@article {pmid41493706,
year = {2026},
author = {Hashemi, M and Shafiei Asheghabadi, P and Moassesfar, M and Mashhadikhan, S and Nasirzade, S and Vasheghani Farahani, A and Mehdizadeh, S and Minaei, S and Rahmani, M and Jamshidian, F and Farahani, N and Reiter, RJ and Taheriazam, A and Hasani Sadi, F and Hushmandi, K and Alimohammadi, M and Rahimzadeh, P and Entezari, M},
title = {MicroRNAs and Long Non-Coding RNAs Affect the Mechanisms Involved in Age-Related Neurodegeneration in a Manner Depending on RNA-Binding Proteins.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {343},
pmid = {41493706},
issn = {1559-1182},
mesh = {Humans ; *RNA, Long Noncoding/metabolism/genetics ; *MicroRNAs/genetics/metabolism ; Animals ; *RNA-Binding Proteins/metabolism/genetics ; *Aging/genetics/pathology/metabolism ; *Neurodegenerative Diseases/genetics/metabolism/pathology ; },
abstract = {Neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), are marked by progressive neuronal loss and aberrant protein aggregation, presenting substantial global healthcare challenges. Recent research has illuminated the pivotal roles of RNA-binding proteins (RBPs) and non-coding RNAs (ncRNAs), notably microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in the molecular pathogenesis of age-related neurodegeneration. RBPs orchestrate RNA metabolism and engage extensively with miRNAs and lncRNAs to modulate gene expression at the post-transcriptional level. Dysregulation of these interactions precipitates pathological phenomena such as protein misfolding, stress granule formation, and disrupted RNA processing, thereby exacerbating neuronal dysfunction and death. Specific miRNAs have been implicated in regulating key neurodegenerative biomarkers, including tau and amyloid-β in AD, motor neuron maintenance in ALS, and survival pathways in HD. Elucidating the intricate interplay between RBPs and ncRNAs holds significant promise for the development of therapeutic strategies aimed at ameliorating RNA-mediated mechanisms in neurodegenerative disorders.},
}

Humans
*RNA, Long Noncoding/metabolism/genetics
*MicroRNAs/genetics/metabolism
Animals
*RNA-Binding Proteins/metabolism/genetics
*Aging/genetics/pathology/metabolism
*Neurodegenerative Diseases/genetics/metabolism/pathology

@article {pmid41493066,
year = {2026},
author = {De Vocht, J and Costello, E and McHutchison, C and Radakovic, R and Foucher, J and McMackin, R and Peelo, C and van den Berg, L and Hardiman, O and Van Damme, P and Pender, N and Abrahams, S and Lulé, D and , },
title = {Prioritizing neuropsychological research and care in Amyotrophic Lateral Sclerosis (ALS): building an international neuropsychological framework for ALS.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-4},
doi = {10.1080/21678421.2025.2610290},
pmid = {41493066},
issn = {2167-9223},
}

@article {pmid41492782,
year = {2026},
author = {Dallaire, JS and Bachand, MP and Shaul, J and Lareau-Trudel, É},
title = {Mortality and Complications of Percutaneous Gastrostomy in Amyotrophic Lateral Sclerosis Patients.},
journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques},
volume = {},
number = {},
pages = {1-23},
doi = {10.1017/cjn.2025.10510},
pmid = {41492782},
issn = {0317-1671},
}

@article {pmid41491573,
year = {2026},
author = {Kuramitsu, Y and Itou, J and Munakata, Y and Okazaki, K},
title = {Transverse incisions improve scar outcomes in anterolateral supine approach total hip arthroplasty: a patient observer scar assessment scale-based study.},
journal = {Arthroplasty (London, England)},
volume = {8},
number = {1},
pages = {2},
pmid = {41491573},
issn = {2524-7948},
abstract = {BACKGROUND: This study compared transverse and longitudinal skin incisions in anterolateral supine (ALS) total hip arthroplasty (THA), focusing on cosmetic and sensory outcomes using the Patient Observer Scar Assessment Scale (POSAS).

METHODS: A retrospective analysis was conducted on 132 hips that underwent primary ALS THA performed by a single surgeon between 2019 and 2024. Longitudinal incisions were used until December 2022, and transverse incisions aligned with relaxed skin tension lines were used thereafter. POSAS 3.0 was used to evaluate scar quality across satisfaction, appearance, and sensory domains.

RESULTS: Baseline characteristics were similar between groups, except for follow-up duration and incision length. No significant differences were found in POSAS scores. However, regression analysis revealed that transverse incision significantly improved satisfaction (P = 0.04) and appearance (P < 0.05). Sensory scores were significantly affected by follow-up duration (P < 0.001).

CONCLUSION: Transverse incisions in ALS THA may enhance cosmetic satisfaction without compromising sensory outcomes. These findings support the potential role of personalized incision planning for improving patient-reported outcomes following THA. Video Abstract.},
}

@article {pmid41490238,
year = {2025},
author = {Ni, S and Chen, K and Wang, H and Chen, S and Qiu, Y and Wang, T and Mo, F and Wang, S and Li, B and Bai, Y and Zhao, J and Zhai, X and Li, Z},
title = {A new paradigm of bidirectional regulation of the gut-spinal cord axis.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-01016},
pmid = {41490238},
issn = {1673-5374},
abstract = {The bidirectional interactions of spinal cord injury, multiple sclerosis, and amyotrophic lateral sclerosis with the gut operate through a distinct gut-spinal cord axis, rather than being fully explained by the conventional gut-brain axis. The spinal cord, with its unique anatomical and physiological features, serves as a central hub of communication. The gut and spinal cord communicate through various pathways, including the immune system and the autonomic and enteric nervous systems. This review summarizes existing clinical and basic research on the relationship between gut homeostasis and spinal cord diseases. First, we present findings from epidemiological studies showing that patients with spinal cord disorders often exhibit altered gut function, which may be influenced by antibiotic exposure and environmental factors. Second, we review the key physiological and anatomical structures of the gut-spinal cord axis, including the intestinal barrier, gut microbiota, and enteric nervous system, all of which are involved in maintaining gut health, as well as sensory neurons, motor neurons, and interneurons in spinal nerve regulation. Third, we describe the roles of the three axes (microbial, immune, and neural) in bidirectional regulation and their pathological mechanisms. Moreover, vicious cycles involving these axes can exacerbate spinal cord disorders. Fourth, we outline potential biomarkers in the gut-spinal cord axis, such as uridine, hypoxanthine, and 5-methoxytryptophan. Fifth, we propose several treatment strategies with potential clinical applications, including fecal microbiota transplantation and the use of probiotics and prebiotics. Finally, this review emphasizes the gut-spinal cord axis as a promising therapeutic target, highlighting the need for multi-omics integration, longitudinal cohort studies, and individualized interventions to resolve existing debates. Overall, the recognition of the gut-spinal cord axis provides a conceptual shift that extends beyond the gut-brain framework.},
}

@article {pmid41490046,
year = {2026},
author = {Maheswari Jawahar, V and Zeng, Y and Armour, EM and Yue, M and Citrano, K and Lovchykova, A and Reeves, MM and Rawlinson, B and DeTure, M and Dunmore, JA and Song, Y and Ball, SK and Wszolek, ZK and Graff-Radford, NR and Boeve, BF and Knopman, DS and Day, GS and Small, SA and Dickson, DW and Ward, ME and Gendron, TF and Zhang, Y and Prudencio, M and Gitler, AD and Petrucelli, L},
title = {TDP-43-mediated alternative polyadenylation is associated with a reduction in VPS35 and VPS29 expression in frontotemporal dementia.},
journal = {PLoS biology},
volume = {24},
number = {1},
pages = {e3003573},
doi = {10.1371/journal.pbio.3003573},
pmid = {41490046},
issn = {1545-7885},
mesh = {Humans ; *Frontotemporal Dementia/genetics/metabolism/pathology ; *DNA-Binding Proteins/metabolism/genetics ; *Polyadenylation/genetics ; Female ; *Vesicular Transport Proteins/genetics/metabolism ; Male ; Aged ; 3' Untranslated Regions/genetics ; Middle Aged ; Aged, 80 and over ; },
abstract = {TAR DNA-binding protein 43 (TDP-43) dysfunction is a hallmark of several neurodegenerative diseases, including frontotemporal dementia, amyotrophic lateral sclerosis, and Alzheimer's disease. Although cryptic exon inclusion is a well-characterized consequence of TDP-43 loss of function, emerging evidence reveals broader roles in RNA metabolism, notably in the regulation of alternative polyadenylation (APA) of disease-relevant transcripts. In the present study, we examined 3' untranslated region lengthening events in the brains of individuals with frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP), focusing on the functional impact of APA dysregulation. To investigate whether TDP-43-mediated APA events occur in the postmortem brain, we measured the 3' untranslated region length of the retromer component vacuolar protein sorting 35 (VPS35) and the ETS transcription factor (ELK1) in the frontal cortex of a large cohort of FTLD-TDP patients and of healthy controls, and evaluated if these APA events are associated with FTLD-TDP clinical characteristic, markers of TDP-43 pathology [e.g., hyperphosphorylated TDP-43 and cryptic stathmin-2 RNA], or the expression of VPS35 and VPS29 proteins, the latter being essential to the retromer complex. We identified robust 3' untranslated region lengthening of VPS35 and ELK1 in FTLD-TDP, which strongly associated with markers of TDP-43 pathology, and ELK1 APA also associated with an earlier age of disease onset. Functionally, VPS35 APA was associated with reduced VPS35 and VPS29 protein expression, and lower VPS35 levels were associated with increased hyperphosphorylated TDP-43 and cryptic stathmin-2 RNA. Together, these data implicate APA dysregulation as a critical downstream consequence of TDP-43 dysfunction and suggest that TDP-43 loss may contribute to retromer impairment through APA-mediated repression of retromer subunits.},
}

Humans
*Frontotemporal Dementia/genetics/metabolism/pathology
*DNA-Binding Proteins/metabolism/genetics
*Polyadenylation/genetics
Female
*Vesicular Transport Proteins/genetics/metabolism
Male
Aged
3' Untranslated Regions/genetics
Middle Aged
Aged, 80 and over

@article {pmid41489446,
year = {2026},
author = {Gairola, J and Kumar, A and Desai, NN and Dedeepya, D},
title = {Methodological considerations in evaluating the impact of adenotonsillectomy on asthma control in children.},
journal = {The Journal of asthma : official journal of the Association for the Care of Asthma},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/02770903.2025.2612523},
pmid = {41489446},
issn = {1532-4303},
abstract = {This letter provides a constructive appraisal of the methodological aspects of Alenezi et al.'s systematic review and meta-analysis examining the impact of adenotonsillectomy on asthma control in children. The authors are commended for their adherence to PRISMA guidelines and for synthesizing data from a large cohort of over 74,000 participants. However, the reliance on observational studies limits causal inference, and the interpretation of heterogeneity could be strengthened through the inclusion of prediction intervals and subgroup analyses. Future research employing advanced statistical approaches and standardized outcome measures would further enhance the methodological rigor and clinical relevance of this valuable work.},
}

@article {pmid41489058,
year = {2026},
author = {Pilotto, F and Toth, TD and Bond, S and Schmitz, A and Diab, R and Tenlep, SYN and Mooney, B and Erni, S and Schobesberger, M and Scheidegger, O and Peitsch, C and Saxena, S},
title = {Engineered GM1 Intersects Between Mitochondrial and Synaptic Pathways to Ameliorate ALS Pathology.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e14128},
doi = {10.1002/advs.202514128},
pmid = {41489058},
issn = {2198-3844},
support = {31ER30_179595//E-Rare/ ; 725825/ERC_/European Research Council/International ; //InnoMedica Schweiz AG/ ; 179436/SNSF_/Swiss National Science Foundation/Switzerland ; //Swiss Foundation for Research on Muscle Diseases/ ; //Spinal Cord Injury/Disease Research Program (SCIDRP), University of Missouri/ ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal condition marked by the degeneration of motor neurons. ALS has been linked to numerous genes with diverse biological roles, reflecting a highly intricate and multifaceted disease process. This diversity poses significant challenges in developing universally effective and bioavailable treatments. Advancing therapeutic strategies require uncovering molecular pathways that are major drivers of ALS. We conducted proteomic analyses of human iPSC-derived motor neurons carrying C9ORF72 mutations, alongside spinal ventral horns from mice with pathogenic C9orf72-mutations. This cross-species approach revealed disruptions in synaptic vesicle release, endoplasmic reticulum (ER) and mitochondrial stress responses as conserved ALS pathogenic mechanisms. Disease progression was associated with accumulation of cytotoxic protein aggregates and oxidative stress. We analyzed the potential of GM1, an established neuroprotective molecule, to reverse these pathogenic features. To enhance the pharmacokinetics of GM1, we developed Talineuren (TLN), a nanoliposome-based formulation of the active pharmaceutical ingredient GM1 ganglioside that improves its bioavailability. GM1 stabilized mitochondrial Ca[2][+] handling, improved energy metabolism, and alleviated ER stress, preventing protein aggregation and restoring cellular proteostasis and counteracted behavioral deficits in C9orf72 and SOD1-G93A mouse models. Together, these findings underscore the central, convergent role for cellular disruptions in ALS and position TLN as a promising therapeutic candidate.},
}

@article {pmid41488805,
year = {2026},
author = {Klassen, P and Alexudis, C and Klose, V and de San José, NG and Huss, A and Bachhuber, F and Soylu, Ö and Fazeli, B and Erhart, D and Laible, M and Anderl-Straub, S and Jesse, S and Otto, M and Ludolph, AC and Tumani, H and Halbgebauer, S},
title = {Increased transmembrane protein 119 (TMEM119) levels in the cerebrospinal fluid of patients with mild cognitive impairment due to Alzheimer's disease suggest early microglial involvement.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {1},
pages = {e70240},
pmid = {41488805},
issn = {2352-8729},
abstract = {INTRODUCTION: We aimed to evaluate the potential of the microglial marker transmembrane protein 119 (TMEM119) in the cerebrospinal fluid (CSF) as a (differential) diagnostic biomarker for neurodegenerative diseases.

METHODS: Following assay validation, we used enzyme-linked immunosorbent assay to measure CSF TMEM119 in 174 patients from six diagnostic groups: Alzheimer's disease (AD, n = 35), amyotrophic lateral sclerosis (ALS, n = 33), cerebral microangiopathy (CM, n = 25), frontotemporal lobar degeneration (FTLD, n = 28), Lewy body diseases (n = 21), and non-neurodegenerative controls (n = 33).

RESULTS: CSF TMEM119 levels were elevated in the AD group compared to the control (p = 0.004), CM (p = 0.005), and FTLD (p = 0.023) groups. Levels were higher in both mild cognitive impairment (MCI-AD) and dementia (ADD) subgroups when compared to controls. For the discrimination of AD from controls, the area under the curve (AUC) was 0.78.

DISCUSSION: Our results indicate that CSF TMEM119 may have potential as a biomarker representing microglial involvement in early and later stages of AD.

