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

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

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

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

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

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

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

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

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

CLINICAL TRIAL NUMBER: Not applicable.

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

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

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

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

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

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

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

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

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

FUNDING: ALS Foundation Netherlands.},
}

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

@article {pmid41083520,
year = {2025},
author = {Specht, O and Stateczny, A},
title = {A novel method for coastal zone bathymetry based on multisensor data fusion and unmanned systems.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {35637},
pmid = {41083520},
issn = {2045-2322},
support = {WN/2025/PZ/05//Uniwersytet Morski w Gdyni/ ; },
abstract = {Existing geospatial data fusion methods in hydrography do not take into account the accuracy of individual measurements when creating a bathymetric map. Consequently, geospatial data acquired by devices with low depth measurement accuracy may lead to a deterioration in the accuracy of coastal zone topography. To address this limitation, this study presents a novel method for coastal bathymetric monitoring based on the integration of multimodal geospatial data collected by unmanned platforms equipped with on-board sensors. These include Single-Beam Echo Sounder (SBES) and MultiBeam EchoSounder (MBES), a photogrammetric camera, and Light Detection and Ranging (LiDAR) from Airborne Laser Scanning (ALS) and Mobile Laser Scanning (MLS). As part of this method, bathymetric and photogrammetric data are processed using three modules: processing depth data, processing shallow-water data, and determining the coastline. After processing, the data are fused using an original weighted average data fusion method, in which weights for individual data sources are determined based on the measurement accuracy. The results demonstrate that the proposed coastal monitoring method effectively minimises redundant geospatial inputs. Notably, the model is parametric, and its accuracy depends on the appropriate selection of processing parameters and fusion settings.},
}

@article {pmid41083392,
year = {2025},
author = {Guo, Y and Li, CJ and Wei, H and Ding, Y and Guo, LJ and Gao, YN},
title = {[Clinical analysis of a motor neuron disease-like phenotype associated with anti-IgLON5 disease].},
journal = {Zhonghua nei ke za zhi},
volume = {64},
number = {10},
pages = {977-983},
doi = {10.3760/cma.j.cn112138-20241018-00695},
pmid = {41083392},
issn = {0578-1426},
mesh = {Humans ; Aged ; Female ; *Autoantibodies/blood ; *Motor Neuron Disease/immunology/diagnosis ; Male ; Phenotype ; *Cell Adhesion Molecules, Neuronal/immunology ; Amyotrophic Lateral Sclerosis/immunology/diagnosis ; Electromyography ; },
abstract = {We report a case of anti-IgLON5 disease with a motor neuron disease-like presentation admitted to the Department of Neurology, Xuanwu Hospital, Capital Medical University in July 2021. The patient was a 71-year-old female who presented with the chief complaint of limb weakness persisting for 4 months. She showed progressive limb weakness accompanied by muscle atrophy. Electromyography (EMG) revealed extensive neurogenic damage. Initial serum evaluation for neural-specific autoantibodies was positive for IgLON5-Ab (1∶100). Repeat testing confirmed IgLON5-Ab positivity with a titer of 1∶1 000. The patient was diagnosed with anti-IgLON5 disease and treated with methylprednisolone and immunoglobulin, leading to clinical improvement. We found four relevant articles reporting a total of 11 similar cases. Thus, in this study, we analyzed a total of 12 cases, including our patient. Based on their clinical manifestations, these cases can be categorized into two types: amyotrophic lateral sclerosis(ALS)type and isolated bulbar type. Six cases-three males and three females-presented with the ALS type. Of these, three cases had diffuse limb weakness accompanied by muscle atrophy(two cases had diffuse hyperreflexia and one had a normal tendon reflex); one case presented with neck extensor weakness and bilateral asymmetric upper extremity weakness and was hyperreflexic at the bilateral patellar tendons; one case displayed asymmetric weakness in both lower limbs with normal deep reflexes, and one case exhibited neck weakness with hyperreflexia. EMG revealed diffuse lower motor neuron disease involving two or three regions. All patients tested positive for serum anti-IgLON5 antibodies. Four were also positive for anti-IgLON5 antibodies in cerebrospinal fluid, two were negative, and six were not tested. Among the 11 patients who received immunotherapy, 4 showed partial improvement in clinical symptoms, 2 exhibited transient improvement, 2 remained stable, and 3 showed no improvement. Testing for IgLON5-Ab should be considered among patients presenting with bulbar symptoms or ALS-like features, especially those with acute or subacute onset, rapid progression, autonomic dysfunction, vocal cord paralysis requiring tracheotomy, cognitive impairment, or involuntary movements. Early diagnosis and treatment may improve clinical symptoms and reduce adverse outcomes.},
}

Humans
Aged
Female
*Autoantibodies/blood
*Motor Neuron Disease/immunology/diagnosis
Male
Phenotype
*Cell Adhesion Molecules, Neuronal/immunology
Amyotrophic Lateral Sclerosis/immunology/diagnosis
Electromyography

@article {pmid41083292,
year = {2025},
author = {Jerath, A and Slessarev, M and Martin, C and D'Aragon, F and Carrier, FM and Senaratne, J and Meggison, H and Hooper, J and Alexandros Cavayas, Y and Goligher, EC and Couture, EJ and Randall, I and Hatzakorzian, R and Jacka, M and Wiener-Kronish, J and Xie, Z and Pinto, RL and Cuthbertson, B and , },
title = {Sedating with volatile anaesthetics for COVID-19 and non-COVID-19 acute hypoxaemic respiratory failure patients in ICU (SAVE-ICU): protocol for a randomised clinical trial.},
journal = {BMJ open},
volume = {15},
number = {10},
pages = {e108441},
pmid = {41083292},
issn = {2044-6055},
mesh = {Humans ; *COVID-19/complications/therapy ; *Respiration, Artificial/methods ; *Respiratory Insufficiency/therapy/etiology ; Intensive Care Units ; *Anesthetics, Inhalation/administration & dosage/therapeutic use ; SARS-CoV-2 ; Canada ; *Hypnotics and Sedatives/administration & dosage ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic ; *Hypoxia/therapy/etiology ; Pragmatic Clinical Trials as Topic ; United States ; },
abstract = {INTRODUCTION: Inhaled anaesthetics can be used in mechanically ventilated critically ill patients to provide sedation. This approach to sedation potentially improves patient and health system outcomes, but further supportive evidence is needed. The objective of the SAVE-ICU clinical trial is to compare the effectiveness of inhaled versus intravenous sedation in ventilated adults with acute hypoxaemic respiratory failure.

METHODS AND ANALYSIS: SAVE-ICU is a multicentre, open-label, pragmatic, randomised controlled trial conducted in 15 intensive care units (ICUs) in Canada and the USA. Eligible patients include mechanically ventilated and sedated adults with acute hypoxemic respiratory failure from COVID-19 or non-COVID causes with PaO2/FIO2 ratio <300 mm Hg. Patients are excluded with a history of malignant hyperthermia, allergy to sedative agents, raised intracranial pressure, need for concomitant prostacyclin, low tidal volumes (<200 mL), one-lung ventilation or pneumonectomy, severe neuromuscular disorder (eg, amyotrophic lateral sclerosis, Guillain-Barré syndrome), pregnancy or moribund status (unlikely to survive >12 hour). A hierarchy of outcomes was identified at the time of trial design, as the trial was launched during the COVID-19 pandemic when study drug shortages, staffing challenges and healthcare system pressures were prevalent and there was a requirement for rapid evidence generation and implementation on this topic. The primary outcome and highest in the hierarchy is hospital mortality (requiring 758 participants). Secondary and lower hierarchical outcomes are ventilator-free days at day 30 (200 patients), quality of life at 3 months (144 participants) and ICU-free days at day 30 (128 participants). Additional secondary outcomes include median daily oxygenation at day 3 (PaO2/FIO2 ratio), need for adjunctive acute respiratory distress syndrome therapies (prone positioning, inhaled nitric oxide, paralysis with a neuromuscular blocking agent and extracorporeal membrane oxygenation) during ICU stay, days alive and free from delirium and coma at day 14, hospital-free days at day 60 and disability score at 3 months and 12 months after enrolment.

ETHICS AND DISSEMINATION: The protocol was approved by all hospital ethics committees and by Health Canada. Informed consent will be obtained from substitute decision makers or deferred consent (as permitted by site ethics board). Trial findings will be shared at the end of the study using peer-review publications, conference presentations and social media as part of the trial knowledge translation plan.

TRIAL REGISTRATION NUMBER: NCT04415060.},
}

Humans
*COVID-19/complications/therapy
*Respiration, Artificial/methods
*Respiratory Insufficiency/therapy/etiology
Intensive Care Units
*Anesthetics, Inhalation/administration & dosage/therapeutic use
SARS-CoV-2
Canada
*Hypnotics and Sedatives/administration & dosage
Randomized Controlled Trials as Topic
Multicenter Studies as Topic
*Hypoxia/therapy/etiology
Pragmatic Clinical Trials as Topic
United States

@article {pmid41083160,
year = {2025},
author = {Vilmann, L and Albrethsen, J and Petersen, JH and Holmboe, SA and Christiansen, P and Main, KM and Cleemann, L and Hansen, KH and Frystyk, J and Hagen, CP and Juul, A},
title = {Bioactive Insulin-like Growth Factor (IGF)-I Concentrations in Children on Growth Hormone Therapy.},
journal = {The Journal of clinical endocrinology and metabolism},
volume = {},
number = {},
pages = {},
doi = {10.1210/clinem/dgaf566},
pmid = {41083160},
issn = {1945-7197},
abstract = {BACKGROUND: Monitoring Insulin-like Growth factor (IGF)-I concentration is recommended during Growth Hormone (GH) therapy (GHT) in children. Supranormal levels of total IGF-I have raised concerns of long-term risks.

AIM: To evaluate bioactive and total IGF-I in healthy and in GH treated children and adolescents.

MATERIAL AND METHOD: A reference population of 570 children (59% girls) from the Copenhagen Puberty Study (COPUS) III and 126 short children (36% girls) with GHD and other non-GHD conditions. We established pediatric, sex-specific reference ranges of serum concentrations of bioactive IGF-I (KIRA) and compared with total IGF-I and IGF-I/IGFBP-3 molar ratio (iSYS) and total IGF-I, -II, IGFBP-3 and ALS (LC-MS/MS) in a subgroup.Further, we compared IGF-I bioactivity with total IGF-I, IGFBP-3 (iSYS) and IGF-I/IGFBP-3 molar ratio during GHT.

RESULTS: Bioactive IGF-I increased with age in healthy children and correlated positively with total IGF-I and IGF-I/IGFBP-3 in healthy males (r=0.61 and r=0.57; p<0.001) and females (r=0.58 and r=0.59; p<0.001) and with IGF-I, -BP-3 and ALS (LC-MS/MS) (r=0.56, r=0.29 and r=0.38; p<0.001). Bioactive IGF-I and IGF-II (r=-0.29; p<0.001) correlated negatively.In 13% (17/126) of the patients bioactive IGF-I was above +2SD whereas total IGF-I was above +2SD in 25% (32/126) patients. Nine patients had both total and bioactive IGF-I above +2SD. In the non-GHD groups bioactive IGF-I SDS were lower than IGF-I SDS (p=0.015).

CONCLUSION: Bioactive IGF-I was within reference ranges in the majority of GH treated children. Monitoring bioactive IGF-I may help optimize GH dosing in specific patient subgroups.},
}

@article {pmid41083054,
year = {2025},
author = {Cao, YB and Zhuang, SP and Huang, ZY and Shi, JY and Lin, HY and Chen, S and Huang, NX and Zou, ZY and Qin, W and Chen, HJ},
title = {Structural atrophy and functional disturbance in the thalamic nuclei of patients with amyotrophic lateral sclerosis.},
journal = {Brain research bulletin},
volume = {232},
number = {},
pages = {111581},
doi = {10.1016/j.brainresbull.2025.111581},
pmid = {41083054},
issn = {1873-2747},
abstract = {OBJECTIVE: This study investigated the structural and functional impairments in thalamic nuclei in amyotrophic lateral sclerosis (ALS) and evaluated their associations with disease severity and diagnostic value.

METHODS: This study was conducted on T1-weighted and resting-state functional magnetic resonance images from 71 ALS patients and 61 healthy controls. In each hemisphere, the thalamus was parcellated into 25 nuclei and subsequently grouped into 6 subregions. The volume and amplitude of low-frequency fluctuation (ALFF, reflecting spontaneous neural activity) in each thalamic subregion were measured and compared between groups. These metrics were then used for correlation and diagnostic analyses.

