@article {pmid41845095,
year = {2026},
author = {Gurunandan, K and Greve, A and Wilmot, E and Henson, RN},
title = {Does signed prediction error drive declarative memory? Evidence from variable choice paradigms.},
journal = {Memory & cognition},
volume = {},
number = {},
pages = {},
pmid = {41845095},
issn = {1532-5946},
support = {EP/Y016815/1//Engineering and Physical Sciences Research Council/ ; SUAG/046/G101400/MRC_/Medical Research Council/United Kingdom ; POS_2023_2_0034//Eusko Jaurlaritza/ ; },
abstract = {Prediction error (PE) is the discrepancy between predictions and new information. For a binary reward outcome, PE may be signed (positive if the outcome was better than predicted and negative if the outcome was worse than predicted) or unsigned (absolute value of "surprise"). Using a "variable choice" paradigm, De Loof et al. (PLOS ONE, 131, Article e0189212, 2018) examined the role of PE in one-shot learning of unknown translations of known words and showed that associative memory for the translation was greater when (financial) reward was more unexpected and lesser when an expected reward was not received (i.e., signed PE); an effect that they replicated in several subsequent studies. However, other work on PE in declarative memory has assumed that memory is greater when an outcome is more unexpected, without any explicit reward (i.e., unsigned PE). We replicated De Loof et al.'s paradigm with and without financial reward, and found that memory was explained slightly better by unsigned PE (Experiments 1A-1B). However, we also identified a potential confound in the paradigm that could explain the results without any role of PE, as confirmed by simulations. We therefore designed a modified version of the paradigm that circumvents this confound (Experiment 2). Results were inconsistent with the PE account. We conclude that variable choice paradigms may not be well-suited to investigate the role of PE in one-shot declarative learning, and that the purported role of signed PE in declarative memory requires further investigation.},
}

@article {pmid41845971,
year = {2026},
author = {Dahlhaus, R and Braun, RJ},
title = {The role of TDP-43 fragments in regular cellular functions and homeostatic failure.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107349},
doi = {10.1016/j.nbd.2026.107349},
pmid = {41845971},
issn = {1095-953X},
abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of motor neurons, leading to severe muscle weakness, loss of voluntary movement, and respiratory failure. A widely noted feature of the disease is the presence of TDP-43 proteinopathies. Under homeostatic conditions, the RNA/DNA-binding protein TDP-43 mainly resides in the nucleus, where it functions to regulate gene expression, controlling not only RNA transcription and splicing, but also stability and transport to the cytoplasm. Upon the arrival at ribosomes, TDP-43 may further moderate translation, acting as a global repressor of protein synthesis. However, in over 95% of ALS cases, TDP-43 mislocalies from the nucleus to the cytoplasm, where it enriches in cytoplasmic inclusions that are marked by the presence of misfolded, ubiquitinated, phosphorylated and fragmented protein species of TDP-43. Although recent studies have tried to untangle the relationship between TDP fragments on the one hand, and cytotoxicity as well as neurodegeneration on the other, the results are still a matter of debate. Here, we review our current understanding of the different TDP fragments derived from proteolytic cleavage as well as alternative splicing, addressing the different N-terminal and C-terminal species and evaluating differences in rodent and primate models. We focus our analysis on the potential homeostatic functions of TDP fragments in the context of viral infections and myelination control, which are potentially pivotally interconnected. The findings illustrate several facets of fragmented TDP-43 protein species in scenarios of enhanced cellular stress. Gaining a detailed understanding could help to reveal new treatment options for ALS and other TDP-43 proteinopathies.},
}

@article {pmid41846014,
year = {2026},
author = {Yang, L and Fan, W and Wang, Z and Wu, M and Chen, Y and Cheng, J and Zhou, F and Guo, Z},
title = {The role of IRF5 in Microglia-Mediated neuroinflammation in ALS.},
journal = {Neuroscience letters},
volume = {},
number = {},
pages = {138580},
doi = {10.1016/j.neulet.2026.138580},
pmid = {41846014},
issn = {1872-7972},
abstract = {The occurrence and development of amyotrophic lateral sclerosis (ALS) involve neuroinflammatory responses, in which microglial activation plays a critical role. IRF5, a key regulator of inflammatory responses, is implicated in the disease mechanisms of various conditions. However, its mechanism in ALS remains unclear. This study found that IRF5 expression was significantly increased in hSOD1-G93A transgenic ALS mice and cell models, primarily localized in activated microglia. Silencing IRF5 altered microglial polarization, suppressed the release of inflammatory factors, enhanced phagocytic function, and reduced motor neuron apoptosis in a co-culture system. Mechanistic studies suggested that IRF5 may regulate microglial function through the NF-κB signaling pathway. This study reveals the key role of IRF5 in microglia-mediated neuroinflammation and neuronal damage in ALS, indicating that targeting IRF5 could represent a promising treatment strategy for this disease.},
}

@article {pmid41846418,
year = {2026},
author = {Ahire, C and Yadav, R and Bhamare, UU and Kaur, G and Palkar, MB},
title = {From Refractory Epilepsy to Neurodegeneration: Emerging Mechanistic and Clinical Insights Into the Ketogenic Diet.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {40},
number = {6},
pages = {e71609},
doi = {10.1096/fj.202503317R},
pmid = {41846418},
issn = {1530-6860},
mesh = {*Diet, Ketogenic/methods ; Humans ; Animals ; *Neurodegenerative Diseases/diet therapy/metabolism ; *Drug Resistant Epilepsy/diet therapy/metabolism ; },
abstract = {The ketogenic diet (KD), a high-fat, low-carbohydrate intervention, is well established for drug-resistant epilepsy and is increasingly explored in neurodegenerative disorders. KD reduces neuronal hyperexcitability through enhanced γ-aminobutyric acid (GABA)ergic transmission and modulation of neurotransmitter balance, underlying its efficacy in refractory epilepsy. Beyond seizure control, emerging evidence suggests KD may influence disease processes in conditions such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and Huntington's disease. Preclinical studies indicate that KD can modulate mitochondrial bioenergetics, oxidative stress, neuroinflammation, neurotransmitter signaling, and gut-brain interactions, though these effects are highly context-dependent and primarily derived from cellular and animal models. Clinical data remain limited, heterogeneous, and short-term, with small cohorts and variable outcome measures. Sustaining adherence and assessing long-term safety remain significant challenges in patient populations. This review summarizes recent experimental and clinical findings, highlighting the molecular and cellular mechanisms through which KD exerts neuroprotective effects. We also evaluate translational evidence and discuss the potential utility of KD as an adjunctive intervention in neurological disease management.},
}

*Diet, Ketogenic/methods
Humans
Animals
*Neurodegenerative Diseases/diet therapy/metabolism
*Drug Resistant Epilepsy/diet therapy/metabolism

@article {pmid41846510,
year = {2026},
author = {Raby, KL},
title = {Synthesizing five decades of research on sensitive caregiving: A commentary on Nivison et al. (2026).},
journal = {Journal of child psychology and psychiatry, and allied disciplines},
volume = {},
number = {},
pages = {},
doi = {10.1111/jcpp.70146},
pmid = {41846510},
issn = {1469-7610},
abstract = {This commentary highlights the contributions of Nivison et al.'s (2026) umbrella meta-analysis synthesizing five decades of research on sensitive caregiving and child development. Integrating findings from numerous meta-analyses, the authors demonstrate that caregiver sensitivity is meaningfully associated with multiple domains of child development. Notably, associations with cognitive and language development are at least as large as those with attachment security and behavior problems, expanding traditional conceptualizations of sensitivity's developmental significance. The findings further indicate substantial consistency across child, parent, and family demographic characteristics, while suggesting amplified benefits in socioeconomically disadvantaged contexts. This commentary underscores key gaps in the literature, including the need for meta-analytic investigations of children's peer competence, self-regulation, and physical health outcomes, as well as the need for refined measurement of caregiving dimensions. Although causal inferences require randomized intervention evidence, the synthesis provides compelling support for sensitive caregiving as a central determinant of healthy development and offers a roadmap for future research and policy.},
}

@article {pmid41846565,
year = {2026},
author = {Denby, K and Connelly, EDS and Glerup, H and Østgård, R and Egsgaard, AL and Vedsted, P and Appel, CW},
title = {Translation and cross-cultural adaptation of the Identification of Spondyloarthritis Questionnaire (IBIS-Q) into Danish for patients with inflammatory bowel disease.},
journal = {Scandinavian journal of gastroenterology},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/00365521.2026.2645081},
pmid = {41846565},
issn = {1502-7708},
abstract = {OBJECTIVES OF THE ARTICLE: Spondyloarthritis (SpA) affects 10-30% of patients with inflammatory bowel disease (IBD). An early diagnosis is essential as a delayed diagnosis of SpA increases the risk of disability and reduces quality of life. However, few screening tools for patients with IBD exist and none are available in Danish. To support early identification of spondyloarthritis symptoms in Danish patients with IBD, this study aimed to translate and cross-culturally adapt the Identification of Spondyloarthritis Questionnaire (IBIS-Q) into Danish and to assess face validity of the Danish version.

MATERIALS AND METHODS: Following Beaton et al.'s six step forward-backward translation guideline, the IBIS-Q was translated and cross-culturally adapted into Danish. This was done through an iterative process with an expert committee of translators, clinicians, methodologists and with inclusion of the IBIS-Q developers. Face validity was assessed through semi-structured interviews with 24 adults with and without arthritis-related symptoms.

RESULTS: Participants generally found the questionnaire easy to understand, and face validity was confirmed. The semantic equivalence of painful and sore in a Danish context was a central topic of discussion within the expert committee. However, only minor modifications were made, including the addition of an introductory paragraph and changing the questionnaire's title.

CONCLUSIONS: Following an international, standardised guideline, the IBIS-Q was successfully translated and cross-culturally adapted into Danish, and face validity was confirmed. The IBIS-Q is the first available questionnaire to assess Danish patients with IBD for SpA symptoms. Psychometric validation of the measurement properties of IBIS-Q is recommended prior to implementation.},
}

@article {pmid41847237,
year = {2026},
author = {Zarco-Martín, MT and Andreo-López, MC and Yagui-Beltrán, MS and Fernández-Soto, ML},
title = {Sarcopenia in amyotrophic lateral sclerosis: a key predictor of respiratory dysfunction and disease progression.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1713253},
pmid = {41847237},
issn = {2296-861X},
abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterized by progressive muscle weakness and respiratory decline. Sarcopenia remains underexplored in terms of prevalence and their relationship with disease progression. We aimed to determine the prevalence of sarcopenia in ALS patients, assess the predictive value of morphofunctional assessment tools for sarcopenia, and explore their relationship with respiratory function and disease progression.

METHODS: A cross-sectional study was conducted with 40 ALS patients at the ALS Multidisciplinary Unit, San Cecilio University Hospital in Granada. Sarcopenia was defined based on the European Working Group of Sarcopenia in Older People 2(EWGSOP2) and malnutrition was diagnosed using GLIM criteria. Morphofunctional status was assessed using: Phase Angle (PA) and body composition by Bioelectrical Impedance Vector Analysis, muscle strength through Handgrip Strength (HGS). Respiratory function was evaluated using Forced Vital Capacity (FVC). Associations between sarcopenia, body composition, respiratory function, and disease severity were analyzed using logistic regression models. Receiver operating characteristic analyses were performed to identify optimal predictive cut-off values.

RESULTS: Sarcopenia was identified in 25% of ALS patients. Compared with non-sarcopenic individuals, sarcopenic patients exhibited significantly lower muscle mass indices, PA, and HGS, along with higher extracellular water percentage (%ECW). Malnutrition was more frequent in sarcopenia group (90% vs. 25%, p < 0.001). Respiratory impairment was more pronounced in sarcopenic patients, with reduced FVC and elevated pCO₂ (p = 0.02), and a greater need for non-invasive mechanical ventilation (NIMV) (70% vs. 10%, p = 0.001). VC correlated positively with body cell mass index (BCMI) (r = 0.450), skeletal muscle mass index (SMI) (r = 0.413), and ALSFRS-R score (r = 0.731; all p < 0.05). Lower PA, BCMI, and ALSFRS-R scores, together with higher %ECW and partial pressure of carbon dioxide (pCO₂), predicted sarcopenia risk. Reduced BCMI, HGS, Short Physical Performance Battery (SPPB) and sarcopenia were associated with the need of NIMV. BCMI (cut-off:8.05 kg/m[2]; AUC:0.889) and ALSFRS-R (cut-off:33 points; AUC:0.884) were the most accurate predictors of sarcopenia and ventilatory support, respectively.

CONCLUSION: This study is the first to assess sarcopenia prevalence in ALS patients using standardized diagnostic criteria. The findings highlight the relationship between sarcopenia, malnutrition, and respiratory decline. PA, BCMI, and respiratory parameters emerge as potential tools for sarcopenia and NIMV risk stratification.},
}

@article {pmid41847382,
year = {2026},
author = {Talbot, SR and Scorrano, F and Gaburro, S and Lainee, P and van Gaalen, MM},
title = {From observation to optimization: behavioral metrics that matter in KPI based home cage monitoring.},
journal = {Frontiers in behavioral neuroscience},
volume = {20},
number = {},
pages = {1694689},
pmid = {41847382},
issn = {1662-5153},
abstract = {Most in vivo scientists would agree that digital biomarkers collected via home-cage monitoring generate valuable data. However, few can tell precisely how valuable. The gap between enthusiasm and evidence has slowed the adoption of digital biomarkers in preclinical research. This framework paper addresses that gap by providing explicit key performance indicators (KPIs), organized into scientific, operational, welfare, and financial categories. We show how return-on-investment calculations differ across pharmaceutical companies, contract research organizations (CROs), and academic institutions. Furthermore, we demonstrate the approach through a worked example in an Amyotrophic Lateral Sclerosis (ALS) mouse model that reduces full-time equivalent (FTE) requirements by half. When successfully integrated, digital biomarkers can generate richer datasets, reduce the number of animals, improve welfare, and enhance translational value. However, successful implementation requires clear performance metrics to justify investment and measure success. We also discuss what these technologies cannot do, because understanding limitations matters as much as understanding benefits.},
}

@article {pmid41850140,
year = {2026},
author = {Gao, Y and Sun, Z and Wei, Q and She, C and Wang, Y and Chen, J and Wang, M and Gui, X and Xia, X and Liu, Y and Wang, X},
title = {Employing an integrated computational simulation strategy to identify high-affinity ligands for TDP-43 amyloid proteins.},
journal = {Bioorganic & medicinal chemistry},
volume = {137},
number = {},
pages = {118634},
doi = {10.1016/j.bmc.2026.118634},
pmid = {41850140},
issn = {1464-3391},
abstract = {Developing high-affinity ligands targeting TDP-43 amyloid species is a potential therapeutic approach for amyotrophic lateral sclerosis (ALS). Here, we propose an integrated computational simulation strategy, which integrates multiple virtual screening methods, molecular dynamics simulations and binding free energy evaluations. Using this strategy, we successfully identified TDPL1, a high-affinity ligand for TDP-43 amyloid proteins. In vitro affinity assays confirmed the computational predictions. Based on the MD simulation results, we further investigated the binding mode between TDPL1 and TDP-43 amyloid proteins. Additionally, steered molecular dynamics simulations were employed to assess the impact of TDPL1 on the stability of β-sheet interactions within the TDP-43 amyloid structure. Our data demonstrate that TDPL1 not only binds effectively to TDP-43 amyloid proteins but also possesses the potential to disrupt the stability of amyloid aggregates. These findings provide a molecular foundation for the future development of diagnostic agents or targeted therapeutics for ALS and related diseases.},
}

@article {pmid41850233,
year = {2026},
author = {Guise, AJ and Ferber, KL and Young, D and Edwards, AL and Sabouri, S and Fraser, KB and Milliman, E and Plowey, ED and Zoghbi, J and Fradette, SM and Graham, DL},
title = {Identification of tofersen PD-response biomarkers in VALOR clinical trial CSF via multiplexed quantitative proteomics.},
journal = {Cell reports. Medicine},
volume = {7},
number = {3},
pages = {102648},
doi = {10.1016/j.xcrm.2026.102648},
pmid = {41850233},
issn = {2666-3791},
mesh = {Humans ; *Proteomics/methods ; *Biomarkers/cerebrospinal fluid ; *Amyotrophic Lateral Sclerosis/drug therapy/cerebrospinal fluid/genetics ; Superoxide Dismutase-1/genetics ; Male ; Female ; Middle Aged ; Adult ; Membrane Glycoproteins/cerebrospinal fluid ; Aged ; },
abstract = {Tofersen, the first approved genetically targeted therapy for amyotrophic lateral sclerosis (ALS), demonstrates significant lowering of plasma neurofilament in adults carrying mutations in the superoxide dismutase 1 (SOD1) gene; however, additional biomarkers of treatment response in ALS are lacking. Here, we analyze longitudinally collected cerebrospinal fluid (CSF) samples from the phase 3 VALOR clinical trial to identify candidate tofersen treatment-response biomarkers in SOD1-ALS via quantitative proteomics. We observe significant modulation from baseline abundance for 56 proteins in tofersen-treated participants relative to placebo, including CSF GPNMB, which is significantly and continuously elevated across all post-baseline timepoints. We orthogonally confirm this observation by GPNMB immunoassay in independent tofersen-treated cohorts. Taken together, these data identify pharmacodynamic-response biomarkers of tofersen treatment that can be measured as early as 4 weeks post-treatment in SOD1-ALS patients and demonstrate the utility of leveraging unbiased proteomic screening integrated with targeted validation methods to identify pharmacodynamic-response biomarkers in clinical trial patient samples.},
}

Humans
*Proteomics/methods
*Biomarkers/cerebrospinal fluid
*Amyotrophic Lateral Sclerosis/drug therapy/cerebrospinal fluid/genetics
Superoxide Dismutase-1/genetics
Male
Female
Middle Aged
Adult
Membrane Glycoproteins/cerebrospinal fluid
Aged

