accelerating the discovery of novel therapeutic strategies. This review highlights the evolution of iPSC technology and its transformative applications in ALS modeling, drug discovery, and therapeutic development.},
}

@article {pmid41178869,
year = {2025},
author = {Shamoon, R and Nashwan, AJ},
title = {Survival outcomes after laparoscopic gastric cancer surgery: The need for stage-specific insights.},
journal = {World journal of gastrointestinal surgery},
volume = {17},
number = {10},
pages = {110668},
pmid = {41178869},
issn = {1948-9366},
abstract = {Gastric cancer remains one of the leading causes of cancer-related mortality worldwide. Advances in surgical techniques, especially laparoscopic surgery, have revolutionized the management of gastric cancer by reducing perioperative morbidity and enabling faster recovery. However, medium- to long-term survival remains understudied, and identifying factors that influence outcomes is essential for improving care. Gan et al's study analyzes the 3-year survival outcomes and prognosis in patients with primary gastric cancer undergoing laparoscopic surgery. The study identifies the important variables associated with survival, including age, tumor node metastasis stage, tumor characteristics, surgical factors, and postoperative complications. While the study provides important data for clinical practice, further research is warranted to refine risk stratification and explore the role of emerging therapies.},
}

@article {pmid41178854,
year = {2025},
author = {Chen, GB and Wang, ZL and Sha, YG and Tang, RM and Liu, ZG and Chen, LJ},
title = {Closing infection pathways: Multidisciplinary disinfection measures reshape gastrointestinal surgical outcomes.},
journal = {World journal of gastrointestinal surgery},
volume = {17},
number = {10},
pages = {108505},
pmid = {41178854},
issn = {1948-9366},
abstract = {Surgical site infections remain a significant challenge in gastrointestinal surgery, despite advances in surgical techniques and antimicrobial therapy. Wang et al's retrospective analysis highlights the transformative potential of comprehensive perioperative disinfection and isolation protocols in gastrointestinal surgery, demonstrating a 55% reduction in postoperative infection rates and attenuation of systemic inflammation. Their findings underscore the critical role of multidisciplinary strategies-such as preoperative povidone-iodine decolonization, intraoperative laminar airflow systems, and strict postoperative wound care-in mitigating infection risk and preserving organ function. However, the study revealed persistent gaps in protocol standardization and compliance monitoring, particularly in resource-limited settings. Although these measures reduce reliance on antibiotics and align with global antimicrobial resistance containment efforts, challenges such as the high cost of technology and issues with contextual adaptability warrant urgent attention. This study conclusively demonstrated that structured perioperative disinfection protocols significantly transform surgical outcomes by creating comprehensive infection barriers that extend beyond traditional antibiotic prophylaxis. Future priorities include prospective multicenter trials to validate efficacy, cost-benefit analyses for equitable implementation, and integration of artificial intelligence-driven innovations to optimize infection prevention. This study redefines infection control as a cornerstone of surgical quality, urging collaborative action to bridge the gap between clinical evidence and real-world practice.},
}

@article {pmid41178826,
year = {2025},
author = {Stern, C and Semendric, I and Shrestha, N and Beasley-Hall, J and Hasanoff, S and Barker, T and Pollock, D and Schubert, C and Giles, L and Vucic, S and Merlin, T and Munn, Z},
title = {Guidelines addressing Motor Neurone Disease (MND): a scoping review.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-16},
doi = {10.1080/17582024.2025.2573608},
pmid = {41178826},
issn = {1758-2032},
abstract = {INTRODUCTION: Motor Neurone Disease (MND) is a debilitating neurodegenerative condition affecting individuals, families, and carers. Evidence-informed care can improve outcomes, and guidelines play a key role in supporting this. A preliminary search showed limited guidelines exist, with none developed for the Australian context. This review aimed to identify existing health and social care guidelines for MND.

METHODS: A scoping review was conducted using Joanna Briggs Institute (JBI) methodology. Guidelines addressing health and social care for people with MND, gene carriers, family members, or carers were included regardless of publication status. Five databases and additional sources were searched. Two reviewers independently screened citations, and data were extracted and analysed descriptively, with qualitative content analysis grouping guideline questions. Reporting followed PRISMA-ScR.

RESULTS: Forty-two guidelines covering 133 questions were included. Most focused on symptom management for people with MND and were produced by professional bodies. Few used GRADE methodology or systematic reviews, and only seven assessed risk of bias. No guideline was developed for Australia.

CONCLUSIONS: A high-quality, evidence-based MND guideline following best practice development methods is needed.},
}

@article {pmid41178766,
year = {2025},
author = {Wang, Y and Hu, J and Zhu, Q and Wang, S and Yu, S},
title = {Emerging Potential of Ras-proximate-1 (Rap1) in Mediating Neurodegenerative Diseases.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X440842251020104840},
pmid = {41178766},
issn = {1875-6190},
abstract = {Neurodegenerative diseases have posed a rising global threat to the aging population, presenting structural and functional impairments in the central nervous system. These progressive disorders, which affect the brain and spinal cord, develop due to the continuous loss of neurons and myelin sheaths. Such specific pathophysiological changes lead to neurological dysfunction in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, resulting in typical motor dysfunctions and cognitive disorders, as well as symptoms like behavioral abnormalities and personality changes. To date, despite various treatments attempting to manage these symptoms, patients' quality of life remains severely deteriorated. A few effective therapeutics are available to mitigate the progression of neurodegenerative injuries. Increasing attention is now focused on molecular regulatory mechanisms, particularly the association between immune regulation and the neurovascular unit. A critical component in this process is Ras-proximate-1 (Rap1), a small Guanosine Triphosphatase (GTPase). Rap1 is determined to regulate glia-mediated immunoinflammatory responses, vascular endothelial function, and neuronal activity. It also modulates synaptic plasticity and mitochondrial function via autophagy-dependent modulation, which are significantly impacted during neuronal degeneration. Additionally, signaling pathways, including PI3K/Akt and ERK, are identified as its downstream effectors. Furthermore, by mediating the permeability of the blood-brain barrier, Rap1 probably influences neuroimmune-vascular modulation throughout the development of neurological disorders. In this review, we investigate recent studies to explore the emerging therapeutic potential of Rap1 in the inflammation-related regulation within neurodegenerative diseases. We also discuss novel treatments and possible targets, including natural medicines and genetic modulation, to enhance therapeutic effects and improve prognosis.},
}

@article {pmid41178159,
year = {2025},
author = {Mosna, S and Dormann, D},
title = {TDP-43 Phosphorylation: Pathological Modification or Protective Factor Antagonizing TDP-43 Aggregation in Neurodegenerative Diseases?.},
journal = {BioEssays : news and reviews in molecular, cellular and developmental biology},
volume = {},
number = {},
pages = {e70084},
doi = {10.1002/bies.70084},
pmid = {41178159},
issn = {1521-1878},
support = {//Deutsche Forschungsgemeinschaft (DFG)/ ; //VERUM Foundation/ ; },
abstract = {TDP-43 is a ubiquitously expressed RNA-binding protein that aggregates in the brains of patients suffering from neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Alzheimer's disease. Aggregated TDP-43 in these diseases is hyperphosphorylated in its C-terminal intrinsically disordered region, while physiological TDP-43 is normally unphosphorylated. Whether TDP-43 phosphorylation is a pathological driver, or rather a protective antagonist of TDP-43 aggregation and consequently neurodegeneration, is still debated and a matter of ongoing research. Here, we review current knowledge about TDP-43 phosphorylation in disease and the kinases and phosphatases that regulate this post-translational modification. We discuss how TDP-43 phosphorylation is thought to shape TDP-43's phase separation, aggregation and toxicity in neurodegenerative diseases. We highlight recent research that provides evidence that hyperphosphorylation antagonizes TDP-43 phase separation and aggregation, and speculate about a potential role of condensates in TDP-43 phosphorylation.},
}

@article {pmid41177774,
year = {2025},
author = {Enichen, EJ and Heydari, K and Li, B and Kvedar, JC},
title = {Can human connection amplify digital health outcomes? Familial involvement in a mobile health app.},
journal = {NPJ digital medicine},
volume = {8},
number = {1},
pages = {637},
pmid = {41177774},
issn = {2398-6352},
abstract = {In “A Randomized Controlled Trial of Mobile Intervention Using Health Support Bubbles to Prevent Social Frailty”, Hayashi et al. investigated the effects of using a mobile health app with family or individually. Greater improvements in social behavior and frailty were noted in participants who used the app with family. In an era of remote healthcare and app-based health interventions, Hayashi et al.’s study reminds of the importance of human connection.},
}

@article {pmid41177667,
year = {2025},
author = {Dobak, S and Pearson, K and McGuire, R and Ellis, AC},
title = {Medical nutrition therapy for ALS: Dietitians' approaches to diagnosing malnutrition, facilitating feeding tube discussions, and mitigating refeeding syndrome risk.},
journal = {Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1002/ncp.70069},
pmid = {41177667},
issn = {1941-2452},
support = {//This research was supported by a quality of care research award from the ALS Association./ ; },
abstract = {BACKGROUND: Persons living with amyotrophic lateral sclerosis (PALS) are at high risk for malnutrition because of disease-related factors such as dysphagia, self-feeding difficulty, and hypermetabolism. Nutrition interventions, including enteral nutrition (EN) initiation after gastrostomy tube (G-tube) placement, are integral to care but can introduce challenges, such as refeeding syndrome. This qualitative analysis explores how registered dietitians (RDs) at US-based outpatient amyotrophic lateral sclerosis (ALS) clinics assess malnutrition, facilitate discussions around G-tube placement, and mitigate refeeding syndrome risk.

METHODS: Six focus groups were conducted with 22 RDs from US ALS clinics. Audio files were transcribed verbatim, and data analyzed by deductive thematic analysis.

RESULTS: RDs reported widespread use of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition indicators for diagnosing malnutrition, with some using the Global Leadership Initiative on Malnutrition criteria. However, RDs described limitations in using these tools for PALS, particularly in differentiating disease-related from malnutrition-related muscle loss. When discussing G-tube placement, RDs described themselves as key informants in multidisciplinary teams, with timing of counseling typically based on symptoms and clinical progression. For refeeding syndrome, most clinics lacked formal protocols, although RDs used preventative practices, including slow initiation and advancement of EN and proactive communication with the care team.

CONCLUSIONS: ALS RDs play a critical and multifaceted role in managing nutrition-related ALS care. There is a need for ALS-specific malnutrition criteria and standard protocols to manage refeeding syndrome in the outpatient setting. RDs' involvement in G-tube discussions underscores their role in supporting patients in medical decision-making.},
}

@article {pmid41177049,
year = {2025},
author = {Varo-Martínez, MÁ and Navarro-Cerrillo, RM},
title = {Understanding defoliation of Pinus plantations in the Mediterranean mountains using tree segmentation and ALS time series.},
journal = {Journal of environmental management},
volume = {395},
number = {},
pages = {127837},
doi = {10.1016/j.jenvman.2025.127837},
pmid = {41177049},
issn = {1095-8630},
abstract = {Forest decline is observed across several spatial and temporal scales. Remote sensing studies have traditionally focused on severe, stand-replacing disturbances such as widespread tree mortality, whereas more gradual declines driven by drought or pest outbreaks have received less attention, largely due to their high spatial and temporal variability and the difficulty of detecting subtle changes in forest canopy and structure. In this study, we explored climatic-driven pine defoliation using time-series Airborne Laser Scanning (ALS) data (2008, 2013, 2018) in Pinus sylvestris and P. nigra plantations in south Spain. We derived three key forest attributes: tree segmentation, height, and defoliation from ALS point clouds using non-parametric methods (e.g., K-nearest neighbors k-NN, Random Forest RF and neural networks NN) and aggregated these at both tree and pixel scales. Then Kernel Density Estimation (SKDE) was used to characterize defoliation patterns. Based on these analyses, we identified temporal defoliation trends and their relationships with environmental and forest drivers. We obtained high accuracy values for tree segmentation, height estimation, and defoliation assessment. Considering the proportion of defoliated categories at tree- and stand-scale assessments, non-defoliated trees and defoliated tree were significantly related to forest attributes SKDE and climate variables. These findings demonstrate that ALS-based approaches can capture gradual forest decline, providing insights into ecological processes and supporting adaptive forest management strategies to adapt forests over space and time.},
}

@article {pmid41176929,
year = {2025},
author = {Akan, T and Akan, S and Alp, S and Ledbetter, CR and Tafti, AP and Arevalo, O and Bhuiyan, MAN},
title = {Deep Learning in neuroimaging for neurodegenerative diseases: State-of-the art, Challenges, and Opportunities.},
journal = {Journal of the neurological sciences},
volume = {478},
number = {},
pages = {123735},
doi = {10.1016/j.jns.2025.123735},
pmid = {41176929},
issn = {1878-5883},
abstract = {Neuroimaging is commonly used to diagnose neurodegenerative diseases (NDDs), providing crucial insights into brain changes before clinical symptoms manifest. Deep learning (DL) for neuroimaging can improve early diagnosis and disease monitoring. Clinical implementation of DL faces challenges in accurately representing real-world data. Recent models, particularly those focused on diagnostic categorization, have achieved high accuracy, but their applicability to patients is limited. Conflicting inferences have been reported, with findings from small cohorts generalizing conclusions without considering inter-scanner, intra- and inter-site variations. A theoretically feasible method involves gathering a comprehensive dataset that encompasses all patient demographics, but this presents practical challenges including harmonization, data incompleteness, class imbalance, and substantial costs. Existing research has also mostly focused on common NDDs like Alzheimer's Disease (AD) and Parkinson's Disease (PD). This contribution expands the literature by looking at a wider range of NDDs, exploring the latest advancements in applying deep learning algorithms to neuroimaging analysis for the diagnosis and monitoring of NDDs, including AD, Frontotemporal Dementia (FTD), Lewy Body Dementia, PD, Huntington's Disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis. We emphasize how these approaches are handling spatial/temporal information available in brain volume imaging data. We conclude by discussing the challenges associated with the use of voxel-based, patch-based, ROI-based, and slice-based approaches in brain volume imaging. These challenges are further compounded by issues such as inter-site and inter-scanner variability, class imbalances in medical datasets, and the scarcity of accurately annotated data, all of which impact the performance and generalizability of deep learning models.},
}

@article {pmid41176390,
year = {2025},
author = {Bensimon, G and Leigh, PN and Tree, T},
title = {Stratifying IL-2 therapy in ALS: integrating biomarkers - Authors' reply.},
journal = {Lancet (London, England)},
volume = {406},
number = {10515},
pages = {2061-2062},
doi = {10.1016/S0140-6736(25)01958-0},
pmid = {41176390},
issn = {1474-547X},
}

@article {pmid41176389,
year = {2025},
author = {Shimazu, Y},
title = {Stratifying IL-2 therapy in ALS: integrating biomarkers.},
journal = {Lancet (London, England)},
volume = {406},
number = {10515},
pages = {2061},
doi = {10.1016/S0140-6736(25)01737-4},
pmid = {41176389},
issn = {1474-547X},
}

@article {pmid41175990,
year = {2025},
author = {Konopka, A},
title = {Perspectives on the utilization of cell-free DNA in amyotrophic lateral sclerosis (ALS) diagnostics and prognostics - insight from cancer research.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107167},
doi = {10.1016/j.nbd.2025.107167},
pmid = {41175990},
issn = {1095-953X},
abstract = {Amyotrophic lateral sclerosis (ALS) remains a devastating neurodegenerative disease with limited diagnostic and prognostic tools. In recent years, cell-free DNA (cfDNA) has emerged as a promising non-invasive biomarker in various clinical settings, particularly in oncology. Despite its potential, the application of cfDNA in ALS is still in its early stages, and several critical gaps must be addressed. This discussion article reviews the current knowledge about cfDNA in ALS and explores its potential applications for disease diagnosis, monitoring, and prognosis. Drawing on the advances made in cancer research, it also examines the challenges that ALS research may face in cfDNA utilization, highlighting lessons learned from oncology. Taken together, these insights point to the urgent need for a comprehensive understanding of cfDNA characteristics specific to ALS. Given the current lack of reliable diagnostic and prognostic biomarkers in ALS, further investigation into cfDNA represents a valuable and necessary scientific endeavor with the potential to transform patient care and disease management.},
}