HIGHLIGHTS: Elevated levels of TMEM119 were observed in the CSF of patients with AD.Increased CSF TMEM119 was seen in MCI-AD patients compared to controls.Elevated levels in MCI-AD underscore early microglial involvement in AD.In the AD group, an association was found between CSF TMEM119 and CSF total tau.CSF TMEM119 may provide valuable information on neuroinflammation.},
}

@article {pmid41488323,
year = {2025},
author = {Lotlikar, MS and Zellmer, JC and Bhattacharyya, R},
title = {Sigma receptors and mitochondria-associated ER membranes are converging therapeutic targets for Alzheimer's disease.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1733659},
pmid = {41488323},
issn = {1662-4548},
abstract = {Alzheimer's disease (AD) begins decades before clinical symptoms emerge. The "amyloid hypothesis" suggests that amyloid-β (Aβ) deposition initiates a cascade of tau hyperphosphorylation, neuroinflammation, and neuronal loss leading to cognitive decline. The recent success of anti-Aβ therapies such as Leqembi in prodromal or mild cognitive impaired patients underscores the importance of early intervention and Aβ clearance. However, safety and cost limitations highlight the need for alternative therapeutic strategies. Small-molecule modulators of Sigma-1 and Sigma-2 receptors (σ1R and σ2R) have emerged as promising candidates for AD treatment. σ1R agonists exhibit neuroprotective and anti-amnestic effects under pathological conditions without affecting normal cognition. Beyond AD, σ1R is implicated in several neurodegenerative diseases including ALS (amyotrophic lateral sclerosis), Parkinson's, and Huntington's diseases, stroke, and epilepsy. σ1R plays a key role at mitochondria-associated ER membranes (MAMs)-specialized lipid raft-like domains that form functional membrane contact sites between the endoplasmic reticulum (ER) and mitochondria. β-secretase (BACE1), γ-secretase, and their substrates APP and palmitoylated APP (palAPP) localize in the MAMs, promoting amyloidogenic Aβ production. MAMs serve as dynamic hubs for inter-organelle communication, calcium signaling, and lipid metabolism. The "MAM hypothesis" proposes that MAM dysregulation drives early AD pathology and persists throughout disease progression, contributing to neurofibrillary tangle formation, calcium imbalance, and neuroinflammation. This review aims to summarize the current understanding of σ1R-mediated regulation of MAMs and its neuroprotective mechanisms, highlighting potential therapeutic opportunities for targeting σ1R in AD and other neurodegenerative disorders.},
}

@article {pmid41486410,
year = {2026},
author = {Wang, F and Zhang, KY and Zhu, LJ and Li, WJ and Wu, Y and Gao, X and Ma, XR and Yin, XH and Wu, JB and Ye, XK and Dong, ZJ and Wang, DX and Zhou, Z and Wang, SD and Han, L and Jiang, ZN and Zhao, JW},
title = {Microglial HVCN1 Deficiency Improves Movement and Survival of SOD1[G93A] ALS Mice by Enhancing Microglial Migration and Neuroprotection.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e12149},
doi = {10.1002/advs.202512149},
pmid = {41486410},
issn = {2198-3844},
support = {STI2030-MajorProjects2021ZD0201705//National Key R&D Program of China/ ; NSFC82371576//National Natural Science Foundation of China/ ; BZZ19J005//National Natural Science Foundation of China/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is an incurable motor neuron disease characterized by progressive loss of motor neurons. Current clinically available drugs targeting neurons show minor survival extension and no motor improvement in ALS patients. This shifts the focus of ALS research toward non-neuronal cells, particularly microglia, a critical driver of ALS pathogenesis. Highly druggable ion channels are key regulators of microglia function. Here, Hydrogen voltage gated channel 1 (HVCN1) was screened out as the most highly expressed ion channel in microglia, and was upregulated in microglia of SOD1[G93A] mice and patients. Deletion of HVCN1 in microglia increased motor neuron survival, rescued the innervated neuromuscular junctions in the muscle, reduced glial activation and decreased the level of both misfolded protein and myelin debris in the ALS mice. Importantly, these pathological improvements were translated into significant motor improvement and survival extension in the ALS mice, exhibiting better effects than the current clinical drugs. HVCN1 deletion enhanced microglia migration and their homeostatic state with elevated neurotrophic functions. Mechanistically, HVCN1 ablation promoted microglial migration via suppressing Akt signaling. Our results identify HVCN1 as a novel promising therapeutic target for ALS, opening a new avenue to further develop specific inhibitors for HVCN1 to alleviates ALS.},
}

@article {pmid41486306,
year = {2026},
author = {Zhuang, SP and Huang, HW and Zeng, JY and Shi, JY and Lin, HY and Chen, S and Wu, Y and Huang, NX and Zou, ZY and Chen, HJ},
title = {Superficial white matter microstructural impairments correlate with functional alterations and disease severity in early-stage amyotrophic lateral sclerosis.},
journal = {La Radiologia medica},
volume = {},
number = {},
pages = {},
pmid = {41486306},
issn = {1826-6983},
support = {Nos. 2023CXA009//Fujian Provincial Health Technology Project/ ; Nos. 2024QNA011//Fujian Provincial Health Technology Project/ ; No.2024J01625//Fujian Provincial Natural Science Foundation of China/ ; Nos. 2024Y9253//Fujian Province Joint Funds for the Innovation of Science and Technology/ ; Nos. 2024Y9256//Fujian Province Joint Funds for the Innovation of Science and Technology/ ; No. S202410392033//College Student Innovation Training Program of Fujian Medical University/ ; },
abstract = {PURPOSE: White matter (WM) damage is a key pathophysiological process in amyotrophic lateral sclerosis (ALS). However, alterations in superficial WM (SWM) have not been systematically explored. This study aimed to assess SWM microstructural changes in early-stage ALS and their associations with cortical functional alterations and disease severity.

METHODS: Forty-two early-stage ALS patients and 48 healthy controls were included. Disease severity was evaluated using the revised ALS Functional Rating Scale (ALSFRS-R). The SWM was identified by sampling voxels along the cortical surface, maintaining a fixed distance (2 mm) from the gray matter/WM interface and removing deep white matter regions. SWM microstructural impairments were evaluated via neurite orientation dispersion and density imaging. Functional disturbances in the cortical regions corresponding to impaired SWM were measured by assessing regional homogeneity (ReHo) that reflects local synchronization of neuronal activity.

RESULTS: Patients showed a decreased neurite density index (NDI) in specific SWM regions, primarily including the bilateral precentral gyrus, supplementary motor area, paracentral lobule, and postcentral gyrus (family-wise error-corrected P < 0.05). Additionally, significant ReHo reductions were observed in cortical regions corresponding to compromised SWM. Both SWM NDI and cortical ReHo values significantly correlated with the ALSFRS-R score. Cortical ReHo alterations mediated the relationship between the SWM NDI value and the ALSFRS-R score (mediation effect = 0.103). SWM NDI assessments effectively identified ALS (area under the curve = 0.725-0.926).

CONCLUSION: Our findings highlight the SWM disruption as a crucial neurobiological substrate involved in early-stage ALS neuropathological mechanisms.},
}

@article {pmid41486180,
year = {2026},
author = {Tarutani, A and Nonaka, T and Ohtani, R and Imai, K and Ito, Y and Tsuji, H and Mochizuki, A and Tamaoka, A and Arai, T and Robinson, AC and Mann, DMA and Kosaka, T and Takahashi, H and Kakita, A and Yoshida, M and Hasegawa, M},
title = {Co-aggregation of annexin A11 and TDP-43 in FTLD/MND with primary lateral sclerosis phenotype.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-025-02210-w},
pmid = {41486180},
issn = {2051-5960},
support = {JP24wm0625120//Japan Agency for Medical Research and Development/ ; JP21wm0425019//Japan Agency for Medical Research and Development/ ; JP24dk0207074h0001//Japan Agency for Medical Research and Development/ ; JP20K16482//Japan Society for the Promotion of Science/ ; JP25K21773//Japan Society for the Promotion of Science/ ; JP24H00624//Japan Society for the Promotion of Science/ ; JPMJCR18H3//Japan Science and Technology Agency/ ; },
abstract = {TDP-43 proteinopathies, such as frontotemporal degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), are classified into five neuropathological subtypes, Types A to E, according to the morphology of TDP-43 inclusions. Recent cryo-electron microscopy analysis of FTLD-TDP cases demonstrated that TDP-43 filaments composing the inclusions are structurally different depending on the subtype, and remarkably, co-assembled heteromeric filaments of TDP-43 and annexin A11 (ANXA11) were identified in Type C. Therefore, the involvement of ANXA11 in TDP-43 proteinopathy should be further examined. Here, we pathologically and biochemically analyzed four cases of primary lateral sclerosis-phenotype FTLD/motor neuron disease (MND) with TDP-43 pathology (PLS-TDP), and found that ANXA11 co-localizes with FTLD-TDP Type A pathology in PLS-TDP. Immunoblot analysis of the PLS-TDP cases revealed that the banding patterns of C-terminal and chymotrypsin-resistant fragments of TDP-43 are distinct from those of FTLD-TDP Types A, B and C. In addition, the N-terminal fragments of ANXA11 appear to be different from those of FTLD-TDP Type C. Filaments extracted from PLS-TDP cases were TDP-43- and ANXA11-immunopositive, suggesting the presence of TDP-ANXA11 heteromeric filaments. These results suggest that co-aggregation of ANXA11 and TDP-43 may serve as a neuropathological and biochemical indicator distinguishing PLS from ALS in FTLD/MND.},
}

@article {pmid41485128,
year = {2026},
author = {Mordes, DA and Smeyers, J},
title = {TBK1 orchestrates autophagy and endo-lysosomal pathways in human neurons.},
journal = {Autophagy},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/15548627.2025.2609924},
pmid = {41485128},
issn = {1554-8635},
abstract = {Haploinsufficiency of TBK1 causes familial ALS and frontotemporal dementia (FTD), yet the mechanisms by which TBK1 loss leads to neurodegeneration remain unclear. Using deep proteomics and phospho-proteomics, we demonstrate that TBK1 regulates select macroautophagy/autophagy factors, targeting cargo receptors and autophagy initiation factors, and also sustains the phosphorylation of the late endosomal marker RAB7A in stem cells and stem cell-derived excitatory neurons. We further uncovered novel TBK1-dependent phosphorylation sites in the key autophagy protein SQSTM1/p62. Loss of TBK1 function results in a cell-autonomous neurodegenerative phenotype characterized by impaired neurite outgrowth and lysosomal dysfunction.},
}

@article {pmid41485061,
year = {2026},
author = {Waldherr, SM and Eck, RJ and Hincks, JC and Currey, HN and Goldberg, M and McMillan, PJ and Saxton, AD and Hulsey-Vincent, HJ and Latimer, CS and Kraemer, BC and Liachko, NF},
title = {Calcineurin depletion coincides with phosphorylated TDP-43 deposition in a mouse model of ALS/FTLD-TDP.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-025-02192-9},
pmid = {41485061},
issn = {2051-5960},
support = {F99AG088436/NH/NIH HHS/United States ; R01SN0064131/NH/NIH HHS/United States ; R01AG066729/NH/NIH HHS/United States ; IK6BX006467//U.S. Department of Veterans Affairs/ ; I01BX005762//U.S. Department of Veterans Affairs/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP) exhibit predominantly cytoplasmic phosphorylated inclusions of the protein TDP-43 as the major neuropathological lesion. Phosphorylated TDP-43 can modify protein aggregation and promote neuronal dysfunction and neurodegeneration in models of ALS and FTLD-TDP. The phosphatase calcineurin has previously been shown to directly dephosphorylate TDP-43 in vitro and prevent accumulation of phosphorylated TDP-43 in vivo in C. elegans. However, it is unknown whether dysregulation of calcineurin contributes to increased TDP-43 phosphorylation and neurodegeneration in the mammalian brain. Here we show in an inducible mouse model of ALS/FTLD-TDP driven by expression and cytoplasmic mislocalization of human TDP-43 (rNLS8 mice), calcineurin protein decreases dramatically in the brain. This depletion coincides with increased levels of the TDP-43 kinase CDC7 and accumulation of phosphorylated TDP-43, and precedes frank neurodegeneration. Using brain-wide single nucleus RNA sequencing (snRNAseq) in symptomatic rNLS8 mice, we find cell-type selective reduced expression of catalytic and regulatory subunits of calcineurin predominantly in GABAergic and glutamatergic neurons. In mouse primary neuron culture and C. elegans models of ALS/FTLD-TDP, we demonstrate activation or overexpression of calcineurin protects against accumulation of phosphorylated TDP-43, neurotoxicity, and neurodegeneration. Taken together, our data suggests calcineurin dysregulation may be a major contributor to loss of brain resilience mechanisms against phosphorylated TDP-43. Restoring calcineurin activity may present a new target for intervening in TDP-43 proteinopathies, including ALS and FTLD-TDP.},
}

@article {pmid41484784,
year = {2026},
author = {Katzenschlager, S and Kaltschmidt, N and Dietrich, M and Fiedler-Kalenka, M and Klemm, S and Kofler, O and Mohr, S and Eisner, C and Neuhaus, C and Simon, C and Weigand, MA and Weilbacher, F and Popp, E},
title = {Prehospital transesophageal echocardiography versus conventional advanced life support in out-of-hospital cardiac arrest (PHTEE-OHCA) - a randomized controlled pilot study.},
journal = {Critical care (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13054-025-05805-w},
pmid = {41484784},
issn = {1466-609X},
abstract = {BACKGROUND: Transesophageal echocardiography during out-of-hospital cardiac arrest can be performed during ongoing chest compressions and may improve resuscitation quality, but its prehospital use has not been systematically evaluated. To assess the feasibility, diagnostic yield, and impact of prehospital TEE on resuscitation metrics and advanced life support (ALS) interventions during OHCA.

METHODS: We conducted a randomized controlled trial in a physician-staffed two-tiered emergency medical service (EMS). Adults with ongoing non-traumatic OHCA were randomized 1:1 to standard ALS or ALS plus TEE. The primary endpoints were hands-off time and chest compression fraction (CCF) from EMS arrival to return of spontaneous circulation (ROSC) or resuscitation termination. Secondary endpoints included ROSC at hospital admission, survival to hospital discharge, neurological status at hospital discharge, and TEE findings. Analyses followed the intention-to-treat principle.

RESULTS: Of 249 screened patients, 35 were randomized and 32 analyzed (TEE n = 15; control n = 17). Median hands-off time was 4 s in both groups. Mean CCF was higher in the TEE group (96.2%) than the control group (91.6%), with a mean difference of 4.6% (95% confidence interval 2.5-6.7; p < 0.001). Sustained ROSC occurred in 40% (TEE) versus 71% (control; p = 0.083). The control group had an eCPR rate of 41%, compared to 20% in the TEE group. Using TEE, an incorrect area of maximal compression or inadequate depth was identified in 23% and 14%, respectively.

CONCLUSION: Prehospital TEE during OHCA was feasible without negatively interfering with CPR metrics, and provided clinically relevant diagnostic information and procedural guidance, warranting further evaluation in larger trials.