@article {pmid41850301,
year = {2026},
author = {Glaubitz, R and Harst, L and Ehm, F and Tesch, F and Barlinn, J and Krause, F and Schwarz, R and Malzahn, J and Werblow, A and Sinz, C and Randig, I and Riedel, T and Kutschker, C and Fiebig, S and Kubitza, J and Cording, M and Wolff, J and Schmitt, J},
title = {Testing a model-based approach for planning and regional coordination of hospital service group offerings: A model project in the East Saxony healthcare cluster.},
journal = {Gesundheitswesen (Bundesverband der Arzte des Offentlichen Gesundheitsdienstes (Germany))},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2771-8616},
pmid = {41850301},
issn = {1439-4421},
abstract = {The hospital reform passed in 2024 will lead to regional and nationwide changes in the German hospital landscape. A joint project to examine the effects of the hospital reform on health care structures in the East Saxony region was initiated by the Center for Evidence-Based Health Care (ZEGV) at Dresden University Hospital, the regional health care coordinators of the four districts in the East Saxony care cluster and the city of Dresden, a statutory health insurance provider (AOK PLUS), and other regional stakeholders. In addition, the aim was to promote cooperation between the stakeholders for the purpose of future regionally coordinated planning for inpatient care. The project involved the application and validation of a model displaying a hospital's relevance for stationary care provision (care relevance model), which was developed in cooperation with the GKV-Spitzenverband (National Association of Statutory Health Insurance Funds) and is based on the performance data of German hospitals in accordance with § 21 KHEntgG (Hospital Remuneration Act). Thirty of the 36 hospital locations in the project region agreed to participate in the project. Both in a questionnaire-based self-assessment provided by the clinics and during a joint cluster conference, the tension between the need for cooperation and individual interests became clear. At this point, the care relevance model developed can scientifically support the dialogue between the stakeholders and thus support inpatient planning.Im Zuge der im Jahr 2024 verabschiedeten Krankenhausreform wird es zu regionalen und deutschlandweiten Veränderungen der Krankenhauslandschaft kommen. Vor diesem Hintergrund wurde ein gemeinsames Projekt des Zentrums für Evidenzbasierte Gesundheitsversorgung (ZEGV) der Hochschulmedizin Dresden mit den Regionalkoordinator:innen für Gesundheit der vier Landkreise im Versorgungscluster Ostsachsen und der Stadt Dresden, der AOK PLUS und weiteren regionalen Akteuren initiiert, um die Auswirkungen der Krankenhausreform auf die Versorgungsstrukturen in der Region Ostsachsen zu untersuchen. Zudem sollte die Kooperation zwischen den Akteuren zum Zweck einer zukünftigen regional abgestimmten Planung für die stationäre Versorgung gefördert werden. Im Projekt erfolgte die Anwendung und Validierung eines Versorgungsrelevanzmodells, welches in Kooperation mit dem GKV-Spitzenverband entwickelt wurde und auf den Leistungsdaten deutscher Krankenhäuser nach § 21 KHEntgG basiert. Dreißig von 36 Krankenhausstandorten in der Projektregion konnten für eine Teilnahme am Projekt gewonnen werden. Sowohl in einer fragebogengestützten Selbstauskunft der Kliniken als auch im Rahmen der zusammenführenden Clusterkonferenz wurde das Spannungsfeld zwischen Kooperationsnotwendigkeiten und Partikularinteressen deutlich. An dieser Stelle kann das entwickelte Versorgungsrelevanzmodell den Dialog zwischen den Akteuren wissenschaftlich begleiten und so die stationäre Planung unterstützen.},
}

@article {pmid41850981,
year = {2026},
author = {Pu, Y and Cao, X},
title = {KLHL6: a proteostatic guardian against T-cell exhaustion.},
journal = {Trends in immunology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.it.2026.02.003},
pmid = {41850981},
issn = {1471-4981},
abstract = {Cheng et al.'s recent study identifies the Cullin3-RING E3 ubiquitin ligase complexes (CRL3) adaptor protein Kelch-like protein 6 (KLHL6) as a proteostasis regulator whose downregulation in chronically stimulated T cells leads to the accumulation of thymocyte selection-associated high mobility group box protein and phosphoglycerate mutase family member 5, driving T-cell dysfunction. This work positions T-cell exhaustion as a proteostatic disorder and highlights KLHL6 as a promising target for cancer immunotherapy.},
}

@article {pmid41842529,
year = {2026},
author = {Zhao, J and Ji, X and Leng, L and Wang, M and Li, Y and Wang, W and Sun, Y},
title = {Integrating terrain and spectral attributes for automated water-land classification using airborne LiDAR without any prior information.},
journal = {Applied optics},
volume = {65},
number = {7},
pages = {2053-2062},
doi = {10.1364/AO.579495},
pmid = {41842529},
issn = {1539-4522},
abstract = {Accurate differentiation between water and land is crucial for flood monitoring, land-use planning, and ecological protection. Airborne laser scanning (ALS) provides high-resolution three-dimensional topographic and intensity data, offering a robust foundation for these applications. However, existing classification approaches largely depend on manually defined thresholds or supervised learning, with limited attention to the underlying synergies among multidimensional features, thereby constraining both accuracy and automation. To address these limitations, this study introduces an unsupervised classification framework based on multi-feature fusion, where four fusion indicators are derived from 14 geometric and radiometric features, enabling fully automated water-land classification. Experiments on two ALS datasets from central Dublin demonstrate that the proposed method substantially outperforms SLIER, fuzzy logic, and elevation-threshold approaches, achieving overall accuracies of 98.3% and 97.3%, with Kappa coefficients of 0.903 and 0.914. Beyond improving classification accuracy and reducing computational complexity, the fusion indicators also enhance digital elevation model (DEM) reconstruction by repairing voids in water regions and refining boundary delineation, thereby reinforcing the value of ALS data for environmental monitoring and disaster management.},
}

@article {pmid41843813,
year = {2026},
author = {Meyer, T and Ticozzi, N and Weber, M and Ravits, J and Lingor, P and Kuźma-Kozakiewicz, M and Boentert, M and Grehl, T and Corcia, P and Povedano Panadés, M and Maier, A and Ingre, C and Cetin, H and Weydt, P and Lunetta, C and van den Berg, L and Ludolph, AC and Brenner, D and Turner, MR and Genge, A},
title = {ALS motor phenotypes: a revised 'OPM' classification.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/21678421.2026.2644277},
pmid = {41843813},
issn = {2167-9223},
abstract = {BACKGROUND: Defining motor phenotypes in amyotrophic lateral sclerosis (ALS) is important for individualized care and optimal therapeutic trial design. The "ALS-OPM" classification is based on the onset region (O), the propagation of motor symptoms (P), and the degree of clinical upper (UMN) and/or lower (LMN) motor neuron dysfunction (M).

METHODS: An international ALS expert focus group was held in September 2025, followed by a consensus process through which revisions of the OPM classification were finalized.

RESULTS: Onset (O1-4) identifies first motor symptoms as relating to the head (O1), distal/proximal arm (O2d/p), respiratory/axial trunk (O3r/a), or distal/proximal leg (O4d/p). Onset symptoms are defined by weakness or slowed, poorly coordinated voluntary movements in the muscles of the head, arm, trunk, or leg, including dysarthria, dysphagia, dysphonia, dyspnea, and axial instability. Propagation (P1(n)) or absence of propagation (P0(n)) of motor symptoms from the onset region to another body region are designated, where n denotes the number of months from onset to propagation or assessment. The degree of UMN dysfunction (slowed, poorly coordinated voluntary movements, hyperreflexia and/or spastic muscle tone, emotional lability) and/or LMN dysfunction (weakness with associated muscle atrophy) is classified as follows: balanced UMN and LMN dysfunction (M0); dominant (M1d) or pure UMN dysfunction (M1p); dominant (M2d) or pure LMN dysfunction (M2p); and dissociated UMN/LMN dysfunction (M3), in which the arms and legs predominantly show LMN and UMN involvement, respectively.

CONCLUSION: The revised ALS-OPM classification aims to make it routine, practical and feasible to capture phenotype in clinical practice and therapeutic trials.},
}

@article {pmid41350059,
year = {2026},
author = {Sarker, SC and Chen, J and Wang, C and He, S and Yu, H and Li, X and Cui, H},
title = {ALS target-site mutations and overexpression synergistically enhance mesosulfuron resistance in Lolium perenne.},
journal = {Pesticide biochemistry and physiology},
volume = {216},
number = {Pt 2},
pages = {106802},
doi = {10.1016/j.pestbp.2025.106802},
pmid = {41350059},
issn = {1095-9939},
mesh = {*Acetolactate Synthase/genetics/metabolism ; *Lolium/genetics/drug effects/enzymology ; *Herbicide Resistance/genetics ; *Sulfonylurea Compounds/pharmacology ; Mutation ; *Herbicides/pharmacology ; *Plant Proteins/genetics/metabolism ; },
abstract = {The invasive weed Lolium perenne (perennial ryegrass) poses a considerable threat to winter wheat crops in China and is hardly controlled by acetolactate synthase (ALS) inhibitors after years of application. In this study, four L. perenne populations from different locations in Henan were collected to evaluate the mechanisms of target site resistance to mesosulfuron-methyl. The resistant index (RI) of these four populations ranged from 122.73 to 149.26 compared to the susceptible population. ALS gene sequencing revealed three specific target site mutations: Pro-197-Thr, Asp-376-Glu, and Trp-574-Leu. Among these, Trp-574-Leu has not been previously reported in L. perenne. Three simultaneous double mutations were found in the same individual: Pro-197-Thr and Asp-376-Glu (Group I); Pro-197-Thr and Trp-574-Leu (Group II); and Asp-376-Glu and Trp-574-Leu (Group III). The gene expression levels of the double mutant groups were significantly higher than those of the susceptible plants. The I50 values obtained from the ALS enzyme assays showed that all three double mutant groups demonstrated a 136.75 to 149-fold increase compared to the enzyme activity of susceptible plants. Molecular docking analysis of mutant ALS proteins with mesosulfuron-methyl indicated that the mutant proteins had a reduced binding affinity to the herbicide. This reduced affinity was due to the disruption of hydrogen bonds and other key interactions, which contributed to increased herbicide resistance. Double target site mutations in a single ALS gene are a crucial mechanism for conferring high levels of mesosulfuron-methyl resistance in L. perenne.},
}

*Acetolactate Synthase/genetics/metabolism
*Lolium/genetics/drug effects/enzymology
*Herbicide Resistance/genetics
*Sulfonylurea Compounds/pharmacology
Mutation
*Herbicides/pharmacology
*Plant Proteins/genetics/metabolism

@article {pmid41350075,
year = {2026},
author = {Wu, G and Chen, Y and Yao, Y and Huang, W and Wu, K},
title = {Integrating network toxicology and molecular docking to uncover mechanisms of novel herbicide-induced neurodegeneration.},
journal = {Pesticide biochemistry and physiology},
volume = {216},
number = {Pt 2},
pages = {106821},
doi = {10.1016/j.pestbp.2025.106821},
pmid = {41350075},
issn = {1095-9939},
mesh = {*Herbicides/toxicity/chemistry ; *Molecular Docking Simulation ; Humans ; *Neurodegenerative Diseases/chemically induced/metabolism ; Protein Interaction Maps ; },
abstract = {Rising global reliance on novel herbicides has outpaced understanding of their potential neurotoxicity. This study employs an integrative network-toxicology pipeline to clarify how five widely used compounds, including mesotrione, topramezone, flufenazopyr, glufosinate-ammonium and beflubutamid-M, may contribute to Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis pathogenesis. We first predicted toxic liabilities in eMolTox, SwissADME and ProTox, then harvested 310 human targets via PubChem, ChEMBL, STITCH and Swiss Target Prediction. Intersection with 3668-3429 disease genes (GeneCards/ OMIM) revealed 91-176 shared targets per disorder. PPI networks constructed in STRING and refined with Cytoscape (MCODE, cytoHubba) and novel NodeIdentifyR algorithm converged on eleven high-impact hub genes: EGFR, GSK3B, SRC, AKT1, MAPT, CASP3, MMP9, MTOR, PTK2, BCL2L1 and MAPK8. GO and KEGG enrichment analyses highlighted apoptosis, PI3K-Akt and MAPK signaling dysregulation. Single-cell and bulk transcriptomic atlases confirmed aberrant expression of these hubs in patient brains; Molecular docking demonstrated low-nanomolar affinities of all herbicides for multiple hub proteins, with mesotrione and topramezone displaying the broadest binding spectra and SRC emerging as a common high-affinity site. Molecular dynamics simulations supported stable binding in a representative herbicide-protein complex. Additionally, in vivo and in vitro experiments using Glufosinate-ammonium exposure corroborated the computational findings, underscoring the robustness of our approach. Together, these results establish a systems-level framework linking environmental herbicide exposure to neurodegeneration and nominate tractable targets for surveillance and therapeutic intervention.},
}

*Herbicides/toxicity/chemistry
*Molecular Docking Simulation
Humans
*Neurodegenerative Diseases/chemically induced/metabolism
Protein Interaction Maps

@article {pmid41350201,
year = {2026},
author = {Hokkoku, K and Inoue, M and Yamada, S and Namba, H and Matsukura, K and Mukai, T and Chiba, T and Hatanaka, Y and Kobayashi, S and Sonoo, M},
title = {Reply to the letter by Marimbun et al. on fasciculation awareness in ALS.},
journal = {Journal of the neurological sciences},
volume = {480},
number = {},
pages = {125677},
doi = {10.1016/j.jns.2025.125677},
pmid = {41350201},
issn = {1878-5883},
}

@article {pmid41350294,
year = {2025},
author = {Williams, SE and Luisi, K and Liang, C and Cane, A and Begier, E},
title = {Methodological Issues in Taquet et al.'s analysis preclude any conclusions regarding AS01 adjuvant's specific role in dementia prevention.},
journal = {NPJ vaccines},
volume = {10},
number = {1},
pages = {255},
pmid = {41350294},
issn = {2059-0105},
abstract = {Taquet et al. evaluated the impact of AS01-adjuvanted vaccines on subsequent dementia diagnosis[1]. The authors conclude: "No difference was observed between the two AS01-adjuvanted vaccines, suggesting that the AS01 adjuvant itself plays a direct role in lowering dementia risk". Although the study offers promising evidence, the inference regarding the role of AS01 adjuvant in dementia prevention is not convincingly supported by the presented data or other published literature[2].},
}

@article {pmid41350409,
year = {2025},
author = {Cheng, S and Zhong, C and Zhu, H and Mu, K and Jiang, H and Zhong, P and Ma, Z and Liu, X and Wang, Z and Liu, R and Ding, Y},
title = {Structural mechanisms and insights on multiple nanobodies binding diverse SOD1 epitopes.},
journal = {Communications biology},
volume = {9},
number = {1},
pages = {30},
pmid = {41350409},
issn = {2399-3642},
mesh = {*Superoxide Dismutase-1/chemistry/metabolism/immunology/genetics ; *Single-Domain Antibodies/chemistry/metabolism/immunology ; Humans ; *Epitopes/chemistry/immunology/metabolism ; Protein Binding ; Amyotrophic Lateral Sclerosis ; Models, Molecular ; Crystallography, X-Ray ; Protein Conformation ; },
abstract = {Copper/zinc superoxide dismutase (SOD1) is a crucial metalloenzyme that mitigates oxidative stress by scavenging superoxide anion radicals. Mutations and aggregation of SOD1 are closely linked to the pathogenesis of amyotrophic lateral sclerosis (ALS). Targeting pathogenic SOD1 with nanobodies presents a promising therapeutic approach. We report the first high-resolution crystal structures of SOD1 in complex with three distinct nanobodies (Nb1, Nb2, and Nb3) and their multimeric assemblies (1:2 and 1:3 stoichiometries), revealing distinct binding epitopes primarily mediated by their complementarity determining regions (CDRs) through hydrogen bonds, salt bridges, and hydrophobic interactions. Structural and biophysical analyses using isothermal titration calorimetry (ITC) and fluorescence-detection size-exclusion chromatography (FSEC) demonstrated that all three nanobodies bind SOD1 simultaneously with nanomolar affinities (KD values ranging from 23.2 nM to 529 nM). Notably, engineered multimeric tandem nanobodies (Nb1-Nb2-Nb3) achieved higher affinity (KD = 4.39 nM) compared to single nanobodies, as validated by ITC. Characterization via dynamic light scattering (DLS) further revealed colloidal stability of SOD1-nanobody complexes. These results provide the first atomic-resolution insights into multi-nanobody targeting of SOD1 without steric interference, establishing a foundation for developing high-affinity tools to detect and manipulate SOD1 in ALS and related neurodegenerative diseases.},
}

*Superoxide Dismutase-1/chemistry/metabolism/immunology/genetics
*Single-Domain Antibodies/chemistry/metabolism/immunology
Humans
*Epitopes/chemistry/immunology/metabolism
Protein Binding
Amyotrophic Lateral Sclerosis
Models, Molecular
Crystallography, X-Ray
Protein Conformation