RESULTS: A volumetric reduction was observed in the bilateral anterior, intralaminar, ventral, and left medial thalamic subregions in the ALS patients (FWE-corrected P < 0.05). A decreased ALFF was observed in the right anterior and ventral thalamic subregions of patients with ALS (FWE-corrected P < 0.05). The volumes of the bilateral intralaminar (left: r = 0.304, P = 0.011; right: r = 0.281, P = 0.018) and ventral (left: r = 0.355, P = 0.003; right: r = 0.335, P = 0.005) thalamic subregions were correlated with disease severity. Compared with the whole-thalamic measurements, the volumetric and ALFF measurements of thalamic subregion demonstrated greater diagnostic performance. The combined volumetric and ALFF measurements in the thalamic subregions further resulted in a significantly increased AUC (0.865, P < 0.001).

CONCLUSIONS: Selective structural and functional damage to thalamic subregions is a feature of ALS and could potentially contribute to future diagnostic approaches and assessments of disease severity.},
}

@article {pmid41082679,
year = {2025},
author = {Tabor Gray, L and Sullivan, S and O'Brien, M and Costello, J and Plowman, E and Garand, KLF},
title = {International Survey of Practice Patterns of Speech-Language Pathologists Working With Patients With Amyotrophic Lateral Sclerosis.},
journal = {American journal of speech-language pathology},
volume = {},
number = {},
pages = {1-12},
doi = {10.1044/2025_AJSLP-25-00064},
pmid = {41082679},
issn = {1558-9110},
abstract = {BACKGROUND: Speech-language pathologists (SLPs) evaluate and treat swallowing and communication impairments in individuals with amyotrophic lateral sclerosis (ALS). Standardized clinical practice guidelines for the evaluation and management of bulbar dysfunction in ALS have not yet been established. This study aimed to describe current international practice patterns of SLPs evaluating and treating bulbar dysfunction in ALS.

HYPOTHESIS: Significant variability in practice patterns will exist across SLPs working in different clinical settings with varied resources.

METHOD: A 26-item Qualtrics survey was electronically distributed to SLPs via e-mail, social media, and professional discussion boards.

RESULTS: Data from 245 respondents across 20 countries and 32 states within the United States were collected, with the final analysis including 214 respondents. Most respondents practiced in metropolitan areas (69%) and worked in multidisciplinary ALS clinics (41%), outpatient clinics (16%), and home health settings (17%). Cranial nerve examination (91%), swallow trials (79%), speech intelligibility tasks (85%), and diadochokinetic speech rates (65%) were frequently included in evaluations. Although 81% of clinics had access to instrumental swallowing evaluations, 32% reported performing them in fewer than 25% of patients. Communication evaluations were offered directly by 58% of clinicians, while 26% referred to an outside SLP and 16% collaborated with device representatives. Most clinicians provided patient education on swallowing (87%) and oral health (83%). However, managed practice varied widely, revealing no standardized treatment that is routinely offered. Barriers to optimal ALS care included time constraints, relevant clinical training, timing of treatment, addressing psychosocial components of care, access to resources, interdisciplinary communication, and insurance coverage (United States only).

DISCUSSION: Findings reveal little consensus on symptomatic bulbar management and intervention timing. Results emphasize the urgent need for the development of a standardized minimal data set to best guide the evaluation and management of bulbar dysfunction in ALS.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.30249997.},
}

@article {pmid41080927,
year = {2025},
author = {Ahmed, SK and Murad, HW and Mahmood, KA and Abdalla, AQ and Rony, MKK and Ravi, RK and Abdullah, L},
title = {Understanding barriers to type 2 diabetes self-management in excessive weight adults: A qualitative study of patient experiences.},
journal = {Journal of diabetes and metabolic disorders},
volume = {24},
number = {2},
pages = {217},
pmid = {41080927},
issn = {2251-6581},
abstract = {BACKGROUND: Diabetes management among excessive weight individuals remains a significant global health challenge, particularly in low- and middle-income regions such as Kurdistan Region, Iraq. Understanding the barriers from the patients' perspective is essential to designing effective, culturally sensitive interventions.

AIM: To explore perceived barriers to type 2 diabetes self-management among excessive weight adults in the Kurdistan Region of Iraq.

METHODS: A qualitative descriptive study was conducted through semi-structured interviews with 20 excessive weight patients diagnosed with type 2 diabetes mellitus. Participants were purposively recruited from hospitals and primary care centers in Kurdistan Region, Iraq. Data were analyzed following Ahmed et al.'s (2025) six-phase thematic analysis process.

RESULTS: In this study, five major themes and nine subthemes were identified, reflecting the multifaceted barriers to diabetes management among excessive weight individuals. Emotional and psychological struggles included persistent depression, anxiety, and diminished motivation often rooted in self-blame. Knowledge gaps and health literacy encompassed confusion due to conflicting dietary advice and a lack of structured education on diabetes management. Structural and environmental constraints involved the unaffordability of healthy food and absence of safe spaces for exercise. Distrust and disconnect in healthcare relationships emerged through perceived judgment by healthcare providers and subsequent avoidance of appointments. Finally, internalized weight stigma was a cross-cutting theme, with participants expressing shame and self-stigmatization.

CONCLUSION: Diabetes self-management among excessive weight patients in Kurdistan is hindered by a web of psychosocial, educational, systemic, and relational factors. Addressing these challenges requires multi-level, culturally tailored, patient-centered interventions that enhance education, reduce stigma, and foster trust between patients and providers.},
}

@article {pmid41080389,
year = {2025},
author = {Devanarayan, P and Sena, R and Johnson, D},
title = {Characterization and Application of Statewide Emergency Medical Services Advanced Life Support Protocols.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e92053},
pmid = {41080389},
issn = {2168-8184},
abstract = {INTRODUCTION: Many emergency medical services (EMS) systems in the United States utilize statewide protocols, but the number, type, and role of these systems in prehospital decision-making are largely unknown.

STUDY OBJECTIVE: To characterize statewide protocols and determine their role in prehospital decision-making.

METHODS: All states were queried for the presence of mandatory statewide Advanced Life Support (ALS)-level EMS protocols. Protocols were categorized as diagnosis-based, symptom-based, procedural, or non-clinical by two fellowship-trained EMS physicians. A data abstraction guide with category examples was included. Discrepancies were resolved by a third blinded EMS physician. The number and type of protocols were compiled, and simple statistics and chi-squared analysis were used to evaluate state-by-state variation.

RESULTS: Nine states have mandatory statewide ALS protocols, totaling 804 individual protocols, including 672 (83.6%) clinical and 132 (16.4%) non-clinical protocols. Symptom-based protocols accounted for 59.5% of the clinical protocols, while 13.2% were diagnosis-based and 27.2% procedural. Per state, there was a median interquartile range (IQR) of 46 (14.5) symptom-based, 8 (8) diagnosis-based, and 17 (22.5) procedural protocols. There was significant variation in the type and number of protocols by state (p < 0.001).

CONCLUSION: Significant variation exists in statewide EMS protocols. While many are symptom-based, a notable portion are diagnosis-based, challenging the notion that paramedics cannot diagnose. These findings suggest a need for higher-level clinical decision-making in EMS. Further research is warranted at other EMS training levels and to inform EMS training programs.},
}

@article {pmid41079689,
year = {2025},
author = {Marchal, N and Janes, WE and Marushak, S and Popescu, M and Song, X},
title = {Enhancing ALS progression tracking with semi-supervised ALSFRS-R scores estimated from ambient home health monitoring.},
journal = {Frontiers in digital health},
volume = {7},
number = {},
pages = {1657749},
pmid = {41079689},
issn = {2673-253X},
abstract = {INTRODUCTION: Clinical monitoring of functional decline in amyotrophic lateral sclerosis (ALS) relies on periodic assessments, which may miss critical changes that occur between visits when timely interventions are most beneficial.

METHODS: To address this gap, semi-supervised regression models with pseudo-labeling were developed; these models estimated rates of decline by targeting Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) trajectories with continuous in-home sensor data from a three-patient ALS case series. Three model paradigms were compared (individual batch learning and cohort-level batch vs. incremental fine-tuned transfer learning) across linear slope, cubic polynomial, and ensembled self-attention pseudo-label interpolations.

RESULTS: Results showed cohort-level homogeneity across functional domains. For ALSFRS-R subscales, transfer learning reduced the prediction error in 28 of 34 contrasts [mean root mean square error (RMSE) = 0.20 (0.14-0.25)]. However, for composite ALSFRS-R scores, individual batch learning was optimal for two of three participants [mean RMSE = 3.15 (2.24-4.05)]. Self-attention interpolation best captured non-linear progression, providing the lowest subscale-level error [mean RMSE = 0.19 (0.15-0.23)], and outperformed linear and cubic interpolations in 21 of 34 contrasts. Conversely, linear interpolation produced more accurate composite predictions [mean RMSE = 3.13 (2.30-3.95)]. Distinct homogeneity-heterogeneity profiles were identified across domains, with respiratory and speech functions showing patient-specific progression patterns that improved with personalized incremental fine-tuning, while swallowing and dressing functions followed cohort-level trends suited for batch transfer modeling.

DISCUSSION: These findings indicate that dynamically matching learning and pseudo-labeling techniques to functional domain-specific homogeneity-heterogeneity profiles enhances predictive accuracy in tracking ALS progression. As an exploratory pilot, these results reflect case-level observations rather than population-wide effects. Integrating adaptive model selection into sensor platforms may enable timely interventions as a method for scalable deployment in future multi-center studies.},
}

@article {pmid41079430,
year = {2025},
author = {Argelazi, RL and Graça, SC and Thomazoni, PV and Moura, CB and Gomes, AC and Kormanski, MK and de Almeida, SSC and Ferreira, YD and Santos, DH},
title = {TBK1 mutation and its role in frontotemporal dementia and amyotrophic lateral sclerosis in Brazilian families.},
journal = {Dementia & neuropsychologia},
volume = {19},
number = {},
pages = {e20240227},
pmid = {41079430},
issn = {1980-5764},
abstract = {UNLABELLED: Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are progressive neurodegenerative diseases with unclear etiology. Mutations in the TBK1 gene are associated with an increased risk of both FTD and ALS, presenting a diverse phenotype that includes the behavioral variant of FTD, primary progressive aphasia, and pure ALS. This mutation is rare, and to date, only one case report on TBK1-related clinical manifestations has been published in Brazil.

OBJECTIVE: To investigate the association between TBK1 gene mutations and the clinical manifestations of FTD and ALS in a Brazilian family, documenting the clinical history and disease progression of three first-degree relatives. Additionally, to conduct a literature review to better understand the impact of this mutation and its implications for neurological practice.

METHODS: Clinical data were collected from three patients in the same family who were receiving care at Dom Pedro II Geriatric Hospital and Central Hospital of the Irmandade da Santa Casa de Misericordia de São Paulo, including information on clinical symptoms, disease progression, and complementary exams - particularly genetic testing to detect and confirm the diagnosis. A detailed analysis of the existing literature on the disease was also conducted to better understand the implications of this mutation.

RESULTS: Three siblings affected by the TBK1 gene mutation were documented, with a unique family history suggesting that this genetic alteration has affected the lineage for several generations.

CONCLUSION: Although rare, frontotemporal dementia with accompanying motor deficits is of significant relevance to neurologists due to its poor prognosis and the potential familial impact on descendants.},
}

@article {pmid41078969,
year = {2025},
author = {Larrea-Schiavon, S and Auerswald, C and Guendelman, S and Graham, J and Infante, C},
title = {Challenges and facilitators to sexual and reproductive health care for undocumented in-transit migrant women in Mexico: a qualitative study.},
journal = {Frontiers in reproductive health},
volume = {7},
number = {},
pages = {1683858},
pmid = {41078969},
issn = {2673-3153},
abstract = {BACKGROUND: The number of international migrants has steadily increased over the past decade. Among them, undocumented in-transit migrant women (UITMW) face heightened vulnerability to gender-based violence and complex sexual and reproductive health (SRH) needs. However, limited evidence exists on the challenges state and non-state actors face in delivering SRH services to this population. This qualitative study explores the barriers encountered by service providers and decision-makers in Mexico when addressing UITMW's social and health needs through an SRH lens, and identifies facilitators that may support more effective service delivery.

METHODS: Between August and November 2023, we conducted 31 in-depth interviews with 36 service providers, migration experts, and local and federal decision-makers in Ciudad Juárez, Chihuahua City, and Mexico City. Guided by McLeroy et al.'s socioecological model, we examined challenges and facilitators at individual, institutional, community, and structural levels. Data were analyzed using a framework analysis approach.

RESULTS: Participants identified 11 challenges and 9 facilitators influencing SRH service provision for UITMW. Key challenges included: (1) policies and resource allocations are shaped by the perception of migration as temporary; (2) growing anti-immigrant sentiment undermine community-level service delivery; (3) religious restrictions in faith-based shelters limit access to certain SRH services; and (4) biases among healthcare providers affect quality of care. Notable facilitators included structural reforms such as strengthened migration and health governance and improved multi-level collaboration to enhance service access.

