@article {pmid42239172,
year = {2026},
author = {Matthews, AM and Whiteley, AM},
title = {The retroelement-derived human protein PEG10 is a regulator of mRNA splicing in neurons.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.05.21.727000},
pmid = {42239172},
issn = {2692-8205},
abstract = {UNLABELLED: Retroelements, including retrotransposons, endogenous retroviruses, and their fragments, as well as rare co-opted or domesticated retroelements, can contribute to neurodegenerative disorders and aging through modulation of gene expression and induction of neuroinflammation. Paternally Expressed Gene 10 (PEG10) is a retroelement-derived human gene that has recently been identified as a putative driver of Amyotrophic Lateral Sclerosis (ALS) and Angelman's Syndrome. PEG10 has been reported to bind nucleic acid and undergoes a complex self-processing pathway that results in gene expression changes when the protein accumulates in cells. Here, we report that PEG10 has selectivity for binding U/G-rich RNAs and influences widespread gene expression changes. PEG10 overexpression mimics the loss of TDP-43 in broad changes to gene expression, including dysregulation of mRNA splicing pathways. Specific changes to mRNA splicing were largely unique between TDP-43 knockdown and PEG10 overexpression, as classic TDP-43 targets including STMN2 were not altered by PEG10. Instead, we identified a unique role for PEG10 in regulating splicing of neuregulin 3 (NRG3) , a ligand for the neuronal receptor ERBB4. In SH-SY5Y cells and in human neurons overexpressing PEG10, NRG3 protein levels were decreased along cellular processes, suggesting that these cells are less competent at signaling through the NRG3/ERBB4 axis. Using human patient data, we observed similar changes to NRG3 splicing in UBQLN2 -mediated ALS, where PEG10 is accumulated, as well as in some cases of sporadic ALS. In conclusion, the retroelement-derived gene PEG10 plays an unexpected role in regulating splicing of neuronal transcripts, which mimics some of the transcript changes observed in human ALS patient samples. Ultimately, this work has implications for the study of PEG10, and mRNA splicing in neurological diseases associated with elevated PEG10 abundance.

HIGHLIGHTS: PEG10 NC expression influences abundance of transcripts implicated in ALS PEG10 NC expression leads to an exon skipping event in neuregulin 3 (NRG3) NRG3 expression is decreased along dendrites of PEG10 NC expressing human neuronsExpression of PEG10 NC mimics changes observed in human ALS.},
}

@article {pmid42239283,
year = {2026},
author = {Reedich, E and Chen, YT and Imhoff-Manuel, R and Li, D and Manuel, M},
title = {Chronic diazepam reveals excessive homeostatic gain in SOD1 [G93A] mouse spinal motoneurons.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.05.16.725609},
pmid = {42239283},
issn = {2692-8205},
abstract = {Motoneurons are under strong pressure to maintain stable motor output throughout an individual life, through homeostatic regulation of their electrical properties. Dysregulated spinal motoneuron excitability has long been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Recent work in SOD1 [G93A] mice suggests that the homeostatic response of motoneurons becomes dysregulated as cellular processes are disrupted by the disease, causing fluctuations in motoneuron electrical properties. Yet, few studies directly test whether ALS motoneurons respond differently than wild type motoneurons to a common chronic perturbation. Here, we used in vivo electrophysiology to test whether motoneurons from pre-symptomatic SOD1 [G93A] mice modulate excitability differently than wild type motoneurons in response to the same homeostatic perturbation: chronic inhibition exerted by the benzodiazepine diazepam. Using linear mixed-effects statistical models, we assessed whether diazepam treatment differentially modulated passive properties, firing behavior, spike properties, and/or synaptic inputs in SOD1 [G93A] versus wild type motoneurons. We identified a significant genotype × treatment interaction effect selectively for properties related to passive membrane integration and spike initiation, including membrane time constant, peak input resistance, and recruitment current. In contrast, firing gain, spike waveform characteristics, and synaptic inputs were largely unaffected. These findings indicate that sustained inhibitory perturbation selectively triggered overactive intrinsic compensatory mechanisms in SOD1 [G93A] motoneurons rather than inducing widespread changes in firing or synaptic transmission. Together, our results provide direct evidence for over-active homeostatic control of motoneuron excitability and support a view of motoneuron dysfunction in ALS as a problem of altered feedback regulation rather than simply hyper- or hypo-excitability.},
}

@article {pmid42240799,
year = {2026},
author = {Saadat, A and Jasińska, M and Cedro, B and Piekarska, A and Flis, DJ and Ziółkowski, W and Pyza, E},
title = {Synaptic Plasticity Changes in the Somatosensory Cortex During Amyotrophic Lateral Sclerosis Progression and After Swim Training in SOD1-G93A Mice.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42240799},
issn = {1559-1182},
abstract = {Somatosensory cortex hyperexcitability is present in the pre-symptomatic stage of amyotrophic lateral sclerosis (ALS) as evidenced by brain recordings, but its synaptic basis remains unclear. We examined synaptic plasticity, the density of asymmetric (putative excitatory) and symmetric (putative inhibitory) synapses, dendritic spine morphology, and the putative excitatory/inhibitory (E/I) ratio in the B2 barrel of the somatosensory cortex in female mice of an ALS mouse model. Transgenic mice, B6SJL-Tg (SOD1*G93A)1Gur/J, were used as the ALS model, and wild-type (WT) B6SJL/F1 mice served as controls. ALS mice were allocated to experimental groups based on disease stage (pre-symptomatic, onset, or terminal) and training condition (swim-trained or untrained). Swim training was applied after the first onset of symptoms (clinical score 1). We analyzed and quantified the density of asymmetric (putative excitatory) and symmetric (putative inhibitory) synapses and E/I ratios using serial electron micrographs to understand how these parameters change during disease progression and whether swim training influences this process. Our results showed stage-dependent alterations in asymmetric (putative excitatory) and symmetric (putative inhibitory) synaptic architecture in ALS. The obtained data showed an increase in the excitatory synaptic density in the presymptomatic ALS mice. This finding is consistent with previous reports of early cortical hyperexcitability and may reflect structural alterations associated with an initial increase in excitatory synapses before disease onset. Importantly, we report here an increase in inhibitory synapses at disease onset. TEM-based synaptic density quantification revealed reduced excitatory synapse density in the B2 barrel of the somatosensory cortex of trained ALS mice compared to WT controls, alongside a trend toward a reduced putative excitatory/inhibitory synaptic ratio. However, as no significant differences were detected between trained and untrained ALS mice, the contribution of swim training to these alterations remains unclear. Notably, swim training was not associated with detectable adverse effects on somatosensory cortex ultrastructure, excitatory synapse density, or the putative excitatory/inhibitory ratio, supporting previous observations that swim training is well tolerated under these experimental conditions. To our knowledge, these results provide the first TEM-based ultrastructural characterization of synaptic architecture in swim-trained SOD1-G93A mice, although further studies are needed to establish the underlying mechanisms and therapeutic relevance in ALS.},
}

@article {pmid42241089,
year = {2026},
author = {Alister, M and Ransom, KJ and Perfors, A},
title = {When a helpful bias is unhelpful: Limitations in reasoning about random and deliberately misleading evidence.},
journal = {Journal of experimental psychology. General},
volume = {},
number = {},
pages = {},
doi = {10.1037/xge0001939},
pmid = {42241089},
issn = {1939-2222},
support = {//Australian Defence Science and TechnologyGroup/ ; //Australian Government/ ; },
abstract = {Social information aids learning: By making assumptions about other people's knowledge and intentions, people can draw strong and accurate inferences from limited data. In this study, we systematically tested people's ability to reason from information providers with different intentions. The task was an adaptation of Shafto et al.'s (2014) rectangle game, where learners guessed a rectangle's size and location based on provided clues. We examined reasoning based on information from four types of providers: a helpful provider, a provider who sampled randomly, and two misleading providers (who could mislead but not lie). We also varied whether people were given a cover story describing the provider in advance or whether they could infer how helpful a provider was based on what the provider shared. Participants learned efficiently from helpful providers, aligning closely with the predictions of a normative Bayesian model, even without a cover story. However, while people usually recognized unhelpful providers, they struggled to identify and respond appropriately to misleading strategies. Overall, our results suggest a helpful bias: In our task, participants assumed helpful intent unless given explicit feedback, and even then, they did not fully adjust in line with Bayesian predictions. People also struggled to overcome this bias when learning from randomly sampled information, especially when they had experience being an information provider themselves (Experiment 3). (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}

@article {pmid42241188,
year = {2026},
author = {Chikktimmegowda, D and Keerthipriya, MS and Vengalil, S and Nashi, S and Baskar, D and Mol, JJ and Joseph, S and Aishwarya, SY and Binesha, PB and Kumar, BD and Chandrika, H and Mehta, M and Roshan, A and Belur, YK and Nalini, A and Thomas, PT},
title = {The Unfinished Breath: Caregiver Perceptions of Terminal Events and Gaps in Amyotrophic Lateral Sclerosis Care in India.},
journal = {Annals of Indian Academy of Neurology},
volume = {},
number = {},
pages = {},
doi = {10.4103/aian.aian_1234_25},
pmid = {42241188},
issn = {0972-2327},
abstract = {BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with a high symptom burden and limited survival. Little is known about the terminal phase experiences, symptom prevalence, and end-of-life care patterns of people with ALS (PALS) in India. This study aimed to assess terminal events and caregiver-reported outcomes in PALS to identify gaps in ALS care delivery in India.

METHODS: A cross-sectional telephonic survey was conducted among bereaved caregivers of PALS enrolled in the Neuropalliative and Supportive Care project between December 2021 and May 2024. A structured, validated questionnaire was used to collect data on demographics, terminal-phase symptoms, medical interventions, and the nature of death as perceived by primary caregivers. Descriptive statistics and appropriate statistical analyses were performed.

RESULTS: A total of 130 caregivers participated in the survey; the majority (57.7%) were sons or daughters. Among the 130 PALS, 76 (58.5%) were men; 56.2% had limb onset and 43.8% had bulbar onset. The mean age at death was 53.5 ± 11.4 years. Most patients (57.7%) died at home, and 29.2% experienced sudden death. Patients who died in the hospital were more likely to be on invasive mechanical ventilation (P < 0.001). The most common terminal symptoms were breathlessness (79.2%), excessive oral secretions (54.6%), followed by anxiety or restlessness (44.6%). Only 20% received bilevel positive airway pressure, and 25.4% were on percutaneous endoscopic gastrostomy. A significant association was found between bulbar onset and assisted feeding (P = 0.002).