@article {pmid41350806,
year = {2025},
author = {Nakamura, R and Tohnai, G and Atsuta, N and Matsuda, Y and Morimoto, S and Ito, D and Katsuno, M and Izumi, Y and Morita, M and Iwata, I and Yabe, I and Nakazato, T and Hattori, N and Hirayama, T and Kano, O and Tamura, A and Suzuki, N and Aoki, M and Shibuya, K and Kuwabara, S and Oda, M and Hashimoto, R and Aiba, I and Ishihara, T and Onodera, O and Yamashita, T and Ishiura, H and Bokuda, K and Shimizu, T and Ikeda, Y and Hasegawa, K and Tanaka, F and Yokota, T and Kanai, K and Noto, YI and Kaji, R and Watanabe, H and Konishi, T and Hasegawa, M and Fukaya, H and Niwa, JI and Doyu, M and Okada, Y and Nakamura, S and Ozawa, F and Okano, H and Nakatochi, M and Sobue, G and , },
title = {A genome-wide association study identifies the GPM6A locus associated with age at onset in ALS.},
journal = {Communications biology},
volume = {8},
number = {1},
pages = {1720},
pmid = {41350806},
issn = {2399-3642},
support = {23FC0201//Ministry of Health, Labour and Welfare (Ministry of Health, Labour and Welfare, Japan)/ ; JP23ek0109492, JP23ak0101111, JP23ak0101124, JP24wm0425009//Japan Agency for Medical Research and Development (AMED)/ ; JP24ak0101216, JP24ak0101222, JP25wn0625519, JP25ak0101216, JP25ak0101222, JP25ek0109617//Japan Agency for Medical Research and Development (AMED)/ ; JP23ek0109538//Japan Agency for Medical Research and Development (AMED)/ ; JP23bm1123046, JP23kk0305024, JP23bm1423002//Japan Agency for Medical Research and Development (AMED)/ ; JP24bm1423003//Japan Agency for Medical Research and Development (AMED)/ ; JP23bm1123046, JP23kk0305024, JP23bm1423002//Japan Agency for Medical Research and Development (AMED)/ ; JP19km0405216//Japan Agency for Medical Research and Development (AMED)/ ; 19K07973//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22K07359//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22K07509//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 19K06523//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22K07359//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 19K07973//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22K07509//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 23K06835//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22K07359//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22K07509//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 25K10781//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 21H05278//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 19K06523//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 23K06975//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22H02988//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 23K06975//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 23K24249//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 21H05278//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 16H06277//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22H04923//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22H03350//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology ; *Genome-Wide Association Study ; Age of Onset ; Female ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Aged ; Genetic Predisposition to Disease ; Adult ; *GPI-Linked Proteins/genetics ; Japan ; },
abstract = {Amyotrophic lateral sclerosis (ALS) exhibits considerable clinical variability, such as differences in age at onset (AAO). Multiple factors, including genetic factors, may underlie this variability; however, the specific determinants remain unclear. To identify genes affecting AAO, we have conducted a genome-wide association study in Japanese patients with ALS (discovery cohort: n = 1808; replication cohort: n = 207). Here, we show that the minor A allele of rs113161727 at the ADAM29-GPM6A locus is associated with a younger AAO in the discovery cohort (effect, -4.27 years; p = 4.60 × 10[-8]); this finding has been confirmed in the replication cohort (p = 0.0068) and meta-analysis (p = 1.08 × 10[-9]). Among 65 ALS patients with a SOD1 mutation, the AAO has been found to be 10.2 years younger in those with the A allele than in those without it (p = 0.002). This variant correlates with GPM6A upregulation in iPSC-derived motor neurons, suggesting GPM6A as a candidate AAO modifier. Overall, our study highlights the impact of genetic modifiers on ALS heterogeneity and provides a potential target for delaying disease onset.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/epidemiology
*Genome-Wide Association Study
Age of Onset
Female
Male
Middle Aged
Polymorphism, Single Nucleotide
Aged
Genetic Predisposition to Disease
Adult
*GPI-Linked Proteins/genetics
Japan

@article {pmid41351663,
year = {2025},
author = {Amirian, R and Merati, A and Babamohamadi, M and Mirahmadi, Y and Esfahani, ML and Rahmani, S and Izadi, Z and Rezazadeh, D},
title = {Navigating the Autophagy Maze: ATG and Their Impact on Neurodegenerative Diseases.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {260},
pmid = {41351663},
issn = {1559-1182},
mesh = {*Autophagy/genetics/physiology ; Humans ; *Neurodegenerative Diseases/genetics/metabolism/pathology ; Animals ; *Autophagy-Related Proteins/metabolism/genetics ; Signal Transduction ; },
abstract = {Autophagy, a tightly regulated process essential for maintaining cellular homeostasis, plays a critical role in the pathogenesis and progression of neurodegenerative diseases (NDs). These disorders-marked by diverse mechanisms and clinical heterogeneity-pose significant challenges in developing effective therapies. Central to the autophagic machinery are autophagy-related genes (ATGs), whose functions and variants are increasingly recognized as pivotal in modulating disease-specific pathways. This review explores the intricate roles of ATGs in NDs, emphasizing the need for a comprehensive understanding of molecular signaling networks, protein-protein interactions, and regulatory checkpoints that may serve as therapeutic targets. We highlight recent advancements in disease modeling, autophagy assays, and biomarker identification that facilitate the translation of ATG-related discoveries into clinical practice. Furthermore, we underscore the importance of interdisciplinary collaboration across academia, industry, clinical medicine, and regulatory bodies to harness the therapeutic potential of autophagy. This article aims to serve as a detailed roadmap for understanding the role of ATGs in NDs and to illuminate promising avenues for future research and therapeutic development.},
}

*Autophagy/genetics/physiology
Humans
*Neurodegenerative Diseases/genetics/metabolism/pathology
Animals
*Autophagy-Related Proteins/metabolism/genetics
Signal Transduction

@article {pmid41352634,
year = {2026},
author = {Geleta, LA and Doyle, C and Garton, FC and Fowler, M and Carr, JM and Akkari, PA and McRae, AF and Rogers, ML and Madakkatel, I and Benyamin, B},
title = {The roles of human endogenous retrovirus in neurodegenerative diseases: A systematic review.},
journal = {Brain, behavior, and immunity},
volume = {132},
number = {},
pages = {106201},
doi = {10.1016/j.bbi.2025.106201},
pmid = {41352634},
issn = {1090-2139},
mesh = {Humans ; *Endogenous Retroviruses/genetics/physiology ; *Neurodegenerative Diseases/virology/genetics ; Alzheimer Disease/virology ; Amyotrophic Lateral Sclerosis/virology ; Parkinson Disease/virology ; Frontotemporal Dementia/virology ; },
abstract = {BACKGROUND: Human endogenous retroviruses (HERVs) constitute ∼8 % of the human genome, far exceeding the 2 % occupied by protein-coding genes. Although most HERV sequences are inactive, some HERV elements can be reactivated under certain conditions and may contribute to neurodegenerative diseases (NDDs). However, the findings vary across different HERV families, disease models, and detection methods. Here, we systematically review and synthesize the available evidence on the role of HERVs in human NDDs and reconcile inconsistencies in the literature.

METHODS: We systematically searched MEDLINE, EMBASE, Cochrane Library, PsycINFO, Scopus, Web of Science, CINAHL, and Emcare to identify relevant studies. Two independent reviewers screened studies, assessed quality, and extracted data. Qualitative synthesis was conducted for all included NDDs, specifically Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Parkinson's disease (PD), and due to data availability, meta-analysis was used to assess the impact of HERVs antibodies on ALS only.

RESULTS: Twenty-six studies (N ranges: 6-485) met the inclusion criteria, with majority focusing on HERV-K and ALS. Across studies, the association between HERV expression and NDDs was inconsistent, particularly for ALS, PD, and FTD, whereas investigations in AD showed a more consistent upregulation of specific HERVs. Studies relying on polymerase chain reaction (PCR) (typically smaller) showed inconsistent associations (21 studies), while RNA sequencing studies reported consistent associations (9 studies). A preliminary meta-analysis revealed a fivefold increase [OR: 5.83; 95 % CI: 4.14, 8.18] in ALS risk among participants with positive HERV antibodies.

CONCLUSIONS: The inconsistencies in HERV involvement across NDDs highlight the need for further studies employing standardized methodologies. RNAseq findings on the association of HERVs expression and NDDs support the need for large-scale RNA sequencing studies (rather than small, PCR studies) and careful tissue selection to clarify HERVs' role in NDDs. The association of HERV-K antibodies with ALS risk and prognosis suggests a significant role in disease, which could help detect biomarkers and used as a target for treatment.},
}

Humans
*Endogenous Retroviruses/genetics/physiology
*Neurodegenerative Diseases/virology/genetics
Alzheimer Disease/virology
Amyotrophic Lateral Sclerosis/virology
Parkinson Disease/virology
Frontotemporal Dementia/virology

@article {pmid41352688,
year = {2026},
author = {Chikuchi, R and Kato, Y and Tomatsu, A and Nishisaki, S and Kawakami, Y and Yoshimura, T and Li, J and Iguchi, Y and Onodera, K and Hashimoto, R and Aiba, I and Nakamura, R and Tohnai, G and Atsuta, N and Sobue, G and Okada, Y and Katsuno, M and Yokoi, S},
title = {The TDP-43[I383V] heterozygous mutation results in increased TDP-43 expression and altered neuronal activity in ALS patient-derived iPSC motor neurons.},
journal = {Neuroscience research},
volume = {222},
number = {},
pages = {105003},
doi = {10.1016/j.neures.2025.105003},
pmid = {41352688},
issn = {1872-8111},
mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Motor Neurons/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; Humans ; *DNA-Binding Proteins/genetics/metabolism ; Animals ; Mutation/genetics ; Rats ; Heterozygote ; Coculture Techniques ; Cells, Cultured ; },
abstract = {TAR-binding protein 43 (TDP-43) is a pathogenic RNA-binding protein associated with amyotrophic lateral sclerosis (ALS). To elucidate the pathogenesis of ALS, we generated induced pluripotent stem cells (iPSCs) from lymphoblastoid cell line (LCL) cells of an ALS patient with the TDP-43[I383V] heterozygous mutation. Furthermore, we generated isogenic wild-type iPSCs from wild-type LCL cells using scarless genome editing with CRISPR/Cas9. A modified iPSC-derived motor neuron culture method utilizing BrainPhys neuronal medium and rat astrocyte co-culture effectively promoted and maintained neuronal activity. Under these conditions, the TDP-43[I383V] heterozygous mutation resulted in increased TDP-43 protein expression through prolonged stabilization. Moreover, mutant iPSC-derived motor neurons showed increased numbers of pre-synapses and altered neuronal activity. These results suggest that the modified motor neuron culture method can help elucidate abnormalities in TDP-43 expression, synapse formation, and neuronal activity caused by the heterozygous TDP-43[I383V] mutation. The model developed in this study has the potential to facilitate the analysis of the early pathological phenotype of ALS.},
}

*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology
*Motor Neurons/metabolism
*Induced Pluripotent Stem Cells/metabolism
Humans
*DNA-Binding Proteins/genetics/metabolism
Animals
Mutation/genetics
Rats
Heterozygote
Coculture Techniques
Cells, Cultured

@article {pmid41352714,
year = {2025},
author = {Maas, D and Spindler, A and Zappi, I and Shapiro, J and Lo Sicco, KI},
title = {Response to Vaz de Faria et al's ''Forehead atrophy in frontal fibrosing alopecia: An ultrasonographic and histopathological study of 10 patients".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.10.159},
pmid = {41352714},
issn = {1097-6787},
}

@article {pmid41352717,
year = {2025},
author = {Doche, I and Vaz de Faria, JR},
title = {Response to Maas et al, "Response to Vaz de Faria et al's "Forehead atrophy in frontal fibrosing alopecia: An ultrasonographic and histopathological study of 10 patients"".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.12.015},
pmid = {41352717},
issn = {1097-6787},
}

@article {pmid41352930,
year = {2026},
author = {Queral-Beltran, A and Lacorte, S and Tauler, R},
title = {GC-orbitrap-HRMS with ROIMCR and MSident targeted and non-targeted analysis of persistent organic pollutants in fish-based certified reference materials.},
journal = {Analytica chimica acta},
volume = {1383},
number = {},
pages = {344892},
doi = {10.1016/j.aca.2025.344892},
pmid = {41352930},
issn = {1873-4324},
mesh = {Animals ; *Gas Chromatography-Mass Spectrometry/standards/methods ; *Fishes ; *Persistent Organic Pollutants ; Reference Standards ; },
abstract = {The use of fish-based reference materials allows the validation of analytical methods used for the monitoring of persistent organic pollutants (POPs) in environmental samples. Thus, the aim of this work has been to apply and validate the Regions of Interest Multivariate Curve Resolution (ROIMCR) procedure, in a first instance, to quantify POPs using two fish-based certified reference materials (CRM) provided by the Institute of Reference Materials (IRMM); and also to identify, with the MSident program, the presence of more POPs in the same samples. Samples were extracted and analyzed by gas chromatography coupled to an Orbitrap mass spectrometer (GC-HRMS). A targeted analysis was performed to quantify the four certified POPs: hexachlorobenzene (HCBz) and hexachlorobutadiene (HCBu) in ERM®-CE100 and pentachlorobenzene (PeCB) and α, β, γ, and δ-hexachlorocyclohexane (HCH) in ERM®-CE103. Quantitative estimations obtained with ROIMCR method were compared with those obtained using the instrument vendor's Xcalibur software. Two tailed t-tests were performed and good agreement was observed between the two approaches and with the certified values. A non-targeted analysis approach was then performed to characterize other unknown POPs present in the samples. Data processed with the ROIMCR method in the non-targeted acquisition mode was complemented with the MSident chemical identification procedure, which allowed the annotation of several polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs), phthalates, and polychlorinated biphenyls (PCBs). The presence of some of these compounds was confirmed with the analysis of validation standard mixture samples containing 43 POPs. The ROIMCR methodology herein proposed allows, in a first instance, the quantitative analysis of multiple unknown contaminants present in the analyzed fish-based certified samples by using GC-HRMS data and also, combined with the MSident program, enables a qualitative analysis which could provide a comprehensive assessment of POP pollution patterns in fish or other environmental samples.},
}

Animals
*Gas Chromatography-Mass Spectrometry/standards/methods
*Fishes
*Persistent Organic Pollutants
Reference Standards

@article {pmid41353609,
year = {2026},
author = {Van Beckhoven, D and Serrien, B and Demeester, R and Van Praet, J and Messiaen, P and Darcis, G and Henrard, S and De Munter, P and Libois, A and Deblonde, J},
title = {Reply to Satapathy et al.'s comment on "Dual cross-sectional and longitudinal perspective on the continuum of HIV care to disentangle natural epidemic evolution from real progress, Belgium 2014-2022".},
journal = {HIV medicine},
volume = {27},
number = {2},
pages = {328-331},
doi = {10.1111/hiv.70163},
pmid = {41353609},
issn = {1468-1293},
}

@article {pmid41354105,
year = {2026},
author = {Mendes Araújo, L and Chianca, T and Persaud, C and Hartung, P and Soares, Y and Almirón, G and João, R},
title = {Respiratory strength training for patients with amyotrophic lateral sclerosis: A meta-analysis of randomized controlled trials.},
journal = {Respiratory medicine},
volume = {251},
number = {},
pages = {108560},
doi = {10.1016/j.rmed.2025.108560},
pmid = {41354105},
issn = {1532-3064},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/rehabilitation/therapy ; Randomized Controlled Trials as Topic ; *Breathing Exercises/methods ; Male ; Middle Aged ; Respiratory Muscles/physiopathology ; *Resistance Training/methods ; Female ; Treatment Outcome ; Aged ; Maximal Respiratory Pressures ; },
abstract = {INTRODUCTION: Respiratory strength training (RST) has been considered as a possible add-on treatment for amyotrophic lateral sclerosis (ALS). However, the benefits of RST are still controversial. We performed a meta-analysis of randomized controlled trials (RCTs) on the efficacy of RST in patients with ALS.

METHODS: PubMed, Embase and Cochrane Central were searched for RCTs comparing the use of RST with sham therapy or minimal device load in patients with ALS. The main outcomes were maximal expiratory pressure (MEP), maximal inspiratory pressure (MIP) and the ALS functioning rating scale (ALSFRS-R) score. Statistical analysis was performed using R software and heterogeneity was assessed with I[2] statistics.

RESULTS: Four RCTs were included with a total of 138 patients. RST was used to treat 69 (50 %) patients. The mean age was 60.2 ± 10.4 years, with 82 (62.3 %) male patients. Follow-up ranged from 2 to 8 months. Subgroup analysis of expiratory muscle training protocols showed a statistically significant improvement in MEP (MD 20.22 cmH2O; 95 % CI 2.66-37.77; p = 0.04). In overall analyses, there was no difference between groups regarding MEP (MD 9.40 cmH2O; 95 % CI -11.57-30.37; p = 0.25), MIP (MD 3.26 cmH2O; 95 % CI -9.23-15.75; p = 0.38), FVC (MD 4.05 %predicted; 95 % CI -0.91-9.01; p = 0.08) and ALSFRS-R score (MD 0.01 points; 95 % CI -0.29-0.32; p = 0.85).