CONCLUSION: This study underscores the complex, multi-level barriers to delivering SRH care to UITMW in Mexico. Findings point to research and policy priorities, including examining the long-term impacts of migration and health policies on SRH service availability, evaluating alternative delivery models, analyzing the role of media in shaping public opinion, and involving UITMW and local stakeholders in policy development. Addressing these gaps could improve SRH outcomes for UITMW and strengthen the broader health system response for both migrant and local populations.},
}

@article {pmid41080007,
year = {2025},
author = {Valentino, AL and Gayle, RI and George, AJ and Fuhrman, AM},
title = {Promoting Ethical Discussions and Decision Making in a Human Services Agency: Updates to LeBlanc et al.'s (2020) Ethics Network.},
journal = {Behavior analysis in practice},
volume = {18},
number = {3},
pages = {1-9},
pmid = {41080007},
issn = {1998-1929},
abstract = {UNLABELLED: Ethical behavior is operant behavior, evoked and maintained by environmental variables; as such, it can be taught. Behavior analysts have focused on effective ways to teach and establish ethical behavior in both individual practitioners and within organizations. Teaching people to notice ethical issues in their environment is an important first step in promoting ethical discussions and decision making. In 2022, the Behavior Analyst Certification Board (BACB) issued two revised ethics codes-one for behavior analysts and one for registered behavior technicians (RBTs). In the current article, we expand upon the work of LeBlanc et al. Behavior Analysis in Practice, 13(4), 905-913, (2020) by updating an Ethics Network and hotline submission form within a human service agency to reflect both new codes of ethics. We provide data for the first 7 months of the updated system and analyze the data for common themes. We detail the updates to our system for readers wishing to create similar infrastructure in other organizations.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40617-023-00785-1.},
}

@article {pmid41077525,
year = {2025},
author = {Campbell, N and Lilley, R and Davie, G and Morgaine, K and Dicker, B and Kool, B},
title = {Prehospital advanced versus basic life support: A cohort study comparing survival to hospital for major trauma patients in New Zealand.},
journal = {Australasian emergency care},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.auec.2025.09.008},
pmid = {41077525},
issn = {2588-994X},
abstract = {OBJECTIVE: To examine the relationship between prehospital Advanced Life Support (ALS) and survival to hospital for major trauma patients in New Zealand and explore its implications for Emergency Medical Service (EMS) practice.

METHODS: A mixed-methods explanatory design was used. Data on major trauma patients attended by road EMS (December 2016-November 2018) was analysed. A multivariable model with propensity scores estimated the odds of survival for patients receiving Advanced versus Basic Life Support (BLS). Semi-structured interviews conducted with EMS stakeholders were analysed using thematic analysis.

RESULTS: Among 1118 patients, 661 (59 %) received ALS. Only 52 (5 %) did not survive to hospital. Multivariable modeling estimated ALS recipients had 1.5 times higher odds of survival than BLS-only recipients (OR 1.49, 95 % CI 0.66-3.35). Interviews with five EMS clinical leaders highlighted two likely influences: clinical judgment and evidence use. Despite imprecise quantitative findings, stakeholders supported ALS based on clinical judgment.

CONCLUSIONS: A tension between population-level results and provision of care based on clinical judgement exists. Quantitative analysis found no evidence that ALS offers a survival benefit, although considerable uncertainty exists, whereas stakeholders perceive ALS has clinical and equity benefits. Future research should assess equity, disability, and quality of life outcomes of ALS.},
}

@article {pmid41077137,
year = {2025},
author = {Nguyen, R and Sauer, J},
title = {Response to Chen et al.'s "Risk of major adverse cardiovascular events and venous thromboembolic events between patients with psoriasis or psoriatic arthritis on tumor necrosis factor inhibitors, interleukin 17 inhibitors, interleukin 12/23 inhibitors, and interleukin 23 inhibitors: An emulated target trial analysis".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.08.129},
pmid = {41077137},
issn = {1097-6787},
}

@article {pmid41077136,
year = {2025},
author = {Long, Q and Li, Y},
title = {Comments on ''Long-term evolution of prepubertal-onset anogenital lichen sclerosus: A 35-year retrospective and cross-sectional study from a single tertiary care maternal and pediatric center''.},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.06.085},
pmid = {41077136},
issn = {1097-6787},
abstract = {We read with interest the article ''Long-term evolution of prepubertal-onset anogenital lichen sclerosus: A 35-year retrospective and cross-sectional study from a single tertiary care maternal and pediatric center'' by Vallée et al.The purpose of this paper is to further discuss the study to enhance the robustness of the conclusions.},
}

@article {pmid41076903,
year = {2025},
author = {Muhire, J and Zhang, FX and Liu, BQ and Hu, J and Wang, X and Pei, D and Di, DL},
title = {HSCCC-Tchebichef moment regression approach for enhanced quantification of oleuropein in olive leaf extracts.},
journal = {Journal of chromatography. A},
volume = {1763},
number = {},
pages = {466445},
doi = {10.1016/j.chroma.2025.466445},
pmid = {41076903},
issn = {1873-3778},
abstract = {Oleuropein, a major bioactive phenolic compound from olive leaves, has attracted considerable interest for its health benefits. Targeted fractionation of oleuropein from crude extracts is hampered by the co-existence of numerous structurally similar metabolites, making conventional chromatographic separation inefficient. Here we describe, for the first time, a compact predictive framework that combines high-speed countercurrent chromatography (HSCCC), discrete Tchebichef moment (TM) feature extraction, and stepwise regression (SR) modelling to quantify oleuropein. Olive leaves were extracted with 80 % ethanol, and the crude extract was subjected to continuous-injection HSCCC in reverse‑phase mode using an ethyl acetate-petroleum ether-water (6:0.06:7) solvent system. HPLC analysed the resulting fractions and reference standards. Chromatograms were converted into two-dimensional matrices from which TMs up to the 20th order were computed. Forward stepwise regression identified a small set of TM coefficients that correlated strongly with oleuropein concentration and yielded a linear predictive model with high accuracy (R[2] > 0.99). In comparison to the MCR-ALS, the TM-based model achieved superior predictive performance using fewer parameters. The integrated HSCCC-TM-SR approach provides a rapid and scalable method for quantifying oleuropein and may be extended to other complex natural products.},
}

@article {pmid41076779,
year = {2025},
author = {Li, W and Wang, X and Zang, S and Zhou, R and Zhou, H and Yue, H and Geng, M and Zhan, Z and Xie, Z and Duan, W},
title = {Discovery of a potent and orally bioavailable 3,3-dimethyl-2-oxoindoline STING inhibitor.},
journal = {European journal of medicinal chemistry},
volume = {301},
number = {},
pages = {118232},
doi = {10.1016/j.ejmech.2025.118232},
pmid = {41076779},
issn = {1768-3254},
abstract = {Stimulator of interferon genes (STING) plays an imperative role in the innate immune response to pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). Overstimulated STING axis has proven to incur multiple autoimmune or inflammatory diseases, such as Aicardi-Goutières syndrome, systematic lupus erythematosus, and amyotrophic lateral sclerosis. Here we report the discovery of a series of 3,3-dimethyl-2-oxoindoline STING inhibitors. We converted the STING agonist G10 to a STING inhibitor 8a by grafting an indole-3-yl group, and extensive structure-activity relationship (SAR) exploration of 8a allowed us to identify compound 10a as a potent and orally bioavailable STING inhibitor. Biological characterization unraveled that 10a significantly suppressed the STING signaling pathway in human monocytes and murine macrophages, potently alleviated cisplatin-induced kidney injury both in vitro and in vivo, as well as achieved robust anti-inflammatory efficacy on STING agonist-induced inflammation mice model through systemic administration. The proposed binding mode of 10a and the STING protein displays that 10a targets the transmembrane domain of STING.},
}

@article {pmid41076128,
year = {2025},
author = {Chen, CC and Chen, SC},
title = {Comments on Hong et al.'s "Radiotherapy Versus Imiquimod for Complex Lentigo Maligna: a Phase 3 Randomized Clinical Trial".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.08.128},
pmid = {41076128},
issn = {1097-6787},
}

@article {pmid41075758,
year = {2025},
author = {Gery, KL and Ramos, S and Lee, JC},
title = {Correlative Raman and immunofluorescence imaging reveals different protein abundance between stress granules induced by oxidative damage.},
journal = {Journal of inorganic biochemistry},
volume = {274},
number = {},
pages = {113091},
doi = {10.1016/j.jinorgbio.2025.113091},
pmid = {41075758},
issn = {1873-3344},
abstract = {Heavy metal toxicity generates reactive oxygen species (ROS) that can contribute to neurodegeneration. Oxidative damage from exposure to metals such as sodium arsenite will activate the integrated stress response and may result in the cytosolic formation of stress granules (SGs), which have been implicated in neurodegenerative disorders such as amyotrophic lateral sclerosis. Here, two different ROS sources, sodium arsenite and hydrogen peroxide, under acute (1 h) and chronic (24 h) conditions, were used to induce SG formation in human osteosarcoma (U-2 OS) cells and investigate if characteristics of SGs could depend on the induction. Specifically, correlative Raman and immunofluorescence imaging (CRIFI) was developed to evaluate the relative protein abundance found in SGs to ascertain their potential as loci for protein accumulation. Interestingly, while there are differences in the punctate-staining phenotypes for different stressors, two types of puncta visualized by CRIFI were common to all treatment conditions, where notably a subset exhibited protein concentration above cytosolic background, indicating that only some SGs are composed of protein-rich, dense phases. Differences in protein abundance between SGs were also observed within a single cell, suggesting that individual SGs can develop differently. These results demonstrate the versatility and the strength of pairing Raman spectroscopy, which allows for probe-free detection of different chemical functional groups, with specific protein localization granted by immunofluorescence, providing new cellular insights unattainable by either modality alone.},
}

@article {pmid41075687,
year = {2025},
author = {Liu, Y and He, S and Gao, H and Wang, X and Zhang, Q and Tian, W and Duan, B and Liu, L},
title = {Co-adsorption behavior of Cr(III) and Cd(II) via direct application of argillaceous limestone.},
journal = {Journal of chromatography. A},
volume = {1763},
number = {},
pages = {466444},
doi = {10.1016/j.chroma.2025.466444},
pmid = {41075687},
issn = {1873-3778},
abstract = {The study investigated the removal of Cr(Ⅲ) and Cd(Ⅱ) by argillaceous limestone (AL) in a binary adsorption system. The results indicate that AL's capacity to adsorb Cr(Ⅲ) is enhanced by the presence of Cd(Ⅱ). Conversely, the presence of Cr(Ⅲ) significantly decreases the adsorption of Cd(Ⅱ). The adsorption mechanisms involve precipitation, chelation, and ion exchange. AL's adsorption behavior was well described by the pseudo-second-order kinetic model, suggesting that the adsorption process was dominated by chemical interactions and the monolayer adsorption pattern. The pH affects adsorption primarily by altering the protonation degree of the AL surface. In the single-component system, the maximum adsorption capacity for Cr(III) reached 30.98 mg·g[-][1] at pH 7.0, while that for Cd(Ⅱ) reached 38.80 mg·g[-][1] at pH 8.0. In the binary system, Cr(Ⅲ) achieved its highest adsorption capacity (42.56 mg·g[-][1]) at pH 6.0, while Cd(Ⅱ) exhibited a maximum capacity of 19.16 mg·g[-][1] at pH 7.0. The presence of Na[+] and Ca[2][+] ions reduced the adsorption efficiency, with greater inhibition observed as ionic strength increased. This study clarifies the composite adsorption behavior of AL in multi-ion systems and can advance the direct application of natural minerals in environmental pollution remediation.},
}