CONCLUSIONS: This study highlights the need for proactive, community-integrated palliative care services and emphasizes the urgency of early intervention and caregiver support to improve end-of-life experiences in PALS in India.},
}

@article {pmid42242586,
year = {2026},
author = {Wong, B and Payne, M and Silva, A and Kurniawan, E and Eidman, AS and Pizzo, D and Rajupalem, R and Lenk, GM and Paulo, JA and Khan, T and Eskelinen, EL and Gygi, SP and Brown, NG and Meisler, MH and Mendiola, AS and Gassaway, BM and Ferguson, CJ},
title = {Early-onset neuroinflammation drives neurodegeneration caused by lysosomal PI(3,5)P2 insufficiency.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107467},
doi = {10.1016/j.nbd.2026.107467},
pmid = {42242586},
issn = {1095-953X},
abstract = {Phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] is a lysosomal signaling lipid whose deficiency, caused by mutations in the PIKfyve complex subunits Fig. 4 or VAC14, underlies a spectrum of fatal neurologic diseases including Charcot-Marie-Tooth type 4 J (CMT4J) and amyotrophic lateral sclerosis (ALS). To map the molecular consequences of PI(3,5)P2 insufficiency in the brain, we performed quantitative proteomic and transcriptomic analyses of three mouse lines bearing distinct loss-of-function mutations in Fig. 4 or Vac14, examining the brain at the presymptomatic and end stages. Strikingly, profound neuroinflammation was already present at postnatal day 5 (before significant neurodegeneration), characterized by complement activation, interferon signaling, and parenchymal infiltration of peripheral myeloid cells and T-cells. Isolated mutant microglia exhibited a markedly pro-oxidative transcriptional state with elevated reactive oxygen species, a partly non-cell-autonomous phenotype, being present in microglia from mice with conditional Fig. 4 inactivation in just neurons and astrocytes. Comparison of early (P5) and late (P25) proteomics data revealed that PI(3,5)P2 insufficiency impairs developmental remodeling of the brain proteome: proteins typically upregulated during postnatal maturation failed to accumulate, implicating lysosomal function in neurodevelopment. We identify coordinated elevation of p53, Fas receptor, inflammatory caspases, Gasdermin D, RIPK1, and ZBP1, consistent with multifactorial inflammatory cell death with features of apoptosis, pyroptosis, and necroptosis. Many of the dysregulated proteins are encoded by genes mutated in lysosomal storage disorders, ALS, CMT, Alzheimer's and Parkinson diseases, extending the pathogenic relevance of PI(3,5)P2 insufficiency. Together, these findings establish that early neuroinflammation is a defining - and likely initiating - feature of neurodegeneration caused by disruption of lysosomal PI(3,5)P2.},
}

@article {pmid42243993,
year = {2026},
author = {Hsieh, WC and Lin, CY and Wu, HC and Weng, EF and Wang, SM},
title = {Hyperoside protects against poly-GR-mediated neurodegeneration via regulation of mitochondrial fission and oxidative stress in C9orf72-associated ALS.},
journal = {Chinese medicine},
volume = {21},
number = {1},
pages = {},
pmid = {42243993},
issn = {1749-8546},
support = {MOST 111-2628-B-039- 006-MY3//National Science and Technology Council/ ; CMU114-MF-04//China Medical University, Taiwan/ ; },
abstract = {BACKGROUND: Arginine-rich poly-glycine-arginine (poly-GR), a toxic dipeptide repeat protein generated from C9orf72 hexanucleotide repeat expansion, drives mitochondrial dysfunction, oxidative stress, and neuronal loss in amyotrophic lateral sclerosis (ALS). Hyperoside, a bioactive flavonoid, exhibits antioxidant and cytoprotective properties, but its therapeutic relevance to C9orf72-associated ALS remains unclear.

PURPOSE: To determine whether hyperoside attenuates poly-GR-induced mitochondrial and oxidative injury and improves neuronal survival in cellular and animal models of C9orf72-ALS.

METHODS: A combined in vitro and in vivo experimental study using motor neuron-like cells and an AAV-mediated neonatal mouse model of poly-GR toxicity. NSC34 cells expressing EGFP-GR50 were analyzed for mitochondrial morphology, membrane potential, ROS generation, antioxidant signaling, and apoptosis using confocal microscopy, CellROX/MitoTracker assays, Western blot analysis, and viability testing. For in vivo assessment, neonatal mice received intracerebroventricular AAV9-EGFP-GR50 followed by intraperitoneal hyperoside (10 mg/kg). Survival, cerebral hemisphere length, and cortical NeuN⁺ neuron numbers were quantified.

RESULTS: Poly-GR expression induced pronounced mitochondrial fragmentation, reduced membrane potential, elevated ROS, and suppressed Nrf2/HO-1/GPx4 signaling, accompanied by increased Drp1 and reduced Opa1 expression. Hyperoside reversed these abnormalities by restoring mitochondrial integrity, normalizing the Drp1/Opa1 balance, enhancing Nrf2 nuclear accumulation, and increasing the expression of HO-1 and GPx4. Hyperoside also reduced cleaved caspase-3 and corrected the Bax/Bcl-2 ratio, improving cell viability under basal and oxidative stress conditions. In vivo, hyperoside modestly prolonged survival, increased cerebral hemisphere length, and significantly preserved cortical neuronal numbers in AAV9-EGFP-GR50 mice.

CONCLUSION: Hyperoside mitigates poly-GR-induced neurotoxicity by alleviating excessive mitochondrial fission, strengthening Nrf2-dependent antioxidant defenses, and suppressing apoptosis. These findings support hyperoside as a promising multi-target therapeutic candidate for C9orf72-associated ALS.},
}

@article {pmid42244138,
year = {2026},
author = {Subbotin, D and Voskanyan, A and Borovikov, A and Marakhonov, A and Bobreshova, A and Rosales-Sabino, M and Murtazina, A},
title = {FLNC Complex Structural Variant Causing Distal Myopathy Identified by Family-Based Genome Sequencing.},
journal = {American journal of medical genetics. Part A},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajmg.a.70223},
pmid = {42244138},
issn = {1552-4833},
support = {25-65-00031//Russian Science Foundation/ ; },
abstract = {Distal myopathies (DM) are clinically and genetically heterogeneous neuromuscular disorders, and identifying a molecular genetic cause may remain challenging in a subset of cases. Moreover, DM may be misdiagnosed as hereditary neuropathies due to overlapping clinical features. Here, we report a novel structural variant in FLNC associated with DM identified through genome sequencing (GS). Two affected relatives initially presented independently with referral diagnoses of Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis. Clinical re-evaluation led to a change of the diagnosis to DM. Muscle MRI revealed a consistent pattern of selective muscle involvement characteristic of DM, enabling identification of six affected individuals within the family. GS was performed in seven family members, including six affected individuals and one unaffected relative. The analysis identified an insertion of two inverted fragments derived from the adjacent intron 2 into exon 3 of the FLNC gene. This complex rearrangement was accompanied by short non-templated nucleotide insertions at the junctions and a 3-bp exonic deletion at the insertion site, ultimately resulting in a frameshift. The structural variant was segregated with disease and was confirmed by Sanger sequencing and one Oxford nanopore long-read sequencing. Our findings expand the mutational spectrum of FLNC-associated disorders and highlight the importance of GS combined with a detailed clinical examination for the diagnosis of DM.},
}

@article {pmid42244301,
year = {2026},
author = {Pu, H and Liu, Y and Xu, Z and Fang, J and Song, T and Qin, C and Lu, J and Luo, Y},
title = {Synergistic Control and Resource Utilization of Carbonyl Sulfur (COS) and Hydrogen Sulfide (H2S) over Oxidized K-Mo Materials.},
journal = {Environmental science & technology},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.est.6c05690},
pmid = {42244301},
issn = {1520-5851},
abstract = {Carbonyl sulfide (COS) and hydrogen sulfide (H2S) coexist extensively in industrial waste gases, yet conventional technologies typically address them separately, leaving synergistic control and resource utilization as ongoing challenges. This study presents a novel approach for the synergistic catalytic transformation of COS/H2S into high-value-added methyl mercaptan (CH3SH). Activity results revealed that the oxidized K-Mo/Al-O catalyst, unexpectedly active, outperforms the common sulfided K-Mo/Al-S catalyst. Characterizations suggested that K-Mo/Al-O undergoes in situ reconstruction into the K-intercalated 1T-MoS2 phase (KxMoS2), subsequently transforming into the K-decorated 2H-MoS2 phase (K/MoS2). Structure-activity relationship confirmed KxMoS2 as the key metastable active phase for the generation of CH3SH, where potassium species acted as the primary active site, while Mo oxide/sulfide species played an assistant role. Temperature-programmed surface reaction of reactants (COS/H2/H2S-TPSR) and in situ diffuse reflectance infrared spectroscopy (in situ DRIFTS) elucidated that the reaction mechanism strongly depends on both reaction temperature and the active phase types, i.e., K2MoO4 precursor follows an Eley-Rideal (E-R)-type direct COS hydrogenation pathway, KxMoS2 exhibits a dual-path E-R mechanism (direct COS hydrogenation at low temperature and indirect hydrogenation at medium temperature), and K/MoS2 primarily follows indirect COS hydrogenation at medium temperatures. This work paves a new avenue for synergistic resource utilization of multicomponent sulfur pollutants.},
}

@article {pmid42235092,
year = {2026},
author = {Wolff, AW and Leha, A and Koch, JC and Demleitner, AF and Neuwirth, C and Friede, T and Weber, M and Lingor, P},
title = {Effects of fasudil on disease spreading in ALS - A MUNIX-based post-hoc analysis of the ROCK-ALS trial.},
journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics},
volume = {23},
number = {4},
pages = {e00936},
doi = {10.1016/j.neurot.2026.e00936},
pmid = {42235092},
issn = {1878-7479},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the spread of muscle weakness across body regions. ROCK-ALS was a multicenter, placebo-controlled phase 2 trial assessing the safety, tolerability, and efficacy of the Rho kinase inhibitor fasudil in ALS patients. A key exploratory objective was to evaluate fasudil's effect on the spread of muscle weakness using the Motor Unit Number Index (MUNIX), an established, quantitative electrophysiological biomarker of lower motor neuron integrity. MUNIX was assessed in 10 muscles at baseline, day 26, day 90, and day 180. In the present post-hoc analysis, correlations were assessed between baseline serum biomarkers-neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP)-and baseline clinical measures (ALSFRS-R, slow vital capacity, and MUNIX-10 sum scores) as well as their monthly rates of change, to explore potential prognostic relationships. For the analysis of disease spreading, muscles were classified as newly affected based on MUNIX decline relative to contralateral values or prior measurements, using thresholds of ≥10%, ≥20%, or ≥30%. Out of 118 participants included in the intention-to-treat population, 78 had full MUNIX datasets at baseline, and 67 had at least one follow-up. Baseline MUNIX-10 sum scores correlated with subsequent ALSFRS-R decline, suggesting prognostic value. Additionally, at day 90, fasudil significantly reduced the number of newly affected muscles compared to placebo in a dose-dependent manner over different thresholds. This supports MUNIX as a sensitive biomarker for monitoring disease spreading and demonstrates that fasudil may attenuate the progression of lower motor neuron involvement in ALS. Trial registration number: NCT03792490 (ClinicalTrials.gov); 2017-003676-31 (Eudra-CT).},
}