TRIAL REGISTRATION: German Clinical Trials Register DRKS00028695 registered on 28 April 2022.},
}

@article {pmid41484575,
year = {2026},
author = {Luo, J},
title = {Revisiting MASLD-based pregnancy risk stratification: a critical appraisal of Jung et al.'s nationwide cohort study.},
journal = {Hepatology international},
volume = {},
number = {},
pages = {},
pmid = {41484575},
issn = {1936-0541},
}

@article {pmid41484230,
year = {2026},
author = {Schneider, K and Spekking, L and Azimi, S and Peltanová, B and Rösel, D and Brown, JS and Gatenby, RA and Brábek, J and Staňková, K},
title = {Migrastatic therapy as a potential game-changer in adaptive cancer treatment.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-33902-x},
pmid = {41484230},
issn = {2045-2322},
support = {24-11903S//Grantová Agentura České Republiky/ ; 24-11903S//Grantová Agentura České Republiky/ ; 24-10672S//Grantová Agentura České Republiky/ ; LX22NPO5102//National Institute for Cancer Research/ ; LX22NPO5102//National Institute for Cancer Research/ ; LX22NPO5102//National Institute for Cancer Research/ ; 955708//European Union's Horizon 2020 research and innovation program/ ; 955708//European Union's Horizon 2020 research and innovation program/ ; VI.Vidi.213.139/NWO_/Dutch Research Council/Netherlands ; },
abstract = {Adaptive therapy, which anticipates and counters the evolution of resistance in cancer cells, has gained significant traction, especially following the success of the Zhang et al.'s protocol in treating metastatic castrate-resistant prostate cancer. While several adaptive therapies have now advanced to clinical trials, none currently incorporates migrastatics, i.e. treatments designed to inhibit cancer cell metastasis. In this study, we propose integrating migrastatics into adaptive therapy protocols and evaluate its potential benefits through a spatial game-theoretic model. Our results demonstrate that combining adaptive therapy with migrastatics effectively delays the onset of metastases and reduces both the number and size of metastases in most cancer scenarios analyzed. Including migrastatics to adaptive therapy not only extends the time to the first metastasis, but also enhances the overall efficacy of adaptive therapies. Our findings suggest a promising new direction for cancer treatment, where adaptive therapy, in combination with migrastatic agents, can target both the evolution of resistance and the metastatic spread of cancer cells.},
}

@article {pmid41483413,
year = {2026},
author = {Khan, T and Mahboob, H and Zehra, M and Saqib, HW and Ahmad, M},
title = {Super excitability at 7 ms: a superior prognostic biomarker beyond CMAP in amyotrophic lateral sclerosis.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {1},
pages = {71},
pmid = {41483413},
issn = {1590-3478},
}

@article {pmid41482475,
year = {2026},
author = {Bernsen, S and Weydt, P},
title = {Hereditary transthyretin amyloidosis with hand weakness and bulbar involvement.},
journal = {Practical neurology},
volume = {},
number = {},
pages = {},
doi = {10.1136/pn-2025-004950},
pmid = {41482475},
issn = {1474-7766},
abstract = {A 76-year-old man developed progressive motor weakness, bulbar symptoms and hand muscle atrophy, initially suspected to be due to motor neurone disease. Unexpected findings on cardiological evaluation identified amyloidosis, and genetic testing confirmed the TTR p.Val50Met mutation, indicating late-onset hereditary transthyretin amyloidosis with a mixed neuropathic and cardiac phenotype. The diagnosis was delayed and complicated by minimal sensory symptoms and the atypical presentation.},
}

@article {pmid41481541,
year = {2026},
author = {Lehto, A and Zapf, A and Hermann, A and Machts, J and Vielhaber, S and Koppenbrink, J and Edbauer, D and Kasper, E and Prudlo, J},
title = {Homozygosity for the C allele at UNC13A rs12608932 seems to compromise cognition in ALS independently of the cognitive domains.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-4},
doi = {10.1080/21678421.2025.2608238},
pmid = {41481541},
issn = {2167-9223},
abstract = {The common single nucleotide polymorphism (SNP) rs12608932 located at a cryptic splice in the UNC13A gene has been reported to modify the clinical phenotype of ALS, but it is unclear whether homozygosity for the C-allele at UNC13A rs12608932 modifies specific domains of cognition in ALS. We analyzed retrospective data from a German cohort and found that the proportion of cognitively or behaviorally impaired patients was higher in the high-risk group of homozygous C-allele carriers. Patients with C/C alleles had lower scores than controls on verbal fluency, executive functioning, and delayed memory recall, but did not differ significantly from other ALS genotypes. Furthermore, informant ratings suggested higher disinhibition in the C/C carriers. These findings indicate that the C/C risk variant of UNC13A rs12608932 may contribute to general cognitive vulnerability rather than domain-specific deficit.},
}

@article {pmid41481500,
year = {2026},
author = {Leon, AM and Sucasaca, A and Choque-Quispe, BM and Medina, WT},
title = {Physical and nutritional properties of meat analogues obtained by high-moisture extrusion with the inclusion of high Andean algae flours: Llaska (Cladophora crispata) and Cushuro (Nostoc sphaericum).},
journal = {Food science and technology international = Ciencia y tecnologia de los alimentos internacional},
volume = {},
number = {},
pages = {10820132251409012},
doi = {10.1177/10820132251409012},
pmid = {41481500},
issn = {1532-1738},
abstract = {Environmental impact of the meat industry and the adverse effects of excessive meat consumption, has prompted the search for sustainable and healthy protein alternatives. This study assessed the physical and textural properties and nutritional profile of two meat analogues processed by high-moisture extrusion, including Llaska (Cladophora crispata) (AL) and Cushuro (Nostoc sphaericum) (AC) flours. Color was evaluated by digital image analysis; textural profile analysis (TPA) was determined by compression tests. The nutritional profile was determined by proximate analysis, spectrophotometric, and chromatographic techniques. AL and AC were green and dark brown, respectively. The luminosity and hue of AC are similar to chicken meat. TPA shows that ALs had a greater degree of hardness and texturization than ACs. AL and AC, processed at a temperature of 135 °C and moisture level of 75% and 65%, respectively, exhibited textures comparable to that of chicken meat. Nutritionally, ACs showed higher antioxidant capacity (∼15,382 μMol Trolox/100 g), ∼30 times higher than chicken meat. Amino acid profiles indicate that both samples provide essential amino acids comparable to chicken meat, which are indispensable in a healthy diet. Consequently, these algae have potential to enrich the nutritional profile of meat analogues as a possible healthy and sustainable alternative to conventional meats.},
}

@article {pmid41481411,
year = {2026},
author = {Ortholand, J and Gensollen, N and Durrleman, S and Du Montcel, ST},
title = {Joint model with latent disease age: Overcoming the need for reference time.},
journal = {Statistical methods in medical research},
volume = {},
number = {},
pages = {9622802251399917},
doi = {10.1177/09622802251399917},
pmid = {41481411},
issn = {1477-0334},
abstract = {Heterogeneity of the progression of neurodegenerative diseases is one of the main challenges faced in developing therapies. Thanks to the increasing number of clinical databases, progression models have allowed a better understanding of this heterogeneity. Joint models have proven their effectiveness by combining longitudinal and survival data. Nevertheless, they require a reference time, which is ill-defined for neurodegenerative diseases, where biological underlying processes start before the first symptoms. In this work, we propose a joint non-linear mixed-effect model with a latent disease age, to overcome this need for a precise reference time. We used a longitudinal model with a latent disease age as a longitudinal sub-model. We associated it with a survival sub-model that estimates a Weibull distribution from the latent disease age. We validated our model on simulated data and benchmarked it with a state-of-the-art joint model on data from patients with Amyotrophic Lateral Sclerosis (ALS). Finally, we showed how the model could be used to describe ALS heterogeneity. Our model got significantly better results than the state-of-the-art joint model for absolute bias on ALS functional rating scale revised score (4.21(SD 4.41) versus 4.24(SD 4.14)(p-value=1.4×10-17)), and mean-cumulative-AUC for right-censored events on death (0.67(0.07) versus 0.61(0.09)(p-value=1.7×10-03)). To conclude, we propose a new model better suited in the context of unreliable reference time.},
}

@article {pmid41480876,
year = {2026},
author = {Majumdar, T and Das, PK and Bisoi, A and Jana, B and Singh, PC},
title = {Three-State Unfolding of Telomeric G-Quadruplexes through Conformational Switching in Crowded Cell-like Conditions.},
journal = {Biochemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.biochem.5c00486},
pmid = {41480876},
issn = {1520-4995},
abstract = {The unfolding of telomeric G-quadruplexes (G4s) is a key step in telomere elongation and regulation. Within cells, the highly crowded intracellular milieu significantly influences the structural stability and dynamics of G4s; however, the molecular mechanism governing their unfolding under such conditions remains poorly understood. In this study, we have investigated the thermal unfolding of various human telomeric G4 sequences in KCl, both in the absence and presence of molecular crowders, using temperature-dependent circular dichroism (CD) spectroscopy combined with singular value decomposition, multivariate curve resolution alternating least-squares (MCR-ALS), and well-tempered metadynamics simulations. In KCl alone, telomeric G4s exhibit a two-state unfolding mechanism, where the hybrid-type topology directly converts into the unfolded random-coil state. In contrast, under crowded conditions, particularly in the presence of hydrophobic crowders, the unfolding follows a three-state pathway involving a distinct intermediate. The hybrid structure initially transitions to a parallel-type topology at elevated temperatures before fully unfolding. This stabilization of the parallel topology arises from preferential interactions between hydrophobic crowders and the exposed loop nucleobases of the parallel G4 form. On the other hand, hydrophilic crowders exert minimal influence on the unfolding pathway, which remains similar to that observed in KCl solution. Overall, these findings provide molecular-level insights into the unfolding process of telomeric G4 DNA in crowded cell-like environments and may be useful in understanding the complex telomere elongation process.},
}

@article {pmid41480618,
year = {2025},
author = {Hu, G and Gogzheyan, C and Panja, S and Sil, S and Gendelman, HE},
title = {Extracellular vesicle-based therapies for neurodegenerative diseases.},
journal = {NeuroImmune pharmacology and therapeutics},
volume = {4},
number = {4},
pages = {377-390},
pmid = {41480618},
issn = {2750-6665},
abstract = {Extracellular vesicles (EVs) are mediators of neurodegeneration and emerging therapeutic tools for central nervous system disorders. On the one hand, they help spread beta amyloid, tau, α-synuclein, TDP-43, and mutant SOD1, contributing to the signs and symptoms of Alzheimer's, Parkinson's, Amyotrophic lateral sclerosis, and Huntington's Diseases. By activating glial cells, they promote chronic neuroinflammation through carrying cytokines, inflammasomes, and chemokines. On the other hand, EVs' ability to transport neuroregulatory products and cross the blood-brain barrier makes them ideal vehicles for drug delivery. Their function can be surface-modified to deliver targeted therapies, including anti-inflammatory and neuroprotective regulatory RNAs, proteins, and lipids, as well as factors that help maintain neural homeostasis. Notably, we suggest that colostrum-derived EVs, enriched with growth factors and immune-regulatory microRNAs, offer a natural, scalable, and biocompatible source for neuroprotective treatment. Although EVs can act as "Janus-faced" entities - serving both as disease initiators and versatile therapeutic vehicles - controlling their activity can enable immune-based therapeutics for neurodegenerative diseases.},
}

@article {pmid41480396,
year = {2025},
author = {Arafat, A and Soliman, SMA and Farghaly, TA and Ebrahim, NAA},
title = {Exercise with induced pluripotent stem cells enhances Wnt1-Lmx1a signaling and dopaminergic neurogenesis to alleviate Parkinsonian symptoms.},
journal = {World journal of stem cells},
volume = {17},
number = {12},
pages = {113924},
pmid = {41480396},
issn = {1948-0210},
abstract = {This article focused on the recent contribution by Jiang et al, who demonstrated that voluntary exercise can significantly potentiate the effects of induced pluripotent stem cell transplantation in a Parkinson's disease (PD) model through activation of the Wnt1-Lmx1a signaling cascade. Jiang et al's findings highlight the role of exercise as a molecular modulator of neurogenesis and support the development of integrated strategies combining physical activity, stem cell transplantation, and biomaterials to improve outcomes in PD. We highlight exercise as a molecular modulator that fosters a neurogenic milieu, recommend examining additional developmental signals (sonic hedgehog, fibroblast growth factor 8, bone morphogenetic protein), and suggest biomaterial-based strategies to support graft survival and integration. We also stress the need to optimize exercise regimens in relation to transplantation, framing these insights within a translational strategy for advancing regenerative therapies in PD.},
}

@article {pmid41480315,
year = {2025},
author = {Wang, CL and Zeng, M and Luo, Y},
title = {Unmasking the high-risk phenotype in autoimmune gastritis: A pathologist's roadmap for the clinician.},
journal = {World journal of gastroenterology},
volume = {31},
number = {48},
pages = {115244},
pmid = {41480315},
issn = {2219-2840},
mesh = {Humans ; *Stomach Neoplasms/pathology/diagnosis/immunology ; *Autoimmune Diseases/pathology/immunology/diagnosis ; *Gastritis/pathology/immunology/diagnosis ; Biopsy ; *Neuroendocrine Tumors/pathology/immunology/diagnosis ; Phenotype ; Risk Factors ; *Precancerous Conditions/pathology/immunology/diagnosis ; *Gastric Mucosa/pathology/immunology ; Risk Assessment ; Pathologists ; Ki-67 Antigen/analysis ; Prognosis ; Disease Progression ; },
abstract = {Li et al's recent work on the risk factors for autoimmune gastritis provides clinical context for the vast majority of gastric neuroendocrine tumors (G-NETs). However, a deeper understanding of the underlying pathology is needed for precise clinical management. Our letter details the predictable stepwise progression of type 1 G-NETs from autoimmune-driven corporal atrophy and hypergastrinemia to a clear microscopic sequence of enterochromaffin-like cell precursor lesions, including linear hyperplasia, micronodular hyperplasia, and dysplasia. We highlight the definitive diagnostic thresholds that separate these precursors from overt neoplasia: The 0.5 mm size rule and the presence of submucosal invasion. We advocate for a "prognostic biopsy protocol" in which pathologists actively report these precursor lesions and use Ki-67 to grade G-NETs, providing a quantitative risk assessment. This pathology-centric approach transforms surveillance, allowing clinicians to act on objective microscopic milestones rather than waiting for macroscopically visible tumors.},
}

Humans
*Stomach Neoplasms/pathology/diagnosis/immunology
*Autoimmune Diseases/pathology/immunology/diagnosis
*Gastritis/pathology/immunology/diagnosis
Biopsy
*Neuroendocrine Tumors/pathology/immunology/diagnosis
Phenotype
Risk Factors
*Precancerous Conditions/pathology/immunology/diagnosis
*Gastric Mucosa/pathology/immunology
Risk Assessment
Pathologists
Ki-67 Antigen/analysis
Prognosis
Disease Progression

@article {pmid41480190,
year = {2025},
author = {Ganzetti, M and Valsasina, P and Barkhof, F and Rocca, MA and Filippi, M and Prados, F and Craveiro, L},
title = {SynSpine: an automated workflow for the generation of longitudinal spinal cord synthetic MRI data.},
journal = {Frontiers in neuroinformatics},
volume = {19},
number = {},
pages = {1649440},
pmid = {41480190},
issn = {1662-5196},
abstract = {BACKGROUND: Spinal cord atrophy is a key biomarker for tracking disease progression in neurological disorders, including multiple sclerosis, amyotrophic lateral sclerosis, and spinal cord injury. Recent MRI advancements have improved atrophy detection, particularly in the cervical region, facilitating longitudinal studies. However, validating atrophy quantification algorithms remains challenging due to limited ground truth data.

OBJECTIVE: This study introduces SynSpine, a workflow for generating synthetic spinal cord MRI data (i.e., digital phantoms) with controlled levels of artificial atrophy. These phantoms support the development and preliminary validation of spinal cord imaging pipelines designed to measure degeneration over time.

METHODS: The workflow consists of two phases: (1) generating synthetic MR images by isolating, extracting and scaling the spinal cord, simulating atrophy on the PAM50 template; (2) performing non-rigid registration to align the synthetic images with the subject's native space, ensuring accurate anatomical correspondence. A proof-of-concept application utilizing the Active Surface and Reg methods implemented in Jim demonstrated its effectiveness in detecting atrophy across various levels of simulated atrophy and noise.