@article {pmid41075396,
year = {2025},
author = {Tse, NY and Orlando, IF and O'Callaghan, C and Taylor, NL and Shine, JM and Zalesky, A and Tu, S and Ahmed, RM and Halliday, GM and Piguet, O and Hodges, JR and Kiernan, MC and Lewis, SJG and Devenney, EM},
title = {Susceptibility to visual hallucinations in the amyotrophic lateral sclerosis-frontotemporal dementia spectrum: The role of dysfunctional attentional networks.},
journal = {Cortex; a journal devoted to the study of the nervous system and behavior},
volume = {192},
number = {},
pages = {213-226},
doi = {10.1016/j.cortex.2025.08.014},
pmid = {41075396},
issn = {1973-8102},
abstract = {Psychotic symptoms are well established across the amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) spectrum and contribute to patient and carer distress and poorer prognosis. However, there are no objective tools to probe these symptoms and the underlying functional neurobiology has been unexplored to date. Leveraging clinical interview, neuropsychological testing, and a validated behavioural paradigm of visual misperception combined with connectome-wide fMRI analysis, we directly probed visual hallucinatory tendencies and the associated cognitive and functional connectivity signatures in ALS-FTD. In 82 participants across the ALS-FTD spectrum (24 ALS patients, 7 ALS-FTD, 31 behavioural-variant FTD [19 C9orf72 expansion carriers and 43 non-carriers] and 20 healthy controls), we showed that an ecologically valid behavioural task was sensitive to hallucinatory tendencies. We observed selective involvement of attentional deficits in visual misperception beyond the influence of executive function and psychomotor speed (r ranging from .344-.603; FDR-corrected at p < .05). Following quality control, data-driven whole-brain fMRI analysis in a subset of 26 patients converged to implicate the attentional systems, wherein abnormally heightened connectivity anchored in the attentional, default mode and executive control networks worsened as a function of visual misperception severity (FWE-corrected p = .042 with 10,000 permutations). Our findings underscore the critical role of attentional disruptions, characterised by altered interactions between top-down and bottom-up attentional, introspective, and salience detection processes, in ALS-FTD visual hallucinatory predisposition. Aligning with current models of hallucination generation postulated in schizophrenia, Parkinson's disease, and dementia with Lewy bodies, our findings point towards common neural underpinnings of psychosis vulnerability shared by ALS-FTD.},
}

@article {pmid41075354,
year = {2025},
author = {Weinreich, M and McDonough, H and Heverin, M and Domhnaill, ÉM and Yacovzada, N and Magen, I and Cohen, Y and Harvey, C and Elazzab, A and Gornall, S and Boddy, S and Alix, JJP and Kurz, JM and Kenna, KP and Zhang, S and Iacoangeli, A and Al-Khleifat, A and Snyder, MP and Hobson, E and Chio, A and Malaspina, A and Hermann, A and Ingre, C and Costa, JV and van den Berg, L and Panadés, MP and van Damme, P and Corcia, P and de Carvalho, M and Al-Chalabi, A and Hornstein, E and Elhaik, E and Shaw, PJ and Hardiman, O and McDermott, C and Cooper-Knock, J},
title = {Optimised machine learning for time-to-event prediction in healthcare applied to timing of gastrostomy in ALS: a multi-centre, retrospective model development and validation study.},
journal = {EBioMedicine},
volume = {121},
number = {},
pages = {105962},
doi = {10.1016/j.ebiom.2025.105962},
pmid = {41075354},
issn = {2352-3964},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is invariably fatal but there are large variations in the rate of progression. The lack of predictability can make it difficult to plan clinical interventions. This includes the requirement for gastrostomy where early or late placement can adversely impact quality of life and survival.

METHODS: We designed a model to predict the timing of gastrostomy requirement in ALS as indicated by 5% weight loss from diagnosis. We considered >5000 different prediction model configurations including spline models and a set of deep learning (DL) models designed for time-to-event prediction. The optimal prediction model was chosen via a Bayesian framework to avoid overfitting. Model covariates were measurements routinely collected at diagnosis; a separate longitudinal model also incorporated weight at six months. We employed a training dataset of 3000 patients from Europe, and two external validation cohorts spanning distinct populations and clinical contexts (United States, n = 299; and Sweden, n = 215). Missing data was imputed using a random forest model.

FINDINGS: The optimal model configuration was a logistic hazard DL model. The optimal model achieved a median absolute error (MAE) between predicted and measured time of 3.7 months, with AUROC 0.75 for gastrostomy requirement at 12 months. To increase accuracy we updated predictions for those who had not received gastrostomy at six months after diagnosis: here MAE was 2.6 months (AUROC 0.86). Combining both models achieved MAE of 1.2 months for the modal group of patients. Prediction performance is stable across both validation cohorts. Missing data was imputed without degrading model performance.

INTERPRETATION: To enter routine clinical practice a prospective study will be required, but we have demonstrated stable performance across multiple populations and clinical contexts suggesting that our prediction model can be used to guide individualised gastrostomy decision making for patients with ALS.

FUNDING: Research Ireland (RI) and Biogen have supported the PRECISION ALS programme.},
}

@article {pmid41074141,
year = {2025},
author = {Gómez-Almería, M and Gonzalo-Consuegra, C and Rodríguez-Cueto, C and Cabañas-Cotillas, M and Jiménez-Amor, A and Machín-Díaz, I and Wittwer, MB and Dzygiel, P and Clemente, D and Grether, U and Fernández-Ruiz, J and de Lago, E},
title = {Relevance of a peripheral site of action outside the brain-blood barrier for the beneficial effects of CB2 receptor activation in experimental ALS in male mice.},
journal = {Cell communication and signaling : CCS},
volume = {23},
number = {1},
pages = {427},
pmid = {41074141},
issn = {1478-811X},
support = {CB06/05/0089//Instituto de Salud Carlos III/ ; CB06/05/0089//Instituto de Salud Carlos III/ ; CB06/05/0089//Instituto de Salud Carlos III/ ; PI24/00447//Instituto de Salud Carlos III/ ; CB06/05/0089//Instituto de Salud Carlos III/ ; PI21/00302//Instituto de Salud Carlos III/ ; PI21/00302//Instituto de Salud Carlos III/ ; CB06/05/0089//Instituto de Salud Carlos III/ ; CB06/05/0089//Instituto de Salud Carlos III/ ; RTI-2018-098885-B-100//Ministerio de Ciencia e Innovación/ ; RTI-2018-098885-B-100//Ministerio de Ciencia e Innovación/ ; RTI-2018-098885-B-100//Ministerio de Ciencia e Innovación/ ; PID2021-128906OB-I00//Ministerio de Ciencia e Innovación/ ; RTI-2018-098885-B-100//Ministerio de Ciencia e Innovación/ ; RTI-2018-098885-B-100//Ministerio de Ciencia e Innovación/ ; },
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/drug therapy ; *Receptor, Cannabinoid, CB2/metabolism/agonists ; Male ; *Blood-Brain Barrier/metabolism/drug effects ; Mice ; Mice, Transgenic ; Motor Neurons/drug effects/metabolism/pathology ; Superoxide Dismutase-1 ; Disease Models, Animal ; DNA-Binding Proteins/genetics/metabolism ; },
abstract = {BACKGROUND: Cannabinoid type 2 receptor (CB2) activation works against neurotoxic events that kill motor neurons in amyotrophic lateral sclerosis. Given that amyotrophic lateral sclerosis is a neuromuscular pathology with the skeletal muscle being also affected, we were interested in deciphering whether peripheral CB2 may contribute in these beneficial effects.

METHODS: To this end, we used two CB2 agonists: (i) RO-6866945, which crosses the blood-brain barrier (BBB) and acts at both Central Nervous System (CNS) and peripheral compartments; and (ii) RO-6871304, which is a peripherally-restricted ligand that activates CB2 outside the BBB. Both agonists have been evaluated in SOD-1 and TDP-43 transgenic male animals.

RESULTS: In both cases, their i.p. administration improved the neurological status of these mice, preserved their spinal motor neurons and attenuated glial reactivity. They also recovered those muscle fibers denervated by the pathology in SOD-1 transgenic mice. To confirm that the efficacy of RO-6871304 is not derived from a possible BBB damage in amyotrophic lateral sclerosis mice that may allow this agonist to reach the CNS, we analyzed their concentrations in neural tissues after acute administration in both experimental models. Our data confirmed that RO-6866945 was detected in the brain, while RO-6871304 was not, whereas both compounds were found in the plasma.

CONCLUSIONS: In summary, our data suggest that CB2 located at peripheral sites (skeletal muscle, immune cells, others) may be responsible of therapeutic effects showed by compounds targeting these receptors in amyotrophic lateral sclerosis. Our study may be of critical importance to move CB2 agonists in amyotrophic lateral sclerosis towards the clinical scenario.},
}

Animals
*Amyotrophic Lateral Sclerosis/metabolism/pathology/drug therapy
*Receptor, Cannabinoid, CB2/metabolism/agonists
Male
*Blood-Brain Barrier/metabolism/drug effects
Mice
Mice, Transgenic
Motor Neurons/drug effects/metabolism/pathology
Superoxide Dismutase-1
Disease Models, Animal
DNA-Binding Proteins/genetics/metabolism

@article {pmid41074071,
year = {2025},
author = {Cole, A and Chege, T and Aman, R and Githuka, G and Muga, R and Aspinall, A and Kokwaro, G},
title = {Health system challenges and facilitators associated with adaptive cycling deployment of multiple first-line treatment for uncomplicated malaria: a pilot study in a malaria-endemic region of Kenya.},
journal = {Malaria journal},
volume = {24},
number = {1},
pages = {328},
pmid = {41074071},
issn = {1475-2875},
support = {PO20/00538//Medicines for Malaria Venture/ ; },
mesh = {Kenya ; Pilot Projects ; *Antimalarials/therapeutic use/administration & dosage ; Humans ; Artemisinins/therapeutic use ; *Malaria/drug therapy ; Female ; Adult ; Male ; Drug Combinations ; Young Adult ; Drug Therapy, Combination ; Adolescent ; Middle Aged ; Artemether, Lumefantrine Drug Combination/therapeutic use ; Amodiaquine/therapeutic use ; },
abstract = {BACKGROUND: Artemisinin-based combination therapy (ACT) has been first-line treatment for uncomplicated malaria in sub-Saharan Africa for over two decades. However, emerging artemisinin partial resistance threatens efficacy. Multiple first-line treatments (MFTs) represent a proposed mitigation strategy, though associated health systems challenges remain unknown. This study evaluated health systems challenges and facilitators for MFT implementation in western Kenya.

METHODS: A 2 year pilot study (June 2020-June 2022) implemented adaptive cycling of four artemisinin-based combinations: Artemether-Lumefantrine (AL), Dihydroartemisin-Piperaquine (DHA-PIP), Amodiaquine-Artesunate (ASAQ), and Pyronaridine-Artesunate (PYR-ART) in western Kenya. Homa Bay (implementation) and Migori (control) counties were compared. Implementation involved 8 month drug cycling on mainland and 12 month cycling on Mfangano Island, while control county continued AL throughout. Adult patients diagnosed with uncomplicated malaria were included (pregnant women and children < 5 years excluded). Health systems assessment used semi-structured questionnaires, key informant interviews, and exit interviews. Outcome measures included diagnostic kit availability, procurement logistics, information system alignment, human resources, stakeholder acceptance, and side effects. Costs were tracked using ingredient approach, and malaria cases compared between counties.

RESULTS: MFT was accepted by key stakeholders. One minor adverse effect (vomiting) was reported. Patients preferred simple once-daily dosing of new drugs over AL's complicated regimen. Major challenges included logistics inefficiencies in drug quantification and stock management, human resource constraints, information system reconfiguration needs, and frequent diagnostic kit stock-outs. Start-up and implementation costs were roughly equal. Economic cost per patient treated was USD 3, lower than reported elsewhere in sub-Saharan Africa. Digital health tools (SMS/WhatsApp) facilitated implementation through improved communication and follow-up. Migori (control) showed 12.5 percentage points higher malaria positivity rates (23.3% vs 10.8%) with better directional consistency. Testing efficiency differed markedly (4.3 vs 9.2 tests per positive case) between counties.