@article {pmid42235125,
year = {2026},
author = {Talbot, K},
title = {Celebrating a breakthrough for amyotrophic lateral sclerosis.},
journal = {Brain : a journal of neurology},
volume = {149},
number = {6},
pages = {1799-1800},
doi = {10.1093/brain/awag174},
pmid = {42235125},
issn = {1460-2156},
}

@article {pmid42235808,
year = {2026},
author = {De Mori Bajolin, F and Tavazzi, E and Bianchi, AM and Mendez, MO},
title = {Robust end-to-end stratification of amyotrophic lateral sclerosis patients via recurrent variational autoencoder and consensus clustering.},
journal = {Journal of biomedical informatics},
volume = {180},
number = {},
pages = {105059},
doi = {10.1016/j.jbi.2026.105059},
pmid = {42235808},
issn = {1532-0480},
abstract = {OBJECTIVE: This study aims to develop a data-driven methodology for stratifying Amyotrophic Lateral Sclerosis (ALS) patients based on longitudinal disease progression patterns, using a novel deep learning framework that combines a Recurrent Variational Autoencoder (RVA) with consensus clustering to identify clinically meaningful subgroups.

METHODS: The RVA integrates Peephole Long Short-Term Memory networks within the Variational Deep Embedding (VaDE) architecture to simultaneously learn latent representations and cluster assignments from multivariate time-series data. The approach incorporates hyperparameter optimization via prediction strength with two-fold cross-validation, consensus clustering, and internal validation metrics (Silhouette Coefficient, Davies-Bouldin index, Calinski-Harabasz index) for optimal cluster selection. The methodology was validated on simulated data and applied to 3076 ALS patients from the PRO-ACT dataset, using ALSFRS-R total scores, domain subscores, and MiToS staging from the first six months of observation.

RESULTS: Simulation experiments demonstrated that consensus clustering consistently outperformed single-model predictions across all noise levels. Applied to the PRO-ACT real data, the framework identified five distinct patient subgroups. These clusters exhibited distinct progression patterns and statistically significant differences in baseline clinical features, disease onset characteristics, and survival outcomes, with median survival ranging from 12.8 months to 27.5 months.

CONCLUSION: The proposed deep learning framework effectively captures the heterogeneous nature of ALS progression and identifies clinically relevant patient subgroups using routine clinical assessments. The stratification provides a foundation for personalized prognosis, optimized clinical trial design, and tailored therapeutic strategies, representing a practical tool for improving ALS patient management.},
}

@article {pmid42236740,
year = {2026},
author = {Moro-Velazquez, L and Wang, H and Gunzler, A and Rao, M and Butala, AA and Clawson, L and Ravichandran, V},
title = {HeyJay! A corpus of atypical speech for spoken language understanding and automatic speech recognition.},
journal = {Scientific data},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41597-026-07497-5},
pmid = {42236740},
issn = {2052-4463},
support = {No grant number//JHU+Amazon ai2ai faculty award/ ; },
abstract = {Speech technologies, such as automatic speech recognition or spoken language understanding, are not usually adapted to atypical speech, i.e., the speech of people with dysarthria, dysphonia, or another type of speech impairment. That prevents atypical speakers from leveraging speech assistants or other human-machine-interaction-powered platforms, which could make their lives easier or increase their independence. In this article, we present HeyJay!, a new corpus of atypical speech in English language from participants with neurodegenerative disorders, including Parkinson's Disease, or Amyotrophic Lateral Sclerosis. The current corpus version comprises 8,669 utterance recordings, including supervised transcriptions and intent annotations. In this study, we demonstrate the validity of the corpus by applying it to automatic speech recognition, spoken language understanding, and data augmentation tasks. Additionally, the dataset includes speech quality ratings for each participant, performed by expert speech and language pathologists. This corpus, the first one with intent annotation of atypical speech that is publicly available, is intended to create more fair speech technologies for atypical speakers by adapting and improving the state of the art, and to facilitate further research in the field.},
}

@article {pmid42236747,
year = {2026},
author = {Yang, J and Li, J and Hou, X and Zheng, Y and Zhao, Z and Zhou, T and Jing, T and Kong, J and Zhang, G and Guo, Y},
title = {Targeting mitophagy for neuroprotection: mechanisms and therapeutic opportunities.},
journal = {npj aging},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41514-026-00424-3},
pmid = {42236747},
issn = {2731-6068},
support = {CSTB2023NSCQ-BHX0119//the Postdoctoral Science Founation Project of the Chongqing Natural Science Foundation/ ; C2024405023//the Natural Science Foundation of Hebei Province/ ; },
abstract = {Mitochondria are essential for neuronal energy production, cellular homeostasis, and overall neuronal function. Due to their high metabolic demands and limited regenerative capacity, neurons are particularly vulnerable to mitochondrial dysfunction, which leads to ATP depletion, excessive reactive oxygen species (ROS) production, and calcium imbalance-ultimately causing oxidative stress, metabolic disruption, and neuronal death. Mitophagy is a selective process that removes damaged mitochondria through the autophagy-lysosome pathway. As a key mechanism of mitochondrial quality control, mitophagy preserves energy production, limits oxidative damage, and maintains mitochondrial network integrity. This process is regulated by pathways such as PINK1-Parkin and receptor-mediated mechanisms involving BNIP3 and FUNDC1, all of which help sustain cellular health by preventing mitochondrial dysfunction. Impaired mitophagy is a common feature of several neurodegenerative diseases, including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), and Huntington's disease, exacerbating mitochondrial damage and neuronal stress. Emerging therapeutic strategies that target mitophagy-ranging from pharmacological agents and gene therapies to dietary interventions-show promise in restoring mitochondrial quality and protecting neurons from degeneration. Nevertheless, challenges remain in translating these findings into effective clinical treatments. Mitophagy represents a critical mechanism for preserving neuronal integrity and offers a compelling target for innovative therapies against neurodegenerative disorders.},
}

@article {pmid42237051,
year = {2026},
author = {Tooley, KM and Dawkins, PC},
title = {A lack of robust cross-domain structural priming effects.},
journal = {Memory & cognition},
volume = {},
number = {},
pages = {},
pmid = {42237051},
issn = {1532-5946},
abstract = {Structural priming effects within language (e.g., Bock, 1986) have guided theory and research on structural representation for several decades. Structural priming has also been observed across domains, such as from mathematics to language (e.g., Scheepers et al., 2011), suggesting highly abstract structural representation within the global cognitive system. Experiment 1 investigated how this effect is impacted by a mathematical structural prime that lacks an overt operator, as is the case with exponents. A weak numerical trend toward a math-to-language priming effect was not found to be statistically significant. Experiments 2-3 sought to replicate Scheepers et al.'s (2011) original math to language priming effects in online and in-person settings, respectively. Separately and combined, these experiments failed to yield significant math to language priming effects, despite robust sample sizes. Bayes factor estimates suggest a null effect was more likely than a priming effect in the combined dataset. These results highlight the fact that cross-domain structural priming is understudied and underspecified, leading to difficulty planning and implementing the types of studies needed to establish when and how abstract structural representations persist across cognitive domains. Recommendations for future research include increasing item numbers and exploring methodologies that measure processing as well as behavioral responses.},
}

@article {pmid42237462,
year = {2026},
author = {Iftesum, M and Sahoo, GR and Sheikh, E and Srivastava, M and Roy, S and Shukla, HD and Biswal, NC and Gartia, MR},
title = {Machine Learning-Integrated Raman Spectroscopy Identifies Race-Associated Biochemical Signatures in Prostate Cancer.},
journal = {Journal of biophotonics},
volume = {19},
number = {6},
pages = {e70293},
doi = {10.1002/jbio.70293},
pmid = {42237462},
issn = {1864-0648},
support = {R35GM150564/GM/NIGMS NIH HHS/United States ; R24GM146107/GM/NIGMS NIH HHS/United States ; R35GM151218/GM/NIGMS NIH HHS/United States ; 2045640//National Science Foundation/ ; },
abstract = {Black men experience disproportionately higher prostate cancer incidence and mortality, yet the underlying biochemical contributors remain unclear. In this study, we integrate Raman spectroscopy with advanced multivariate and machine-learning methods to characterize molecular differences in clinical formalin-fixed, paraffin-embedded (FFPE) prostate tissues from Black and White patients. Raman spectra were corrected using ICA-PLS, wavelet-denoised, and unmixed with Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) to quantify cellular components. Random forest (RF) models were trained on denoised spectra to classify cancer versus control tissues. MCR-ALS revealed elevated protein, collagen, lipid, and nucleic acid signatures in tumors from Black patients, aligning with clinically observed aggressive disease phenotypes. RF classification achieved > 90% accuracy, 95% sensitivity, 85% specificity, and an AUC > 0.96, demonstrating robust diagnostic performance. These findings show that Raman spectroscopy integrated with computational analysis provides a powerful label-free approach to probe biochemical drivers of racial disparities in prostate cancer.},
}

@article {pmid42237527,
year = {2026},
author = {Zoubi, M and Weydt, P and Kobeleva, X},
title = {Attentional Function in Patients With Amyotrophic Lateral Sclerosis is Moderated by Age and Education.},
journal = {Brain and behavior},
volume = {16},
number = {6},
pages = {e71511},
doi = {10.1002/brb3.71511},
pmid = {42237527},
issn = {2162-3279},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/psychology ; Female ; Male ; *Executive Function/physiology ; Middle Aged ; *Attention/physiology ; Aged ; Educational Status ; Age Factors ; Reaction Time/physiology ; Neuropsychological Tests ; Adult ; },
abstract = {PURPOSE: Besides motor brain regions, amyotrophic lateral sclerosis (ALS) affects non-motor regions such as front temporal regions, affecting various cognitive domains.

