@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},
doi = {10.1136/bmjopen-2025-102624},
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 = {},
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 = {},
doi = {10.64898/2025.12.06.25341403},
pmid = {41409685},
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/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 = {},
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},
doi = {10.1111/ene.70403},
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},
doi = {10.1002/alz.70989},
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},
doi = {10.1002/cre2.70198},
pmid = {41398684},
issn = {2057-4347},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Humans ; *Microsurgery/methods ; Male ; Female ; Middle Aged ; Adult ; Wound Healing ; Treatment Outcome ; Root Canal Therapy/methods ; Periapical Tissue/surgery ; Aged ; },
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
Male
Female
Middle Aged
Adult
Wound Healing
Treatment Outcome
Root Canal Therapy/methods
Periapical Tissue/surgery
Aged

@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.},
}

@article {pmid41392206,
year = {2025},
author = {Wang, W and Wen, C},
title = {Determining MCID threshold for Knee Society Score to assess patient satisfaction in knee arthroplasty.},
journal = {NPJ digital medicine},
volume = {8},
number = {1},
pages = {757},
pmid = {41392206},
issn = {2398-6352},
abstract = {This Matters Arising questions the MCID threshold for the Knee Society Score in Xiaodi Liu et al.’s study, noting that it represents an excessively large proportion of the total score and may not accurately capture the minimal meaningful change perceived by patients. We suggest adopting MCID thresholds defined by Wu et al. or Alejandro et al., derived from patient-reported satisfaction and supported by robust sample sizes.},
}

@article {pmid41398118,
year = {2025},
author = {Dunlop, RA and Cox, PA and Mehta, P and Stommel, EW and Banack, SA},
title = {miRNA Biomarkers Diagnose Amyotrophic Lateral Sclerosis in Circulating Blood.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {298},
pmid = {41398118},
issn = {1559-1182},
mesh = {*Amyotrophic Lateral Sclerosis/blood/diagnosis/genetics ; Humans ; Biomarkers/blood ; Female ; Middle Aged ; Male ; *MicroRNAs/blood/genetics ; Aged ; Adult ; Area Under Curve ; Sensitivity and Specificity ; },
abstract = {A rapid, accurate diagnostic test for amyotrophic lateral sclerosis (ALS) would reduce diagnostic delays and improve patient outcomes. We extracted eight circulating miRNAs from 788 blood plasma samples and analyzed them using qPCR for ALS diagnostic accuracy. The biomarker parameters were established previously using 449 individual blood samples and applied prospectively to an independent cohort for validation of a predictive model. The primary outcome was ALS classification accuracy as measured by diagnostic sensitivity, specificity, positive and negative predictive values (PPV, NPV), and area under the curve (AUC). The secondary outcome was comparative fold-regulation values determined prior to data collection. The diagnostic test had an AUC of 0.98 (95% CI 0.97-0.99), with 97% sensitivity (95% CI 96-98), 93% specificity (95% CI 90-96), 93% PPV (95% CI 91-96), and 97% NPV (95% CI 96-98). The fold-regulation values exceeded or were equal to prior calculated values. Streamlined methods resulted in higher diagnostic accuracy, cut both assay time and cost, reduced technical barriers, and enhances the feasibility for widespread clinical adoption. The high accuracy of this diagnostic biomarker suggests that continued evaluation is warranted.},
}

*Amyotrophic Lateral Sclerosis/blood/diagnosis/genetics
Humans
Biomarkers/blood
Female
Middle Aged
Male
*MicroRNAs/blood/genetics
Aged
Adult
Area Under Curve
Sensitivity and Specificity

@article {pmid41398098,
year = {2025},
author = {Pieper, AA and Paul, BD},
title = {Hydrogen Sulfide Signaling in Neurodegenerative Movement Disorders.},
journal = {Handbook of experimental pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1007/164_2025_757},
pmid = {41398098},
issn = {0171-2004},
abstract = {Hydrogen sulfide (H2S) is a gaseous signaling molecule, also known as a gasotransmitter, present in nearly all mammalian organs. It plays crucial roles in regulating various physiological processes in both the brain and peripheral systems. The body maintains tight control over H2S levels, as both excessive and deficient levels can disrupt normal physiological functions and lead to disease. H2S has a significant impact on cognitive and motor functions, which are often compromised in neurodegenerative disorders. It modulates signaling and metabolism primarily by post-translationally modifying reactive cysteine residues on proteins through sulfhydration, also known as persulfidation. This chapter reviews the signaling mechanisms regulated by H2S in neurodegenerative diseases that significantly affect motor function, specifically focusing on Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), spinocerebellar ataxia (SCA), and Leigh syndrome (LS), as well as other mitochondrial disorders. While PD, HD, and SCA are linked to decreased levels of H2S, elevated levels of H2S are associated with ALS, DS, and LS. We also explore potential therapeutic applications of modulating H2S levels in the brain.},
}

@article {pmid41397872,
year = {2026},
author = {Tam, SB and Waldeck, NJ and Wright, M and Mojsilovic-Petrovic, J and Baker, EM and Kiskinis, E and Bass, J and Kalb, RG},
title = {A role for the cholinergic neuron circadian clock in RNA metabolism and mediating neurodegeneration.},
journal = {Life science alliance},
volume = {9},
number = {3},
pages = {},
doi = {10.26508/lsa.202503508},
pmid = {41397872},
issn = {2575-1077},
mesh = {*Circadian Clocks/genetics/physiology ; Animals ; Humans ; Mice ; *Cholinergic Neurons/metabolism/physiology ; *RNA/metabolism/genetics ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Transcriptome/genetics ; Neurodegenerative Diseases/genetics/metabolism ; ARNTL Transcription Factors/genetics/metabolism ; Alternative Splicing/genetics ; RNA-Binding Proteins/metabolism/genetics ; Circadian Rhythm/genetics ; Male ; Gene Regulatory Networks ; Gene Expression Regulation ; Spinal Cord/metabolism ; },
abstract = {Circadian clocks are encoded by a transcription-translation feedback loop that aligns physiological processes with the solar cycle. Previous work linking the circadian clock to the regulation of RNA-binding proteins (RBPs) provides a foundation for the vital examination of their mechanistic connections in the context of amyotrophic lateral sclerosis (ALS)-a fatal neurodegenerative disease commonly marked by disrupted RBP function. Here, we reveal that the spinal cord cholinergic neuron rhythmic transcriptome is enriched for genes associated with ALS and other neurodegenerative diseases. We show that there is time-of-day-dependent expression of ALS-linked RBP transcripts and rhythmic alternative splicing of genes involved in microtubule cytoskeleton organization, intracellular trafficking, and synaptic function. Through in silico analysis of RNA sequencing data from sporadic ALS patients, we find that gene expression profiles altered in disease correspond with rhythmic gene networks. Finally, we report that clock disruption through cholinergic neuron-specific deletion of clock activator BMAL1 increases neurodegeneration and drives time-of-day-dependent alternative splicing of RNA processing genes. Our results establish a role for the cholinergic neuron circadian clock in RNA metabolism and mediating neurodegeneration.},
}

*Circadian Clocks/genetics/physiology
Animals
Humans
Mice
*Cholinergic Neurons/metabolism/physiology
*RNA/metabolism/genetics
Amyotrophic Lateral Sclerosis/genetics/metabolism
Transcriptome/genetics
Neurodegenerative Diseases/genetics/metabolism
ARNTL Transcription Factors/genetics/metabolism
Alternative Splicing/genetics
RNA-Binding Proteins/metabolism/genetics
Circadian Rhythm/genetics
Male
Gene Regulatory Networks
Gene Expression Regulation
Spinal Cord/metabolism

@article {pmid41397557,
year = {2025},
author = {Esposto, J and Stock, NL and Huber, RJ and Martic, S},
title = {Differential binding of copper and zinc to a TDP-43 RNA recognition motif decapeptide and disulfide formation at residues C173/5 revealed by ESI-MS/MS.},
journal = {Analytical biochemistry},
volume = {},
number = {},
pages = {116031},
doi = {10.1016/j.ab.2025.116031},
pmid = {41397557},
issn = {1096-0309},
abstract = {Copper (Cu) and zinc (Zn) metal ions play important roles in the proper functioning and localization of neurological proteins, such as transactive response DNA-binding protein 43 (TDP-43), which is linked to amyotrophic lateral sclerosis (ALS). Previous experimental and computational studies have identified putative Zn-binding regions within the RNA recognition motif 1 (RRM1) of TDP-43. However, Cu-binding interactions have been less explored despite their redox activity in regulating thiol (C173/175) conversion to disulfide within the RRM1 domain, influencing protein structure and function. Herein, the structural characterization and fragmentation pattern analysis of a TDP-43 decapeptide (166-HMIDGRWCDC-175), within RRM1, coordinated to Cu(II) and Zn(II) ions using electrospray ionization tandem mass spectrometry (ESI-MS/MS) was conducted under non-denaturing conditions. Higher-energy collision dissociation (HCD) fragmentation analysis identified that Cu(II) prefers His/Met residues, while Zn(II) was weakly coordinated to various binding sites in the peptide, specifically His, Met, Glu, Cys, Trp and Asp residues. Computational modeling using a metal ion binding server (MIB2) confirmed the binding sites and coordination sphere of metal-peptide complexes. No significant coordination to C173 and C175 was observed with Cu or Zn, as identified by using a double Cys mutant peptide. A complete thiol-to-disulfide conversion was observed in the presence of Cu(II)/(I) only, which was confirmed by the comparison of a preformed intramolecular disulfide peptide. Overall, unique differential coordination environments were observed for each metal ion with the peptide. The study provides new insights into metal ion interactions with TDP-43 RRM1 peptide, leading to a greater understanding of metal homeostasis in TDP-43 protein biochemistry and neurodegeneration.},
}

@article {pmid41397217,
year = {2025},
author = {Vijayasimha, M},
title = {Toward neonatal analytical stewardship: building on Cadamuro et al.'s minimum-volume framework.},
journal = {Clinical chemistry and laboratory medicine},
volume = {},
number = {},
pages = {},
pmid = {41397217},
issn = {1437-4331},
}

@article {pmid41396714,
year = {2025},
author = {Haenssler, AE and Okada, J and Eshghi, M and Clark, A and Iyer, A and Richburg, BD and Cavanaugh, R and Onnela, JP and Burke, KM and Berry, JD and Green, JR and Connaghan, KP},
title = {What can vowel acoustics reveal about the communicative participation of people living with ALS?.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/21678421.2025.2598433},
pmid = {41396714},
issn = {2167-9223},
abstract = {Objective: Bulbar dysfunction often diminishes the accuracy and speed of the tongue, lip, and jaw movements necessary for speech production. Vowel acoustic features derived from speech recordings can serve as sensitive markers of articulatory accuracy and movement timing. We examined whether degraded speech caused by amyotrophic lateral sclerosis (ALS), assessed through vowel acoustic features, was associated with communicative participation restrictions. As a secondary aim, we assessed the association of two global speech characteristics, rate and intelligibility, with vowel features and communicative participation. Materials & Methods: Thirty-three people with ALS (plwALS) recorded a reading passage and completed surveys using a smartphone application. Speaking rate and acoustic vowel features (duration, vowel articulation index [VAI]) were extracted from the recordings. Three speech-language pathologists rated speech intelligibility. Communicative participation was assessed using the Communicative Participation Item Bank (CPIB) short form. Bivariate correlation, partial correlation, and regression analyses were used to evaluate the associations between vowel features, intelligibility, speaking rate, and CPIB scores. Results: Significant bivariate correlations, ranging from rs = -0.39 to rs = 0.64, were found between speech variables and CPIB scores. A combined regression model including VAI, vowel duration, and sex explained 52% of the variance in CPIB scores. Including speaking rate or intelligibility in the partial correlation analysis attenuated the associations between vowel acoustics and CPIB. Conclusions: Vowel features and global dysarthria characteristics are linked to communicative participation in ALS. Clinical practices designed to target vowel production, speaking rate, and intelligibility may help to maintain daily communication in ALS.},
}

@article {pmid41396667,
year = {2025},
author = {Drake, RE and Bond, GR and Becker, DR},
title = {Letter to the Editor regarding Schrader et al.'s (2025) "Work and recovery from substance use disorder in Veterans Affairs".},
journal = {Psychiatric rehabilitation journal},
volume = {},
number = {},
pages = {},
doi = {10.1037/prj0000680},
pmid = {41396667},
issn = {1559-3126},
abstract = {Comments on an article by S. W. Schrader et al. (see record 2026-54463-001). Schrader et al. recently reported on VA programs for veterans in early stages of recovery from substance use disorder (SUD), finding that 78% of 78 veterans elected to receive therapeutic work activity, which has a primary goal of clinical recovery rather than employment, and only 22% selected programs focusing on competitive employment. Three possible interpretations may explain Schrader et al.'s anomalous finding and deserve further research. They are discussed in the current commentary. (PsycInfo Database Record (c) 2025 APA, all rights reserved).},
}

@article {pmid41396654,
year = {2025},
author = {Šakotić, RJ and Crişan, I},
title = {Laying the Groundwork for Clinical Neuropsychology in Romania: Beliefs and Practices of Psychologists Regarding Validity Testing in Clinical Assessment.},
journal = {Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists},
volume = {},
number = {},
pages = {},
doi = {10.1093/arclin/acaf116},
pmid = {41396654},
issn = {1873-5843},
abstract = {OBJECTIVE: The present study aimed to explore and document Romanian psychologists' practices and beliefs regarding validity testing in clinical assessment, given the lack of neuropsychology as a practice field in this country.

METHOD: We developed a questionnaire addressing several key aspects, including demographic and professional information, and beliefs and practices related to validity testing in clinical assessment. The questionnaire was distributed to all practitioners licensed in clinical psychology registered on the official website of the Romanian College of Psychologists (RCP). The final sample consisted of 344 practitioners, 312 of whom had been active in assessments during the previous year.