CONCLUSION: Adaptive cycling MFT implementation is feasible in Kenya with adequate planning and addressing health systems challenges. Stakeholder engagement and continuous training were critical for success. Policy implications and regional cooperation potential warrant exploration in other sub-Saharan African countries with different deployment contexts.},
}

Kenya
Pilot Projects
*Antimalarials/therapeutic use/administration & dosage
Humans
Artemisinins/therapeutic use
*Malaria/drug therapy
Female
Adult
Male
Drug Combinations
Young Adult
Drug Therapy, Combination
Adolescent
Middle Aged
Artemether, Lumefantrine Drug Combination/therapeutic use
Amodiaquine/therapeutic use

@article {pmid41073781,
year = {2025},
author = {Vogan, K},
title = {A plasma proteomic signature for ALS.},
journal = {Nature genetics},
volume = {57},
number = {10},
pages = {2349},
doi = {10.1038/s41588-025-02384-y},
pmid = {41073781},
issn = {1546-1718},
}

@article {pmid41073493,
year = {2025},
author = {Montazeri, S and Bijani, S and Rashidzadeh, H and Ramazani, A and Andalib, S and Kalantari-Hesari, A and Cheraghi, G and Hosseini, MJ},
title = {Application of edaravone-loaded nanogel in alleviating behavioral deficits and oxidative stress in schizophrenia rat model.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {35468},
pmid = {41073493},
issn = {2045-2322},
support = {4000397//National Institute for Medical Research Development/ ; },
mesh = {Animals ; *Oxidative Stress/drug effects ; *Schizophrenia/drug therapy/metabolism ; *Edaravone/administration & dosage/pharmacology ; Rats ; Disease Models, Animal ; *Nanogels/chemistry ; Male ; Glutathione/chemistry ; *Behavior, Animal/drug effects ; Rats, Sprague-Dawley ; Prefrontal Cortex/drug effects/metabolism ; },
abstract = {Schizophrenia is considered as a main one of the public health issues, and imposes numerous burdens on patients and society. We previously reported, the pathophysiology of schizophrenia is influenced by inflammation and mitochondrial dysfunction. Edaravone (EDV) as a potent antioxidant with neuroprotective traits, has been approved for the treatment of amyotrophic lateral sclerosis (ALS), effecting through neutralizing soluble/insoluble peroxyl radicals. However, the main disadvantages of EDV are its low stability in aqueous media, poor water solubility, and un-optimized bioavailability. To effectively address these obstacles, nanogel was utilized as the drug vehicle. The decoration of nanogel surface with glutathione (GSH) was carried out to elevate edaravone's brain delivery. The probable improvement in drug delivery of edaravone loaded GSH-nanogel is the main hypothesis of this study. In order to mimic schizophrenia-like behaviors, we applied two month of post-weaning social isolation stress (PWSI) to rodent model. The choice of PWSI model was made due to the maturation and development of prefrontal cortex and hippocampus during adolescence. In addition to causing oxidative stress and upregulating genes linked to innate immunity in the prefrontal cortex (PFC), the data showed that PWSI triggered schizophrenia-like behaviors in rats. This study demonstrated that treatment with edaravone loaded GSH-nanogel decreased the impact of PWSI on behavioral dysfunctions and oxidative stress in the PFC of rats. Edaravone loaded GSH-nanogel (GSH-PMAA-EDV) down-regulated Toll-like receptor 4 (Tlr-4) and AMP-activated protein kinase (Ampk) gene expression which are involved in inflammation and cellular energy homeostasis, respectively. Increase immunoreactivity feedback and Brain-derived neurotrophic factor (Bdnf) as direct impact in neurogenesis and neural cell plasticity was observed in EDV loaded GSH-nanogel treated groups. edaravone loaded GSH-nanogel (100 µg/kg) in comparison to free form of edaravone (5 mg/kg) revealed more beneficial effects, which might be useful for future clinical use especially for the treatment of schizophrenia.},
}

Animals
*Oxidative Stress/drug effects
*Schizophrenia/drug therapy/metabolism
*Edaravone/administration & dosage/pharmacology
Rats
Disease Models, Animal
*Nanogels/chemistry
Male
Glutathione/chemistry
*Behavior, Animal/drug effects
Rats, Sprague-Dawley
Prefrontal Cortex/drug effects/metabolism

@article {pmid41073371,
year = {2025},
author = {Liu, RY and Yin, KF and He, SY and Su, WM and Duan, QQ and Wen, XJ and Chen, T and Shen, C and Li, JR and Cao, B and Chen, YP},
title = {Viral infections and the risk of neurodegenerative diseases: a comprehensive meta-analysis and systematic review.},
journal = {Translational psychiatry},
volume = {15},
number = {1},
pages = {388},
pmid = {41073371},
issn = {2158-3188},
mesh = {Humans ; *Neurodegenerative Diseases/epidemiology/virology ; *Virus Diseases/epidemiology/complications ; *Amyotrophic Lateral Sclerosis/epidemiology/virology ; *Parkinson Disease/epidemiology/virology ; Risk Factors ; *Alzheimer Disease/epidemiology/virology ; },
abstract = {BACKGROUND: Viral infections have been implicated in the pathogenesis of neurodegenerative diseases (NDs); however, evidence linking specific viruses to Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) remains inconclusive. This study conducted a meta-analysis and systematic review to investigate these associations.

METHODS: Thorough searches were conducted across Embase, PubMed, Cochrane Library, Web of Science and Scopus until May 18, 2025, to identify observational studies investigating the relationship between viral infections and the risk of NDs, including AD, PD, and ALS. Meta-analyses were executed using a random-effects model with Stata MP18.0.

RESULTS: A total of 34,417 articles were identified, of which 73 met the eligibility criteria for inclusion in the meta-analysis, and 48 were included in the systematic review. The analysis demonstrated that infections with cytomegalovirus (CMV) (odds ratio [OR] = 1.41; 95% confidence interval [CI]: 1.03, 1.93), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (OR = 1.88; 95% CI: 1.53, 2.32), hepatitis C virus (HCV) (OR = 1.39; 95% CI: 1.14, 1.69), and human herpesvirus (HHV) (OR = 1.24; 95% CI: 1.02, 1.51) were associated with an increased risk of AD. Regarding PD, infections with hepatitis B virus (HBV) (OR = 1.18; 95% CI: 1.04, 1.35) and HCV (OR = 1.29; 95% CI: 1.18, 1.41) were identified as risk factors. Conversely, no significant correlation was found between any viral infection and the risk of ALS.

CONCLUSION: This meta-analysis supports the role of select viral infections in AD and PD pathogenesis. However, no association was found between viral infections and ALS, warranting further large, multicenter, and longitudinal studies to elucidate mechanisms and confirm causality.},
}

Humans
*Neurodegenerative Diseases/epidemiology/virology
*Virus Diseases/epidemiology/complications
*Amyotrophic Lateral Sclerosis/epidemiology/virology
*Parkinson Disease/epidemiology/virology
Risk Factors
*Alzheimer Disease/epidemiology/virology

@article {pmid41073116,
year = {2025},
author = {Barry, C and Farquhar, M and Hawkes, M and Massey, C and Cross, JL},
title = {Understanding the complexity of living with, and managing, secretions in motor neuron disease/amyotrophic lateral sclerosis (MND/ALS/ALS): protocol for a complex intervention systematic review.},
journal = {BMJ open},
volume = {15},
number = {10},
pages = {e103704},
doi = {10.1136/bmjopen-2025-103704},
pmid = {41073116},
issn = {2044-6055},
mesh = {Humans ; Systematic Reviews as Topic ; *Amyotrophic Lateral Sclerosis/therapy/physiopathology/complications ; *Motor Neuron Disease/therapy/physiopathology/complications ; Research Design ; Quality of Life ; *Bodily Secretions ; },
abstract = {INTRODUCTION: Motor neuron disease/amyotrophic lateral sclerosis (MND/ALS/ALS) is an incurable disease which leads to muscle weakness that worsens over time. MND/ALS is highly heterogeneous in its presentation, with many people experiencing a rapidly progressive trajectory of symptoms. Many people living with MND/ALS (plwMND/ALS) experience a combination of flaccidity and spasticity of the muscles involved in speech, swallowing, breathing and coughing. This makes it challenging to deal with the saliva and mucous ('secretions") produced by the body. Failure to manage these problems effectively can lead to accumulation and aspiration of secretions, which may cause pneumonia and respiratory insufficiency. Knowing the best way to treat this problem is a challenge. Systematic reviews report substantive ongoing uncertainty regarding secretions management (SM). Little is known about the comparative effectiveness of secretion management interventions, their impact on quality of life and acceptability for plwMND/ALS and their unpaid/family.

METHODS AND ANALYSIS: A complex intervention systematic review of SM for plwMND/ALS and/or their carers will be conducted using an iterative logic model approach, designed in accordance with the principles and guidance laid out in a series of articles published by the Agency for Healthcare Research and Quality on complex intervention reviews . Eight electronic databases will be searched for publications between 1996 and present: Ovid Embase, EBSCO CINAHL, EBSCO Academic Search Ultimate, Scopus, EBSCO PsycInfo, Ovid MEDLINE and the Social Sciences Citation Index. This will be supplemented by hand searching of reference lists of included studies. Two reviewers will independently screen the results for potentially eligible studies using AS Review Lab (a semi-automated machine learning tool). Study selection, data extraction and risk of bias assessment, using Gough's Weight of Evidence Framework, will be independently performed by two reviewers. A framework thematic synthesis approach will be employed to analyse and report quantitative and qualitative data. The reporting will be conducted in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis Complex Intervention Extension Statement and Checklist.

ETHICS AND DISSEMINATION: This review will involve the secondary analysis of published information; therefore, ethical approvals are not required. Dissemination will be via presentation at scientific meetings, presentations to MND/ALS support groups and publications in peer-reviewed journals.

PROSPERO REGISTRATION NUMBER: CRD42025102364.},
}

Humans
Systematic Reviews as Topic
*Amyotrophic Lateral Sclerosis/therapy/physiopathology/complications
*Motor Neuron Disease/therapy/physiopathology/complications
Research Design
Quality of Life
*Bodily Secretions

@article {pmid41072625,
year = {2025},
author = {de Natale, ER and Verghese, JP and Terry, A and Wilson, H and Khosropanah, P and Wright, H and Passamonti, L and Evans, KC and Comley, RA and Tsukada, H and Passchier, J and Searle, G and Pererva, E and Whittington, A and Gunn, R and Rabiner, EA and Politis, M},
title = {An in vivo PET/CT investigation of mitochondrial complex 1, sigma 1, and synaptic vesicle 2 A in patients with amyotrophic lateral sclerosis.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107138},
doi = {10.1016/j.nbd.2025.107138},
pmid = {41072625},
issn = {1095-953X},
abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder which pathology is still largely unclear.

OBJECTIVES: To perform an in vivo cross-sectional investigation of mitochondrial complex 1 (MC1), synaptic vesicle 2 A (SV2A), and sigma-1 receptor (S1R) expression in ALS patients using the PET radioligands [[18]F]BCPP-EF, [[11]C]UCB-J, and [[11]C]SA4503.

METHODS: Sixteen ALS patients (twelve males, mean age: 57.49 ± 12.08 years) and sixteen healthy controls underwent clinical assessment, MRI, and PET imaging with [[18]F]BCPP-EF, [[11]C]UCB-J, and [[11]C]SA4503. Patients were stratified based on disease the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) progression rate into slow, and moderate/fast progressors. Volume of distribution (VT) of predefined regions of interest, corrected for partial volume effects, was the primary outcome.

RESULTS: Across the ALS cohort, [[18]F]BCPP-EF binding was reduced in the amygdala (-13.9 %, F = 4.938 p = 0.034). Moderate/fast progression ALS patients exhibited [[18]F]BCPP-EF binding loss in the hippocampus (-20.0 %), amygdala (-21.4 %), cerebellum (-19.5 %), insular cortex (-19.3 %), temporal lobe (-19.0 %), and anterior cingulate (-18.7 %) (all p < 0.05); and [[11]C]SA4503 binding loss in the caudate (-20.6 %), pallidus (-26.8 %), amygdala (-20.2 %), hippocampus (-17.4 %), insular cortex (-16.9 %), accumbens (-17.0 %), anterior cingulate (-16.4 %) and temporal lobe (-19.8 %) compared to controls (all p < 0.05). In moderate/fast progressors, [[18]F]BCPP-EF loss in the insular cortex, amygdala, anterior cingulate, and temporal lobe correlated with lower ALSFRS-R scores (p < 0.05).

CONCLUSIONS: Our findings reveal loss of MC1 and S1R in ALS, suggesting mitochondrial dysfunction associated with disease progression. This work provides initial insights of mitochondrial and receptor pathology in ALS, potentially guiding future biomarker development and therapeutic interventions.},
}

@article {pmid41072581,
year = {2025},
author = {Schundler, SF and Amber, KT},
title = {Response to Cao et al.'s "Efficacy, safety, and B-cell depletion capacity of three rituximab dosing regimens in the treatment of moderate-to-severe pemphigus vulgaris and pemphigus foliaceus: a 52-week clinical trial".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.08.126},
pmid = {41072581},
issn = {1097-6787},
}

@article {pmid41070779,
year = {2025},
author = {Lewis, KN and Craig, GA and Mason, J and Tomas, D and Cuic, B and Walker, AK and Gonsalvez, DG and Turner, BJ and Barton, SK},
title = {Oligodendroglial Densities and Myelin Structure Are Altered in TDP-43 Related Amyotrophic Lateral Sclerosis.},
journal = {Glia},
volume = {},
number = {},
pages = {},
doi = {10.1002/glia.70090},
pmid = {41070779},
issn = {1098-1136},
support = {BGRF2002//Bethlehem Griffiths Research Foundation Grant/ ; //Jane Frances Hayes and Frederick William Hayes Charitable Trust Project Grant/ ; 2001675//National Health & Medical Research Council (NHMRC) Ideas Grant/ ; DIS-202303-00887//FightMND Discovery Project Grant/ ; //Rebecca L. Cooper Al & Val Rosenstrauss Medical Research Fellowship/ ; //Motor Neuron Disease Research Australia PhD Top-Up Scholarship/ ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of motor neurons. However, the surrounding glia, including oligodendrocytes, also exhibit ALS pathology and TDP-43 related dysfunction. Given that oligodendrocytes, the myelinating cells of the central nervous system, are essential for motor neuron function, they may play an underappreciated role in ALS. Here, we have extensively characterized the oligodendrocyte lineage and myelin integrity in the TDP-43[Q331K] mouse model of ALS. In the lumbar spinal cord of end-stage male TDP-43[Q331K] mice (TDP-43), compared to wild-type littermates (WT), oligodendrocyte precursor cell (OPC) density, oligodendrocyte proliferation, and differentiation were all increased. There was no correlative increase in the density of mature oligodendrocytes, which was determined to be due to an increase in oligodendroglial apoptosis. In end-stage mice, myelin reflectance was increased in the dorsal column of TDP-43 mice, while electron microscopy showed myelin damage and misfolding in the TDP-43 mice. Our data suggest that the oligodendrocyte lineage is impacted in TDP-43 related ALS.},
}

@article {pmid41070481,
year = {2025},
author = {Doğan, V and Şenormanci, Ö},
title = {Validity and Reliability of the Affective Lability Scale-18 (ALS-18) Turkish Form in the Non-Clinical Group.},
journal = {Turk psikiyatri dergisi = Turkish journal of psychiatry},
volume = {36},
number = {},
pages = {18},
doi = {10.5080/u27329},
pmid = {41070481},
issn = {2651-3463},
mesh = {Humans ; Female ; Male ; Reproducibility of Results ; Turkey ; Psychometrics ; Adult ; *Psychiatric Status Rating Scales/standards ; Middle Aged ; Young Adult ; Factor Analysis, Statistical ; Surveys and Questionnaires ; *Affective Symptoms/diagnosis/psychology ; },
abstract = {OBJECTIVE: Affective lability, which is an important aspect of mood dysregulation, is seen in many psychiatric conditions. The aim of this study is to examine the psychometric properties of the Affective Lability Scale-18 in the Turkish sample of the non-clinical group.