@article {pmid41175647,
year = {2025},
author = {Singh, A and Gupta, I and Saha, P and Hole, A and Anthony, F and Natu, A and Smoot, DT and Ashktorab, H and Chilakapati, MK and Gupta, S},
title = {Raman spectroscopy for detecting gastric and liver cancer cells that entered a tolerant persistence state to survive cisplatin chemotherapy.},
journal = {Biochemical and biophysical research communications},
volume = {790},
number = {},
pages = {152891},
doi = {10.1016/j.bbrc.2025.152891},
pmid = {41175647},
issn = {1090-2104},
abstract = {The persistence of minimal residual disease (MRD), a small population of tumor cells that survive therapy but remain below the limit of conventional detection methods, often leads to relapse. The residual disease is attributed to drug-tolerant persister (DTP) cells at the cellular level. In the present study, the differences in drug-tolerant persister cells, which represent a transient, reversible survival state, and drug-resistant cells, which reflect a stable, fixed phenotype of gastric and liver cancer cell lines, were investigated. The ultramicroscopic and confocal studies revealed a phenotypic shift in DTP cells induced upon drug treatment, characterized by cytoplasmic expansion, enhanced mitochondrial biogenesis, and active intercellular communication, potentially contributing to the survival of the drug-tolerant cells. The observed morphological alterations in a cell's physical characteristics are associated with underlying biochemical changes. Further, Raman spectroscopy provides a non-invasive method for studying biochemical alterations; Raman spectral analysis demonstrated precision in distinguishing with significant accuracy between DTP cells compared to resistant and parental cells. Multivariate Curve Resolution-alternating least squares (MCR-ALS) analysis showed alteration of lipid, nucleic acid, and protein-related features. The accumulation of lipid vacuoles inside the cytoplasm of DTP cells, and gene set enrichment analysis (GSEA) showed significant downregulation of metabolic pathways purine and pyrimidine, highlighting the potential metabolic shift in imparting a survival advantage to DTP cells. Thus, Raman analysis has confirmed the biochemical changes and provides proof of concept for identifying cisplatin-induced DTP and resistant tumor cells for a better therapeutic approach in resistant and relapse management.},
}

@article {pmid41175435,
year = {2025},
author = {Aphale, P and Dokania, S and Shekhar, H},
title = {Optimising intermittent pneumatic compression for peripherally inserted central catheter-related thrombosis prevention in traumatic brain injury: A critical appraisal of Liang et al.'s randomised controlled trial.},
journal = {Australian critical care : official journal of the Confederation of Australian Critical Care Nurses},
volume = {38},
number = {6},
pages = {101457},
doi = {10.1016/j.aucc.2025.101457},
pmid = {41175435},
issn = {1036-7314},
}

@article {pmid41175185,
year = {2025},
author = {Yang, T and Wang, Y and Yan, X and Qiu, Y and Lin, T and Luo, J and Tong, J and Mao, J and Dai, Y and Yu, Y and Zhao, M and Yang, G},
title = {Association between Onodera's prognostic nutritional Index and ultrasound-measured muscle thickness in amyotrophic lateral sclerosis: a retrospective cross-sectional study.},
journal = {Annals of medicine},
volume = {57},
number = {1},
pages = {2578733},
doi = {10.1080/07853890.2025.2578733},
pmid = {41175185},
issn = {1365-2060},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/complications/pathology/physiopathology ; Male ; Female ; Retrospective Studies ; Middle Aged ; Ultrasonography ; Cross-Sectional Studies ; Aged ; Prognosis ; *Nutritional Status ; *Nutrition Assessment ; *Muscle, Skeletal/diagnostic imaging/pathology ; Adult ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) causes progressive muscle wasting. Ultrasound-measured thickness captures this loss. Nutritional status influences ALS prognosis, yet the link between Onodera's Prognostic Nutritional Index (OPNI) and muscle thickness is unclear.

OBJECTIVE: To assess whether OPNI correlates with thickness of the first dorsal interosseous (FDI), biceps brachii (BB) and masseter (MM) muscles, and to judge OPNI's utility as a practical nutrition marker in ALS.

METHODS: In this retrospective study of 150 ALS patients, ultrasound quantified FDI, BB and MM thickness. Patients were stratified by OPNI quartile. Group differences were tested with ANOVA/Kruskal-Wallis. Multivariable generalized linear models, adjusting for age, sex, ALSFRS-R, King's stage, comorbidities and lifestyle factors, examined independent associations; restricted cubic splines probed non-linearity.

RESULTS: Muscle thickness rose progressively across OPNI quartiles (p < 0.05 for trend). After full adjustment, each 1-point OPNI increase predicted 0.008 cm thicker FDI (95% CI 0.003-0.014; p = 0.004), 0.022 cm thicker BB (95% CI 0.005-0.039; p = 0.011) and 0.011 cm thicker MM (95% CI 0.002-0.020; p = 0.013). Spline analysis supported a linear relationship.

CONCLUSION: Higher OPNI independently predicts greater muscle thickness, indicating that better nutritional status parallels reduced muscle wasting in ALS. OPNI's low cost and rapid availability support its use to flag patients for early nutritional intervention.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnostic imaging/complications/pathology/physiopathology
Male
Female
Retrospective Studies
Middle Aged
Ultrasonography
Cross-Sectional Studies
Aged
Prognosis
*Nutritional Status
*Nutrition Assessment
*Muscle, Skeletal/diagnostic imaging/pathology
Adult

@article {pmid41175163,
year = {2025},
author = {Baindoor, S and Gibriel, HAY and Kool, L and Su, J and Demaegd, KC and Venø, MT and Van Den Berg, LH and Kjems, J and Van Es, MA and Prehn, JHM},
title = {Serum small non-coding RNA define molecular subtypes in amyotrophic lateral sclerosis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/21678421.2025.2574690},
pmid = {41175163},
issn = {2167-9223},
abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with variable site of onset, disease progression rates and survival times. Early-stage ALS characteristics are shared with other conditions, posing diagnostic challenges and resulting in diagnosis delays. We investigated tRNA-derived small RNAs (tsRNAs) and microRNAs (miRNAs) which are stable and abundantly expressed small non-coding RNAs (sncRNAs) as potential diagnostic serum biomarkers, comparing them to healthy controls and ALS mimics, and gained pathophysiological insights from dysregulated sncRNAs.

METHODS: We analyzed small RNA-seq data from 158 patients with ALS, 60 healthy controls and 39 patients with neurological conditions that mimic ALS to identify differentially expressed sncRNAs. A classifier was built to evaluate their diagnostic potential, followed by hierarchical clustering to identify ALS molecular subtypes. Finally, we performed gene ontology and pathway analysis to identify pathways disrupted within subtypes.

RESULTS: We identified several dysregulated tsRNAs and miRNAs and assessed their diagnostic potential using an extreme gradient boosting (XGBoost) classifier. Our models achieved an accuracy of 87.16% and 82.23% in classifying patients with ALS from healthy controls and ALS mimics, respectively. We identified four sncRNA expression-based ALS molecular subtypes with one C9orf72 enriched cluster. Further analysis of identified differentially expressed sncRNAs showed their involvement in neuronal pathways.

CONCLUSION: Our study identified potential sncRNA-based diagnostic serum biomarkers and associated molecular subtypes which can be further studied to match clinical parameters and develop subtype specific biomarkers and therapeutic strategies for ALS.},
}

@article {pmid41175111,
year = {2025},
author = {Sewell-Green, AR and Kuiper, M and Holdom, CJ and Beelen, A and Ngo, ST and Steyn, FJ and Matthews-Rensch, KL},
title = {Examining the impact and role of lipid classes on the risk of amyotrophic lateral sclerosis (ALS) onset: a systematic review and GRADE analysis of the evidence.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/21678421.2025.2574685},
pmid = {41175111},
issn = {2167-9223},
abstract = {BACKGROUND: This study aimed to synthesize existing research on pre-diagnostic blood lipid levels and the risk of amyotrophic lateral sclerosis (ALS) onset in adults, and the quality of this evidence.

METHODS: A systematic review was conducted (8 March 2024, updated 19 June 2025) across six databases (PubMed, Embase, CINAHL, Scopus, Cochrane Library, and Web of Science) following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, identifying adult clinical studies of blood lipids measured prior to ALS onset. Studies with high risk of bias, assessed using the Quality in Prognostic Studies tool, were excluded. Standardized mean difference and 95% confidence intervals were calculated. Study outcomes were categorized by lipid class as indicating reduced, no effect, or increased ALS risk. Certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.

RESULTS: Of 7222 studies identified, eight (n = 7 sterol lipids, n = 1 fatty acids) met inclusion. No significant differences in sterol lipids were observed between ALS cases and controls (I[2] = 69.9-77.3%). Most studies reported no association or increased risk between ALS onset and higher total cholesterol, triglycerides, LDL-C, HDL-C, or LDL/HDL ratio. For HDL-C, two studies showed protective associations. A single fatty acid study reported increased disease risk with higher arachidonic acid and reduced risk with higher alpha-linoleic acid. Certainty of evidence was low to very low.

CONCLUSION: Circulating sterol lipid levels were inconsistently associated with ALS risk. The overall low certainty of evidence, and variability of findings across studies call for research using standardized designs, high-resolution lipid profiling, and robust causal inference approaches to clarify the role of lipids in ALS risk.},
}

@article {pmid41174816,
year = {2025},
author = {Eldh, AC and Bergström, A and Hälleberg-Nyman, M and Kim, B and Rycroft-Malone, J},
title = {Nuancing the continuum from ideal to real-world implementation: a letter to the editor on Nilsen et al.},
journal = {Implementation science communications},
volume = {6},
number = {1},
pages = {113},
pmid = {41174816},
issn = {2662-2211},
abstract = {Nilsen et al.'s (Implement Sci Commun 6:90, 2025) proposal to distinguish between implementation efficacy and effectiveness, and to situate implementation studies along a continuum from ideal to real-world conditions, offers a valuable conceptual advance. In this commentary, we acknowledge the contribution of their debate while highlighting potential limitations of applying a single-axis continuum to a field heavily characterized by contextual complexity. Drawing from decades of healthcare quality improvement, we argue that implementation interventions often blend efficacy-like and effectiveness-like elements, making neat classification difficult. We further suggest that oversimplification risks obscuring the realities of organizational change. Instead, we propose a double-axis model that considers both the implementation intervention and the context in which it unfolds. Economic evaluation likewise requires nuanced approaches that go beyond their proposed continuum indicator tool ("Implementation PRECIS"). To constructively extend Nilsen et al.'s contribution, we advocate for integration of the tool with existing approaches to evaluation, co-production with stakeholders, and empirical validation across diverse settings. While no implementation endeavor is ideal, advancing discourse around how efficacy and effectiveness are conceptualized can support more pragmatic, context-responsive, and sustainable improvements in healthcare.},
}

@article {pmid41174654,
year = {2025},
author = {Haddad, R and Fallu, JS and Huỳnh, C and D'Arcy, L and Song, Y and Dagenais, C},
title = {Implementation and evaluation of a knowledge translation process to optimize the adoption of harm reduction in cannabis use by practitioners working with youth in Quebec: a mixed-methods study.},
journal = {Health research policy and systems},
volume = {23},
number = {1},
pages = {147},
pmid = {41174654},
issn = {1478-4505},
support = {2023-0PTR-322652//Ministère de la Santé et des Services sociaux/ ; },
mesh = {Humans ; Quebec ; *Harm Reduction ; *Translational Research, Biomedical ; Adolescent ; Female ; Male ; *Health Personnel ; *Marijuana Abuse/prevention & control ; Surveys and Questionnaires ; Adult ; Attitude of Health Personnel ; Health Knowledge, Attitudes, Practice ; *Marijuana Smoking ; },
abstract = {BACKGROUND: Cannabis use initiation is highly common among youth. Harm reduction in cannabis use (HR-c) has proven effective in minimizing the potential harms of the substance. However, its adoption by health and social services (HSS) practitioner's remains limited owing to several obstacles. This study marks the final phase of a broader research initiative. It aims to: (1) present the implementation of a knowledge translation (KT) plan developed to enhance HR-c adoption and formulate actionable strategies to support its applicability; and (2) evaluate its immediate and short-to-medium-term effects.

METHODS: Ziam et al.'s (2024) evaluation framework guided our description of the KT plan implementation and our evaluation of its effects. Using a non-probabilistic sampling method, we recruited managers and practitioners from four residential facilities for youth in Quebec (N = 19). Two KT strategies - policy briefs and deliberative dialogues - were implemented, during which participants co-developed final actions to optimize HR-c adoption. A mixed-methods evaluation followed, involving a questionnaire with five scales and semi-structured interviews. Data were analyzed using post-parallel analysis, combining descriptive statistics and thematic analysis to assess the KT plan's implementation and effects. Cronbach's alpha of the subscales was calculated to assess their internal consistency.

RESULTS: The final actions formulated with participants addressed HR-c, youth and organizations. Quantitative findings revealed: (1) a high appreciation for the deliberative dialogues; (2) positive attitudes toward HR-c; (3) negative attitudes toward abstinence-based treatments; (4) participants' favourable perception of their training level in HR-c; and (5) a strong intention to implement the proposed actions. The qualitative findings revealed that participants were using the transferred knowledge (e.g., HR-c strategies applicable by youth) and planned to disseminate the formulated actions within their teams to enhance practices.

CONCLUSIONS: A systematic and multidirectional KT process was implemented to optimize HR-c adoption among HSS practitioners working with youth in Quebec, serving as a model for similar interventions. The study reinforced HR-c applicability, facilitated its adoption and contributed to the formulation of concrete implementation actions. Future research should examine the long-term impact of KT initiatives on HR-c adoption and explore strategies to support practitioners in applying the transferred knowledge.},
}

Humans
Quebec
*Harm Reduction
*Translational Research, Biomedical
Adolescent
Female
Male
*Health Personnel
*Marijuana Abuse/prevention & control
Surveys and Questionnaires
Adult
Attitude of Health Personnel
Health Knowledge, Attitudes, Practice
*Marijuana Smoking

@article {pmid41174170,
year = {2025},
author = {Joseph, BJ and Marshall, KA and Harley, P and Mann, JR and Alessandrini, F and Vanoye, CG and Chi, W and Prudencio, M and Simkin, D and Kao, TT and Desai, RR and Keuss, MJ and Barattucci, S and Zanovello, M and Mehta, PR and DeKeyser, JM and Limone, F and Lee, J and Brown, AL and Leyton-Jaimes, MF and Nash, LA and Juan, IGS and Aronica, E and Wainger, BJ and Shah, M and Goswami, A and Shneider, NA and Dickson, DW and Burrone, J and Zhang, C and Wichterle, H and Petrucelli, L and Watts, JK and George, AL and Fratta, P and Eggan, K and Kiskinis, E},
title = {TDP-43-dependent mis-splicing of KCNQ2 triggers intrinsic neuronal hyperexcitability in ALS/FTD.},
journal = {Nature neuroscience},
volume = {},
number = {},
pages = {},
pmid = {41174170},
issn = {1546-1726},
support = {R01NS104219//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; NS108874//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; NS108874//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; RF1NS120992//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; NS108874//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; NS108874//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; U54NS123743//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01NS125018//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; R35GM145279//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; R35NS097273//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; },
abstract = {Motor neuron hyperexcitability is a broadly observed yet poorly understood feature of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Nuclear depletion and cytoplasmic aggregation of the RNA splicing protein TAR DNA-binding protein 43 (TDP-43) are observed in most ALS and FTD patients. Here we show that TDP-43 dysfunction causes mis-splicing of KCNQ2, which encodes a voltage-gated potassium channel (Kv7.2) that regulates neuronal excitability. Using iPSC-derived neurons and postmortem ALS/FTD brain and spinal cord tissue we find widespread, disease-specific and TDP-43-specific skipping of an exon encoding the KCNQ2 pore domain. The mis-spliced mRNA escapes degradation and is translated into a nonfunctional protein with severely reduced ion conductance that aggregates in the endoplasmic reticulum and causes intrinsic hyperexcitability in ALS neuronal models. This event, which correlates with higher phosphorylated TDP-43 levels and earlier age of disease onset in patients, can be rescued by splice-modulating antisense oligonucleotides that dampen hyperexcitability in induced pluripotent stem cell cortical neurons and spinal motor neurons with TDP-43 depletion. Our work reveals that nuclear TDP-43 maintains the fidelity of KCNQ2 expression and function and provides a mechanistic link between established excitability disruption in ALS/FTD patients and TDP-43 dysfunction.},
}

@article {pmid41174080,
year = {2025},
author = {Berhanu, D and Martins, G and Antunes, AP and Abegão Pinto, L and Fragata, I and Tavares Ferreira, J and Lucas Neto, L},
title = {Novel and classic imaging signs of increased intracranial pressure.},
journal = {Neuroradiology},
volume = {},
number = {},
pages = {},
pmid = {41174080},
issn = {1432-1920},
abstract = {PURPOSE: The arachnoid bulk ratio was recently described by Berhanu et al. on ultrasonography (US) as a potentially useful surrogate for intracranial pressure (ICP). We aimed to evaluate this novel neuroimaging index using magnetic resonance imaging (MRI) and determine the accuracy of the novel and classic imaging signs to diagnose increased ICP.