RESULTS: Our findings revealed several cultural particularities, including the preference of 49.4% of the sample for employing the Tree Drawing Test (Koch, K. (1954). Der Baumtest - Der Baumzeichenversuch als psychodiagnostisches Hilfsmittel. Hans Huber. Romanian translation by Mocanu, S. (2002). Testul Arborelui - Diagnosticul psihologic cu ajutorul testului arborelui. Profex. Bucuresti) - a projective drawing technique - as a validity test. Only 16.7% of practitioners reported using empirically supported validity tests in clinical evaluations, and several performance validity tests were reported by 2-12.5% of the sample. Additionally, the prevalence of malingering was estimated to be 5%-20% and most respondents associated it with personality disorders.

CONCLUSIONS: The results indicate a need to bridge the gap between science and practice by adopting evidence-based approaches within the Romanian assessment culture. Our survey offers novel empirical insights into the current state of validity assessment in Romania, thereby contributing foundational knowledge that may support the legitimization and further development of neuropsychology within the national context.},
}

@article {pmid41396532,
year = {2025},
author = {Sabey, TB and Shanklin, BC and Colquitt, JA and Baer, MD},
title = {The approach-inhibition theory of power: A meta-analytic test and synthesis.},
journal = {Psychological bulletin},
volume = {151},
number = {10},
pages = {1245-1279},
doi = {10.1037/bul0000500},
pmid = {41396532},
issn = {1939-1455},
mesh = {Humans ; *Inhibition, Psychological ; *Psychological Theory ; *Power, Psychological ; *Cognition ; *Affect/physiology ; },
abstract = {Keltner et al. (2003) presented an integrative theory of the social implications of possessing power. Their theory-the approach-inhibition theory of power-quickly became the dominant lens for empirical investigations of how power influences a person's cognition, affect, and behavior. Despite the many benefits of Keltner et al.'s theory, the past 20 years of research have surfaced several potential issues with the theory, including empirical dissensus, mediational ambiguity, and questions about cognitive versus affective primacy. The purpose of this study is to resolve these issues by conducting the first meta-analytic synthesis of the literature on the outcomes of power. Specifically, we tested Keltner et al.'s propositions that power is positively related to the approach-oriented outcomes of attention to rewards, automatic cognition, positive affect, and disinhibited behavior and negatively related to the inhibition-oriented outcomes of attention to threats, controlled cognition, negative affect, and inhibited behavior. Our meta-analysis included a final set of 1,712 effect sizes from 813 independent samples of 432 manuscripts with 269,534 participants. Our analysis demonstrates that the theory is well-supported; approach associations are larger than inhibition associations; power influences behavior indirectly through attention, cognition, and affect; and those indirect effects are largely conveyed through affect. Based on these findings, we suggest several future directions that scholars can take as the literature on power continues to evolve. (PsycInfo Database Record (c) 2025 APA, all rights reserved).},
}

Humans
*Inhibition, Psychological
*Psychological Theory
*Power, Psychological
*Cognition
*Affect/physiology

@article {pmid41396347,
year = {2025},
author = {Vandermorris, A and Metzger, DL and Vyver, E and Harrison, M and Wong, S and , },
title = {Correction: Response to Kulatunga Moruzi et al.'s (2025) "The Cass Review and Gender-Related Care for Young People in Canada: A Commentary on the Canadian Paediatric Society Position Statement on Transgender and Gender-Diverse Youth".},
journal = {Archives of sexual behavior},
volume = {},
number = {},
pages = {},
doi = {10.1007/s10508-025-03391-0},
pmid = {41396347},
issn = {1573-2800},
}

@article {pmid41396180,
year = {2025},
author = {Xu, X and Zhou, Q and Zhang, X and Li, T and Niu, L and Xu, G and Chen, S and Shao, Y and Le, W},
title = {Untargeted metabolomics based on LC-MS and GC-MS reveal metabolic reprogramming and putative biomarkers in amyotrophic lateral sclerosis.},
journal = {Chinese medical journal},
volume = {},
number = {},
pages = {},
pmid = {41396180},
issn = {2542-5641},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with unknown etiology. The absence of reliable biochemical and imaging markers often delays diagnosis and limits treatment effectiveness. As metabolic reprogramming is increasingly recognized as a hallmark of ALS, a comprehensive untargeted metabolomics analysis was employed to identify critical metabolic perturbations in ALS and explore novel candidate biomarkers with potential utility in clinical diagnosis.

METHODS: Plasma from two independent cohorts comprising 399 participants (170 ALS patients, 200 healthy controls, and 29 ALS-unrelated neurological disease controls) was included. Cohort 1 was recruited from Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital (April 2020-September 2022), and cohort 2 from Sichuan Academy of Sciences-Sichuan Provincial Hospital, Ruijin Hospital, Shanghai Jiaotong University Affiliated Sixth People's Hospital, and The First Affiliated Hospital of Dalian Medical University (October 2022-February 2023). Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approaches were used to identify metabolic alterations and potential diagnostic biomarkers for ALS. Complementary multivariable and univariable statistical approaches were applied to characterize disease-specific metabolic reprogramming in ALS. In addition, the receiver operating characteristic (ROC) curve was used to assess the discriminatory power of differential metabolites, and binary logistic regression analysis was used to construct a multivariate biomarker model.

RESULTS: Metabolic changes of ALS were mainly observed in amino acids, fatty acyls , and purines. Inosine and hypoxanthine were found to be the most significantly and critically dysregulated metabolites in ALS. Aminoacyl-transfer ribonucleic acid (tRNA) biosynthesis and amino acid metabolism were regarded as the most significantly perturbed pathways. Across both cohorts, 26 metabolites were consistently changed. Notably, a biomarker panel comprising hypoxanthine, inosine, and trigonelline was constructed using binary logistic regression, achieving excellent diagnostic performance in distinguishing ALS from controls, with an area under the ROC curve of 0.982 in cohort 1 (sensitivity 0.970, specificity 0.940) and 0.934 in cohort 2 (sensitivity 0.942, specificity 0.791).

CONCLUSION: The disturbed pathways and biomarker candidates identified in this study may provide novel insights into ALS pathogenesis and improve diagnostic strategies.},
}

@article {pmid41395499,
year = {2025},
author = {Li, L and Yang, W and Hong, Y and He, Q and Lu, X and Wang, H and Tao, P and Shu, C and Chen, M and Bao, G and Jiang, L},
title = {Identification of Nanoplastics by Probing the Viscous Nanoenvironment.},
journal = {Small science},
volume = {5},
number = {12},
pages = {e202500430},
pmid = {41395499},
issn = {2688-4046},
abstract = {With the growing prevalence of global microplastic and nanoplastic pollution, the accumulation of nanoplastics in the human body has increased, heightening the risk of noncommunicable diseases including cancer, cardiovascular disease, and amyotrophic lateral sclerosis. However, the development of fluorescent probes for detecting nanoplastics remains challenging due to the lack of reactive sites on nanoplastics for conventional design of responsive probes. In this work, a novel strategy for the sensitive detection of nanoplastics by probing the viscous nanoenvironment surrounding them is presented. This study synthesizes a cationic fluorescent probe, Purification by silica gel column chromatography (CH2Cl2/MeOH) provided (E)-2-(2-(4-(dimethylamino)nanphthalen-1-yl)vinyl)-1,3,3-trimethyl-3H-indol-1-ium (named HCY due to its structural similarity to hemicyanine dyes) as a tawny solid (HCY), via a simple one-step reaction. HCY demonstrates high sensitivity to nanoplastics, achieving an 8.5-fold fluorescence enhancement in the presence of carboxylated polystyrene nanoplastics, with a detection limit of 0.153 μg mL[-1]. Moreover, HCY exhibits excellent biocompatibility, enabling the monitoring of nanoplastics level in living cells and visualization of nanoplastics distribution in zebrafish. This work offers a new design strategy for responsive fluorescent probes and provides a promising avenue for detecting environmental pollutants.},
}

@article {pmid41395267,
year = {2025},
author = {Roy, T and Al-Chalabi, A and Iacoangeli, A and Al Khleifat, A},
title = {Biomarkers in ALS trials: from discovery to clinical utility.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1636303},
pmid = {41395267},
issn = {1662-4548},
abstract = {INTRODUCTION: Motor neuron disease (MND), also known as amyotrophic lateral sclerosis (ALS), is a progressive neurodegenerative disorder characterized by motor neuron degeneration, leading to muscle weakness, paralysis, and eventual respiratory failure. Despite advances in understanding its pathology, effective therapies remain limited, underscoring the need for reliable biomarkers to aid early diagnosis, monitor disease progression, and optimize clinical trials. This systematic review explores the role of biomarkers in ALS, focusing on their application in clinical trials to accelerate therapeutic development and enhance patient care.

METHODS: A comprehensive search of PubMed, EMBASE, MedLine, and Google Scholar identified 93 studies investigating various biomarkers, including neurofilament light chain (NFL), inflammatory markers, genetic markers like SOD1 and C9orf72, and imaging modalities.

RESULTS: NFL emerged as a robust biomarker, strongly correlating with disease progression and therapeutic response, and was frequently used in trials like RESCUE-ALS and CENTAUR. Genetic biomarkers, such as C9orf72 and SOD1 mutations, provided insights into ALS mechanisms and informed targeted therapeutic approaches. Emerging biomarkers, such as retroviral elements, show potential but require further validation. Included studies span key trials such as Lighthouse-II, MIROCALS, and MND-SMART.

DISCUSSION: This systematic review evaluates which biomarkers are currently validated for monitoring disease progression and therapeutic response in ALS clinical trials, including protein, genetic, inflammatory, metabolic, and imaging markers. It also highlights the critical role of biomarkers in advancing MND clinical trials by enabling adaptive trial designs, patient stratification, and the use of surrogate endpoints, thereby reducing trial duration and improving efficiency. The review also highlights the translational gap between biomarker discovery and clinical application, emphasizing their potential to optimize trial design and patient stratification. While biomarkers like NFL have transformed trial methodologies, challenges such as disease specificity and inter-patient heterogeneity persist. Future efforts should focus on multimodal biomarker approaches to achieve comprehensive disease assessment and advance personalized therapeutic strategies, ultimately improving outcomes for patients with MND.},
}

@article {pmid41395145,
year = {2025},
author = {Yi, X and Zhou, W and Cheng, C and Chen, X},
title = {Remimazolam-remifentanil general anaesthesia without muscle relaxants for percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis: A retrospective analysis.},
journal = {Indian journal of anaesthesia},
volume = {69},
number = {12},
pages = {1413-1416},
pmid = {41395145},
issn = {0019-5049},
}

@article {pmid41394713,
year = {2025},
author = {Ross, D and Lewis, O and McLean, O and Bhanot, S and Donahue, S and Baker, R and Dias, R and Eagerton, D and Mohanty, V and Mohanty, BK},
title = {Thermally activated irreversible homogenization of G-quadruplexes in an ALS/FTD-associated gene.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.06.02.657482},
pmid = {41394713},
issn = {2692-8205},
abstract = {UNLABELLED: A significant proportion of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) cases exhibit a substantial copy number expansion of the hexanucleotide GGGGCC/GGCCCC sequence in the C9ORF72 gene. The GGGGCC sequence forms a non-canonical DNA structure called a G-quadruplex (G4) which has been associated with the disease states and with nucleic acid condensate formation. G4s can fold into various topologies, which can differentially impact fidelity of DNA synthesis. However, how G4 conformational heterogeneity and its regulation impact hexanucleotide repeat expansion is unclear, and important clues may lie in the thermodynamic properties of different G4 topologies. Here, we use temperature-swept CD spectroscopy to observe configurational homogenization of an initially heterogeneous population of G4s over a small range of temperatures, demonstrating thermally activated behavior. We further show that this reaction is irreversible, since subsequent temperature sweeps do not show CD shifts from non-parallel to parallel G4 topologies. Finally, we provide an analytical theory based on a two-state thermodynamic model which is compatible with experimental evidence, and we discuss alternate mechanisms for the homogenization transition. These findings suggest that kinetic regulation of non-canonical DNA structures may play a role in cellular homeostasis or disease pathogenesis.