CONCLUSION: In this meta-analysis of RCTs including patients with ALS, expiratory muscle training was associated with increased MEP compared with sham or minimal load. However, no statistically significant associations were found for overall RST in MIP, FVC, MEP, and ALSFRS-R.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/rehabilitation/therapy
Randomized Controlled Trials as Topic
*Breathing Exercises/methods
Male
Middle Aged
Respiratory Muscles/physiopathology
*Resistance Training/methods
Female
Treatment Outcome
Aged
Maximal Respiratory Pressures

@article {pmid41354564,
year = {2025},
author = {Mouhi, S and Pio, T and Andersen, J},
title = {Revisiting oligodendrocytes in amyotrophic lateral sclerosis using human multicellular stem cell models.},
journal = {Trends in cell biology},
volume = {},
number = {},
pages = {},
pmid = {41354564},
issn = {1879-3088},
support = {F31 NS135955/NS/NINDS NIH HHS/United States ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration, muscle wasting, and eventual paralysis. The clinical and genetic complexity along with rapid disease progression has hindered efforts to model the disease and develop effective treatments. Rodent models and human tissue studies point to dysfunction in oligodendrocyte lineage cells early in disease, although the underlying mechanisms remain unclear. Advances in stem cell research have introduced novel platforms to investigate cells in the oligodendrocyte lineage and their interactions with neurons and other glial cells in complex human genetic backgrounds. This Review summarizes the literature implicating oligodendrocyte lineage cells in ALS and discusses both the potential and limitations of in vitro-derived cultures to shed light on their vulnerabilities and cellular interactions.},
}

@article {pmid41354852,
year = {2025},
author = {Oraha, J and Wagner, R and Bergh, S and Lee, NJ and Kirik, D and Petersén, Å},
title = {Differential effects of overexpression of mutant huntingtin and TDP-43 in agouti-related protein neurons in the arcuate nucleus of the hypothalamus in mice.},
journal = {Acta neuropathologica communications},
volume = {13},
number = {1},
pages = {253},
pmid = {41354852},
issn = {2051-5960},
mesh = {Animals ; *DNA-Binding Proteins/genetics/metabolism ; *Neurons/metabolism/pathology ; *Agouti-Related Protein/metabolism/genetics ; Male ; *Arcuate Nucleus of Hypothalamus/metabolism/pathology ; Female ; Mice ; Mice, Transgenic ; *Nerve Tissue Proteins/genetics/metabolism ; Huntingtin Protein ; Humans ; Mutation/genetics ; *Nuclear Proteins/genetics/metabolism ; Mice, Inbred C57BL ; },
abstract = {The spectrum of frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) and Huntington disease (HD) are fatal neurodegenerative disorders with no major disease-modifying therapies. Recent work has shown that the hallmark pathological proteins TAR DNA binding protein of 43 kDa (TDP-43) in FTD/ALS and mutant huntingtin (mHTT) in HD may be interlinked. Furthermore, these disorders share early features of altered metabolism and psychiatric symptoms that have been suggested to arise from pathology in the hypothalamus, an important brain region involved in the regulation of metabolism and emotions. Agouti-related protein (AgRP)-expressing neurons localised exclusively to the arcuate nucleus (ARC) of the hypothalamus are key modulators of body weight regulation and food seeking behaviour, and they have recently been implicated in anxiety- and anhedonic-like processes. The aim of this study was to investigate the effects of overexpression of TDP-43 or mHTT in AgRP-expressing neurons on metabolic, behavioral and neuropathological features in mice. Flex-switch adeno associated viral vectors expressing human wild-type TDP-43, mHTT or green fluorescent protein to serve as a control, were injected into male and female AgRP-Cre mice to target the ARC using stereotactic surgery. We demonstrate targeted overexpression of transgenes including formation of mHTT inclusions in the ARC of the hypothalamus. Overexpression of mHTT led to a significant reduction in AgRP fibres in the hypothalamus 21 weeks post-injection, as well as higher food consumption in female mice. Overexpression of TDP-43 did not lead to the development of any metabolic or behavioral phenotypes in the mice. Our data suggest that AgRP neurons in the ARC are protected from the toxic effects resulting from overexpression of TDP-43 whereas they display some sensitivity to mHTT overexpression resulting in mHTT inclusion formation, reduction in AgRP fibers and sex-specific effects on food consumption. Taken together, other hypothalamic neuronal populations may be more important for the development of non-motor features resulting from overexpression of TDP-43 and mHTT in the hypothalamus.},
}

Animals
*DNA-Binding Proteins/genetics/metabolism
*Neurons/metabolism/pathology
*Agouti-Related Protein/metabolism/genetics
Male
*Arcuate Nucleus of Hypothalamus/metabolism/pathology
Female
Mice
Mice, Transgenic
*Nerve Tissue Proteins/genetics/metabolism
Huntingtin Protein
Humans
Mutation/genetics
*Nuclear Proteins/genetics/metabolism
Mice, Inbred C57BL

@article {pmid41354869,
year = {2025},
author = {Tahedl, M and Kleinerova, J and McKenna, MC and Siah, WF and Hardiman, O and Hengeveld, JC and Doherty, MA and McLaughlin, RL and Tan, EL and Hutchinson, S and Bede, P},
title = {Putative mitochondrial components of frontotemporal lobar degeneration: topological correlations between mitochondrial density and atrophy in FTLD/FTD phenotypes.},
journal = {Journal of neurology},
volume = {273},
number = {1},
pages = {11},
pmid = {41354869},
issn = {1432-1459},
support = {(HRB EIA-2017-019/HRBI_/Health Research Board/Ireland ; JPND-Cofund-2-2019-1/HRBI_/Health Research Board/Ireland ; SFI SP20/SP/8953/SFI_/Science Foundation Ireland/Ireland ; },
mesh = {Humans ; Male ; Female ; Atrophy/pathology ; *Frontotemporal Lobar Degeneration/pathology/diagnostic imaging/metabolism/genetics ; Middle Aged ; Aged ; *Mitochondria/pathology/metabolism ; *Frontotemporal Dementia/pathology/diagnostic imaging ; Phenotype ; Magnetic Resonance Imaging ; *Brain/pathology/diagnostic imaging ; Prospective Studies ; },
abstract = {BACKGROUND: Frontotemporal lobar degeneration encompasses a spectrum of clinically, radiologically, and molecularly heterogeneous conditions. Clinical phenotypes are defined based on predominant neuropsychological manifestations and the selective involvement of specific brain regions determines the core symptoms, disability profiles, and care needs. While the unique anatomical patterns of cortical and subcortical degeneration along the FTLD/FTD spectrum are well recognised, the molecular basis of this selective vulnerability remains unclear.

METHODS: A large prospective neuroimaging study has been undertaken to explore topological associations between phenotype-specific atrophy patterns and physiological mitochondrial density along the FTLD/FTD spectrum. Patients with behavioural variant FTD (bvFTD), nonfluent variant primary progressive aphasia (nfvPPA), semantic variant primary progressive aphasia (svPPA), C9orf72-positive ALS-FTD, C9orf72-negative ALS-FTD, and a cohort of healthy controls (HC) were included. FTD phenotypes were first contrasted to healthy controls and the resulting voxelwise maps were correlated to physiological mitochondrial density maps.

RESULTS: We have identified voxelwise associations between atrophic change and physiological mitochondrial density. The resulting correlation coefficients over the entire GM mask revealed weak topological associations with r = 0.217 in C9NEG ALS-FTD, r = 0.251 in C9POS ALS-FTD, r = 0.213 in bvFTD, r = 0.182 in nfvPPA, and r = 0.292 in svPPA at p FWE < 0.001. Our region-of-interest analyses revealed moderate-to-strong regional associations between mitochondrial density and focal degenerative change with r values above 0.65 in multiple brain regions in all five FTD subgroups. Brain regions exhibiting the most significant associations between volume loss and mitochondrial density in each FTD subgroup are the very regions that define the core clinical manifestations of the given phenotype.

DISCUSSION: Cortical and subcortical brain regions with high physiological mitochondrial density are particularly vulnerable to neurodegenerative change in FTD. While these anatomical associations do not indicate direct causation, mitochondrial metabolism may represent an important component in the cascade of focal degeneration.},
}

Humans
Male
Female
Atrophy/pathology
*Frontotemporal Lobar Degeneration/pathology/diagnostic imaging/metabolism/genetics
Middle Aged
Aged
*Mitochondria/pathology/metabolism
*Frontotemporal Dementia/pathology/diagnostic imaging
Phenotype
Magnetic Resonance Imaging
*Brain/pathology/diagnostic imaging
Prospective Studies

@article {pmid41355168,
year = {2025},
author = {Cline, LL and Biggs, R and Butler, JS and Nichols, C},
title = {A Systems-Approach to Addressing the US Rural Veterinarian Shortage Through Collaborative Problem-Solving Training and Education.},
journal = {New directions for student leadership},
volume = {2025},
number = {188},
pages = {97-105},
doi = {10.1002/yd.70028},
pmid = {41355168},
issn = {2373-3357},
mesh = {Humans ; *Problem Solving ; *Education, Veterinary/organization & administration ; *Leadership ; *Veterinarians/supply & distribution ; *Rural Population ; United States ; Oklahoma ; Cooperative Behavior ; Workforce ; },
abstract = {The shortage of rural veterinarians in the United States poses significant challenges to food security, public health, and the agricultural economy. This article explores two systems-based training strategies to address this issue through two case studies: the Integrated Beef Cattle Program (IBCP) in the College of Veterinary Medicine (CVM) at Oklahoma State University (OSU) and the development of adaptive leadership and collaborative problem-solving capacity among rural veterinarians at Pat Dye Clinics. Grounded in Heifetz et al.'s (2009) adaptive leadership framework and Kirton's (2011) Adaption-Innovation Theory (A-I theory), these initiatives demonstrate how leadership development and cognitive diversity can enhance recruitment, retention, and resilience in rural veterinary practice. Findings suggest that integrating leadership learning in veterinary education and professional development can serve as a critical leverage point for systemic change.},
}

Humans
*Problem Solving
*Education, Veterinary/organization & administration
*Leadership
*Veterinarians/supply & distribution
*Rural Population
United States
Oklahoma
Cooperative Behavior
Workforce

@article {pmid41355171,
year = {2026},
author = {Lağap, AC and Harma, M},
title = {Does Your Love Lift Me Higher? A Direct Replication of the Energising Role of Secure Relationships.},
journal = {International journal of psychology : Journal international de psychologie},
volume = {61},
number = {1},
pages = {e70144},
doi = {10.1002/ijop.70144},
pmid = {41355171},
issn = {1464-066X},
mesh = {Humans ; Female ; Male ; *Motivation ; *Love ; Adult ; *Object Attachment ; Young Adult ; *Interpersonal Relations ; Adolescent ; },
abstract = {Previous work has revealed that priming people with significant others increases feelings of security and energy, and in turn, boosts exploration motivations. In this preregistered study, we directly replicated Luke et al.'s (2012) Study 2 (N = 281). We found similar results as the replicated study regarding increased security feelings and exploration motivations on the self-report measures after the priming. However, we did not find any support for the increased energy feelings after the attachment security priming. In addition, contrary to Luke et al.'s (2012) results, energy feelings did not mediate the relationship between security priming and exploration motivations. A discussion of null findings, along with the limitations of self-reports and potential misinterpretation of the mediational analyses, follows. We also discuss possible future implications of the current findings.},
}

Humans
Female
Male
*Motivation
*Love
Adult
*Object Attachment
Young Adult
*Interpersonal Relations
Adolescent

@article {pmid41355735,
year = {2025},
author = {Pal, P and Carrer, M and Weiss, L and Jaime, OG and Cheng, C and Shmara, A and Boock, V and Bosch, D and Youssef, M and Fazeli, Y and Afetian, M and Grossman, TR and Hicks, MR and Jafar-Nejad, P and Kimonis, V},
title = {Antisense oligonucleotides targeting valosin-containing protein ameliorate muscle pathology and molecular defects in cell and mouse models of multisystem proteinopathy.},
journal = {Clinical and translational medicine},
volume = {15},
number = {12},
pages = {e70530},
pmid = {41355735},
issn = {2001-1326},
support = {1297770//Muscular Dystrophy Association/ ; //Cure VCP Disease Inc. Ionis Pharmaceuticals, Inc./ ; },
mesh = {Animals ; *Valosin Containing Protein/genetics/metabolism/antagonists & inhibitors ; Mice ; *Oligonucleotides, Antisense/pharmacology/therapeutic use ; Disease Models, Animal ; Humans ; Muscle, Skeletal/pathology ; Muscular Dystrophies, Limb-Girdle/genetics ; Frontotemporal Dementia/genetics ; Myositis, Inclusion Body ; Osteitis Deformans/genetics ; },
abstract = {BACKGROUND: Valosin-containing protein (VCP) related disease, also known as multisystem proteinopathy 1 (MSP1), is an autosomal dominant disease caused by gain-of-function pathogenic variants of the VCP gene. The disease presents with variable combinations of inclusion body myopathy, early-onset Paget's disease of bone, frontotemporal dementia and may also overlap with familial amyotrophic lateral sclerosis. There is currently no treatment for this progressive disease associated with early demise resulting from proximal limb girdle and respiratory muscle weakness. We hypothesise that regulating VCP hyperactivity to normal levels can reduce the disease pathology.

MAIN TOPICS COVERED: In this study, we assessed the effect of antisense oligonucleotides (ASOs) specifically targeting the human VCP gene in the patient (R155H) iPSC-derived skeletal muscle progenitor cells (SMPCs). ASOs were well tolerated up to a concentration of 5 µM and significantly reduced VCP protein expression in the SMPCs by 48% (95% CI [39-56]). We also treated the transgenic mouse model of VCP disease with the overexpressed humanised VCP severe A232E pathogenic gene variant (VCP A232E mice) with weekly subcutaneous ASO injections starting from 6 months of age for 3 months. In the skeletal muscle of transgenic mice, ASOs resulted in 30% (95% CI [27-32]) knockdown of VCP protein compared with control ASO. The ASO-mediated reduction of VCP expression in muscle tissue was associated with improvement in autophagy flux and reduction in TAR DNA binding protein 43 (TDP-43) expression, hallmarks of VCP related MSP1. In addition, ASO-treated VCP A232E mice showed improvements in functional tests of muscle strength, such as rotarod and inverted screen test compared with mice treated with control ASO.

CONCLUSIONS: These results suggest that targeting VCP could be beneficial in preventing the progression of the VCP myopathy and hold promise for the treatment of patients with VCP related MSP1.

KEY POINTS: VCP multisystem proteinopathy 1 is caused by gain-of-function pathogenic variants of the VCP gene. VCP targeting ASOs were well tolerated and significantly reduced VCP, TAR DNA binding protein 43 (TDP 43), and autophagy protein expression in the (R155H) iPSC-derived skeletal muscle progenitor cells (SMPCs). The ASOs reduced VCP, TDP-43, and autophagy flux expression, and improved functional tests of muscle strength in the humanized VCP A232E mice.},
}

Animals
*Valosin Containing Protein/genetics/metabolism/antagonists & inhibitors
Mice
*Oligonucleotides, Antisense/pharmacology/therapeutic use
Disease Models, Animal
Humans
Muscle, Skeletal/pathology
Muscular Dystrophies, Limb-Girdle/genetics
Frontotemporal Dementia/genetics
Myositis, Inclusion Body
Osteitis Deformans/genetics

@article {pmid41356579,
year = {2025},
author = {Seyam, MK and Shaik, RA and Miraj, M and Alzahrani, NS and Shaik, AR and Ajmera, P and Kalra, S and Miraj, SA and Shawky, GM and Nurani, KM and A, P},
title = {Effect of mobile phone applications on medication adherence among patients with coronary artery diseases: A scoping review.},
journal = {World journal of cardiology},
volume = {17},
number = {11},
pages = {114140},
pmid = {41356579},
issn = {1949-8462},
abstract = {Patients with cardiovascular disease rely on medication to achieve favorable long-term clinical results. Poor adherence has been linked to a relative increase in mortality of 50%-80% as well as higher health care costs. This scoping review thus aimed to explore the evidence of the effects of mobile health care apps on medication adherence in patients with cardiovascular diseases. A comprehensive data search and extraction was done in line with the updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews checklist. A total of 10 studies were included for the review. The mean pooled improvement in adherence was found to be 18% and the most effective tool was the digital therapeutics app discussed in Li et al's study. Smartphones and apps enhance coronary artery disease management by promoting medication compliance. Challenges include data security and smartphone usage among the elderly. Tailored apps or voice assistants offer potential solutions.},
}

@article {pmid41356587,
year = {2025},
author = {Liu, HR and Weng, JL},
title = {Interpreting fractional flow reserve-guided percutaneous coronary intervention vs coronary artery bypass grafting outcomes.},
journal = {World journal of cardiology},
volume = {17},
number = {11},
pages = {113225},
pmid = {41356587},
issn = {1949-8462},
abstract = {Kataveni et al's meta-analysis offers an important contemporary synthesis of randomized evidence comparing fractional flow reserve-guided percutaneous coronary intervention and coronary artery bypass grafting (CABG) in multivessel coronary artery disease (CAD). The pooled analysis found no significant difference in all-cause mortality or stroke, yet CABG was superior in reducing myocardial infarction, major adverse cardiac events, and repeat revascularization. These results confirm CABG's durability even in the era of physiological lesion assessment and second-generation drug-eluting stents. From a traditional Chinese medicine (TCM) perspective, multivessel CAD corresponds to syndromes such as "heart vessel obstruction" and "Qi and blood stagnation", in which local blockage is compounded by systemic imbalance. While revascularization addresses the structural impediment to blood flow, TCM approaches, including herbal medicine, acupuncture, and lifestyle therapy, aim to improve microcirculation, reduce inflammation, and support recovery, potentially mitigating recurrent ischemic events. This commentary argues that future research should integrate optimal revascularization strategies with rigorously evaluated TCM interventions to address both the anatomical and systemic dimensions of CAD and improve long-term patient outcomes.},
}

@article {pmid41359166,
year = {2025},
author = {Gondim, FAA and Fernandes, JMA and Dutra Junior, AM and Thomas, FP},
title = {Four families with slowly progressive ALS due to p.Val120Leu SOD1 variant in Northeast Brazil.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-5},
doi = {10.1080/21678421.2025.2597943},
pmid = {41359166},
issn = {2167-9223},
abstract = {Objective: SOD1 mutations are the second most prevalent variants in amyotrophic lateral sclerosis (ALS). Epidemiological data about SOD1 mutations are scarce in Brazil. Here, we report the clinical and genetic findings of four Brazilian families with p.Val120Leu SOD1 variant. Methods: This study is part of an epidemiological study of the prevalence of ALS conducted in the State of Ceará, Brazil. We reviewed the medical records of families with p.Val120Leu (c.358G > C, exon 5) SOD1 variant seen at the Walter Cantídio University Hospital, Federal University of Ceará, Brazil. Results: We identified 15 patients from 4 families with p.Val120Leu SOD1 variant among 251 ALS patients. Of these, six were personally examined and had ALS confirmed and five had confirmatory genetic testing (four homozygous and one heterozygous). C9orf72 testing was normal in the heterozygous patient. In two families, three older heterozygous patients (genetically tested) had no signs or symptoms of ALS. The mean age of symptom onset was 46.7 ± 13.4 years. Features of ALS in the four families were very similar, with prolonged disease duration and upper and lower motor neuron involvement, fulfilling the Revised El Escorial, Awaji, and Gold Coast diagnostic criteria. All examined living patients had limb onset and a few bulbar symptoms. Conclusion: p.Val120Leu SOD1 variant leads to slowly progressive ALS with incomplete penetrance. Our findings are similar to a previous report of ALS due to p.Asp90Ala SOD1 variant.},
}