METHODS: Patients with suspected increased ICP were recruited to undergo optic nerve US and MRI before invasive ICP measurement. We included a total of 23 participants and determined the correlation of the novel ratio with ICP, compared to the optic nerve sheath diameter (ONSD), and we assessed the diagnostic accuracy of the novel and classic imaging signs through receiver operating characteristic (ROC) curve analysis.

RESULTS: The arachnoid bulk ratio and ONSD were significantly larger in individuals with increased ICP on MRI (36% and 16%,p < 0.001) and on US (39% and 13%,p < 0.001). The ratio correlated very strongly with ICP on MRI and US (rs = 0.89 and rs = 0.92), outperforming the ONSD (MRI:rs = 0.67 and US:rs = 0.63). The Berhanu et al.'s ratio predicted increased ICP with a sensitivity of 100% and a specificity of 91% on MRI. The classic imaging signs with highest accuracy were the transverse sinus stenosis and ONSD, with a sensitivity of 89% and 91% and specificity of 100% and 92%,respectively.

CONCLUSIONS: This novel ratio, which selectively assesses the perineural fluid space, provides an accurate prediction of ICP on MRI. When combined with classic imaging signs, it serves as a useful non-invasive surrogate in the clinical approach to these patients.},
}

@article {pmid41173979,
year = {2025},
author = {Zhao, Y and Savelieff, MG and Li, X and Guo, K and Wang, K and Li, M and Li, B and Iyer, G and Sakowski, SA and Zhao, L and Teener, SJ and Bakulski, KM and Dou, JF and Traynor, BJ and Karnovsky, A and Batterman, SA and Hur, J and Goutman, SA and Sartor, MA and Feldman, EL},
title = {Gene expression signatures from whole blood predict amyotrophic lateral sclerosis case status and survival.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {9631},
pmid = {41173979},
issn = {2041-1723},
support = {R01NS127188//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01NS120926//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; P30ES017885//U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences (NIEHS)/ ; R01ES030049//U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences (NIEHS)/ ; 20-IIA-532//Amyotrophic Lateral Sclerosis Association (ALS Association)/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/blood/mortality/diagnosis ; Male ; Female ; Middle Aged ; *Transcriptome ; Prognosis ; Gene Expression Profiling ; Case-Control Studies ; Machine Learning ; Aged ; Adult ; ROC Curve ; Sequence Analysis, RNA ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a rare and fatal neurodegenerative disease with a median survival of only 2 to 4 years from diagnosis. Improved tools are needed to shorten diagnostic delays and improve prognostication to benefit clinical care. Herein, we profiled whole blood gene expression by RNA sequencing in a large cohort of ALS participants (n = 422) versus controls (n = 272). Several machine learning classifiers trained on our detailed gene expression dataset accurately predicted case-control status, including in a fully independent external test cohort, achieving an area under the receiver operating characteristic curve of 0.894 with the best performing model. Integrating gene expression features with clinical variables improved our ability to discriminate ALS cases into shorter, intermediate, and longer survival in an external dataset. Finally, we identified ALS-relevant pathways in our blood transcriptomics dataset as well as "core genes" that overlapped with gene expression changes occurring in the primary disease tissue, facilitating a drug perturbation analysis that identified several candidates. Overall, our results highlight the potential diagnostic and prognostic applications of whole blood gene expression data, with important implications for improving ALS clinical care.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/blood/mortality/diagnosis
Male
Female
Middle Aged
*Transcriptome
Prognosis
Gene Expression Profiling
Case-Control Studies
Machine Learning
Aged
Adult
ROC Curve
Sequence Analysis, RNA

@article {pmid41173878,
year = {2025},
author = {Sharaireh, A and Guevara-Ferrer, M and Ludlaim, AM and Humphries, JD and Phillips, AM and Dowsey, AW and Zhang, Z and Counsell, JR and Unwin, RD and Mole, SE and Rahim, AA and McKay, TR},
title = {CLN7 protein functions at the interface between endolysosomes and stress granules to promote cell survival.},
journal = {Cell death & disease},
volume = {16},
number = {1},
pages = {772},
pmid = {41173878},
issn = {2041-4889},
mesh = {Humans ; *Lysosomes/metabolism ; *Neuronal Ceroid-Lipofuscinoses/metabolism/pathology/genetics ; Cell Survival ; *Stress Granules/metabolism ; Induced Pluripotent Stem Cells/metabolism ; *Endosomes/metabolism ; Neural Stem Cells/metabolism ; Mitochondria/metabolism ; },
abstract = {Inherited biallelic mutations in the CLN7 gene result in the variant late infantile onset neuronal ceroid lipofuscinosis, a subtype of Batten disease (BD), a severe and fatal childhood neurodegenerative disease. Intriguingly, CLN7 genetic variants have also been associated with retinopathies, amyotrophic lateral sclerosis, and frontotemporal dementia. CLN7 encodes a transmembrane protein localizing to endolysosomal membranes with outward-facing chloride channel activity. Loss of CLN7 function results in cortical neurons accumulating swollen lipofuscin-containing lysosomes, leading to neuroinflammation and neurodegeneration. The molecular mechanisms underlying CLN7 BD neuropathology are not completely understood. We have generated iPSC lines from two CLN7 BD patients and age-matched unaffected controls to interrogate intracellular molecular phenotypes in iPSC-derived neural progenitor cells (iNPC). Taking a multi-omics approach we have identified disease-modified activities in endolysosomal transport in iNPC[BD] that lead to lysosomal dysfunction and decreased mitophagy, resulting in the accumulation of metabolically defective mitochondria. We further observe a breakdown in nuclear functions that centre on RNA processing and nuclear export, linking to CLN7 protein interactions at the stress granule. We have identified dual and distinct functions for CLN7, promoting cell survival during the cellular stress response. CLN7 loss of function in BD results in neuronal apoptosis.},
}

Humans
*Lysosomes/metabolism
*Neuronal Ceroid-Lipofuscinoses/metabolism/pathology/genetics
Cell Survival
*Stress Granules/metabolism
Induced Pluripotent Stem Cells/metabolism
*Endosomes/metabolism
Neural Stem Cells/metabolism
Mitochondria/metabolism

@article {pmid41173461,
year = {2025},
author = {Gunderson, R and Smith, L and Cornell, PY and Carder, P and Thomas, K},
title = {Medicaid Mechanisms and State Licensure: Pathways to Payment in Assisted Living.},
journal = {Journal of the American Medical Directors Association},
volume = {},
number = {},
pages = {105961},
doi = {10.1016/j.jamda.2025.105961},
pmid = {41173461},
issn = {1538-9375},
abstract = {OBJECTIVES: To document and highlight the variation in the types of assisted living (AL) licensed settings eligible for Medicaid home and community-based services (HCBS) payment.

DESIGN: Observational descriptive study.

SETTING AND PARTICIPANTS: We examined 32,991 licensed AL communities across all 50 states and the District of Columbia, representing 215 unique license combinations operating in 2019. We analyzed 6 Medicaid mechanisms: 1915(b), 1915(c), and 1115 waivers, and 1905(a), 1915(i), and 1915(k) state plan amendments.

METHODS: We empirically reviewed the waivers and state plans active in 2019 providing Medicaid-paid care and documented any eligible AL licenses. We compared the characteristics of eligible and ineligible AL licenses, including geography, number of AL communities represented, and AL capacity.

RESULTS: Overall, 89% of AL communities operated under a license type that is eligible for Medicaid payment through a waiver, state plan amendment, or other contracting mechanism. Forty-five states and DC employed a mechanism to reimburse care in AL with Medicaid payments, most having a 1915(c) waiver; 13 states that authorized Medicaid-reimbursed care in AL limited this benefit to a subset of licenses. AL communities operating under a license type that granted Medicaid contract eligibility had a smaller average capacity than those operating under licenses that did not allow for Medicaid payment.

CONCLUSIONS AND IMPLICATIONS: This paper builds on previous research that found associations between the percentage and concentration of dually enrolled residents in AL and state-level Medicaid payment mechanisms. We found that although most AL communities are eligible to accept Medicaid payment, the proportion of eligible ALs differs across states. Our research suggests that Medicaid policy may affect the accessibility of AL not only at the state level but also based on the type of license, which determines the type of care and services an AL can provide.},
}

@article {pmid41172144,
year = {2025},
author = {Saenz-Martinez, E and de Cerain, AL and Azqueta, A},
title = {The Use of DNA Repair Inhibitors and the Comet Assay- An Overview.},
journal = {Mutagenesis},
volume = {},
number = {},
pages = {},
doi = {10.1093/mutage/geaf025},
pmid = {41172144},
issn = {1464-3804},
abstract = {The standard comet assay detects DNA strand breaks (SBs) and alkali-labile sites (ALS), but these lesions are nonspecific. They may result directly from genotoxic agents or arise as intermediates during the repair of other DNA damage, such as oxidised bases or DNA bulky adducts. Different approaches have been developed to generate or trap these repair intermediates, making them detectable with the comet assay. Recently, the combination of the comet assay with DNA repair inhibitors like hydroxyurea (HU) and cytosine arabinoside (Ara-C) has been proposed to detect bulky DNA adducts. These lesions are mainly repaired through nucleotide excision repair (NER), a process that transiently produces SBs when damaged oligonucleotides are excised. Normally, these intermediates are rapidly repaired by DNA resynthesis and ligation. However, by inhibiting this repair step, SBs persist and can be detected by the comet assay. This strategy has been applied in various fields, including genotoxicity testing, environmental toxicology, human biomonitoring, and studies on DNA repair kinetics. This review focuses specifically on the use of HU, Ara-C, and aphidicolin (APC) in in vitro experiments to evaluate the utility and specificity of this method for detecting different types of DNA lesions. Notably, in approximately 70% of studies reviewed, the inclusion of DNA repair inhibitors led to a significant increase in DNA damage, highlighting the added value of this approach. However, although the method enhances sensitivity to bulky adducts, it also responds to other types of damage, such as those induced by alkylating or oxidative agents.},
}

@article {pmid41171761,
year = {2025},
author = {Smeyers, J and Oses-Prieto, JA and Yadanar, L and Wang, M and Iadarola, M and Lu, S and Wang, KS and Watanabe, TH and Debnath, J and Burlingame, AL and Mordes, DA},
title = {Phospho-proteome profiling in human neurons reveals targets of TBK1 in ALS/FTD-associated autophagy networks.},
journal = {Cell reports},
volume = {44},
number = {11},
pages = {116494},
doi = {10.1016/j.celrep.2025.116494},
pmid = {41171761},
issn = {2211-1247},
abstract = {Loss-of-function variants in TBK1, encoding a protein kinase, are strongly associated with familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, how haploinsufficiency for TBK1 leads to age-related neurodegeneration remains unresolved. Here, we utilize sets of isogenic induced pluripotent stem cells (iPSCs) with loss of TBK1 or loss of optineurin (OPTN) for quantitative global proteomics and phospho-proteomics in both stem cells and excitatory neurons. We found that TBK1 sustains the abundance and phosphorylation of its interacting adapter proteins, AZI2/NAP1, TANK, and TBKBP1/SINTBAD. Moreover, TBK1 regulates the phosphorylation of endo-lysosomal proteins, such as GABARAPL2, the late-endosome GTPase RAB7A, and selective autophagy cargo receptor proteins-including novel phospho-sites in p62/SQSTM1-in neurons. Finally, we provide a census of the phospho-proteome in nascent human neurons for further studies. Overall, TBK1 serves as a point of convergence in ALS/FTD-linked endo-lysosomal networks that act in a cell-autonomous manner to maintain protein homeostasis in neurons.},
}

@article {pmid41171417,
year = {2025},
author = {Xiao, L and Guo, J and Tang, G and Xiao, Z},
title = {Comment on "Air-stable double halide perovskite Cs2CuBiBr6: synthesis and memristor application" by A. Betal, A. Chetia, D. Saikia, K. Karmakar, G. Bera, N. V. Dambhare, A. K. Rath and S. Sahu, Phys. Chem. Chem. Phys., 2025, 27, 3150.},
journal = {Physical chemistry chemical physics : PCCP},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5cp00194c},
pmid = {41171417},
issn = {1463-9084},
abstract = {The recent claim by Betal et al. (Phys. Chem. Chem. Phys., 2025, 27, 3150) of synthesizing the air-stable Cs2CuBiBr6 double perovskite challenges the established thermodynamic instability of Cu(I)-based halide perovskites. Through rigorous reanalysis of their data, we demonstrate three critical inconsistencies: (1) X-ray diffraction patterns diverge markedly from simulated Cs2CuBiBr6 and Cs2AgBiBr6 patterns; (2) energy-dispersive X-ray spectroscopy reveals a Cu(I) : Bi(III) atomic ratio of ∼2 : 3, violating the 1 : 1 stoichiometry required for A2B(I)B(III)X6 perovskites; and (3) the reported bandgap (2.93 eV) exceeds that of Cs2AgBiBr6 (1.8-2.3 eV), contradicting the chemical trend predicted by density functional theory. Further, thermodynamic analysis confirms Cs2CuBiBr6's intrinsic instability (with a large negative decomposition energy of -35 meV per atom), disfavoring its synthesis. These findings bring into question Betal et al.'s claims and underscore the profound challenges in stabilizing Cu(I)-based double perovskites, urging stringent validation of structural, compositional, and thermodynamic data in perovskite research.},
}

@article {pmid41171096,
year = {2025},
author = {Deng, X and Bradshaw, GA and Kalocsay, M and Mitchison, T},
title = {Tubulin regulates stability and localization of STMN2 by binding preferentially to its soluble form.},
journal = {The Journal of cell biology},
volume = {224},
number = {12},
pages = {},
doi = {10.1083/jcb.202502192},
pmid = {41171096},
issn = {1540-8140},
support = {RR220032//Cancer Prevention and Research Institute of Texas/ ; R35GM131753/GM/NIGMS NIH HHS/United States ; },
mesh = {*Tubulin/metabolism ; Humans ; Protein Binding ; Animals ; Protein Stability ; Proteasome Endopeptidase Complex/metabolism ; trans-Golgi Network/metabolism ; Proteolysis ; Cell Membrane/metabolism ; HEK293 Cells ; Protein Transport ; Solubility ; },
abstract = {The small, tubulin-binding protein STMN2 is highly expressed in neurons and is implicated in amyotrophic lateral sclerosis. STMN2 degrades rapidly and accumulates at axotomy sites, suggesting fast turnover is crucial for its neuroprotective function. We show that STMN2 was primarily degraded by the ubiquitin-proteasome system. Its membrane-targeting N-terminal domain promoted fast turnover, whereas its tubulin-binding domain promoted stabilization. Proximity labeling and imaging showed that tubulin binding reduced STMN2 targeting to trans-Golgi network membranes. Pull-down assays showed that tubulin binds preferentially to soluble over membrane-bound STMN2. Our observations suggest that STMN2 interconverts between a soluble, tubulin-bound form and a membrane-bound, tubulin-free form, and is rapidly degraded when released from both membranes and tubulin. We propose that tubulin binding sequesters and stabilizes STMN2, while its neuroprotective function involves an unknown membrane activity.},
}

*Tubulin/metabolism
Humans
Protein Binding
Animals
Protein Stability
Proteasome Endopeptidase Complex/metabolism
trans-Golgi Network/metabolism
Proteolysis
Cell Membrane/metabolism
HEK293 Cells
Protein Transport
Solubility