SIGNIFICANCE: The GGGGCC repeats in the C9ORF72 gene expand in copy number in certain neurodegenerative diseases, forming non-canonical DNA structures called G-quadruplexes (G4) which are associated with the pathological state. However, why the repeat expansion occurs is not known, and a key may lie in the thermodynamic stability of certain G4 conformations. Here, we use CD spectroscopy to experimentally report thermally activated heat-induced G4 conformation homogenization, from a heterogeneous population to the parallel configuration. We derive an analytical biophysical theory which is compatible with this experimental observation, which is shown to be irreversible. Our in vitro tuning of the free energy landscape that modulates G4 conformational fidelity motivates a search for possible in vivo enzymatic regulators.},
}

@article {pmid41394711,
year = {2025},
author = {Mehta, PR and Solomon, T and Pickles, S and Harley, P and Barioglio, M and Schweingruber, C and Marrero-Gagliardi, A and Gao, Y and Mattedi, F and Barattucci, S and Lin, LT and Ryadnov, E and Zanovello, M and Cammack, AJ and Isaacs, AM and Burrone, J and Shaw, CE and Keuss, MJ and Petrucelli, L and Fratta, P and Ruepp, MD},
title = {U7 small nuclear RNA splice-switching therapeutics for STMN2 and UNC13A in Amyotrophic Lateral Sclerosis.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.26.690143},
pmid = {41394711},
issn = {2692-8205},
abstract = {TDP-43 nuclear depletion in amyotrophic lateral sclerosis (ALS) causes de-repression of cryptic exons (CEs) in multiple transcripts, including UNC13A and STMN2 , disrupting synaptic transmission and neurite outgrowth. We developed a therapeutic U7 snRNA (tU7) approach that suppresses TDP-43-dependent mis-splicing, restores target gene expression, rescues neuronal functions in human iPSC-derived neurons, and shows target engagement in vivo , positioning tU7-mediated splicing correction as a promising therapeutic strategy for ALS.},
}

@article {pmid41394670,
year = {2025},
author = {O'Connor, JT and Loo, HQ and Guo, C and Pickles, S and Sundali, S and Jawahar, VM and Dickson, DW and Bloom, AJ and Petrucelli, L and Gitler, AD and Milbrandt, J and DiAntonio, A},
title = {TDP-43 suppression of ATP8A2 cryptic splicing implicates phosphatidylserine-driven neuroinflammation in ALS/FTD.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.21.689833},
pmid = {41394670},
issn = {2692-8205},
abstract = {Inappropriate externalization of phosphatidylserine (PS) is a candidate mechanism of pathogenic neuroinflammation, a critical driver of neurodegenerative disease. ATP8A2, a flippase that maintains PS on the plasma membrane inner leaflet, is mutated in both Wabbler-lethal mice and patients with the ataxia syndrome CAMRQ4. Here, we identify ATP8A2 as a target of TDP-43 cryptic exon suppression, and demonstrate that ATP8A2 loss leads to immune-mediated neurodegeneration. ATP8A2 splicing is significantly dysregulated following TDP-43 depletion in human neurons and in brains of patients with Amyotrophic Lateral Sclerosis-Frontotemporal Dementia (ALS-FTD). In mice, Atp8a2 loss increases PS exposure and promotes neuroinflammation. Depletion of peripheral macrophages rescues motor axon degeneration and doubles Atp8a2 knockout mouse lifespan, while depletion of both peripheral macrophages and central microglia quadruples lifespan and improves coordination. Hence, ATP8A2 is a pathologically relevant TDP-43 target and inhibition of phagocytic immune cell attack against neurons is a potential treatment for patients with CAMRQ4 and ALS-FTD.},
}

@article {pmid41394659,
year = {2025},
author = {Tendulkar, S and Wu, T and Strickland, A and Hackett, AR and Sato-Yamada, Y and Mao, X and Sasaki, Y and Milbrandt, J and Bloom, J and DiAntonio, A},
title = {Dysregulated lactate metabolism synergizes with ALS genetic risk factors to accelerate motor decline.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.24.690227},
pmid = {41394659},
issn = {2692-8205},
abstract = {Neurons rely on glial lactate shuttling for metabolic support, which declines with aging and in neurodegenerative disease. Full disruption of lactate shuttling in peripheral nerves causes progressive axon degeneration, but we were interested to understand how partial disruption, a scenario more relevant to aging and disease, contributes to neurodegeneration risk. Pyruvate and lactate are interconverted by lactate dehydrogenases (LDHA and LDHB) in both lactate producing and consuming cells. We therefore began by investigating Ldhb knockout mice (loss of LDHA, the dominant LDH in liver and muscle, caused embryonic lethality), and discovered that they develop progressive neuromuscular junction atrophy and functional decline without axon degeneration. Because even Ldhb+/- heterozygosity significantly affects motor behavior, we also wondered about a potential link to congenital disease and pursued this by identifying rare loss-of-function LDHB variants among ALS patients. Next, to better understand how LDHB loss leads to motor decline, we selectively deleted it in defined cell types. SC-specific deletion caused robust motor defects, whereas motor neuron-specific deletion has little effect. Reasoning that neuronal LDHB deficiency could model age-associated decline in lactate metabolism, we asked whether it would interact with ALS genetic risk. Indeed, motor-neuron LDHB deficiency synergizes with relatively mild ALS risk variants, TDP43-Q331K and Sod1-D83G knock-in alleles, to produce early motor neuropathy, indicating that LDHB loss enhances disease risk. These findings establish lactate metabolism as a modifier of motor system vulnerability and highlight it as a therapeutic target in peripheral as well as central neurodegeneration.},
}

@article {pmid41394638,
year = {2025},
author = {Sutter, AB and Buksh, BF and Mojsilovic-Petrovic, J and Dalton, C and Till, NA and Morgan, DC and MacMillan, DWC and Kalb, RG},
title = {The molecular mechanism of uptake and cell-to-cell transmission of arginine-containing dipeptide repeat proteins.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.25.690484},
pmid = {41394638},
issn = {2692-8205},
abstract = {UNLABELLED: Micro-satellite repeat expansion of the 5' GGGGCC 3' sequence in the C9orf72 gene is the most common monogenic form of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Dipeptide repeat proteins (DPRs) translated from the mutant allele can be detected in postmortem brains of afflicted individuals. The arginine containing peptides, poly-PR and poly-GR, are particularly noxious to cells. Both have been shown to undergo cell-cell transmission, but the underlying mechanisms are not understood. We found rapid internalization and nucleolar localization of bath-applied hemagglutinin (HA) tagged poly-PR with twenty repeats (HA-PR 20) in cell lines and neurons. Small molecule and RNAi approaches implicated a temperature-dependent, fluid phase endocytosis mechanism in HA-PR 20 uptake. We sought to identify DPR-related cell surface uptake factors using a high-resolution proximity labeling technique developed in the MacMillan group, termed µMap. DPR-iridium conjugates identified candidate cell-surface proteins which were interrogated in an RNAi screen. Focusing on our strongest candidate, chondroitin sulfate proteoglycan 4 (CSPG4), we showed that cellular uptake of HA-PR 20 is blocked by inhibition of glycosaminoglycan chain synthesis (using drugs or RNAi) and knockdown or ablation of CSPG4 (using RNAi or CRISPR editing). Reduction of CSPG4 protected PR 20 -induced neuronal toxicity. We used a dual reporter system to interrogate in vitro neuron-to-neuron transmission of PR 50 and found that PR 50 synthesized by one neuron readily spread to neighboring neurons. Transmission was significantly reduced when CSPG4 was knocked down. These results suggest CSPG4 is an important factor in poly-PR internalization and transmission and therefore may be a therapeutic target to slow DPR transmission and disease progression.

SIGNIFICANCE STATEMENT: A GGGGCC hexanucleotide repeat expansion in the C9orf72 gene is the most common monogenic form of ALS/FTD. This expansion leads to dipeptide repeat protein (DPR) production through non-canonical translation of repeat-containing RNA. DPRs have been shown to transmit between cells, but how this occurs is not well understood. We identified the cell surface protein chondroitin sulfate proteoglycan 4 (CSPG4) as a mediator of the uptake and intercellular spread of toxic arginine-rich DPRs. Targeting CSPG4 may provide a strategy to block DPR transmission and slow disease progression.},
}

@article {pmid41393525,
year = {2025},
author = {Guedes, A and de Camargo, OP and Matos, EP and Carreiro, MC and Rios, FF and Guimarães, AHS and Meyer, KA and de Lima, NFL and Barreto, BG and de Mattos, ESR and Antunes, CR and Barreto, ESR},
title = {EVALUATION OF A DECADE OF ONCOLOGICAL-ORTHOPEDIC PROCEDURES IN BRAZIL (2015-2024) AND THE IMPACT OF COVID-19.},
journal = {Acta ortopedica brasileira},
volume = {33},
number = {spe3},
pages = {e297250},
pmid = {41393525},
issn = {1413-7852},
abstract = {OBJECTIVE: To evaluate the regional distribution of hospital admission authorizations (AIH), total and average hospitalization cost (AHC), average length of stay, number of deaths and mortality rate related to oncological-orthopedic procedures funded by the Unified Health System (SUS) between 2015 and 2024, with an emphasis on the impact of the COVID-19 pandemic.

METHODS: Ecological study with time series based on data obtained from the SUS Hospital Information System, analyzed by Brazilian regions in the pre-pandemic, pandemic and post-pandemic periods. Regional differences were calculated using ANOVA or Kruskal-Wallis. The impact of the pandemic was analyzed using T-tests and ARIMA with intervention. Statistical analysis was performed in R.

RESULTS: 9,120 AIHs were recorded, mostly in the Southeast (4,375) and South (2,252) regions. Multiple regional variations were found for all the variables evaluated. Only the AHC was impacted - there was an increase in costs per procedure; The other variables maintained the trend after the beginning of the pandemic.

CONCLUSIONS: Despite the increase in the AHC, we did not observe significant variation in the number of AIH, ALS, and MR when analyzing the pre-pandemic and pandemic periods, suggesting that there was no direct impact on the performance of the analyzed procedure. Level of Evidence III; Retrospective f comparative study e.},
}

@article {pmid41393069,
year = {2025},
author = {Yan, K and Deng, J and Yong, Y and Bi, F},
title = {Proteomic Identification of ALDOA as a Pathogenic TDP-43 Interaction Partner in ALS.},
journal = {Degenerative neurological and neuromuscular disease},
volume = {15},
number = {},
pages = {123-132},
pmid = {41393069},
issn = {1179-9900},
abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons, and its pathogenesis has not been fully elucidated. TAR DNA-binding protein 43 (TDP-43), as one of the key pathogenic genes in ALS, participates in the disease process through interactions with various proteins. This study aims to investigate the interaction mechanism between TDP-43 and aldolase A (ALDOA) in ALS.

METHODS: HEK293T cell models transfected with wild-type and mutant TDP-43 (TDP-43[M337V]) plasmids were constructed. The interaction between TDP-43 and ALDOA was analyzed through proteomic screening of specific peptides and co-immunoprecipitation, and the co-localization of the two in cells was detected by immunofluorescence. Changes in ALDOA expression levels after intervention with mutant TDP-43 were detected by Western blot and quantitative real-time PCR.

RESULTS: Proteomic analysis identified ALDOA as a potential interacting protein of TDP-43. Protein-protein interaction (PPI) analysis, co-immunoprecipitation, and immunofluorescence experiments further confirmed that both wild-type and mutant TDP-43 interact with ALDOA. Western blot and quantitative real-time PCR results showed that, compared with the wild-type TDP-43 group, the ALDOA expression was significantly increased in the TDP-43[M337V] mutant group.

CONCLUSION: TDP-43 interacts with ALDOA in ALS, and the TDP-43[M337V] mutation significantly promotes ALDOA expression, suggesting that ALDOA may be involved in the pathogenesis of TDP-43-mediated ALS. These findings provide new insights into the pathogenesis of ALS and highlight a potential therapeutic target.},
}

@article {pmid41392874,
year = {2025},
author = {Jung, HJ and Cheong, EN and So, J and Kang, HW and Choi, Y and Lee, EJ and Kim, H and Lim, YM},
title = {ALS With and Without Upper Motor Neuron Signs: A Comparative Study Supporting the Gold Coast Criteria.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.70288},
pmid = {41392874},
issn = {2328-9503},
support = {2023IP0108//Asan Institute for Life Sciences, Asan Medical Center/ ; RS-2023-00211443//Ministry of Science and ICT, South Korea/ ; },
abstract = {OBJECTIVE: The Gold Coast criteria permit diagnosis of amyotrophic lateral sclerosis (ALS) even without upper motor neuron (UMN) signs. However, whether ALS patients with UMN signs (ALSwUMN) and those without (ALSwoUMN) share similar characteristics and prognoses remains unclear. This study compared clinical features, disease progression, electrophysiological findings, biomarker profiles, imaging parameters, and survival between these groups.

METHODS: ALS patients diagnosed according to the Gold Coast criteria were classified into ALSwUMN (n = 51) and ALSwoUMN (n = 20) groups. We evaluated clinical data, motor evoked potentials (MEP), and serum biomarkers, including cardiac Troponin T, neurofilament light chain, glial fibrillary acidic protein, and brain-derived neurotrophic factor. Imaging parameters, including cortical thickness and white matter volume, were also evaluated. Survival was analyzed using the Kaplan-Meier method.

RESULTS: The groups showed broadly similar clinical features, disease progression, and biomarker profiles. Abnormal MEPs were more frequent in ALSwUMN (94.0%) than in ALSwoUMN (63.2%, p = 0.017). Both groups demonstrated cortical thinning in the precentral and entorhinal regions compared to healthy controls. ALSwUMN exhibited thinning in the lateral orbitofrontal, insular, and temporal pole regions, while ALSwoUMN showed thinning in the pars opercularis. White matter volume was reduced in both groups in the thalamus, cerebellum, and amygdala, with additional brainstem atrophy in ALSwUMN. No significant survival difference was observed.

INTERPRETATION: Despite minor distinctions in electrophysiological and imaging findings, ALSwoUMN had overall comparable clinical profiles and outcomes to ALSwUMN. These findings support recognizing ALSwoUMN within the ALS spectrum under the Gold Coast criteria.},
}

@article {pmid41392526,
year = {2025},
author = {Maitland, S and Birkbeck, M and Schofield, I and Best, L and Scott, J and Blamire, A and Whittaker, RG},
title = {MRI of Neurogenic Human Motor Units Following Poliomyelitis.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70107},
pmid = {41392526},
issn = {1097-4598},
support = {//NIHR Newcastle Biomedical Research Centre/ ; },
abstract = {INTRODUCTION/AIMS: Surviving motor units in neurogenic diseases demonstrate collateral reinnervation. Scanning electromyography (EMG) reveals normal motor unit corridor length, but with "silent regions," suggesting that reinnervation does not result in increased motor unit size but may increase motor unit complexity. Motor unit magnetic resonance imaging (MUMRI) pairs MR imaging with electrical nerve stimulation to visualize individual motor units. This study aimed to assess the motor unit dimensions and complexity in patients with previous poliomyelitis compared to healthy controls.

METHODS: Patients with a history of polio were recruited from the British Polio Fellowship, compared to a retrospective cohort of healthy controls. They underwent medical history and examination of lower limb power, fatigue assessment (fatigue severity score, FSS), and a 3 T MUMRI scan of the less-affected lower limb. The cross-sectional area, maximum, and minimum Feret diameter of the motor unit territories in tibialis anterior were calculated. Motor unit complexity was computed using the Hausdorff box-counting method.

RESULTS: Of 12 polio survivors, n = 8 (6 female) were suitable for analysis and were compared to 19 controls. The mean motor unit maximum Feret diameter was 10.3 ± 3.1 mm compared to 8.4 ± 5.2 mm in controls (p = 0.34). The mean shape complexity was 0.59 ± 0.12 compared to 0.45 ± 0.2 in controls (p = 0.03).