@article {pmid41359202,
year = {2025},
author = {Guerra-Hernández, J and Mauro-Gutiérrez, F and Rodríguez-Puerta, F and Pascual, A},
title = {Scaling and sampling dependencies of forest canopy height mapping towards jurisdictional biomass reporting using airborne LiDAR and small-area estimation.},
journal = {Carbon balance and management},
volume = {21},
number = {1},
pages = {12},
pmid = {41359202},
issn = {1750-0680},
support = {2023.15225.TENURE.008//Fundação para a Ciência e a Tecnologia/ ; PID2022-140104OA-I00//Spanish Ministry of Science and Innovation/ ; },
abstract = {Consolidated airborne laser scanning (ALS) programs, satellite imagery and spaceborne structural measurements have enabled major advances in canopy height mapping that translate towards the forest carbon biomass arena. However, we must carefully evaluate the cost of using fine-grained canopy height products to predict biomass under calibration models scoped at the scale of inventory plots. In this study, we estimated biomass using field plots and ALS metrics before predicting biomass over a jurisdiction of ~ 15,500 km[2] in Spain using 10 m, 25 m, 44 m, and 100 m as prediction scales. We altered the scale of ALS-based biomass predictors in 10 sub-jurisdictions intensively surveyed by the Spanish National Forest Inventory (NFI) before estimating mean and total biomass using three options: (i) traditional NFI design-based (DB) estimation, (ii) a model-based (MB) approach using scale-varying canopy height metrics from ALS and NFI plots, and (iii) an small-area estimation (SAE) implemntation designed for sub-jurisdictional domains. Higher uncertainties - relative standard errors (SE) - were found for DB, particularly at sub-jurisdictional and stratum levels. We observed a consistent increase in uncertainty for MB estimation from the finest 10 m scale up to 100 m. In MB estimation, the maximum relative bias reached 11% for 10-m predictions compared to the baseline estimate at the NFI sampling native resolution. The bias associated with the prediction scale ranged from + 5% (25 m) to -8% (100 m). The mean biomass estimates for SAE generally ranged between DB and MB but at lower uncertainty to the former, especially as the NFI sampling becomes scarcer and not enough for solid inference of biomass mean. The SEA statistics helped to disentangle biomass comparisons between ALS-based inference and the traditional NFI estimation that do not incorporate remote sensing data.},
}

@article {pmid41359433,
year = {2025},
author = {Zulhairy-Liong, NA and Edgar, S and Ellis, M and Zhu, D and Lai, K and Capelle, DP and Sabirin, S and Pek, EW and Nair, P and Ang, CM and Kennerson, ML and Shahrizaila, N and Ahmad-Annuar, A},
title = {Novel and rare variants in amyotrophic lateral sclerosis genes identified in Malaysian patients.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/21678421.2025.2582832},
pmid = {41359433},
issn = {2167-9223},
abstract = {There is limited information on the genetic architecture of amyotrophic lateral sclerosis (ALS) in Southeast Asian populations. To address this knowledge gap, we performed 1) SOD1 (exon 1-4), FUS (exon 13-15), TARDBP (exon 6) and ATXN2 repeat expansion screening in 201 multi-ethnic Malaysian (Malay, Chinese, Indian and others) ALS patients, 2) C9orf72 repeat expansion testing in 179 subset patients, and 3) a panel of 61 ALS-associated genes screening in 112 subset cases using either whole genome (n = 21) or exome (n = 91) sequencing datasets. Among the patients, the observed mutational frequencies in key ALS genes were: SOD1 3.0% (6/201), C9orf72 2.2% (4/179), ATXN2 2.0% (4/201), FUS 1.5% (3/201), and TARDBP 1.5% (3/201). Of the 112 cases that underwent WGS/WES, 6.3% (7/112) comprised of pathogenic and likely pathogenic variants in FIG4 (p.Lys657Serfs*2), FUS (p.Arg485Profs*32), TARDBP (p.Ile383del), NEK1 (p.Ile633Asnfs*28), GRN (c.599-1G > C), CYP27A1 (p.Met1Thr) and SPAST (p.Glu449Gly). Additionally, 42.9% (48/112) had at least one variant of uncertain significance (VUS) in 34 genes. Notably, in the 24 genes classified as 'definitive' by the ClinGen ALS Spectrum Disorders Gene Curation Expert Panel, five patients (4.5%, 5/112) harbored more than one likely pathogenic variant and/or VUS. However, burden analysis revealed no significant differences in clinical characteristics between patients with varying numbers of variants. Our findings highlight the utility of next-generation sequencing in elucidating the genetic basis of ALS in Malaysian and Southeast Asian ethnic groups, including the identification of several novel variants of clinical interest as well as increasing diagnostic yield up to 47.7%.},
}

@article {pmid41359530,
year = {2025},
author = {Rees, L and Lam, CF and Du, QS and Yu, A and Wong, MN and Xie, H},
title = {Exploring the duality of voice habit: Testing and extending theory and measurement.},
journal = {The Journal of applied psychology},
volume = {},
number = {},
pages = {},
doi = {10.1037/apl0001326},
pmid = {41359530},
issn = {1939-1854},
support = {//National Natural Science Foundation of China/ ; //Hong Kong General Research Fund/ ; },
abstract = {Scholars increasingly recognize the existence of voice habit, wherein employees speak up automatically without considering relevant situational factors, being able to control their impulse to voice, and exerting effort in deciding whether to voice. However, a lack of theory testing and an absence of a psychometrically valid measure have called into question its theoretical usefulness as well as its construct validity. Moreover, contrary to Lam et al.'s (2018) theorizing on the interpersonal costs and intrapersonal benefits of voice habit, research on the reticence bias suggests the opposite: Habitual voicers may gain interpersonal benefits by experiencing higher supervisor liking, but they may also suffer intrapersonal costs by experiencing voice regret. Integrating these divergent insights with theorizing on voice habit, we predict that voice habit may elicit supervisor liking when supervisors perceive habitual voicers as having higher prosocial motives or behavioral integrity, even though habitual voicers may experience regret in work units with a weaker voice climate. Results from a multiwave, multisource field study with 435 employees and 135 supervisors using a 12-item validated scale of voice habit support our hypotheses. Our work provides a direct test and extension of the recently proposed theorizing on voice habit and introduces a psychometrically valid measure for future research use. Our findings also empirically support the dual nature of voice habit, highlighting both its potential functional interpersonal outcomes in relation to supervisors and its potential dysfunctional intrapersonal outcomes for habitual voicers. (PsycInfo Database Record (c) 2025 APA, all rights reserved).},
}

@article {pmid41359535,
year = {2026},
author = {Bollen, C and van Grunsven, J},
title = {In defense of the double empathy problem hypothesis: An urgently needed alternative to fallacies and injustices in mainstream autism research.},
journal = {Psychological review},
volume = {133},
number = {2},
pages = {507-514},
doi = {10.1037/rev0000605},
pmid = {41359535},
issn = {1939-1471},
support = {//Netherlands Organisation for Scientific Research/ ; },
mesh = {Humans ; *Empathy ; *Autistic Disorder/psychology ; *Autism Spectrum Disorder/psychology ; *Psychological Theory ; },
abstract = {In their theoretical note, "The Double Empathy Problem: A Derivation Chain Analysis and Cautionary Note," Livingston et al. (2024) took a critical look at the double empathy problem hypothesis (DEPH). While they acknowledge that the DEPH offers promising insights, and while their critical note seems, at times, to be written with an eye to furthering and expanding DEPH, the main point they ultimately drive home is that DEPH has a "precarious theoretical and evidence base" and that, given this (allegedly) shaky foundation, applying DEPH "into real-world applications may have unintended and potentially harmful consequences for autistic people and those with similar conditions" (Livingston et al., 2024, p. 10). In this theoretical note, we take a critical look at Livingston et al.'s critique of DEPH, arguing that their warning note is problematic both from an ethical and philosophy of science point of view. (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}

Humans
*Empathy
*Autistic Disorder/psychology
*Autism Spectrum Disorder/psychology
*Psychological Theory

@article {pmid41360043,
year = {2026},
author = {Chis-Ciure, R},
title = {The unbearable hardness of inferring being: Comment on "preliminaries to artificial consciousness" by Evers et al.},
journal = {Physics of life reviews},
volume = {56},
number = {},
pages = {87-90},
doi = {10.1016/j.plrev.2025.12.004},
pmid = {41360043},
issn = {1873-1457},
mesh = {*Consciousness ; Humans ; Brain/physiology ; },
abstract = {This commentary commends Evers et al.'s multidimensional heuristic for structuring artificial consciousness research while arguing it cannot, as stated, adjudicate the nomological possibility of phenomenal consciousness, which is at stake in current debates. Behavioral-cognitive "profiles" lack a justified principle linking function to experience, and the awareness case study illustrates how externally specified goals can just as well underwrite as-if (pseudo-intentional) control rather than original intentionality. Moreover, the proposed heuristic overlooks that substrate similarity is currently indispensable for justifiably inferring the presence of consciousness beyond the validated case of the adult human brain. Given all this, the framework seems to provide a blueprint for building a more sophisticated philosophical zombie; it does not-and cannot-tell us whether anyone is there.},
}

*Consciousness
Humans
Brain/physiology

@article {pmid41360752,
year = {2026},
author = {Ma, JY and Wang, X and Cai, Y and Wang, G and Lu, M and Feng, K and Zhao, Y and Wu, X and Zhang, X and Wu, H and Yu, W and Ma, M and Ge, Z and Zhang, Y},
title = {Anionic Liposomes as Optimal Membrane Fusion Carriers Enabling in Situ Multiplexed Detection of Extracellular Vesicle MicroRNAs.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {13},
number = {10},
pages = {e19758},
pmid = {41360752},
issn = {2198-3844},
support = {2022YFA1205802//National Key Research and Development Program of China/ ; 2022YFC2406504//National Key Research and Development Program of China/ ; 82572399//National Natural Science Foundation of China/ ; 82302370//National Natural Science Foundation of China/ ; BF2024062//Frontier Technologies R&D Program of Jiangsu/ ; BK20230836//Natural Science Foundation of Jiangsu Province/ ; KYCX24_0471//Postgraduate Research & Practice Innovation Program of Jiangsu Province/ ; CXJH_SEU 25140//SEU Innovation Capability Enhancement Plan for Doctoral Students/ ; },
mesh = {*Extracellular Vesicles/genetics/metabolism ; Humans ; *Liposomes/chemistry ; *MicroRNAs/analysis/genetics ; Liquid Biopsy/methods ; *Membrane Fusion ; Anions/chemistry ; Biomarkers, Tumor ; },
abstract = {Extracellular vesicle (EV) microRNAs (miRNAs) are promising liquid biopsy biomarkers for non-invasive diagnosis, monitoring, and therapeutic evaluation of cancer. However, sensitive EV miRNA detection is hindered by complex pre-analytical processing. Here, the authors present an anionic liposome (AL) assisted membrane fusion strategy enabling one-step multiplexed quantification of EV miRNAs directly from plasma without EV isolation or RNA extraction, termed EValarm (Anionic Liposome Assisted miRNAs Monitoring for Extracellular Vesicles). Liposomes encapsulating probes are prepared using a microfluidic chip, achieving catalytic signal amplification after target recognition of miRNA. Systematic lipid screening identified ALs as optimal carriers, exhibiting minimal background and superior sensitivity compared to cationic and neutral liposomes. The AL-based assay delivered accuracy comparable to quantitative PCR with a streamlined workflow. Applied to 106 clinical samples from lymphoma patients and healthy controls, integration with artificial intelligence achieved high accuracy (AUC > 0.99). In summary, this study demonstrates a platform enabling direct and sensitive plasma EV miRNA detection, offering strong potential for clinical translation in cancer liquid biopsy.},
}

*Extracellular Vesicles/genetics/metabolism
Humans
*Liposomes/chemistry
*MicroRNAs/analysis/genetics
Liquid Biopsy/methods
*Membrane Fusion
Anions/chemistry
Biomarkers, Tumor

@article {pmid41361184,
year = {2025},
author = {Taquet, M and Todd, JA and Harrison, PJ},
title = {Reply to: Methodological Issues in Taquet et al.'s analysis preclude any conclusions regarding AS01 adjuvant's specific role in dementia prevention.},
journal = {NPJ vaccines},
volume = {10},
number = {1},
pages = {256},
pmid = {41361184},
issn = {2059-0105},
}

@article {pmid41361196,
year = {2025},
author = {Zhao, R and Bai, Y and Zhang, S and Zhu, J and Liu, H and Ni, G},
title = {An open dataset of multidimensional signals based on different speech patterns in pragmatic Mandarin.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {1934},
pmid = {41361196},
issn = {2052-4463},
mesh = {Humans ; *Speech ; Electroencephalography ; *Language ; Brain-Computer Interfaces ; Electromyography ; China ; Brain/physiology ; },
abstract = {Speech is essential for human communication, but millions of people lose the ability to speak due to conditions such as amyotrophic lateral sclerosis (ALS) or stroke. Assistive technologies like brain-computer interfaces (BCIs), can convert brain signals into speech. However, these technologies still face challenges in decoding accuracy. This issue is especially challenging for tonal languages like Mandarin Chinese. Furthermore, most existing speech datasets are based on Indo-European languages, which hinders our understanding of how tonal information is encoded in the brain. To address this, we introduce a comprehensive open dataset, which includes multimodal signals from 30 subjects using Mandarin Chinese across overt, silent, and imagined speech modes, covering electroencephalogram (EEG), surface electromyogram (sEMG), and speech recordings. This dataset lays a valuable groundwork for exploring the neural encoding of tonal languages, investigating tone-related brain dynamics, and improving assistive communication strategies. It supports cross-linguistic speech processing research and contributes to data-driven neural speech decoding technology innovations.},
}

Humans
*Speech
Electroencephalography
*Language
Brain-Computer Interfaces
Electromyography
China
Brain/physiology

@article {pmid41361897,
year = {2025},
author = {Rosenfeld, J and Abrahams, S and McHutchinson, C and Ajroud-Driss, S and Weber, M and Paganoni, S and Mitsumoto, H and Genge, A and Grosskreutz, J and Van Den Berg, L and Andrews, J and Kiernan, MC},
title = {Utility of patient subgrouping in ALS clinical trials: a World Federation of Neurology white paper.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/21678421.2025.2593308},
pmid = {41361897},
issn = {2167-9223},
abstract = {The heterogeneity among the amyotrophic lateral sclerosis (ALS)/MND patient population is well recognized but not well understood. Such heterogeneity may represent a significant confound in our current and prior clinical trials as certain subgroups of patients might have a selective response (or resistance) to a novel therapeutic. The basis on which to segregate the patient population is, however, unclear. The ALS/MND Committee of the World Federation of Neurology (WFN) convened a symposium to discuss various strategies that might be considered for separating (stratifying) the population to further study. The results of that conference are presented here as a white paper, reflecting current understanding of several of the various criteria that could be implemented to divide the patient population as presented and discussed at that meeting. Consideration of grouping patients based on phenotype, cognitive involvement, imaging, or electrophysiology is presented here.},
}

@article {pmid41362129,
year = {2025},
author = {Ma, T and Zhu, H and Zhu, J and Zhao, J and Zhao, X},
title = {Evaluation of pathogenicity, host resistance, biological properties and chemical control of Xanthomonas fragariae Strain JD1 causing angular leaf spot on strawberry.},
journal = {Plant disease},
volume = {},
number = {},
pages = {},
doi = {10.1094/PDIS-10-25-2070-RE},
pmid = {41362129},
issn = {0191-2917},
abstract = {Angular leaf spot (ALS), caused by the quarantine pathogen Xanthomonas fragariae, is a major bacterial disease threatening global strawberry production. In China, its continued spread across multiple regions poses a significant and persistent epidemiological threat to the strawberry industry. Recently, ALS has emerged as a great threat to strawberry industry in the Jiande, Zhejiang province (located at 29°N, 119°E). This study reports the first isolation and characterization of X. fragariae strain JD1 from symptomatic strawberry leaves in Jiande, Zhejiang Province. The identification of strain JD1 was confirmed through species-specific PCR, analysis of colony characteristics, and phylogenetic clustering based on 16S rRNA and HrpB gene sequences. Pathogenicity assays revealed strain JD1 resulted in water-soaked lesions progressing to necrotic patches on leaves, along with systemic colonization of crown tissues showing water-soaked, reddish-brown lesions without cavity formation. Additionally, resistance evaluation across six strawberry cultivars revealed that 'Yue Xiu' was the most susceptible, followed closely by 'Jiande Hong', 'Hong Yu', 'Li Fen', and 'Hong Yan', while 'Fen Yu' exhibited the highest resistance. Biological characterization showed that strain JD1 grows optimally at 25°C and pH 7.0, with significant inhibition observed at 35°C and under acidic (pH 4) or alkaline (pH 9) conditions. In bactericide screening, tetramycin and benziothiazolinone were identified as highly effective against JD, followed by sintracin acetate aqueous with minor efficacy, whereas kasugamycin and quinoline copper showed limited or no efficacy. Collectively, these findings not only emphasize the threat posed by X. fragariae strain JD1 to strawberry production but also provide critical insights that inform integrated management strategies, including the use of resistant cultivars, environmental controls, and targeted bactericides, for controlling ALS.},
}

@article {pmid41364388,
year = {2025},
author = {Levine, AA and Rucker, JA and Cockerham, A and Cartner, J and Chambers, JD},
title = {U.S. health plan coverage of Neuromuscular Disease Therapies: An assessment of policy availability and restrictions.},
journal = {Journal of neuromuscular diseases},
volume = {},
number = {},
pages = {22143602251405815},
doi = {10.1177/22143602251405815},
pmid = {41364388},
issn = {2214-3602},
abstract = {BACKGROUND: Health plan policies managing neuromuscular disease (NMD) therapies may impose burdensome requirements on patients and providers. While prior research has explored payer restrictions for rare NMD treatments, limited evidence exists on policies specifically governing therapy initiation and reauthorization.

OBJECTIVES: To examine initial and reauthorization coverage policies for therapies targeting five NMDs-Duchenne muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy, generalized myasthenia gravis, and Lambert-Eaton myasthenic syndrome-across all U.S. state Medicaid programs and leading commercial health plans.

METHODS: We constructed a database of coverage decisions issued by 50 states and DC Medicaid programs and 35 major commercial insurers, including both fee-for-service and managed care organizations. We analyzed (1) policy availability and coverage frequency, (2) initial coverage requirements (e.g., subgroup restrictions, step therapy, prescriber type), (3) reauthorization criteria, and (4) approval durations.

RESULTS: Of 1204 potential decisions, 908 (75%) had publicly available policies. Of these, 558 (46%) included reauthorization criteria. Among covered therapies, 96% imposed restrictions beyond FDA label indications. Requirements varied by payer type, NMD, and therapy. Average approval durations were 6 months for initial coverage and 10 months for reauthorization.

