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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

History, 19th Century
*Neurology/history
Humans

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

@article {pmid41417753,
year = {2025},
author = {Lam, P and Zygmunt, DA and Bennett, M and Ashbrook, A and Hefty, J and Martin, PT},
title = {Gne deletion in adult mice can cause thrombocytopenia, anemia, myopathy, bleeding, and death.},
journal = {Journal of neuromuscular diseases},
volume = {},
number = {},
pages = {22143602251405918},
doi = {10.1177/22143602251405918},
pmid = {41417753},
issn = {2214-3602},
abstract = {The GNE gene encodes the UDP-GlcNAc-2-epimerase/ManNAc kinase, a bifunctional enzyme required for the synthesis of sialic acid. The mouse Gne gene is essential for embryonic development, but humans with recessive partial loss of function GNE mutations can develop infantile thrombocytopenia, juvenile amyotrophic lateral sclerosis, or adult-onset myopathy (GNE myopathy). We have created inducible Gne[lox/lox] gene deletion mice to study how loss of Gne in adult mice relates to these disease states. Systemic Gne gene deletion in tamoxifen-treated Rosa-CreER[T2]/Rosa-CreER[T2]Gne[lox/lox] mice caused uniform fatality within 30 days of gene deletion with spontaneous bleeding, thrombocytopenia, and anemia. Skeletal myofiber-specific Gne deletion in tamoxifen-treated HSA-CreER[T2/+]Gne[lox/lox] mice had no bleeding and no muscle pathology at 60 or 270 days post-treatment. Intramuscular injection of AAV.MCK.GFP-Cre in Gne[lox/lox] mice also showed little to no evidence of muscle pathology, while AAV.CMV.GFP-Cre caused extensive muscle damage, reduced muscle force, and changed expression of markers for muscle regeneration, muscle cell senescence, muscle denervation, and muscle atrophy. These data demonstrate that Gne is an essential gene in adult mice that can mimic aspects of human hematologic and muscle diseases caused by GNE mutations, but suggests induction of muscle disease requires loss of gene GNE expression in cell types beyond skeletal myofibers.},
}

@article {pmid41417080,
year = {2025},
author = {Zafar, U and Abdullah, M and Butt, TN and Uddin, MMZ and Masood, MH and Chu, LC and Zaheer, A},
title = {A bibliometric analysis of the 100 most cited radiology papers on pancreatic diseases (1990-Present).},
journal = {Abdominal radiology (New York)},
volume = {},
number = {},
pages = {},
pmid = {41417080},
issn = {2366-0058},
abstract = {PURPOSE: To map the intellectual evolution of pancreatic radiology through a comprehensive bibliometric analysis of the 100 most-cited articles, identifying influential contributors and publications, geographical and institutional patterns, and delineating the thematic and technological trends shaping research from 1990 to the present.

METHODS: A systematic search of the Scopus database, conducted on May 11, 2025, identified the top 1,000 most-cited pancreatic radiology records between 1990 and 2025. Two reviewers independently screened articles for a primary focus on pancreatic imaging within core radiology journals. The final 100 articles were analyzed using the Bibliometrix R package to evaluate publication trends, contributor influence, and collaborative networks. The conceptual structure and thematic evolution of the field were mapped using VOSviewer (version 1.6.20).

RESULTS: The median citation count was 223 (IQR: 190.2-264.5). A significant temporal bias was evident: the most-cited article was Balthazar et al.'s 1990 study on CT in pancreatitis (1,424 citations), while a 2015 deep learning paper achieved the highest citation velocity (58.5 citations/year). Analysis of research topics revealed a strong oncologic focus, with pancreatic neoplasms accounting for 51% of all articles. CT was the predominant imaging modality (55%), followed by MRI (24%). The research ecosystem was concentrated, with the United States contributing 46 articles and Radiology publishing 44 of the top 100 papers. Leading institutions included Johns Hopkins University and the Mayo Clinic. Co-authorship network analysis identified Megibow AJ as the researcher with the highest network centrality, highlighting the importance of collaborative hubs.

CONCLUSION: This bibliometric analysis charts the field's evolution from foundational CT/MRI applications to the current AI frontier. Our findings serve as a guide to the characteristics of high-impact research, highlighting a consistent focus on oncology, driven by key authors and US institutions. While historical benchmarks focused on morphological assessment, citation metrics confirm computational methods as the principal driver of future innovation.},
}

@article {pmid41417044,
year = {2025},
author = {Rott, N and Reinsch, L and Dirks, B and Böttiger, BW},
title = {[The new European Resuscitation Council (ERC) guidelines 2025-Overview of the most important changes; the first 3-5 min are decisive].},
journal = {Die Anaesthesiologie},
volume = {},
number = {},
pages = {},
pmid = {41417044},
issn = {2731-6866},
abstract = {In October 2025 the new resuscitation guidelines of the European Resuscitation Council (ERC) were published. In the chapter on advanced life support (ALS) for adults the update emphasizes topics such as efficient ventilation with adequate chest compressions, early defibrillation, identification and treatment of reversible causes as rapidly as possible and the administration of epinephrine in cases of non-defibrillatable cardiac arrest. The aim of the guidelines is to sustainably improve survival rates after cardiac arrest through structured and evidence-based care systems.},
}

@article {pmid41416937,
year = {2025},
author = {Jensen, TR and Jacobs, I and Kverková, K and Lalić, L and Polonyiová, A and Stehlík, P and Reber, SA and Osvath, M},
title = {T. rex cognition was T. rex-like-A critical outlook on diverging views of the neurocognitive evolution in dinosaurs.},
journal = {Anatomical record (Hoboken, N.J. : 2007)},
volume = {},
number = {},
pages = {},
doi = {10.1002/ar.70074},
pmid = {41416937},
issn = {1932-8494},
abstract = {A recent debate has emerged between Caspar et al. (2024) and Herculano-Houzel (2023) on inferring extinct dinosaur cognition by estimating brain neuron counts. While thought-provoking, the discussion largely overlooks the function of cognition, as well as partly neglects the difficulties involved in estimating neuron numbers, which according to us leads to oversimplified conclusions. We use this exchange as a springboard to further explore how extinct cognition might be studied and the potential pitfalls involved. One of the main emphases is on introducing basic concepts and contemporary views of cognition and its evolution. In relation to this, we highlight the shift in thermobiology during the Mesozoic-from ectothermy to endothermy-and its major impact on cognition and brain evolution. We also examine the challenges of estimating neuron counts in extinct dinosaurs based on current knowledge and take issue with several aspects of the approaches used by both Caspar et al. and Herculano-Houzel. At the same time, we challenge Caspar et al.'s claim that telencephalic neuron numbers, if estimable, would be largely uninformative about extinct dinosaur cognition, while also disagreeing with Herculano-Houzel's somewhat reductive view. We further emphasize the value of comparative cognitive studies in extant animals, alongside neural correlates, to infer the cognitive evolution of non-avian dinosaurs. We briefly outline how cognition is studied in living species and the extent to which such research can inform evolutionary inference. Our focus here is on non-avian theropods, as they are central to the current debate and belong to the lineage that led to modern birds.},
}

@article {pmid41415845,
year = {2025},
author = {Harsa, HS and González Domenech, CM and Prvulović, M and Agirbasli, Z and Bagherzadehsurbagh, E and Simeunović, V and Naziri, E and Adesemoye, E and Yigit Cinar, A and Mukherjee, A and Laranjo, M and Vidović, B and Alves, E and Vukojević, A and Özmen Toğay, S and Düven, G and Saar, H and Salminen, S and Matalas, A and Paveljšek, D and Schneider, E and Liwinski, T and Chassard, C and Vergères, G and Bär, C and Praćer, S},
title = {The effects of Lactobacillus and/or Bifidobacterium in fermented foods on cognitive health: a systematic review.},
journal = {Frontiers in nutrition},
volume = {12},
number = {},
pages = {1682419},
pmid = {41415845},
issn = {2296-861X},
abstract = {BACKGROUND: Psychobiotics are microorganisms that modulate brain function via the gut-brain axis and are increasingly studied for their cognitive benefits. Lactobacillus and Bifidobacterium species, widely present in fermented foods, are considered safe and may influence cognition by modulating neuroinflammation, neurotransmitters, and gut barrier integrity. This systematic review examined the effects of foods fermented with these species on cognitive performance in healthy adults and individuals with mild cognitive impairment.

METHODS: We conducted the systematic review following EFSA guidelines, Cochrane methodology, and a PROSPERO protocol, using CADIMA for study selection and data extraction. PubMed, Scopus, and Cochrane Library were searched (1 January 1970-31 August 2023) for human intervention and observational studies assessing cognitive outcomes after ingestion of foods fermented with Lactobacillus or Bifidobacterium. Eligible populations included healthy adults and individuals with mild cognitive impairment; studies involving disease were excluded. Screening, data extraction, and bias assessment followed Muka et al.'s 24-step guide using ROBINS and Cochrane/CADIMA frameworks. Evidence was synthesized narratively, while a non-systematic component examined food characteristics, potential mechanisms, and factors affecting bioavailability of bioactive constituents.

RESULTS: We included 21 studies (8 interventional, 13 observational). The majority of studies reported benefits, particularly in episodic memory, executive functions, and global cognition, but evidence was limited by inadequate controls, small sample sizes, short interventions, inconsistent domain assessment, and incomplete food characterization. Observational studies had larger populations and longer follow-ups but were limited by exposure assessment and depth of cognitive testing.