METHOD: We performed a behavioral study using the attention network test (ANT) to examine two components of attention (alerting, executive condition) and two degrees of difficulty (conflict condition) in 27 patients with ALS with no reported symptoms suggestive of cognitive impairment and 26 matched control participants.

FINDINGS: Using a modified ANT that accounted for ALS-induced motor impairment by focusing on relative reaction times, we could demonstrate its feasibility even in severely paralyzed patients. Relative reaction time differences were comparable to controls, demonstrating the task's ability to correct for motor bias. When focusing on relative reaction times, in both groups we found intact executive and conflict effects. Furthermore, ALS patients had comparable task accuracies when reacting to congruent and incongruent easy targets. However, the task accuracy of ALS patients was significantly lower compared to controls when reacting to the incongruent hard target. This effect was enhanced by the interaction effect of ALS diagnosis and age.

CONCLUSION: Our results suggest a significant interaction between age and ALS pathology, potentially leading to a breakdown of cognitive resources at higher levels of executive demand. We hypothesize that subclinical executive vulnerability in ALS patients becomes apparent when additional detrimental factors, such as aging, are present in patients. While we did not test co-pathologies in our cohort, co-occurring neurodegenerative or vascular processes might have contributed to this result. Our findings highlight the importance of cognitive screening for ALS patients above 60 years, even in the absence of subjective and collateral history of cognitive impairment.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/psychology
Female
Male
*Executive Function/physiology
Middle Aged
*Attention/physiology
Aged
Educational Status
Age Factors
Reaction Time/physiology
Neuropsychological Tests
Adult

@article {pmid42237658,
year = {2026},
author = {Vesevick, DR and Ghosh, S and Kalmes, A and Ozdinler, PH and Gautam, M},
title = {Neuroprotective Effects of RNS60 in TDP-43 Pathology-Associated Amyotrophic Lateral Sclerosis.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70289},
pmid = {42237658},
issn = {1097-4598},
support = {//Revalesio/ ; //Queen B Foundation/ ; //A Long Swim/ ; },
abstract = {INTRODUCTION: TDP-43 pathology is broadly observed in the cerebral cortex of patients with amyotrophic lateral sclerosis (ALS). RNS60, an experimental treatment for acute ischemic stroke and ALS, enhanced mitochondrial biogenesis and function in other preclinical models. We investigated whether RNS60 improved mitochondrial stability and upper motor neuron (UMN) health in a TDP-43 mouse model of ALS.

METHODS: prpTDP-43[A315T]-UeGFP mice, in which UMNs express green fluorescent protein (eGFP), and WT-UeGFP mice were treated with RNS60 or placebo intraperitoneally every other day from post-natal day (P) 30 until P90. Astrogliosis and microgliosis in brain and spinal cord were quantified by immunocytochemistry. Mitochondrial ultrastructure was studied via electron microscopy, and mitochondrial function was assessed using flow cytometry. Neuromuscular junction (NMJ) integrity was assessed in gastrocnemius, tibialis, and diaphragm muscles.

RESULTS: RNS60 treatment reduced defective mitochondria in UMNs (prpTDP-43[A315T] + vehicle: 53.2% ± 0.71%; prpTDP-43[A315T] + RNS60: 19.6% ± 1.4%, p = 0.0001) and spinal motor neurons (prpTDP-43[A315T] + vehicle: 70.1% ± 0.4.48%; prpTDP-43[A315T] + RNS60: 33.5% ± 4.43%, p = 0.001). It increased mitochondrial membrane polarization (prpTDP-43[A315T]-UeGFP + vehicle: 7184 ± 1689 mean intensity; prpTDP-43[A315T]-UeGFP+RNS60: 22120 ± 4818 mean intensity, p = 0.032), reduced the extent of astrogliosis and microgliosis in motor cortex and spinal cord, protected UMNs compared to placebo, and enhanced the proportion of intact NMJs in leg and diaphragm muscles (prpTDP-43[A315T]-UeGFP + vehicle: 29.6% ± 3.6%; prpTDP-43[A315T]-UeGFP + RNS60: 64.3% ± 4.4%, p = 0.0002).

DISCUSSION: These results suggest that RNS60 treatment promotes motor neuron health in ALS by protecting mitochondrial structure and function, preserving NMJ integrity, and reducing gliosis.},
}

@article {pmid42237814,
year = {2026},
author = {Kulkarni, NP and Thulasidharan, A and Soory, A and Goel, P and Sarkar, S and Kelkar, V and Ratnaparkhi, GS},
title = {Fos regulates age-dependent neuroinflammation in VAPBALS.},
journal = {Disease models & mechanisms},
volume = {},
number = {},
pages = {},
doi = {10.1242/dmm.052810},
pmid = {42237814},
issn = {1754-8411},
support = {2023/SL03//EMSTAR/ ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive loss of motor function. We have developed a Drosophila model of ALS8 (VAPBP58S) using CRISPR/Cas9 genome editing. VAPB is an ER-based adapter protein associated with and regulating intracellular membrane:membrane contact sites. VAPB P58S flies show progressive age-dependent motor deficits and a shortened lifespan, paralleling features of the human disease. VAPBP58S brains exhibit age-dependent neuroinflammation, as measured by whole-transcriptome quantitative mRNA sequencing, suggesting a broad, low-grade enhancement of signalling across multiple immune pathways (Toll, IMD, Jak-STAT, and Jun-kinase). We implicate glial cells in the brain as the site of brain inflammation and identify Drosophila Fos (Kayak) as a key modulator of age-dependent inflammation. In accordance, we find that overexpression of wild-type kayak or its dominant-active variant kayakK357R in glia reduces inflammation and, concomitantly, improves motor function. In contrast, knockdown of glial kayak accelerates age-dependent deterioration of motor function and enhances neuroinflammation. Our study underscores the roles of glial-modulated brain inflammation in dictating ALS8 progression and identifies kayak as a central negative regulator of neuroinflammation in disease.},
}

@article {pmid42237817,
year = {2026},
author = {Biondi, A and Gray, E and Aggreh, M and Jones, E and Collingwood, A and Knox, L and Bredin, A and Setters, D and Talbot, K and Al-Chalabi, A},
title = {The Motor Neuron Disease Register for England, Wales, and Northern Ireland: Protocol for a Population Register.},
journal = {JMIR research protocols},
volume = {15},
number = {},
pages = {e86458},
doi = {10.2196/86458},
pmid = {42237817},
issn = {1929-0748},
abstract = {BACKGROUND: Despite the existence of several regional registries in the United Kingdom, gaps in geographic coverage have limited the ability to produce accurate national estimates of incidence, prevalence, and regional variation for motor neuron disease (MND). To address these challenges, a comprehensive national register encompassing England, Wales, and Northern Ireland was established to support epidemiological studies, health care planning, and clinical research.

OBJECTIVE: The primary objective of the MND Register is to provide a centralized research database aggregating clinical and demographic data to facilitate high-quality research. Secondary objectives include estimating disease incidence and prevalence, identifying regional differences in care and survival, evaluating potential disease clustering, and supporting data linkage and clinical trial recruitment.

METHODS: Eligible patients are those aged 16 years or older with a confirmed MND diagnosis made by a consultant neurologist. Data are collected prospectively and retrospectively through standardized templates, available via Microsoft Access, Microsoft Excel, or the REDCap (Research Electronic Data Capture; Vanderbilt University) web platform, and include up to 34 demographic and clinical variables. Additional self-reported data can be contributed through the Telehealth in MND-Research platform. All data are securely stored in the King's College London Trusted Research Environment, undergo standardized preprocessing, and may be linked to National Health Service and national datasets for epidemiological analyses.

RESULTS: The register includes data on over 11,000 individuals with MND, of whom nearly 7000 are currently alive. Postcode data are available for more than 4300 patients, enabling future geospatial analyses. By October 2025, 60 clinical sites were participating in the register, with around 50 actively submitting data.

CONCLUSIONS: The MND Register represents one of the largest national registries for MND worldwide, providing a robust foundation for epidemiological modeling, clinical research, and health care planning. Ongoing efforts to expand prospective data collection, improve completeness, and integrate digital tools will further enhance its impact and support national and international MND research collaborations.},
}

@article {pmid42238865,
year = {2026},
author = {Bouras, A and Adio, AA and Kumar, R and Phadke, R and Rice, SW and Mody, K and Ndu, A},
title = {Primary Tibiotalocalcaneal Nailing vs Open Reduction and Internal Fixation for Fragility Ankle Fractures in Older Adults: A Markov Model.},
journal = {Foot & ankle orthopaedics},
volume = {11},
number = {2},
pages = {24730114261450956},
pmid = {42238865},
issn = {2473-0114},
abstract = {BACKGROUND: Fragility ankle fractures are common in the elderly population. The cost-effectiveness of primary tibiotalocalcaneal (TTC) nailing compared with open reduction and internal fixation (ORIF) in this population remains unclear.

METHODS: We constructed a Markov cohort model with a 4-year time horizon to compare TTC nailing vs ORIF for fragility ankle fractures in patients aged 75 years and older. All complication rates were derived from the McDonald et al's (2025) systematic review and meta-analysis. Costs were in 2024 US dollars with 3% annual discounting for costs and outcomes. Probabilistic and deterministic sensitivity analyses were performed.

RESULTS: In the base case, ORIF yielded 3.210 quality-adjusted life years (QALYs) (95% credible interval [CrI] 2.785-3.584) at $30 091 (95% CrI $21 426-$40 852) compared with 3.207 QALYs (95% CrI 2.783-3.581) at $33 583 (95% CrI $23 741-$45 447) for TTC nailing. ORIF dominated incremental cost (+$3492, 95% CrI -$11 467 to +$18 273) and incremental QALYs (-0.003, 95% CrI -0.009 to +0.002). The cost differential was driven by the $3000 higher index procedure cost for TTC, partially offset by lower superficial infection (2.1% vs 10.2%). Probabilistic sensitivity analysis demonstrated 33% probability of cost-effectiveness at $100 000/QALY. All 4 scenario analyses confirmed that ORIF dominated.

CONCLUSION: Under McDonald's pooled estimates, TTC nailing is dominated by ORIF for fragility ankle fractures in older adults. The lower superficial infection rate with TTC does not offset its higher procedure cost and higher rates of nonunion and hardware failure. These findings support ORIF as the preferred strategy from a cost-effectiveness standpoint, although the small incremental differences should be considered alongside clinical factors when selecting treatment.