CONCLUSIONS: Many plans lacked publicly accessible policies, and most covered therapies were subject to restrictive requirements. These barriers-such as step therapy, narrow prescriber criteria, and short approval periods-may delay treatment and disrupt care continuity. Findings underscore the need for greater transparency and reform in prior authorization and pharmacy benefit design to support timely access to NMD therapies.},
}

@article {pmid41364409,
year = {2025},
author = {Matur, Z and Deveci, Ş and Erdal, Y},
title = {Correlations of cerebrospinal fluid neurofilament light chain levels with clinical and electromyography findings in amyotrophic lateral sclerosis.},
journal = {Irish journal of medical science},
volume = {},
number = {},
pages = {},
pmid = {41364409},
issn = {1863-4362},
abstract = {BACKGROUND: This study aimed to examine correlations between cerebrospinal fluid neurofilament light chain (CSF NfL) levels, and clinical and electrophysiological findings in amyotrophic lateral sclerosis (ALS). Compare CSF NfL and total protein levels between ALS and other central nervous system (CNS) neurodegenerative disorders.

METHODS: This retrospective study analyzed 46 ALS patients (Gold Coast criteria) and 33 non-ALS neurodegenerative controls. We documented time from symptom onset to diagnosis, revised ALS Functional Rating Scale (ALSFRS-R) scores at CSF sampling, initial involvement regions (bulbar/cervical/lumbosacral), and extent of lower motor neuron (LMN) involvement.

RESULTS: ALS patients had significantly higher CSF NfL levels than non-ALS controls (4221 ± 2585 vs. 3004 ± 2788 pg/mL, p = 0.025). In the ALS group, CSF NfL levels showed significant inverse correlation with ALSFRS-R scores (r = -0.332, p = 0.024), and patients demonstrating involvement in all four-region on needle electromyography exhibited the highest CSF NfL levels. Among the ALS cohort 18 patients (39%) had died by the last follow-up, and patients who died during the study exhibited significantly higher baseline CSF NfL levels (median: 5115 pg/mL) compared to surviving patients (median: 3276 pg/mL; p = 0.007).

CONCLUSIONS: Our study demonstrated that CSF NFL levels were significantly elevated in ALS compared to other neurodegenerative disorders. Higher CSF NFL concentrations correlated with more rapid functional decline, more extensive LMN degeneration, and poorer survival outcomes.},
}

@article {pmid41365006,
year = {2026},
author = {Hamzeloo, M and Bogenschütz, L and Hackländer, RPM and Bermeitinger, C},
title = {Evaluating the generalizability of the normative odor rating across cultures: Evidence from a German-speaking sample.},
journal = {Acta psychologica},
volume = {262},
number = {},
pages = {106056},
doi = {10.1016/j.actpsy.2025.106056},
pmid = {41365006},
issn = {1873-6297},
mesh = {Humans ; Male ; Female ; *Odorants ; Adult ; Young Adult ; *Olfactory Perception/physiology ; *Cross-Cultural Comparison ; Germany ; *Recognition, Psychology/physiology ; Adolescent ; Language ; *Smell/physiology ; },
abstract = {Olfactory perception varies across cultures, yet the cross-cultural generalizability of normative odor ratings remains underexplored. This study investigates the generalizability of normative odor ratings to a German-speaking sample by assessing 24 odors across eight dimensions-familiarity, frequency, pleasantness, irritability, context availability, discriminability, age of acquisition, and verbalizability-in 124 German-speaking participants (Mage = 22.36, SD = 3.24). Building on Moss et al.'s (2016) methodology with English-speaking participants, we examined the consistency of these dimensions, the influence of odor familiarity, and the role of odor-specific properties versus individual differences. Results revealed significant intercorrelations among the dimensions, except for age of acquisition, which negatively correlated with others, confirming the importance of early exposure in olfactory perceptual saliency and linguistic accessibility. For high-familiar odors, strong correlations with Moss et al.'s ratings were found for familiarity (r = 0.805), frequency (r = 0.799), pleasantness (r = 0.792), context availability (r = 0.794), discriminability (r = 0.967), and verbalizability (r = 0.844), and age of acquisition (r = 0.750), but not for irritability (r = 0.495). Low-familiar odors showed only a moderate correlation for verbalizability (r = 0.530), highlighting the role of exposure in cross-cultural consistency. Variance across odors significantly exceeded variance across participants, indicating reliable differentiation by odor properties. These findings suggest that normative odor ratings show strong cross-sample consistency across the two samples, particularly for familiar odors. This study supports the utility of normative ratings in olfactory research while highlighting the role of familiarity and context in cross-cultural perception.},
}

Humans
Male
Female
*Odorants
Adult
Young Adult
*Olfactory Perception/physiology
*Cross-Cultural Comparison
Germany
*Recognition, Psychology/physiology
Adolescent
Language
*Smell/physiology

@article {pmid41365015,
year = {2026},
author = {Svendsen, O and Stevens, MWR and Hamamura, T and Harpas, I and Radunz, M and King, DL},
title = {Reporting quality standards in gaming disorder treatment evidence: A systematic review.},
journal = {Acta psychologica},
volume = {262},
number = {},
pages = {106063},
doi = {10.1016/j.actpsy.2025.106063},
pmid = {41365015},
issn = {1873-6297},
mesh = {Humans ; *Video Games ; *Psychotherapy/standards ; Randomized Controlled Trials as Topic/standards ; *Internet Addiction Disorder/therapy ; *Research Design/standards ; },
abstract = {BACKGROUND: The treatment evidence base for gaming disorder (GD) has grown steadily over the past two decades. A systematic review by King et al. (2017) of 30 studies reported that GD treatment studies tended to favor psychotherapy approaches, but the research was limited by poor reporting standards as assessed by the Consolidated Standards of Reporting Trials (CONSORT) framework. This systematic review aimed to conduct a follow up evaluation of the reporting quality of subsequent GD treatment studies.

METHODS: A literature search of six databases yielded 51,056 records, which resulted in 31 eligible studies after screening. Each study's reporting quality was assessed using the CONSORT statement, and then these assessments were compared to King et al.'s (2017) review.

RESULTS: This review identified several methodological improvements since 2017: 61 % of studies were randomized controlled trials (vs. 40 % in 2017), 90 % included control groups (vs. 63 %), and follow-up duration increased to 6.1 months (vs. 3.5 months; p = .032). Reporting improved for participant flow (87.1 % vs. 43.3 %; p = .001) and group-level statistics (74.2 % vs. 36.7 %; p = .003), but some areas showed no improvement.

DISCUSSION: There have been several improvements in GD treatment study design and reporting, including controls, randomization and follow up, reflecting an increasing number of higher quality trials for the condition. Most of the studies with higher reporting quality (i.e., scoring ≥30/46 on the CONSORT framework) were psychotherapy-based. Future research should employ designs with longer follow-ups, broader assessment of outcomes, and standardized ICD-11-aligned tools. Pharmacological treatments, including novel pharmacotherapies for other addictions (e.g., Naltrexone), are underexplored and lack high quality evidence.},
}

Humans
*Video Games
*Psychotherapy/standards
Randomized Controlled Trials as Topic/standards
*Internet Addiction Disorder/therapy
*Research Design/standards

@article {pmid41365127,
year = {2026},
author = {Kulappu Arachchige, SN and Abeykoon, AMH and Stevenson, MA and Kanci Condello, A and Shil, PK and Tulman, ER and Szczepanek, SM and Silbart, LK and Underwood, GJ and Noormohammadi, AH and Geary, SJ and Wawegama, NK and Browning, GF},
title = {Assessment of tracheal mucosal thicknesses is a preferable method for evaluation of the immunogenicity of Mycoplasma gallisepticum vaccines in poultry.},
journal = {Vaccine},
volume = {72},
number = {},
pages = {128063},
doi = {10.1016/j.vaccine.2025.128063},
pmid = {41365127},
issn = {1873-2518},
mesh = {Animals ; *Mycoplasma gallisepticum/immunology ; *Bacterial Vaccines/immunology/administration & dosage ; *Poultry Diseases/prevention & control/immunology/microbiology ; *Mycoplasma Infections/prevention & control/veterinary/immunology ; *Trachea/pathology/immunology ; Chickens ; Vaccines, Attenuated/immunology/administration & dosage ; *Mucous Membrane/pathology ; *Immunogenicity, Vaccine ; Vaccine Efficacy ; Poultry ; Vaccination ; Air Sacs/pathology ; },
abstract = {Live-attenuated vaccines are commonly used to control chronic respiratory disease (CRD) caused by Mycoplasma gallisepticum in poultry. A previous review found that measures of tracheal lesions are better indicators of the validity of a vaccine efficacy test than air sac lesions. Here we extend those observations by comparing the raw tracheal mucosal thickness (TMT) and gross air sac lesion score (ALS) data from published vaccine efficacy studies to provide insights into standardising methods for evaluation of M. gallisepticum vaccine efficacy by identifying the most discriminative and reproducible parameter to demonstrate the efficacy of vaccines and the validity of immunogenicity tests. Our analyses revealed that a higher proportion of trials detected a ≥ 80 % effectiveness of challenge based on TMT, with a significantly lower number of biological replicates, than ALS. Furthermore, a significantly higher proportion of vaccinated-and-challenged groups had a proportion protected of ≥80 %, a reduction in lesions of ≥30 % and a mitigated fraction of ≥0.80, with a significantly lower number of biological replicates, compared to the positive-control group when analyses were based on TMT rather than ALSs. These findings indicate that TMT is a more discriminative and reproducible parameter to assess the efficacy of a vaccine and the validity of an efficacy test, and hence that this should be the primary outcome variable used to evaluate M. gallisepticum vaccine efficacy studies. Furthermore, the ability of TMT to discriminate these groups with fewer biological replicates enhances animal welfare by reducing the number of animals needed for efficacy studies.},
}

Animals
*Mycoplasma gallisepticum/immunology
*Bacterial Vaccines/immunology/administration & dosage
*Poultry Diseases/prevention & control/immunology/microbiology
*Mycoplasma Infections/prevention & control/veterinary/immunology
*Trachea/pathology/immunology
Chickens
Vaccines, Attenuated/immunology/administration & dosage
*Mucous Membrane/pathology
*Immunogenicity, Vaccine
Vaccine Efficacy
Poultry
Vaccination
Air Sacs/pathology

@article {pmid41366746,
year = {2025},
author = {Huang, J and Liu, Y and Li, M and He, R and Tang, Z and Lei, Y and Zha, Y and Wei, J},
title = {Safety and efficacy of botulinum toxin injection for sialorrhea in amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {BMC neurology},
volume = {25},
number = {1},
pages = {496},
pmid = {41366746},
issn = {1471-2377},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, with 80% of ALS patients experiencing bulbar weakness at some stage of the disease. ALS patients with bulbar weakness often suffer from troublesome sialorrhea. Botulinum toxin injection, as a neuromuscular blocker, has been widely used in the treatment of sialorrhea. This paper evaluates the safety and efficacy of botulinum toxin injections for the treatment of sialorrhea in ALS patients through a systematic review and meta-analysis.

METHODS: A systematic review and meta-analysis was conducted by searching eight databases, including PubMed, EMBASE, and CNKI, up to April 13, 2025. Eligible randomized controlled trials and quasi-experimental studies were analyzed using Review Manager 5.4 and Stata software.

RESULTS: Thirteen studies (2 RCTs, 11 quasi-experimental studies) with 130 ALS patients were included. Botulinum toxin significantly reduced sialorrhea and improved quality of life (Z = 10.98, p < 0.00001; RD = 0.82, 95% CI: 0.67–0.97). The treatment effect was independent of toxin type (p = 0.48), injection site (p = 0.17), and ultrasound guidance use (p = 0.44).

CONCLUSION: Botulinum toxin appears to be a safe and effective option for managing sialorrhea in ALS patients, regardless of injection technique. However, given that most included studies were observational, further validation through high-quality RCTs is warranted.

TRIAL REGISTRATION: This meta-analysis has been registered with Prospero, and the registration number is CRD420251029441. The registration period is April 9, 2025.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12883-025-04515-8.},
}

@article {pmid41366786,
year = {2025},
author = {Saracino, D and Cipriano, L and Houot, M and Querin, G and Rinaldi, D and Rametti-Lacroux, A and Wallon, D and Gerardin, E and Couratier, P and Boncoeur, MP and Lebouvier, T and , and Colliot, O and Pradat, PF and Migliaccio, R and Le Ber, I},
title = {Quantifying multimodal longitudinal brain changes in presymptomatic C9orf72 disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {12},
pages = {e70902},
pmid = {41366786},
issn = {1552-5279},
support = {PRTS2015-2019PREV-DEMALS//ANR/DGOS - Assistance Publique-Hôpitaux de Paris (Dr Le Ber)/ ; ANR-10-IAIHU-06//Agence Nationale de la Recherche (Dr Le Ber)/ ; 2019-JPW2-0005-01STRATALS//JPND/ANR (Dr Pradat and Dr Le Ber)/ ; ANR-23-IACL-0008, PRAIRIE-PSAI//Agence Nationale de la Recherche as part of the "France 2030" program/ ; ANR-19-P3IA-0001, projectPRAIRIE3IAInstitute//Agence Nationale de la Recherche as part of the "Investissements d'avenir" program/ ; 101136607, projectCLARA//European Union's HORIZON EUROPE Framework Programme/ ; },
mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/genetics/diagnostic imaging/pathology ; *Brain/pathology/diagnostic imaging ; *C9orf72 Protein/genetics ; Disease Progression ; *Frontotemporal Dementia/genetics/diagnostic imaging/pathology ; *Gray Matter/pathology/diagnostic imaging ; Longitudinal Studies ; Magnetic Resonance Imaging ; *White Matter/pathology/diagnostic imaging ; },
abstract = {INTRODUCTION: The presymptomatic phase of frontotemporal dementia and amyotrophic lateral sclerosis associated with C9orf72 repeat expansion features widespread structural brain changes. We aimed at fulfilling the unmet need of quantitative magnetic resonance imaging (MRI)-derived measures suitable for disease tracking.

METHODS: We compared the profile of longitudinal gray (GM) and white matter (WM) changes in 66 presymptomatic carriers and 52 controls over 3-year follow-up and appraised their annualized rate of change (ARC).

RESULTS: Both putamen (p < 0.01) and left insula (p = 0.005) volumes declined the most in carriers over 40, with an ARC up to four-fold higher than in controls. Increases in mean diffusivity occurred first in the left uncinate fasciculus, followed by thalamo-cortical bundles (p < 0.05), associated with higher neurofilament levels.

DISCUSSION: Our study highlighted the GM and WM structures showing the greatest longitudinal decline during the preclinical stage, whose ARC may serve as an MRI-derived biomarker for longitudinal surveillance and therapeutic outcome.

CLINICAL TRIAL REGISTRATION: NCT02590276 and NCT05358431.

HIGHLIGHTS: We studied longitudinal multimodal MRI changes in presymptomatic C9orf72 disease. Carriers displayed faster atrophy in putamen, insula and cerebellar regions. Mean diffusivity increased mainly in uncinate and thalamo-cortical tracts. These differences were even more significant in older (> 40) participants. We proposed targeted annualized rate of change as a quantitative biomarker.},
}

Aged
Female
Humans
Male
Middle Aged
*Amyotrophic Lateral Sclerosis/genetics/diagnostic imaging/pathology
*Brain/pathology/diagnostic imaging
*C9orf72 Protein/genetics
Disease Progression
*Frontotemporal Dementia/genetics/diagnostic imaging/pathology
*Gray Matter/pathology/diagnostic imaging
Longitudinal Studies
Magnetic Resonance Imaging
*White Matter/pathology/diagnostic imaging

@article {pmid41366852,
year = {2025},
author = {Barahona-López, C and Plans-Beriso, E and Diez-Echave, P and Hernández, O and de Larrea, NF and Craciun, O and García-Ovejero, E and Petrova, D and Fernández-Martínez, NF and Arruabarrena-Blanco, E and Babb-de-Villiers, C and Turner, H and Jimenez, RC and Erady, C and Wilson, H and Fernández-Navarro, P and García-Esquinas, EG and Kuhn, I and Sánchez, P and Rodríguez-Artalejo, F and Sánchez, MJ and Moreno, V and Blackburn, L and Pollán, M and Kroese, M and Perez-Gomez, B},
title = {Personalized prevention of neurodegenerative diseases: scoping review and evidence gap map.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {12},
pages = {e70980},
pmid = {41366852},
issn = {1552-5279},
support = {001/WHO_/World Health Organization/International ; 10040946//UKRI/ ; 101057721//Horizon Europe / H2020 Health/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/prevention & control/genetics ; Biomarkers ; *Precision Medicine/methods ; Evidence Gaps ; },
abstract = {Neurodegenerative diseases represent a major public health challenge due to their high prevalence and poor prognosis. Identifying biomarkers to stratify individuals by their risk of developing these diseases may help to define new personalized prevention interventions. The objective of this study was to conduct a scoping review of biomarkers for primary and secondary personalized prevention of neurodegenerative diseases. The search targeted biomarkers in adults or high-risk subpopulations in clinical or public health settings for Alzheimer's disease, vascular dementia, Lewy body disease, frontotemporal dementia, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis. Ultimately, 286 papers were included in the review and the interactive gap map. There is a strong focus on Alzheimer's disease, and most papers included -omics-based biomarkers and/or used artificial intelligence. Genetics/genomics are at the forefront of current scientific research, although there is a notable gap in studying gene-environment interactions, and studies in clinical settings are still scarce. HIGHLIGHTS: Research indicates a strong focus on Alzheimer´s disease and limited research in other diseases. Genetics and genomics are at the forefront of current scientific research. We found biomarkers for predicting progression in mild cognitive decline. There is a notable gap in studying gene-environment interactions. Studies investigating biomarkers in a clinical context are still scarce.},
}

Humans
*Neurodegenerative Diseases/prevention & control/genetics
Biomarkers
*Precision Medicine/methods
Evidence Gaps

@article {pmid41367793,
year = {2025},
author = {Yu, L and Yang, Z and Ming, Z and Zeng, S},
title = {Evaluation of ascending aorta and radial artery elasticity in patients with type 2 diabetes mellitus via velocity vector imaging.},
journal = {Quantitative imaging in medicine and surgery},
volume = {15},
number = {12},
pages = {12044-12054},
pmid = {41367793},
issn = {2223-4292},
abstract = {BACKGROUND: A decrease in arterial elasticity may contribute to accelerated atherosclerosis, the sequelae of which are the most common causes of death in type 2 diabetes mellitus (T2DM) patients. The aim of this study was to assess ascending aorta (AA) and radial artery (RA) elasticity in T2DM patients via velocity vector imaging (VVI).