@article {pmid41171075,
year = {2025},
author = {Cazzola, J and Talpo, F and Faravelli, G and Donati, C and Maramai, S and Saletti, M and Giuliani, G and Paolino, M and Cappelli, A and Anzini, M and Sommi, P and Vitali, A and Sala, A and Trucco, A and Biella, GR and Spaiardi, P},
title = {Evaluation of a New Riluzole-Based Compound VA945 on Sodium and Potassium Conductances Expressed by SH-SY5Y- Derived Neurons.},
journal = {Journal of neurochemistry},
volume = {169},
number = {11},
pages = {e70280},
pmid = {41171075},
issn = {1471-4159},
mesh = {*Riluzole/pharmacology/analogs & derivatives ; Humans ; *Neurons/drug effects/metabolism ; *Neuroprotective Agents/pharmacology ; Cell Line, Tumor ; Potassium/metabolism ; *Potassium Channels ; Sodium/metabolism ; Membrane Potentials/drug effects ; Patch-Clamp Techniques ; *Sodium Channels ; Dose-Response Relationship, Drug ; },
abstract = {Riluzole (Rilutek), a derivative of benzothiazole, acts as a neuroprotective agent by inhibiting voltage-dependent sodium (Na[+]) and delaying rectifier potassium (K[+]) currents. By doing so, it helps reduce excitotoxicity, a key pathogenetic mechanism in various neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Although riluzole is a clinically approved treatment for ALS, it is not fully effective, particularly in advanced stages of the disease. In this study, we functionally characterized a newly synthetized riluzole-based compound, VA945, with potentially enhanced neuroprotective effects. By means of SH-SY5Y human neuroblastoma cells differentiated into neurons, we assessed using whole-cell patch-clamp techniques the effects of VA945 on voltage-dependent Na[+] and K[+] currents at extracellular concentrations of 5, 50, and 100 μM. The compound reduced maximal activation and inactivation of Na[+] conductance, as well as maximal activation of K[+] conductance, across all tested concentrations. We also observed shifts of the activation and inactivation curves to more hyperpolarized potentials along with changes in the slope factor (k), indicating an altered voltage sensitivity of voltage-dependent K[+] and Na[+] channels. While the activation kinetics of both channels remained unaffected, and the inactivation kinetics of Na[+] were unchanged, we noted a slowdown in the deactivation kinetics of the K[+] channels. Altogether, these findings suggest that VA945 exerts multi-target pharmacological effects on neuronal voltage-dependent ion currents critically involved in excitotoxicity and neurodegeneration, across a wide range of concentrations. This warrants further ex vivo and/or in vivo studies to explore its potential as a neuroprotective agent.},
}

*Riluzole/pharmacology/analogs & derivatives
Humans
*Neurons/drug effects/metabolism
*Neuroprotective Agents/pharmacology
Cell Line, Tumor
Potassium/metabolism
*Potassium Channels
Sodium/metabolism
Membrane Potentials/drug effects
Patch-Clamp Techniques
*Sodium Channels
Dose-Response Relationship, Drug

@article {pmid41170888,
year = {2025},
author = {Geoffrion, D and Mikhail, D and Rizk, M and Harissi Dagher, M},
title = {Letter to the Editor: Comment on Adamovich-Zeitlina et al's "Clinical Outcomes of Boston Type 1 Keratoprosthesis With and Without Endophthalmitis During the Covid-19 Pandemic".},
journal = {Ocular immunology and inflammation},
volume = {},
number = {},
pages = {1-2},
doi = {10.1080/09273948.2025.2583219},
pmid = {41170888},
issn = {1744-5078},
abstract = {Authors reported an 18% rate of endophthalmitis in Boston type 1 keratoprosthesis (KPro) patients, higher than previously reported rates. Most cases occurred during the COVID-19 pandemic, likely due to reduced access to care. Bandage contact lens wear was found to be protective, supporting its role as standard of care in KPro eyes. Black patients experienced higher rates of endophthalmitis, highlighting disparities in eye care. Vancomycin prophylaxis did not reduce the risk of endophthalmitis in KPro eyes and may increase the number of fungal cases, supporting the selective use of topical antibiotics. Despite the higher incidence of endophthalmitis in this study, visual outcomes remained stable, emphasizing the importance of lifelong follow-up and equitable access to care for all KPro patients.},
}

@article {pmid41169598,
year = {2025},
author = {Yip, MK and Au Yeung, M and Poon, WT},
title = {Two Families With Amyotrophic Lateral Sclerosis Founder Mutation TARDBP p.G298S in Hong Kong.},
journal = {Cureus},
volume = {17},
number = {10},
pages = {e95667},
pmid = {41169598},
issn = {2168-8184},
abstract = {Amyotrophic lateral sclerosis (ALS), which is characterized by progressive deterioration of upper and lower motor neurons resulting in severe muscle atrophy, respiratory failure, and death, is a rare and fatal neurodegenerative disease. TARDBP p.G298S was recently identified as a founder mutation in southern Chinese. This article first presented case summaries of three ALS patients: two families with TARDBP p.G298S presenting with heterogeneous clinical phenotypes, including a case with an unusual extraocular muscle onset. A review of TARDBP p.G298S cases reported worldwide was conducted, surveying the age and site of onset, disease duration, and motor neuron involvement. Finally, an overview of genetic mutations reported locally for ALS was presented, showing that TARDBP p.G298S is a common mutation detected in this locality. This article highlighted the distinct clinical manifestations and genetic background in ALS patients and will be useful for developing genetic screening and counseling strategies in Hong Kong and southern China.},
}

@article {pmid41169507,
year = {2025},
author = {Shao, W and Albagli, EA and Jansen-West, K and Daughrity, LM and Tong, J and Hysi, A and Jiang, P and Todd, TW and Lee, E and Alepuz, DZ and Carlomagno, Y and Yue, M and Dunmore, JA and Castanedes-Casey, M and Otero, PC and Kurti, A and Prudencio, M and Cook, CN and Dickson, DW and Gendron, TF and Petrucelli, L and Zhang, YJ},
title = {Endolysosomal dysfunction impairs proteostasis and induces neurodegeneration in vivo.},
journal = {iScience},
volume = {28},
number = {10},
pages = {113460},
pmid = {41169507},
issn = {2589-0042},
abstract = {Transactive response (TAR) DNA-binding protein 43 (TDP-43) inclusions are a pathological hallmark of the frontotemporal dementia (FTD)-amyotrophic lateral sclerosis (ALS) spectrum. Dysfunction of the endolysosomal system, which plays a crucial role in protein trafficking and maintaining proteostasis, has been implicated in FTD-ALS pathogenesis. While the impact of endolysosomal dysfunction on TDP-43 pathology remains unclear, we demonstrated that disrupting the endolysosomal pathway by expressing the constitutively active endosomal protein, Rab5[Q79L], induces TDP-43 aggregation in cultured cells. Here, we generated a mouse model expressing GFP-tagged Rab5[Q79L], demonstrating that GFP-Rab5[Q79L] mice exhibit early motor deficits and endolysosomal dysfunction, including enlarged endosomes, abnormal lysosome morphology, and p62- or ubiquitin-positive inclusions. These mice also developed significant neuronal loss, neuroinflammation, phosphorylated TDP-43 (pTDP-43) inclusions, and nuclear envelope and nuclear pore structural defects reminiscent of FTD-ALS. Accordingly, GFP-Rab5[Q79L] mice will prove useful in expanding our understanding of endolysosomal dysfunction in proteostasis and pTDP-43 pathology.},
}

@article {pmid41169217,
year = {2025},
author = {Mirshahvaladi, S and Gaire, BP and Kashani, SA and Guha, A and Koronyo, Y and Fuchs, DT and You, Y and Black, KL and Paulo, JA and Graham, SL and Gupta, V and Mirzaei, M and Koronyo-Hamaoui, M},
title = {Retinal proteomics in neurodegeneration: Insights into ocular and brain disorders.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00291},
pmid = {41169217},
issn = {1673-5374},
abstract = {Dysregulated proteome in the retina represents a promising avenue for discovering novel therapeutic targets and noninvasive diagnostic biomarkers for neurodegenerative diseases with ocular manifestations. Advanced mass spectrometry-based proteomics techniques have shown considerable potential in investigating the retinal proteome in diseases such as glaucoma, age-related macular degeneration, diabetic retinopathy, retinitis pigmentosa, as well as Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease. Recent proteomics innovations are overcoming challenges such as limited sample size and protein coverage that previously hindered comprehensive retinal proteome analysis. Notably, the incorporation of artificial intelligence-driven computational pipelines, including Graphics Processing Unit-accelerated deep learning architectures, has markedly enhanced the precision and effectiveness of retinal proteomics. These advances facilitate high-resolution identification of novel protein signatures within large-scale multi-omics datasets. Furthermore, the integration of advanced artificial intelligence with state-of-the-art big data infrastructures supports the early detection of biomarkers and therapeutic targets in neurodegenerative diseases with ocular involvement, offering unprecedented disease specificity and sensitivity. In addition to these computational strides, emerging complementary and alternative technologies continue to provide valuable tools for retinal analysis, expanding the potential for identifying biomarker and therapeutic targets in both ophthalmic and neurodegenerative disorders. This review summarizes recent advancements in retinal proteomics, with a particular focus on neurodegenerative and ocular diseases.},
}

@article {pmid41169216,
year = {2025},
author = {Chisholm, CG and McAlary, L and Lum, JS},
title = {From translation to stabilization and degradation: A multifaceted approach for the treatment of superoxide dismutase 1-associated amyotrophic lateral sclerosis.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00778},
pmid = {41169216},
issn = {1673-5374},
}

@article {pmid41169204,
year = {2025},
author = {Setsu, S and Okano, H and Morimoto, S},
title = {Advancements in differentiation of induced pluripotent stem cells into specialized neuronal subtypes.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00630},
pmid = {41169204},
issn = {1673-5374},
abstract = {The ability to generate specialized human neurons from induced pluripotent stem cells has revolutionized neuroscience, regenerative medicine, and drug discovery. Since their discovery, induced pluripotent stem cells have emerged as an ethically favorable and versatile platform to model human neurological diseases, offering new insights beyond traditional animal models. In the past decade, rapid advances have enabled the efficient differentiation of induced pluripotent stem cells into diverse neuronal subtypes, including glutamatergic neurons, GABAergic neurons, dopaminergic neurons, serotonergic neurons, motor neurons, sensory neurons, Purkinje cells, sympathetic neurons, parasympathetic neurons, and noradrenergic neurons. Tailored combinations of developmental signaling molecules, transcription factor programming, and small molecule modulation have dramatically improved the reproducibility, scalability, and functional maturity of these differentiated neurons. These advancements are particularly timely as they underpin the next generation of disease modelling platforms, high-throughput drug screening systems, and emerging cell-based therapies for conditions such as Parkinson's disease, amyotrophic lateral sclerosis, epilepsy, and Alzheimer's disease. Moreover, the field is moving toward standardized, chemically defined protocols and improved validation pipelines, including electrophysiological assays and molecular profiling, to ensure the authenticity and maturity of induced pluripotent stem cell-derived neurons. Notably, recent breakthroughs in sympathetic and parasympathetic neuron derivation are expanding the scope of induced pluripotent stem cell technology into autonomic nervous system research and cardiac neuromodulation studies. However, challenges remain, including variability across induced pluripotent stem cell lines, incomplete neuronal maturation, and scalability constraints for clinical-grade applications. Addressing these hurdles through optimization of patterning cues, co-culture systems, and advanced bioprocessing strategies will be crucial to realizing the full translational potential of induced pluripotent stem cell-derived neurons. Collectively, the methodologies and developments summarized here mark a major step toward achieving faithful, efficient, and scalable generation of human neurons in vitro, laying the foundation for personalized neurology and regenerative medicine.},
}

@article {pmid41167574,
year = {2025},
author = {Rush, CL and Lester, EG and Mehta, K and Seward, M and Vranceanu, AM},
title = {Patient and Care-Partner Voices in ALS: Shaping Behavioral Health and Collaborative Care.},
journal = {Journal of pain and symptom management},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jpainsymman.2025.10.020},
pmid = {41167574},
issn = {1873-6513},
abstract = {CONTEXT: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease. Nearly half of people with ALS (pALS) and their care partners experience significant emotional distress, particularly around the time of diagnosis, yet behavioral health needs are inconsistently addressed.

OBJECTIVES: To explore perspectives of pALS and care partners regarding emotional distress, behavioral health needs and preferences, and access to behavioral health resources within their clinics and communities.

METHODS: 134 participants (88 pALS and 46 care partners) were recruited through ALS Y nonprofit listservs to complete an online survey developed by the study team. The survey included closed- and open-ended questions assessing behavioral health history, current needs, access to services, and preferred care approaches.

RESULTS: Participants (59.7%, n = 80) self-reported lack of behavioral health screening, 47.7% (n = 42) of pALS reported new behavioral health diagnoses after ALS diagnosis. 46 (52.3%) of pALS and 32 (69.6%) of care partner proxies expressed a need for behavioral health care at time of ALS diagnosis and were open to a range of provider types. Open-ended responses noted limited time, need for ALS-tailored behavioral health care, and feeling overwhelmed post-diagnosis.

CONCLUSION: Findings highlight current gaps and opportunity to enhance behavioral health within interdisciplinary care. Embedding brief, flexible interventions delivered by a range of trained providers-particularly at key transitions-may support emotional well-being, care engagement, and quality of life for pALS and care partners.},
}

@article {pmid41166771,
year = {2025},
author = {Shibuya, E and Miki, Y and Tanaka, MT and Ueno, T and Shimoyama, S and Tatara, Y and Nishijima, H and Arai, A and Suzuki, C and Mori, F and Wakabayashi, K and Tomiyama, M},
title = {Cerebrospinal fluid-driven extracellular vesicle as a potential diagnostic biomarker for multiple system atrophy.},
journal = {Journal of the neurological sciences},
volume = {478},
number = {},
pages = {123738},
doi = {10.1016/j.jns.2025.123738},
pmid = {41166771},
issn = {1878-5883},
abstract = {Given that Parkinsonian disorders, including Parkinson's disease (PD) and multiple system atrophy-parkinsonism (MSA-P), often have similar clinical presentations, making a clinical diagnosis can be challenging. In the present study, we extracted and analyzed extracellular vesicles (EVs) from the cerebrospinal fluid of individuals diagnosed with PD (N = 16), MSA-P (N = 16), and amyotrophic lateral sclerosis (ALS) (N = 16), with the latter serving as the control group. Transcriptomic analysis identified 7426 and 8003 differentially expressed RNAs between MSA and ALS, and MSA and PD, respectively. Four transcripts (RN7SL3, RN7SL1, MIR19B2, and SYF2P2) were among the top six transcripts upregulated in MSA-P compared with both ALS and PD. Proteomic analysis revealed notable changes in the levels of corneodesmosin, psoriasin (S100A7), and dystroglycan1 in MSA-P compared with ALS and PD. Notably, S100A7 mRNA levels were also significantly lower in MSA than in the other diseases examined. Furthermore, we found a positive correlation between S100A7 mRNA levels and the heart mean/mediastinum mean ratio on [123]I-metaiodobenzylguanidine myocardial scintigraphy, whereas SYF2P2 mRNA levels were negatively correlated with both the asymmetry index on dopamine transporter scans and Mini Mental State Examination scores. A positive correlation was found between S100A7 levels and motor symptoms. In distinguishing MSA-P from PD, MIR19B2 exhibited the highest Area Under Curve (AUC) of 0.867, demonstrating 100 % sensitivity and 68.7 % specificity. Conversely, the results for CDSN showed an AUC value of 0.847, with 58.3 % sensitivity and 100 % specificity. These combined transcriptomic and proteomic biomarkers could serve as valuable diagnostic tools for MSA.},
}

@article {pmid41165792,
year = {2025},
author = {Goerdt, LA and Brandl, C and Schuster, AK and Rauscher, FG and Finger, RP and Mauschitz, MM},
title = {[Neurodegeneration and retinal changes-A literature overview].},
journal = {Zeitschrift fur Gerontologie und Geriatrie},
volume = {},
number = {},
pages = {},
pmid = {41165792},
issn = {1435-1269},
abstract = {BACKGROUND: The eyes and the central nervous system (CNS) develop from the same embryonic tissue which explains why retinal changes have been observed in various neurological and neurodegenerative diseases. These changes can be visualized in vivo on a cellular and subcellular level using optical coherence tomography (OCT). This article summarizes which retinal changes occur and how these could be used as potential biomarkers of neurodegenerative diseases.