DISCUSSION: Polio survivors demonstrate motor units with normal dimensions but increased shape complexity, indicating nonuniform collateral reinnervation largely limited to existing territories. The size and shape of motor units could help in understanding the physiological processes behind reinnervation, both in polio and other neurogenic diseases such as amyotrophic lateral sclerosis.},
}

@article {pmid41392158,
year = {2025},
author = {Le Friec, J and Mourier, H and Couly, S and Cubedo, N and Dubois, K and Meunier, J and Delprat, B and De Zordo-Banliat, A and Ayad, T and Virieux, D and Su, TP and Lasbleiz, C and Maurice, T and Liévens, JC},
title = {Positive modulation of sigma-1 receptor: a new weapon to mitigate disease progression in amyotrophic lateral sclerosis.},
journal = {Translational neurodegeneration},
volume = {14},
number = {1},
pages = {68},
pmid = {41392158},
issn = {2047-9158},
support = {grant 23667//AFM-Téléthon/ ; },
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy/genetics/pathology ; *Receptors, sigma/metabolism/agonists ; Sigma-1 Receptor ; Zebrafish ; Disease Progression ; Mice ; Humans ; Mice, Transgenic ; Motor Neurons/drug effects/metabolism ; Disease Models, Animal ; C9orf72 Protein/genetics ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterised by degeneration of motor neurons, leading to muscle weakness and progressive paralysis. Currently, no treatment is available to halt or reverse the progression of the disease. Oxidative stress, mitochondrial dysfunction, accumulation of unfolded proteins and inflammation are interconnected key actors involved in ALS. A potent therapeutic strategy would be to find molecules that break this vicious circle leading to neuronal dysfunction and death. Targeting sigma-1 receptor (S1R) could meet this objective, as this chaperone protein modulates many cell survival mechanisms. So far, the impact of S1R activation in ALS has been studied using specific agonists and mostly on the SOD1 mutation that represents only 2% of patients. In the present study, the impact of two different S1R activators, the reference agonist PRE-084 and the positive modulator OZP002, was compared on two key ALS genes: TDP43 and C9orf72.

METHODS: The dissociation of S1R from Binding immunoglobulin Protein (BiP) was determined using ELISA. OZP002 toxicity was compared to PRE-084 on zebrafish larvae with increasing concentrations. The efficacy of OZP002 and PRE-084 was evaluated on the locomotor escape response of zebrafish expressing mutant TDP43 or one C9orf72 toxic dipeptide. Their effects on NRF2 target gene expression were studied by qPCR. The beneficial effect was further examined on the locomotor performances of TDP43[A315T] mice using rotarod and beam walking tests. We also performed analysis on motor neuron loss and glial reactivity.

RESULTS: OZP002 is a positive modulator of S1R, that increases the dissociation of the S1R-BiP complex induced by orthosteric agonists. S1R activation by both OZP002 and PRE-084 restored the locomotor response of ALS zebrafish expressing either TDP43 or one C9orf72 toxic dipeptide. The neuroprotection was due at least in part to the NRF2 cascade stimulation but not with a direct interaction. More importantly, OZP002 and PRE-084 prevented locomotor defects and degeneration of spinal motor neurons in TDP43[A315T] transgenic mice. Astroglial and microglial reactivities were also reduced by both activators.

CONCLUSIONS: We here emphasize the therapeutic value of S1R activation in mitigating ALS pathology. Additionally, we show that the positive modulators pave the way for the development of new S1R-activating compounds for ALS treatment.},
}

Animals
*Amyotrophic Lateral Sclerosis/metabolism/drug therapy/genetics/pathology
*Receptors, sigma/metabolism/agonists
Sigma-1 Receptor
Zebrafish
Disease Progression
Mice
Humans
Mice, Transgenic
Motor Neurons/drug effects/metabolism
Disease Models, Animal
C9orf72 Protein/genetics

@article {pmid41391687,
year = {2025},
author = {Donison, N and Hintermayer, MA and Palik, J and Fisher, J and Volkening, K and Strong, MJ},
title = {MAPK family members differentially regulate pThr175 tau-mediated pathogenicity.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107223},
doi = {10.1016/j.nbd.2025.107223},
pmid = {41391687},
issn = {1095-953X},
abstract = {The phosphorylation of tau is a critical determinant of both its physiological function and the induction of pathological misfolding and aggregation. We have previously provided evidence that tau phosphorylation at Thr175 results in the exposure of the N-terminal phosphatase-activating domain (PAD) leading to the subsequent phosphorylation of Thr231, and formation of tau oligomers. A number of tauopathies, including chronic traumatic encephalopathy (CTE), amyotrophic lateral sclerosis with cognitive impairment (ALSci), and experimental traumatic brain injury (TBI) have been proposed to be associated with this cascade of events. However, the cellular mechanism by which Thr175 tau is phosphorylated remains unclear. In this study we identified ERK2, JNK1, and p38 as candidate kinases through molecular and histological analyses in a rodent model of TBI, where increased kinase activity and protein interaction were associated with pThr175 tau. We confirmed that both ERK2 and JNK1 are capable of phosphorylating Thr175 tau in vitro, but only ERK2-mediated phosphorylation of Thr175 tau induced the pathological cascade characterized by PAD exposure and the generation of oligomeric, truncated and neurofibrillary tau. Thr175 phosphorylation was also associated with an altered interaction between tau and the molecular chaperone protein DnaJC7, which regulates tau misfolding. Additionally, we observed that pThr175 and pThr231 tau were increased by oxidative stress, which was associated with the activation of the MAPK signaling pathways. These findings further clarify the mechanisms leading to Thr175 tau phosphorylation and its role in pathological tau formation by identifying ERK1 and JNK2 as important cellular mediators.},
}

@article {pmid41389646,
year = {2025},
author = {Bhatia, S and Mohanty, V and Balappanavar, AY and Sarkar, C and Malhotra, S and Gupta, R},
title = {Fostering the concept of "inclusion oral health" through experiential learning: A mixed-methods approach to explaining health inequities to dental students.},
journal = {Social science & medicine (1982)},
volume = {390},
number = {},
pages = {118859},
doi = {10.1016/j.socscimed.2025.118859},
pmid = {41389646},
issn = {1873-5347},
abstract = {BACKGROUND: "Inclusion oral health" (IOH) is an emerging framework focusing on developing innovative solutions to tackle oral health inequities. We intend to provoke reflection, stimulate discussion, and give students practice in responding to the needs of vulnerable population. Newer experiential teaching models have shown substantial potential for affecting values and behaviors of dental students towards underserved population. Hence, it was our aim to teach third-year dental students about IOH while simultaneously comparing the effectiveness of conventional and experiential teaching methods.

METHOD: All third-year dental students (n = 40) enrolled at a teaching dental hospital in New Delhi, India, were allocated into groups A (standard teaching, n = 20) and B (experiential teaching, n = 20). Data were collected from January to March 2023. A questionnaire based on the theme was used for pre-post assessment. A didactic lecture on the topic was delivered to both groups. Group B participants were further shown an educational movie and a field visit to a shelter. Reflections were collected from both groups using Rolfe et al.'s reflective model. Statistical and thematic analysis was performed.

RESULTS: After the intervention, knowledge of group B participants (Δk = 28.9) was higher than A (Δk = 15.8) (p = 0.04). There was a shift in the attitude of students towards community service and social responsibility, especially among the group B participants. Thematic analysis of "Reflections" revealed 6 themes under 3 main domains.

CONCLUSION: Thematic analysis shed light on the learning continuum for creating socially-sensitive and proactive dental workforce. Contemporary concepts like IOH should be woven into the dental curriculum to introduce students to critical thinking and realistic problem-solving. Experiential teaching was effective in educating the concept through engagement and critical reflection.},
}

@article {pmid41389988,
year = {2025},
author = {Gomez-Almeria, M and Martinez-Gonzalez, L and Matos, AT and Rodriguez-Cueto, C and Vaz, AR and Martín-Baquero, R and Pérez de la Lastra, C and Infantes, R and Fernández-Ruiz, J and Palomo, V and Gil, C and Brites, D and Martinez, A and de Lago, E},
title = {Assessment of the therapeutic effect of IGS2.7, a CK1δ protein kinase inhibitor, in combination with riluzole for the treatment of ALS-associated TDP-43 proteinopathy.},
journal = {Neuropharmacology},
volume = {},
number = {},
pages = {110804},
doi = {10.1016/j.neuropharm.2025.110804},
pmid = {41389988},
issn = {1873-7064},
abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease for which no effective treatments currently exist. The FDA and EMA have approved only riluzole, a drug that modestly extends patient survival by 3 to 18 months. In our research, we have identified a novel CK1δ inhibitor, IGS2.7, which modulates TDP-43 proteinopathy, the main ALS pathological hallmark, in both patient-derived cellular models and TgTDP-43 mice. To assess the potential of IGS2.7 as a therapeutic candidate and considering riluzole remains the standard care for ALS patients, we evaluated its effects in combination with riluzole. Our results demonstrate that co-administration of IGS2.7 and riluzole at effective doses does not cause adverse effects. However, no additional therapeutic benefit was observed beyond that of IGS2.7 monotherapy, suggesting that IGS2.7 may be viable as either a stand-alone treatment or as an adjunct to riluzole. Notably, when suboptimal doses of both drugs were administered, a combined effect was observed. This suggests that, once IGS2.7 reaches clinical testing, its use together with lower doses of riluzole may enhance therapeutic efficacy while potentially minimizing side effects. Additional in vivo pre-clinical studies will be required to further evaluate this possibility, although only clinical trials will ultimately determine its clinical relevance.},
}

@article {pmid41389796,
year = {2025},
author = {Alessandrini, F and Wright, M and Kurosaki, T and Perloff, OS and Ngo, M and Kofler, JK and Donnelly, CJ and Maquat, LE and Kiskinis, E},
title = {TDP-43 dysfunction compromises UPF1-dependent mRNA metabolism in ALS.},
journal = {Neuron},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuron.2025.11.001},
pmid = {41389796},
issn = {1097-4199},
abstract = {Up-frameshift protein 1 (UPF1)-mediated mRNA decay maintains transcriptome integrity and cellular homeostasis. However, its role in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by TAR DNA-binding protein 43 (TDP-43) pathology and disrupted mRNA metabolism in motor neurons (MNs), remains unresolved. Here, we integrated RNA sequencing (RNA-seq) after UPF1 knockdown with RNA immunoprecipitation (RIP)-seq of phosphorylated UPF1 to delineate direct UPF1 targets in induced pluripotent stem cell (iPSC)-derived MNs. These transcripts are enriched for autophagy and structurally characterized by GC-rich, long 3' untranslated regions (3' UTRs). UPF1 activity, measured by this transcript signature, is diminished in TDP-43-depleted and ALS patient MNs. Mechanistically, TDP-43 depletion impairs UPF1 phosphorylation; the two proteins interact in an RNA-dependent manner and co-aggregate in pathological inclusions in ALS tissue. Transcriptomic analyses reveal convergent regulation of alternative polyadenylation and 3' UTR length by UPF1 and TDP-43, processes disrupted in ALS models and patient neurons. Our study defines the mRNA surveillance network of UPF1 in MNs and uncovers a link between RNA decay, TDP-43 dysfunction, and ALS neurodegeneration.},
}

@article {pmid41389317,
year = {2025},
author = {Argo, A and Puntarello, M and Malta, G and Tarantino, M and Midiri, M and Pellerito, S and Albano, GD and Zerbo, S},
title = {Verification of the persistence of sperm traces under different chain-of-custody conditions. Care pathway and justice for victims of sexual violence and abuse.},
journal = {Forensic science, medicine, and pathology},
volume = {},
number = {},
pages = {},
pmid = {41389317},
issn = {1556-2891},
abstract = {The primary aim of this study was to verify the persistence of seminal traces under varying chain-of-custody conditions, along with determining how different contamination factors, time intervals between collection, and storage methods influence the detectability of semen in the context of sexual assault cases. This study combined laboratory and field analyses to simulate real-case scenarios. Three forensic detection tools-Sperm Tracker Lab, Sperm Tracker Spray, and RSID™ tests-were evaluated on multiple substrates (skin, hair, nylon, cotton, and car interiors) and under various contamination conditions, including the presence of blood, dust, soil, and bodily fluids. Detection techniques included contact-pressure methods (Sperm Tracker Lab), application on uneven surfaces (Sperm Tracker Spray), fluorescence-based searches with ALS (alternative light sources), and immunochromatographic testing (RSID™ kits) for sperm-specific proteins. Positive findings were confirmed via microscopic examination and DNA analysis. All the samples were labelled and stored following strict chain-of-custody protocols. Sperm Tracker Spray demonstrated consistent effectiveness, successfully detecting minimal volumes (1-2 µL) across a wide range of materials. Conversely, ALS showed reduced sensitivity, especially in the presence of diluted or minimal traces and on textured or dark fabrics. RSID™ kits provided reliable confirmation of the presence of semen, even when environmental or biological contamination was present. Accurate and thorough documentation of the chain of custody proved essential for preserving sample authenticity and reducing the risk of error. The findings underscore the importance of a multidisciplinary forensic approach combining specialized reagents, confirmatory immunochromatographic testing, and rigorous adherence to chain-of-custody procedures. This integrated strategy enhances the reliability of seminal trace detection in investigations of sexual assault. Moreover, verifying trace persistence under diverse conditions contributes significantly to the evidentiary value of forensic samples in judicial contexts.},
}