METHODS: We enrolled 50 patients with T2DM and 52 age- and sex-matched nondiabetic individuals as controls. All the participants underwent echocardiography and RA ultrasound examinations. AA elasticity parameters, i.e., ascending aortic mean longitudinal strain (ALS), ascending aortic global circumferential strain (ACS), ascending aortic fractional area change (FAC), and RA elasticity parameters, i.e., radial arterial mean longitudinal strain (RLS) and radial arterial global circumferential strain (RCS), were evaluated with VVI. The differences in arterial elasticity parameters between diabetic and non-diabetic patients were evaluated by a paired t-test. Spearman correlation coefficients were calculated to demonstrate the relationship between arterial elasticity parameters and clinical risk factors and cardiovascular biometrics in T2DM patients.

RESULTS: We found that the T2DM group presented significantly lower ALS, ACS, FAC, RLS and RCS values than the control group did (all P<0.05). There were significant associations between all arterial elasticity parameters and glycosylated hemoglobin (HbA1c) and diabetes duration (ALS and HbA1c: r=-0.36, ALS and diabetes duration: r=-0.52, ACS and HbA1c: r=-0.32, ACS and diabetes duration: r=-0.38, FAC and HbA1c: r=-0.36, FAC and diabetes duration: r=-0.32, RLS and HbA1c: r=-0.39, RLS and diabetes duration: r=-0.46, RCS and HbA1c: r=-0.31, RCS and diabetes duration: r=-0.39, respectively; P<0.01). Additionally, the ALS was significantly negatively correlated with fasting plasma glucose (FPG) (r=-0.30, P<0.05).

CONCLUSIONS: The elasticity of the AA and RA in T2DM patients was impaired. Decreased arterial elasticity was associated with poor blood glucose control and a longer duration of diabetes. Further studies are needed to assess the clinical value of VVI findings for predicting future cardiac events.},
}

@article {pmid41368443,
year = {2025},
author = {Shamsi, A and Alrouji, M and AlOmeir, O and Tasqeruddin, S and Dinislam, K and Zuberi, A},
title = {Correction: CRISPR-Cas9: bridging the gap between aging mechanisms and therapeutic advances in neurodegenerative disorders.},
journal = {Frontiers in cellular neuroscience},
volume = {19},
number = {},
pages = {1739705},
doi = {10.3389/fncel.2025.1739705},
pmid = {41368443},
issn = {1662-5102},
abstract = {[This corrects the article DOI: 10.3389/fncel.2025.1681891.].},
}

@article {pmid41369024,
year = {2025},
author = {Correa-Arrieta, C and Castellar-Leones, S and Ruiz-Ospina, E and Diaz-Ruiz, J and Sanchez-Peñarete, D and Rodriguez-Cruz, W and Bravo-Espejo, J and Uriza-Prias, DM and Ortiz-Corredor, F},
title = {Amyotrophic lateral sclerosis in Colombia: a population-based study of incidence and socioeconomic determinants.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/21678421.2025.2597944},
pmid = {41369024},
issn = {2167-9223},
abstract = {Background and Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with variable global incidence. In Latin America, limited population-level data hinder accurate burden estimation and public health planning. This study estimated ALS incidence in Colombia from 1984 to 2024, analyzing regional distribution patterns and the demographic and socioeconomic profiles of affected individuals. Methods: This cross-sectional, population-based study analyzed 2185 clinically confirmed ALS cases reported to the Colombian National Institute of Health. Diagnoses were established using El Escorial or Gold Coast criteria. Annual and cumulative incidence rates were estimated using national population data. Demographic, geographic, and socioeconomic variables were classified under international standards, and all statistical analyses were performed using Python (version 3.12). Results: A total of 2185 ALS cases diagnosed between 1984 and 2024 were included. For the most recent decade (2015-2024), the national cumulative incidence was 41.46 per million inhabitants, with a steady increase in annual incidence. Bogotá and Caldas showed the highest cumulative incidence, whereas Chocó and Casanare reported the lowest. The mean age at diagnosis was 59.9 years, with a slight male predominance (male-to-female ratio 1.11:1). Socioeconomic disparities were evident: 18.0% of patients had no formal education, and over 40% were economically inactive at diagnosis. Conclusions: ALS incidence in Colombia is lower than that reported in high-income regions, but shows pronounced geographic and socioeconomic heterogeneity. These findings underscore the need to strengthen diagnostic capacity, improve equitable access to neurology services, and advance research on environmental and genetic determinants of ALS in Latin America.},
}

@article {pmid41370023,
year = {2026},
author = {Ding, W and Guo, J and Lu, Y and Li, X},
title = {Nocturnal hypoxemia mediates age-related sleep fragmentation in amyotrophic lateral sclerosis: a polysomnographic case-control study.},
journal = {Acta neurologica Belgica},
volume = {126},
number = {1},
pages = {251-258},
pmid = {41370023},
issn = {2240-2993},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/physiopathology ; Male ; Female ; Middle Aged ; Polysomnography ; *Hypoxia/physiopathology/etiology ; Aged ; Case-Control Studies ; *Sleep Deprivation/physiopathology/etiology ; *Aging/physiology ; Adult ; },
abstract = {OBJECTIVE: To evaluate sleep architecture disruptions in amyotrophic lateral sclerosis (ALS) using polysomnography (PSG) and identify clinical/demographic correlates for targeted interventions.

METHODS: Forty definite/probable ALS patients (revised El Escorial criteria) without primary sleep disorders and 40 age/sex/BMI-matched controls underwent full polysomnography (PSG). Sleep parameters (total sleep time [TST], sleep efficiency [SE], wake after sleep onset [WASO], N1-N3, rapid eye movement [REM] sleep), respiratory indices (AHI, minimum peripheral oxygen saturation (min SpO₂), SpO₂ range/coefficient of variation [CV]), and clinical metrics (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised [ALSFRS-R], Hospital Anxiety and Depression Scale [HADS]) were compared. Multivariate regression identified independent sleep predictors, and mediation analysis quantified min SpO₂'s role in age-sleep fragmentation relationships.

RESULTS: ALS patients showed significantly reduced TST (371.54 ± 67.62 vs. 495.13 ± 45.69 min, p = 0.004), SE (69.95 ± 13.79 vs. 85.10 ± 7.03%, p = 0.009), N2 sleep (127.33 ± 56.75 vs. 204.28 ± 67.16 min, p = 0.013), N3 sleep (61.70 ± 33.67 vs. 91.90 ± 44.06 min, p = 0.021), and REM sleep (66.09 ± 35.85 vs. 84.66 ± 37.65 min, p = 0.012) alongside elevated WASO (131.70 ± 78.82 vs. 64.26 ± 44.18 min, p = 0.015). Nocturnal oxygenation was impaired (min SpO₂: 89.3 ± 3.1% vs. 93.7 ± 2.4%, p < 0.001; SpO₂ CV: 3.7 ± 1.5% vs. 1.8 ± 0.9%, p < 0.001), though AHI and REM AHI were comparable (AHI: p = 0.087; REM AHI: p = 0.134). Age (β = -0.28, p = 0.02) and min SpO₂ (β = 0.31, p = 0.01) independently predicted TST. Mediation analysis confirmed min SpO₂ partially explains age-related TST reduction (indirect effect: -0.14, 95% CI: -0.28 to - 0.03; accounting for 43.8% of the total effect).

CONCLUSION: Our data confirm profound sleep architecture disruption and nocturnal hypoxemia in ALS independent of primary sleep disorders. Critically, we establish min SpO₂ as a partial mediator of age-related sleep fragmentation, suggesting that early management of hypoxemia may improve sleep quality. Larger prospective studies validating these mechanisms and their impact on disease progression are warranted.},
}

Humans
*Amyotrophic Lateral Sclerosis/complications/physiopathology
Male
Female
Middle Aged
Polysomnography
*Hypoxia/physiopathology/etiology
Aged
Case-Control Studies
*Sleep Deprivation/physiopathology/etiology
*Aging/physiology
Adult

@article {pmid41371413,
year = {2025},
author = {Spindler, A and Maas, D and Zappi, I and Senna, MM and Shapiro, J and Lo Sicco, KI},
title = {Response to Huang et al.'s ''Real-world efficacy of ritlecitinib in treating alopecia areata across various anatomical sites: potential rapid response predictors".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.10.161},
pmid = {41371413},
issn = {1097-6787},
}

@article {pmid41371952,
year = {2026},
author = {Dalton, C and Mojsilovic-Petrovic, J and Safren, N and Snoznik, C and Gebis, KK and Wang, YZ and Sutter, AB and Lamitina, T and Savas, JN and Kalb, RG},
title = {Ubiquitin Proteasome System Components, RAD23A and USP13, Modulate TDP-43 Solubility and Neuronal Toxicity.},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume = {46},
number = {4},
pages = {},
pmid = {41371952},
issn = {1529-2401},
support = {R01 NS124802/NS/NINDS NIH HHS/United States ; S10 OD032464/OD/NIH HHS/United States ; R35 NS122257/NS/NINDS NIH HHS/United States ; R01 NS052255/NS/NINDS NIH HHS/United States ; R21 NS087077/NS/NINDS NIH HHS/United States ; },
mesh = {Animals ; Humans ; HEK293 Cells ; *DNA-Binding Proteins/metabolism/genetics/toxicity/chemistry ; Rats ; *Neurons/metabolism ; *Proteasome Endopeptidase Complex/metabolism ; Solubility ; *DNA Repair Enzymes/metabolism/genetics ; Caenorhabditis elegans ; },
abstract = {At autopsy, >95% of ALS cases display a redistribution of the essential RNA binding protein TDP-43 from the nucleus into cytoplasmic aggregates. The mislocalization and aggregation of TDP-43 is believed to be a key pathological driver in ALS. Due to its vital role in basic cellular mechanisms, direct depletion of TDP-43 is unlikely to lead to a promising therapy. Therefore, we have explored the utility of identifying genes that modify its mislocalization or aggregation. We have previously shown that loss of rad-23 improves locomotor deficits in TDP-43 Caenorhabditis elegans models of disease and increases the degradation rate of TDP-43 in cellular models. To understand the mechanism through which these protective effects occur, we generated an inducible mutant TDP-43 HEK293 cell line. We find that knockdown of RAD23A reduces insoluble TDP-43 levels in this model and primary rat cortical neurons expressing human TDP-43[A315T] Utilizing a discovery-based proteomics approach, we then explored how loss of RAD23A remodels the proteome. Through this proteomic screen, we identified USP13, a deubiquitinase, as a new potent modifier of TDP-43 induced aggregation and cytotoxicity. We find that knockdown of USP13 reduces the abundance of sarkosyl insoluble mTDP-43 in both our HEK293 model and primary rat neurons, reduces cell death in primary rat motor neurons, and improves locomotor deficits in C. elegans ALS models.},
}

Animals
Humans
HEK293 Cells
*DNA-Binding Proteins/metabolism/genetics/toxicity/chemistry
Rats
*Neurons/metabolism
*Proteasome Endopeptidase Complex/metabolism
Solubility
*DNA Repair Enzymes/metabolism/genetics
Caenorhabditis elegans

@article {pmid41373461,
year = {2025},
author = {Butcher, EL and Arthur, S},
title = {Emerging Roles of Bile Acids in Neuroinflammation.},
journal = {International journal of molecular sciences},
volume = {26},
number = {23},
pages = {},
pmid = {41373461},
issn = {1422-0067},
mesh = {Humans ; *Bile Acids and Salts/metabolism ; *Neuroinflammatory Diseases/metabolism/pathology ; Animals ; Gastrointestinal Microbiome ; Signal Transduction ; Biomarkers/metabolism ; Blood-Brain Barrier/metabolism ; Inflammation/metabolism ; Central Nervous System/metabolism ; },
abstract = {Bile acids, once considered mere digestive detergents, have emerged as multifaceted signaling molecules with systemic influence extending far beyond the gastrointestinal tract. Recent discoveries reveal their capacity to modulate immune responses, cross the blood-brain barrier, and interact with central nervous system (CNS) cells through their receptors. Neuroinflammation, a key driver of neurodegenerative and neuroimmune disorders, is increasingly linked to bile acid signaling pathways that regulate glial activation, cytokine production, and neuronal survival. This review compiles the current evidence connecting bile acids to CNS inflammation, highlighting mechanistic insights, disease-specific alterations, and the gut-microbiome-bile acid-brain axis. It also explores the therapeutic potential of bile acid derivatives and receptor modulators, as well as their emerging role as biomarkers in conditions such as Alzheimer's disease, multiple sclerosis, and hepatic encephalopathy. Despite promising advances, critical gaps remain, including the need for bile receptor mapping in human CNS cells, standardized CNS bile acid profiling, and longitudinal metabolomic studies. Bridging these gaps may unlock new strategies for targeting neuroinflammation through bile acid-immune crosstalk.},
}

Humans
*Bile Acids and Salts/metabolism
*Neuroinflammatory Diseases/metabolism/pathology
Animals
Gastrointestinal Microbiome
Signal Transduction
Biomarkers/metabolism
Blood-Brain Barrier/metabolism
Inflammation/metabolism
Central Nervous System/metabolism

@article {pmid41373533,
year = {2025},
author = {Apolloni, S and Tortoriello, S and Milani, M and Rossi, S},
title = {Extracellular Matrix Remodeling in Motor Neuron Diseases.},
journal = {International journal of molecular sciences},
volume = {26},
number = {23},
pages = {},
pmid = {41373533},
issn = {1422-0067},
support = {GR-2021-12375436//Ministero della Salute/ ; PNRR project "Rome Technopole - Innovation Ecosystem"//European Union/ ; },
mesh = {Humans ; *Extracellular Matrix/metabolism/pathology ; *Motor Neuron Disease/metabolism/pathology ; Animals ; Amyotrophic Lateral Sclerosis/metabolism/pathology ; Motor Neurons/metabolism/pathology ; },
abstract = {The extracellular matrix (ECM) constitutes a dynamic scaffold composed of both cellular and non-cellular elements that not only ensure tissue integrity but also regulate signaling events crucial for development and homeostasis. While its dysregulation has long been investigated in cancer, fibrosis, and autoimmunity, increasing evidence implicates ECM remodeling in neurodegenerative diseases, including motor neuron diseases (MNDs). Amyotrophic lateral sclerosis and spinal muscular atrophy, the most studied MNDs, both exhibit profound ECM alterations that influence synaptic connectivity, glial reactivity, and neuroinflammation. This review outlines recent data on ECM dynamics in MNDs, highlighting shared and disease-specific mechanisms, their potential as biomarkers, and therapeutic opportunities targeting the ECM environment to preserve neuronal function and slow disease progression.},
}

Humans
*Extracellular Matrix/metabolism/pathology
*Motor Neuron Disease/metabolism/pathology
Animals
Amyotrophic Lateral Sclerosis/metabolism/pathology
Motor Neurons/metabolism/pathology

@article {pmid41373580,
year = {2025},
author = {Salvany, S and Hernández, S and Casanovas, A and Gras, S and Piedrafita, L and Bosch-Queralt, M and Schwab, MH and Calderó, J and Esquerda, JE and Tarabal, O},
title = {Chronic Overexpression of Neuronal NRG1-III in Mice Causes Long-Term Detrimental Changes in Lower Motor Neurons, Neuromuscular Synapses and Motor Behaviour.},
journal = {International journal of molecular sciences},
volume = {26},
number = {23},
pages = {},
pmid = {41373580},
issn = {1422-0067},
support = {PID2021-122785OB-I00//Ministerio de Ciencia e Innovación/ ; 202005-30//Marató de TV3 Foundation/ ; },
mesh = {Animals ; *Motor Neurons/metabolism/pathology ; *Neuromuscular Junction/metabolism/pathology ; *Neuregulin-1/genetics/metabolism ; Mice ; Mice, Transgenic ; Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *Motor Activity ; Disease Models, Animal ; Spinal Cord/metabolism/pathology ; Calcium/metabolism ; },
abstract = {Neuregulins (NRGs) are ligands of tyrosine kinase receptors from the ErbB family and play multiple developmental roles. NRG1-ErbB signaling regulates myelination and has been associated with amyotrophic lateral sclerosis (ALS) pathology. Given the potential therapeutic relevance of this pathway for motor neuron (MN) diseases, we employed a transgenic (TG) mouse with persistent neuronal overexpression of neuregulin type III (NRG1-III) to investigate its impact on the neuromuscular system. We performed an analysis of phenotypic changes in this TG model, including motor behavior, neuropathological evaluation by immunocytochemistry and ultrastructural examination of the spinal cord, peripheral nerves, and neuromuscular junctions (NMJs). Calcium dynamics in cultured MNs were also examined. We found that cholinergic C-boutons on TG MNs, where NRG1-III typically accumulates, exhibited upregulation of C-bouton-associated proteins and expansion of the subsynaptic cistern (SSC)-associated endoplasmic reticulum. Calcium imaging revealed altered homeostasis in TG MNs, accompanied by the upregulation of molecules linked to axonal plasticity. At NMJs, regressive changes involving autophagic dysregulation were observed. These alterations were accompanied by increased motor activity in behavioral tests. Overall, our findings indicate that persistently elevated NRG1-III signaling compromises MN connectivity and long-term health, a factor to consider when developing therapeutic strategies for neurodegenerative diseases such as ALS.},
}

Animals
*Motor Neurons/metabolism/pathology
*Neuromuscular Junction/metabolism/pathology
*Neuregulin-1/genetics/metabolism
Mice
Mice, Transgenic
Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics
*Motor Activity
Disease Models, Animal
Spinal Cord/metabolism/pathology
Calcium/metabolism