CONCLUSION: Consumption of foods fermented with Lactobacillus and/or Bifidobacterium species may offer promising cognitive benefits. However, following EFSA's guidance on the substantiation of health claims, the current evidence is "neither convincing nor sufficient" to establish a causal relationship. Well-designed studies with thorough product characterization are needed to substantiate effects and support potential health claims.

This study was registered at the Open Science Framework (10.17605/OSF.IO/Z6GRW).},
}

@article {pmid41414999,
year = {2025},
author = {Kamadi, EN and Shah, J and Hooker, J and Jenkins, TM and Sokhi, DS},
title = {Clinical phenotypes of motor neurone disease in a Kenyan hospital-based population.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1662690},
pmid = {41414999},
issn = {1664-2295},
abstract = {BACKGROUND: Motor neurone disease (MND) presentation is globally heterogenous and data on the clinical phenotype in Sub-Saharan Africa (SSA) is scarce. We sought to address this by describing the profile of MND patients in a Kenyan hospital-based population.

METHODS: The medical charts of all adult MND patients assessed in the facility between January 2010 and December 2023 were retrospectively reviewed. The biographical data and clinical features of these patients were captured from their electronic and manual health records and statistical analysis performed.

RESULTS: In total, 160 patients had their data analyzed. The male to female ratio was 1.76:1. The median age at presentation was 55.0 (IQR: 45.0-68.0) years with a median diagnosis delay of 4.0 (IQR: 2.0-8.5) months. The site of first symptom onset was the lower limbs in 34.4% and the bulbar region in 33.1% [95% CI (26.4-42.5%)]. Notably, 59% of the patients were not tested for HIV and amongst those tested, 13.9% were HIV positive on ART. Majority (56.2%) of the patients were on Riluzole.

CONCLUSION: This Kenyan case series of MND patients demonstrated a higher rate of bulbar onset disease [33.1, 95% CI (26.4-42.5%), p = 0.018] in comparison to what has been demonstrated in other African studies. A finding that supports geographic variation in MND presentation and that emphasizes the need for region specific genetic studies.},
}

@article {pmid41412960,
year = {2025},
author = {Goutman, SA and Stouffer, DG and Jang, DG and Park, J and Murdock, BJ and Auchus, RJ},
title = {Sex Hormones Associate With Amyotrophic Lateral Sclerosis Risk and Survival.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.70281},
pmid = {41412960},
issn = {2328-9503},
support = {R01TS000339/ACL/ACL HHS/United States ; AL200064//U.S. Department of Defense/ ; //Eric and Linda Novak/ ; //James and Margaret Hiller/ ; //Robert A. Epstein and Joan M. Chernoff-Epstein Emerging Scholar Fund/ ; //Stanford Morris ALS Research Fund/ ; K23ES027221/NH/NIH HHS/United States ; R01ES030049/NH/NIH HHS/United States ; R01NS120926/NH/NIH HHS/United States ; R01NS127188/NH/NIH HHS/United States ; //University of Michigan/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) risk differs by sex and age, implicating sex hormones as potential modifiers. This study examined plasma levels of biologically active sex hormones and their association with ALS odds and survival in cases (females n = 131, males n = 189) and controls (females n = 138, males n = 150) from the University of Michigan Pranger ALS Clinic. Higher 11-ketotestosterone levels were associated with increased ALS odds. In females, higher estrone, androstenedione, and 11-hydroxyandrostenedione were associated with increased ALS odds, while elevated estrone and estradiol predicted shorter survival. These findings highlight the potential significance of sex hormones in ALS.},
}

@article {pmid41411702,
year = {2025},
author = {Lebkuecher, AL and Coslett, HB and Buxbaum, LJ},
title = {The cognitive neuropsychology of action semantics: A review.},
journal = {Cortex; a journal devoted to the study of the nervous system and behavior},
volume = {194},
number = {},
pages = {159-190},
doi = {10.1016/j.cortex.2025.11.008},
pmid = {41411702},
issn = {1973-8102},
abstract = {The conceptual knowledge that mediates our ability to use familiar objects, understand viewed actions, and engage in communication about actions is often termed "action semantics". The underlying format, cognitive organization, and neural substrates of these representations are matters of active scientific investigation. This review synthesizes the large and diverse literature on action semantics in individuals with neurological disorders characterized by prominent motor deficits (e.g., Parkinson's disease and Amyotrophic lateral sclerosis), as well as those for whom motor deficits are often less prominent (e.g., Alzheimer's disease, Frontotemporal Dementia, stroke). Research in these two groups of disorders is strikingly "siloed" and offers many contradictory findings with respect to whether action semantic representations are abstract (i.e., "disembodied") or grounded in sensory and motor features that reflect the way knowledge was acquired. Findings across these populations also disagree as to whether action semantic representations are organized somatotopically or with a semantic feature-based architecture, and mediated by anterior motor-related or relatively posterior sensory-related brain regions. Many of these disparate findings can be reconciled with consideration of a multidimensional, multimodal representational architecture mediated by a distributed left-lateralized network of brain regions. We provide suggestions for specific methodological approaches for research with neurological populations that may further our understanding of the format, organization, and neural substrates of action semantics.},
}

@article {pmid41411011,
year = {2025},
author = {Lawley, KS and Kang, TW and Rech, RR and Karmakar, M and Carroll, R and Perez Gomez, AA and Amstalden, K and Jones-Hall, Y and Threadgill, DW and Welsh, CJ and Young, CR and Brinkmeyer-Langford, C},
title = {The association between virus-induced spinal cord pathology and the genetic background of the host.},
journal = {Journal of neuropathology and experimental neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnen/nlaf127},
pmid = {41411011},
issn = {1554-6578},
support = {//National Institute for Neurological Disorders and Stroke (NINDS)/ ; R01 NS103934/NS/NINDS NIH HHS/United States ; 2P30 ES029067//National Institute for Environmental Health Sciences (NIEHS)/ ; DGE 1746932//National Science Foundation Graduate Research/ ; },
abstract = {Theiler's murine encephalomyelitis virus (TMEV) infection in mice has been used to study diverse neurological diseases, including multiple sclerosis and epilepsy. In this investigation, 5 strains of collaborative cross (CC) mice were infected with TMEV and examined clinically and histologically at days 4, 14, and 90 post-infection (dpi). All CC strains tested exhibited lumbar spinal cord and/or ventral peripheral nerve lesions by 14 dpi; CC027, CC023, and CC078 strains exhibited lesions at 4 dpi. At 90 dpi, lesions were remnants of the inflammatory responses associated with earlier infection; there was skeletal muscle atrophy in the CC023 strain. Increased microglial/macrophage reactivity was observed in all strains at 4 and 14 dpi, but not at 90 dpi. TMEV mRNA expression was greatest in the CC023 and CC078 strains at the acute timepoints; TMEV was completely cleared in all mice at 90 dpi. The neuropathological and clinical profiles in CC023 mice, mainly at 14 dpi, share some clinical and histologic features with those in amyotrophic lateral sclerosis patients. This work demonstrates how viral infection might interact with the genetic background of a susceptible individual to contribute to the onset, clinical presentation and persistence of lesions despite viral clearance.},
}

@article {pmid41409685,
year = {2025},
author = {Ran, X and Wuu, J and Qin, ZS and Cooper-Knock, J and Granit, V and Grignon, AL and Li, Y and Lin, E and Fernandez, MC and Colato, D and Carberry, N and Lill, CM and Piazza, P and Malaspina, A and Benatar, M},
title = {Predicting Phenoconversion to Clinically Manifest ALS: Results of a Large-Scale Proteomic Study.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41409685},
support = {R01 NS105479/NS/NINDS NIH HHS/United States ; U54 NS092091/NS/NINDS NIH HHS/United States ; },
abstract = {The study of pre-symptomatic amyotrophic lateral sclerosis (ALS) and the design of disease prevention trials are greatly hampered by our inability to predict which unaffected carriers of ALS-associated pathogenic variants will phenoconvert to clinically manifest disease, and when. In this longitudinal Olink Explore high-throughput proteomic study, 516 serially collected plasma samples from 33 phenoconverters, 35 patients with ALS, 10 pre-symptomatic pathogenic variant carriers and 59 controls were included. We identified 81 proteins whose concentrations changed prior to phenoconversion; characterized the longitudinal trajectory of these proteins; and identified a core panel of 19 proteins that, collectively, predicted phenoconversion over the 0.5- to 5-year time horizons (areas under curve 0.80-0.89) and yielded estimates of time-to-phenoconversion with a mean absolute error of 1.6 years. These findings were replicated in UK Biobank data, confirming pre-symptomatic increases in several proteins (e.g. NEFL, EDA2R, CA3) and that a multi-protein panel outperformed NEFL alone in estimating time-to-phenoconversion. This work sheds light on the biology of pre-symptomatic ALS. Moreover, our identification of a panel of novel susceptibility/risk biomarkers based on empirical longitudinal data furthers the ultimate goal of ALS prevention.},
}

@article {pmid41408351,
year = {2025},
author = {Ibragimov, U and Giordano, NA and Amaresh, S and Getz, T and Matuszewski, T and Steck, AR and Li, Y and Blum, EH and Tuttle, J and Pipalia, H and Cooper, HLF and Carpenter, JE},
title = {Implementation outcomes and strategies of a peer recovery coach program: findings from a qualitative assessment in the U.S. South, 2024-2025.},
journal = {Addiction science & clinical practice},
volume = {20},
number = {1},
pages = {95},
pmid = {41408351},
issn = {1940-0640},
support = {R01CE003509/ACL/ACL HHS/United States ; R01CE003509/CC/CDC HHS/United States ; },
mesh = {Humans ; *Peer Group ; *Substance-Related Disorders/rehabilitation/therapy ; Qualitative Research ; *Emergency Service, Hospital ; Male ; Female ; Georgia ; Adult ; Program Evaluation ; Middle Aged ; *Mentoring ; Interviews as Topic ; },
abstract = {INTRODUCTION: Successful implementation of peer recovery coach (PRC) programs may help improve linkage to services and clinical outcomes for emergency department (ED) patients with substance use disorder (SUD). However, literature on implementation outcomes and strategies of PRC programs is limited. We conducted a qualitative assessment of implementation outcomes and strategies for an ED-based PRC program in Atlanta, Georgia.