@article {pmid41389101,
year = {2025},
author = {Li, Y and Zhou, Y and Yu, L and Bi, Y and Yi, L and Li, C and Liu, Y},
title = {Myeloid Irf5 Deficiency Enhances the Therapeutic Efficacy of IMD-0354 in a TDP-25-Induced Neurodegeneration Model.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {290},
pmid = {41389101},
issn = {1559-1182},
support = {H2024206009//the Hebei Natural Science Foundation/ ; 81901290//the National Natural Science Foundation of China/ ; },
mesh = {Animals ; *Interferon Regulatory Factors/deficiency/metabolism ; *DNA-Binding Proteins/toxicity/metabolism ; Macrophages/metabolism/drug effects ; Mice, Knockout ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; Apoptosis/drug effects ; Motor Neurons/metabolism/drug effects/pathology ; Mitochondria/metabolism/drug effects ; Cell Line ; Amyotrophic Lateral Sclerosis/drug therapy ; Neuroprotective Agents/pharmacology/therapeutic use ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology ; *Nerve Degeneration/drug therapy/pathology/metabolism ; *Myeloid Cells/metabolism/drug effects ; },
abstract = {Neuroinflammation is recognized as a key contributor to the pathogenesis and progression of amyotrophic lateral sclerosis (ALS), with dysregulated innate immune activation implicated in exacerbating neuronal injury. However, the molecular mechanisms by which macrophages contribute to neurodegeneration in motor neurons harboring TAR DNA-binding protein 43 (TDP-43) mutations are not fully understood. M1 macrophages were generated from the bone marrow of Irf5 knockout or wild-type mice and co-cultured with the NSC34 motor neuron-like cell line overexpressing the C-terminal fragment of TDP-43 (TDP-25) using a Transwell system. Mitochondrial alterations, and apoptosis were evaluated through Western blotting, flow cytometry, and transmission electron microscopy. IMD-0354 mitigated mitochondrial dysfunction and apoptosis induced by TDP-25 exposure. This neuroprotective effect was attenuated in the presence of pro-inflammatory macrophages. Notably, the absence of Irf5 expression in macrophages amplified the protective efficacy of IMD-0354. Irf5 expression in macrophages may modulate the therapeutic efficacy of IMD-0354 in the context of TDP-43-associated proteinopathy, indicating a potential target for enhancing treatment strategies in ALS-related neurodegeneration through inhibiting inflammation.},
}

Animals
*Interferon Regulatory Factors/deficiency/metabolism
*DNA-Binding Proteins/toxicity/metabolism
Macrophages/metabolism/drug effects
Mice, Knockout
Mice
Disease Models, Animal
Mice, Inbred C57BL
Apoptosis/drug effects
Motor Neurons/metabolism/drug effects/pathology
Mitochondria/metabolism/drug effects
Cell Line
Amyotrophic Lateral Sclerosis/drug therapy
Neuroprotective Agents/pharmacology/therapeutic use
*Neurodegenerative Diseases/drug therapy/metabolism/pathology
*Nerve Degeneration/drug therapy/pathology/metabolism
*Myeloid Cells/metabolism/drug effects

@article {pmid41388206,
year = {2025},
author = {Schmitt, P and Schumann, P and Koerbs, A and Lin, HJ and Grehl, T and Weyen, U and Petri, S and Rödiger, A and Steinbach, R and Großkreutz, J and Bernsen, S and Weydt, P and Wolf, J and Günther, R and Baum, P and Metelmann, M and Weishaupt, JH and Streubel, B and Kasper, DC and Koc, Y and Kettemann, D and Norden, J and Walter, B and Münch, C and Spittel, S and Maier, A and Körtvélyessy, P and Meyer, T},
title = {Motor phenotypes and neurofilament light chain in genetic amyotrophic lateral sclerosis-results from a multicenter screening program.},
journal = {Journal of neurology},
volume = {273},
number = {1},
pages = {22},
pmid = {41388206},
issn = {1432-1459},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/blood/physiopathology/diagnosis ; *Neurofilament Proteins/blood ; Male ; Female ; Middle Aged ; C9orf72 Protein/genetics ; Phenotype ; Aged ; RNA-Binding Protein FUS/genetics ; Superoxide Dismutase-1/genetics ; Adult ; Disease Progression ; Cohort Studies ; DNA-Binding Proteins/genetics ; },
abstract = {OBJECTIVE: In genetic amyotrophic lateral sclerosis (ALS), the clinical phenotypes, disease progression and neurofilament light chain (NfL) levels are incompletely characterized.

METHODS: In a total cohort of 1988 ALS patients, a subcohort of genetic ALS linked to C9orf72 (n = 137), SOD1 (n = 54), TARDBP (n = 27), and FUS (n = 19) was investigated. The phenotypes of onset region, propagation and motor neuron involvement were analyzed according to the OPM classification. Serum NfL (sNfL) was measured and related to ALS progression (ALSPR, monthly change of ALS Functional Rating Scale-Revised). To quantify NfL elevation relative to ALSPR, the logNfL(index), the log-transformed ratio of sNfL to ALSPR was calculated.

RESULTS: C9orf72-associated ALS showed frequent bulbar onset (n = 42.6%), higher ALSPR (0.95, SD 0.84), highest NfL (116.3, SD 72.7 pg/mL) and logNfL(index) (5.02, SD 0.88). SOD1-ALS had mostly limb onset (n = 96.1%), slower ALSPR (0.57, SD 0.60), high NfL (76.1, SD 61.4 pg/mL) and a comparably high logNfL(index) (4.94, SD 1.03). FUS-ALS exhibited mostly limb onset (82.4%), lower motor neuron dysfunction (70.6%), a wide range of faster (22.2%) to slower ALSPR (55.6%), lower NfL (66.2, SD 32.9) and logNfL(4.65, SD 0.9). TARDBP-ALS displayed the lowest ALSPR (0.53, SD 0.52), the lowest NfL (43.3, SD 31.8 pg/mL) and the lowest logNfL(index) (4.40, SD 0.7).

CONCLUSION: In C9orf72-ALS, the phenotype and NfL profile are close to typical ALS. The finding of distinct phenotypes and NfL patterns in SOD1-, FUS- and TARDBP-associated ALS underscores the relevance of genetic ALS for prognostic counseling, clinical trial design, treatment expectations and unraveling of pathogenic mechanisms in ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/blood/physiopathology/diagnosis
*Neurofilament Proteins/blood
Male
Female
Middle Aged
C9orf72 Protein/genetics
Phenotype
Aged
RNA-Binding Protein FUS/genetics
Superoxide Dismutase-1/genetics
Adult
Disease Progression
Cohort Studies
DNA-Binding Proteins/genetics

@article {pmid41386880,
year = {2025},
author = {Eshak, D and Arumugam, M},
title = {Integrative analysis of transcriptomics and drug-target networks identifies SMN1 as a novel biomarker and therapeutic target for amyotrophic lateral sclerosis.},
journal = {Journal, genetic engineering & biotechnology},
volume = {23},
number = {4},
pages = {100615},
doi = {10.1016/j.jgeb.2025.100615},
pmid = {41386880},
issn = {2090-5920},
abstract = {Amyotrophic lateral sclerosis (ALS) is a prevalent and debilitating neurodegenerative disorder characterized by the selective degeneration of motor neurons. This study aims to unravel the molecular mechanisms underlying ALS through an integrated analysis of drug-target networks and gene expression data. Gene expression datasets related to ALS, including GSE115130 and GSE76220, were retrieved from the GEO database and systematically analyzed. Differential gene expression (DEG) analysis identified key upregulated and downregulated genes, while weighted gene co-expression network analysis (WGCNA) uncovered gene modules associated with ALS pathology. DEG analysis revealed genetic insights into ALS by pinpointing genes potentially involved in disease development and progression. WGCNA provided a systems-level understanding of ALS mechanisms, identifying highly correlated gene clusters and their relationship with clinical ALS characteristics. In the GSE115130 dataset, 6,105 genes were upregulated and 6,069 were downregulated. Conversely, the GSE76220 dataset showed 4,850 upregulated genes and 7,691 downregulated genes. Using the STRING database, a protein-protein interaction (PPI) network was constructed to investigate the functional relationships among ALS-associated genes. The findings highlighted the significant role of the survival motor neuron 1 (SMN1) gene in ALS, particularly in sporadic cases. Additionally, drug-target network mapping identified potential therapeutic targets and candidate drugs, offering valuable insights into the molecular mechanisms of ALS and possible interventions. This integrative approach underscored SMN1 as a novel diagnostic biomarker and potential therapeutic target for ALS, emphasizing its critical role in disease pathogenesis. These findings pave the way for further mechanistic studies and clinical validation, aiming to enhance therapeutic strategies for ALS.},
}

@article {pmid41386291,
year = {2025},
author = {Andersen, CA and Jenssen, C and Poppleton, A and Leceaga, E and Kosiak, M and Iacob, MS and Skendi, M and Frese, T and Løkkegaard, T and Homar, V and Rüttermann, V and Ewertsen, C},
title = {Point-of-care ultrasound in primary care - EFSUMB core curriculum and training recommendations, a position paper.},
journal = {Ultraschall in der Medizin (Stuttgart, Germany : 1980)},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2771-2848},
pmid = {41386291},
issn = {1438-8782},
abstract = {English abstract: Frontline physicians working in primary care increasingly use diagnostic ultrasound examinations and simple ultrasound-guided procedures as part of their daily practice. Primary care is organized in many ways across Europe and as a result, primary care physicians have different qualifications in terms of using and integrating point-of-care ultrasound in patient care. To ensure high quality and standardized practice across Europe, this position paper of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) describes training recommendations and a generic core curriculum for frontline physicians working in primary care. The core curriculum was developed through a Delphi process and includes basic ultrasound examinations corresponding to the EFSUMB competence level 1 for medical ultrasound practice. The training recommendations are intended to build a common foundation while national adjustments must be made to ensure relevance in the clinical setting and patient population. German abstract: In der Primärversorgung tätige Ärzte setzen zunehmend diagnostische Ultraschalluntersuchungen und einfache ultraschallgesteuerte Verfahren als Teil ihrer täglichen Routine ein. Die Primärversorgung ist in Europa sehr unterschiedlich organisiert, sodass die Qualifikationen der Ärzte, die Point-of-Care-Ultraschall in der primären Patientenversorgung einsetzen und integrieren, sehr unterschiedlich sind. Mit dem Ziel, eine hohe Qualität und standardisierte Ausübungspraxis in ganz Europa zu gewährleisten, stellt dieses Positionspapier der European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Ausbildungsempfehlungen und ein PoCUS Basis-Curriculum für in der Primärversorgung tätige Ärzte vor. Das Basis-Curriculum wurde im Rahmen eines Delphi-Verfahrens entwickelt und umfasst grundlegende Ultraschalluntersuchungen, die dem EFSUMB-Kompetenzniveau 1 für die medizinische Ultraschallpraxis entsprechen. Die Ausbildungsempfehlungen sollen eine gemeinsame Grundlage schaffen, wobei durch nationale Anpassungen die Relevanz für das konkrete klinische Umfeld und die betreuten Patientengruppen sichergestellt werden muss.},
}

@article {pmid41387380,
year = {2025},
author = {Savasan-Sogut, M and Campos-Melo, D and Strong, MJ},
title = {3'UTR variants of ALS-linked RNAs modify subcellular and cellular phenotypes.},
journal = {The FEBS journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/febs.70364},
pmid = {41387380},
issn = {1742-4658},
support = {SOP-160442/CAPMC/CIHR/Canada ; },
abstract = {While most human genes express mRNA 3'untranslated region (3'UTR) variants of different lengths, their impact on cell physiology and disease remains largely unknown. Here, we studied 3'UTR length heterogeneity in amyotrophic lateral sclerosis (ALS) and determined that three ALS-linked transcripts exhibit lengthening of their 3'UTRs in patient samples. We investigated phenotypical effects in a neuronal cell line expressing these 3'UTRs and observed that expression of these unique 3'UTRs induces morphological changes at different levels. Among the most expressed 3'UTR variants in ALS, NEFH 3'UTR-Long induces the formation of nuclear RNA clusters, and Superoxide Dismutase 1 3'UTR-Long diminishes filopodia in the plasma membrane. Sequestosome 1 3'UTR-Long did not show major changes in nuclear RNA clusters or filopodia. Our findings provide the first evidence that 3'UTRs can modulate cellular phenotype independent of the coding region, further expanding the impact of alterations in mRNA biogenesis in ALS.},
}

@article {pmid41386992,
year = {2025},
author = {Myers, AK and Sakheim, M and Rivell, C and Fengler, C and Festa, LK and Guerra, KM and Jarrahy, L and Shin, R and Case, M and Chapman, C and Basel, L and Springer, S and Kern, N and Gidicsin, J and Cho, G and Kim, S and Tighiouart, M and Golden, JA},
title = {Anxiety-associated behaviors following ablation of Miro1 from cortical excitatory neurons.},
journal = {eNeuro},
volume = {},
number = {},
pages = {},
doi = {10.1523/ENEURO.0436-25.2025},
pmid = {41386992},
issn = {2373-2822},
abstract = {Autism spectrum disorder, schizophrenia, and bipolar disorder are neuropsychiatric conditions that manifest early in life with a wide range of phenotypes, including repetitive behavior, agitation, and anxiety (American Psychological Association, 2013). While the etiology of these disorders is incompletely understood, recent data implicate a role for mitochondrial dysfunction (Norkett et al., 2017; Khaliulin et al., 2025). Mitochondria dynamically translocate to intracellular compartments to support energetics and free-radical buffering; failure to achieve this localization results in cellular dysfunction (Picard et al., 2016). Mitochondrial Rho-GTPase 1 (Miro1) resides on the outer mitochondrial membrane and facilitates microtubule-mediated mitochondrial motility and homeostasis (Fransson et al., 2003). The loss of MIRO1 is reported to contribute to the onset/progression of neurodegenerative diseases, including amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease (Kay et al., 2018). We have hypothesized that MIRO1 also has a role in nervous system development and function (Lin-Hendel et al., 2016). To test this, we ablated Miro1 from cortical excitatory progenitors by crossing floxed Miro1 mice with Emx1-Cre mice and used mice of either sex for experiments. We found that mitochondrial mis-localization in migrating excitatory neurons was associated with reduced brain weight, decreased cortical volume, and subtle cortical disorganization. Adult Miro1 conditional mutants exhibit agitative-like behaviors, including decreased nesting behavior and abnormal home cage activity. The mice exhibited anxiety-like behavior and avoided confined spaces, features that have been linked to several human behavioral disorders. Our data link MIRO1 function with mitochondrial dynamics in the pathogenesis of several neuropsychiatric disorders and implicate intracellular mitochondrial dynamics to some anxiety-like behaviors.Significance Statement Neuropsychological disorders such as autism spectrum disorder, schizophrenia, and bipolar disorder have overlapping endophenotypes. While the mechanisms underlying these disorders are poorly understood, recent evidence implicates mitochondrial dysfunction and cellular mis-localization playing a role. Mitochondria support energy requirements and other physiological functions in cells. Previous research from our lab has shown distinct dynamic localization patterns within migrating excitatory and inhibitory neurons during development. To further examine the importance of mitochondrial localization, we ablated MIRO1, a protein important for coupling mitochondria to motor proteins, in excitatory neurons. The mis-localization of mitochondria in migrating excitatory neurons is associated with diminished motor skills and anxiety-like behavior in post-natal mice.},
}