METHOD: A total of 615 individuals (312 females and 303 males) who did not have a past or current psychiatric disorder were included in the study. The participants were administered sociodemographic data form, Affective Lability Scale-18, Difficulties in Emotion Regulation Scale, and Beck Depression Inventory. The participants were divided into 4 groups; a pilot group, EFA (exploratory factor analysis) group, CFA (confirmatory factor analysis) group and test-retest group.

RESULTS: The factor analysis conducted for the construct validity of the scale, revealed similar results to that of the original scale. The Cronbach’s alpha internal consistency coefficient was 0.92 for the EFA group and 0.92 for the CFA group. The test-retest reliability coefficient was 0.82. Difficulties in Emotion Regulation Scale (DERS) and Beck’s Depression Inventory (BDI) were used tp measure validity. The correlation between the total scores of participants on the ALS-18 and their scores on the DERS and BDI was determined to be positive and moderate (r=0.38, r=41).

CONCLUSION: The Affective Lability Scale-18 in the Turkish sample, three sub-dimensions, anxiety/depression, depression/elevation, anger and the general factor all have sufficient internal consistency and it has been demonstrated that the scale can be applied in our country to evaluate the situations in which affect variability is evaluated.},
}

Humans
Female
Male
Reproducibility of Results
Turkey
Psychometrics
Adult
*Psychiatric Status Rating Scales/standards
Middle Aged
Young Adult
Factor Analysis, Statistical
Surveys and Questionnaires
*Affective Symptoms/diagnosis/psychology

@article {pmid41070448,
year = {2025},
author = {ElDabour, MA},
title = {Circumferential clues: strain patterns and arrhythmia risk in pulmonary regurgitation.},
journal = {Cardiology in the young},
volume = {},
number = {},
pages = {1-2},
doi = {10.1017/S1047951125110032},
pmid = {41070448},
issn = {1467-1107},
abstract = {Slim et al.'s paper provided an insight into the differences between repaired tetralogy of Fallot and isolated pulmonary regurgitation in their strain. Repaired tetralogy of Fallot had higher right ventricular circumferential strain, while isolated pulmonary regurgitation relied on longitudinal strain more. This allowed the authors to infer that repaired tetralogy of Fallot can withstand more chronic regurgitation before valve replacement is necessary. We highlighted new findings relevant to this paper. Arrhythmia in repaired tetralogy of Fallot is associated with a reduced global circumferential strain of the right ventricle. Specifically, a value of below -14% was associated with a 6.3 times increase in the risk for an arrhythmic event. We believe this would be beneficial for patients when considered for valve replacements, suggesting modification of current valve replacement guidelines to include strain thresholds alongside current volumetric thresholds. However, the data for isolated pulmonary regurgitation remains scarce. Further investigation is needed to provide clearer timelines for valve replacement. We emphasised the importance of exploring the underlying architecture of repaired tetralogy of Fallot patients' hearts and why they could generate more global circumferential strain. We acknowledged the broader effect of this paper and its specific benefit in our country, Egypt. This paper provided insights useful for broader global health impact, especially in low-income countries.},
}

@article {pmid41070136,
year = {2025},
author = {Jadeja, N and Ali, N and Dratch, L and Stanislaw, C and Barvin, D and Fournier, CN and Lichten, L},
title = {Exploring Motivation and Emotional Experience in Observational Research for Individuals at Risk of ALS/FTD Spectrum Disorders.},
journal = {Neurology. Clinical practice},
volume = {15},
number = {6},
pages = {e200538},
pmid = {41070136},
issn = {2163-0402},
abstract = {BACKGROUND AND OBJECTIVES: Numerous observational studies are available to asymptomatic individuals at risk to carry or known carriers of pathogenic variations associated with amyotrophic lateral sclerosis and frontotemporal degeneration (ALS-FTD) spectrum disorders. Little is known about such individuals' motivations for participation or the impact on their emotional well-being.

METHODS: Asymptomatic at-risk adults, with or without genetic status known, were recruited through social media advocacy groups and by National Society of Genetic Counselors ALS-FTD special interest group members. Interviews were conducted through secure videoconferencing. Two coders independently analyzed interview transcripts, followed by thematic content analysis.

RESULTS: Twelve participants (9 status-aware and 3 status-unaware) were interviewed, representing experience with 11 observational studies. Some motivations for participation aligned with previous literature, including altruism, health focus, and intellectual interest. Motivations unique to this population stemmed from the hereditary nature of the disease, including fear of future disease onset and the desire to establish a relationship with a specialized clinical care team, reflecting individual, familial, and societal factors. Benefits of participation included meeting these motivational goals, social connection and support, psychological well-being, and practical benefits. Challenges to participation fell into research-related (e.g., struggles with the observational nature of research), disease-related (e.g., anxiety about disease risk), and logistical (e.g., travel and study procedures) categories. Compared with status-unaware participants, status-aware participants more frequently cited individual motivators for research participation and encountered more research-related challenges when their participation did not align with their anticipated personal health benefits. Interviewees found relationships with providers through research to be rewarding but noted confusion between research and clinical care as a significant challenge.

DISCUSSION: Participation in observational research helps address unmet emotional and medical needs for asymptomatic individuals who are at risk of ALS-FTD spectrum disorders. However, some of these needs are beyond the scope of research, highlighting the need for new models of clinical care for at-risk individuals.},
}

@article {pmid41069745,
year = {2025},
author = {Hino, S and Iijima, Y and Nakayama, N and Horie, N and Kaneko, T},
title = {Macroglossia Caused by Venous Congestion in a Patient With Amyotrophic Lateral Sclerosis.},
journal = {Clinical case reports},
volume = {13},
number = {10},
pages = {e71122},
pmid = {41069745},
issn = {2050-0904},
abstract = {The macroglossia in this patient appeared largely related to impaired venous return from the tongue and neck after coil embolisation, rather than to tongue pseudohypertrophy due to denervation atrophy with fatty replacement caused by ALS.},
}

@article {pmid41069215,
year = {2025},
author = {Revolinski, SR and Amaral, M and Savic, M and Burke, IC},
title = {Genome-wide scan reveals CYP450 metabolism and stress response regulation underlying sulfosulfuron resistance in Bromus tectorum.},
journal = {Pest management science},
volume = {},
number = {},
pages = {},
doi = {10.1002/ps.70300},
pmid = {41069215},
issn = {1526-4998},
support = {//U.S. Department of Agriculture/ ; //Washington Grain Commission/ ; },
abstract = {BACKGROUND: Cheatgrass (Bromus tectorum L.) is a problematic weed species in the wheat cropping systems in the rainfed crop production areas of the inland Pacific Northwest (PNW) and now is becoming resistant to multiple modes of action. To identify mechanisms of non-target site acetohydroxy-acid/acetolactase synthase (AHAS/ALS) inhibitor resistance, 123 B. tectorum accessions were treated with three sulfosulfuron treatments (3.5, 35 and 350 g ha[-1]). A genome-wide association study (GWAS) was performed using the results from the spray trials to unravel the mechanisms underlying sulfosulfuron resistance in B. tectorum.

RESULTS: A single nucleotide polymorphism (SNP) explained up to 48% of observed phenotypic variation of sulfosulfuron resistance in B. tectorum but was not located near the AHAS/ALS gene in the genome. Candidate genes included members of the cytochrome P450 (CYP450) 71 gene family, heat shock-related proteins and a regulator of a heat shock-related protein. Additionally, the analysis revealed hormonal regulators, and genes involved in abiotic stress response as candidate genes.

CONCLUSION: Non-target site resistance for sulfosulfuron is present in B. tectorum populations of the inland PNW. A heat shock-related protein 70 regulator and an auxin response factor gene was near the SNP that explained 48% of the variation in the GWAS, indicating auxin regulation and stress response pathways are involved in the resistance of B. tectorum populations to sulfosulfuron. The heat shock-factor protein 70 regulated by the heat shock-related protein 70 regulator was found on another significant SNP and the SNPs those two genes were on have a significant interaction. Additionally, the GWAS analysis indicated CYP450 genes are likely involved in resistance. © 2025 Society of Chemical Industry.},
}

@article {pmid41069067,
year = {2025},
author = {Arshad, F and Udupi, GA and Hk, A and Somaraj, A and Jeevendra Kumar, D and Alladi, S},
title = {Expanding the genetic spectrum of corticobasal syndrome: novel CCNF p.M394L variant from a South Asian cohort.},
journal = {Neurocase},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/13554794.2025.2573318},
pmid = {41069067},
issn = {1465-3656},
abstract = {Corticobasal syndrome (CBS) is a rare neurodegenerative disorder characterized by asymmetric motor symptoms, cognitive impairment, and cortical dysfunction. While CCNF gene mutations have been reported in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), their role in CBS spectrum remains unexplored. This study aimed to investigate a 48-year-old patient of South Asian origin, presenting with progressive cognitive decline, behavioral disturbances, and asymmetric motor symptoms characteristic of overlap CBS syndrome. Detailed cognitive and behavioral assessments were conducted, along with brain imaging and whole-exome sequencing. Structural modeling was performed to assess the functional impact of the novel CCNF variant. The family history indicated an autosomal dominant inheritance pattern of progressive cognitive decline, further suggesting genetic predisposition. Brain imaging revealed asymmetric atrophy and hypometabolism in the left temporoparietal and prefrontal regions. Genetic analysis identified a novel heterozygous missense variant (p.Met394Leu) in the CCNF gene. Structural modeling and in-silico prediction tools suggested deleterious effects, though its functional significance remains uncertain. The study reports a potential link between CCNF variants and CBS in a South Asian family, expanding the genetic spectrum of overlap CBS. While the findings suggest potential pathogenicity, further research is required to confirm this association and elucidate the underlying mechanisms.},
}

@article {pmid41068958,
year = {2025},
author = {Benito-Casado, C and Durán-Mateos, E and Ferrer-Donato, Á and García, GB and Domínguez-Rubio, R and Povedano, M and Fernandez-Martos, CM},
title = {White adipose tissue undergoes pathological dysfunction in the TDP-43[A315T] mouse model of amyotrophic lateral sclerosis (ALS).},
journal = {Acta neuropathologica communications},
volume = {13},
number = {1},
pages = {213},
pmid = {41068958},
issn = {2051-5960},
support = {LCF/PR/HR19/52160016//"la Caixa" Banking Foundation and co-funded by Fundación Luzón/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/pathology/genetics/metabolism ; Animals ; *DNA-Binding Proteins/genetics/metabolism ; Disease Models, Animal ; *Adipose Tissue, White/pathology/metabolism ; Male ; Humans ; Mice ; Female ; Leptin/blood ; Mice, Transgenic ; Middle Aged ; Aged ; Mice, Inbred C57BL ; Obesity/pathology ; },
abstract = {White adipose tissue (WAT) has a crucial role in maintaining systemic energy homeostasis. Numerous biological pathway studies have highlighted the importance of adipokines in regulating metabolic pathways and contributing to metabolic dysfunction in animal models and patients with ALS. Despite these associations, the specific molecular mechanisms remain poorly understood. Moreover, the direct contribution of WAT to the energy metabolism abnormalities observed in ALS has yet to be clearly defined. The current study sought to identify perturbances in WAT, main source of leptin, during the clinical course of the disease in TDP-43[A315T] mice using histological, proteomic, and molecular biological techniques. We present the first evidence of a significant histological alteration in WAT prior to the symptomatic stage of the disease in TDP-43[A315T] mice, providing novel insights into pathological features earlier in the onset of symptoms, and showing WAT as a target organ for ALS. In human ALS cases, we found that circulating leptin levels at the time of diagnosis were lower in the plasma of men with ALS who were overweight or obese and had rapidly progressive ALS, emphasizing the importance of considering sex-specific approaches when analysing adipokines essential for body weight control.},
}