METHODS: We conducted qualitative interviews with 27 program participants (ED patients with SUD served by PRC program) and 29 service providers and partners (peer recovery coaches, ED physicians and staff, SUD treatment and other service providers) in October 2023 - March 2025. We transcribed audio-recordings and analyzed data using rapid qualitative analysis approach mapping emerging themes to Proctor's model of implementation outcomes and Leeman et al.'s implementation strategies framework.

RESULTS: We identified two major themes related to implementation outcomes: (1) PRC program acceptability (patients' positive interactions with PRCs) and (2) appropriateness (sub-themes include: successful linkage to community services; PRC program as an important resource for patients; added value of PRC team; no negative impact on ED workflow). Themes related to implementation strategies include (1) streamlined communication between PRC and ED teams (direct communication via electronic medical records system, single contact phone number, informing ED service providers of clinical and program outcomes), (2) addressing barriers to community-based services (preparing patient's medical documentation, insurance, transportation to community services); (3) supportive supervision of PRCs (addressing daily and long-term issues through regular meetings; limiting caseload; and providing orientation, on-job training and mental health support) and (4) addressing telehealth implementation challenges (ensuring access to electronic medical records system).

CONCLUSION: This study outlines key implementation outcomes and strategies for PRC programs, offering practical guidance for successful ED-based PRC program implementation.},
}

Humans
*Peer Group
*Substance-Related Disorders/rehabilitation/therapy
Qualitative Research
*Emergency Service, Hospital
Male
Female
Georgia
Adult
Program Evaluation
Middle Aged
*Mentoring
Interviews as Topic

@article {pmid41408263,
year = {2025},
author = {Doughty, J and Booth, J and Smith, M and Saini, K and Paisi, M and Rodriguez, A and Levine, A and Bedos, C and Muirhead, V and Martins de Barros, C and Freeborn, C},
title = {Unmasking oral health stigma: a qualitative scoping review.},
journal = {BMC oral health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12903-025-07329-9},
pmid = {41408263},
issn = {1472-6831},
abstract = {INTRODUCTION: Health-related stigma can limit access to care, impair adherence to treatment, and negatively impact mental health and quality-of-life. Oral health stigma, defined as stigma arising from oral conditions that diverge from sociocultural norms, operates through labelling, stereotyping, othering, and exclusion. Oral health stigma can lead to shame, diminished self-confidence, and avoidance of dental care, creating a self-perpetuating cycle of poor oral health and reinforcing internalised and anticipated stigma. While previous research has explored the social implications of oral appearance, little is known about the broader concept of oral health stigma or strategies to mitigate it.

METHODS: This scoping review adopted Levac et al.'s six-stage framework. The review utilised data from qualitative studies to explore lived experiences of oral health stigma and consider ways to mitigate it. Patient and public involvement (PPI) informed the development of the research question, search strategy, and interpretation of findings.

RESULTS: Seventy-two qualitative studies were included, comprising 2,455 participants. Themes included stigma associated with physical appearance and attractiveness, judgement, labelling, and stereotyping. Consequences included low self-esteem, social exclusion, impacts to care seeking behaviours, and efforts to conceal oral appearance. Participants highlighted the transformative value of dental care and described coping strategies to build resilience. Other proposed solutions included fostering social connection and implementing trauma-informed, non-judgemental dental care.

CONCLUSION: Oral health stigma has significant social and psychological consequences and impacts on care-seeking behaviours. Addressing it requires targeted interventions at multiple levels, including individual, community, professionals and wider system / policy.},
}

@article {pmid41407165,
year = {2025},
author = {Ghosh, N and Ghosh, J and Ghosh, S and Sinha, K and Sil, PC},
title = {Nutraceutical interventions for neuroprotection: a comprehensive review.},
journal = {Biochemical pharmacology},
volume = {245},
number = {},
pages = {117637},
doi = {10.1016/j.bcp.2025.117637},
pmid = {41407165},
issn = {1873-2968},
abstract = {Nutraceuticals, bioactive compounds derived from food sources, are emerging as promising agents for neuroprotection, particularly through their modulation of gut health. Unlike conventional single-molecule therapeutics that often target isolated pathways, nutraceuticals offer a multi-targeted approach by influencing the gut-brain axis, a bidirectional communication network linking the gut microbiota and the central nervous system. Key nutraceuticals such as probiotics, prebiotics, polyphenols, omega-3 fatty acids, and vitamins have been shown to beneficially alter microbiota composition, reduce intestinal inflammation, and strengthen gut barrier integrity. These changes can significantly influence brain function by modulating neurotransmitter activity and systemic immune responses. This review compares the holistic action of nutraceuticals with the more focused effects of single-molecules, particularly in the context of neurodegenerative diseases like Alzheimer's, Parkinson's, Huntington's Disease and Motor Neuron Diseases like amyotrophic lateral sclerosis. It discusses how nutraceuticals may mitigate key pathological features of these conditions-including neuroinflammation, oxidative stress, and mitochondrial dysfunction, through gut-mediated pathways. Despite their potential, challenges remain regarding the standardization of formulations, bioavailability, dosage optimization, and long-term safety. Further clinical research is needed to validate the efficacy of nutraceuticals as complementary or alternative strategies to traditional neuroprotective agents.},
}

@article {pmid41406788,
year = {2025},
author = {Vijayakumar, S and Schwaighofer, A and de Juan, A and Rocha de Oliveira, R and Mach-Aigner, A and Lendl, B and Ramer, G},
title = {Fusion of incomplete QCL-IR and ECD datasets using MCR-ALS to extend the viable concentration range for studying protein denaturation.},
journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy},
volume = {349},
number = {},
pages = {127340},
doi = {10.1016/j.saa.2025.127340},
pmid = {41406788},
issn = {1873-3557},
abstract = {While several techniques exist to study the secondary structure of proteins, mid-IR and electronic circular dichroism spectroscopy are complementary techniques that stand out for liquid measurements due to their non-destructive nature, broad applicability and ease of use. CD spectroscopy however is only used to measure low protein concentrations and suffers from signal interferences from common buffers. With advances in laser-technology, the achievable pathlengths used in IR-spectroscopy have increased with the use of external cavity quantum cascade lasers (EC-QCL) as light sources. This has not only enabled protein denaturation to be studied without aggregates clogging the measurement cell, as was the case with shorter pathlengths, but also expanded the concentration range that can be measured with the technique. Yet, the concentration range where both IR and CD measurements can be made has only a small overlap. In this study, the IR and CD spectra obtained during the thermal denaturation of α-chymotrpysin (α-CT) in the overlapping concentration range of the two spectroscopy techniques, between 10mgmL[-1] to 40mgmL[-1], are used to extract more information about the denaturation process of the protein and its concentration dependence. To this end, the protein denaturation spectra from both methods between 20°C to 80°C are fused and analyzed using multivariate curve resolution-alternating least squares (MCR-ALS), a bilinear unmixing technique that provides thermal profiles and pure fingerprints of the protein conformations involved in the denaturation process. However, in these measurements, a large and information-dense part of the CD spectra found at the lowest UV wavelengths cannot be used due to the saturated signal linked to high protein concentration levels. A modified version of MCR-ALS is hence introduced to overcome this issue, which allows all available information to be used without sacrificing the quality of the fit. The prowess of the adapted MCR-ALS technique as a tool for data fusion was demonstrated by not only providing a better fit than the individual models (CD and IR spectra analyzed separately), but also by aiding in squeezing out information about a third protein conformation that forms during the denaturation of α-CT.},
}