RESULTS: SynSpine successfully generates synthetic spinal cord images with varying atrophy levels. Non-rigid registration did not significantly affect atrophy measurements. Atrophy estimation errors, estimated using Active Surface and Reg methods, varied with both simulated atrophy magnitude and noise level, exhibiting region-dependent differences. Increased noise led to higher measurement errors.

CONCLUSION: This work presents a novel and modular framework for simulating spinal cord atrophy data using digital phantoms, offering a controlled setting for testing spinal cord analysis pipelines. As the simulated atrophy may over-simplify in vivo conditions, future research will focus on enhancing the realism of the synthetic dataset by simulating additional pathologies, thus improving its application for evaluating spinal cord atrophy in clinical and research contexts.},
}

@article {pmid41479978,
year = {2025},
author = {Chang, X},
title = {The impact of phrasing on advice-taking under gain and loss frames in a reinforcement learning paradigm.},
journal = {Frontiers in psychology},
volume = {16},
number = {},
pages = {1693546},
pmid = {41479978},
issn = {1664-1078},
abstract = {INTRODUCTION: Grounded in Behrens et al.'s (2008) advice-taking paradigm, this study investigates how advice phrasing (positive vs. negative) and task framing (gain vs. loss) influence the extent to which individuals integrate advice during decision-making. Rather than focusing on isolated choice outcomes, we examined the cognitive processes underlying advice use through a reinforcement learning (RL) framework.

METHODS: Across two experiments (N = 38 and N = 74), participants completed probabilistic decision-making tasks while receiving trial-by-trial advice. Computational modeling was used to estimate the latent advice reference weight (ω), reflecting reliance on advice throughout the learning process, as well as the advice-specific learning rate (α a). Behavioral measures of advice-taking (advice-choice consistency) were analyzed alongside modeling-derived parameters.

RESULTS: Both behavioral indices and parameter estimates showed that participants relied more on positively phrased advice than negatively phrased advice. Moreover, advice phrasing interacted with task framing: positively phrased advice exerted a stronger influence under the gain frame, whereas negatively phrased advice was more influential under the loss frame. This interaction was robustly captured by the modeled advice-weight parameter (ω), although not consistently evident in behavioral choice patterns. Modeling results further showed that the advice-specific learning rate (α a) was significantly higher for positively phrased advice, suggesting greater updating from such information.

DISCUSSION: These findings provide a mechanistic understanding of how social (advice phrasing) and contextual (task framing) features jointly shape advice integration and inform more effective communication strategies in decision-making contexts.},
}

@article {pmid41479929,
year = {2025},
author = {Bagrodia, A and Vaithiyam, V and Laguduva Mohan, S},
title = {Large colorectal lesions: Expanding the boundaries of endoscopic management.},
journal = {World journal of gastrointestinal endoscopy},
volume = {17},
number = {12},
pages = {115008},
pmid = {41479929},
issn = {1948-5190},
abstract = {Large colorectal lesions (≥ 3 cm) present a significant therapeutic challenge due to their potential for malignancy and the technical difficulties they encounter. Endoscopic resection techniques, including endoscopic mucosal resection, endoscopic submucosal dissection, and endoscopic full-thickness resection, have revolutionized the management of these lesions by offering organ-preserving alternatives to surgery with favorable outcomes. We read with great interest and commended Zhu et al for their valuable study on the endoscopic treatment of large colorectal lesions. Zhu et al's study provides crucial real-world evidence regarding the safety and effectiveness of advanced endoscopic resection techniques in this challenging patient group. These findings support the possibility of achieving high rates of complete resection with acceptable adverse event profiles, reinforcing the role of endoscopic mucosal resection and submucosal dissection in routine practice. This editorial also offers a comprehensive review of the current literature, discusses its clinical implications, explores future directions, and compares endoscopic resection methods with surgical options. Zhu et al's study findings not only validate the efficacy of advanced endoscopic resection but also signify a paradigm shift from surgical to organ-preserving strategies in colorectal oncology, a transformation that requires deliberate system-wide training and capacity building.},
}

@article {pmid41479723,
year = {2025},
author = {Jing, C and Liu, K},
title = {Taming colonic anastomotic leakage: Wisdom from the ancient Chinese legend of Yu the Great.},
journal = {World journal of gastrointestinal surgery},
volume = {17},
number = {12},
pages = {113423},
pmid = {41479723},
issn = {1948-9366},
abstract = {Colonic anastomotic leakage (AL) remains the most severe complication of colorectal surgery, significantly increasing morbidity, mortality, and healthcare burdens. The ideal solution - complete AL prevention without a defunctioning stoma - has long eluded surgeons and patients. Hu et al proposed total enteric flow diversion using a modified ileostomy tube with an inflatable balloon, demonstrating its efficacy in completely preventing AL in porcine models. This innovation echoes the ancient legend of Yu the Great, a Chinese hero renowned for taming the Yellow River's catastrophic floods. Unlike his father, who failed by merely building embankments to block water, Yu succeeded by dredging channels to redirect floods seaward. This paradigm of "diversion over obstruction" applies equally to AL prevention. Beyond Hu et al's balloon technique, alternatives like the C-seal, the SafeHeal Colovac+ anastomosis protection device and Tong et al's biodegradable stent-based diverting techniques show promise in clinical trials. Key challenges remain: Diversion efficiency, device migration risks, and patient tolerance. We must accelerate such like breakthroughs in non-stoma diversion strategies to transform AL management.},
}

@article {pmid41479703,
year = {2025},
author = {Wan, P and Zhou, SQ and Ke, QH},
title = {Very early recurrence after pancreatic cancer resection: Unmasking the "biological R2" enigma and rethinking prognostic paradigms.},
journal = {World journal of gastrointestinal surgery},
volume = {17},
number = {12},
pages = {114403},
pmid = {41479703},
issn = {1948-9366},
abstract = {Pancreatic ductal adenocarcinoma (PDAC), a "silent killer" with elusive early symptoms and poor prognosis, sees nearly half of patients experience recurrence within a year post-curative-intent surgery. Very early recurrence (VER), defined as recurrence within 12 weeks postoperatively and first termed "biological R2 resection" by Belfiori et al, remains a clinical puzzle. Martlı et al's recent retrospective cohort study offers crucial insights into this understudied issue, identifies predictive factors that challenge long-held beliefs, and calls for a rethink of risk stratification and postoperative management for PDAC patients. Martlı et al studied 303 PDAC patients at a high-volume center from 2019 to 2024, with VER affecting 9.24% (28 patients) of the cohort. The study's strength lies in combining traditional statistical analyses and machine learning (random forest modeling) to capture nonlinear relationships between clinicopathological factors and VER risk. Key findings include: (1) Poorly differentiated (G3) tumors are the strongest VER predictor (OR = 2.43, P < 0.001; random forest importance score = 0.35), with 92.85% of VER patients having G3 tumors (vs 45.81% of non-VER patients); (2) Contrary to prior studies, pancreatic head tumors (89.28% of VER patients vs 83.66% of non-VER patients, P = 0.031) were linked to VER; (3) Elevated red cell distribution width is a weaker predictor (random forest importance score = 0.20, P = 0.03 for group difference, P = 0.079 in multivariate analysis); and (4) VER correlates with significantly higher 6-month mortality (32.44% vs 14.77% in non-VER patients, P = 0.032).},
}

@article {pmid41479097,
year = {2026},
author = {Stamatelopoulos, D and Papakonstantinou, E and Bacopoulou, F and Vlachakis, D},
title = {Polyphenols from Olive Oil: A Promising Therapeutic Approach for Neurodegenerative Diseases.},
journal = {Advances in experimental medicine and biology},
volume = {1490},
number = {},
pages = {343-349},
pmid = {41479097},
issn = {0065-2598},
mesh = {*Olive Oil/chemistry/therapeutic use ; Humans ; *Polyphenols/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology ; *Neuroprotective Agents/therapeutic use ; Animals ; Oxidative Stress/drug effects ; Antioxidants/therapeutic use ; Diet, Mediterranean ; Anti-Inflammatory Agents/therapeutic use ; },
abstract = {Neurodegenerative diseases such as Alzheimer's, Parkinson's, ALS, and Huntington's disease pose a growing global health challenge due to their prevalence in aging populations and their devastating impact on cognitive and motor functions. Current treatments focus on symptom management, with no options available to reverse neuronal damage. Emerging evidence highlights the potential role of extra virgin olive oil (EVOO) polyphenols in neuroprotection, particularly in the context of the Mediterranean diet, which is associated with lower rates of neurodegenerative disorders. EVOO's rich polyphenolic compounds, including hydroxytyrosol, oleuropein, tyrosol, and oleocanthal, exhibit potent antioxidant, anti-inflammatory, and neuroprotective properties. These bioactive molecules have shown potential in modulating disease-specific pathways, such as reducing oxidative stress, inhibiting abnormal protein aggregation, and regulating neuroinflammation. This paper explores the therapeutic potential of olive oil polyphenols for neurodegenerative diseases, detailing their mechanisms of action across different conditions. Our findings suggest that incorporating EVOO into dietary and medical interventions could serve as a promising strategy for mitigating neurodegenerative disease progression and enhancing cognitive health.},
}

*Olive Oil/chemistry/therapeutic use
Humans
*Polyphenols/therapeutic use/pharmacology
*Neurodegenerative Diseases/drug therapy/metabolism/pathology
*Neuroprotective Agents/therapeutic use
Animals
Oxidative Stress/drug effects
Antioxidants/therapeutic use
Diet, Mediterranean
Anti-Inflammatory Agents/therapeutic use

@article {pmid41478512,
year = {2025},
author = {Strohmer, B and Grosh, K and Montañana-Rosell, R and Mora, S and Ausborn, J and Allodi, I},
title = {Spinal circuit mechanisms constrain therapeutic windows for ALS intervention: A computational modeling study.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107253},
doi = {10.1016/j.nbd.2025.107253},
pmid = {41478512},
issn = {1095-953X},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive breakdown of neural circuits which leads to motoneuron death. Earlier work from our lab showed that dysregulation of inhibitory V1 interneurons precedes the degeneration of excitatory V2a interneurons and motoneurons and that stabilizing V1-motoneuron connections improved motor function and saved motoneurons in the SOD1[G93A] ALS mouse model. However, the optimal timing for this intervention remains unclear. To address this, we developed a spiking neural network model of spinal locomotor circuits to simulate healthy and ALS-like conditions. By modeling changes in network connectivity and synaptic dynamics, we predict that V1 dysregulation induces an imbalance in motoneuron output which results in flexor-biased activity, leading to the disruption of flexor-extensor coordination, and potentially contributing to selective vulnerability of flexor motoneurons. Stabilizing V1 synapses preserved motor output even after motoneuron loss, suggesting that therapeutic benefit is possible into symptomatic stages. However, model predictions also highlighted that after sustained synaptic loss and the development of slower synaptic dynamics within the network, synaptic stabilization leads to maladaptive extensor-biased activity, suggesting that excitatory/inhibitory balance impacts treatment effectiveness. Finally, the model indicated that V1 stabilization could lead to rescue of the V2a excitatory interneurons, a finding that we were able to confirm experimentally in the SOD1[G93A] ALS mouse model. By exploring different scenarios of synaptic loss and cell dysregulation during synaptic stabilization, our models provide a framework for predicting candidate time windows for spinal circuit interventions, which may guide future preclinical investigations.},
}

@article {pmid41477570,
year = {2025},
author = {Almalki, MG and Abdel-Aziem, AA},
title = {Validation and cross-cultural adaptation of an Arabic version of the chronic pain self-efficacy scale.},
journal = {Hong Kong physiotherapy journal : official publication of the Hong Kong Physiotherapy Association Limited = Wu li chih liao},
volume = {45},
number = {2},
pages = {143-155},
pmid = {41477570},
issn = {1013-7025},
abstract = {BACKGROUND: Self-efficacy in pain sufferers includes beliefs about one's capacity to tolerate pain. For usage by Arabic-speaking individuals, the Chronic Pain Self-Efficacy Scale (CPSS), which was initially developed in English, must be translated and modified into the Arabic language.

OBJECTIVE: To assess the CPSS's psychometric qualities for subjects suffering from chronic pain in Arabic.

METHODS: This was a cross-sectional survey that followed Beaton et al.'s guidelines. The CPSS underwent cross-cultural adaptation and Arabic translation in the initial phase. Then, the reliability and validity of the Arabic version of CPSS were examined. A total of 329 patients completed the questionnaire (40.7% males and 59.3% females).

RESULTS: The subscales had good internal consistency, the Cronbach's alpha was 0.870 for subscale 1 (self-efficacy for managing pain), 0.935 for subscale 2 (physical function self-efficacy), and 0.925 for subscale 3 (coping with other symptoms self-efficacy). Test-retest total scores had an acceptable intraclass correlation coefficient (ICC) of 0.743 (95% CI -0.29 to -0.196, p = 0 . 92). When performing principal component analysis with varimax rotation [exploratory factor analysis (EFA)> 0 . 4 ], the test is helpful. Regarding construct validity, the correlation between the total score of Beck depression inventory (BDI) and CPSS subscales and total score have significant moderate negative correlations (r =- 0 . 479 ; p = 0 . 001) except the pain management subscale has significantly weak negative correlations (r =- 0 . 345 ; p = 0 . 001).

CONCLUSION: The Arabic version seems to be a reliable and valid instrument for evaluating a person's self-efficacy in chronic pain among Arabic-speaking individuals making it a good and acceptable instrument.},
}

@article {pmid41477139,
year = {2025},
author = {Syamal, M},
title = {Treatment of Neurogenic Voice Disorders.},
journal = {World journal of otorhinolaryngology - head and neck surgery},
volume = {11},
number = {4},
pages = {541-547},
pmid = {41477139},
issn = {2589-1081},
abstract = {This overview serves as a foundational resource for clinicians caring for neurologically complex patients presenting with voice complaints. Neurogenic voice disorders are diverse in their clinical presentations and therapeutic approaches. A thorough medical history, including family history, detailed laryngeal examination, voice assessments, and neuroimaging, are imperative, as well as a multidisciplinary, collaborative approach with neurologists, speech language pathologists, and patient caregivers. Disorders such as amyotrophic lateral sclerosis (ALS), cerebrovascular accidents (strokes), Huntington's disease, myasthenia gravis (MG), Parkinson's disease (PD), and voice tremor should be understood by otolaryngologists. Each condition presents unique challenges and requires tailored treatment strategies ranging from supportive therapies and pharmacological interventions to surgery. Voice management techniques, including the use of botulinum toxin for hyperkinetic disorders and deep brain stimulation for refractory cases, are highlighted as promising interventions.},
}

@article {pmid41476442,
year = {2025},
author = {Kato, N and Hashida, G and Sahara, W},
title = {Short-Term Effects of Exercise Therapy on Muscle Characteristics in Patients With Mild-to-Moderate Amyotrophic Lateral Sclerosis: A Preliminary Case Series Study.},
journal = {Cureus},
volume = {17},
number = {12},
pages = {e100383},
pmid = {41476442},
issn = {2168-8184},
abstract = {BACKGROUND: Exercise therapy is recommended for patients with amyotrophic lateral sclerosis (ALS), but its effects on muscle mass and intramuscular conditions remain unclear. In recent years, ultrasonography has enabled the simple and non-invasive estimation of muscle mass and intramuscular conditions. This study aimed to investigate the short-term effects of exercise therapy on muscle characteristics in patients with mild-to-moderate ALS using ultrasonography.