OBJECTIVE: The article gives an overview of the literature on the relationship between neurodegeneration, OCT-based retinal characteristics and cognitive functions.

METHODS: A literature search was carried out in PubMed until February 2025. The search terms "neurodegeneration", "dementia", "mild cognitive impairment", "mild neurocognitive disorder", "OCT", "OCT angiography (OCT-A)", "retinal biomarkers", "retinal layer", "RNFLT", and "GCL" were used. Relevant publications were reviewed, analyzed and summarized.

RESULTS: In OCT‑A Alzheimer's disease, frontotemporal dementia, vascular dementia, amyotrophic lateral sclerosis, multiple sclerosis (MS) and Parkinson's disease demonstrate an association with a reduced retinal nerve fiber layer (RNFL) and the ganglion cell layer (GCL) thickness as well as an enlarged foveal avascular zone.

CONCLUSION: So far retinal changes could not be specifically assigned to a particular form of neurodegenerative disease,; however, they could be meaningful in neuropsychological/radiological examinations and for longitudinal monitoring, as already recommended for MS. Further longitudinal studies are needed to identify and validate retinal biomarkers (patterns).},
}

@article {pmid41165282,
year = {2025},
author = {Roedl, K and Genbrugge, C},
title = {Managing cardiac arrest in the intensive care unit.},
journal = {Current opinion in critical care},
volume = {},
number = {},
pages = {},
doi = {10.1097/MCC.0000000000001319},
pmid = {41165282},
issn = {1531-7072},
abstract = {PURPOSE OF REVIEW: This review aims to explore the distinct clinical characteristics, epidemiology, treatment approaches, and research needs concerning cardiac arrest in the intensive care unit (ICU-CA), a specific subset of in-hospital cardiac arrest (IHCA). While IHCA remains a major cause of mortality, recent data indicate improved outcomes, with a notable variation in incidence and survival depending on the location, particularly within the ICU setting.

RECENT FINDINGS: Recent studies underscore that ICU-CA differs significantly from general IHCA in etiology, monitoring, and treatment environment. Although incidence rates vary widely (4-78 per 1000 ICU admissions), recent data suggest a stabilization. Causes of ICU-CA often involve noncardiac factors such as septic shock and respiratory failure. Treatment is typically guided by general advanced life support (ALS) protocols, but ICU-specific resources such as real-time monitoring, invasive pressure measurements, transesophageal echocardiography, and the potential for extracorporeal cardiopulmonary resuscitation offer unique advantages. The COVID-19 pandemic highlighted the vulnerability of ICU patients, with respiratory causes dominating and extremely poor outcomes reported.

SUMMARY: In summary, ICU-CA represents a distinct clinical entity requiring tailored research. Future directions should prioritize international registries, validation of predictive models using artificial intelligence, and clarification of do-not-resuscitate practices to improve outcomes and resource allocation in this critically ill population.},
}

@article {pmid41165081,
year = {2025},
author = {Chalitsios, CV and Gao, J and Coupland, CAC and Cox, JH and Turner, MR and Thompson, AG},
title = {Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Have Distinct Prediagnostic Blood Biochemical Profiles.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78082},
pmid = {41165081},
issn = {1531-8249},
abstract = {OBJECTIVE: Identifying modifiable factors influencing amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) risk is important for prevention. Blood biomarkers, particularly cholesterol, have been associated with neurodegenerative risk, but findings in ALS are inconsistent, and data on FTD are limited.

METHODS: We conducted a population-based cohort study using UK primary care records from QResearch linked with Hospital Episode Statistics. Adults with biomarker data recorded between 1998 and 2023 were included. We examined associations of low- and high-density lipoprotein cholesterol (LDL-C and HDL-C), total cholesterol, triglycerides, creatinine, creatine kinase, and HbA1c with ALS and FTD risk. Cox proportional hazards models were used to estimate associations. Two-sample Mendelian randomization (MR) was applied to explore genetically predicted associations of selected biomarkers.

RESULTS: There were up to 2,695 ALS and 781 FTD diagnoses, with a median follow-up duration of 9.4 and 10.5 years, respectively. Higher LDL-C (hazard ratio [HR]per 1-SD = 1.07, 95% confidence interval [CI] = 1.02-1.11) and total cholesterol levels (HRper 1-SD = 1.06, 95% CI = 1.02-1.10) were linearly associated with higher ALS risk. Age-stratified analysis showed a stronger association for total cholesterol in those ≥ 60 years (HRper 1-SD = 1.08, 95% CI = 1.04-1.13, Pinteraction = 0.003). Higher creatinine was inversely associated with FTD risk (HRper 1-SD = 0.90, 95% CI = 0.83-0.97), supported by MR (odds ratio [OR] inverse variance weighted (IVW), per 1-SD = 0.73, 95% CI = 0.56-0.96). HbA1c showed a U-shaped association with FTD (Pnon-linearity = 0.006).

INTERPRETATION: LDL and total cholesterol may provide insights into early disease changes or the etiology of ALS, whereas creatinine and HbA1c may be relevant for FTD. Research in monogenic ALS and FTD is needed to determine whether these biomarkers inform targeted prevention or intervention strategies. ANN NEUROL 2025.},
}

@article {pmid41164993,
year = {2025},
author = {Kathiravel, T and Ghahari, S and Awada, B and Gucciardi, E and Kessler, D},
title = {South Asian-Tamil Older Adults Accessing Diabetes-Related Health Care Services in the Greater Toronto Area, Canada: An Interpretive Descriptive Study.},
journal = {Canadian journal on aging = La revue canadienne du vieillissement},
volume = {},
number = {},
pages = {1-13},
doi = {10.1017/S0714980825100354},
pmid = {41164993},
issn = {1710-1107},
abstract = {Tamil immigrants in Canada face high rates of Type II Diabetes Mellitus (T2DM) and significant barriers in accessing T2DM-related services. These barriers are often amplified for older adults, whose age-related needs intersect with cultural, linguistic, and socioeconomic factors. This study explored the lived experiences of Tamil older adults accessing T2DM-related health care services in the Greater Toronto Area. A qualitative interpretive description approach was used, involving in-depth semi-structured interviews with nine Tamil older adults. Participants were recruited through purposive and snowball sampling. Thematic analysis was applied, with findings organized using Levesque et al.'s framework (). Five key themes were identified: (1) timely and informed diabetes management, (2) reliance on trusted health service providers, (3) reliance on others for transportation, (4) financial factors, and (5) navigating health care through cultural and communication factors. Identified themes can inform potential solutions to improve access including centralized resource hubs, culturally tailored education programs, affordable transportation options, and an integrated health care approach.},
}

@article {pmid41164103,
year = {2025},
author = {},
title = {Edaravone for amyotrophic lateral sclerosis.},
journal = {Australian prescriber},
volume = {48},
number = {5},
pages = {182-183},
pmid = {41164103},
issn = {0312-8008},
}

@article {pmid41164053,
year = {2025},
author = {Luan, Z and Narvaez-Correa, IV and Kandimalla, J and Valles, RG and Piriyawat, P},
title = {Clinical Reasoning and Diagnostic Challenge in a 23-Year-Old Man With Rapidly Progressive Dysphagia and Hypophonia: Juvenile-Onset Amyotrophic Lateral Sclerosis Caused by a FUS Gene Mutation.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e93369},
pmid = {41164053},
issn = {2168-8184},
abstract = {Dysphagia and dysphonia of unclear etiology in young adults pose a significant diagnostic challenge, as these symptoms are more commonly attributed to benign or structural causes rather than serious neurodegenerative disease. The absence of classic neuromuscular signs such as limb weakness, hyperreflexia, or fasciculations can delay consideration of motor neuron disease, particularly when bulbar symptoms occur in isolation. We describe a previously healthy 23-year-old man who presented with rapidly progressive dysphagia and hypophonia, initially misattributed to infectious causes. Despite an extensive workup for structural, autoimmune, and infectious causes, no clear etiology was identified. Neurologic examination revealed predominantly bulbar dysfunction, and electrodiagnostic studies showed acute to subacute denervation changes in the tongue and trapezius muscles. Genetic testing confirmed juvenile-onset amyotrophic lateral sclerosis due to a pathogenic FUS gene mutation (p.Pro525Leu). This case highlights the importance of including motor neuron disease in the differential diagnosis of rapidly progressive bulbar symptoms of unknown origin. It highlights the importance of early electrodiagnostic testing and genetic evaluation in establishing a diagnosis.},
}

@article {pmid41163920,
year = {2025},
author = {Vlad, S and Ciobanu, DI and Fulop, J and Matei, N and Cristea, DI and Szabo-Alexi, M and Blaga, FN and Ianc, D and Ilies, AB},
title = {Postural deficiencies prevalence and correlation with foot conditions, body composition, and coordination, in Romanian preadolescents children: descriptive observational study.},
journal = {Frontiers in pediatrics},
volume = {13},
number = {},
pages = {1621792},
pmid = {41163920},
issn = {2296-2360},
abstract = {BACKGROUND: Correct posture during preadolescence is crucial for harmonious physical development and long-term musculoskeletal health. The examination of spinal and lower limb deficiencies in this age group represents a highly relevant and underexplored topic.

OBJECTIVE: To determine the prevalence of postural deficiencies among Romanian preadolescents and to assess their correlations with body composition, coordination, and foot morphology.

METHODS: A total of 983 children aged 8-12 years (507 boys, 51.6%; 476 girls, 48.4%) were recruited from six middle schools in Oradea, Bihor County, Romania. Postural assessment followed Kendall et al.'s protocol using a plumb line and grid chart. Plantar pressure and center of gravity displacement were evaluated through baropodometry, while general coordination was assessed using the Matorin test.

RESULTS: Forward head posture was the most prevalent deficiency (641/983, 65.2%). Boys exhibited a higher prevalence of kyphosis (n = 448, 52.3%) compared with girls (n = 368,40.4%), while scoliosis occurred more frequent in girls (n = 306, 33.6%) vs. (n = 257, 26.1%). Significant correlations were observed between ankle valgus and scoliosis [x[2](1) = 7.87, p = .005], flatfoot and scoliosis [x[2](1) = 7.87, p = .005], and flatfoot and coordination deficits [x[2](3) = 22.96, p = .005].

CONCLUSIONS: Forward head posture emerged as the most common spinal deficiency. Notable associations were identified between body composition and kyphosis, hyperlordosis, and ankle valgus, as well as between flatfoot, scoliosis, and impaired coordination. These findings underscore the importance of early detection and the implementation of targeted prevention programs to address postural deficiencies during childhood.},
}

@article {pmid41162772,
year = {2025},
author = {Zhan, Z and Cao, D},
title = {Enhancing the rigor of oliceridine-sufentanil comparisons in hysteroscopic surgery: key methodological considerations-a comment on Ke et al.'s study.},
journal = {Journal of anesthesia},
volume = {},
number = {},
pages = {},
pmid = {41162772},
issn = {1438-8359},
}

@article {pmid41162076,
year = {2025},
author = {Guan, Y and Liu, L and Xiong, Z and Li, C and Liu, C and Sun, Y and Ji, M},
title = {Omics analysis reveals key genes mediating herbicide resistance in Digitaria sanguinalis.},
journal = {Pesticide biochemistry and physiology},
volume = {215},
number = {},
pages = {106693},
doi = {10.1016/j.pestbp.2025.106693},
pmid = {41162076},
issn = {1095-9939},
mesh = {*Herbicide Resistance/genetics ; *Herbicides/pharmacology ; *Digitaria/genetics/drug effects/metabolism ; Cytochrome P-450 Enzyme System/genetics/metabolism ; Plant Proteins/genetics/metabolism ; Proteomics ; Plant Weeds/genetics/drug effects ; Transcriptome ; Gene Expression Regulation, Plant/drug effects ; },
abstract = {Digitaria sanguinalis (L.) Scop is recognized as one of the most problematic agricultural weeds, with chemical control remaining a crucial management strategy. However, increased selection pressures have led to the emergence of resistant populations that reproduce and establish themselves as dominant communities, thereby severely jeopardizing crop yields. It is especially crucial to reveal the resistance mechanism of D.Sanguinalis, and the lack of weed histology resources has always been an obstacle to the study of resistance mechanism, nowadays, with the development of histology technology, the combination of multi-omics applied to the identification of weed resistance genes is becoming more and more perfect. In our previous study, we have preliminarily demonstrated that the resistance of D.Sanguinalis to ALS inhibitors is related to the increase of P450 enzyme activity. Here, we employed single-molecule real-time (SMRT) sequencing technology to obtain full-length transcripts of D. sanguinalis. Using DIA proteomics, we identified upregulated herbicide-metabolizing proteins, which were validated via PRM analysis. By integrating the transcriptomic and proteomic results, we identified CYP709B2 and CYP74B2 as key effector genes that mediate resistance in D. sanguinalis. We elucidated the resistance patterns and specific genes associated with D. sanguinalis, thereby enriching the bioinformatics resources available for this species and providing a foundation for herbicide-resistant weed management.},
}

*Herbicide Resistance/genetics
*Herbicides/pharmacology
*Digitaria/genetics/drug effects/metabolism
Cytochrome P-450 Enzyme System/genetics/metabolism
Plant Proteins/genetics/metabolism
Proteomics
Plant Weeds/genetics/drug effects
Transcriptome
Gene Expression Regulation, Plant/drug effects

@article {pmid41160951,
year = {2025},
author = {Madhavi, K and Kandadai, RM and Kola, S and Borgohain, R and Prasad, VVSRK},
title = {Unveiling a rare case: Novel TBK1 variant mimicking as multiple system atrophy-like phenotype.},
journal = {Parkinsonism & related disorders},
volume = {141},
number = {},
pages = {108102},
doi = {10.1016/j.parkreldis.2025.108102},
pmid = {41160951},
issn = {1873-5126},
}

@article {pmid41158661,
year = {2025},
author = {Tao, F and Lin, M and Meng, X and Huang, L and Zhuo, B and Jiang, S and Deng, S and Meng, Z and Shi, J},
title = {Copper homeostasis and cuproptosis: implications for neurodegenerative diseases.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1688554},
pmid = {41158661},
issn = {1663-4365},
abstract = {Copper (Cu) is a vital trace element required for sustaining life and is involved in numerous critical metabolic processes within the body. Cuproptosis, a newly recognized type of Cu-dependent cell death, is mechanistically distinct from apoptosis, autophagy, pyroptosis, and ferroptosis. It is characterized by abnormal Cu accumulation and aberrant interactions with key enzymes of the tricarboxylic acid (TCA) cycle, which lead to protein aggregation, loss of iron-sulfur cluster proteins, and proteotoxic stress, ultimately leading to cell death. Recent studies have revealed that Cu dyshomeostasis and cuproptosis are intricately linked to the pathological progression of several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), Wilson's disease (WD), and Menkes disease (MD). In this review, we systematically elucidate the systemic Cu metabolism, the molecular mechanisms of cuproptosis, and its intricate interplay with different neurodegenerative disorders. We also examined the relationship between cuproptosis and other types of cell death. Finally, we discuss therapeutic strategies targeting cuproptosis and Cu dyshomeostasis to combat neurodegenerative diseases and propose potential directions for future research.},
}

@article {pmid41157172,
year = {2025},
author = {Carata, E and Destino, M and Tenuzzo, BA and Panzarini, E},
title = {Inter-Organ Crosstalk in Neurodegenerative Disease.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {10},
pages = {},
pmid = {41157172},
issn = {2075-1729},
abstract = {Inter-organ communication plays a vital role in the pathogenesis of neurodegenerative diseases (ND), including Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic Lateral Sclerosis (ALS). Emerging research highlights the involvement of the gut-brain axis, immune system, and peripheral metabolic systems in modulating neuroinflammation, protein misfolding, and neuronal dysfunction by releasing cytokines, adipokines, growth factors, and other soluble factors, which in turn affect neuronal health and systemic inflammation. This review explores the complex bidirectional interactions between the brain and peripheral organs, including the gut, adipose tissue, liver, muscle, bone and immune system. Notably, the gut microbiome's role in neurodegenerative diseases through the gut-brain axis, the impact of adipose tissue in inflammation and metabolic regulation, and the muscle-brain axis with its neuroprotective myokines are also discussed. Additionally, we examine the neuro-immune axis, which mediates inflammatory responses and exacerbates neurodegeneration, and liver-brain axis that is implicated in regulating neuroinflammation and promoting disease progression. Dysregulation of inter-organ pathways contributes to the systemic manifestations of neurodegenerative diseases, offering insights into both potential biomarkers and therapeutic targets, and, in turn, promising strategies for preventing, diagnosing, and treating neurodegenerative diseases.},
}