@article {pmid41406304,
year = {2025},
author = {Geva, M and Goldberg, YP and Leitner, ML and Cruz-Herranz, A and Hand, R and Chen, K and Gershoni Emek, N and Tan, AM and Paganoni, S and Berry, JD and Macklin, EA and Shefner, JM and Cudkowicz, ME and Hayden, MR},
title = {Pridopidine treatment in ALS: subgroup analyses from the HEALEY ALS Platform trial.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/21678421.2025.2597935},
pmid = {41406304},
issn = {2167-9223},
abstract = {Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with limited treatment options. Pridopidine, a selective sigma-1 receptor agonist, was evaluated in Regimen D of the HEALEY ALS Platform Trial. Although the primary endpoint (ALS Functional Rating Scale-Revised (ALSFRS-R) total score accounting for survival at 24 weeks) was not met, a predefined subgroup analysis suggested slowed disease progression in ALS patients with definite and early disease (<18 months from onset). This report presents an exploratory analysis that further investigates pridopidine in rapidly progressing participants with definite/probable ALS and early-disease, where treatment effects may be more pronounced. Methods: The randomized, double-blind, placebo-controlled phase 2 trial assigned participants to pridopidine 45 mg bid or placebo, and placebo patients were shared across four trial regimens. The primary outcome was ALSFRS-R total score, with secondary outcomes assessing respiratory, bulbar, and speech functions. Results: Of 163 participants randomized to Regimen D, 72 met subgroup criteria (pridopidine: n = 37; shared placebo: n = 35). At week 24, pridopidine slowed ALSFRS-R total score decline (32%; Δ2.90, p = 0.03) and slowed decline of ALSFRS-R respiratory function (62%; Δ1.20, p = 0.03) and dyspnea (88%; Δ0.85, p = 0.005). ALSFRS-R-Bulbar function stabilized, with articulation and speaking rate declines reduced by 93% (Δ0.43, p = 0.0007) and 70% (Δ0.43, p = 0.002), respectively. Pridopidine was well-tolerated, with a safety profile comparable to placebo. All p values are nominal. Conclusion: Post hoc subgroup analysis suggests therapeutic benefits of pridopidine in patients that had definite/probable ALS and with early-disease progression, supporting further evaluation in a Phase 3 trial.},
}

@article {pmid41405451,
year = {2025},
author = {Liampas, I and Kimiskidis, VK and Zouvelou, V and Veltsista, D and Moscholouri, A and Triantafyllou, E and Daponte, A and Xirou, S and Sterpi, AE and Salakou, S and Poulidou, V and Arnaoutoglou, M and Tsouris, Z and Ralli, S and Dardiotis, E and Papagiannopoulos, S and Zampetakis, A and Zaganas, Ι and Mitsias, P and Giannakis, A and Konitsiotis, S and Kefalas, F and Alexiou, E and Stoiloudis, P and Parissis, D and Kiamelidis, S and Terzoudi, A and Tsivgoulis, G and Rentzos, M and Chroni, E},
title = {Greek Registry for Amyotrophic Lateral Sclerosis (ALS-GR): An Observational Cohort of Individuals With ALS Across 11 Specialized Centers in Greece.},
journal = {European journal of neurology},
volume = {32},
number = {12},
pages = {e70403},
pmid = {41405451},
issn = {1468-1331},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/diagnosis/physiopathology/drug therapy/therapy ; Greece/epidemiology ; *Registries ; Male ; Middle Aged ; Female ; Aged ; Cohort Studies ; Disease Progression ; Adult ; Riluzole/therapeutic use ; },
abstract = {BACKGROUND: Epidemiological studies on amyotrophic lateral sclerosis (ALS) in Greece are scarce and outdated.

METHODS: We performed an observational cohort study in 11 specialized centres across Greece. Adult individuals with ALS diagnosed based on the Gold Coast criteria were recruited. Data were collected on socio-demographics, somatometrics, comorbidities, early life exposures, disease-related parameters, riluzole intake, motor and non-motor symptoms, as well as functional progression. Follow-up evaluations were scheduled on approximately 6-9-12-18-24 months. Our aim was to identify shortcomings in the monitoring of patients with ALS in specialized centers, delineate the course of the disease, and capture factors related to the earlier occurrence of ALS and potential diagnostic delays.

RESULTS: A total of 229 ALS patients were included in the present registry. The average age of diagnosis was 63.7 years, with an average 12.8-month interval between symptom onset and diagnosis. The presence of bulbar symptoms at onset was associated with shorter diagnostic delays. Systematic physical exercise was strongly linked to the earlier onset of symptoms. Disease progression was slower during the prediagnostic stage, more precipitous over the first year following diagnosis, and milder thereafter (~1-point monthly decline in ALSFRS-R on average, post-diagnosis). The majority of associated motor and non-motor symptoms accumulated over time. The overwhelming majority of patients were prescribed the liquid form of riluzole, which exhibited an excellent tolerability profile. Greek islands are probably the most underprivileged in terms of specialized monitoring of ALS cases.

CONCLUSIONS: The present observational cohort study mapped key aspects and shortcomings of ALS management in Greece.},
}

Humans
*Amyotrophic Lateral Sclerosis/epidemiology/diagnosis/physiopathology/drug therapy/therapy
Greece/epidemiology
*Registries
Male
Middle Aged
Female
Aged
Cohort Studies
Disease Progression
Adult
Riluzole/therapeutic use

@article {pmid41404692,
year = {2025},
author = {Żur-Wyrozumska, K},
title = {A case of an ALS patient with an SQSTM1 mutation - implications for the p62/NF-κB/Nrf2/autophagy pathways in the selection of individualised therapeutic strategies: a preliminary report.},
journal = {Folia medica Cracoviensia},
volume = {65},
number = {3},
pages = {173-183},
doi = {10.24425/fmc.2025.156692},
pmid = {41404692},
issn = {0015-5616},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/drug therapy ; *Sequestosome-1 Protein/genetics ; Middle Aged ; Female ; NF-E2-Related Factor 2/genetics/metabolism ; Autophagy/genetics ; NF-kappa B/genetics ; Mutation ; Signal Transduction ; },
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) represents a heterogeneous group of neurodegenerative disorders sharing a common ALS phenotype but arising from diverse genetic and molecular mechanisms. Among the genes implicated in ALS, SQSTM1, encoding the multifunctional protein p62, plays a pivotal role in maintaining neuronal homeostasis through the regulation of autophagy and the crosstalk between NF-κB and Nrf2 pathways. Disruption of these mechanisms contributes to oxidative stress, neuroinflammation, and protein aggregation in motor neurons.

MATERIAL AND METHODS: A comprehensive genetic analysis, including next-generation sequencing (NGS), whole-exome sequencing (WES), and multiplex ligation-dependent probe amplification (MLPA), was performed in a patient clinically diagnosed with ALS. Literature data regarding the role of SQSTM1, NF-κB/Nrf2 signaling, and autophagy modulation in ALS pathogenesis were reviewed to contextualize the findings.

CASE PRESENTATION: We describe a 49-year-old woman with a 12-month history of progressive - bulbar-onset ALS. Genetic testing revealed a heterozygous SQSTM1 c.1175C>T (p.Pro392Leu) variant inherited from her father, classified as likely pathogenic. The patient received dimethyl fumarate (Nrf2 activator), celecoxib (NF-κB inhibitor), and rapamycin (mTOR pathway modulator) as part of an individualized treatment strategy.

DISCUSSION: Mutations in SQSTM1 contribute to ALS pathogenesis through dysregulation of autophagy, impaired protein clearance, and excessive neuroinflammation mediated by NF-κB activation. The interplay between NF-κB and Nrf2 signaling pathways suggests that targeted therapeutic modulation may attenuate neurodegeneration. The patient's case illustrates the clinical and molecular heterogeneity of ALS and supports the concept of pathway-specific, precision medicine approaches.

CONCLUSIONS: This case highlights the relevance of SQSTM1-related pathogenic mechanisms within the heterogeneous ALS spectrum and underscores the importance of advanced genetic testing for identifying candidates for personalized therapy.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/drug therapy
*Sequestosome-1 Protein/genetics
Middle Aged
Female
NF-E2-Related Factor 2/genetics/metabolism
Autophagy/genetics
NF-kappa B/genetics
Mutation
Signal Transduction

@article {pmid41404604,
year = {2025},
author = {Jilani, SB and Ashok, N and Bomble, YJ and Guss, AM and Olson, DG},
title = {Engineering Clostridium thermocellum for production of 2,3-butanediol from cellulose.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.28.691234},
pmid = {41404604},
issn = {2692-8205},
abstract = {Clostridium thermocellum is a promising host for consolidated bioprocessing due to its ability to directly ferment cellulose into fuels and chemicals. However, natural product formation in this organism is limited. Here, we report engineering C. thermocellum for the production of 2,3-butanediol (23BD), a valuable industrial chemical. We functionally expressed a thermophilic 23BD pathway in this organism resulting in a 23BD titer of 19.7 mM from cellulose, representing a metabolic yield of 24%. We used a cell-free systems biology approach to identify limiting steps in the 23BD pathway, revealing that exogenous 23BD dehydrogenase (BDH) activity was essential for production, while native acetolactate synthase (ALS) and acetolactate decarboxylase (ALDC) activities were present but limiting in the parent strain. This approach also revealed redox balance limitations. We demonstrated that this improved understanding of redox balance limitations could be used to increase 23BD titer in vivo, showing that adding acetate could be used to increase 23BD yield. This work establishes a foundation for developing C. thermocellum into a robust platform for 23BD production directly from cellulose and highlights the utility of cell-free systems for guiding metabolic engineering in non-model organisms.},
}

@article {pmid41403635,
year = {2025},
author = {Li, CY and Xie, WX and You, HP and Hu, HR and Chen, ZY},
title = {A multi-stage genomic approach to uncover druggable gene targets and neural pathways in postpartum depression.},
journal = {Archives of medical science : AMS},
volume = {21},
number = {5},
pages = {2047-2057},
pmid = {41403635},
issn = {1734-1922},
abstract = {INTRODUCTION: Postpartum depression (PPD) is a severe emotional disorder affecting women worldwide, with significant impacts on maternal and infant health. Its genetic contributors and biological mechanisms are poorly understood. Identifying druggable genes and clarifying their causal roles may offer insights for developing more effective treatments.