LEVEL OF EVIDENCE: Level IV, economic modeling.},
}

@article {pmid42228326,
year = {2026},
author = {Dey, A and Das, R and Uppal, S},
title = {FUS modulates R-loops by functionally interacting with RNase H1.},
journal = {Human cell},
volume = {39},
number = {6},
pages = {},
pmid = {42228326},
issn = {1749-0774},
mesh = {*RNA-Binding Protein FUS/physiology/metabolism/genetics ; Humans ; *Ribonuclease H/metabolism ; *R-Loop Structures/genetics/physiology ; HeLa Cells ; Transcription, Genetic/genetics ; RNA/metabolism/genetics ; DNA Damage/genetics ; RNA Polymerase II/metabolism ; },
abstract = {R-loops are three-stranded nucleic acid structures consisting of an RNA:DNA hybrid and a displaced single-stranded DNA, typically formed during transcription. Emerging evidence indicates that R-loops are not merely transcriptional byproducts, but serve as functional regulatory structures that influence chromatin organization, transcriptional pausing, and RNA processing. However, dysregulated accumulation of R-loops can induce DNA damage and genomic instability, necessitating precise mechanisms for their regulation. This study aims to elucidate the role of the RNA-binding protein FUS (Fused in Sarcoma), a protein mutated in Amyotrophic Lateral Sclerosis (ALS) and cancer, in modulating R-loop dynamics. Knockdown of FUS in HeLa cells resulted in a significant increase in global R-loop levels, as assessed by immunofluorescence and dot blot assays. Proximity ligation assay (PLA) demonstrated that FUS is in close proximity to R-loops and nascent RNA. Further, FUS was found to interact with RNase H1, a key endonuclease involved in R-loop resolution, in an R-loop dependent manner, as demonstrated by PLA and co-immunoprecipitation assay. Importantly, in vitro assays show that FUS enhances RNase H1-mediated degradation of RNA:DNA hybrids. Moreover, FUS depletion reduces RNase H1 proximity to elongating RNA polymerase II, suggesting altered engagement of RNase H1 with the transcription machinery. These findings highlight a crucial role for FUS-RNase H1 axis in regulating R-loop levels, providing insights into the potential mechanisms underlying R-loop-associated pathologies in neurodegenerative diseases linked to FUS.},
}

*RNA-Binding Protein FUS/physiology/metabolism/genetics
Humans
*Ribonuclease H/metabolism
*R-Loop Structures/genetics/physiology
HeLa Cells
Transcription, Genetic/genetics
RNA/metabolism/genetics
DNA Damage/genetics
RNA Polymerase II/metabolism

@article {pmid42229207,
year = {2026},
author = {Pavey, N and Tu, S and Foster, S and Geevasinga, N and Calma, A and Tsuji, Y and Kiernan, MC and Vucic, S and Menon, P},
title = {Cortical changes in amyotrophic lateral sclerosis: comparing biomarkers of glymphatic flow and cortical excitability.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {190},
number = {},
pages = {2111949},
doi = {10.1016/j.clinph.2026.2111949},
pmid = {42229207},
issn = {1872-8952},
abstract = {OBJECTIVE: The pathogenesis of amyotrophic lateral sclerosis (ALS) involves a multistep process, with a central role for cortical hyperexcitability and misfolded protein accumulation. The glymphatic system mediates clearance of misfolded proteins, yet its role in modulating cortical excitability is unknown. This study aims to determine whether glymphatic dysfunction is associated with cortical hyperexcitability, thereby linking impaired protein clearance to excitotoxic neurodegeneration in ALS.

METHODS: Glymphatic function was assessed using diffusion tensor imaging analysis along perivascular spaces (DTI-ALPS) and correlated with measures of corticomotoneuronal function assessed by transcranial magnetic stimulation (TMS). The DTI-ALPS index and cortical excitability testing were performed in 35 ALS patients and compared to 25 age-matched controls. The DTI-ALPS index was correlated with TMS and clinical measures.

RESULTS: A significant reduction in the DTI-ALPS index was observed in ALS (p = 0.016), along with cortical hyperexcitability evident as shortened cortical silent period (CSP) duration (p = 0.001) and reduced short interval intracortical inhibition (p < 0.001). The DTI-ALPS index significantly correlated with CSP duration (R = 0.48, p = 0.027). The DTI-ALPS index was significantly reduced in ALS participants with mild functional impairment. The possibility that reduced DTI-ALPS index represents an epiphenomenon of tract degeneration cannot be completely excluded.

CONCLUSION: This study identified a potential association between impaired glymphatic clearance and disrupted GABAB-mediated cortical inhibition, suggesting that glymphatic dysfunction may play a role in the neurodegenerative cascade in ALS.

SIGNIFICANCE: Glymphatic dysfunction may be associated with impaired cortical inhibition, thereby contributing to cortical hyperexcitability in ALS and providing further mechanistic insight.},
}

@article {pmid42229507,
year = {2026},
author = {Swanson, E and Dohle, E and Bashford, L and Horsfall, HL and Jovanovic, L and Muirhead, W and Brannigan, JFM},
title = {Recalibration of implantable brain-computer interfaces to enable long-term independent use - a systematic review.},
journal = {Journal of neural engineering},
volume = {},
number = {},
pages = {},
doi = {10.1088/1741-2552/ae7694},
pmid = {42229507},
issn = {1741-2552},
abstract = {Implantable brain-computer interfaces (iBCIs) decode neural signals to generate command signals for effector devices to restore lost functions, such as movement or speech. However, maintaining device performance over time requires recalibration of decoding algorithms due to inherent instability in neural signals. Objective: To systematically review recalibration procedures in iBCIs for patients with motor impairments, focusing on the clinical implications of recalibration requirements and strategies which can enable long-term, independent use. Approach: A systematic search was conducted across EMBASE, MEDLINE, and CINAHL databases to identify studies involving recalibration of iBCIs. Data on recalibration frequency, duration, staff requirements, and location were extracted and analysed. Main Results: Recalibration practices varied widely amongst studies and were typically performed according to predetermined study protocols, rather than practical need following deteriorating device performance. Common practices include manual recalibration requiring a specialist research team, semi-automatic recalibration which could be performed by a non-specialist caregiver, and automatic recalibration methods whereby patients did not require assistance. Devices utilising electrocorticography (ECoG) recording arrays generally required less frequent recalibration compared to those using microelectrode arrays (MEAs). Extended independent use was more frequently reported with ECoG-based iBCIs. Significance: Reducing recalibration frequency or complexity can improve patient autonomy, which is crucial for enhancing long-term independent iBCI use in home and clinical settings. ECoG iBCIs typically have a low recalibration burden due to inherent signal stability. Conversely, MEA iBCIs typically involve a higher recalibration burden, though recent studies have reduced this by incorporating spectral data and continuously updating models. Despite this progress, recalibration procedures are often not fully defined in iBCI studies, and where they are, they usually relate to the study protocol rather than the clinically meaningful recalibration requirement due to worsening device performance. Future studies should continue to develop user-friendly recalibration procedures and outline the clinically relevant recalibration requirements where possible.},
}

@article {pmid42229706,
year = {2026},
author = {Alqahtani, SM and Afzal, M and Afzal, O and Alabbas, A and Phalak, P and Goyal, K},
title = {Platelet-derived extracellular vesicles as neurodegenerative disease biomarkers.},
journal = {Clinica chimica acta; international journal of clinical chemistry},
volume = {},
number = {},
pages = {121130},
doi = {10.1016/j.cca.2026.121130},
pmid = {42229706},
issn = {1873-3492},
abstract = {Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are increasingly prevalent worldwide and have not yet been adequately diagnosed, especially because they require minimally invasive, non-invasive techniques. Although established blood-based biomarkers, such as plasma p-tau217, neurofilament light chain (NfL), and GFAP, have shown clinical utility, limitations in sensitivity and scalability remain. Platelets, anucleate cytoplasmic fragments originating from megakaryocytes, are the primary producers of extracellular vesicles in the peripheral blood. These vesicles contain disease-specific cargo, including amyloid-β, α-synuclein, tau, disease-associated glycoproteins, and microRNAs (miRNAs) derived from platelets. Recent findings suggest that the cargo of platelet-derived extracellular vesicles (pEVs) may be associated with neurodegenerative changes linked to disease severity. However, validation through a prospective multicenter study is necessary. A systematic narrative review was performed by searching the PubMed, Scopus, and Web of Science databases with the keywords "platelet-derived extracellular vesicles," "platelet microvesicles," "neurodegeneration," and "biomarkers" (inception through April 2026). This review discusses the biogenesis of pEV, their composition in relation to blood markers, and their pathomechanistic roles, such as platelet-mediated blood-brain barrier disruption, neuroinflammation, and misfolded protein seeding. The diagnostic evidence of pEV-associated cargo in neurodegenerative diseases is critically evaluated and contextualized with current blood markers. Key preanalytical considerations, including the selection of anticoagulants, isolation procedures, storage conditions, and the number of freeze-thaw cycles, as well as analytical considerations, such as flow cytometric calibration, single-vesicle resolution, and multiplexed platforms, are examined for their applicability in clinical laboratory settings. The emphasis is on reporting according to the MISEV and the harmonization between laboratories. The limitations of this study are the small heterogeneous cohorts, lack of preanalytical handling standardization, ex vivo platelet activation artifact, and lack of external validation.},
}

@article {pmid42230361,
year = {2026},
author = {Barba, L and Steinacker, P and Halbgebauer, S and Oeckl, P and Landwehrmeyer, B and Weishaupt, J and Verde, F and Ticozzi, N and Silani, V and Levin, J and Schönecker, S and Kornhuber, J and Prudlo, J and Schroeter, ML and Fassbender, K and Fliessbach, K and Diehl-Schmid, J and Jahn, H and Lauer, M and Dorst, J and Rosenbohm, A and Abu-Rumeileh, S and Anderl-Straub, S and Söntgerth, M and Böhm, F and Wiltfang, J and Otto, M},
title = {Serum neurofilaments for motoneuron and dementia diseases: a German multicenter cohort study.},
journal = {Journal of neurology},
volume = {273},
number = {6},
pages = {},
pmid = {42230361},
issn = {1432-1459},
support = {JCS24/02//Martin Luther Christian University/ ; CS22/06//Martin-Luther-University Halle-Wittenberg/ ; RF-2021-12374238)//Ministero della Salute/ ; TelDem//Sächsische Aufbaubank/ ; 100757914//EFRE InfraProNet/ ; },
abstract = {BACKGROUND: Serum neurofilament light and heavy chains (sNfL and sNfH) have been assessed as neuronal markers for amyotrophic lateral sclerosis (ALS) and dementias. Whereas sNfL has robust literature, systematic studies on sNfH are lacking. Here, we aimed to assess the diagnostic value of sNfH in comparison to sNfL in a broad range of neurodegenerative disorders.