@article {pmid41156446,
year = {2025},
author = {Polit, M and Chmielewska-Walczak, J and Sobol, M and Domitrz, I and Niemczyk, K},
title = {Safety of FEES Performed by Speech-Language Pathologists and Physicians-Evidence Supporting Task Sharing from a Retrospective Observational Study of 964 Consecutive Examinations.},
journal = {Nutrients},
volume = {17},
number = {20},
pages = {},
pmid = {41156446},
issn = {2072-6643},
mesh = {Humans ; Retrospective Studies ; *Speech-Language Pathology ; Female ; Male ; *Deglutition Disorders/diagnosis ; Middle Aged ; Aged ; *Physicians ; Adult ; Deglutition ; Aged, 80 and over ; Young Adult ; },
abstract = {(1) Background: Fiberoptic Endoscopic Evaluation of Swallowing (FEES) is one of the two gold-standard tools for assessing oropharyngeal dysphagia (alongside Videofluoroscopic Swallowing Study). Although generally considered safe, concerns about complications persist, particularly in systems where FEES is not routine and professional roles differ. The aim of this study was to evaluate the safety of FEES performed by both speech-language pathologists (SLPs) and physicians, in order to provide evidence of its safety in a healthcare system where the procedure is not yet widely established and to identify patient subgroups potentially at higher risk of procedure-related complications. (2) Methods: This retrospective study analyzed 964 consecutive FEES procedures. Examinations were carried out by trained SLPs or physicians. Data included demographics, clinical status, operator qualifications, setting, and complications, classified as minor (vomiting, poor tolerance, early termination) or major (laryngospasm, epistaxis). (3) Results: The overall complication rate was 1.14% (11/964): 0.6% minor and 0.5% major. All events were self-limiting. Complication rates did not differ between SLPs (1.05%) and physicians (1.23%) or by experience, setting, drug use, penetration-aspiration scale score, or nasogastric tube. Four complications occurred in amyotrophic lateral sclerosis patients, suggesting higher risk. (4) Conclusions: FEES is safe and well tolerated when performed by either physicians or SLPs. These findings underscore the value of task sharing in dysphagia diagnostics, demonstrating that a shared model increases service capacity, reduces delays, and facilitates timely management of dysphagia.},
}

Humans
Retrospective Studies
*Speech-Language Pathology
Female
Male
*Deglutition Disorders/diagnosis
Middle Aged
Aged
*Physicians
Adult
Deglutition
Aged, 80 and over
Young Adult

@article {pmid41156220,
year = {2025},
author = {Pupillo, E and Bianchi, E and Leone, MA and Corbo, M and Filosto, M and Padovani, A and Risi, B and Vedovello, M and dell'Era, V and Cerri, F and Morelli, C and Diamanti, L and Ceroni, M and Falzone, Y and Rigamonti, A and Vitelli, E},
title = {Understanding Long-Term Survival in ALS: A Cohort Study on Subject Characteristics and Prognostic Factors.},
journal = {Journal of clinical medicine},
volume = {14},
number = {20},
pages = {},
pmid = {41156220},
issn = {2077-0383},
abstract = {Background: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease with variable clinical progression. While median survival is 2-4 years, 5-15% of individuals survive for longer. Methods: We conducted a retrospective, observational study using a population-based ALS register in Lombardy, Italy, to identify the clinical characteristics of long-term ALS survivors (≥10 years). Incident cases included in two periods (1998-2002 and 2008-2012) were considered. Results: A total of 828 ALS cases were included. Median survival for the entire cohort was 2.2 years (IQR 1.1-4.4). However, long-term survival was observed in 7% of individuals at 10 years, and 3% at 15 years. Long-survivors had a median survival of 13.4 years, significantly longer than the 1.9 years of non-long-survivors (IQR 1.0-3.6). Long-survivors were younger at disease onset and diagnosis, had longer diagnostic delay, and were more likely to have had a spinal onset. The cohort also showed a higher proportion of males among long-term survivors (75% vs. 59%). No significant difference in survival was observed between the two examined periods. Conclusions: Our findings suggest that long-term ALS survival is likely influenced by a complex interplay of clinical, genetic, and environmental factors, along with the intrinsic rate of motor neuron degeneration.},
}

@article {pmid41155689,
year = {2025},
author = {Ruffo, P and Perrone, B and Perrone, F and De Amicis, F and Iuliano, R and Bucci, C and Messina, A and Conforti, FL},
title = {The Other Side of the Same Coin: Beyond the Coding Region in Amyotrophic Lateral Sclerosis.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {10},
pages = {},
pmid = {41155689},
issn = {1424-8247},
support = {2022XTM2S3//Ministero dell'università e della ricerca/ ; P20225J5NB//Ministero dell'università e della ricerca/ ; },
abstract = {Transposable elements (TEs), once regarded as genomic "junk," are now recognized as powerful regulators of gene expression, genome stability, and innate immunity. In the context of neurodegeneration, particularly Amyotrophic Lateral Sclerosis (ALS), accumulating evidence implicates TEs as active contributors to disease pathogenesis. ALS is a fatal motor neuron disease with both sporadic and familial forms, linked to genetic, epigenetic, and environmental factors. While coding mutations explain a subset of cases, advances in long-read sequencing and epigenomic profiling have unveiled the profound influence of non-coding regions-especially retrotransposons such as LINE-1, Alu, and SVA-on ALS onset and progression. TEs may act through multiple mechanisms: generating somatic mutations, disrupting chromatin architecture, modulating transcriptional networks, and triggering sterile inflammation via innate immune pathways like cGAS-STING. Their activity is normally repressed by epigenetic regulators, including DNA methylation, histone modifications, and RNA interference pathways; however, these controls are compromised in ALS. Taken together, these insights underscore the translational potential of targeting transposable elements in ALS, both as a source of novel biomarkers for patient stratification and disease monitoring, and as therapeutic targets whose modulation may slow neurodegeneration and inflammation. This review synthesizes the current knowledge of TE biology in ALS; integrates findings across molecular, cellular, and systems levels; and explores the therapeutic potential of targeting TEs as modulators of neurodegeneration.},
}

@article {pmid41155541,
year = {2025},
author = {Perez, DM},
title = {α1A-Adrenergic Receptor as a Target for Neurocognition: Cautionary Tale from Nicergoline and Quinazoline Non-Selective Blockers.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {10},
pages = {},
pmid = {41155541},
issn = {1424-8247},
support = {RO1AG066627/GF/NIH HHS/United States ; },
abstract = {Decades ago, previous studies that used non-selective ergot derivatives suggested that blockage of the α1A-adrenergic receptor mildly increased cognition through increased blood flow to the brain due to vasodilation and, thus, could be used as a treatment for dementia. However, further studies indicated that nicergoline was non-specific and hit many different targets. Today, a similar scenario is developing with the use of non-selective α1-AR antagonists of the quinazoline class, referred to as "osins", as potential treatments for COVID-19/SARS, post-traumatic stress disorder, cancer, and neurodegenerative disorders, such as Parkinson's, Alzheimer's, and amyotrophic lateral sclerosis. While there is extensive evidence of neuroprotection from many clinical trials, the mechanism of action of quinazolines is often not α1-AR-mediated but keyed to its glycolysis-enhancing effects through activation of the enzyme phosphoglycerate kinase 1 (PGK1). These studies have incorrectly labeled the α1A-adrenergic receptor as an "old target" to treat Alzheimer's and other neurocognitive diseases, hampering drug development. This review will summarize these and other studies to indicate that activation, not blockage, of norepinephrine's actions, through α1A-AR, mediates cognitive, memory, and neuroprotective functions that may reverse the progression of neurocognitive diseases.},
}

@article {pmid41155507,
year = {2025},
author = {Sonkodi, B and Nagy, ZF and Keller-Pintér, A and Klivényi, P and Molnár, MJ and Széll, M},
title = {Genetic Variants in SDC3, KCNA2, KCNK1, KCNK16, and Heat Shock Transcription Factor-1 Genes: An Exploratory Analysis Supporting the Piezo2 Channelopathy Hypothesis in Amyotrophic Lateral Sclerosis Onset.},
journal = {International journal of molecular sciences},
volume = {26},
number = {20},
pages = {},
pmid = {41155507},
issn = {1422-0067},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *Ion Channels/genetics ; *Kv1.2 Potassium Channel/genetics ; *Heat Shock Transcription Factors/genetics ; Female ; Male ; Middle Aged ; *Channelopathies/genetics ; Genetic Predisposition to Disease ; Adult ; Genetic Variation ; Aged ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a multisystem progressive neurodegenerative disease. A recent theory of ALS onsetting pathogenesis proposed that the initiating primary damage is an acquired irreversible intrafusal proprioceptive terminal PIEZO2 channelopathy with underlying genetic and environmental risk factors. This Piezo2 channelopathy may also disrupt the ultrafast proton-based oscillatory signaling to motor neurons through vesicular transporter 1 (VGLUT1) and to the hippocampus through VGLUT2. As a result, it may gradually degenerate motor neurons in which process Kv1.2 ion channels are gradually depleted. It also gradually depletes heat shock transcription factor-1 (HSF-1) in the hippocampus, hence negatively affecting adult hippocampal neurogenesis. Syndecans, especially syndecan-3 (SDC3) in the nervous system, may act as critical players in the maintenance of the crosstalk between Piezo ion channels. Hence, our goal was to reanalyze the potential pathogenic gene variants from the cohort of our previous ALS study with a special focus on the aforementioned genes. Reanalysis of data formerly acquired by whole-exome sequencing of 21 non-related adult ALS patients was carried out with a focus on 28 genes. Accordingly, we identified charge-altering variants of SDC3 in 13 patients out of 21 that may contribute to the impairment of the Piezo crosstalk, and the progressive loss of the proposed proton-based signaling to motor neurons and to the hippocampus. A variant of uncertain significance was identified in the KCNA2 gene that may facilitate the faster loss of Kv1.2 ion function on motor neurons when Piezo2 channelopathy prevails. Not to mention that one variant was identified in the potassium current rectifying ion channels encoding KCNK1 and KCNK16 genes that may also propel the ALS disease process and provide the autoimmune-like pathogenic background. Moreover, Piezo2 channelopathy likely promotes diminishing HSF1 function in the hippocampus in the presence of the identified HSF1 variant. The current findings may support the ALS onsetting acquired irreversible Piezo2 channelopathy-induced pathogenesis. However, the preliminary nature of these findings needs validation and further functional studies on cohorts with a larger sample size in the future.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/pathology
*Ion Channels/genetics
*Kv1.2 Potassium Channel/genetics
*Heat Shock Transcription Factors/genetics
Female
Male
Middle Aged
*Channelopathies/genetics
Genetic Predisposition to Disease
Adult
Genetic Variation
Aged

@article {pmid41155480,
year = {2025},
author = {Turpo-Peqqueña, AG and Valencia-Arce, RJ and Del-Carpio-Carrazco, FL and Quispe-Ppacco, DJ and Carbajal-Llerena, PF and Loza-Chipa, HR and Vásquez-Macedo, AS and Gómez, B},
title = {Inhibition of Casein Kinase 1δ as a Novel Therapeutic Strategy for Amyotrophic Lateral Sclerosis: A Theoretical Study.},
journal = {International journal of molecular sciences},
volume = {26},
number = {20},
pages = {},
pmid = {41155480},
issn = {1422-0067},
mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/enzymology ; *Casein Kinase Idelta/antagonists & inhibitors/chemistry/metabolism ; Molecular Docking Simulation ; Humans ; Molecular Dynamics Simulation ; *Protein Kinase Inhibitors/chemistry/pharmacology/therapeutic use ; Protein Binding ; },
abstract = {Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disease characterized by the degeneration of motor neurons and the pathological accumulation of phosphorylated TDP-43. Casein kinase one delta (CK1δ) has been identified as a key regulator of this aberrant phosphorylation, making it a promising therapeutic target. In this theoretical study, 26 structurally diverse compounds were evaluated against CK1δ using molecular docking, molecular dynamics simulations, and binding free energy calculations. Among them, BZH exhibited the most stable interaction with CK1δ (-46.53±1.94 kcal/mol). An inverse correlation was observed between theoretical affinity and experimental IC50 values, supporting the predictive validity of the computational approach. Pharmacokinetic analysis indicated that IMF and BIP show good oral absorption and the ability to cross the blood-brain barrier. At the same time, the toxicological profile classified all compounds in toxicity Class IV (moderate risk). Additionally, dynamic migration toward an alternative pocket was observed during simulation, highlighting the importance of considering protein flexibility in drug design. This study proposes BZH, IMF, and BIP as promising CK1δ inhibitors for future experimental validation in the treatment of ALS.},
}

*Amyotrophic Lateral Sclerosis/drug therapy/enzymology
*Casein Kinase Idelta/antagonists & inhibitors/chemistry/metabolism
Molecular Docking Simulation
Humans
Molecular Dynamics Simulation
*Protein Kinase Inhibitors/chemistry/pharmacology/therapeutic use
Protein Binding

@article {pmid41155167,
year = {2025},
author = {Sharbafshaaer, M and Pepe, R and Notariale, R and Canale, F and Tedeschi, G and Tessitore, A and Bergamo, P and Trojsi, F},
title = {Beyond Antioxidants: The Emerging Role of Nrf2 Activation in Amyotrophic Lateral Sclerosis (ALS).},
journal = {International journal of molecular sciences},
volume = {26},
number = {20},
pages = {},
pmid = {41155167},
issn = {1422-0067},
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; Humans ; *NF-E2-Related Factor 2/metabolism/genetics ; Animals ; *Antioxidants/metabolism ; Oxidative Stress ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder involving the progressive degeneration of upper and lower motor neurons. While oxidative stress, RNA-binding protein (RBP) pathology, mitochondrial dysfunction, and glial-neuronal dysregulation is involved in ALS pathogenesis, current therapies provide limited benefit, underscoring the need for multi-target disease-modifying strategies. Nuclear factor erythroid 2-related factor 2 (Nrf2), classically regarded as a master regulator of redox homeostasis, has recently emerged as a central integrator of cellular stress responses relevant to ALS. Beyond its canonical antioxidant function, Nrf2 regulates critical pathways involved in mitochondrial quality control, proteostasis, nucleocytoplasmic transport, RNA surveillance, and glial reactivity. Experimental models demonstrate that astrocyte-specific Nrf2 activation enhances glutathione metabolism, suppresses neuroinflammation, promotes stress granule disassembly, and reduces RBP aggregation. In C9orf72-linked ALS, Nrf2 activation mitigates dipeptide repeat protein toxicity and restores RNA processing fidelity via modulation of nonsense-mediated decay and R-loop resolution. Recent advances in Nrf2-targeted interventions including Keap1-Nrf2 protein-protein interaction inhibitors, dual Nrf2/HSF1 activators, and cell-type-selective Adeno-associated virus 9 (AAV9) vectors show promise in preclinical ALS models. These multimodal approaches highlight Nrf2's therapeutic versatility and potential to address the upstream convergence points of ALS pathogenesis. Taken together, positioning Nrf2 as a systems-level regulator offers a novel framework for developing precision-based therapies in ALS. Integrating Nrf2 activation with RNA- and glia-directed strategies may enable comprehensive modulation of disease progression at its molecular roots.},
}

*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics
Humans
*NF-E2-Related Factor 2/metabolism/genetics
Animals
*Antioxidants/metabolism
Oxidative Stress