MATERIAL AND METHODS: We identified drug-related genes and screened gene expression quantitative trait loci (eQTL) from the eQTLGen consortium and genotype tissue expression (GTEx) v8 dataset, focusing on 13 brain tissues, along with Qi et al.'s meta-study on the cerebral cortex. Mendelian randomization (MR) analyses were used to investigate causal relationships between gene expression and PPD risk. Replication analyses in an independent PPD cohort validated initial findings, and meta-analysis combined MR results. Summary-data-based MR (SMR) and heterogeneity in dependent instruments (HEIDI) tests were also performed, followed by colocalization analyses to assess shared causal variants. Mediation analyses were conducted to explore how genetic effects may influence brain connectivity patterns.

RESULTS: From 5,883 druggable genes, 37 showed potential causal links to PPD. Replication analyses confirmed 9 of these genes, with 4 remaining significant in meta-analysis. SMR and HEIDI analyses focused on CLCN7, which showed robust evidence for causal involvement in PPD. Colocalization analyses suggested shared causal variants, and mediation analyses revealed that CLCN7's genetic risk is partially mediated by left- to right-hemisphere visual network white-matter structural connectivity.

CONCLUSIONS: Our analysis identified CLCN7 as a potential causal factor in PPD, with its effect mediated through brain connectivity. These findings offer targets for future studies and therapeutic strategies for PPD.},
}

@article {pmid41403093,
year = {2025},
author = {Ghaderi, S and Mohammadi, S and Kalra, S},
title = {Hippocampal Subfield Integrity and Age-Driven Neural Correlates of Appetite Loss in Amyotrophic Lateral Sclerosis.},
journal = {Journal of magnetic resonance imaging : JMRI},
volume = {},
number = {},
pages = {},
doi = {10.1002/jmri.70206},
pmid = {41403093},
issn = {1522-2586},
abstract = {BACKGROUND: Appetite loss is a non-motor symptom in amyotrophic lateral sclerosis (ALS) linked to poorer prognosis. While the hippocampus regulates "meal memory", a key cognitive modulator of eating behavior, its structural role in ALS-related appetite loss is unknown.

PURPOSE: To determine if hippocampal subfield integrity influences appetite dysregulation in ALS and to evaluate the strength of neuroanatomical versus demographic factors.

STUDY TYPE: Cross-sectional secondary analysis.

POPULATION: Thirty-two patients with ALS (mean age: 58.97 ± 8.91 years; 24 males) and 22 non-neurodegenerative controls (NNDc) (mean age: 53.86 ± 9.98 years; 16 males).

FIELD STRENGTH/SEQUENCE: 3T; 3D T1-weighted magnetization-prepared rapid gradient-echo (MP2RAGE) and 3D T2-weighted turbo spin-echo (T2-SPACE) sequences.

ASSESSMENT: Appetite was measured using the Council on Nutrition Appetite Questionnaire (CNAQ). Hippocampal subfield volumes (CA1, CA2/3, CA4/DG, stratum radiatum/lacunosum/moleculare [SRLM], subiculum) and asymmetry indices were segmented from T1w and T2w images using the HIPS automated pipeline.

STATISTICAL TESTS: Analysis of Covariance (ANCOVA) (adjusting for age, sex, body mass index (BMI), total intracranial volume (TIV), and subfield volumes/asymmetry) and hierarchical multiple regression analyses were used. Significance was set at p < 0.05.

RESULTS: Patients with ALS (adjusted mean: 29.51 ± 0.53) had significantly lower adjusted CNAQ scores compared to controls (adjusted mean: 31.98 ± 0.66; mean difference: -2.47, partial η[2] = 0.195). In the ANCOVA model, left SRLM volume was the only significant neuroanatomical covariate (F [1, 30] = 6.45, partial η[2] = 0.177). However, hierarchical regression revealed that age was the only consistent independent predictor of CNAQ scores (B = -0.158), explaining the largest variance (ΔR[2] = 0.165). Hippocampal volumes and asymmetry did not remain significant predictors after adjusting for age (left SRLM: p = 0.853; SRLM asymmetry: p = 0.868).

DATA CONCLUSION: Appetite loss is a non-motor symptom in ALS. While associated with lower left SRLM volume at the group level, appetite decline is more robustly and independently associated with advancing age.

EVIDENCE LEVEL: 3.

TECHNICAL EFFICACY: 3.},
}

@article {pmid41402228,
year = {2025},
author = {Vovard, B and Faure-de Baets, J and Codron, P and Allain, P and Cassereau, J},
title = {Assessment of social cognition impairments in patients with amyotrophic lateral sclerosis: How can it be improved? A systematic review.},
journal = {Revue neurologique},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neurol.2025.11.003},
pmid = {41402228},
issn = {0035-3787},
abstract = {OBJECTIVES: The aim of this review was to evaluate the current evidence on which part of social cognition is impaired in amyotrophic lateral sclerosis (ALS) patients among emotion recognition, affective empathy and Theory of Mind (ToM) and to suggest improvements in social cognition testing protocols.

METHODS: A systematic review was conducted according to PRISMA guidelines. We included controlled cross-sectional or longitudinal studies published in English before September 1, 2024, that assessed social cognition in non-demented ALS patients. Searches were performed in Medline, Embase, Web of Science, and PsycINFO using specific MeSH terms. Studies using social cognition tests as a primary or secondary outcome were included.

RESULTS: Thirty-four studies were analyzed. Impairments in emotion recognition - especially for negative emotions - were frequently reported, even in cognitively preserved ALS patients. Results for cognitive ToM were mixed and may be confounded by executive dysfunction or test limitations. In contrast, affective ToM deficits were more consistently identified. However, no included study directly assessed affective empathy. Tests used in the reviewed studies were often overly specific and lacked ecological validity, which may explain inconsistent results across domains and weak correlations with imaging or executive function.

CONCLUSION: Social cognition is increasingly recognized as a key non-motor domain affected in ALS. However, current assessment tools may lack the sensitivity and ecological validity needed to capture real-life deficits. The implementation of dynamic, multimodal assessments such as real-life social interaction tests or tests like the Movie Assessment for Social Cognition (MASC) could improve detection and guide clinical interventions but remain to be validated for ALS patients.},
}

@article {pmid41401652,
year = {2025},
author = {Braverman, A and Frenkel, A and Schwarzfuchs, D and Jaffe, E and Bitan, Y},
title = {Verbal and visual information exchange in EMS-to-ED patient handovers: An observational and attitudinal study.},
journal = {International emergency nursing},
volume = {84},
number = {},
pages = {101735},
doi = {10.1016/j.ienj.2025.101735},
pmid = {41401652},
issn = {1878-013X},
abstract = {BACKGROUND: Although effective information exchange during emergency medical services (EMS)-to-emergency department (ED) patient handovers is critical for care continuity and patient safety, handover communication patterns and information gaps remain poorly characterized.

OBJECTIVE: To characterize verbal and visual information exchange patterns in EMS-to-ED handovers while comparing EMS and ED staff perceptions of handover quality.

METHODS: This was a dual-methods study conducted at a tertiary medical center in Israel (June-November 2024) in which 83 EMS-to-ED handovers [35 advanced life support (ALS), 48 basic life support (BLS)] were directly observed. We documented information elements, duration, and communication patterns via a structured checklist. In addition, an electronic survey (Qualtrics) of 103 participants (62 EMS, 41 ED staff) was used to assess perceptions with 6-point Likert scales. Statistical analyses utilized Mann-Whitney U tests, effect sizes (Cohen's d), and 95 % confidence intervals (CIs).

RESULTS: The handovers were dominated by verbal communication (97.6 %, 95 % CI: 91.6-99.3 %) of brief duration [ALS: Median = 40 s, interquartile range (IQR) 35-45; BLS: Median = 25 s, IQR 25-35]. Significant information gaps included: pre-hospital treatment details, which were absent in 36.1 % of the handovers (95 % CI: 26.6-46.9 %), allergy details in 55.4 %, and demographic details in 61.4 %. The ALS teams provided more complete information than did BLS teams (treatment: 94 % vs. 46 %, p < 0.001; allergies: 60 % vs. 33 %, p = 0.02). EMS documentation was available in only 7.2 % of handovers (95 % CI: 3.4-14.9 %). Patient background documents were valued more by ED staff than by EMS personnel (Median = 4.84 vs. 3.44, p < 0.001, d = 0.98), and they reported higher confidence in using received information (Median = 4.12 vs. 3.15, p < 0.001, d = 0.78).