METHODS: We measured with immunoassays sNfH and sNfL in patients recruited in the multicenter German Frontotemporal Lobar Degeneration (FTLD) Consortium (n = 340) and in a single-center German cohort (n = 290). We assessed the diagnostic accuracy of serum biomarkers for ALS and dementia subtypes and their relationship with cognitive impairment.

RESULTS: sNfH and sNfL were significantly increased in ALS (n = 90) vs. controls (n = 109) and ALS mimics (n = 56, p < 0.001), with sNfL showing higher discriminative accuracy (AUC = 0.94-0.95) than sNfH (AUC = 0.87-0.88). sNfH/sNfL ratio did not improve the diagnostic performance. Both markers were elevated in patients with dementia (n = 289) vs. controls (p < 0.001). sNfL was higher in behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA) and Creutzfeldt-Jakob disease (CJD) than in Alzheimer's disease (AD), whereas sNfH was similar in AD, PPA and bvFTD. sNfL, but not sNfH, was correlated with cognitive impairment at baseline and cognitive decline at follow-up in AD and bvFTD.

CONCLUSIONS: sNfH and sNfL are elevated in motoneuron and dementia disorders. sNfH showed good discriminative accuracy for ALS, which was slightly lower than that of sNfL. sNfL, but not sNfH, showed prognostic value for assessing cognitive decline in dementia.},
}

@article {pmid42230882,
year = {2026},
author = {Morishita, H and Umezawa, K and Kojima, M},
title = {Alkyl shikimates promote proliferation of human dermal fibroblasts and exhibit structure-activity relationships.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-55244-y},
pmid = {42230882},
issn = {2045-2322},
abstract = {Alkyl shikimates (SAEs) bearing linear and branched alkyl groups (R) ranging from CH3 to C5H11 were synthesized and assayed for proliferative activity toward human dermal fibroblasts; proliferation increase (PRA), measured using a CCK-8 assay kit, was used as the primary endpoint. Several SAEs exhibited significant PRA, depending on the concentration added to the culture medium and alkyl group structure. However, shikimic acid (SA) added to the culture medium did not induce fibroblast proliferation. SAEs with CH3, C2H5, and C3H7 alkyl groups (SAE-1, SAE-2, and SAE-3a,b) induced a 30-50% increase in cell proliferation at a concentration of 5.5 mM, while SAEs with a C4H9 groups (SAE-4a,b,c) showed low PRA and those with a C5H11 groups (SAE-5a,b,c) exhibited strong cytotoxicity (CYT: decrease in cell viability) at this concentration. The proliferation rates of SAEs at 5.5 mM correlated significantly with their calculated log P (ClogP) values, which reflect hydrophobicity and cell membrane permeability (quadratic regression; coefficient of determination, r[2] = 0.977-0.953. Based on these results, we proposed a mechanism in which membrane-permeable SAEs could form complexes with carboxylesterase (CES) present in dermal fibroblasts and be subsequently hydrolyzed into SA and alcohols (ALs) intracellularly, with the resulting SA potentially inducing PRA. In contrast, SA added extracellularly cannot enter cells due to its high hydrophilicity and therefore cannot induce PRA. In order to evaluate the stability of the proposed complexes, we estimated binding energies between CES and SAEs by quantum mechanical methods; however, the results showed no significant differences in binding energy attributable to alkyl chain length or steric effects of the SAE alkyl groups. The most plausible explanation for the differences in PRA among SAEs is that intracellularly regenerated SA promotes fibroblast proliferation, whereas the regenerated ALs may cause CYT. Alkyl group-dependent differences in AL toxicity may account for the concentration-dependent variation in SAE-induced PRA. In fact, when the CYT of linear alkyl alcohols (ALs-1, 2, 3a, 4a, and 5a) was measured by CCK-8 at a concentration of 100 mM, the results showed that differences in AL alkyl chain length significantly influenced cell viability, which was consistent with their ClogP values (CYT order; R = C5H11 > C4H9 > C3H7 > C2H5 ≥ CH3).},
}

@article {pmid42232224,
year = {2026},
author = {Cortes-Flores, H and Torrandell-Haro, G and Brinton, RD},
title = {Anti-inflammatory and immunomodulatory therapies are associated with reduced risk of age-associated neurodegenerative diseases: impact of sex and treatment duration.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1818660},
pmid = {42232224},
issn = {1663-4365},
abstract = {INTRODUCTION: Neurodegenerative diseases (NDDs) including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and non-AD dementias share chronic neuroinflammatory mechanisms that contribute to neuronal injury and disease progression. While anti-inflammatory therapies (AITs) are associated with reduced neurodegenerative disease risk, knowledge regarding the impact of biological sex and treatment duration across multiple NDDs remains limited.

METHODS: We conducted a retrospective cohort analysis using a large propensity-score-matched population (n = 190,308; 95,154 treated vs. 95,154 untreated) to evaluate associations between long-term AIT exposure and incidence of major NDDs. Disease-specific and combined outcomes were assessed across drug classes (NSAIDs, corticosteroids, immunomodulators), sex, age, and therapy duration.

RESULTS: AIT exposure was associated with a significantly lower risk of developing any NDD (RR = 0.47, 95% CI 0.43-0.48, p < 0.0001) and was equally effective in both sexes. Risk reduction was observed for each age-associated disease: AD (RR = 0.40), non-AD dementia (RR = 0.51), PD (RR = 0.43), MS (RR = 0.25), and ALS (RR = 0.48). Among drug classes, immunomodulators conferred the greatest reduction (RR = 0.19), followed by corticosteroids (RR = 0.41) and NSAIDs (RR = 0.42). Duration analyses revealed a graded benefit, with RR declining from 0.94 (< 1 year) to 0.25 (> 6 years). Risk reduction was greatest in older participants (75-79 years).

DISCUSSION: Chronic use of anti-inflammatory or immunomodulatory therapies was associated with significantly reduced incidence of multiple neurodegenerative diseases in both sexes. The strongest effects were observed with immunomodulator use and prolonged therapy duration, suggesting that sustained modulation of systemic inflammation confers broad neuroprotective effects in both sexes. These findings highlight the potential of targeting immune-inflammatory pathways for neurodegenerative disease prevention and can inform prospective mechanistic and interventional studies.},
}

@article {pmid42232333,
year = {2026},
author = {Chalitsios, CV and Turner, MR},
title = {Considering prediagnostic environmental modifiers of progression in amyotrophic lateral sclerosis.},
journal = {BMJ neurology open},
volume = {8},
number = {1},
pages = {e001702},
pmid = {42232333},
issn = {2632-6140},
}

@article {pmid42233796,
year = {2026},
author = {Nolan, HA and Dunford, L},
title = {A qualitative exploration of medical educators' familiarity and perspectives regarding trauma-informed approaches in medical education.},
journal = {Medical teacher},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/0142159X.2026.2681193},
pmid = {42233796},
issn = {1466-187X},
abstract = {INTRODUCTION: Evidence demonstrates profound impacts of trauma, on both physical and mental health across the lifespan, making trauma a significant public health issue. Current understanding of traumatic events acknowledges origins from social, structural, as well as interpersonal sources. Trauma-informed approaches (TIAs) provide a framework for interactions with those affected, and advocate for accommodation of trauma impacts throughout individual practice, and in organisations and systems to prevent retraumatisation. While TIAs are increasingly recommended in healthcare policy, evidence suggests these are not consistently incorporated in medical education. Educators are key stakeholders in embedding this practice, yet their perspectives have not been evaluated, representing a critical knowledge gap.

METHODS: We applied Brown et al.'s proposed Trauma-Informed Medical Education (TIME) framework (2021) that integrates trauma-informed principles throughout educational content and context as a conceptual model in this qualitative exploration of educator knowledge and practice. Educators at UK medical schools were invited to participate in semi-structured interviews exploring familiarity with TIAs, benefits and drawbacks. Data were analysed using reflexive thematic analysis.

RESULTS: Twenty-three educators from 16 medical schools were interviewed. Knowledge, routes to familiarisation and practice varied considerably among participants, who broadly recognised need for and value of TIAs. Practice often mirrored trauma-informed principles. Motivations related to person-centred care, inclusive education, and learner wellbeing, with concerns regarding avoidance of distressing content. Compatibility of TIME recommendations with education and healthcare contexts was discussed, with facilitators, and more commonly, barriers identified.

DISCUSSION: Variable knowledge, opportunistic familiarisation, and individually determined practice indicate the need for more precise understanding of evidence regarding trauma sources and impacts and TIAs amongst education stakeholders at all levels to harness benefits. Wider contextual factors are not addressed in the current framework. Greater consideration of contextual factors and more cohesive approaches across medical education, alongside stakeholder engagement, are needed to meet healthcare policy intentions.},
}

@article {pmid42234085,
year = {2026},
author = {Rinner, C},
title = {Ethical justification of coercive public health policies must be premised upon their safety and efficacy.},
journal = {Monash bioethics review},
volume = {},
number = {},
pages = {},
pmid = {42234085},
issn = {1836-6716},
support = {NFRFR-2022-00305//New Frontiers in Research Fund/ ; },
abstract = {This commentary on Johnson et al. (2025) argues that ethical justification of a public health policy is void if the underlying intervention has not been shown, beyond reasonable doubt, to be effective, necessary, proportionate, and safe. I respond to Johnson et al.'s (2025) explorations with examples of coercive policies during the COVID-19 crisis. Frequently, the scientific evidence underpinning pandemic response measures has shifted, weakening or nullifying their original purpose. Such measures can no longer be ethically justified, and contemporary concerns regarding lockdown and mask policies as well as vaccination requirements were not properly considered by public health authorities.},
}