@article {pmid41386904,
year = {2025},
author = {eBioMedicine, },
title = {The accelerating pace of amyotrophic lateral sclerosis research.},
journal = {EBioMedicine},
volume = {122},
number = {},
pages = {106079},
doi = {10.1016/j.ebiom.2025.106079},
pmid = {41386904},
issn = {2352-3964},
}

@article {pmid41386298,
year = {2025},
author = {Ealy, A and Serapiglia, AM and Panicker, N},
title = {Sterile Innate Immune Mechanisms in Neurodegenerative diseases.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {111039},
doi = {10.1016/j.jbc.2025.111039},
pmid = {41386298},
issn = {1083-351X},
abstract = {Neurodegenerative diseases are characterized by the dysfunction and death of susceptible neuronal populations. Increasing evidence has demonstrated that sustained neuroinflammation and activation of innate immune complexes underlie neurodegeneration, worsening disease progression and outcomes. Sterile inflammation (which occurs in the absence of infection) can be triggered by neurodegenerative disease-associated misfolded proteins. These studies highlight the need to decipher the complexities of innate immune signaling mechanisms and their contribution to neuropathology. In this review, we focus on major neurodegenerative diseases that have a well-documented neuroinflammatory component: Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS) and Frontotemporal Dementia (FTD). In the context of these diseases, we discuss recent advances in innate-immune mechanisms that have been demonstrated to partake in disease progression and neurodegeneration. These include evolutionarily conserved innate-immune signaling complexes whose uncontrolled activation amplifies neurodegeneration, damaging lipid droplets that accumulate within myeloid cells and prevent their ability to clear toxic protein aggregates, as well as genome-wide studies implicated genes/proteins. The individual and/or concerted actions of these pathways could be leveraged to rationally target the pathogenesis or progression of neurodegenerative diseases.},
}

@article {pmid41385186,
year = {2025},
author = {Mitsiadou, D and Xirodimas, DP and Polanowska, J},
title = {NEDD8, stress granules, and amyotrophic lateral sclerosis: unveiling the therapeutic potential of the NEDP1 protease.},
journal = {Essays in biochemistry},
volume = {},
number = {},
pages = {},
doi = {10.1042/EBC20253036},
pmid = {41385186},
issn = {1744-1358},
abstract = {Protein quality control (PQC) systems are crucial for maintaining cellular proteostasis, particularly under stress that promotes misfolded protein accumulation. A central component of this response is the assembly of stress granules (SGs), cytoplasmic condensates of RNA and proteins that temporarily stall translation. Aberrant SG dynamics, often linked to mutations in SG proteins, contribute to neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), where persistent protein aggregates are hallmarks. This review examines the emerging role of the ubiquitin-like modifier NEDD8 and its deconjugating enzyme NEDP1 in regulating SG homeostasis. Recent studies identify NEDP1 as a critical factor controlling SG clearance. Inhibition of NEDP1 enhances SG turnover, prevents pathological solidification, and promotes the disassembly of toxic aggregates through hyper-NEDDylation of PARP1, a DNA repair enzyme that also governs SG dynamics. Unlike broad-spectrum PARP1 inhibitors, which can impair DNA repair and cause cytotoxicity, NEDP1 inhibition offers a stress-specific approach that preserves normal cellular functions. Encouragingly, NEDP1 inhibition effectively causes aggregate elimination in ALS patient-derived fibroblasts and restores motility in Caenorhabditis elegans disease models. Altogether, these findings highlight NEDP1 as a key regulator of SG regulation and a promising therapeutic target for ALS and related neurodegenerative disorders.},
}

@article {pmid41385026,
year = {2025},
author = {Kara, NS and Ozisik, O and Baudot, A and Slachtova, L},
title = {Investigating the Potential Roles of Environmental Exposures on the Pathology of Amyotrophic Lateral Sclerosis by Overlap Analysis.},
journal = {Neurotoxicity research},
volume = {43},
number = {6},
pages = {51},
pmid = {41385026},
issn = {1476-3524},
support = {AMX-19-IET-007//Initiative d'Excellence d'Aix-Marseille Université/ ; PRIMUS UK 21/MED/012//Univerzita Karlova v Praze/ ; OP JAK MSCA//Ministerstvo Školství, Mládeže a Tělovýchovy/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; Humans ; *Environmental Exposure/adverse effects ; Vehicle Emissions/toxicity ; Pesticides/toxicity ; Toluene/toxicity ; Smoking/adverse effects ; Computational Biology ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease causing motor neuron loss. 90-95% of ALS cases are sporadic, and the interplay of genetic predispositions and environmental exposures is essential in ALS pathology. Several neurotoxic exposures, such as smoking, pesticides, and organic solvents, have been implicated as affecting the risk of ALS. However, it is unclear how these exposures impact specific cellular mechanisms and influence ALS risk. We investigated the potential mechanisms of toxicity of diesel exhaust, toluene, pesticides, and smoking on ALS pathology through a bioinformatics approach. We retrieved the gene sets targeted by these environmental exposures, and the gene sets involved in ALS-associated biological processes. We performed overlap analysis to assess the statistical significance of the overlap between the gene sets associated with environmental exposures and those linked to ALS. Response to oxidative stress, synaptic signaling, lipid metabolic process, cellular oxidant detoxification, and regulation of gliogenesis significantly overlapped with the gene sets targeted by each of the four environmental exposures. Contrarily, chaperone-mediated autophagy, DNA repair, and regulation of action potential, significantly overlapped only with the gene sets targeted by diesel exhaust, pesticides, and toluene, respectively. Finally, transport across the blood-brain barrier, vesicle-mediated transport, actin filament-based transport, autophagy, transport to the Golgi and subsequent modification of proteins, metabolism of lipids, regulation of neurotransmitter receptor levels, and axon guidance significantly overlapped only with the gene set targeted by tobacco smoke pollution. This study aims to investigate the molecular relationships between neurotoxic exposures and ALS by overlap analysis, providing a framework that can be applied to investigate other exposure-disease interactions.},
}

*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism
Humans
*Environmental Exposure/adverse effects
Vehicle Emissions/toxicity
Pesticides/toxicity
Toluene/toxicity
Smoking/adverse effects
Computational Biology

@article {pmid41384353,
year = {2025},
author = {Yu, H and Zhang, X and Liu, Z and Zhang, L},
title = {Explaining Isoform Selectivity of c-Jun N-Terminal Kinase 3 (JNK3) Inhibitors through Its Development and Structural Insights.},
journal = {Journal of medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jmedchem.5c01488},
pmid = {41384353},
issn = {1520-4804},
abstract = {c-Jun N-terminal kinase 3 (JNK3), a member of the mitogen-activated protein kinase (MAPK) family, is selectively enriched in the brain. It plays a significant role in the pathogenesis of neurodegenerative disorders, glaucoma, amyotrophic lateral sclerosis, and cancer, which makes it a promising drug target. However, the advancement of JNK3 inhibitors has been challenged by limited isoform selectivity. This article explains the pathway regulated by JNK3 and the unique functions of JNK3. A detailed structural analysis of JNK3 complexes with ligands is presented to uncover the molecular basis of binding interactions. The inhibitors are systematically classified according to their chemical scaffolds, and the reason for their isoform selectivity was discussed, providing a structural rationale for the evolution of JNK3 inhibitor design. The perspective concludes with an exploration of the challenges in the discovery of selective JNK3 inhibitors and proposes innovative strategies to surmount these obstacles.},
}

@article {pmid41384008,
year = {2025},
author = {Gutral, J and Cypryańska, M and Nezlek, JB},
title = {A Polish language version of Wood et al.'s multidimensional Authenticity Scale.},
journal = {Current issues in personality psychology},
volume = {13},
number = {4},
pages = {254-260},
pmid = {41384008},
issn = {2353-561X},
abstract = {BACKGROUND: There is considerable interest among personality psychologists in authenticity. To provide researchers with a tool to study dispositional authenticity among speakers of Polish, we created a Polish language version of Wood et al.'s multidimensional measure of authenticity. Wood et al.'s measure has 12 items and measures three constructs: four items for selfalienation; authentic living; and accepting external influence.

PARTICIPANTS AND PROCEDURE: Participants were 825 Polish adults (M age = 42.7, SD = 15.4; 50% women) who were recruited by a professional survey company. Participants completed the newly developed measure of authenticity, and for validation purposes, they completed measures of Ryff's model of well-being, self-esteem, satisfaction with life, and stress, the same measures used by Wood et al.

RESULTS: A confirmatory factor analysis found that the Polish version of the scale had the same three factors as the original measure developed by Wood et al., and the loadings of the items on the factors were consistent with those presented by Wood et al. The three scales of the new measure were reliable. Moreover, relationships between the authenticity scales and the validation measures were similar to those reported by Wood et al.

CONCLUSIONS: The present results suggest that our proposed Polish language version of Wood et al.'s multidimensional authenticity scale measures a similar set of constructs to those measured by the original English language scale. Therefore, we believe our new measure should be useful for researchers interested in studying dispositional authenticity among Polish language speakers.},
}

@article {pmid41383013,
year = {2025},
author = {Hor, JH and Ow, JR and Ng, W and Ramasamy, B and Tabaglio, T and Hui Lim, KN and Bin Muzakar, MI and Wen Lim, VJ and Gurrampati, RR and Rajarethinam, R and Ngo, ST and Ramadass, V and Ling, SC and Lakshmanan, M and Wee, KB and Ng, SY},
title = {Depletion of BLOC1S1 with splice-switching oligonucleotides in ALS motor neurons improves mitochondrial respiration and rescues disease phenotypes.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2025.12.026},
pmid = {41383013},
issn = {1525-0024},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressing and debilitating neurodegenerative disease, yet the mechanisms underlying disease onset and progression remain poorly understood, particularly in sporadic ALS. Emerging evidence suggests that mitochondrial dysfunction and metabolic dysregulation are central to ALS pathophysiology. A key feature of ALS motor neurons (MNs) is hyper-acetylation of mitochondrial proteins, which disrupt mitochondrial respiration and energy homeostasis. In this study, we identify BLOC1S1 (also known as GCN5L1) as a novel regulator of mitochondrial acetylation in ALS. We demonstrate that BLOC1S1 is significantly upregulated in ALS patient-derived MNs, post-mortem motor cortices, and spinal cords of ALS mouse models. Functional studies in induced pluripotent stem cell (iPSC)-derived MNs reveal that BLOC1S1 depletion rescues key disease phenotypes. Therefore, we develop an efficacious splice-switching antisense oligonucleotide (SSO) that induces nonsense-mediated decay of BLOC1S1 transcripts as a potential therapeutic candidate. Besides mitigating ALS-relevant cellular deficits in MN cultures from diverse genetic backgrounds, it was validated to extend disease-free and overall survival that is associated with improved rotarod performance in an ALS mouse model. These findings establish BLOC1S1 as a critical modifier of disease progression in ALS and highlight its potential as a novel therapeutic target.},
}

@article {pmid41381924,
year = {2025},
author = {Soares, ÁM and de Paula Cruz, ECO and da Silva, LG and de Sousa, YG and Távora, DGF and de Albuquerque, LAF},
title = {Anatomical references for the transopercular approach to the insula: a 1.5 Tesla magnetic resonance study.},
journal = {Neurosurgical review},
volume = {49},
number = {1},
pages = {63},
pmid = {41381924},
issn = {1437-2320},
mesh = {Humans ; *Magnetic Resonance Imaging/methods ; Female ; Male ; Adult ; Middle Aged ; *Insular Cortex/anatomy & histology/surgery ; *Cerebral Cortex/anatomy & histology/surgery ; Young Adult ; Aged ; Adolescent ; Brain Mapping/methods ; },
abstract = {OBJECTIVE: This study aimed to establish the topographic relation of the limiting sulci of the insula with structures on the brain surface, in addition to determining a new anatomical point to objectively identify the Berger-Sanai quadrants.

METHODS: 1.5 Tesla MRI was used to analyze 100 insulas and their relation to the brain surface. The projection of the anterior (ALS), superior (SLS), and inferior (ILS) limiting sulci of the insula onto the brain surface was determined, together with the relations between these sulci and the anterior Sylvian point (ASP), the inferior frontal sulcus (IFS), and the superior temporal sulcus (STS). The central point of the Berger-Sanai quadrants was identified based on the inferior Rolandic point (IRP). The projection of this central point onto the insula and the brain surface were also identified.