CONCLUSIONS: Because EMS-to-ED handovers rely almost exclusively on brief verbal communication, they are vulnerable to information loss. Critical safety-relevant information (allergies, medications) is frequently omitted, with BLS teams showing greater gaps than ALS teams. Structured handover protocols may improve information completeness and continuity of care by incorporating digital tools to complement verbal communication.},
}

@article {pmid41401197,
year = {2025},
author = {Yang, L and Liu, T and Li, HG and Wang, G and Deng, S},
title = {Functional divergence of ALMTs mediates organic acid transport and callose synthesis for aluminum tolerance in rose myrtle.},
journal = {Plant physiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/plphys/kiaf655},
pmid = {41401197},
issn = {1532-2548},
abstract = {Ionic aluminum (Al) forms in acidic soils and inhibits plant growth, even at low concentrations. Rose myrtle (Rhodomyrtus tomentosa), a shrub native to tropical and subtropical regions, thrives in acidic-Al soils. Here, we found that mild concentrations of Al promote rose myrtle growth. Transcriptomic disturbances induced by low or high Al stress were predominantly non-overlapping in the species. Mild Al stress (0.1 mM Al3+) enhanced rose myrtle root elongation through the upregulation of xyloglucan metabolism, nutrient uptake and utilization, and auxin transport. In contrast, high Al stress (1 mM Al3+) activated detoxification pathways, including the secretion of organic acid and glutathione metabolism. Members of the aluminum-activated malate transporter (ALMT) family, particularly the conserved RtALMT11 and variable RtALMT18, play a pivotal role in Al tolerance. Heterologous expression of RtALMT11 and RtALMT18 complemented the Al-sensitive phenotype of almt1-KO Arabidopsis (Arabidopsis thaliana). High Al3+ induced the expression of RtALMT11, mediating the synthesis of callose, which may serve as a physical barrier to mitigate Al penetration and facilitate vacuolar Al sequestration. RtALMT18 pre-emptively regulated internal defense in the stele independently of aluminum load, while also functioning as a proton/malate transporter. Beyond enhancing Al tolerance, RtALMT18 promoted the growth of transgenic Arabidopsis and poplar (Populus alba×P. glandulosa, "84K"). The functional divergence within the ALMT family reveals distinct roles in promoting the growth of rose myrtle under low Al conditions and during the high-Al detoxification process. These findings uncover Al's dual role as both a growth promoter and stress inducer, offering insights for developing Al-tolerant crops and rehabilitating acidic soils.},
}

@article {pmid41400574,
year = {2025},
author = {Huang, S and Li, A and Ling, Y and Yang, X and Wang, J and Yuan, J and Qin, D and Yao, X},
title = {Pharmacological Activation of Mitophagy Confers Neuroprotective Benefits for Amyotrophic Lateral Sclerosis.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2025.1224},
pmid = {41400574},
issn = {2152-5250},
abstract = {Amyotrophic lateral sclerosis (ALS) is a rare and devastating neurodegenerative disease characterized by the progressive degeneration of motor neurons in the brain and spinal cord, for which no cure currently exists. Previous studies have shown that abnormal mitochondrial homeostasis and defective mitophagy occur in neurodegenerative diseases, including ALS. Here, we provide evidence that PINK1-Parkin-dependent mitophagy is impaired in multiple ALS mouse models, including the SOD1[G93A], TDP43[A315T], and rNLS8 strains, leading to the accumulation of damaged mitochondria in affected motor neurons. These findings suggest that mitophagy may be a druggable target for ALS treatment. A classical mitophagy agonist, urolithin A (UA) was used in this study. UA-induced mitophagy antagonizes ALS pathologies in the ALS SOD1[G93A] transgenic C. elegans model in a pink-1 (PTEN-induced kinase 1)- and pdr-1 (Parkinson's disease-related 1)-dependent manner. Furthermore, pharmacological activation of mitophagy by UA improves locomotor behavior, delays motor neuron degeneration and reduces neuroinflammation in ALS SOD1[G93A] transgenic mice. In conclusion, our results establish impaired mitophagy as a hallmark of ALS motor neuron degeneration and demonstrate that its pharmacological activation offers a neuroprotective strategy with therapeutic potential.},
}

@article {pmid41400569,
year = {2025},
author = {Vacchiano, V and Cherici, A and Criante, MS and Mengoli, E and Fonti, C and Bonan, L and de Pasqua, S and Donadio, V and Giannoccaro, MP and Rizzo, G and Quarta, CC and Marzocchi, E and Taggi, F and Liguori, R and , },
title = {Cognitive and behavioral impairment may influence shared care planning and treatment decisions in amyotrophic lateral sclerosis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/21678421.2025.2597937},
pmid = {41400569},
issn = {2167-9223},
abstract = {Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting motor neurons, often accompanied by cognitive and/or behavioral impairments. Shared Care Planning (SCP) involves a collaborative decision-making process, playing a key role in aligning medical treatments with patient values. This study aimed to investigate potential associations between neuropsychological impairment and treatment decisions in ALS patients. Methods: We included 118 ALS patients who had completed at least the cognitive section of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). As part of routine clinical practice, patients were invited to participate in Shared Care Planning (SCP) discussions regarding key medical interventions, namely noninvasive ventilation (NIV), artificial nutrition via PEG/RIG, and tracheostomy. Results: SCP discussions were initiated with 78% of patients. NIV was accepted by 96% of patients, PEG/RIG by 63.9% and tracheostomy by 17.8%. Patients who accepted PEG/RIG were more frequently female (p = 0.047) and had significantly lower adjusted scores on the total ECAS (p = 0.027), ALS-specific domains (p = 0.020), verbal fluency (p = 0.012), and semantic fluency (p = 0.042), compared to those who refused PEG/RIG. Acceptance of tracheostomy was more common among younger patients (p < 0.001) and those with cognitive or behavioral impairments (p = 0.014). Binary logistic regression analysis, using tracheostomy acceptance as the dependent variable and age, sex, and Strong's diagnostic categories as independent variables, revealed a significant association with age (p = 0.002) and with certain Strong's categories, particularly ALS with combined cognitive and behavioral impairment (ALS-CBI) (p = 0.031). Conclusions: Cognitive and behavioral impairment appeared to increase the likelihood of consenting to invasive treatments in ALS patients.},
}

@article {pmid41399798,
year = {2025},
author = {Ghosh, S and Debnath, I and Bhunia, S and Nandi, S and Ashique, S and Nayak, A and Mallick, S and Basak, S},
title = {Decoding natural products for neuroprotection: Pathway networks and structural insights for drug development.},
journal = {Chinese herbal medicines},
volume = {17},
number = {4},
pages = {643-672},
pmid = {41399798},
issn = {2589-3610},
abstract = {Neurodegenerative diseases (NDs), including Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis, are progressive disorders marked by neuronal dysfunction and death, driven by pathological mechanisms such as oxidative stress, mitochondrial dysfunction, neuroinflammation, apoptosis, and protein misfolding. Despite scientific advances, current treatments remain largely palliative, underscoring the need for multitargeted therapeutic strategies. This narrative review synthesizes preclinical and clinical evidence to explore the neuroprotective potential of natural products, with a focus on their ability to modulate key molecular pathways implicated in NDs. A comprehensive literature search across Scopus, ScienceDirect, PubMed, MDPI, and Web of Science identified relevant studies. Bioactive compounds such as curcumin, resveratrol, ginsenosides, quercetin, and marine-derived molecules like fucoxanthin and phlorotannin demonstrated antioxidant, anti-inflammatory, anti-amyloidogenic, and mitochondrial-protective effects by modulating pathways including PI3K/Akt, NF-κB, and Nrf2/ARE, thereby mitigating neuronal damage and promoting cell survival. Natural products from diverse sources, including honey, ginseng, marine macroalgae, and cyanobacteria, exhibited broad-spectrum neuroprotective properties, with advances in nano-formulations improving bioavailability and brain penetration. Furthermore, emerging approaches such as gene-drug interaction studies and scaffold-based drug design offer promising avenues for enhancing clinical translation. While natural products provide a holistic, multitargeted approach to combat NDs, challenges related to bioavailability and therapeutic translation persist, necessitating future research that integrates advanced drug delivery systems, precision medicine, and synthetic modifications to develop innovative and effective treatment paradigms.},
}

@article {pmid41399686,
year = {2026},
author = {Riyapan, S and Chokvanich, W and Chakorn, T and Somboonkul, B and Chantanakomes, J and Phinyo, N and Konwitthayasin, P and Buangam, K and Saengsung, P},
title = {Implementation of high-performance CPR by basic life support (BLS) personnel: a pilot study in Thailand.},
journal = {Resuscitation plus},
volume = {27},
number = {},
pages = {101164},
pmid = {41399686},
issn = {2666-5204},
abstract = {BACKGROUND: High-performance cardiopulmonary resuscitation (HP-CPR) is a structured, pit-crew-style resuscitation model that has been shown to improve performance in advanced life support (ALS) systems. However, its applicability in volunteer-based basic life support (BLS) settings remains uncertain. This study aimed to describe the implementation of HP-CPR training for BLS personnel in Bangkok, Thailand, and to evaluate its impact on BLS performance using video-based process indicators, as well as to report patient- and system-level characteristics before and after the intervention.

METHODS: We conducted a single-centre, before-and-after study of adults with non-traumatic out-of-hospital cardiac arrest (OHCA) managed by the Siriraj EMS Centre between July 2022 and January 2025. HP-CPR training for BLS personnel was delivered over a fivemonth period. The primary outcome was BLS performance, assessed through predefined process indicators using video review. Secondary outcomes included system-level characteristics and clinical outcomes.