*Amyotrophic Lateral Sclerosis/pathology/genetics/metabolism
Animals
*DNA-Binding Proteins/genetics/metabolism
Disease Models, Animal
*Adipose Tissue, White/pathology/metabolism
Male
Humans
Mice
Female
Leptin/blood
Mice, Transgenic
Middle Aged
Aged
Mice, Inbred C57BL
Obesity/pathology

@article {pmid41068773,
year = {2025},
author = {Storey, S and Cleeve, A and Endler, M},
title = {Implementing telemedicine for medical abortion within the public health system: a qualitative study on implementation bottlenecks and solutions in South Africa.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {3421},
pmid = {41068773},
issn = {1471-2458},
mesh = {South Africa ; Humans ; *Telemedicine/organization & administration ; Qualitative Research ; *Abortion, Induced/methods ; Female ; Pregnancy ; Health Services Accessibility ; Interviews as Topic ; Adult ; },
abstract = {BACKGROUND: Abortion in South Africa is legal, but there are still many barriers to access and high utilisation of the informal sector. Telemedicine for medical abortion is an alternative model that has been found to be a safe, effective, and acceptable option to increase access to abortion services. This study aimed to understand how key informants view telemedicine for medical abortion and how they view potential bottlenecks and solutions concerning implementation in the public sector of South Africa.

METHODS: We conducted interviews between February and March 2023 with 19 key informants across telemedicine and medical abortion provision, policy, and research. Through a qualitative design, we analysed the interviews using inductive content analysis. We used Baker et al.'s model of the implementation pathway to conceptualise and discuss the findings.

RESULTS: The findings showed that respondents perceived telemedicine as a valuable complement to in-clinic care to increase access to safe abortions. Respondents identified clinical concerns and logistical challenges as implementation bottlenecks and believed these could be overcome with innovative thinking and by drawing on existing resources. They suggested that research, leadership, collaboration, and policy alignment would help increase stakeholder willingness and capacity to build health system readiness. Across the implementation process, respondents viewed it necessary to consider users' needs and adapt to contextual differences.

CONCLUSIONS: This study identified telemedicine as a valuable model for increasing access to safe abortion services. Respondents outlined considerations and actionable steps to overcome implementation bottlenecks and guide the implementation of telemedicine for medical abortion in the public sector of South Africa and similar settings.},
}

South Africa
Humans
*Telemedicine/organization & administration
Qualitative Research
*Abortion, Induced/methods
Female
Pregnancy
Health Services Accessibility
Interviews as Topic
Adult

@article {pmid41067460,
year = {2025},
author = {Mont, MA and Marino, J},
title = {A Rebuttal to Conrad et al.'s "Commentary on 'A Phase 3 Active-Controlled Trial of Liposomal Bupivacaine via Adductor Canal Block for Total Knee Arthroplasty'".},
journal = {The Journal of arthroplasty},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.arth.2025.10.002},
pmid = {41067460},
issn = {1532-8406},
}

@article {pmid41066257,
year = {2025},
author = {Fuentes-Guerra, Á and Cipriani, GA and González-García, C and Botta, F},
title = {Drift-diffusion modeling of accuracy and reaction times: A deeper insight into retrospective attention.},
journal = {Journal of experimental psychology. Human perception and performance},
volume = {51},
number = {11},
pages = {1461-1463},
doi = {10.1037/xhp0001349},
pmid = {41066257},
issn = {1939-1277},
support = {//Spanish Ministry of Science and Innovation and the State Research Agency/ ; //MCIN/AEI/10.13039/501100011033/ ; //European Union Next Generation EU/PRTR/ ; //European Social Fund Plus ESF+/ ; //University of Granada/ ; },
mesh = {Humans ; *Attention/physiology ; *Reaction Time/physiology ; *Memory, Short-Term/physiology ; *Models, Psychological ; *Psychomotor Performance/physiology ; *Cues ; Adult ; Young Adult ; },
abstract = {Retrospective attention refers to the prioritization of contents held in working memory, a process investigated using the retro-cueing paradigm. This process is evidenced by the retro-cueing benefit, characterized by better performance for retrospectively cued trials. However, traditional statistical analyses fall short in distinguishing between decisional and nondecisional processes underlying this benefit. A pivotal contribution by Shepherdson et al. (2018) addressed this gap by applying drift-diffusion modeling which integrates both accuracy and reaction time measures to disentangle these processes. Their key contribution lies in demonstrating that retro-cues enhance the quality of working memory contents and enable their retrieval in advance of decision making-effects that occur independently of shifts in decision criteria. Building on Shepherdson et al.'s work, we encourage future drift-diffusion model-based retro-cueing studies to pursue precise, mutually exclusive hypothesis testing and to integrate behavioral and neural data to more clearly distinguish between competing explanations of the retro-cueing benefit. (PsycInfo Database Record (c) 2025 APA, all rights reserved).},
}

Humans
*Attention/physiology
*Reaction Time/physiology
*Memory, Short-Term/physiology
*Models, Psychological
*Psychomotor Performance/physiology
*Cues
Adult
Young Adult

@article {pmid41066153,
year = {2025},
author = {Su, W and Zhang, C and Sun, L and Xu, H and Zhang, G and Xue, F and Leng, Q and Niu, Y and Wu, R},
title = {Multifaceted Mechanisms of Cyprosulfamide in Mitigating Mesosulfuron-Methyl Phytotoxicity in Maize Seedlings: GST Activation, Oxidative Stress Alleviation, and Target-Site Competition.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c07590},
pmid = {41066153},
issn = {1520-5118},
abstract = {Mesosulfuron-methyl (MS), a sulfonylurea herbicide used in wheat, poses significant residual phytotoxicity risks to subsequent maize (Zea mays L.) crops. This study evaluated the protective role of the safener cyprosulfamide (CSA) through physiological, biochemical, and molecular analyses. MS treatment drastically reduced maize shoot length and fresh weight by 80.74% and 74.24%, respectively, while CSA pretreatment significantly relieved these inhibitory effects, with the mitigation rates of shoot length and fresh weight reaching 66.3% and 63.57%, respectively. Physiologically, CSA alleviated MS-induced chlorophyll and carotenoid losses and reduced oxidative stress by lowering malondialdehyde (MDA) levels (23.39% at 6 days after sowing) while enhancing superoxide dismutase (SOD) and glutathione S-transferase (GST) activity. Molecularly, CSA upregulated nine GST genes, competitively bound to ZmALS1/2, increasing acetolactate synthase (ALS) activity by 70-146%, and reduced MS residues in shoots (4.02%) and roots (33.78%). These findings demonstrate CSA's multifunctional detoxification mechanism, combining gene activation, antioxidant regulation, and target-site competition, offering a viable strategy to mitigate herbicide carryover in crop rotations. CSA application could significantly reduce MS phytotoxicity, advancing sustainable herbicide management.},
}

@article {pmid41065501,
year = {2025},
author = {Soleimanifard, N and Seyedalipour, B and Baziyar, P and Hosseinkhani, S},
title = {Understanding Structural Destabilization and Amyloid Aggregation in ALS-Related Neurodegenerative Disorder: An In Silico and Experimental Analysis of SOD1 Variants.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.5c00350},
pmid = {41065501},
issn = {1948-7193},
abstract = {Protein misfolding has been reported as a common symptom in many neurodegenerative diseases, leading to the formation of protein aggregates. Metal ions (holo form) are critical for the folding and function of WT-SOD1, whereas their absence (apo form) can lead to aggregation and misfolding under physiological conditions. Therefore, this study investigates the role of mutations/metal deficiencies in the metal binding loop and how the mutations affect the SOD1 aggregation process in amyotrophic lateral sclerosis through an experimental and computational approach. Molecular dynamic (MD) simulation results show a significant difference in apo-SOD1 compared to holo-SOD, which is consistent with experimental studies. Dictionary of Secondary Structure in Proteins (DSSP), Fourier-transform infrared (FTIR), and Circular dichroism (CD) results confirmed a tendency for increased β-sheet formation in the apo-SOD1 form, which can be attributed to protein aggregation. The observed conformational changes under amyloidogenic conditions suggest that the hydrophobic pockets in apo-SOD1 are more exposed compared to holo-SOD1, as confirmed by ANS fluorescence. Thermodynamic investigations with GdnHCl demonstrated that mutation/metal deficiency are necessary to trigger the misfolding and aggregation of SOD1. Our results show that apo/holo SOD1 variants induce the formation of aggregated species under physiological conditions. These aggregates are detected by Congo red and ThT fluorescence and further validated by transmission electron microscopy (TEM) imaging. Overall, mutations in loop IV and structural abnormalities such as mutation/metal deficiency and reduced disulfide bonds synergistically lead to reduced thermodynamic stability of SOD1 variants, facilitating the formation of amyloid/amorphous aggregates. Ultimately, this study could serve as a basis for new research to develop new treatments for neurological disorders, and help to better understand the role of mutation in the formation of amyloid aggregates and identify different factors in ALS disease.},
}

@article {pmid41065069,
year = {2025},
author = {Shan, Y and Jing, W and Zhang, H and Liu, Y and Wei, S and Wu, F and Pan, W},
title = {Amyotrophic lateral sclerosis rehabilitation management and non-pharmacological symptomatic treatment: A review.},
journal = {International journal of clinical pharmacology and therapeutics},
volume = {},
number = {},
pages = {},
doi = {10.5414/CP204744},
pmid = {41065069},
issn = {0946-1965},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that lacks effective treatment options for the prevention of progression. Relieving swallowing difficulties, reducing breathing difficulties, and alleviating muscle spasms are essential to improving the quality of life in patients with ALS. Many symptoms can be treated clinically with medication; however, the evidence level of related research is relatively low. Rehabilitation management can aid in improving various functional impairments and enhancing quality of life. This review introduces and describes the relevant evaluations of rehabilitation and nonpharmacological symptomatic treatment methods for functional disorders from the perspectives of motor and nonmotor symptoms. This review may promote the popularization of ALS rehabilitation management and provide an additional reference for ALS treatment.},
}

@article {pmid41064775,
year = {2025},
author = {Bazarova, T and Montiel-Company, JM and Gil-Loscos, FJ},
title = {Exploring the Impact of Dentine Hypersensitivity: Validation of the Spanish DHEQ-15 and Its Cultural Adaptation.},
journal = {Journal of clinical and experimental dentistry},
volume = {17},
number = {9},
pages = {e1043-e1049},
pmid = {41064775},
issn = {1989-5488},
abstract = {BACKGROUND: Dentine hypersensitivity (DH) is a common condition with varying patient perceptions, making diagnosis and management challenging. Patient-reported outcome measures, such as the Dentine Hypersensitivity Experience Questionnaire (DHEQ-15), provide valuable insights into its impact on daily life. This study aimed to adapt and validate the Spanish version of the DHEQ-15 for use in Spain, ensuring its reliability and relevance for Spanish-speaking patients.

MATERIAL AND METHODS: A structured translation and cross-cultural adaptation process followed Beaton et al.'s (2000) methodology. Spanish-speaking participants aged 35-60 completed the DHEQ-15. Psychometric properties were assessed through factor analysis for construct validity, Cronbach's alpha for internal consistency, and the intraclass correlation coefficient (ICC) for test-retest reliability. Sociodemographic factors such as gender, age, and education level were also analyzed.

RESULTS: The Spanish DHEQ-15 was well-received. It showed excellent internal consistency (Cronbach's alpha = 0.958) and high test-retest reliability (ICC = 0.932). Factor analysis identified three main dimensions: Restrictions-Coping, Psychosocial Impact, and Identity explaining 76% of score variance. The questionnaire was easy to complete, with an average completion time of 4 minutes. Women scored higher in 'Restrictions-Coping,' while age and education level showed no significant associations.