RESULTS: The following measurements were calculated: the mean anteroposterior distance between the ASP and ALS, 3.2 mm ± 0.7 mm; the mean craniocaudal distance from the ASP to the SLS, 10.5 mm ± 1.8 mm; the mean craniocaudal distance between the IFS and SLS, 15.5 mm ± 2.5 mm; the mean craniocaudal distance from the end of the IFS to the SLS, 13.5 mm ± 2.9 mm; the mean craniocaudal distance between the STS and ILS, 4.0 mm ± 1.9 mm; the mean craniocaudal distance from the end of the STS to the ILS, 6.1 mm ± 2.4 mm; and the mean laterolateral distance from the STS to the ILS, 22.7 mm ± 3.5 mm. The central point of the Berger Sanai quadrants was determined to be over the Sylvian fissure, at a mean distance of 7.3 mm ± 1.2 mm anterior to the IRP. This point projected over the precentral gyrus in 79% of cases and the posterior short gyrus of the insula in 68%.

CONCLUSIONS: The data obtained in this study demonstrate a close topographic relationship between easily identifiable structures on the brain surface (ASP, IFS and STS) and the limiting sulci of the insula. We propose a simple, novel way to find the central point of the Berger Sanai quadrants based on their relation with the IRP. The findings determined here can assist neurosurgeons in locating the insula, especially in transopercular approaches.},
}

Humans
*Magnetic Resonance Imaging/methods
Female
Male
Adult
Middle Aged
*Insular Cortex/anatomy & histology/surgery
*Cerebral Cortex/anatomy & histology/surgery
Young Adult
Aged
Adolescent
Brain Mapping/methods

@article {pmid41381656,
year = {2025},
author = {Riley, S and Nguyen, V and Bhattacharjee, R and Ng, PQ and Ritchie, T and Kamath, KS and Fisk, I and Gecz, J and Kumar, R and Searle, IR},
title = {TMT-based quantitative proteomic assessment of Vicia sativa induced neurotoxicity by β-cyano-L-alanine and γ-glutamyl-β-cyano-L-alanine in SH-SY5Y cells.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-30121-2},
pmid = {41381656},
issn = {2045-2322},
support = {BB/V018108/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; LP200200957//Australian Research Council/ ; LP200200957//Australian Research Council/ ; LP200200957//Australian Research Council/ ; UA720//South Australian Grains and Industry Trust/ ; },
abstract = {β-cyano-L-alanine (BCA) and γ-glutamyl-β-cyano-L-alanine (GBCA) are the primary antinutritional compounds in Vicia sativa, a high-protein, drought-tolerant legume. While their neurotoxicity in monogastric animals has been reported, the molecular basis remains largely unknown. In this study, we optimised a rapid in vitro assay using retinoic acid-differentiated SH-SY5Y human neuroblastoma cells to assess BCA and GBCA toxicity, and then applied Tandem mass tags (TMT)-mass spectrometry (MS)-based quantitative proteomics to identify dysregulated proteins. BCA treatment dysregulated the proteins involved in DNA damage, translation, and oxidative stress, many of which are associated with neurodegenerative diseases such as amyotrophic lateral sclerosis and Alzheimer's disease, as well as various cancers. In contrast, GBCA impacted the proteins linked to mitosis, cell cycle regulation, and apoptosis pathways. Interestingly, the absence of overlapping dysregulated proteins between BCA- and GBCA-treated cells suggested that the two toxins likely induce neurotoxicity via distinct mechanisms. These findings offer new insights into the molecular and cellular alterations caused by V. sativa toxins and their implications for animal feed safety.},
}

@article {pmid41381004,
year = {2025},
author = {Maas, D and Spindler, A and Zappi, I and Shapiro, J and Lo Sicco, KI},
title = {Response to Olsen et al's ''Summation and recommendations for the safe and effective use of topical and oral minoxidil".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.09.118},
pmid = {41381004},
issn = {1097-6787},
}

@article {pmid41380670,
year = {2025},
author = {Fujioka, Y and Ishigaki, S},
title = {Decoding ALS from the tail end of RNA.},
journal = {Cell genomics},
volume = {5},
number = {12},
pages = {101102},
doi = {10.1016/j.xgen.2025.101102},
pmid = {41380670},
issn = {2666-979X},
mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; Humans ; Polyadenylation/genetics ; RNA, Messenger/genetics/metabolism ; Transcriptome/genetics ; Brain/metabolism ; },
abstract = {In this issue of Cell Genomics, McKeever et al.[1] generate a single-nucleus transcriptomic atlas of ALS/FTLD brain and reveal widespread alternative polyadenylation changes. Their findings highlight 3' end RNA processing as a central integrator of stress responses, cell-type specificity, and disease susceptibility, offering new mechanistic insight and potential therapeutic directions.},
}

*Amyotrophic Lateral Sclerosis/genetics/metabolism
Humans
Polyadenylation/genetics
RNA, Messenger/genetics/metabolism
Transcriptome/genetics
Brain/metabolism

@article {pmid41380476,
year = {2025},
author = {Gu, Y and Chen, Y and Tang, X and Guo, J and Hu, J and Yang, W and Li, J and Chen, X and Fan, D and Chen, GB and He, J and Ren, Y and Dong, Y and Sato, C and Chen, Y and Zinman, L and Rogaeva, E and Zhang, M},
title = {Multi-omics analyses identify potential epigenetic loci associated with survival in amyotrophic lateral sclerosis across diverse populations.},
journal = {EBioMedicine},
volume = {123},
number = {},
pages = {106071},
doi = {10.1016/j.ebiom.2025.106071},
pmid = {41380476},
issn = {2352-3964},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease, with highly diverse survival time. However, genetic and epigenetic factors influencing ALS survival across diverse populations remain unclear.

METHODS: We performed whole-genome sequencing (WGS) and DNA methylome array in blood DNA of patients with ALS. For survival analysis, we used Cox proportional hazards model for genetic variants, DNA methylation (DNAm) of CpG sites or CpG-SNPs in Chinese and Canadian cohorts, followed by meta-analysis. We performed pathway enrichment analysis for candidate genes inferred from DNAm events associated with survival. In paired genome and methylome data, we analysed the effect of the candidate CpG-SNP genotypes on DNAm status.

FINDINGS: Genome-wide cross-population meta-analysis of common variants in 511 patients with ALS showed a suggestive association of CAV1/CAV2 rs117002347 genotypes with survival. Epigenome-wide cross-population meta-analysis in 459 patients revealed that ALS survival was significantly linked to DNAm of 88 CpGs on 40 genes, and highlighted the AMPK and cytoskeleton pathways. Epigenome-wide cross-population meta-analysis of CpG-SNPs in 459 patients identified 8 loci on 4 genes, including BAG6 (cg27014438/rs28732154), which was further validated in another 204 patients with ALS. Moreover, analysis of paired genome/epigenome data (n = 454) indicated that BAG6 rs28732154 genotypes may modulate cg27014438 methylation, which is also a cis-eQTM of BAG6 expression in blood.

INTERPRETATION: Our study identified BAG6 cg27014438 methylation as a potential epigenetic modifier of ALS survival. BAG6 cg27014438 methylation is modulated by rs28732154 genotypes, and linked to BAG6 expression. Our findings extended our understanding of epigenetic modifiers in ALS survival.

FUNDING: This work was supported by the National Natural Science Foundation of China (82071430, 82371878) (MZ), Shanghai Municipal Natural Science Foundation General Program (22ZR1466400) (MZ), the Fundamental Research Funds for the Central Universities (MZ), the G. Harry Sheppard Memorial Research Fund, and Canadian Consortium on Neurodegeneration in Aging (ER).},
}

@article {pmid41379813,
year = {2025},
author = {Dashnaw, CM and Gonzalez, M and Abdolvahabi, A and Bassett, PT and Lato, TJ and Balamurali, R and Guberman-Pfeffer, MJ and Shaw, BF},
title = {Heteroaggregation of Wild-Type and ALS Mutant SOD1.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.5c00632},
pmid = {41379813},
issn = {1948-7193},
abstract = {The presence of wild-type (WT) Cu, Zn superoxide dismutase-1 (SOD1) can increase the toxicity of mutant SOD1 proteins linked to amyotrophic lateral sclerosis (ALS). The mechanism of synergy is unclear but might involve interactions between WT and mutant SOD1 in native or non-native states. One unanswered question is will the diverse rates of mutant SOD1 homofibrillization converge in the presence of WT SOD1? To answer this question, we assessed the coaggregation of mutant and WT SOD1 in vitro, including (i) how WT SOD1 affected the formation rate and stability of mutant fibrils and (ii) the proximity of WT and mutant SOD1 in heterofibrils. For most mutations studied, the presence of WT SOD1 slowed nucleation and propagation of mutant fibrils while increasing fibril thermostability. The D90A SOD1 protein was one exception: WT SOD1 had a nearly negligible effect on its rate of nucleation. The cross-seeding of soluble mutant SOD1 with WT fibrils (and of soluble WT SOD1 with mutant fibrils) suggests that both proteins can occupy the same fibril. Mass spectrometry of heterofibrils treated with an NHS-ester cross-linker (∼8 Å) suggested that WT and E100G mutant SOD1 are colocalized in heterofibrils, possibly stacked in an alternating configuration.},
}

@article {pmid41379346,
year = {2025},
author = {Canosa, A and Callegaro, S and Manera, U and Vasta, R and Cabras, S and Di Pede, F and De Mattei, F and Palumbo, F and Iazzolino, B and Dei Giudici, A and Matteoni, E and Zocco, G and Minerva, E and Maccabeo, A and Pellegrino, G and Pascariu, D and Grassano, M and Piombino, P and Testa, M and Polverari, G and Fuda, G and Merulla, I and Casale, F and Gallone, S and Moglia, C and Calvo, A and Pagani, M and Chiò, A},
title = {Brain metabolic connectivity in ALS due to C9ORF72 hexanucleotide expansion: a [[18]F]FDG-PET study.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {},
number = {},
pages = {},
pmid = {41379346},
issn = {1619-7089},
abstract = {PURPOSE: Our aim was to investigate brain metabolic connectivity, as assessed via [[18]F]FDG-PET, in ALS patients carrying the C9ORF72 expansion (C9-ALS).

METHODS: We compared brain metabolism of C9-ALS and patients without mutations of the main ALS-related genes (ctrl-ALS) through the two-sample t-test model of SPM12. Metabolic clusters showing a significant difference between the two groups were used as seed regions for an interregional correlation analysis (IRCA) in each group to evaluate metabolic connectivity.

RESULTS: As compared to ctrl-ALS, C9-ALS showed a relative hypometabolism in bilateral thalamus and left precentral and postcentral gyri, and a relative hypermetabolism in bilateral cerebellum and brainstem. In the IRCA, a positive correlation was found between the thalamic seed region and the cingulate cortex, including its anterior part. This correlation was broader in C9-ALS than in Ctrl-ALS. A negative correlation between the thalamic seed region and the sensorimotor cortex was only found in C9-ALS. In the IRCA, based on the cerebellar/brainstem cluster, positive correlations with the seed region substantially represented autocorrelation in both groups. Negative correlation, which mainly included frontal cortices, was more extensive in C9-ALS than in Ctrl-ALS.

CONCLUSION: In the comparison with ctrl-ALS, C9-ALS showed a relatively lower metabolism in the thalami and a relatively higher metabolism in the brainstem and the cerebellum. As compared to ctrl-ALS, C9-ALS showed a predominant involvement of the salience network, which is related to cognitive and behavioural control. The cerebellum might be recruited to cope with cognitive impairment to a greater extent in C9-ALS than in ctrl-ALS.},
}

@article {pmid41379273,
year = {2025},
author = {Zhang, R and Gao, B and Li, R and Zhou, R},
title = {Meta-analysis of the effects of dance- and movement-based kinesthetic games on cognitive function in older adults with cognitive impairment (CI) under different intervention periods.},
journal = {Aging clinical and experimental research},
volume = {37},
number = {1},
pages = {343},
pmid = {41379273},
issn = {1720-8319},
support = {24YJC890031//he Ministry of Education 's Youth Fund Project for Humanities and Social Sciences/ ; 22PJC094//Shanghai Pujiang Program/ ; },
mesh = {Humans ; *Cognitive Dysfunction/therapy/psychology ; Aged ; *Cognition/physiology ; *Video Games ; *Dancing ; *Dance Therapy/methods ; Male ; Randomized Controlled Trials as Topic ; *Exercise Therapy/methods ; Female ; },
abstract = {OBJECTIVE: To evaluate the effects of different types and durations of exergame interventions on cognition in elderly individuals with cognitive impairment (CI) through a meta-analysis.

METHODS: A computerized search was conducted in databases including Cochrane Library, PubMed, Web of Science, Embase, and CNKI from database inception to September 2025. Quality assessment and data extraction were performed on the included studies. Results measures included the MoCA , MMSE, etc. The study designs were randomized controlled trials or qua-si-experimental studies. The Cochrane Handbook's risk of bias tool was used for quality assessment, and Rev Man 5.0 software was employed to conduct meta-analyses on the ef-fects of dance-based and movement-based exergames on cognitive function in elderly CI patients.

RESULTS: A total of 13 studies involving 433 CI patients were included. Analysis of the 13 studies showed that dance-based exergaming was significantly superior to exercise-based exergaming in cognitive ability (SMD = 0.73, P < 0.01); interventions lasting ≥8 weeks were more effective than those lasting <8 weeks (SMD = 1.01, P = 0.02).