RESULTS: Of 423 patients screened, 214 met the inclusion criteria (110 pre-intervention; 104 post-intervention). Video recordings were available for 39 cases. Post-training, significant improvements were observed in two performance indicators: "counting during CPR" (0.0 % vs. 66.7 %, p < 0.01) and the "hover technique" (0.0 % vs. 62.5 %, p < 0.01). Other indicators, including uninterrupted CPR, assisted ventilation, AED use, and data handover, improved but did not reach statistical significance. Secondary outcomes-including AED use, CPR initiation by BLS, prehospital return of spontaneous circulation (ROSC), and survival outcomes-showed no significant differences between phases.

CONCLUSION: Following HP-CPR training, improvements were observed in selected BLS process indicators. However, further research is needed with larger sample sizes to assess the long-term impact of HP-CPR training in volunteer-based EMS systems.},
}

@article {pmid41399419,
year = {2025},
author = {Chen, HW},
title = {Axial Spinal Traction as a Potential Modulator of Cerebrospinal and Glymphatic Circulation in Neurodegenerative Diseases: A Technical Report and Biomechanical Hypothesis.},
journal = {Cureus},
volume = {17},
number = {12},
pages = {e99153},
pmid = {41399419},
issn = {2168-8184},
abstract = {Impairment of glymphatic function contributes to the accumulation of metabolic and proteinaceous waste products implicated in neurodegenerative diseases such as Alzheimer's disease, frontotemporal dementia, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and certain spinocerebellar ataxias. Pelvis-stabilized axial spinal traction (PSAST) is a biomechanical technique designed to produce brief, controlled cranio-caudal elongation of the vertebral column and spinal dural sac, potentially generating transient pressure gradients capable of influencing cerebrospinal fluid (CSF) dynamics and glymphatic circulation. The technique has been applied in the author's musculoskeletal practice for more than eight years without observed persistent or treatment-related adverse effects, although such practice-based experience does not constitute a formal safety evaluation. Improved sleep quality has been the most consistently reported patient-perceived response to PSAST, a clinically notable observation given the dependence of glymphatic function on consolidated slow-wave sleep. These practice-based observations provide preliminary, hypothesis-generating support for exploring whether controlled axial elongation may modulate cerebrospinal and glymphatic physiology. To the best of the author's knowledge, this report presents the first peer-reviewed technical description of a reproducible, whole-axis axial spinal traction procedure with defined force parameters intended to examine potential modulation of CSF and glymphatic circulation. The report outlines the PSAST protocol and its biomechanical rationale and safety considerations and proposes its potential relevance as a noninvasive, investigational approach for conditions associated with impaired glymphatic function.},
}

@article {pmid41399314,
year = {2025},
author = {Chung, WKV and Chan, KP and Hsu, DY and Ma, YKS and Chan, LYE and Ng, SH and Chow, SLE and Hong, YF and Chan, YHJ and Ma, YK and Lee, S and Lui, WCJ and Cheng, HWB},
title = {A 10-year service evaluation of a multidisciplinary neuro-palliative care model in motor neuron disease: Impact on palliative care service delivery & advance care planning.},
journal = {Palliative medicine},
volume = {},
number = {},
pages = {2692163251396020},
doi = {10.1177/02692163251396020},
pmid = {41399314},
issn = {1477-030X},
abstract = {BACKGROUND: Multidisciplinary neuro-palliative care has been increasingly recommended for the management of patients with motor neuron disease. While international guidelines have highlighted the importance of early palliative care referral, the best model of practice has not been well-defined.

AIM: The objective of this study is to evaluate the outcomes of a structured multidisciplinary neuro-palliative care model developed in regional hospitals in Hong Kong.

DESIGN: A 10-year retrospective chart review.

SETTING/PARTICIPANTS: Adult motor neuron disease patients under care of three regional hospitals in Hong Kong. Data of patients under the care of multidisciplinary neuro-palliative care taskforce and those who were not were analyzed.

RESULTS: There were 140 motor neuron disease patients included in study. Patients in multidisciplinary neuro-palliative care group received more healthcare intervention and palliative care services, including occupational therapist (92.86% vs 78.57%, p = 0.021), dietician (67.35% vs 42.86%, p = 0.007) and speech therapist (96.94% vs 76.19%, p = 0.000) services, community support by non-governmental organizations (74.49% vs 19.05%, p = 0.000) and formal bereavement support (78.26% vs 17.07%, p = 0.000). Significantly more patients in multidisciplinary neuro-palliative care group had completed Advance Medical Directives (46.94% vs 4.76%, p = 0.000). Patients under multidisciplinary care had longer survival compared to those who were not (HR 0.539, 95% CI 0.372-0.782, p = 0.001). This remains significant after adjusting for factors affecting survival in multivariate analysis.

CONCLUSIONS: Multidisciplinary neuro-palliative care demonstrated benefits in motor neuron disease patients in terms of better care coordination and service delivery, higher rate of Advance Medical Directive completion, with possible better survival observed. Future prospective studies are warranted to assess the impact on patient-centered outcomes.},
}

@article {pmid41399249,
year = {2025},
author = {Dellarole, IL and Aprea, V and Catania, M and Battipaglia, C and Romeo, A and Villa, C and Burato, A and Celauro, L and Bella, ED and Riva, N and Salvi, E and Rossi, G and Fede, GD and Legname, G and De Houwer, JFH and Alberici, A and Borroni, B and Seelaar, H and van Swieten, JC and Moda, F and Caroppo, P},
title = {Detection of TDP-43 seeds in CSF of presymptomatic and symptomatic genetic FTD/ALS.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {12},
pages = {e70989},
pmid = {41399249},
issn = {1552-5279},
support = {PNRR-MCNT2-2023-12377336//Ministero della Salute/ ; 2021-650-104//JPND/ ; },
mesh = {Humans ; *DNA-Binding Proteins/cerebrospinal fluid/genetics ; *Frontotemporal Dementia/genetics/cerebrospinal fluid/diagnosis ; Male ; Female ; Middle Aged ; C9orf72 Protein/genetics ; *Amyotrophic Lateral Sclerosis/genetics/cerebrospinal fluid/diagnosis ; Progranulins/genetics ; Mutation/genetics ; Aged ; tau Proteins/genetics/cerebrospinal fluid ; Adult ; Biomarkers/cerebrospinal fluid ; Neurofilament Proteins/cerebrospinal fluid/genetics ; },
abstract = {INTRODUCTION: Seed amplification assays (SAAs) have shown promising results in detecting misfolded transactive response (TAR) DNA-binding protein 43 (TDP-43) in cerebrospinal fluid (CSF) of genetic frontotemporal dementia (FTD). To date, the use of SAA has yet to be evaluated in presymptomatic individuals.

METHODS: Thirty patients carrying GRN or C9orf72 mutations, 2 microtubule-associated protein tau (MAPT) carriers, 14 presymptomatic subjects, and 27 controls underwent CSF collection. We used SAA for detecting misfolded TDP-43 (TDP-43_SAA) and single molecule array (SIMOA) technology for neurofilament light chain (NfL) dosage.

RESULTS: TDP-43 seeding activity was detected in 67% of TDP-43-linked symptomatic patients, with a specificity of 93%. Almost half of presymptomatic subjects tested positive, mostly GRN carriers. Interestingly, among TDP-43_SAA positive presymptomatic individuals, two GRN carriers underwent phenoconversion.

DISCUSSION: TDP-43_SAA can also detect misfolded TDP-43 in the CSF of presymptomatic individuals. A possible link exists between positive TDP-43_SAA and conversion to the symptomatic phase.

HIGHLIGHTS: Seed amplification assay of transactive response (TAR) DNA-binding protein 43 (TDP-43_SAA) can detect misfolded TDP-43 in the cerebrospinal fluid (CSF) of patients with genetic frontotemporal dementia (FTD), linked to GRN and C9orf72 mutations. TDP-43_SAA can detect misfolded TDP-43 also in the CSF of presymptomatic individuals. In both groups, most TDP-43_SAA positive cases were carriers of GRN mutation. Two GRN carriers that resulted TDP-43_SAA positive converted to the symptomatic phase of the disease.},
}

Humans
*DNA-Binding Proteins/cerebrospinal fluid/genetics
*Frontotemporal Dementia/genetics/cerebrospinal fluid/diagnosis
Male
Female
Middle Aged
C9orf72 Protein/genetics
*Amyotrophic Lateral Sclerosis/genetics/cerebrospinal fluid/diagnosis
Progranulins/genetics
Mutation/genetics
Aged
tau Proteins/genetics/cerebrospinal fluid
Adult
Biomarkers/cerebrospinal fluid
Neurofilament Proteins/cerebrospinal fluid/genetics

@article {pmid41398973,
year = {2025},
author = {Veh, A and Ewald, M and da Cruz Neris Geßner, V and Giridhar, NJ and Hutchings, AJ and Stigloher, C and Binotti, B and Heinze, KG and Lüningschrör, P},
title = {Age-dependent removal of Atg9-containing vesicle accumulations in motoneuron disease models by physical exercise.},
journal = {Translational neurodegeneration},
volume = {14},
number = {1},
pages = {69},
pmid = {41398973},
issn = {2047-9158},
support = {DFG LU 2347/3-1//Deutsche Forschungsgemeinschaft/ ; 218894163//Deutsche Forschungsgemeinschaft/ ; F-N-439//Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburg/ ; Z-12 to KGH//Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburg/ ; },
mesh = {Animals ; *Physical Conditioning, Animal/physiology ; Mice ; Disease Models, Animal ; *Synaptic Vesicles/metabolism/pathology ; *Motor Neuron Disease/metabolism/pathology ; Autophagy/physiology ; *Autophagy-Related Proteins/metabolism ; Motor Neurons/metabolism ; Neuromuscular Junction/metabolism/pathology ; Mice, Knockout ; Mice, Transgenic ; Mice, Inbred C57BL ; },
abstract = {BACKGROUND: Atg9-containing vesicles are enriched in synapses and undergo cycles of exo- and endocytosis similarly to synaptic vesicles, thereby linking presynaptic autophagy to neuronal activity. Dysfunction of presynaptic autophagy is a pathophysiological mechanism in motoneuron disease (MND), which leads to impaired synaptic integrity and function. Here, we asked whether boosting neuronal activity by physical exercise modulates the cellular and motor phenotypes of Plekhg5-deficient mice, an MND model with defective presynaptic autophagy.