METHODS:  Ambulatory patients with ALS and an ALS Functional Rating Scale-Revised (ALSFRS-R) score of ≥30 underwent moderate-intensity exercise therapy for 3-4 weeks. Primary outcome measures included muscle strength (handgrip strength (HGS) and ankle dorsiflexion strength (ADFS)), muscle thickness (MT), echo intensity (EI), and the ratio of muscle strength to muscle thickness for both the forearm muscles and the tibialis anterior muscle. The Bayesian Wilcoxon signed-rank test was used to compare outcomes before and after the intervention.

RESULTS:  Six consecutive patients with ALS (median age: 75.5 years; three males (50%) and three females (50%); four with bulbar onset (66.7%) and two with upper limb onset (33.3%)) were included. Following the intervention, the muscle thickness of the forearm muscles and the tibialis anterior muscle decreased. However, qualitative muscle characteristics were partially maintained or improved: the echo intensity of the forearm muscles was maintained, and the ratio of ankle dorsiflexion strength to muscle thickness of the tibialis anterior muscle showed a large increase.

CONCLUSION:  In patients with mild-to-moderate ALS, exercise therapy resulted in short-term qualitative changes in muscle, while a concurrent reduction in muscle mass may have attenuated these effects. The benefits of exercise therapy may have been counteracted by muscle mass loss, suggesting the need for future studies to investigate the combined effects of exercise and nutritional therapy on muscle characteristics and activities of daily living (ADL).},
}

@article {pmid41476438,
year = {2025},
author = {Oza, R},
title = {Physical Activity as an Intervention for Frailty Syndrome: A Narrative Review.},
journal = {Cureus},
volume = {17},
number = {12},
pages = {e100293},
pmid = {41476438},
issn = {2168-8184},
abstract = {Frailty is a geriatric syndrome characterised by a decline in functional reserves as the body ages, resulting in increased disability, comorbidity, and mortality. With trends towards ageing populations, frailty syndrome becomes more clinically relevant, highlighting the importance of appropriately preventing and managing the characteristics of frailty syndrome. Risk factor modification is recommended to delay or prevent the onset of frailty, including physical activity alongside other modifiable behaviours such as diet. Ageing is associated with chronic low-grade inflammation, resulting in reduced muscle protein synthesis and increased resistance to insulin, which both contribute to sarcopenia. Sarcopenia underpins key characteristics of frailty, including weakness and slow speed. Physical activity stimulates anabolic pathways and improves insulin resistance, reducing sarcopenia. Moreover, aerobic exercise is responsible for increasing the VO2 peak, whilst resistance exercise improves muscle strength, both of which are known to decrease in frail elders. This narrative review primarily explored the effectiveness of physical activity in reducing the risk of the onset of frailty syndrome through a narrative review of the relevant literature concerning this subject. A secondary focus of this narrative review is to compare the success of alternative interventions for preventing frailty, relative to physical activity. Physical activity interventions have been shown to improve components of frailty scoring and selected biological markers of frailty, with evidence suggesting physical activity is an effective single-domain intervention for frailty; however, multidomain approaches may result in a greater overall improvement in frailty prevention. Further research is required to identify the types of exercise that modify specific aspects of Fried et al.'s frailty criteria (FFC), as well as what interventions can be used alongside physical activity, to holistically treat all characteristics of frailty syndrome.},
}

@article {pmid41476266,
year = {2026},
author = {Cai, F and Xu, D and Yang, D and Huang, F and Song, X and Jiang, Q and Wan, S and Zhao, Y and Zhou, J},
title = {Multidimensional predictors of fatigue in amyotrophic lateral sclerosis: a cross-sectional study in China.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-33192-3},
pmid = {41476266},
issn = {2045-2322},
support = {Grant No. ZY2025Q006//Hubei Provincial Administration of Traditional Chinese Medicine/ ; Grant No. 82575246//National Natural Science Foundation of China/ ; GZY-KJS-2025-008 and Joint Fund, 2023AFD128//Science and Technology Special Project of State Administration of Traditional Chinese Medicine and Hubei Provincial Natural Science Foundation/ ; },
}

@article {pmid41475669,
year = {2025},
author = {Mirzalieva, O and Reed, RE and Haas, AL and Juncker, MA and Logarbo, P and Klein, JM and Worthylake, D and Desai, SD},
title = {ISG15 dysregulates endoplasmic reticulum-mitochondrial contacts and calcium homeostasis in Ataxia telangiectasia.},
journal = {Cellular signalling},
volume = {},
number = {},
pages = {112347},
doi = {10.1016/j.cellsig.2025.112347},
pmid = {41475669},
issn = {1873-3913},
abstract = {Dysregulation of endoplasmic reticulum and mitochondrial (ER:Mit) contacts and mitochondrial calcium (mitCa[2+]) homeostasis are found in several neurodegenerative disorders, including Ataxia Telangiectasia (A-T). However, the cellular basis of these defects remains unclear. Previously, we demonstrated that the aberrantly elevated Interferon-Stimulated Gene 15 (ISG15) pathway inhibits protein polyubiquitylation, its dependent protein turnover, and mitophagy pathways in A-T. Literature indicates that silencing of mitochondrial ubiquitin ligase 1 (MUL1) stabilizes mitofusin2 (MFN2) and attenuates mitCa[2+] uptake from ER to Mit (mitCa[2+]influx) in primary neurons. We have replicated these findings in apparently healthy fibroblasts. We hypothesized that elevated ISG15 may inhibit ubiquitin-dependent MUL1-mediated degradation of MFN2 and dysregulate ER:Mit contacts and mitCa[2+] homeostasis in A-T fibroblasts. Concurrently, MFN2 is stabilized in A-T, MUL1-silenced A-T, MUL1/ISG15-silenced A-T vs ISG15-silenced A-T fibroblasts. Moreover, the number of ER:Mit contacts is increased in A-T vs ISG15-silenced A-T fibroblasts. Notably, mitCa[2+]efflux is significantly attenuated in A-T vs ISG15-silenced A-T fibroblasts in which mitCa[2+]efflux is restored to levels comparable to those observed in normal fibroblasts. The mitCa[2+]efflux remains attenuated in MUL1 and MUL1/ISG15-silenced A-T fibroblasts. We conclude that ISG15 impairs MUL1/MFN2-mediated regulation of ER:Mit contacts and attenuates mitCa[2+]efflux, which may, in turn, cause Ca[2+] overload-mediated mitochondrial damage in A-T. These findings suggest that ISG15 silencers may correct mitochondrial abnormalities and improve mitochondrial health in A-T patients and in those with other neurodegenerative disorders in which ISG15 is elevated, such as ALS.},
}

@article {pmid41475349,
year = {2025},
author = {Dubey, SK and Chaubey, D and Ikenaga, C and Lin, WW and Bellen, HJ and Lloyd, TE},
title = {Aberrant nuclear pore complex degradation contributes to neurodegeneration in VCP disease.},
journal = {Neuron},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuron.2025.11.017},
pmid = {41475349},
issn = {1097-4199},
abstract = {Defective nucleocytoplasmic transport (NCT) has emerged as a contributing factor in the pathogenesis of neurodegenerative diseases and aging. Valosin-containing protein (VCP) is an AAA+ATPase required for disassembly of protein complexes, and mutations in VCP cause neurodegenerative and neuromuscular diseases. We find that VCP is required for quality control of nuclear pore complexes (NPCs) by extracting selected nucleoporins from NPCs for proteasome-mediated degradation. Pathogenic VCP variants cause a reduction in nucleoporins in Drosophila, induced pluripotent stem cell (iPSC)-derived motor neurons, and muscle biopsies from patients, indicating a dominant gain-of-function mechanism. Mechanistically, disease-associated mutations in VCP result in increased recruitment to NPCs through interactions with Ufd1-Npl4, leading to the removal of a subset of nucleoporins from NPCs and disrupting NCT. These findings show that the VCP-Ufd1-Npl4 pathway regulates NPC quality control and that disease-associated variants aberrantly activate the VCP-Ufd1-Npl4 complex to degrade NPCs and disrupt NCT.},
}

@article {pmid41475066,
year = {2025},
author = {Kaji, R and Nishi, Y and Ishida, T and Takase, T and Ueda, T and Maeda, T and Izumi, Y and , },
title = {Clinical safety of ultra-high-dose methylcobalamin in patients with amyotrophic lateral sclerosis: Open-label extension of a phase 2/3 randomized controlled study.},
journal = {Journal of the neurological sciences},
volume = {480},
number = {},
pages = {125701},
doi = {10.1016/j.jns.2025.125701},
pmid = {41475066},
issn = {1878-5883},
abstract = {OBJECTIVE: To develop combined therapies for amyotrophic lateral sclerosis (ALS), we investigated the long-term safety of ultra-high-dose methylcobalamin (50-mg intramuscular, twice weekly) in patients with advanced ALS.

METHODS: As an open-label extension of a multicenter, randomized, double-blind, placebo-controlled phase 2/3 study, patients were enrolled and administered methylcobalamin 50 mg intramuscularly twice weekly for up to 52 weeks.

RESULTS: In total, 144 patients (mean age, 62.1 years; 61.1 % male) were included, and the overall disease duration was 53.2 ± 17.9 months, with 85.4 % of patients having an ALS severity stage ≥3. The incidence of adverse events was 94.4 %, and adverse drug reactions occurred in 3.5 % of patients, which included proteinuria (2.1 %) and single cases of supraventricular arrhythmia, increased blood urea, and hypertension (0.7 % each). None led to discontinuation or death. The survival rate at 52 weeks was 85.7 %, and as shown for the following patient subgroups: by ALS severity (stage 1-2, 100 %; 3, 85.3 %; 4, 82.8 %; 5, 82.0 %) and by presence of tracheostomy (with, 88.8 %; without, 84.1 %). The median change in the ALS functional rating scale total score from baseline to 52 weeks was -1.0.

CONCLUSION: There were no particular safety issues as reported in the phase 2/3 study and no clear deterioration in survival rate or physical function when ultra-high-dose methylcobalamin was administered intramuscularly in patients with advanced ALS. This regimen could be a candidate for initial therapy with further add-on to overcome ALS in the future.},
}

@article {pmid41474642,
year = {2026},
author = {Luo, H and Yang, Y and Cao, X and Deng, C and Chen, H},
title = {Unveiling the Genetic Association Between Hemoglobin Concentration and Amyotrophic Lateral Sclerosis.},
journal = {Brain and behavior},
volume = {16},
number = {1},
pages = {e71152},
doi = {10.1002/brb3.71152},
pmid = {41474642},
issn = {2162-3279},
support = {82171422//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/blood ; *Hemoglobins/genetics/metabolism ; Genome-Wide Association Study ; Motor Neurons/metabolism ; Mendelian Randomization Analysis ; Induced Pluripotent Stem Cells/metabolism ; Genetic Predisposition to Disease ; Polymorphism, Single Nucleotide ; },
abstract = {BACKGROUND: Although previous studies have suggested an association between hemoglobin (Hb) concentration and amyotrophic lateral sclerosis (ALS), the precise cause-and-effect relationship between them is still unclear. This study aims to investigate the causal correlation between Hb concentration and ALS, and explore the potential genes related to their association.

METHODS: We extracted summary statistical data of Hb concentration and ALS from genome-wide association studies (GWAS), performed Mendelian randomization (MR) analyses, and conducted RNA sequencing of motor neurons different from ALS patient-derived induced pluripotent stem cells (iPSCs), followed by an intersection analysis between differentially expressed genes (DEGs) in ALS motor neurons and selected instrumental variables (IVs) associated with Hb concentration.

RESULTS: As a result, Hb concentration had a negative causal relationship with the risk of ALS, established through IVW (OR = 0.854; 95% CI: 0.767-0.951; p = 0.00418) of the univariable MR analysis. A multivariable MR further confirmed that this causal link remained robust, even when accounting for confounders including systolic blood pressure, total cholesterol levels, body mass index, LDL cholesterol, diastolic blood pressure, and smoking. Importantly, genetically predicted ALS did not show a causal connection to Hb concentration. Additionally, RNA sequencing analysis and qRT-PCR results revealed that transcripts for BACH1 and FLVCR1 were upregulated, while those for TRIM58 were downregulated in SOD1[D90A] ALS motor neurons, compared to the control. In motor neurons differentiated from a sporadic ALS patient-derived iPSCs, qRT-PCR showed increased transcript levels of BACH1, and decreased transcript levels of FLVCR1 and TRIM58. These three genes were intersected with harmonized SNPs between Hb concentration and ALS.

CONCLUSION: Our study concludes that genetically predicted Hb concentration exhibited an independent inverse causal association with the risk of developing ALS, with potential involvement of genes such as BACH1, FLVCR1, and TRIM58.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/metabolism/blood
*Hemoglobins/genetics/metabolism
Genome-Wide Association Study
Motor Neurons/metabolism
Mendelian Randomization Analysis
Induced Pluripotent Stem Cells/metabolism
Genetic Predisposition to Disease
Polymorphism, Single Nucleotide

@article {pmid41472414,
year = {2025},
author = {Wu, J and Tao, Z and Cao, J and Hu, W and Jiang, M and Li, Y and Cao, H and Liao, M and Zhao, N},
title = {Cytochrome P450 and glutathione S-transferase may confer bensulfuron-methyl resistance in Cyperus iria.},
journal = {Pest management science},
volume = {},
number = {},
pages = {},
doi = {10.1002/ps.70492},
pmid = {41472414},
issn = {1526-4998},
support = {2021YFD1700100//National Key Research and Development Program of China/ ; X202510364082//College Students' Innovation Training Project in Anhui Agricultural University/ ; },
abstract = {BACKGROUND: Rice flatsedge (Cyperus iria L.) is one of the most troublesome weeds infesting rice fields across China. Bensulfuron-methyl, an acetolactate synthase (ALS)-inhibiting herbicide, has been widely used for the control of Cyperaceae weeds in rice production. However, long-term and extensive use of this herbicide has resulted in the evolution of resistant C. iria populations. In this study, a suspected bensulfuron-methyl-resistant (R) population collected from a rice field that survived field-recommended applications was investigated to elucidate its resistance level and underlying mechanism.

RESULTS: Compared with a susceptible (S) population, the R population exhibited a high level of resistance to bensulfuron-methyl [resistance index (RI) = 12.88] and cross-resistance to metazosulfuron (RI = 11.66), bispyribac-sodium (RI = 9.10) and penoxsulam (RI = 6.35). No mutations were detected in the ALS gene, and ALS expression levels did not differ significantly between the R and S plants. Pretreatment with the cytochrome P450 inhibitor malathion and the glutathione S-transferase inhibitor 4-chloro-7-nitrobenzoxadiazole effectively reversed bensulfuron-methyl resistance in R plants. Liquid chromatography tandem mass spectrometry analysis showed that the R plants metabolized bensulfuron-methyl significantly faster than the S plants. RNA sequenccing analysis revealed remarkable upregulation of CYP97A3 and GSTF1 in the R population, while molecular docking indicated strong binding affinities between both enzymes and bensulfuron-methyl at their active sites.