CONCLUSION: Dance-based exergames significantly improve cognition in elderly individu-als with CI, with better effects observed in long-term interventions. However, more high-quality studies are needed to verify these findings and to supplement analyses on ex-ercise dose effects.},
}

Humans
*Cognitive Dysfunction/therapy/psychology
Aged
*Cognition/physiology
*Video Games
*Dancing
*Dance Therapy/methods
Male
Randomized Controlled Trials as Topic
*Exercise Therapy/methods
Female

@article {pmid41378777,
year = {2025},
author = {González-Velasco, Ó and Parlato, R and Yilmaz, R and Decker, L and Menge, S and Freischmidt, A and Yang, X and Tulasi, N and Brenner, D and Andersen, PM and Forsberg, KME and Schlachetzki, JCM and Brors, B and Voith von Voithenberg, L and Weishaupt, JH},
title = {Somatic gene mutations in the motor cortex of patients with sporadic amyotrophic lateral sclerosis.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awaf460},
pmid = {41378777},
issn = {1460-2156},
abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of cortical and spinal motor neurons. Mendelian germline mutations often cause familial ALS (fALS) but only approximately ten percent of sporadic ALS cases (sALS). We leveraged DNA and single cell RNA-sequencing data from autopsy tissue to explore the presence of somatic mosaic variants in sALS cases. Deep targeted panel sequencing of known ALS disease genes in motor cortex tissue revealed an enrichment of low allele frequency variants in sALS, but not in fALS with an identified monogenic cause. In silico analysis predicted increased pathogenicity of mosaic mutations in various known ALS mutational hot spots. In particular, we identified the somatic FUS variant p.E516X, located in an established hotspot for germline ALS mutations, which leads to nucleo-cytoplasmic mislocalization and aggregation typical for ALS FUS pathology. Additionally, we performed somatic variant calling on single cell RNA-sequencing data from sALS tissue and revealed a specific accumulation of somatic variants in excitatory neurons, reinforcing a neuron-autonomous disease initiation. Collectively, this study indicates that somatic mutations within the motor cortex, especially in excitatory neurons, may contribute to sALS development.},
}

@article {pmid41377708,
year = {2025},
author = {Khalid, YA and Saad, MB and Nasreddin, ME},
title = {Assessing junior doctors' knowledge and attitude on advanced life support in Egypt: a cross-sectional study.},
journal = {African journal of emergency medicine : Revue africaine de la medecine d'urgence},
volume = {15},
number = {4},
pages = {100927},
pmid = {41377708},
issn = {2211-4203},
abstract = {INTRODUCTION: Cardiovascular diseases are a leading cause of mortality worldwide, with cardiac arrest survival heavily dependent on timely and effective resuscitation efforts. Junior doctors often serve as first responders in hospitals, yet their advanced life support (ALS) knowledge and training adequacy remain underinvestigated in Egypt. This study assessed the knowledge and attitudes of junior doctors in Egypt regarding basic life support (BLS) and ALS, identified knowledge gaps, and suggests improvements in resuscitation training programs.

METHODS: A cross-sectional survey was conducted among 184 junior doctors, including house officers, general practitioners, and residents, across multiple healthcare centres in Egypt. Data was collected via an online questionnaire based on European Resuscitation Council guidelines, evaluating demographic factors, BLS/ALS knowledge, and attitudes toward cardiac arrest management. Statistical analysis explored associations between knowledge scores and participant characteristics.

RESULTS: Participants demonstrated inadequate knowledge with mean BLS and ALS scores of 59 % and 61.8 %, respectively. Significant deficiencies were noted in pediatric resuscitation, cardiac arrest diagnosis, IV access, and capnography interpretation. Residents and those attending ALS workshops scored significantly higher (p < 0.05), while prior clinical exposure did not correlate with higher knowledge scores. Most participants (91.3%) expressed a need for further ALS training.

DISCUSSION: Junior doctors in Egypt show deficient ALS knowledge with critical gaps that may impact patient outcomes. Structured ALS training and curriculum reforms are urgently needed to enhance emergency preparedness and improve cardiac arrest survival.},
}

@article {pmid41377283,
year = {2025},
author = {Imtiaz, E and Mahato, RK and Soomro, S and Jadoon, M and Intikhab, S},
title = {Nanomedicine-enhanced delivery of CRISPR-Cas13 for RNA editing in C9orf72-associated ALS.},
journal = {Annals of medicine and surgery (2012)},
volume = {87},
number = {12},
pages = {9167-9168},
pmid = {41377283},
issn = {2049-0801},
}

@article {pmid41376376,
year = {2025},
author = {Shi, Y and Zhao, T and Peng, L and Wang, P and Huang, X and Xu, F and Tan, Y and Peng, S and Xiong, T and Bai, Y and Liu, X and Wei, C and Zhang, W and Ding, H},
title = {Investigating the shared genetic architecture between post-traumatic stress disorder and neurodegenerative diseases: a large-scale genomewide cross-trait analysis.},
journal = {International journal of surgery (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1097/JS9.0000000000004347},
pmid = {41376376},
issn = {1743-9159},
abstract = {BACKGROUND: Post-traumatic stress disorder (PTSD), the most prevalent psychopathological consequence following traumatic events, profoundly impacts human life amidst global societal pressures. Emerging twin and family studies suggest that individuals with stress-related disorders face an elevated risk of neurodegenerative diseases, yet the genetic underpinnings of this association remain poorly understood.

METHODS: Here, we present a comprehensive framework elucidating this genetic basis. Using bivariate causal mixture models (MiXeR), we quantified polygenic overlap between PTSD (N = 1,280,933) and four neurodegenerative phenotypes (N = 115,803- 487,511), leveraging summary statistics from the largest PTSD genome-wide association study to date. Conditional/conjunction false discovery rate (FDR) analysis identified shared genomic loci.

RESULTS: MiXeR revealed considerable genetic variant sharing between neurodegenerative diseases and PTSD. Subsequent conjunction FDR analysis pinpointed 15 distinct shared loci. ρ-HESS local genetic correlation analysis identified seven significant local genetic correlations, with Chr6: 61,880,512-63,552,888 emerging as the most significant shared locus between PTSD and Alzheimer's disease. Cross-trait analyses using MTAG and CPASSOC identified 174 PTSD risk loci associated with at least one psychiatric disorder. Protein-coding genes mapped to known and novel shared loci exhibited specific spatial developmental trajectories. Through a framework incorporating five fundamental TWAS algorithm models, we identified 27 novel susceptibility genes that passed rigorous screening. Polygenic risk score (PRS) stratification in the UK Biobank cohort revealed dose-dependent relationships between PRS and risks of Alzheimer's disease, multiple sclerosis, and Parkinson's disease, with limited support for ALS and PTSD.

CONCLUSIONS: These findings illuminate the shared genetic architecture between PTSD and neurodegenerative phenotypes, advancing our understanding of their neurobiological interconnections. And enhance statistical power for detecting shared loci, thereby refining the characterization of common genetic mechanisms underlying PTSD and neurodegenerative pathologies.},
}

@article {pmid41376117,
year = {2025},
author = {Ali, YY and Fares, NV and Ayad, MF and Abbas, MM},
title = {Toward Practical and Sensitive Fluorescence Analysis: Factorial Design-Optimized o-Phthalaldehyde Derivatization for Synchronous Spectrofluorimetric Determination of Modafinil in Plasma and Dosage Form.},
journal = {Luminescence : the journal of biological and chemical luminescence},
volume = {40},
number = {12},
pages = {e70383},
doi = {10.1002/bio.70383},
pmid = {41376117},
issn = {1522-7243},
mesh = {*o-Phthalaldehyde/chemistry ; *Modafinil/blood/analysis ; Spectrometry, Fluorescence/methods ; Humans ; Limit of Detection ; Tablets ; Molecular Structure ; Fluorescence ; },
abstract = {The current research discusses a simple, sensitive, and practical spectrofluorimetric method for Modafinil (MDF) analysis. MDF can improve the fatigue symptoms associated with amyotrophic lateral sclerosis. MDF's aliphatic primary amide moiety can undergo base-catalyzed condensation with o-phthalaldehyde to give a highly fluorescent isoindoline derivative measured at 445 nm using synchronous spectrofluorimetry with Δλ of 110 nm. Different factors were studied using a two-level factorial design to reach the optimum conditions for the analysis. The method validation was carried out following the International Conference on Harmonization guidelines. The calibration curve was established to illustrate how relative fluorescence intensity varies with MDF concentration, and linearity was attained over the range of 10-7000 ng mL[-1], with an average recovery of 100.51% ± 0.91%. The limit of detection (LOD) was determined to be 3.21 ng mL[-1] while the quantitation limit (LOQ) was found to be 9.74 ng mL[-1]. The developed method demonstrated its effectiveness in determining MDF in tablets and spiked human plasma with recoveries of 100.43% ± 0.16 and 96.07% ± 1.55, respectively. MoGAPI, AGREE, and BAGI assessments yielded scores of 72, 0.62, and 70, respectively. The results show that the method is user-friendly and can be used in routine applications.},
}

*o-Phthalaldehyde/chemistry
*Modafinil/blood/analysis
Spectrometry, Fluorescence/methods
Humans
Limit of Detection
Tablets
Molecular Structure
Fluorescence

@article {pmid41375912,
year = {2025},
author = {Sancho, J and Ferrer, S and Signes-Costa, J},
title = {Noninvasive Ventilation Effectiveness in Amyotrophic Lateral Sclerosis.},
journal = {Journal of clinical medicine},
volume = {14},
number = {23},
pages = {},
doi = {10.3390/jcm14238609},
pmid = {41375912},
issn = {2077-0383},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons; respiratory problems are the leading cause of death and hospital admissions and are secondary to progressive weakness of the respiratory muscles and upper airway. Noninvasive ventilation (NIV) can increase survival, alleviate symptoms, reduce hospital admissions, and improve the quality of life of these patients. The key factor in respiratory management of patients with ALS is achieving effective NIV; ineffective NIV has a negative impact on survival, with a reduction of up to 50% compared to patients with an effective technique. The most common cause of ineffective NIV is air leaks; other causes include upper airway obstruction events, residual hypoventilation, hyperventilation, and upper airway obstruction secondary to an oronasal mask. Regular monitoring of the effectiveness of NIV is essential given its impact on survival; the key tools that detect the main problems are the presence of hypoventilation symptoms, arterial blood gases, nocturnal oximetry and capnography, and built-in ventilator software. Different measures have been proposed to address the ineffectiveness of NIV, such as fitting the mask to reduce air leaks, increasing ventilatory support for residual hypoventilation, decreasing ventilatory support for hyperventilation, or a trial with a nasal mask to address oronasal interface effects. In the case of obstruction, the most common measure is to increase positive expiratory pressure during NIV. These measures enable NIV to be effective in 58% of cases, achieving a survival rate similar to that of patients who have effective NIV from the outset.},
}

@article {pmid41375893,
year = {2025},
author = {Gratzer, A and Gdynia, N and Sasse, N and Beese, R and Winterholler, C and Bauer, Y and Schröter, C and Gdynia, HJ},
title = {Rehabilitation in Amyotrophic Lateral Sclerosis: Recommendations for Clinical Practice and Further Research.},
journal = {Journal of clinical medicine},
volume = {14},
number = {23},
pages = {},
doi = {10.3390/jcm14238590},
pmid = {41375893},
issn = {2077-0383},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative condition characterized by the degeneration of upper and lower motor neurons. This degeneration leads to a gradual muscle weakness, dysarthria, dysphagia, respiratory insufficiency, and, in some patients, alterations in cognitive and behavioral performance. Regardless of advancements made in pharmacological and gene-targeted interventions, a definitive curative treatment remains elusive. Consequently, rehabilitation plays a pivotal role in preserving autonomy, participation, and overall quality of life. This review outlines the current evidence and clinical approaches related to multidisciplinary rehabilitation in ALS. It covers physical and occupational therapy, respiratory, speech and language, psychological, and palliative care domains. Evidence supports moderate tailored exercise programs, early respiratory therapy, and structured management of mobility deficits, spasticity, pain, dysphagia, and communication impairments as key elements of symptomatic treatment. Psychological and social support, which includes the involvement of caregivers and relatives, enhances emotional well-being and coping resilience. Even with progressive development of gene-targeted and disease-modifying therapies, rehabilitation will stay relevant for maintaining long-term motor function. This review highlights the need for standardized, evidence-based rehabilitation protocols and intensified neurorehabilitation research to strengthen clinical outcomes and quality of life as key therapeutic goals in ALS management.},
}

@article {pmid41375620,
year = {2025},
author = {Krysiak, D and Ćwiertnia, M and Wójcik, M and Babik, P and Suchanek, Ł and Jaskiewicz, F and Trojak-Piętka, J and Szlagor, M and Pollok-Waksmańska, W and Kawecki, M and Ilczak, T},
title = {Analysis of Medical Response Team Interventions and the Impact of Certified Training on the Treatment of Patients with Hypoglycaemia-A Simulation Study.},
journal = {Journal of clinical medicine},
volume = {14},
number = {23},
pages = {},
doi = {10.3390/jcm14238318},
pmid = {41375620},
issn = {2077-0383},
abstract = {Background/objectives: The effectiveness of emergency medical procedures administered to a patient in a life-threatening condition depends, to a large degree, on the knowledge and skills of medical response team personnel. Their competencies can be developed through participation in training and then verified during emergency medicine championships. Methods: The research was conducted on the basis of one of the tasks carried out during the '16th International Winter Championships in Emergency Medicine'. The task was completed by 28 Polish emergency response teams from ambulance stations across the country. The teams carried out a simulated scenario related to procedures with a patient with hypoglycaemia. The teams' interventions were assessed in accordance with European Resuscitation Council (ERC) guidelines by judges selected from among academic lecturers and ERC instructors. Results: The research showed that 86% of the teams obtained the maximum number of points for adhering to safety procedures. Further, 61% of the teams obtained the maximum of 6 points for the initial assessment, with the average number of points obtained by the teams being 5.54. The average number of points for the physical examination was 21.04, with only one team obtaining the maximum result of 26 points. Additionally, 57% of the teams obtained the maximum number of 6 points for the medical consultation, with the average obtained by the teams being 5.43. The teams obtained, on average, 8.18 points for the correct treatment of hypoglycaemia, with 68% of the teams obtaining the maximum of 9 points. The research demonstrated a positive correlation between the quality of patient examination and the collection of medical data, and the effectiveness of hypoglycaemia treatment. It was also shown that if the team leader had completed an ALS course, they obtained higher scores for the treatment of hypoglycaemia, although this finding is specific to this scenario. Conclusions: The teams demonstrated generally high performance in a simulated hypoglycaemia scenario. More complete assessment and history-taking were associated with higher treatment scores. Correct treatment was achieved in 79% of ALS-led teams versus 44% of non-ALS teams, although this observation is specific to this simulation and should not be generalised.},
}