@article {pmid41373649,
year = {2025},
author = {Mukhija, S and Hering, L and Schreiner, SJ and Lehner, F and Loosli, J and Togni, C and Otto, F and Ziegler, M and Weiss, T and Jung, HH and Briel, N},
title = {Multimodal Biomarker Characterization of the ALS/FTD Spectrum: A Real-World Clinical Dataset Analysis.},
journal = {International journal of molecular sciences},
volume = {26},
number = {23},
pages = {},
pmid = {41373649},
issn = {1422-0067},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/cerebrospinal fluid/blood/metabolism ; *Biomarkers/blood/cerebrospinal fluid ; *Frontotemporal Dementia/diagnosis/blood/cerebrospinal fluid/metabolism ; Male ; Female ; tau Proteins/cerebrospinal fluid/blood ; Middle Aged ; Aged ; Cross-Sectional Studies ; Retrospective Studies ; Neuroimaging ; },
abstract = {Diagnosis and prognosis of the amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) spectrum remain largely dependent on clinical assessments due to a lack of established fluid biomarkers. While neurofilaments and the cerebrospinal fluid (CSF) phosphorylated-tau/total-tau ratio (pTau:tTau) have been studied, their limitations, including their lack of clinical implementation and low specificity, necessitate multimodal approaches. This study aimed to characterize the biological features of the ALS/FTD spectrum through integration of clinically available parameters. We conducted a retrospective, single-center, cross-sectional study analyzing routinely collected clinical, neuroimaging, CSF, and serum data from 229 samples, including 45 from patients with ALS, 26 from patients with FTD, 158 from patients with other neurodegenerative diseases, and 29 from cognitively healthy controls. We implemented propensity score-weighted comparisons, an F1 score-based optimal cut-point determination for the pTau:tTau ratio, and a regularized XGBoost-based multimodal feature modeling approach. The biomarker and model performance was evaluated by the area under the precision-recall curve (AUC-PR). Feature importance analysis identified characteristic indicators of the ALS/FTD spectrum. Consistent with the prior literature, the pTau:tTau ratio was significantly reduced in ALS/FTD, but the classification performance was modest (AUC-PR 0.32). A multimodal model integrating clinical, biofluid, and neuroimaging features achieved a notably better performance (AUC-PR 0.75). Feature importance analysis revealed an ALS/FTD signature beyond the pTau:tTau ratio characterized by higher global cognition, younger age, an altered Aβ42/pTau ratio, and immunoglobulin changes (CSF IgG:IgA, serum IgG). Integration of clinical routine data centered on tau, amyloid, and immunological pathophysiology as well as temporal disease dynamics provide a contextualized biological characterization of the ALS/FTD spectrum. This approach offers a foundation for hypothesis generation regarding ALS/FTD pathophysiology and biomarker-supported diagnosis.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/cerebrospinal fluid/blood/metabolism
*Biomarkers/blood/cerebrospinal fluid
*Frontotemporal Dementia/diagnosis/blood/cerebrospinal fluid/metabolism
Male
Female
tau Proteins/cerebrospinal fluid/blood
Middle Aged
Aged
Cross-Sectional Studies
Retrospective Studies
Neuroimaging

@article {pmid41373784,
year = {2025},
author = {Basavarajappa, BS and Subbanna, S},
title = {From Synaptic Plasticity to Neurotoxicity: Endocannabinoid Influence on Addiction and Neurodegeneration.},
journal = {International journal of molecular sciences},
volume = {26},
number = {23},
pages = {},
pmid = {41373784},
issn = {1422-0067},
mesh = {Humans ; *Endocannabinoids/metabolism ; *Neuronal Plasticity ; Animals ; *Neurodegenerative Diseases/metabolism ; *Substance-Related Disorders/metabolism ; Receptors, Cannabinoid/metabolism ; },
abstract = {The endocannabinoid system (eCBS) is a versatile neuromodulatory network that orchestrates synaptic plasticity, reward processing, and neuronal homeostasis. Increasing evidence implicates eCBS dysregulation in both addiction and neurodegenerative (ND) disorders, suggesting overlapping molecular and cellular mechanisms underlying these conditions. This review synthesizes recent advances in understanding how eCBS components-cannabinoid receptors (CB1 and CB2), endogenous ligands (anandamide and 2-arachidonoylglycerol), and their metabolic enzymes-modulate dopaminergic and glutamatergic signaling within reward and reinforcement circuits. Chronic exposure to drugs of abuse, including alcohol, opioids, cocaine, and methamphetamine, perturbs eCBS homeostasis, promoting oxidative stress, neuroinflammation, excitotoxicity, mitochondrial dysfunction, and protein aggregation-pathological features common to Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis. These overlapping mechanisms disrupt neuronal integrity and contribute to progressive neurotoxicity, highlighting shared pathogenic pathways between addiction and neurodegeneration. Despite these advances, critical gaps remain in delineating how substance-induced eCBS alterations precipitate neurodegenerative cascades. Addressing these gaps will be essential for harnessing the eCBS as a therapeutic target to mitigate addiction-driven neurotoxicity and age-related cognitive decline.},
}

Humans
*Endocannabinoids/metabolism
*Neuronal Plasticity
Animals
*Neurodegenerative Diseases/metabolism
*Substance-Related Disorders/metabolism
Receptors, Cannabinoid/metabolism

@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 = {},
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.},
}

@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 = {},
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 {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 = {},
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 {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 {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 {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 {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 {pmid41378777,
year = {2026},
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 = {149},
number = {3},
pages = {778-784},
doi = {10.1093/brain/awaf460},
pmid = {41378777},
issn = {1460-2156},
support = {AIH23//AI Health Innovation Cluster/ ; YI 209/1-1, AOBJ 680080//Deutsche Forschungsgemeinschaft/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *Motor Cortex/metabolism/pathology ; *Mutation/genetics ; Female ; Male ; Middle Aged ; Aged ; *RNA-Binding Protein FUS/genetics ; },
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 10% 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.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/pathology
*Motor Cortex/metabolism/pathology
*Mutation/genetics
Female
Male
Middle Aged
Aged
*RNA-Binding Protein FUS/genetics

@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 {pmid41379346,
year = {2026},
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 = {53},
number = {4},
pages = {2786-2798},
pmid = {41379346},
issn = {1619-7089},
mesh = {Humans ; *C9orf72 Protein/genetics ; *Fluorodeoxyglucose F18 ; Male ; *Amyotrophic Lateral Sclerosis/genetics/diagnostic imaging/metabolism ; Female ; Middle Aged ; *Positron-Emission Tomography ; *Brain/metabolism/diagnostic imaging ; Aged ; *DNA Repeat Expansion ; Adult ; },
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.},
}

Humans
*C9orf72 Protein/genetics
*Fluorodeoxyglucose F18
Male
*Amyotrophic Lateral Sclerosis/genetics/diagnostic imaging/metabolism
Female
Middle Aged
*Positron-Emission Tomography
*Brain/metabolism/diagnostic imaging
Aged
*DNA Repeat Expansion
Adult

@article {pmid41379813,
year = {2026},
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 = {17},
number = {1},
pages = {90-108},
doi = {10.1021/acschemneuro.5c00632},
pmid = {41379813},
issn = {1948-7193},
mesh = {*Superoxide Dismutase-1/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Humans ; Mutation/genetics ; *Superoxide Dismutase/genetics/metabolism ; *Protein Aggregates ; },
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.},
}

*Superoxide Dismutase-1/genetics/metabolism
*Amyotrophic Lateral Sclerosis/genetics/metabolism
Humans
Mutation/genetics
*Superoxide Dismutase/genetics/metabolism
*Protein Aggregates

@article {pmid41380476,
year = {2026},
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},
pmid = {41380476},
issn = {2352-3964},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/mortality ; DNA Methylation ; *Epigenesis, Genetic ; Polymorphism, Single Nucleotide ; Male ; Female ; Middle Aged ; CpG Islands ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; *Genetic Loci ; Aged ; Genotype ; Epigenomics/methods ; Whole Genome Sequencing ; Multiomics ; },
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).},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/mortality
DNA Methylation
*Epigenesis, Genetic
Polymorphism, Single Nucleotide
Male
Female
Middle Aged
CpG Islands
Genome-Wide Association Study
Genetic Predisposition to Disease
*Genetic Loci
Aged
Genotype
Epigenomics/methods
Whole Genome Sequencing
Multiomics

@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},
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 {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 {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 = {16},
number = {1},
pages = {510},
pmid = {41381656},
issn = {2045-2322},
support = {LP200200957//Australian Research Council/ ; UA720//South Australian Grains and Industry Trust/ ; BB/V018108/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; },
mesh = {Humans ; *Proteomics/methods ; Cell Line, Tumor ; Tandem Mass Spectrometry ; *Proteome ; *Dipeptides/toxicity ; Apoptosis/drug effects ; Oxidative Stress/drug effects ; *Alanine/analogs & derivatives/toxicity ; },
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.},
}

Humans
*Proteomics/methods
Cell Line, Tumor
Tandem Mass Spectrometry
*Proteome
*Dipeptides/toxicity
Apoptosis/drug effects
Oxidative Stress/drug effects
*Alanine/analogs & derivatives/toxicity

@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 {pmid41383013,
year = {2026},
author = {Hor, JH and Ow, JR and Ng, W and Ramasamy, B and Tabaglio, T and Lim, KNH and Bin Muzakar, MI and Lim, VJW 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 = {BLOC1S1 depletion via splice-switching oligonucleotides improves mitochondrial respiration and rescues ALS phenotypes.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {34},
number = {3},
pages = {1672-1683},
pmid = {41383013},
issn = {1525-0024},
mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism/therapy/pathology ; Animals ; *Mitochondria/metabolism/genetics ; Humans ; Mice ; Disease Models, Animal ; Motor Neurons/metabolism ; Phenotype ; *Oligonucleotides, Antisense/genetics ; Cell Respiration ; Induced Pluripotent Stem Cells/metabolism ; *RNA Splicing ; *Oligonucleotides/genetics ; },
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, postmortem motor cortices, and spinal cords of ALS mouse models. Functional studies in induced pluripotent stem cell-derived MNs reveal that BLOC1S1 depletion rescues key disease phenotypes. Therefore, we develop an efficacious splice-switching antisense oligonucleotide 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.},
}

*Amyotrophic Lateral Sclerosis/genetics/metabolism/therapy/pathology
Animals
*Mitochondria/metabolism/genetics
Humans
Mice
Disease Models, Animal
Motor Neurons/metabolism
Phenotype
*Oligonucleotides, Antisense/genetics
Cell Respiration
Induced Pluripotent Stem Cells/metabolism
*RNA Splicing
*Oligonucleotides/genetics

@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 {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 = {68},
number = {24},
pages = {25665-25688},
doi = {10.1021/acs.jmedchem.5c01488},
pmid = {41384353},
issn = {1520-4804},
mesh = {*Mitogen-Activated Protein Kinase 10/antagonists & inhibitors/metabolism/chemistry ; Humans ; *Protein Kinase Inhibitors/chemistry/pharmacology ; Structure-Activity Relationship ; Animals ; Models, Molecular ; Protein Isoforms/metabolism/antagonists & inhibitors ; },
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.},
}

*Mitogen-Activated Protein Kinase 10/antagonists & inhibitors/metabolism/chemistry
Humans
*Protein Kinase Inhibitors/chemistry/pharmacology
Structure-Activity Relationship
Animals
Models, Molecular
Protein Isoforms/metabolism/antagonists & inhibitors

@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 {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 = {69},
number = {5},
pages = {},
pmid = {41385186},
issn = {1744-1358},
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/drug therapy ; Humans ; Animals ; *Stress Granules/metabolism ; *NEDD8 Protein/metabolism ; },
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.},
}

*Amyotrophic Lateral Sclerosis/metabolism/drug therapy
Humans
Animals
*Stress Granules/metabolism
*NEDD8 Protein/metabolism

@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 {pmid41386298,
year = {2026},
author = {Ealy, A and Serapiglia, AM and Panicker, N},
title = {Sterile innate immune mechanisms in neurodegenerative diseases.},
journal = {The Journal of biological chemistry},
volume = {302},
number = {2},
pages = {111039},
pmid = {41386298},
issn = {1083-351X},
support = {R00 AG066862/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Immunity, Innate ; *Neurodegenerative Diseases/immunology/pathology ; Animals ; Amyotrophic Lateral Sclerosis/immunology/pathology ; Parkinson Disease/immunology/pathology ; Alzheimer Disease/immunology/pathology ; Signal Transduction ; Multiple Sclerosis/immunology/pathology ; },
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, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and frontotemporal dementia. 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.},
}

Humans
*Immunity, Innate
*Neurodegenerative Diseases/immunology/pathology
Animals
Amyotrophic Lateral Sclerosis/immunology/pathology
Parkinson Disease/immunology/pathology
Alzheimer Disease/immunology/pathology
Signal Transduction
Multiple Sclerosis/immunology/pathology

@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},
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 {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 {pmid41386992,
year = {2026},
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 = {13},
number = {1},
pages = {},
pmid = {41386992},
issn = {2373-2822},
support = {R01 NS100007/NS/NINDS NIH HHS/United States ; R56 NS100007/NS/NINDS NIH HHS/United States ; },
mesh = {Animals ; *rho GTP-Binding Proteins/genetics/metabolism/deficiency ; *Anxiety/metabolism/genetics/pathology ; Mice ; *Neurons/metabolism ; Male ; *Mitochondrial Proteins/genetics/metabolism ; *Cerebral Cortex/metabolism/pathology ; Mitochondria/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Behavior, Animal/physiology ; Female ; Disease Models, Animal ; },
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 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 (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 (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 studied mice of both sex. We found that mitochondrial mislocalization 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 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 several anxiety-like behaviors.},
}

Animals
*rho GTP-Binding Proteins/genetics/metabolism/deficiency
*Anxiety/metabolism/genetics/pathology
Mice
*Neurons/metabolism
Male
*Mitochondrial Proteins/genetics/metabolism
*Cerebral Cortex/metabolism/pathology
Mitochondria/metabolism
Mice, Inbred C57BL
Mice, Knockout
Behavior, Animal/physiology
Female
Disease Models, Animal

@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 {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 {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 {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 {pmid41389646,
year = {2026},
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},
mesh = {Humans ; *Students, Dental/psychology/statistics & numerical data ; *Oral Health/education ; *Problem-Based Learning/methods ; India ; Male ; Female ; Education, Dental/methods ; Surveys and Questionnaires ; Adult ; *Health Status Disparities ; },
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.},
}

Humans
*Students, Dental/psychology/statistics & numerical data
*Oral Health/education
*Problem-Based Learning/methods
India
Male
Female
Education, Dental/methods
Surveys and Questionnaires
Adult
*Health Status Disparities

@article {pmid41389796,
year = {2026},
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 = {114},
number = {4},
pages = {640-660.e10},
pmid = {41389796},
issn = {1097-4199},
support = {R01 NS134166/NS/NINDS NIH HHS/United States ; R21 NS131713/NS/NINDS NIH HHS/United States ; R35 GM149268/GM/NIGMS NIH HHS/United States ; R01 NS127187/NS/NINDS NIH HHS/United States ; R01 GM059614/GM/NIGMS NIH HHS/United States ; R01 NS104219/NS/NINDS NIH HHS/United States ; I01 BX002466/BX/BLRD VA/United States ; R21 GM147719/GM/NIGMS NIH HHS/United States ; R01 AG086270/AG/NIA NIH HHS/United States ; P30 AG066468/AG/NIA NIH HHS/United States ; },
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Humans ; *DNA-Binding Proteins/metabolism/genetics ; *RNA, Messenger/metabolism ; *Trans-Activators/metabolism/genetics ; *Motor Neurons/metabolism ; *RNA Helicases/metabolism ; Induced Pluripotent Stem Cells/metabolism ; Phosphorylation ; 3' Untranslated Regions ; Animals ; },
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.},
}

*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology
Humans
*DNA-Binding Proteins/metabolism/genetics
*RNA, Messenger/metabolism
*Trans-Activators/metabolism/genetics
*Motor Neurons/metabolism
*RNA Helicases/metabolism
Induced Pluripotent Stem Cells/metabolism
Phosphorylation
3' Untranslated Regions
Animals

@article {pmid41389988,
year = {2026},
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 = {285},
number = {},
pages = {110804},
doi = {10.1016/j.neuropharm.2025.110804},
pmid = {41389988},
issn = {1873-7064},
mesh = {*Riluzole/administration & dosage/pharmacology/therapeutic use ; Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; Humans ; Mice ; *Neuroprotective Agents/pharmacology/administration & dosage ; Drug Therapy, Combination ; *Casein Kinase Idelta/antagonists & inhibitors/metabolism ; *TDP-43 Proteinopathies/drug therapy ; *Protein Kinase Inhibitors/pharmacology/administration & dosage/therapeutic use ; Mice, Transgenic ; Male ; Dose-Response Relationship, Drug ; DNA-Binding Proteins/metabolism/genetics ; Disease Models, Animal ; },
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 3-18 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.},
}

*Riluzole/administration & dosage/pharmacology/therapeutic use
Animals
*Amyotrophic Lateral Sclerosis/drug therapy/metabolism
Humans
Mice
*Neuroprotective Agents/pharmacology/administration & dosage
Drug Therapy, Combination
*Casein Kinase Idelta/antagonists & inhibitors/metabolism
*TDP-43 Proteinopathies/drug therapy
*Protein Kinase Inhibitors/pharmacology/administration & dosage/therapeutic use
Mice, Transgenic
Male
Dose-Response Relationship, Drug
DNA-Binding Proteins/metabolism/genetics
Disease Models, Animal

@article {pmid41391687,
year = {2026},
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 = {218},
number = {},
pages = {107223},
doi = {10.1016/j.nbd.2025.107223},
pmid = {41391687},
issn = {1095-953X},
mesh = {Animals ; *tau Proteins/metabolism ; Phosphorylation ; Male ; *Brain Injuries, Traumatic/metabolism/pathology ; Humans ; Rats ; Mice ; Rats, Sprague-Dawley ; *Tauopathies/metabolism/pathology ; Mice, Inbred C57BL ; Threonine/metabolism ; Mitogen-Activated Protein Kinase 8/metabolism ; },
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.},
}

Animals
*tau Proteins/metabolism
Phosphorylation
Male
*Brain Injuries, Traumatic/metabolism/pathology
Humans
Rats
Mice
Rats, Sprague-Dawley
*Tauopathies/metabolism/pathology
Mice, Inbred C57BL
Threonine/metabolism
Mitogen-Activated Protein Kinase 8/metabolism