CONCLUSION: These results reveal that enhanced expression of CYP97A3 and GSTF1 may contribute to bensulfuron-methyl resistance in C. iria, highlighting the role of metabolic detoxification in the evolution of non-target-site resistance in this species. © 2025 Society of Chemical Industry.},
}

@article {pmid41471389,
year = {2025},
author = {Gershoni Emek, N and Tan, AM and Geva, M and Fekete, A and Abate, C and Hayden, MR},
title = {Pridopidine, a Potent and Selective Therapeutic Sigma-1 Receptor (S1R) Agonist for Treating Neurodegenerative Diseases.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {12},
pages = {},
doi = {10.3390/ph18121900},
pmid = {41471389},
issn = {1424-8247},
abstract = {Pridopidine is a highly selective sigma-1 receptor (S1R) agonist in clinical development for Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). The S1R is a ubiquitous chaperone protein enriched in the central nervous system and regulates multiple pathways critical for neuronal cell function and survival, including cellular stress responses, mitochondrial function, calcium signaling, protein folding, and autophagy. S1R has a crucial role in the ER mitochondria-associated membrane (MAM), whose dysfunction is implicated in several neurodegenerative diseases. By activating the S1R, pridopidine corrects multiple cellular pathways necessary to the cell's ability to respond to stress, which are disrupted in neurodegenerative diseases. Pridopidine restores MAM integrity; rescues Ca[2+] homeostasis and autophagy; mitigates ER stress, mitochondrial dysfunction, and oxidative damage; and enhances brain-derived neurotrophic factor (BDNF) axonal transport and secretion, synaptic plasticity, and dendritic spine density. Pridopidine demonstrates neuroprotective effects in in vivo models of neurodegenerative diseases (NDDs). Importantly, pridopidine demonstrates the biphasic dose response characteristic of S1R agonists. In clinical trials in HD and ALS, pridopidine has shown benefits across multiple endpoints. Pridopidine's mechanism of action, modulating core cellular survival pathways, positions it as a promising candidate for disease modification for different nervous system disorders. Its broad therapeutic potential includes neurodevelopmental disorders, and rare diseases including Wolfram syndrome, Rett syndrome, and Vanishing White Matter Disease. Here, we review the experimental data demonstrating pridopidine's S1R-mediated neuroprotective effects. These findings underscore the therapeutic relevance of S1R activation and support further investigation of pridopidine for the treatment of different neurodegenerative diseases including ALS and HD.},
}

@article {pmid41468784,
year = {2025},
author = {Palanivel, V and Salkar, A and Shenoy, A and Eva, TA and Perera, R and Chitranshi, N and Gupta, V and You, Y and Mirzaei, M and Graham, SL and Gupta, V and Basavarajappa, D},
title = {Neuropeptide Y at the crossroads of neurodegeneration: Mechanistic insights and emerging therapeutic strategies.},
journal = {Neuropeptides},
volume = {115},
number = {},
pages = {102583},
doi = {10.1016/j.npep.2025.102583},
pmid = {41468784},
issn = {1532-2785},
abstract = {Neuropeptide Y (NPY), a widely distributed and highly conserved neuropeptide, plays a central role in the regulation of diverse physiological processes, including stress responses, energy homeostasis, vascular tone, and immune modulation, via activation of its receptor subtypes. Beyond its physiological roles, the dysregulation of NPY expression has been documented in several neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Machado-Joseph disease, and retinal disorders such as diabetic retinopathy and glaucoma. These alterations in NPY levels and receptor activity highlight its potential not only as a biomarker for disease progression but also as a promising therapeutic target. Previous evidence revealed that NPY exerts neuroprotection by alleviating excitotoxicity, oxidative stress, mitochondrial dysfunction, and neuroinflammation while concurrently facilitating neurogenesis, synaptic plasticity, and cellular resilience. NPY activates receptor-mediated intracellular signaling cascades like PI3K/Akt, MAPK/ERK, and p38K, that control cellular survival, proteostasis, and inflammation and thereby influence disease trajectories. Understanding NPY operation with these mechanisms can unveil new avenues for targeted therapy. Current insights into the complex roles of NPY in neurodegeneration are discussed in this review, and their implications in diagnostic and treatment strategies are addressed.},
}

@article {pmid41468379,
year = {2025},
author = {Spencer, BE and Irwin, DJ and Van Deerlin, VM and Suh, E and Lee, EB and Elman, L and Quinn, CC and Amado, D and Baer, M and Grossman, M and Wolk, DA and McMillan, CT},
title = {Polygenic associations with clinical and neuropathological trait heterogeneity across TDP-43 proteinopathies.},
journal = {PloS one},
volume = {20},
number = {12},
pages = {e0338398},
doi = {10.1371/journal.pone.0338398},
pmid = {41468379},
issn = {1932-6203},
mesh = {Humans ; *Multifactorial Inheritance ; *TDP-43 Proteinopathies/genetics/pathology ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide ; Male ; Female ; *DNA-Binding Proteins/genetics ; Aged ; Phenotype ; Middle Aged ; Genetic Predisposition to Disease ; },
abstract = {TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration with TDP-43 (FTLD-TDP), and limbic-predominant age-related TDP-43 encephalopathy, encompass a spectrum of clinical and neuropathological traits. Despite mounting evidence for shared genetic risk across TDP-43 proteinopathies, the modifiers of individual-level traits are unknown. We aimed to identify polygenic contributions to trait heterogeneity across TDP-43 proteinopathies. We used weighted correlation analysis of GWAS summary statistics for ALS, FTLD-TDP, and hippocampal sclerosis of aging (HS-Aging) to identify data-driven clusters of highly correlated single nucleotide polymorphisms (SNPs). We performed gene ontology enrichment analysis for each identified cluster. We derived cluster-specific polygenic scores and evaluated their association with clinical and neuropathological traits in an independently evaluated sample of individuals who met neuropathological and/or genetic criteria for FTLD-TDP or ALS (n = 260). We identified 5 distinct data-driven clusters, including 3 GWAS phenotype-specific clusters (FTLD-TDP, ALS, HS-Aging) and 2 clusters representing the overlap between a pair of GWAS phenotypes (ALS-FTLD and FTLD-HS). Pathway analysis revealed biologically meaningful associations including distinct GWAS phenotype-specific processes within clusters. Cluster-specific ALS and FTLD-TDP polygenic risk each associated with individual-level clinical traits, even within the context of autosomal dominant mutation carriers, where higher ALS polygenic risk associated with neuromuscular impairment and higher FTLD-TDP polygenic risk associated with cognitive-behavioral impairment. Moreover, higher FTLD-TDP polygenic risk associated with higher TDP-43 burden within characteristic FTLD-TDP brain regions. We suggest that there are polygenic modifiers of clinical and neuropathological traits across TDP-43 proteinopathies that may contribute to individual-level differences, including likelihood for developing FTLD or ALS.},
}

Humans
*Multifactorial Inheritance
*TDP-43 Proteinopathies/genetics/pathology
*Amyotrophic Lateral Sclerosis/genetics/pathology
Genome-Wide Association Study
Polymorphism, Single Nucleotide
Male
Female
*DNA-Binding Proteins/genetics
Aged
Phenotype
Middle Aged
Genetic Predisposition to Disease

@article {pmid41467445,
year = {2025},
author = {Dikwella, N and Lingor, P and Tzeplaeff, L},
title = {Seeing amyotrophic lateral sclerosis in a multi-omic perspective.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-01010},
pmid = {41467445},
issn = {1673-5374},
}

@article {pmid41467443,
year = {2025},
author = {Yang, Y and Chen, M and Ding, L and Liu, J and Luo, J and Yan, R and Ning, J and Xie, S and Li, X and Ren, Z and Zhou, R and Chen, Z},
title = {Mitochondria-associated endoplasmic reticulum membranes and calcium ion exchange: A novel direction for aging and neurodegenerative diseases.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00857},
pmid = {41467443},
issn = {1673-5374},
abstract = {Mitochondria-associated endoplasmic reticulum membranes serve as crucial signaling hubs mediating communication between the endoplasmic reticulum and mitochondria, and play a central role in calcium ion exchange. This dynamic interface regulates key cellular processes including bioenergetic metabolism, apoptosis, autophagy, and stress responses. Dysregulation of calcium transport associated with mitochondria-associated endoplasmic reticulum membranes can disrupt intracellular homeostasis, leading to mitochondrial dysfunction, oxidative stress, and neuronal death, which are hallmarks of aging and neurodegenerative diseases. This review systematically examines the functions of protein complexes within mitochondria-associated endoplasmic reticulum membranes and the pathogenic mechanisms of calcium signaling regulated by these membranes in neurodegenerative disorders. It places particular emphasis on structural alterations in calcium ion transport machinery as a common mechanism underlying various neurodegenerative diseases. In Alzheimer's disease, mitochondria-associated endoplasmic reticulum membranes exhibit a hyperactive state, promoting the generation of amyloid-β and enhancing calcium ion flux from the endoplasmic reticulum to the mitochondria. In contrast, in Parkinson's disease and amyotrophic lateral sclerosis, the activity of mitochondria-associated endoplasmic reticulum membranes is reduced, leading to a decline in mitochondrial calcium ion buffering capacity and exacerbating excitotoxicity. Proteins residing in mitochondria-associated endoplasmic reticulum membranes are disrupted across various neurodegenerative diseases, resulting in abnormal communication between the endoplasmic reticulum and mitochondria. Recent studies indicate that mitochondria-associated endoplasmic reticulum membranes play a bidirectional role in disease progression, and compensatory mechanisms often exacerbate the pathological process. Therapeutic strategies aimed at preserving the integrity of mitochondria-associated endoplasmic reticulum membranes hold promise for alleviating neurodegenerative damage. Therefore, calcium ion exchange mediated by mitochondria-associated endoplasmic reticulum membranes plays a key role in aging and neurodegenerative diseases, making it a highly promising therapeutic target.},
}

@article {pmid41467440,
year = {2025},
author = {Akbergenov, R and Wolfer, DP and Gillingham, D and Shcherbakov, D},
title = {Error-prone translation as a driver of proteostasis collapse and neurodegeneration.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00795},
pmid = {41467440},
issn = {1673-5374},
abstract = {Error-prone translation, resulting in inaccuracies in protein synthesis, is increasingly recognized as a critical contributor to proteostasis disruption and the pathogenesis of age-related neurological disorders. In recent years, numerous studies have elucidated that stochastic errors during mRNA translation may act as a molecular "tipping point" initiating pathogenic protein misfolding. A detailed analysis of how translation errors lead to protein misfolding, aggregation, and subsequent neurotoxicity will facilitate the identification of promising therapeutic targets for neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This article explores the contribution of mistranslation to proteostasis decline, focusing on the unique vulnerabilities of neuronal cells. We review the sources of translation errors, effects of ribosomal ambiguity and error-restrictive mutations, role of proteostatic mechanisms (such as molecular chaperones, ubiquitin-proteasome system, and unfolded protein response), and provide a unified perspective that links age-related translational infidelity to neurodegeneration. By synthesizing the most recent data obtained with genetically modified cellular and animal model studies, we highlight how age-associated decline in translational fidelity exacerbates proteostasis failure and propose potential therapeutic interventions targeting translation accuracy to mitigate neurodegeneration.},
}

@article {pmid41467439,
year = {2025},
author = {Dong, T and Zhang, T and Wang, H and Zhang, J and Abdullah, R and Sun, B and Peng, G},
title = {Microbiota-gut-brain axis and bile acids-driven neuromodulation.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00927},
pmid = {41467439},
issn = {1673-5374},
abstract = {Bile acids emerge as multifunctional signaling molecules with dual hepatic and microbial origins, acting through farnesoid X receptor and Takeda G protein coupled receptor 5 to influence inflammation and metabolism. Their dysregulation is consistently observed across various neurodegenerative diseases. The microbiota-gut-brain axis is a pivotal conduit for bile acids-driven neuromodulation, while sex-specific bile acid profiles and signaling pathways introduce critical biological heterogeneity. Emerging translational evidence indicates the promise of bile acids as biomarkers and therapeutic targets, yet highlights the critical hurdles that need to be addressed to realize precision interventions. Our core findings are: (1) Bile acids are far more than mere metabolic byproducts. They orchestrate core pathological processes such as neuroinflammation and energy metabolism. Their functions, whether neuroprotective or neurotoxic, are highly context-dependent, varying with cell type and disease-specific pathological backgrounds, thus exhibiting a potent "double-edged sword" effect. (2) The "microbiota-bile acids-brain axis" serves as a crucial bridge linking peripheral metabolic dysregulation to central nervous system pathology. (3) Sexual dimorphism emerges as a fundamental biological variable essential for understanding the heterogeneity in bile acid profiles and disease susceptibility. The primary contribution of this work is the proposal of an integrated "microbiota-bile acids-sex" framework that systematically describes the key scientific challenge of the context-dependent, dual roles of bile acids. Ultimately, this review champions a paradigm shift from a traditional brain-centric view to a systemic, metabolic perspective, establishing the bile acid system as a promising target for future precision therapeutic interventions.},
}

@article {pmid41467438,
year = {2025},
author = {Zhao, J and Wang, J and Guo, X},
title = {Organoids: Key advances, optimization, and technological iterations in their application to neurodegenerative diseases.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00924},
pmid = {41467438},
issn = {1673-5374},
abstract = {Organoid technology, as an innovative approach, has shown great potential in disease modeling, target screening, and the development of treatment strategies. However, traditional organoids still have three major limitations in research: the absence of specific cell types, the lack of blood-brain barrier structure, and insufficient reproducibility of experimental results. In recent years, researchers have gradually overcome these limitations by introducing innovative techniques such as advanced culture methods, microfluidic systems, bioprinting, organoid transplantation, and assembloid construction. This progress has facilitated the widespread application of organoids in the study of neurodegenerative diseases. This paper aims to systematically review the technological innovations of organoids in the study of neurodegenerative diseases. By summarizing classical organoid construction strategies and their limitations, it emphasizes the value of organoids in comprehensive applications within neurodegenerative disease research. In this review, we focus on five specific neurodegenerative diseases: Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and frontotemporal dementia. Research in these diseases demonstrates that organoids improve experimental accessibility and reduce development cycles in disease modeling, target discovery, and therapeutic strategy formation. Using customized equipment and gene editing techniques, these organoids can be tailored to specific needs, providing pathophysiologically relevant disease models and enhancing our understanding of neurodegenerative diseases. Although organoid technology has demonstrated significant advantages in disease research, its potential for treating neurodegenerative diseases has not yet been fully explored, which may become an important direction for future research.},
}