@article {pmid41154657,
year = {2025},
author = {Nhieu, J and Wei, LN},
title = {Targeting CRABP1 Signalosomes in Managing Neurodegeneration.},
journal = {Biomolecules},
volume = {15},
number = {10},
pages = {},
pmid = {41154657},
issn = {2218-273X},
support = {R01NS132277//National Institute of Health/ ; },
mesh = {Humans ; Animals ; *Receptors, Retinoic Acid/metabolism/genetics ; *Neurodegenerative Diseases/metabolism/drug therapy ; Signal Transduction/drug effects ; Tretinoin/metabolism/pharmacology ; },
abstract = {Retinoic acid (RA) binds RA (RAR) and Retinoid X (RXR) receptors to elicit biological effects by regulating transcription. RA is also known to have non-canonical activities mediated, primarily, by cellular retinoic acid-binding protein 1 (CRABP1) which forms protein complexes named "CRABP1 signalosomes" to regulate cytosolic signaling independent of RARs/RXRs. This review focuses on therapeutic applications in neurodegeneration by targeting CRABP1 signalosomes including CRABP1-MAPK, CRABP1-CaMKII, CRABP1-eIF2α, and others recently identified from our proteomic studies. The mouse Crabp1 gene is regulated by various epigenetic factors and is important for the health of multiple cell types including motor neurons (MNs). In humans, CRABP1 gene expression is reduced in ALS- and SMA-patient MNs. RA is a therapeutic agent for leukemias and dermatological disorders and is being investigated for managing neurodegenerative diseases, but its therapeutic effects are accompanied by RAR-mediated toxic effects. We have uncovered a novel class of synthetic retinoids that bind CRABP1 without acting on RARs, circumventing RAR-mediated toxic effects. These first-generation CRABP1-selective compounds C3, C4, and C32 target CRABP1-MAPK and/or CRABP1-CaMKII signalosomes. This knowledge, together with emerging structural information, sheds lights on the strategies in designing next-generation CRABP1-signalosome-selective retinoids for the management of neurodegenerative diseases.},
}

Humans
Animals
*Receptors, Retinoic Acid/metabolism/genetics
*Neurodegenerative Diseases/metabolism/drug therapy
Signal Transduction/drug effects
Tretinoin/metabolism/pharmacology

@article {pmid41154611,
year = {2025},
author = {Moțățăianu, A and Ion, V and Dumitreasă, M and Ormenișan, I and Farczadi, L and Andone, S and Bălașa, R and Roman, MM},
title = {Short-Chain Fatty Acid Profiles in Amyotrophic Lateral Sclerosis: Longitudinal Effects of Disease and Mediterranean Diet Intervention.},
journal = {Biomolecules},
volume = {15},
number = {10},
pages = {},
pmid = {41154611},
issn = {2218-273X},
support = {PN-III-P1-1.1-TE-2021-0960 within PNCDI III.//Ministerul Cercetării, Inovării și Digitalizării (Ministry of Research, Innovation, and Digitization) CNCS-UEFISCDI/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/diet therapy ; *Diet, Mediterranean ; *Fatty Acids, Volatile/blood ; Male ; Female ; Middle Aged ; Aged ; Prospective Studies ; Gastrointestinal Microbiome ; Longitudinal Studies ; Adult ; Propionates/blood ; },
abstract = {Background: Amyotrophic lateral sclerosis (ALS) evolution is influenced by many dietary factors, biochemical and hormonal inter-relations and gut microbiota. This study focuses on dynamics by conducting a plasmatic quantitative analysis of six of the main short-chain fatty acids (SCFAs) for ALS patients and the shifts in circulating SCFA profiles during ALS progression as well as their potential responsiveness or change due to dietary modulation. Methods: A 12-month prospective study in parallel with control group determinations was conducted. The patients diagnosed with ALS were evaluated at the start of the study (T0) followed by a six-month observation time frame (T1) and after another six months of a Mediterranean diet intervention (T2). Plasma SCFAs were determined using liquid chromatography coupled to mass spectrometry to showcase the plasmatic profiles. Correlation between plasma levels of SCFAs and patients' clinical characteristics next to correlations between plasma SCFA levels at T1 and T2 were performed. Results: A significant increase between control group and patients at T0 was observed for acetic, propionic, butyric and hydroxy-butyric acid. Hexanoic acid levels stagnated and 4-methyl-valeric acid concentrations decreased. Evolutions from T1 and T2 impacted acetate, propionate and 4-methyl-valerate. Conclusions: The study offers a better understanding regarding the differences in SCFA levels in ALS patients. The Mediterranean diet may impact the levels of acetic and propionic acid, indicating the modulation of SCFA production by gut microbiota.},
}

Humans
*Amyotrophic Lateral Sclerosis/blood/diet therapy
*Diet, Mediterranean
*Fatty Acids, Volatile/blood
Male
Female
Middle Aged
Aged
Prospective Studies
Gastrointestinal Microbiome
Longitudinal Studies
Adult
Propionates/blood

@article {pmid41153670,
year = {2025},
author = {Santurtún, A and Pérez-Soberón, L and Sedano, MJ and Riancho, J},
title = {Amyotrophic Lateral Sclerosis Patients Show Higher Urinary Levels of Lead and Copper: A Pilot Case-Control Study.},
journal = {Biomedicines},
volume = {13},
number = {10},
pages = {},
pmid = {41153670},
issn = {2227-9059},
support = {PI23/00905//Instituto de Salud Carlos III/ ; INT24/0060//Instituto de Salud Carlos III/ ; INT24/04//Instituto de Investigación Marqués de Valdecilla/ ; },
abstract = {Background/Objectives: Amyotrophic Lateral Sclerosis (ALS) is the most frequent neurodegenerative disease affecting motor neurons. Sporadic ALS cases, which represent over 90% of the total, result from the interaction between genetic predisposition, aging, and environmental factors. Regarding natural environmental risk factors, the analysis of the role of exposure to heavy metals is of particular interest due to the well-known neurological effects of certain compounds. This study aims to compare the levels of heavy metals in urine samples in a cohort of patients with ALS who have not changed their living environment with the levels found in healthy controls (HCs). Methods: A cross-sectional case-control (14 patients with ALS vs. 28 HC) observational study was conducted in which urine samples were analyzed for five heavy metals (lead, manganese, selenium, copper, and zinc) using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Results: The patients with ALS showed significantly higher urine levels of lead (p < 0.001) and copper (p = 0.007) and a subtle increase in manganese concentrations (p = 0.043). Urine samples reflect recent exposures, so if the source of metals was related to the residential environment (the patients in the present study had not moved), dietary habits, or certain activities or hobbies that had not changed since diagnosis, it would be representative. Conclusions: In this pilot study, patients with ALS presented higher urinary levels of lead, manganese, and copper. Future larger studies are needed to elucidate the precise role of these heavy metals in ALS pathogenesis.},
}

@article {pmid41153395,
year = {2025},
author = {De La Cerna, JLO and Talubo, NDD and Villanueva, BHA and Tsai, PW and Tayo, LL},
title = {Conserved Blood Transcriptome Patterns Highlight microRNA and Hub Gene Drivers of Neurodegeneration.},
journal = {Genes},
volume = {16},
number = {10},
pages = {},
doi = {10.3390/genes16101178},
pmid = {41153395},
issn = {2073-4425},
mesh = {*MicroRNAs/genetics/blood ; Humans ; *Neurodegenerative Diseases/genetics/blood ; *Transcriptome/genetics ; Gene Regulatory Networks ; Gene Expression Profiling ; RNA, Messenger/genetics ; Gene Expression Regulation ; },
abstract = {Background/Objectives: Neurodegenerative diseases (NDs) such as Alzheimer's (AD), Parkinson's (PD), Huntington's (HD), and Amyotrophic Lateral Sclerosis (ALS) are clinically distinct but share overlapping molecular mechanisms. Methods: To identify conserved systemic signatures, we analyzed blood RNA-Seq datasets using Weighted Gene Co-Expression Network Analysis (WGCNA), differential expression, pathway enrichment, and miRNA-mRNA network mapping. Results: Two modules, the red and turquoise, showed strong preservation across diseases. The red module was enriched for cytoskeletal and metabolic regulation, while the turquoise module involved immune, stress-response, and proteostatic pathways. Discussion: Key hub genes, such as HMGCR, ACTR2, MYD88, PTEN, EP300, and regulatory miRNAs like miR-29, miR-132, and miR-146a, formed interconnected networks reflecting shared molecular vulnerabilities. The absence of classical heat shock proteins in preserved blood modules highlights tissue-specific expression differences between blood and neural systems. Several hub genes overlap with known pharmacological targets, suggesting potential in translational relevance. Conclusions: Together, these findings reveal conserved blood-based transcriptional modules that suggest parallel central neurodegenerative processes and may support future biomarker development and possible therapeutic exploration.},
}

*MicroRNAs/genetics/blood
Humans
*Neurodegenerative Diseases/genetics/blood
*Transcriptome/genetics
Gene Regulatory Networks
Gene Expression Profiling
RNA, Messenger/genetics
Gene Expression Regulation

@article {pmid41153386,
year = {2025},
author = {Papapanagiotou, AP and Vasilakoglou, I and Alvanou, MV and Giantsis, IA and Madesis, P and Eleftherohorinos, IG},
title = {Blackgrass (Alopecurus myosuroides Huds.) Multiple Resistance to ACCase- and ALS-Inhibitors and Its Competition with Winter Wheat.},
journal = {Genes},
volume = {16},
number = {10},
pages = {},
doi = {10.3390/genes16101169},
pmid = {41153386},
issn = {2073-4425},
mesh = {*Poaceae/genetics/drug effects/growth & development ; *Herbicide Resistance/genetics ; *Acetyl-CoA Carboxylase/antagonists & inhibitors/genetics ; Herbicides/pharmacology ; *Triticum/drug effects/genetics/growth & development ; *Acetolactate Synthase/antagonists & inhibitors/genetics ; *Plant Proteins/genetics/antagonists & inhibitors ; Plant Weeds/drug effects/genetics ; Heterocyclic Compounds, 2-Ring ; Propionates ; Pyridines ; },
abstract = {Background/Objectives: The herbicide resistance of blackgrass (Alopecurus myosuroides Huds.) is one of the most serious problems in the winter cereal monoculture in Europe. Recently, Greek farmers expressed complaints of reduced susceptibility of this weed to winter wheat herbicides. Keeping this in mind, this study focused on the investigation of blackgrass resistance to herbicides at both phenotypic and molecular levels. Methods: Whole-plant rate-response pot assays were conducted to study the possible evolution of resistance (cross- or multiple-resistance) in a blackgrass population to ACCase- and ALS-inhibiting herbicides. Analysis of the ACCase gene sequence, herbicide metabolism study and competition with winter wheat studies were also conducted. Results: High levels of cross-resistance mainly to the ACCase post-emergence clodinafop-propargyl, medium to fenoxaprop-P-ethyl, cycloxydim, pinoxaden, as well as lower levels of resistance to ALS-inhibitors (mesosulfuron-methyl + iodosulfuron-methyl-sodium and pyroxsulam) were confirmed. In addition, the pre-emergence soil-applied herbicides chlorotoluron + diflufenican and prosulfocarb provided excellent control of the S and R blackgrass populations. The analysis of the ACCase gene sequence revealed a point mutation at position 1781, resulting in an amino acid substitution from isoleucine (Ile) to leucine (Leu). Furthermore, the combined application of the herbicides with piperonyl butoxide (PBO, applied 2 h before herbicide application) indicated that there was herbicide metabolism, which may be mediated by cytochrome P450. The R blackgrass population, when grown in competitive interaction with winter wheat, produced more tillers and aboveground fresh weight compared to the S population and caused greater reduction in winter wheat. Conclusions: The results suggest that a blackgrass population has developed multiple resistance to ACCase- and ALS-inhibiting herbicides, due to ACCase gene mutation and herbicide metabolism. No fitness cost and no compromised competitive ability associated with the blackgrass resistance were observed.},
}

*Poaceae/genetics/drug effects/growth & development
*Herbicide Resistance/genetics
*Acetyl-CoA Carboxylase/antagonists & inhibitors/genetics
Herbicides/pharmacology
*Triticum/drug effects/genetics/growth & development
*Acetolactate Synthase/antagonists & inhibitors/genetics
*Plant Proteins/genetics/antagonists & inhibitors
Plant Weeds/drug effects/genetics
Heterocyclic Compounds, 2-Ring
Propionates
Pyridines

@article {pmid41152540,
year = {2025},
author = {Yan, C and Zhang, J and Yang, Y and Zeng, X and Xiao, G},
title = {Virulence factors, biofilm formation and antifungal resistance in Candida albicans from recurrent vulvovaginal candidiasis patients: a comparative study.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {37557},
pmid = {41152540},
issn = {2045-2322},
mesh = {*Biofilms/drug effects/growth & development ; Humans ; *Candidiasis, Vulvovaginal/microbiology/drug therapy ; *Candida albicans/drug effects/genetics/physiology/pathogenicity/isolation & purification ; *Virulence Factors/genetics/metabolism ; Female ; *Drug Resistance, Fungal/genetics ; *Antifungal Agents/pharmacology ; Microbial Sensitivity Tests ; Fungal Proteins/genetics/metabolism ; Adult ; Fluconazole/pharmacology ; Gene Expression Regulation, Fungal ; },
abstract = {Recurrent vulvovaginal candidiasis (RVVC) is a common, refractory fungal infection affectingwomen, primarily caused by Candida albicans. The interplay among fungal virulence factors, biofilm formation, and antifungal resistance is crucial in the pathogenesis of RVVC. This study compared 50 Candida albicans isolates from RVVC patients and 50 from asymptomatic vaginal colonizers. Antifungal susceptibility testing was performed using the broth microdilution method. Biofilm formation was assessed via crystal violet staining, and the expression levels of virulence factor hydrolases (SAP, PL, Lip) and cell wall protein genes (ALS1, ALS3, HWP1) were analyzed using phenotypic assays and quantitative real-time PCR (qRT-PCR). Pearson correlation analysis was used to evaluate the relationships among these parameters and antifungal resistance. RVVC isolates exhibited significantly higher MICs for fluconazole, voriconazole, and itraconazole. Biofilm formation ability and the expression levels of SAP, PL, Lip, ALS1, ALS3, and HWP1 were also significantly higher in RVVC isolates. A moderate correlation was observed between antifungal drug MIC values and biofilm OD, while a weak correlation existed between MIC values and ALS/HWP1 gene expression. Notably, hydrolase expression showed no significant correlation with resistance. Candida albicans from RVVC patients demonstrated enhanced biofilm formation, virulence factor expression, and antifungal resistance. Biofilm-mediated drug tolerance may be a key mechanism underlying the refractoriness of RVVC. Targeting biofilm formation and virulence factor genes may offer novel strategies for managing RVVC.},
}

*Biofilms/drug effects/growth & development
Humans
*Candidiasis, Vulvovaginal/microbiology/drug therapy
*Candida albicans/drug effects/genetics/physiology/pathogenicity/isolation & purification
*Virulence Factors/genetics/metabolism
Female
*Drug Resistance, Fungal/genetics
*Antifungal Agents/pharmacology
Microbial Sensitivity Tests
Fungal Proteins/genetics/metabolism
Adult
Fluconazole/pharmacology
Gene Expression Regulation, Fungal

@article {pmid41152189,
year = {2025},
author = {Snyder, A and Samra, K and Wu, T and Russell, LL and Farren, J and Crook, J and Haselhuhn, T and Porter, K and Szabo, M and Duckett, A and Lin, F and Danielian, L and Traynor, BJ and Scholz, SW and Boeve, BF and Rosen, HJ and Rohrer, JD and Kwan, JY},
title = {Integrating a motor domain enhances disease severity scales in an FTD-ALS spectrum cohort.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {10},
pages = {e70786},
doi = {10.1002/alz.70786},
pmid = {41152189},
issn = {1552-5279},
support = {U01AG045390//The National Institute on Aging/ ; U54NS092089//The National Institute on Aging/ ; U19AG063911//The National Institute on Aging/ ; //The Intramural Research Program of the National Institutes of Health/ ; /NS/NINDS NIH HHS/United States ; },
mesh = {Humans ; Male ; *Severity of Illness Index ; Female ; *Frontotemporal Dementia/diagnosis/physiopathology ; Middle Aged ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; Aged ; Longitudinal Studies ; Cohort Studies ; Neuropsychological Tests ; },
abstract = {INTRODUCTION: The Genetic Frontotemporal Initiative (GENFI) and Advancing Research and Treatment in Frontotemporal Lobar Degeneration (ARTFL)-Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) Longitudinal Frontotemporal Lobar Degeneration Study (ALLFTD) consortia developed Clinical Dementia Rating (CDR)-derived scales with a motor domain to overcome systematic underestimation of disease severity by the CDR. We calculated disease severity scores using these scales in a mixed neurodegenerative cohort and correlated them with objective motor measures.