CONCLUSIONS: The Spanish DHEQ-15 has been successfully adapted and validated in Spain, demonstrating high reliability and validity. It is a viable and effective tool for assessing the impact of DH on the quality of life of Spanish-speaking populations. Key words:Dentine hypersensitivity, Validation, Quality of life, Questionnaire.},
}

@article {pmid41064708,
year = {2025},
author = {Posa, A and Kornhuber, M},
title = {A Very Rare Setx Gene Variant (C.2750T>C) In a 72-year-old Man with Amyotrophic Lateral Sclerosis and an Unremarkable Family History. Should Genetic Testing be Routinely Performed in all Patients?.},
journal = {European journal of case reports in internal medicine},
volume = {12},
number = {10},
pages = {005706},
pmid = {41064708},
issn = {2284-2594},
abstract = {UNLABELLED: Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative multisystem disease with loss of spinal, bulbar and cortical upper and lower motor neurons resulting in progressive and generalised paralysis. Unfortunately, many aspects of this disease remain unclear. In the age of next generation sequencing, numerous gene variants have been discovered that are associated with ALS. In this article, a 72-year-old male underwent a medical history interview, clinical neurological examinations, neuropsychological tests, electrophysiological examinations (electromyography, electroneurography, somatosensory evoked potentials), computed tomography scan of the head and the cervical spine, blood and cerebrospinal fluid tests and a genetic analysis. The results of these examinations provided the definitive diagnosis of ALS. Whole-exome sequencing revealed the very rare genetic finding of the SETX Class-4 variant c.2750T>C (p.Met917Thr). The case presented here discusses the role of the SETX gene as a possible pathogenetic variant of adult-onset ALS. It demonstrates the relevance of genetic screening for gene variants of ALS in routine diagnostics. The precise classification of disease-related gene variants is of great relevance for clinical practice.

LEARNING POINTS: Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative multisystem disease with loss of spinal, bulbar and cortical upper and lower motor neurons resulting in progressive and generalised paralysis.The case presented here describes a very rare variant in the SETX gene (heterozygous Class-4 variant c.2750T>C, p.Met917Thr) in an adult man with sporadic rapidly progressive ALS, with an unremarkable family history.This case demonstrates the relevance of genetic screening for gene variants of ALS in routine diagnostics, both in sporadic and familial cases. This may add to the accuracy of diagnosis and may improve genetic counselling for rare diseases.},
}

@article {pmid41063967,
year = {2025},
author = {Yoganathan, K and Trubshaw, M and Kohl, O and Gohil, C and Echeverria-Altuna, I and Dharmadasa, T and Northall, A and Zokaei, N and Lester, D and Garcia, G and Collins, A and Amein, B and Nobre, AC and Talbot, K and Thompson, AG and Woolrich, M and Turner, MR},
title = {Reduced beta bursting underpins loss of corticomuscular coherence in amyotrophic lateral sclerosis.},
journal = {Brain communications},
volume = {7},
number = {5},
pages = {fcaf339},
pmid = {41063967},
issn = {2632-1297},
abstract = {Biomarkers of disease activity that holistically capture motor system dysfunction are needed to accelerate drug discovery in amyotrophic lateral sclerosis. Magnetoencephalography is a sensitive, non-invasive measure of cortical neurophysiology. Corticomuscular coherence reflects the functional coupling of cortical oscillations with downstream muscle activity recorded by electromyography. Cortical beta frequency bursting is known to represent a core feature of the neurophysiology underpinning movement. This study aimed to characterize disruption of beta frequency activity in both cortex and muscle to refine the understanding of corticomuscular coherence loss in amyotrophic lateral sclerosis. The study analysed 42 people living with amyotrophic lateral sclerosis and 33 healthy age-matched controls. Participants undertook an isometric hand gripping task during magnetoencephalography. Muscle contraction was measured using bipolar surface electromyography recordings at both forearms. All participants performed 120 trials of the gripper task bilaterally, and 60 trials unilaterally on each side. For each trial type, the mean corticomuscular coherence over trials was calculated for each participant and the groups were compared via cluster-based permutations tests. Beta burst metrics were calculated for the motor cortex (magnetoencephalography) and flexor forearm muscles (surface electromyography) including burst fractional occupancy, burst duration and amplitude. During muscular contraction, beta frequency corticomuscular coherence from the motor cortices contralateral to the gripper task was markedly reduced in amyotrophic lateral sclerosis patients, despite no significant difference in grip strength compared with controls. Source localization analysis showed globally reduced corticomuscular coherence in amyotrophic lateral sclerosis with significant differences in the motor regions contralateral to the engaged hand. There were no significant beta frequency activity changes in the engaged-hand electromyography signal in amyotrophic lateral sclerosis compared with controls. In contrast, analysis of the cortical motor regions revealed reduced rate of beta bursting and higher amplitude during the contraction phase of the task in amyotrophic lateral sclerosis. The corticomuscular coherence disruption in amyotrophic lateral sclerosis appears driven more by cerebral pathology than by muscle denervation. Equal grip strength during the task implies compensatory pathways in disease that are not captured by corticomuscular coherence. Interneuronal dysfunction may underlie the disruption to motor cortex beta bursting. Motor cortical beta frequency metrics have potential as secondary outcome measures in therapeutic trials and need exploration as prodromal markers in asymptomatic individuals genetically predisposed to amyotrophic lateral sclerosis.},
}

@article {pmid41063391,
year = {2025},
author = {Inoue, K and Toyooka, K and Fujimura, H and Ueda, K and Kaido, M and Yamamoto, Y and Izumi, Y},
title = {Familial ALS With p. L127S (L126S) Variant of the Cu/Zn SOD1 Gene: A Report of Two New Cases and Literature Review.},
journal = {Neuropathology : official journal of the Japanese Society of Neuropathology},
volume = {45},
number = {6},
pages = {e70028},
pmid = {41063391},
issn = {1440-1789},
support = {25wm0625126s0301//Japan Agency for Medical Research and Development/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Middle Aged ; Female ; *Superoxide Dismutase-1/genetics ; Male ; Adult ; Motor Neurons/pathology ; Inclusion Bodies/pathology ; },
abstract = {Herein, we report two autopsy cases of familial ALS with a p. L127S (L126S) SOD1 variant. Case 1 involved a 62-year-old woman who presented with lower-extremity muscle weakness with lower motor neuron signs. The patient developed bulbar palsy and died of respiratory failure 9 years after onset. Case 2 (the second son of Case 1) presented with lower-extremity muscle weakness at the age of 38 years, with upper and lower motor neuron signs and died of respiratory failure 8 years after onset. The pathological findings in both cases predominantly consisted of lower motor neuron loss and degeneration of the lateral and posterior funiculi. Numerous conglomerate hyaline inclusions (CHIs) were observed in the remaining motor neurons. Vacuole formation was observed inside the inclusions, sometimes with granular structures. Some inclusions were positive for ubiquitin, p62, and SOD1. Electron microscopy revealed that CHIs were composed of neurofilaments and expanded mitochondria. By literature review, ALS with p. L127S disclosed a male-dominant incidence rate, a variety of ages at onset, and low penetrance. The initial symptom was exclusively lower limb weakness. One-third of the patients only showed lower motor neuron signs and half did not present with bulbar symptoms. The neuropathological findings commonly observed in ALS with p. L127S variants were mainly the degeneration of lower motor neurons and the sensory system, including the posterior column, Clarke's nucleus, and the associated cerebellar system. The formation of intracytoplasmic hyaline inclusions was also a prominent feature. ALS with p. L127S variant should be included in the possible diagnosis of slowly progressive muscle weakness in the lower extremities, with or without family history or upper motor neuron signs. The loss of lower motor neurons and the accumulation of neurofilaments in the remaining neurons are key to the pathological diagnosis for ALS with p. L127S variant.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/pathology
Middle Aged
Female
*Superoxide Dismutase-1/genetics
Male
Adult
Motor Neurons/pathology
Inclusion Bodies/pathology

@article {pmid41063344,
year = {2025},
author = {Ito, H and Machida, K and Fujino, Y and Hasumi, M and Sakamoto, S and Nagai, Y and Imataka, H and Taguchi, H},
title = {Canonical translation factors eIF1A and eIF5B modulate the initiation step of repeat-associated non-AUG translation.},
journal = {Nucleic acids research},
volume = {53},
number = {18},
pages = {},
pmid = {41063344},
issn = {1362-4962},
support = {JP26116002//MEXT/ ; JP18H03984//MEXT/ ; JP21H04763//MEXT/ ; JP20H05925//MEXT/ ; //AMED/ ; JP21gm1410008//CREST/ ; //JST/ ; JPMJFS2112//JSPS/ ; 24KJ1067//JSPS/ ; //Uehara Memorial Foundation/ ; //Mitsubishi Foundation/ ; //Daiichi Sankyo/ ; //KAKENHI/ ; },
mesh = {Humans ; HEK293 Cells ; *Eukaryotic Initiation Factors/genetics/metabolism/physiology ; *Eukaryotic Initiation Factor-1/genetics/metabolism/physiology ; *Peptide Chain Initiation, Translational ; *Protein Biosynthesis ; *DNA Repeat Expansion ; Codon, Initiator ; Neoplasm Proteins ; Nerve Tissue Proteins ; },
abstract = {Nucleotide repeat expansions, such as the GGGGCC repeats in C9orf72, associated with C9-ALS, are linked to neurodegenerative diseases. These repeat sequences undergo a noncanonical translation known as repeat-associated non-AUG (RAN) translation. Unlike canonical translation, RAN translation initiates from non-AUG codons and occurs in all reading frames. To identify potential regulators of RAN translation, we employed a bottom-up approach using a human factor-based reconstituted cell-free translation system to recapitulate RAN translation. This approach revealed that omission of either eIF1A or eIF5B enhanced the translation in all reading frames of C9orf72-mediated RAN translation (C9-RAN), suggesting that eIF1A and eIF5B act as repressors of RAN translation. eIF1A and eIF5B are known to contribute to the fidelity of translation initiation. In HEK293T cells, double knockdown of eIF1A and eIF5B further promoted C9-RAN compared to single knockdowns, indicating that these factors regulate C9-RAN through distinct initiation steps. Furthermore, under eIF1A knockdown conditions, the enhancement of RAN translation via the integrated stress response (ISR) was not observed in HEK293T cells, indicating that eIF1A is involved in the ISR-mediated non-AUG translation.},
}

Humans
HEK293 Cells
*Eukaryotic Initiation Factors/genetics/metabolism/physiology
*Eukaryotic Initiation Factor-1/genetics/metabolism/physiology
*Peptide Chain Initiation, Translational
*Protein Biosynthesis
*DNA Repeat Expansion
Codon, Initiator
Neoplasm Proteins
Nerve Tissue Proteins

@article {pmid41062766,
year = {2025},
author = {Bordon, Y},
title = {Autoimmune T cells identified in ALS.},
journal = {Nature reviews. Immunology},
volume = {},
number = {},
pages = {},
pmid = {41062766},
issn = {1474-1741},
}

@article {pmid41062721,
year = {2025},
author = {Ramasubramanian, B and Ganguly, D and Rao, RP and Ramakrishna, S},
title = {Progress, pitfalls, and prospects in emerging materials for aluminum-sulfur batteries.},
journal = {Communications chemistry},
volume = {8},
number = {1},
pages = {301},
pmid = {41062721},
issn = {2399-3669},
abstract = {Aluminium-sulfur (Al-S) batteries have emerged as a promising post-lithium alternative owing to aluminium's abundance, safety, and high theoretical capacity. However, their practical implementation is impeded by key challenges such as sluggish Al[3+] redox kinetics, polysulfide shuttle effects, and volumetric changes of the electrodes during cycling. This review critically analysis recent advancements in host structural design engineering, new electrocatalysts, and electrolyte aimed at overcoming these limitations. Advanced host frameworks include 2D/3D porous structures, MXene-based multilayers, and single-atom doped materials that facilitate efficient sulfur confinement, enhance conductivity, and catalyse redox reactions. Embedded catalysts like Mo6S8 and CoS2 within nitrogen-doped carbons lower the decomposition barrier of Al2S3, promote stable Al-polysulfide conversion, and extend cycle life. Electrolyte optimization through ionic liquids, molten salts, and halide-modified systems further enhances ion mobility, suppresses passivation, and supports stable sulfur utilization. Emerging hybrid electrolytes combining high-donicity solvents with ionic or molten salt phases offer synergistic gains in redox kinetics and thermal stability. Density functional theory (DFT) guided designs elucidate key host-electrolyte-polysulfide interactions, revealing pathways for tailored material selection and performance enhancement. These integrated strategies pave the way for high-energy, long-lasting Al-S batteries that perform reliably at both room and elevated temperatures.},
}

@article {pmid41061972,
year = {2025},
author = {Mao, PC and Wei, KC and Weng, CT},
title = {Response to Bar et al.'s "Early Initiation of Hydroxychloroquine in Cutaneous Lupus Erythematosus to Prevent Progression to Systemic Lupus Erythematosus: A Long-term Follow-up Study".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.03.108},
pmid = {41061972},
issn = {1097-6787},
}