@article {pmid41467429,
year = {2025},
author = {Liang, X and Qin, R and Qin, Q and Xu, W and Xu, H and Lai, X and Shao, L and Li, C and Xie, M and Xiong, X and Tang, Q and Chen, L},
title = {Therapeutic potential of astrocyte transdifferentiated neurons.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00554},
pmid = {41467429},
issn = {1673-5374},
abstract = {The permanent functional deficits resulting from the inability of adult mammalian central nervous system neurons to regenerate after injury present a significant clinical challenge. While traditional stem cell transplantation strategies continue to encounter ethical concerns and the risk of immune rejection, this impasse has shifted regenerative medicine research toward targeting endogenous astrocytes. Due to their intrinsic plasticity, widespread distribution throughout the central nervous system, and affinity for neurodevelopmental lineage, astrocytes are a unique target for in situ neuronal regeneration. This review systematically elucidates the core regulatory network governing astrocyte transdifferentiation, identifying 10 key signaling pathways, such as Wnt signaling pathway, that form a cascade regulatory system. Directed overexpression of transcription factors such as NeuroD1, Ascl1, or Neurog2 can directly initiate neuronal phenotypic conversion. Meanwhile, small molecule compounds such as valproic acid combined with CHIR99021 activate endogenous neurogenic programs by inhibiting the bone morphogenetic protein signaling axis. Notably, polypyrimidine tract binding protein 1 (PTB) gene silencing significantly enhances transdifferentiation efficiency by suppressing the microRNA 124/re1 silencing transcription factor (miR-124/REST) feedback loop. From a translational perspective, a multidimensional evaluation system based on morphological, molecular marker, and electrophysiological properties has demonstrated considerable therapeutic potential. In stroke models, NeuroD1-mediated transdifferentiation replenished approximately 30% of lost cortical neurons and improved motor coordination, evidenced by enhanced performance in food pellet retrieval, grid walking, and cylinder tests compared with controls. In spinal cord injury studies, SOX2-induced glutamatergic neurons moderately reduced glial scar density by about 25%, permitting regenerating axons to pass through while preserving the supportive structure of scar. In neurodegenerative contexts, PTB inhibition yielded functionally mature dopaminergic neurons and reconstructed nigrostriatal pathways in Parkinson's disease models. In Alzheimer's disease models, adeno-associated virus-delivered NeuroD1 induced whole-brain neural circuit remodeling, generating 500,000 new neurons widely distributed across the cortex and hippocampus, accompanied by improved cognitive performance. Current technical limitations include off-target effects of adeno-associated virus vectors, which cause nonspecific gene expression and require rigorous validation via Cre-loxP lineage tracing. Transdifferentiation efficiency is also highly influenced by regional microenvironments: gray matter astrocytes show higher conversion rates than those in white matter, and oxidative stress increases apoptosis among newly generated neurons. Clinical translation is further constrained by the safety of delivery systems and the aging tissue microenvironment, where transforming growth factor beta 1 is often elevated. Ferroptosis inhibitors have been shown to nearly double the survival rate of transdifferentiated cells, offering a novel strategy to mitigate oxidative damage. Based on current evidence, astrocyte transdifferentiation enables neural functional recovery across multiple disease models through endogenous repair mechanisms. Future advances should focus on optogenetically inducible vectors for spatiotemporal precision, non-viral delivery systems to mitigate vector-related risks, and integration of long-term safety validation in non-human primates with single-cell multi-omics technologies to facilitate the clinical translation of personalized regenerative therapies.},
}

@article {pmid41467421,
year = {2025},
author = {Huerta, TJ and Urbina-Muñoz, V and Urra-Alvarez, V and Villablanca, C and Gomez-Perez, LS and Saavedra, B and Contreras, T and Vidal, RL},
title = {Cell-based immunotherapy for neurodegenerative disease: A promising avenue.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00816},
pmid = {41467421},
issn = {1673-5374},
abstract = {Neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and Huntington's disease are characterized by progressive neuronal loss and chronic neuroinflammation, with current treatments remaining largely symptomatic. This review explores the potential of cell-based immunotherapy as a disease-modifying strategy. Advances in stem cell biology and immune engineering have facilitated the development of therapies using mesenchymal stem cells, chimeric antigen receptor T cells, macrophages, regulatory T cells, modified macrophages, and monoclonal antibodies. These approaches aim to regulate immune mechanisms implicated in neurodegeneration, such as microglial activation, systemic inflammation, and immune checkpoint dysregulation. Notably, macrophage-mediated delivery systems, such as genetically modified cells expressing neurotrophic factors or antioxidant enzymes, have demonstrated neuroprotective effects. Likewise, emerging data support T-cell modulation and monoclonal antibody development as therapeutic targets in amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and Huntington's disease. We highlight current preclinical findings, underlying mechanisms, and translational challenges, emphasizing that immunomodulatory cell therapies represent a promising avenue for precision medicine in neurodegenerative diseases.},
}

@article {pmid41467385,
year = {2025},
author = {Zhou, Z and Zhao, Y and Fan, X and Zhang, J and Niu, R and Ma, Y and Xie, F and Tang, P and Mei, X and Zhang, L and Deng, J},
title = {CD11c+ microglia: From basic research to clinical application.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00868},
pmid = {41467385},
issn = {1673-5374},
abstract = {CD11c+ microglia are a functionally specialized subpopulation of microglia that play a crucial role in the pathophysiological processes of various central nervous system diseases. This review synthesizes compelling evidence that CD11c+ microglia exhibit unique transcriptomic and phagocytic characteristics. These characteristics distinguish them from homeostatic microglia and support their specialized functions. During development, CD11c+ microglia are crucial for the maturation of oligodendrocytes and the integrity of white matter, particularly in regions such as the corpus callosum and cerebellum. In preclinical models of neurodegenerative diseases (such as Alzheimer's disease and amyotrophic lateral sclerosis) and central nervous system injuries (such as stroke and spinal cord injury), they are consistently associated with neuroprotective phenotypes. CD11c+ microglia exhibit enhanced phagocytic capacity near amyloid plaques and damaged neurons, helping to clear pathological protein aggregates and cell debris, thereby reducing neurotoxicity and promoting a repair environment. The current consensus is that specific microenvironmental cues, particularly hazard signaling molecules (DAMPs) and cytokines (such as interferon-γ), are the main drivers of the differentiation and activation of CD11c+ microglia. Among these, the TREM2-APOE signaling axis is a key and widely accepted regulatory pathway for their survival, proliferation, and functional status. The plasticity of CD11c+ microglia is regulated by multiple signaling pathways, including CSF1R, SIRPα-CD47, IFN-γ, and the complement cascade. Emerging therapeutic strategies aim to regulate their activities through gene targeting, metabolic intervention, and immune regulation using TREM2 agonists, CSF1R inhibitors, or nanopharmacological methods. However, challenges remain in defining specific CD11c+ biomarkers, understanding environment-dependent functions, and achieving targeted delivery. Future prospects depend on clearly addressing individual developmental issues, deciphering the molecular switches that control phenotypic plasticity, and developing highly specific therapeutic strategies to leverage their beneficial functions, thereby paving the way for new intervention methods for neurological diseases.},
}

@article {pmid41466523,
year = {2025},
author = {Watabe, K},
title = {Praja1 E3 ubiquitin ligase and the role it plays in neurodegeneration.},
journal = {The FEBS journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/febs.70383},
pmid = {41466523},
issn = {1742-4658},
abstract = {Protein aggregation and transmission are hallmarks of neurodegenerative diseases. Praja1 E3 ubiquitin ligase has been shown to suppress the aggregation of causative proteins in amyotrophic lateral sclerosis, frontotemporal lobar degeneration, Parkinson's disease, Huntington's disease, and spinocerebellar degeneration, which include transactivation response DNA-binding protein of 43 kDa, fused in sarcoma, superoxide dismutase 1, α-synuclein, huntingtin, and ataxin-3. Aoki et al. demonstrated that Praja1 ubiquitinates and degrades tau, a key molecule in tauopathies such as Alzheimer's disease, Pick's disease, progressive supranuclear palsy, and corticobasal syndrome, furthering our understanding of the role of Praja1 in neurodegenerative diseases and potential therapeutic approaches.},
}

@article {pmid41466416,
year = {2025},
author = {Howard, I and Simmons, Z},
title = {Does the ACT Have ImpACT for ALS?.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70117},
pmid = {41466416},
issn = {1097-4598},
}

@article {pmid41466038,
year = {2025},
author = {Cauchi, RJ and Tosolini, AP},
title = {ALS: a field in motion.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {44791},
pmid = {41466038},
issn = {2045-2322},
}

@article {pmid41465514,
year = {2025},
author = {Riku, Y and Brion, JP and Ando, K and Uchihara, T and Iwasaki, Y},
title = {The Determinant of Tau Spreading in Alzheimer's Disease: Dependent on Senile Plaque, Neural Circuits, or Spatial Proximity?.},
journal = {International journal of molecular sciences},
volume = {26},
number = {24},
pages = {},
doi = {10.3390/ijms262412088},
pmid = {41465514},
issn = {1422-0067},
support = {JPMH23FC1008//MHLW Research on rare and intractable diseases Program/ ; 23K06935, 25K22597, and 25K10781//JSPS-KAKENHI/ ; },
mesh = {Humans ; *Alzheimer Disease/metabolism/pathology ; *tau Proteins/metabolism ; *Plaque, Amyloid/metabolism/pathology ; Animals ; Neurofibrillary Tangles/metabolism/pathology ; Amyloid beta-Peptides/metabolism ; Brain/metabolism/pathology ; },
abstract = {Alzheimer's disease (AD) is neuropathologically characterized by tau-immunopositive neurofibrillary tangles (NFTs) and amyloid-β (Aβ)-immunopositive senile plaques. According to the widely accepted amyloid cascade hypothesis, Aβ pathology represents the upstream event in AD pathophysiology and induces tau aggregation. However, numerous studies have suggested that tau aggregates correlate more closely with neuronal loss and regional brain atrophy than with Aβ depositions. Tau aggregation in AD demonstrates a hierarchical spreading pattern beginning in the transentorhinal cortex, but the mechanisms underlying this spreading manner of lesions remain to be elucidated. This review aims to address current controversies regarding tau pathology in AD from the perspectives of both the 'amyloid cascade' and 'tauopathy' hypotheses. From the 'amyloid cascade' viewpoint, Aβ deposition prominently involves distal axon and axon terminals, and in some regions, there are anatomical correspondences between axonal Aβ pathology and cytoplasmic tau aggregations (e.g., a close relationship between senile plaques in the molecular layer of the hippocampal dentate gyrus and NFTs in the transentorhinal cortex). Nevertheless, this model cannot explain the whole body of hierarchical spreading of tau aggregation because notable spaciotemporal discrepancies also exist in many regions. From the 'tauopathy' perspective, the distribution of tau aggregates in AD involves key nodes within the memory circuits. Also, experimental studies have suggested that patient-derived tau exhibits seeding and neuron-to-neuron propagation properties. Interestingly, tau aggregation in AD appears to spread laterally in a proximity-dependent, cortico-cortical fashion rather than along long-range memory circuits. This contrasts with the system-selective, poly-nodal degenerations seen in four-repeat tauopathies, amyotrophic lateral sclerosis, or spinocerebellar degenerations. Moreover, the proportions of three-repeat and four-repeat isoforms shift during the maturation of NFTs in AD. Overall, spreading patterns of tau-pathology in AD cannot be fully explained by Aβ pathology and also differ from the system degeneration seen in other tauopathies.},
}

Humans
*Alzheimer Disease/metabolism/pathology
*tau Proteins/metabolism
*Plaque, Amyloid/metabolism/pathology
Animals
Neurofibrillary Tangles/metabolism/pathology
Amyloid beta-Peptides/metabolism
Brain/metabolism/pathology

@article {pmid41465496,
year = {2025},
author = {López-Royo, T and Gascón, E and Moreno-Martínez, L and Macías-Redondo, S and Zaragoza, P and Manzano, R and Osta, R},
title = {Region-Specific Expression Patterns of lncRNAs in the Central Nervous System: Cross-Species Comparison and Functional Insights.},
journal = {International journal of molecular sciences},
volume = {26},
number = {24},
pages = {},
doi = {10.3390/ijms262412069},
pmid = {41465496},
issn = {1422-0067},
support = {PI21/00372//Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER) "Una manera de hacer Europa" from the European Union/ ; CB18/05/0037//CIBERNED/ ; A19_23R//Consolidated Groups from Gobierno de Aragón/ ; PRTR-C17.I1//The Spanish Ministry of Science and Innovation with funds from the European Union NextGenerationEU, from the Recovery, Transformation and Resilience Plan/ ; FPU19/05625//Ministerio de Universidades from Gobierno de España/ ; PT20/00109//Instituto de Salud Carlos III/ ; },
mesh = {*RNA, Long Noncoding/genetics/metabolism ; Animals ; Humans ; Male ; Female ; Mice ; *Central Nervous System/metabolism ; Spinal Cord/metabolism ; Species Specificity ; Brain/metabolism ; Gene Expression Profiling ; Organ Specificity ; },
abstract = {Increasing evidence demonstrates that long noncoding RNAs (lncRNAs) are crucial for brain evolution and proper development and function of the central nervous system (CNS), exhibiting specific time-, spatial-, and sex-biassed expression patterns. This study investigated whether region-specific spatial expression patterns of brain-relevant lncRNAs are conserved between the mouse and human CNS. Demonstrating such cross-species conservation informs the translational value of mouse models for lncRNA biology. To test this, the expression of 14 lncRNAs was studied in the adult CNS of mice and humans across three different regions (spinal cord, brainstem, and frontal cortex), and age effects were assessed in mice. The results demonstrated conserved expression patterns between the two species, with region-specific changes. The frontal cortex exhibited high expression of Meg3, Miat, and Pvt1 lncRNAs, while the spinal cord showed high levels of Hotair and Gas5. Additionally, Malat1 displayed lower levels in females compared to males in the spinal cord compared to other regions. Finally, through GO functional enrichment analysis and literature review, this study emphasizes the role of lncRNAs in CNS physiology and disease, suggesting their involvement in neurological processes and conditions such as cortical development, neuronal synapsis, schizophrenia, Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. Overall, this research highlights the importance of further investigating the role of lncRNAs in brain function and their potential as key players in neurological disorders, opening the door to explaining the high region- and sex-specific effects of these disorders.},
}

*RNA, Long Noncoding/genetics/metabolism
Animals
Humans
Male
Female
Mice
*Central Nervous System/metabolism
Spinal Cord/metabolism
Species Specificity
Brain/metabolism
Gene Expression Profiling
Organ Specificity

@article {pmid41465278,
year = {2025},
author = {Marzetti, E and Di Lorenzo, R and Calvani, R and Coelho-Júnior, HJ and Landi, F and Pesce, V and Picca, A},
title = {Linking Cell Architecture to Mitochondrial Signaling in Neurodegeneration: The Role of Intermediate Filaments.},
journal = {International journal of molecular sciences},
volume = {26},
number = {24},
pages = {},
doi = {10.3390/ijms262411852},
pmid = {41465278},
issn = {1422-0067},
support = {D1.2024//Università Cattolica del Sacro Cuore/ ; D1.2025//Università Cattolica del Sacro Cuore/ ; Ricerca Corrente 2025//Italian Ministry of Health/ ; DM 1557 11.10.2022//European Commission/ ; 2022YNENP3//Italian Ministry of University and Research/ ; },
mesh = {Humans ; *Mitochondria/metabolism/pathology ; Animals ; *Neurodegenerative Diseases/metabolism/pathology ; *Intermediate Filaments/metabolism/pathology ; *Signal Transduction ; Neurons/metabolism/pathology ; },
abstract = {Mitochondrial dysfunction is a pivotal contributor to neurodegeneration. Neurons heavily rely on mitochondrial oxidative metabolism and therefore need highly efficient quality control mechanisms, including proteostasis, mitochondrial biogenesis, fusion-fission dynamics, and mitophagy, to sustain bioenergetics and synaptic function. With aging, deterioration of mitochondrial quality control pathways leads to impaired oxidative phosphorylation, excessive reactive oxygen species generation, calcium imbalance, and defective clearance of damaged organelles, ultimately compromising neuronal viability. Pathological protein aggregates, such as α-synuclein in Parkinson's disease, β-amyloid and tau in Alzheimer's disease, and misfolded superoxide dismutase 1 and transactive response DNA-binding protein 43 in amyotrophic lateral sclerosis, further aggravate mitochondrial stress, establishing self-perpetuating cycles of neurotoxicity. Such mitochondrial defects underscore mitochondria as a convergent pathogenic hub and a promising therapeutic target for neuroprotection. Intermediate filaments (IFs), traditionally viewed as passive structural elements, have recently gained attention for their roles in cytoplasmic organization, mitochondrial positioning, and energy regulation. Emerging evidence indicates that IF-mitochondria interactions critically influence organelle morphology and function in neurons. This review highlights the multifaceted involvement of mitochondrial dysfunction and IF dynamics in neurodegeneration, emphasizing their potential as targets for novel therapeutic strategies.},
}