@article {pmid42234776,
year = {2026},
author = {Guo, C and Chen, K and Vatsavayai, S and Akiyama, T and Liu, C and Zeng, Y and Sianto, O and Yang, E and Bombosch, J and Powell, R and Zhen, S and Mekhoubad, S and Morrie, RD and Miller, G and Ilic, D and Boll, M and Parnell, E and Penzes, P and Lipstein, N and Green, EM and Petrucelli, L and Seeley, WW and Gitler, AD},
title = {Cryptic splicing in synaptic and membrane excitability genes links TDP-43 loss to neuronal dysfunction.},
journal = {Science translational medicine},
volume = {18},
number = {852},
pages = {eaeb8517},
doi = {10.1126/scitranslmed.aeb8517},
pmid = {42234776},
issn = {1946-6242},
abstract = {TAR DNA binding protein 43 (TDP-43) pathology is a defining pathological hallmark of multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). A major feature of TDP-43 pathology is its nuclear depletion, leading to the aberrant inclusion of cryptic exons during RNA splicing. STMN2 and UNC13A have emerged as prominent TDP-43 splicing targets, but the broader impact of TDP-43-dependent cryptic splicing on neuronal function remains unclear. Here, we report previously unidentified TDP-43 splicing targets critical for membrane excitability and synaptic function, including KALRN, RAP1GAP, SYT7, and KCNQ2. Using human stem cell-derived neurons, we showed that TDP-43 reduction induces cryptic splicing and down-regulation of these genes, resulting in impaired excitability and synaptic transmission. In postmortem brains from patients with FTD, these cryptic splicing events occurred selectively in neurons with TDP-43 pathology. Suppressing individual cryptic splicing events using antisense oligonucleotides partially restored neuronal function, and combined targeting almost fully rescued the synaptic deficit caused by TDP-43 loss. Together, our findings provide evidence that cryptic splicing in these synaptic and membrane excitability genes is not only a downstream marker but instead a direct driver of neuronal dysfunction, establishing a mechanistic link between TDP-43 pathology and neurodegeneration in ALS and FTD.},
}

@article {pmid42002732,
year = {2026},
author = {Atwa, H and Shehata, MH and Kumar, AP and Alansari, R and Al-Ansari, A and Deifalla, A},
title = {Readiness for self-directed learning among first-year medical and nursing students at the Arabian Gulf University in Bahrain.},
journal = {BMC medical education},
volume = {26},
number = {1},
pages = {},
pmid = {42002732},
issn = {1472-6920},
abstract = {BACKGROUND: Self-directed learning (SDL) is a fundamental skill in health professions education, enabling students to take ownership of their learning and adapt to evolving healthcare challenges. Understanding SDL readiness among students is crucial for optimizing curriculum design and enhancing lifelong learning competencies. This study aimed to explore SDL readiness among first-year medical and nursing students at the College of Medicine and Health Sciences, Arabian Gulf University (CMHS-AGU) in Bahrain.

METHODS: A cross-sectional study was conducted among first-year medical and nursing students at the CMHS-AGU. Data were collected using an electronic questionnaire that included demographic information and Fisher et al.’s validated 40-item Self-Directed Learning Readiness Scale (SDLRS). The scale measured students’ readiness across self-management, desire for learning, and self-control. Descriptive statistics, independent t-tests, one-way ANOVA, and correlation analyses were conducted using IBM SPSS v.25. Effect sizes were reported as Cohen’s d for two-group comparisons and eta-squared (η²) for multi-group comparisons. A p-value < 0.05 was considered statistically significant.

RESULTS: A total of 410 students participated (Medicine: 202, Nursing: 208), yielding a response rate of 83.7%. The mean total SDLRS score was 151.96 (SD = 20.75), indicating overall high SDL readiness, though with notable subgroup variability. Nursing students had significantly higher SDLRS scores (159.78 ± 16.02) than medical students (143.90 ± 21.97) (p < 0.001; Cohen’s d = 0.83, large effect). Female students demonstrated greater SDL readiness than males (155.26 ± 20.78 vs. 143.58 ± 18.21, p < 0.001; Cohen’s d = 0.58, medium effect). Country of origin was also a significant differentiator (p < 0.001; η² = 0.132), with Bahraini students scoring highest and Omani students lowest. Higher SDLRS scores were further associated with graduation from American or International Baccalaureate curricula (p < 0.001; η² = 0.066), lack of reliance on private tutoring (p = 0.004), regular engagement in extracurricular activities (p = 0.001), and the frequent use of educational technology, including artificial intelligence (p < 0.001).

CONCLUSION: First-year medical and nursing students generally demonstrated SDL readiness above the high threshold; however, this aggregate finding warrants cautious interpretation, and significant differences were observed based on academic program, gender, nationality, and prior educational experiences. Nursing students and female participants exhibited higher readiness, potentially reflecting early variations in learning orientation and professional socialization. The findings underscore the need for targeted interventions, particularly for medical students transitioning from highly structured curricula, to foster essential SDL competencies. Future research should utilize mixed-methods and learning analytics to examine the longitudinal development of these critical lifelong learning skills.},
}

@article {pmid42153537,
year = {2026},
author = {Shi, J and Wu, Y and Liu, X and Xia, W and Wu, J and Lou, J and Zhang, X and Zhang, J and Yang, N and Chi, W and Xiang, L and Zhang, Y and Shu, Y and Miao, R and Zhao, J and Zhu, X and Qi, J and Xiao, J and Zhou, K},
title = {MOTS-c, a mitochondrial-derived peptide, ameliorates lysosomal membrane permeability and improves survival of soft tissue transplantation.},
journal = {Autophagy},
volume = {},
number = {},
pages = {1-30},
doi = {10.1080/15548627.2026.2677180},
pmid = {42153537},
issn = {1554-8635},
abstract = {Distal ischemic necrosis remains a major challenge in reconstructive surgery. Mitochondria and lysosomes interact via signaling and membrane contacts to maintain cellular homeostasis. Mitochondrial-derived peptide MOTS-c, encoded by the MT-RNR1/12S rRNA open reading frame, enhances mitochondrial function by reducing reactive oxygen species (ROS) and stabilizing the membrane potential, potentially preserving lysosomal integrity and reducing lysosomal membrane permeabilization (LMP). This study investigated the protective effects and underlying mechanisms of MOTS-c in ischemic flaps. RNA sequencing explored MOTS-c mechanisms in ischemic flaps. Tissue clearing, laser speckle contrast imaging and Doppler analyses revealed improved blood flow perfusion following MOTS-c treatment. Histological staining (HE, Masson, F-CHP) demonstrated enhanced angiogenesis and collagen remodeling. Western blotting, ELISA, and immunofluorescence were used to assess pyroptosis, macroautophagy/autophagy, LMP, and MAPK1/ERK2-MAPK3/ERK1-NFKB/NF-κB pathway-related proteins. MOTS-c reduced endothelial pyroptosis, enhanced autophagy, and attenuated LMP in ischemic flaps. Mechanistically, in vivo overexpression of PLA2G4A/cPLA2 (phospholipase A2, group IVA (calcium, calcium dependent)) via AAV confirmed that MOTS-c enhances autophagy and reduces pyroptosis and LMP by suppressing PLA2G4A phosphorylation. Furthermore, MOTS-c inhibited PLA2G4A via the MAPK1-MAPK3-NFKB signaling cascade, thereby reducing LMP and enhancing flap survival. These findings suggest that MOTS-c restores cellular homeostasis by targeting the PLA2G4A-LMP axis, representing a promising therapeutic strategy for improving outcomes in ischemic flap surgery.Abbreviations: AA = arachidonic acid, AAV = adeno-associated virus, ACTA2/α-SMA = actin alpha 2, smooth muscle, aorta, ALs = autolysosomes, BECN1 = beclin 1, CASP1 = caspase 1, CQ = chloroquine, CTSB = cathepsin B, CTSD = cathepsin D, CTSL = cathepsin L, Co-IP = co-immunoprecipitation, DEGs = differentially expressed genes, ELISA = enzyme-linked immunosorbent assay, F-CHP = 5-FAM-conjugated collagen hybridizing peptide staining, GSDMD = gasdermin D, GO = gene Ontology, GPT/ALT = glutamic pyruvic transaminase, soluble, GOT1/AST = glutamic-oxaloacetic transaminase 1, soluble, HE = hematoxylin-eosin, HUVECs = human umbilical vein endothelial cells, IP/MS = immunoprecipitation coupled with mass spectrometry, IL1B/IL-1β = interleukin 1 beta, IL18 = interleukin 18, IP = intraperitoneal injection, IV = intravenous injection, LDBF = laser Doppler blood flow, LMP = lysosomal membrane permeability, MAP1LC3/LC3 = microtubule-associated protein 1 light chain 3, MAPK = mitogen-activated protein kinase, NAGLU = alpha-N-acetylglucosaminidase (Sanfilippo disease IIIB), NFKB/NF-κB = nuclear factor kappa B, NLRP1 = NLR family pyrin domain containing 1, NLRP3 = NLR family pyrin domain containing 3, PECAM1/CD31 = platelet/endothelial cell adhesion molecule 1, PLA2G4A/cPLA2 = phospholipase A2, group IVA (cytosolic, calcium-dependent), PYCARD/ASC = PYD and CARD domain containing, PIK3C3/VPS34 = phosphatidylinositol 3-kinase catalytic subunit type 3, PMA = phorbol 12-myristate 13-acetate, ROS = reactive oxygen speciesSQSTM1/p62 = sequestosome 1, SPR = surface plasmon resonance, scRNA-seq = single-cell RNA sequencing, UMAP = uniform manifold approximation and projection, WB = western blotting.},
}

@article {pmid42183611,
year = {2026},
author = {Ji, F and Dai, M and Wang, Z and Dai, E and Kang, R and Klionsky, DJ and Tang, D and Huang, Y and Sun, Y and Liu, T},
title = {Mammalian lysophagy: mechanisms and pathophysiological implications.},
journal = {Autophagy},
volume = {},
number = {},
pages = {1-16},
doi = {10.1080/15548627.2026.2679642},
pmid = {42183611},
issn = {1554-8635},
abstract = {Lysophagy is a form of selective macroautophagy/autophagy that preserves lysosomal integrity by eliminating damaged lysosomes. Lysosomal membrane permeabilization can arise from diverse physiological and pathological insults, including proteotoxic stress, crystalline particles, pathogens and chemical perturbations, and occurs along a continuum ranging from transient nanoscale lesions to catastrophic rupture. Cells respond to lysosomal injury through a hierarchical quality-control network in which membrane repair, lysophagic removal and lysosomal regeneration operate in a coordinated manner. Damage recognition involves sensing of exposed lumenal glycans and membrane lipids, followed by ubiquitin-dependent tagging that recruits selective autophagy receptors and activates the core autophagy machinery to form lysophagosomes. Lysophagy is closely integrated with membrane repair pathways, metabolic signaling and innate immune responses that together determine lysosomal fate. Dysregulated lysosomal quality control has been implicated in diverse diseases, including neurodegeneration, infection, cancer and chronic inflammatory disorders. In this review, we summarize current mechanistic insights and emerging experimental approaches for studying lysosomal quality control and lysophagy in mammalian cells.Abbreviations: ALR, autophagic lysosome reformation; ALS, amyotrophic lateral sclerosis; ATG8, mammalian Atg8-family protein; ER, endoplasmic reticulum; ESCRT, endosomal sorting complexes required for transport; LAMPs, lysosome associated membrane proteins; LIR, LC3-interacting region; LLOMe, L-leucyl-L-leucine methyl ester; LMP, lysosomal membrane permeabilization; PITT, phosphoinositide-initiated membrane tethering and lipid transport; PtdIns3K, class III phosphatidylinositol 3-kinase; PtdIns3P, phosphatidylinositol-3-phosphate; PtdIns4P, phosphatidylinositol-4-phosphate; ROS, reactive oxygen species; V-ATPase, vacuolar-type H[+] -ATPase.},
}