METHODS: The CDR plus National Alzheimer's Coordinating Center (NACC) Frontotemporal Lobar Degeneration (FTLD), CDR + NACC FTLD-M (Motor), and Multidomain Impairment Rating (MIR) scores and motor measures were determined and correlated in 242 participants.

RESULTS: Both CDR + NACC FTLD-M and MIR showed increased disease severity scores and correlated with motor measures. These findings were held in 81 amyotrophic lateral sclerosis (ALS) participants and correlated with the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale. Including a motor domain required fewer study participants in a simulated clinical trial sample size calculation.

DISCUSSION: With a motor domain, CDR + NACC FTLD-M and MIR improve disease severity classification and correlate with quantitative motor assessments. This addition more fully captures the extent of symptoms across the FTD-ALS spectrum and improves clinical trial efficiency.

HIGHLIGHTS: CDR + NACC FTLD-M and MIR strongly correlate with objective motor measures. The enhanced scales improve disease severity classification in FTD and ALS. Greater clinical trial efficiency is achieved using these enhanced scales.},
}

Humans
Male
*Severity of Illness Index
Female
*Frontotemporal Dementia/diagnosis/physiopathology
Middle Aged
*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology
Aged
Longitudinal Studies
Cohort Studies
Neuropsychological Tests

@article {pmid41152089,
year = {2025},
author = {Tabugo, SR},
title = {Mangrove microbiomes as hidden ecological gatekeepers.},
journal = {Trends in microbiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tim.2025.10.009},
pmid = {41152089},
issn = {1878-4380},
abstract = {Mangroves are known worldwide but their concealed network of microbiomes is poorly understood. Huang et al., on genomic indicators, Siblos and Tabugo's 16S rRNA sequencing of the mangrove microbiome, and Dechavez et al.'s culture-dependent survey collectively highlight the ecological significance of mangroves, their conservation potential, and their role as key ecological gatekeepers.},
}

@article {pmid41151740,
year = {2025},
author = {Bhatia, T and Godad, A},
title = {Disrupted proteostasis and ionic imbalance in TDP-43 and tauopathies: Dual drivers of neurodegeneration.},
journal = {Life sciences},
volume = {382},
number = {},
pages = {124055},
doi = {10.1016/j.lfs.2025.124055},
pmid = {41151740},
issn = {1879-0631},
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's Disease (AD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), are characterized by progressive neuronal dysfunction and protein aggregation. There is a growing body of evidence suggesting that the collapse of proteostasis, the failure of protein homeostasis, is an important contributor to neurotoxicity. In this review, we suggest that this collapse is exacerbated by ionic dysregulation, an important but under-addressed cause of neurodegeneration. Importantly, breakdowns in chloride, bicarbonate, sodium, and calcium homeostasis alter fundamental aspects of cellular physiology, including important aspects of TDP-43 phase separation and tau hyperphosphorylation and aggregation. We suggest that the relationship of proteostasis failure and ionic dysregulation is a bidirectional feedback loop that accelerates the progression of neurodegeneration. Some therapeutic strategies aimed at correcting these mechanisms-including small-molecule chaperone inducers, autophagy inducers, and ion-channel modulators-might hold the potential for disease modification. In this review, we document the complex intersections of proteostasis failure and ionic dysregulation in TDP-43 and tauopathies and provide new ideas for therapies and future studies.},
}

@article {pmid41151289,
year = {2025},
author = {Gao, Y and Zheng, B and Peng, X and Ma, N and Qi, Y and Lan, X and Wang, Y and Zha, H and Zhou, C and Liu, F and Zhao, Q and Cao, H and Wang, L and Qiu, Y and Zheng, J and Guo, J},
title = {Lead exposure induces ferroptosis in ALS cell models by activating the MAPK/ERK signaling pathway.},
journal = {Ecotoxicology and environmental safety},
volume = {306},
number = {},
pages = {119301},
doi = {10.1016/j.ecoenv.2025.119301},
pmid = {41151289},
issn = {1090-2414},
abstract = {Lead is a potent toxicant that exerts deleterious effects on multiple organ systems within the human body. Existing evidence suggests that lead exposure may contribute to the progression of amyotrophic lateral sclerosis (ALS). However, the precise mechanism remains unclear and the experimental evidence is currently lacking. This study establishes an ALS cell model exposed to lead to investigate the potential relationship between lead exposure and ALS, and targets ferroptosis to elucidate the possible mechanism of lead exposure in ALS pathogenesis. Our findings demonstrate that lead exposure results in the accumulation of ROS and MDA in hSOD1[G93A] cells, accompanied by increased iron content, reduced GSH levels, mitochondrial vacuolization, and disruption of the cristae structure, upregulationation of ACSL4 protein levels, and inactivation of SLC7A11 and GPX4, ultimately triggering ferroptosis. The bioinformatics analyses and cellular experiments of the present study suggest that activation of the MAPK/ERK signaling pathway plays a crucial role in the ferroptosis process of ALS cells induced by lead exposure. This study not only provides new experimental evidence of the link between lead exposure and ALS but also elucidates the possible mechanism by which lead exposure contributes to the pathogenesis of ALS, demonstrating that the prevention of ferroptosis through targeting the MAPK/ERK signaling pathway may offer a promising intervention strategy for addressing lead-related ALS pathogenesis issues.},
}

@article {pmid41149991,
year = {2025},
author = {Kwiatkowska, A and Grzeczkowicz, A and Lipko, A and Kazimierczak, B and Granicka, LH},
title = {Emerging Approaches to Mitigate Neural Cell Degeneration with Nanoparticles-Enhanced Polyelectrolyte Systems.},
journal = {Membranes},
volume = {15},
number = {10},
pages = {},
pmid = {41149991},
issn = {2077-0375},
abstract = {Counteracting neurodegenerative diseases (NDs) presents a multifaceted challenge in the aging societies of Western countries. Each year, millions of people worldwide are affected by such ailments as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), multiple sclerosis (MS), spinal cord injury, ischemic stroke, motor neuron disease, spinal muscular atrophy, spinocerebellar ataxia, and amyotrophic lateral sclerosis (ALS). Advancements in modern biomaterial technologies present substantial opportunities for the field of regenerative medicine. Nevertheless, limitations arise from the requirement that biomaterial design be tailored to the specific biological parameters of the target cell types with which they are intended to interact. Such an opportunity creates nanomaterials involving nanoparticles. The surface chemistry of nanoparticles, especially when functionalized with bioactive agents, enhances biocompatibility and facilitates interactions with nervous cells. Herein, we review contemporary strategies in the application of biomaterials for nerve regeneration, with particular emphasis on nanomaterials and biocompatible polyelectrolyte layers, which the authors identify as having the most significant potential to drive transformative advances in regenerative medicine in the near future.},
}

@article {pmid41149812,
year = {2025},
author = {Marjanovic, A and Stefanova, E and Viric, V and Palibrk, A and Mandić Stojmenović, G and Stojković, T and Stojadinovic, L and Basta, I and Novakovic, I and Stević, Z and Jankovic, M},
title = {Genetic and Clinical Insights into ALS/FTD: Profiling a Rare Cohort to Explore Spectrum Heterogeneity.},
journal = {Journal of personalized medicine},
volume = {15},
number = {10},
pages = {},
pmid = {41149812},
issn = {2075-4426},
support = {200110/WT_/Wellcome Trust/United Kingdom ; },
abstract = {Background: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are recognized as a spectrum of neurodegenerative disorders with overlapping clinical, pathological, and genetic features. The identification of C9orf72 hexanucleotide repeat expansion as the most common genetic cause of both conditions has prompted further investigation of genetic modifiers that may contribute to disease heterogeneity. We aimed to analyze the frequency of C9orf72 repeat expansions and potential modifying roles of APOE, ATXN1, and ATXN2 in Serbian ALS/FTD patients. Methods: Our study included an ALS/FTD cohort (n = 22) and healthy controls (n = 94). Repeat sizing in C9orf72, ATXN1 and ATXN2 was performed by fluorescent polymerase chain reaction (PCR) and capillary electrophoresis, while repeat-primed PCR was used to confirm C9orf72 expansions. APOE genotyping was conducted using real-time PCR assays targeting SNPs rs429358 and rs7412. Results: In the ALS/FTD cohort, 31.82% of the patients had heterozygous C9orf72 repeat expansion. The most common APOE genotype among patients was ε3/ε3 (72.73%). Intermediate-length ATXN1 alleles (32-44 repeats) were detected in 13.64% of patients and ATXN2 intermediate-length alleles (27-33 repeats) were found in 9% of patients. No significant differences were observed between ALS/FTD patients and controls in APOE ε4 frequency or intermediate ATXN1/ATXN2 repeats. Conclusions: Larger, population-specific studies and meta-analyses are needed to better understand the role of genetic modifiers in ALS/FTD pathogenesis and their influence on clinical heterogeneity. By integrating genetic and clinical data, this study represents a step toward the development of precision medicine strategies for ALS/FTD.},
}

@article {pmid41149102,
year = {2025},
author = {Mauriello, L and Cuozzo, A and Pezzella, V and Isola, G and Spagnuolo, G and Iorio-Siciliano, V and Ramaglia, L and Blasi, A},
title = {Oral Health Status in Patients with Amyotrophic Lateral Sclerosis: A Scoping Review.},
journal = {Dentistry journal},
volume = {13},
number = {10},
pages = {},
pmid = {41149102},
issn = {2304-6767},
abstract = {Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative syndrome which often leads to progressive muscular dysfunction and therefore oral health deterioration. The aim of this scoping review is to evaluate oral health status in ALS patients focusing on the importance of dental care in improving patient's quality of life. Methods: A comprehensive literature search was conducted on PubMed, Scopus, Web of Science, and Embase databases until June 2025 using a combination of keywords and MeSH terms related to ALS and oral health. Studies were screened and selected based on inclusion and exclusion criteria, focusing on human clinical data reporting oral health outcomes in ALS. Results: Eight studies met the inclusion criteria. The findings showed a high prevalence of oral complications in bulbar-onset ALS patients. Common issues included reduced tongue mobility, poor oral hygiene, sialorrhea, and decreased masticatory function were evaluated. Conclusions: Oral health impairment in ALS patients frequently contributes to systemic risks and reduced quality of life. A dental expert may play an important role in multidisciplinary care teams in terms of early diagnosis and conservative treatment of oral diseases ranging from periodontal disease to temporomandibular disorders (TMD). Personalized oral hygiene strategies and adjunctive therapies may serve as key elements in maintaining overall health and patient comfort in ALS. Therefore, the objective of the following review was to evaluate oral health complication in patients with ALS, highlighting the impact of oral care on patients' quality of life.},
}

@article {pmid41148800,
year = {2025},
author = {Salmaso, V and Menin, S and Moro, S and Spalluto, G and Federico, S},
title = {Adenosine Receptors in Neuroinflammation and Neurodegeneration.},
journal = {Cells},
volume = {14},
number = {20},
pages = {},
pmid = {41148800},
issn = {2073-4409},
mesh = {Humans ; *Receptors, Purinergic P1/metabolism ; *Neurodegenerative Diseases/metabolism ; Animals ; *Neuroinflammatory Diseases/metabolism ; Adenosine/metabolism ; *Inflammation/metabolism ; },
abstract = {Adenosine plays a crucial role in various pathophysiological conditions, including neuroinflammation and neurodegeneration. Neuroinflammation can be either beneficial or detrimental to the central nervous system, depending on the intensity and duration of the inflammatory response. Across a wide range of brain disorders, neuroinflammation contributes to both the onset and progression of disease. Notably, neuroinflammation is not limited to conditions primarily classified as neuroinflammatory but is also a key factor in other neurological disorders, including life-threatening neurodegenerative diseases. All four adenosine receptor subtypes (A1, A2A, A2B, and A3) are implicated, to varying degrees, in these conditions. This review aims to summarize the roles of individual adenosine receptor subtypes in neuroinflammation and neurodegenerative diseases, emphasizing their therapeutic potential. While some therapeutic applications are well-established with clinically approved drugs, others warrant further investigation due to their promising potential.},
}

Humans
*Receptors, Purinergic P1/metabolism
*Neurodegenerative Diseases/metabolism
Animals
*Neuroinflammatory Diseases/metabolism
Adenosine/metabolism
*Inflammation/metabolism

@article {pmid41148458,
year = {2025},
author = {Goel, F and Kumar, D and Singh, P and Rai, SN and Yadav, DK},
title = {Molecular crosstalk between miRNAs and lncRNAs in neurodegenerative disease pathways.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {16},
pmid = {41148458},
issn = {1573-4978},
mesh = {Humans ; *RNA, Long Noncoding/genetics/metabolism ; *MicroRNAs/genetics/metabolism ; *Neurodegenerative Diseases/genetics/metabolism/therapy ; Gene Expression Regulation ; Animals ; Signal Transduction ; Gene Regulatory Networks ; },
abstract = {Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS), are characterized by progressive neuronal degeneration and dysfunction. Of recent interest, a series of studies have been targeting the role of non-coding RNAs, particularly miRNAs and lncRNAs, in regulating gene expression and influencing cellular pathways that may play a critical role in the pathogenesis of these diseases. miRNAs regulate many biological processes by degrading or repressing the translation of target mRNAs, whereas lncRNAs act as scaffolds, sponges, and guides to control gene expression and cellular activities. Both miRNAs and lncRNAs participate in neurodegenerative mechanisms such as protein aggregation, inflammation, oxidative stress, and neuroinflammation. While targeting miRNAs and lncRNAs holds promise for potential therapeutic benefits, problems persist with their efficient delivery, specificity, and off-target effects. New techniques like viral vectors, lipid nanoparticles, and CRISPR-based gene editing will further enhance the development of therapies based on miRNA and lncRNA. Moreover, their interaction with regulatory networks may present new avenues toward understanding disease mechanisms and guiding therapeutic design. This review covers the role of miRNAs and lncRNAs in neurodegenerative disorders, their therapeutic potential, challenges, and future directions in ncRNA-based treatment approaches.},
}

Humans
*RNA, Long Noncoding/genetics/metabolism
*MicroRNAs/genetics/metabolism
*Neurodegenerative Diseases/genetics/metabolism/therapy
Gene Expression Regulation
Animals
Signal Transduction
Gene Regulatory Networks

@article {pmid41148120,
year = {2025},
author = {Chan, TK and Wei, X and Ma, L and Wang, H and Liao, P and Matsuda, Y},
title = {Resistance Gene-Guided Discovery of a Fungal Spirotetramate as an Acetolactate Synthase Inhibitor.},
journal = {Journal of the American Chemical Society},
volume = {},
number = {},
pages = {},
doi = {10.1021/jacs.5c16272},
pmid = {41148120},
issn = {1520-5126},
abstract = {Biosynthetic gene clusters (BGCs) of bioactive natural products occasionally encode resistant versions of the proteins they inhibit, offering opportunities for resistance gene-guided genome mining to uncover natural products with predictable modes of action. In this study, we developed a genome mining tool designed to identify fungal BGCs harboring putative resistance genes. Applying this tool to approximately 2500 fungal genomes, we identified a BGC designated as the pts cluster, which encodes an acetolactate synthase (ALS) homologue. Functional characterization of the pts cluster resulted in the identification of pterrespiramide A (1), featuring unique spirotetramate and cis-decalin moieties. Consistent with the predicted activity, 1 was confirmed as an ALS inhibitor and exhibited both antifungal and herbicidal activities. This study illuminates the potential of resistance gene-guided genome mining as a powerful strategy for accelerating the discovery of previously undescribed bioactive natural products.},
}

@article {pmid41147470,
year = {2025},
author = {van Alphen, CMJ},
title = {[Diagnostiek als startpunt voor groei en herstel].},
journal = {Tijdschrift voor psychiatrie},
volume = {67},
number = {8},
pages = {430},
pmid = {41147470},
issn = {0303-7339},
}

@article {pmid41147458,
year = {2025},
author = {},
title = {Correction to "TSPO Expression and [18F]DPA-714 PET/CT Imaging as Pathogenetic and Diagnostic Biomarkers in Symptomatic Stages of Skeletal Muscle Fiber Degeneration in SOD1-G93A ALS Mice".},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {39},
number = {21},
pages = {e71204},
doi = {10.1096/fj.202503924},
pmid = {41147458},
issn = {1530-6860},
}