Humans
*Mitochondria/metabolism/pathology
Animals
*Neurodegenerative Diseases/metabolism/pathology
*Intermediate Filaments/metabolism/pathology
*Signal Transduction
Neurons/metabolism/pathology

@article {pmid41464650,
year = {2025},
author = {Sonaglioni, A and Nicolosi, GL and Lombardo, M and Baravelli, M and Muti, P},
title = {Comparative Meta-Analysis of Left Ventricular Mechanics in Takotsubo Syndrome and Anterior STEMI Due to Left Anterior Descending Artery Occlusion.},
journal = {Journal of clinical medicine},
volume = {14},
number = {24},
pages = {},
doi = {10.3390/jcm14248748},
pmid = {41464650},
issn = {2077-0383},
support = {N/A//Ministero della Salute/ ; },
abstract = {Background: Takotsubo syndrome (TTS) often mimics anterior ST-elevation myocardial infarction (STEMI) caused by left anterior descending (LAD) occlusion, yet the two entities differ fundamentally in pathophysiology and mechanical behavior. Two-dimensional speckle-tracking echocardiography (2D-STE) enables detailed assessment of left ventricular (LV) deformation beyond conventional ejection fraction (LVEF). This meta-analysis compared global and regional LV strain patterns in TTS versus LAD-related anterior STEMI during the acute phase. Methods: A systematic search of PubMed, Embase, and Scopus through October 2025 identified observational case-control studies directly comparing TTS and angiographically confirmed anterior STEMI, with LV mechanics assessed by 2D-STE. Random-effects models were used to pool standardized mean differences (SMDs) for LVEF; global longitudinal strain (GLS); apical, mid-ventricular, and basal longitudinal strain (ALS, MLS, BLS); and global radial strain (GRS). Heterogeneity (I[2]), publication bias (funnel plots, Egger's test), meta-regression, and leave-one-out sensitivity analyses were performed. Results: Six studies comprising 221 TTS and 290 anterior STEMI patients met the inclusion criteria. TTS patients were older, predominantly female, and had fewer metabolic risk factors, while LV size was comparable. LVEF was significantly lower in TTS (SMD -1.149; 95% CI -2.20 to -0.10; p = 0.032), with stable findings across sensitivity analyses and no evidence of publication bias. GLS, ALS, MLS, and BLS showed only a non-significant trend toward greater impairment in TTS, and these comparisons were limited by marked inter-study heterogeneity. In contrast, GRS was significantly and consistently more reduced in TTS (SMD -1.284; 95% CI -1.59 to -0.98; p < 0.001), indicating more profound global radial dysfunction. Meta-regression showed no significant influence of demographic factors or vendor-specific software on LVEF or GLS differences. Conclusions: Compared with LAD-related anterior STEMI, TTS is associated with more severely depressed LVEF and markedly impaired radial strain, while longitudinal strain differences remain inconclusive and suggest only a potential trend toward greater dysfunction, reflecting the limited and heterogeneous evidence. These findings are consistent with diffuse, stress-induced myocardial stunning in TTS and suggest that 2D-STE may aid differentiation between stress cardiomyopathy and ischemic infarction in the acute setting, although longitudinal strain parameters should be interpreted cautiously and regarded as hypothesis-generating.},
}

@article {pmid41464612,
year = {2025},
author = {Klumb, S and Haley, L and Hathaway, C and Irby, J and Cheng, J and Rumley, J},
title = {Degenerative Cervical Myelopathy Diagnosis and Its Differentiation from Neurological Mimics, MS and ALS: A Literature Review.},
journal = {Journal of clinical medicine},
volume = {14},
number = {24},
pages = {},
doi = {10.3390/jcm14248711},
pmid = {41464612},
issn = {2077-0383},
abstract = {Multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and degenerative cervical myelopathy (DCM) share features that may confound diagnosis. DCM is caused by degenerative changes in the cervical spine leading to spinal cord compression and injury, resulting in significant disability. Misdiagnosis of DCM for a similar neurological condition can lead to further spinal cord damage from delayed surgical treatment. Here we review the diagnostic criteria, clinical signs and symptoms, and imaging typical for DCM, and two of its clinical mimics, MS and ALS. Shared motor symptoms of all three conditions can make diagnosis difficult, especially early in disease course. Noteworthy differences include neck and shoulder pain in DCM, visual disturbances in MS, and bulbar symptoms and the absence of sensory deficits in ALS. In DCM and MS, MRI is used to support the diagnosis, with specific findings on MRI that differentiate DCM versus MS. In ALS, MRI is used to rule out differential diagnoses. Applying the diagnostic criteria for MS and ALS, as well as understanding the typical presentation and MRI findings of DCM, is crucial. Through discussion of these conditions, this review aims to help limit misdiagnosis rates, allowing for early management, which can improve long-term patient outcomes.},
}

@article {pmid41463333,
year = {2025},
author = {Tendero-Lopez, D and Dominguez, M and Aguilar-Aragon, M},
title = {Modelling Neural Disorders with the D. melanogaster Larval Peripheral and Adult Dopaminergic Systems.},
journal = {Biomolecules},
volume = {15},
number = {12},
pages = {},
doi = {10.3390/biom15121677},
pmid = {41463333},
issn = {2218-273X},
mesh = {Animals ; *Drosophila melanogaster/metabolism ; Larva/metabolism ; *Disease Models, Animal ; Humans ; *Dopamine/metabolism ; *Dopaminergic Neurons/metabolism/pathology ; *Nervous System Diseases/metabolism ; Parkinson Disease/metabolism ; },
abstract = {The increasing prevalence of neurological disorders highlights the need for disease animal models to elucidate the underlying biomolecular and cellular mechanisms of disease and to facilitate studies aimed at developing effective treatments. The fruit fly Drosophila melanogaster, at both larval and adult stages, can serve as an effective model for different human-relevant neurological diseases. Larvae are particularly suited for studying peripheral nervous system disorders, such as Charcot-Marie-Tooth and amyotrophic lateral sclerosis, while adults enable investigations of higher-order cognitive functions and age-related conditions, including Parkinson's disease and depression-like behaviours. Combining larval and adult models offers a complementary framework to dissect the biomolecular pathways of neurological disorders and accelerate preclinical research.},
}

Animals
*Drosophila melanogaster/metabolism
Larva/metabolism
*Disease Models, Animal
Humans
*Dopamine/metabolism
*Dopaminergic Neurons/metabolism/pathology
*Nervous System Diseases/metabolism
Parkinson Disease/metabolism

@article {pmid41463293,
year = {2025},
author = {Xie, V and Franco, MC and Martin, LJ},
title = {Human Mutant Dynactin Subunit 1 Causes Profound Motor Neuron Disease Consistent with Possible Mechanisms Involving Axonopathy, Mitochondriopathy, Protein Nitration, and T-Cell-Mediated Cytolysis.},
journal = {Biomolecules},
volume = {15},
number = {12},
pages = {},
doi = {10.3390/biom15121637},
pmid = {41463293},
issn = {2218-273X},
support = {1R01NS107417-04A1/NH/NIH HHS/United States ; },
mesh = {Animals ; *Dynactin Complex/genetics/metabolism ; Humans ; Mice ; *Motor Neuron Disease/genetics/pathology/metabolism ; *Mitochondria/metabolism/pathology ; Motor Neurons/metabolism/pathology ; *T-Lymphocytes/metabolism/immunology/pathology ; Axons/pathology/metabolism ; Mutation ; Spinal Cord/pathology/metabolism ; },
abstract = {Mutations in the gene encoding the p150 subunit of the dynactin complex (DCTN1) are linked to amyotrophic lateral sclerosis, spinal and bulbar muscular atrophy, and Perry syndrome. These neurodegenerative diseases can cause muscle weakness and atrophy, parkinsonian-like symptoms, and paralysis. To examine the evolution of neuropathology caused by a mutation in DCTN1 and cellular mechanisms of disease for therapeutic discovery, we characterized mice expressing either human wildtype or mutant (G59S) DCTN1. Neuron-specific expression of mutant, but not wildtype, DCTN1 caused fatal age-related paralytic disease and motor neuron (MN) degeneration in the spinal cord with axonopathy and chromatolysis without apoptotic morphology. MNs became positive for cleaved caspase-3, cleaved caspase-8, and nitrated Hsp90. Mitochondria accumulated and appeared fragmented and dysmorphic and then were lost. This pathology was accompanied by invasion of CD95- and CD8-positive mononuclear T cells into the ventral horn and accumulation of TNFα and IL9. Administration of the mitochondrial division inhibitor-1 (Mdivi-1) protected MNs and extended the lifespan of G59S-DCTN1 mice. A mitochondrial permeability transition pore inhibitor also extended lifespan. Thus, mutant DCTN1 causes degeneration of MNs associated with axonopathy, mitochondriopathy, nitrative stress, and caspase activation. It appears as retrograde neurodegeneration and inflammatory T-cell-like cytolysis. Mitochondria are possible therapeutic targets in DCTN1-linked neurodegenerative disorders.},
}

Animals
*Dynactin Complex/genetics/metabolism
Humans
Mice
*Motor Neuron Disease/genetics/pathology/metabolism
*Mitochondria/metabolism/pathology
Motor Neurons/metabolism/pathology
*T-Lymphocytes/metabolism/immunology/pathology
Axons/pathology/metabolism
Mutation
Spinal Cord/pathology/metabolism

@article {pmid41463070,
year = {2025},
author = {Goyal, NA and Andrews, JA and Oskarsson, BE and Wiedau, MH and Kasarskis, EJ and Forrest, BD and Zhang, R and Bracci, PM and Davis, MW and Azhir, A and McGrath, MS},
title = {Quantitative Measures of Time to Loss of 15% Vital Capacity and Survival Extension in Slowly Progressive Amyotrophic Lateral Sclerosis (ALS) Patients Treated with the Immune Regulator NP001 Suggests an Immunopathogenic Subset of ALS.},
journal = {Biomedicines},
volume = {13},
number = {12},
pages = {},
doi = {10.3390/biomedicines13123060},
pmid = {41463070},
issn = {2227-9059},
support = {Neuvivo - NP001//Ari Azhir/ ; },
abstract = {Background/Objectives: Overall survival in patients with amyotrophic lateral sclerosis (ALS) is linked to the rate of predicted respiratory vital capacity (PVC) loss. The objective of this study was to test whether changes in quantitative PVC measures over time linked to survival would define an immunopathogenic subset of ALS responsive to NP001, a regulator of innate immunity. Methods: In a retrospective study, data from intent-to-treat (ITT) population of two phase 2 trials of NP001 were evaluated for over time changes in PVC, time-to-event (TTE) loss of 15% PVC and PVC change from baseline, as linked to survival outcomes in patients treated with NP001 vs placebo. Results: Treatment with NP001 was associated with a significantly lower risk compared to placebo in the loss of 15% PVC over six months (p = 0.01; HR = 0.60, 95% CI: 0.39, 0.90). Data from the two trials were subsequently divided by a disease progression rate (DPR) value of 0.50 units of ALSFRS-R score lost per month for analysis of slow vs. rapid disease. In ALS patients with slowly progressive disease (DPR < 0.50), TTE PVC changes from baseline were slowed (p < 0.0005) and overall survival extended significantly (18.5 months) in NP001-treated vs. placebo groups. The rapidly progressive ALS patients (DPR ≥ 0.50) treated with NP001 showed no significant difference in PVC change or survival from the placebo group. Conclusions: These hypothesis-generating observations suggest that inflammation might play a significant role in the loss of respiratory function in a major subset of ALS patients.},
}

@article {pmid41462986,
year = {2025},
author = {Vauti, F and Eilers, L and Kroll, A and Köster, RW},
title = {Genomic Organization, Evolutionary Conservation and Expression of Ataxin-2 and Ataxin-2-like Genes Underscore the Suitability of Zebrafish as a Model Organism for SCA2 and Related Diseases.},
journal = {Biomedicines},
volume = {13},
number = {12},
pages = {},
doi = {10.3390/biomedicines13122974},
pmid = {41462986},
issn = {2227-9059},
support = {11-76251- 2714/2024 (ZN4545)//This project was supported by the BrightBrain initiative, which is funded by zu-kunft.niedersachsen, the joint science funding program of the Lower Saxony Ministry of Science and Culture and the Volkswagen Foundation/ ; },
abstract = {Background/Objectives: The Ataxin-2 protein (ATXN2) plays an essential role in RNA metabolism and many cellular processes. Dysregulation or mutation of the Ataxin-2 gene (ATXN2) can lead to neurodegenerative diseases such as spinocerebellar ataxia type 2 (SCA2) and amyotrophic lateral sclerosis (ALS). Despite numerous efforts in this field in other animal models, little is known about Atxn2 in zebrafish. In this study, we aim to investigate the potential suitability of zebrafish as a model for Atxn2-related diseases by performing basic analyses on Atxn2. Methods: We performed a bioinformatic protein analysis of Atxn2 from zebrafish and its paralog Atxn2l in relation to human and other vertebrate homologues. Based on a structural analysis of the atxn2 and atxn2l genes, the expression of the predicted transcripts was detected by RT-PCR and the spatiotemporal expression pattern was determined by whole-mount in situ hybridization. Results: We found similarities between the protein sequences of Atxn2 and Atxn2l in zebrafish and their functional domains with those of orthologs in humans and other vertebrates. The predicted transcripts of atxn2 and atxn2l were experimentally verified and their spatiotemporal expression patterns were determined during zebrafish development. Splicing variants were detected for both genes, suggesting a different role for the isoforms in different tissues. Conclusions: These findings provide new insights into the atxn2 and atxn2l genes, suggesting the zebrafish as a suitable animal model for functional studies and research on disease modeling of SCA2 and ALS.},
}

@article {pmid41462890,
year = {2025},
author = {Fajkić, A and Belančić, A and Lam, YW and Rački, V and Pilipović, K and Janković, T and Mežnarić, S and Mršić-Pelčić, J and Vitezić, D},
title = {Novel Translational Concept: Axon-to-Muscle Exosomal Signaling as an Emerging Therapeutic Target in Spinal Muscular Atrophy.},
journal = {Biomedicines},
volume = {13},
number = {12},
pages = {},
doi = {10.3390/biomedicines13122876},
pmid = {41462890},
issn = {2227-9059},
abstract = {Spinal muscular atrophy (SMA) has transitioned from a uniformly fatal disease to a treatable condition, yet incomplete neuromuscular recovery underscores the limits of current SMN-restorative therapies. Emerging data implicate disrupted axon-to-muscle exosomal signaling as an important, overlooked driver of residual dysfunction. Exosomes, nanovesicles mediating bidirectional neuronal-muscular communication, carry synaptic organizers, trophic factors, and microRNAs essential for neuromuscular junction integrity. SMN deficiency alters exosomal biogenesis and cargo, leading to loss of agrin-MuSK signaling, impaired β-actin transport, and muscle atrophy. Comparative insights from amyotrophic lateral sclerosis and muscular dystrophy reveal that stem-cell-derived or engineered exosomes restore synaptic stability, enhance regeneration, and cross biological barriers safely. Thus, we speculate herein on a translational model integrating exosome-based therapies with existing genetic interventions to achieve durable, systems-level recovery in SMA. Exosomal profiling may further yield minimally invasive biomarkers for disease monitoring and treatment optimization, establishing vesicle-mediated communication as a novel therapeutic axis in neuromuscular medicine.},
}

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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