METHODS: To characterize the vesicle accumulations in Plekhg5-deficient mice, we performed immunohistochemical staining, electron microscopy, and super-resolution imaging. Following voluntary running wheel exercise, we quantified the histopathological changes within the spinal cord and at neuromuscular junctions using an unbiased machine-learning approach. Additionally, we analyzed the motor performance of the animals by measuring their grip strength. To assess changes in the autophagic flux upon physical exercise in vivo, we utilized mRFP-GFP-LC3 expressing mice. The presence of Atg9-containing vesicle clusters in SOD1[G93A] was analyzed to examine the relevance of this pathological feature in a second MND model.

RESULTS: We found marked accumulations of Atg9-containing vesicles at presynaptic sites of Plekhg5-deficient mice, which could be cleared by four weeks of voluntary running wheel exercise in young but surprisingly not in aged Plekhg5-deficient mice. However, physical exercise in aged mice led to synaptic vesicle sorting into the Atg9-containing vesicle accumulations without their removal. In line with these findings, short-term voluntary exercise triggered motoneuron autophagy in young but not old mice. Pointing to a broader role of Atg9-containing vesicles in the pathophysiology of MND, we also found Atg9-containing vesicle accumulations in SOD1[G93A] mice, a well-established ALS model. Strikingly, physical exercise in presymptomatic SOD1[G93A] mice resulted in a reduction of the vesicle accumulations.

CONCLUSIONS: Our data highlight the essential role of Atg9 in presynaptic autophagy and suggest that boosting autophagy by physical exercise provides a tool to maintain presynaptic function at the early but not late stages of Plekhg5-associated MND and possibly amyotrophic lateral sclerosis.},
}

Animals
*Physical Conditioning, Animal/physiology
Mice
Disease Models, Animal
*Synaptic Vesicles/metabolism/pathology
*Motor Neuron Disease/metabolism/pathology
Autophagy/physiology
*Autophagy-Related Proteins/metabolism
Motor Neurons/metabolism
Neuromuscular Junction/metabolism/pathology
Mice, Knockout
Mice, Transgenic
Mice, Inbred C57BL

@article {pmid41398684,
year = {2025},
author = {Fuad, NA and Pitros, P and Brown, G and Besi, E},
title = {Will L-PRF Be the Future of Endodontic Microsurgery? A Series of Case Reports.},
journal = {Clinical and experimental dental research},
volume = {11},
number = {6},
pages = {e70198},
pmid = {41398684},
issn = {2057-4347},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Humans ; *Microsurgery/methods ; Periapical Tissue/surgery ; Root Canal Therapy/methods ; Treatment Outcome ; Wound Healing ; },
abstract = {OBJECTIVES: This case series aimed to evaluate the healing potential of apical tissues with large periapical radiolucencies (> 10 mm) after apical microsurgery with L-PRF. The secondary objectives were to evaluate L-PRF's benefits and adverse effects as well as to aid in the development of a clinical protocol.

MATERIALS AND METHODS: This case series was conducted in accordance with the Preferred Reporting Items for Case Reports in Endodontics (PRICE) 2020 guidelines. Thirteen patients with persistent endodontic infections, unresponsive to nonsurgical root canal treatment/retreatment, were treated at the Restorative and Oral Surgery Departments with endodontic microsurgery. L-PRF preparation followed Choukroun et al. (2001) and the L-PRF 2018 guidelines under the supervision of an experienced consultant. Postoperative follow-up included a phone call at 24 h to assess pain, swelling, and daily functions. Sutures were removed at 7 days, and a 6-month clinical and radiographic review was conducted. The clinical assessment included patient-reported symptoms and extraoral and intraoral examinations. Periapical radiographs were assessed for periapical healing based on Rud et al.'s (1972) radiographic criteria. Radiographs were reviewed by one clinician under standardized conditions.

RESULTS: Histopathological analyses identified 76.9% (n = 10) radicular cysts and 23.0% (n = 3) periapical granulomas from the 13 cases. At the 6-month review, 76.9% (n = 10) showed incomplete healing, 15.4% (n = 2) demonstrated complete healing, and 7.7% (n = 1) had incomplete healing at 4 months. All patients remained asymptomatic with no reported complaints. Radiographic assessments showed a significant reduction in the size of periapical radiolucency in all cases. At 24 h, 69.2% (n = 9) reported no pain, while mild pain was noted in 15.4% (n = 2). Swelling was observed in 69.2% (n = 9) and absent in 15.4% (n = 2), with missing records for 15.4% (n = 2).

CONCLUSION: L-PRF appears beneficial in endodontic microsurgery. However, larger, low-bias studies with extended follow-up periods are needed for definitive conclusions on its application.},
}

Humans
*Microsurgery/methods
Periapical Tissue/surgery
Root Canal Therapy/methods
Treatment Outcome
Wound Healing

@article {pmid41398488,
year = {2025},
author = {Seabrooke, T and Modirrousta-Galian, A and Higham, PA},
title = {Re-examining the bad news game: No evidence of improved discrimination of Indian true and fake news headlines.},
journal = {Psychonomic bulletin & review},
volume = {33},
number = {1},
pages = {13},
pmid = {41398488},
issn = {1531-5320},
mesh = {Humans ; *Deception ; India ; Adult ; *Truth Disclosure ; Male ; Female ; Young Adult ; *Discrimination, Psychological ; *Communication ; },
abstract = {Gamified inoculation interventions such as the Bad News game are a widely adopted approach to mitigating the influence of misinformation. While Bad News has been predominately studied with participants from Western, Educated, Industrialized, and Rich Democracies (WEIRD), one recent study (Iyengar et al., Applied Cognitive Psychology, 37:290-303, 2023) assessed its efficacy in an Indian sample. In that study, participants rated the reliability of a series of Indian news headlines in a pre-test, played Bad News, and completed a post-test with a different set of headlines. Participants showed better discrimination of true and fake headlines in the post-test than the pre-test. This finding contrasts with a meta-analysis showing that Bad News primarily produces a conservative response bias rather than improving discrimination (Modirrousta-Galian and Higham, Journal of Experimental Psychology: General, 152:2411-2437, 2023). The current preregistered study used the same design as Iyengar et al., although participants of Indian nationality (N = 150) were recruited via Prolific and the allocation of news headlines to the pre-test and post-test was counterbalanced. When both counterbalancing conditions were included, no significant differences in discrimination or response bias appeared between the pre-test and post-test. When only the counterbalancing condition matching Iyengar et al.'s experiment was examined, no significant effect on discrimination was observed, but a conservative response bias shift was seen in the post-test. This finding suggests that the Bad News game may be less effective for improving discrimination than previously thought - an important consideration given its popularity as an intervention to combat misinformation.},
}

Humans
*Deception
India
Adult
*Truth Disclosure
Male
Female
Young Adult
*Discrimination, Psychological
*Communication

@article {pmid41398473,
year = {2025},
author = {Moffatt, C and Arora, A and Vaeth, KF and Guzman, BB and Bhardwaj, G and Hoelscher, A and Gifford, LB and Russ, HA and Dominguez, D and Taliaferro, JM},
title = {TDP-43 directly inhibits mRNA accumulation in neurites through modulation of mRNA stability.},
journal = {The EMBO journal},
volume = {},
number = {},
pages = {},
pmid = {41398473},
issn = {1460-2075},
support = {R01NS122911//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R35GM133385//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R35GM142864//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; F31GM151819//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; F31GM155957//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; T32GM136444//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; },
abstract = {The subcellular localization of many mRNAs to neuronal projections allows neurons to efficiently and rapidly react to spatially restricted external cues. However, for most of these RNAs, the mechanisms that govern their localization are unknown. Here, using subcellular fractionation and single-molecule RNA FISH, we found that loss of TDP-43 results in increased accumulation of hundreds of mRNAs in neurites. Using high-throughput functional assays in cells and high-throughput binding assays in vitro, we subsequently identified specific regions within these mRNAs that mediate their TDP-43-dependent localization and interaction with TDP-43. We found that the same regions also mediated TDP-43-dependent mRNA instability, suggesting a mechanism by which TDP-43 regulates mRNA localization. ALS-associated mutations in TDP-43 resulted in similar mRNA mislocalization phenotypes as did TDP-43 loss in mouse dorsal root ganglia and human iPS-derived motor neurons. These findings establish TDP-43 as a direct negative regulator of mRNA abundance in neurites and suggest that mislocalization of specific transcripts may occur in ALS patients.},
}