@article {pmid42223005,
year = {2026},
author = {Kafetsios, K and Strand, PS},
title = {The cultural plasticity of intimacy behavior: A socioecological attachment perspective.},
journal = {The Behavioral and brain sciences},
volume = {49},
number = {},
pages = {e105},
doi = {10.1017/S0140525X25102707},
pmid = {42223005},
issn = {1469-1825},
mesh = {Humans ; *Object Attachment ; *Interpersonal Relations ; Female ; *Culture ; *Sexual Behavior/psychology ; Male ; *Social Behavior ; },
abstract = {Gender imbalances in intimacy behavior reflect culturally contingent expressions of attachment organization rather than fixed gender differences. Building on Wahring et al.'s model, we apply the Biobehavioral Cultural Model of Attachment to show how affiliative behaviors vary with socioecological conditions, early reinforcement patterns, and cultural norms, offering a dynamic, context-sensitive account of intimacy across diverse settings.},
}

Humans
*Object Attachment
*Interpersonal Relations
Female
*Culture
*Sexual Behavior/psychology
Male
*Social Behavior

@article {pmid42223083,
year = {2026},
author = {Zhang, Q and Valério, M and Grünewald, L and Borges-Araújo, L and Grünewald, F and Wang, S and Marrink, SJ and Gong, Y and Souza, PCT},
title = {Coarse-Grained Simulations Reveal Salt- and Length-Dependent Condensation of G4C2 RNA Repeats.},
journal = {The journal of physical chemistry letters},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jpclett.6c00916},
pmid = {42223083},
issn = {1948-7185},
abstract = {RNA-RNA interactions drive the formation of biomolecular condensates via liquid-liquid phase separation (LLPS), but their underlying molecular mechanisms remain poorly understood. Here, we employ Martini 3 coarse-grained molecular simulations to investigate phase transitions of G4C2 RNA repeats─sequences implicated in neurodegenerative disorders such as ALS and FTD─across varying salt concentrations. The model captures salt-dependent transitions from dispersed to condensed-like states and suggests that dominant interaction patterns, including Watson-Crick-like and G-G contacts, shift with ionic strength. Notably, longer RNA sequences maintain phase-separated states at salt concentrations that dissolve shorter ones, in line with experimental observations. Our findings demonstrate the ability of the Martini coarse-grained model to reproduce key biophysical features of RNA LLPS, including sequence-length dependence and interaction specificity. This work provides molecular-level insight into RNA-driven phase separation and reveals how sequence composition and ionic strength govern the emergence and stability of RNA-rich assemblies.},
}

@article {pmid42223334,
year = {2026},
author = {He, C and Liu, Z and Yuan, Y and Tang, L and Wang, M and Li, Y and Zhao, Q and Weng, L and Du, J and Wu, H and Hu, F and Xu, R and Guo, J and Shen, L and Tang, B and Wang, J},
title = {Distinct UNC13A Haplotype Blocks Define Disease Severity and Survival in Chinese Amyotrophic Lateral Sclerosis.},
journal = {European journal of neurology},
volume = {33},
number = {6},
pages = {e70653},
doi = {10.1111/ene.70653},
pmid = {42223334},
issn = {1468-1331},
support = {2021YFA0805202//the National Key R&D Program of China/ ; STI2030‑MajorProjects2021ZD0201803//National Science and Technology Innovation 2030 Major Program/ ; 82371445//the National Natural Science Foundation of China/ ; 82171431//the National Natural Science Foundation of China/ ; 20242BAB26135//the Jiangxi Provincial Natural Science Foundation/ ; 20243BCE51002//the Ganpo Outstanding Talents Support Program-Cultivation Project for Academic and Technical Leaders in Key Disciplines/ ; gpyc20240194//the Ganpo Talents Program-Innovation Leading Talent Project (Medical and Health Care Category)/ ; 202510014//the Jiangxi Provincial Health Technology Project/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/mortality/diagnosis ; Haplotypes ; Female ; Male ; Asian People/genetics ; Middle Aged ; Polymorphism, Single Nucleotide ; *Nerve Tissue Proteins/genetics ; Severity of Illness Index ; Genetic Predisposition to Disease/genetics ; Genome-Wide Association Study ; Aged ; Adult ; East Asian People ; },
abstract = {BACKGROUND: UNC13A is a genetic modifier of amyotrophic lateral sclerosis (ALS) in European populations, but its role in Chinese patients remains incompletely characterized. We investigated the spectrum of UNC13A variation and its impact on disease risk and progression in a Chinese ALS cohort.

METHODS: We performed an integrated genetic analysis of 1,533 Chinese ALS patients and 1,405 controls, including rare variant burden testing, genome-wide survival analysis, haplotype mapping, and conditional analyses. An integrated clinical-genetic prognostic score was developed and validated.

RESULTS: Rare deleterious UNC13A variants were not associated with ALS risk. We identified two independent haplotype blocks with distinct clinical impacts. Block 1 (tagged by rs75421007) was associated with reduced baseline muscle strength (p = 0.030), while Block 2 (tagged by rs78549703), a brain-specific splicing QTL, was the primary driver of survival heterogeneity. The European variant rs12608932 showed a survival association in single-marker analysis (p = 0.024), but conditional analyses revealed its effect was not independent of Block 2. An integrated prognostic score combining clinical factors and Block 2 haplotype stratified patients into low-, intermediate-, and high-risk groups (median survival: 52.6, 37.1, and 32.0 months; p < 0.001), with decision curve analysis confirming clinical utility.

CONCLUSIONS: This study delineates UNC13A genetic architecture in Chinese ALS, identifying two independent haplotype blocks that differentially influence disease severity and survival. The Block 2 haplotype, which includes a brain sQTL, is a major determinant of survival heterogeneity and may inform patient stratification in future studies.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/mortality/diagnosis
Haplotypes
Female
Male
Asian People/genetics
Middle Aged
Polymorphism, Single Nucleotide
*Nerve Tissue Proteins/genetics
Severity of Illness Index
Genetic Predisposition to Disease/genetics
Genome-Wide Association Study
Aged
Adult
East Asian People

@article {pmid42224592,
year = {2026},
author = {Galloway, DA and Patterson, HL and Hoye, ML and Shen, T and Shabsovich, M and Schoch, KM and Ly, CV and Miller, TM},
title = {miR-146a is a pleiotropic regulator of motor neuron degeneration.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {23},
pages = {e2526314123},
doi = {10.1073/pnas.2526314123},
pmid = {42224592},
issn = {1091-6490},
support = {R01NS078398//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; F31NS092340//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons. Here, we have profiled motor neuron microRNAs (miRNAs) during motor neuron degeneration in vivo to gain a better understanding of ALS pathophysiology. We demonstrate that one miRNA, miR-146a, is downregulated in diseased motor neurons despite upregulation in bulk tissue. Genetic deletion of miR-146a significantly extended survival in SOD1[G93A] mice with heterozygous animals demonstrating the largest benefit. A corresponding reduction in spinal cord gliosis but not motor neuron loss was observed. Finally, we observed that a proportion of miR-146a knockout animals develop spontaneous paralysis, motor neuron loss and chronic neuroinflammation with advanced age. Together these findings demonstrate that a single miRNA influences multiple aspects of motor neuron disease and highlights the complex role for neuroinflammation in ALS pathogenesis.},
}

@article {pmid42225765,
year = {2026},
author = {Costello, E and Kiyui, K and Brennan, C and Obain, NN and Leonard, S and Heverin, M and Barbey, F and Dyer, J and Rueda-Delgado, L and Diggin, S and Tunbridge, E and Marston, H and Lai, RYK and Hargreaves, R and Shinobu, L and Nguyen, V and Hake, AM and Dawson, G and Latzman, R and Buick, A and Murphy, B and Hardiman, O and Pender, N},
title = {Longitudinal cognitive assessment using the Cumulus NeuLogiq platform in amyotrophic lateral sclerosis and frontotemporal dementia.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-53099-x},
pmid = {42225765},
issn = {2045-2322},
abstract = {People living with ALS (plwALS) and/or FTD (plwFTD) often experience cognitive and behavioural changes. However, detection can be confounded due to factors like fatigue and testing anxiety. Cumulus neuroscience developed NeuLogiq[(R)], a multi-modal neurocognitive platform that can be used in clinic or at home, providing an ecologically valid measure of cognition. This study examined the feasibility and usability of NeuLogiq in plwALS, plwFTD, and controls, and compared performance on gold standard neuropsychological assessments with corresponding NeuLogiq digital assessments. Over 8 months, plwALS (n = 11), plwFTD (n = 7), and matched healthy controls (n = 10) completed longitudinal full neuropsychological assessment, as well as three 25-minute NeuLogiq Platform sessions every 2 weeks in their homes. Participants adhered well to the study schedule, conducting over 32/54 sessions on average. All groups rated usability in the 'good' or 'excellent' range and had > 80% complete data. Baseline group differences were detectable on both NeuLogiq digital assessments and benchmark neuropsychological assessments of similar cognitive domains. Longitudinal mixed effects models found that the ALS group showed decline on NeuLogiq measures of emotion recognition and speech fluency. These findings suggest that the NeuLogiq platform is feasible and usable for plwALS and plwFTD, and can identify cognitive deficits to a similar extent as benchmark assessments over time.},
}

@article {pmid42225893,
year = {2026},
author = {Pervaiz, I and Blazier, AS and Nyarko-Danquah, I and Wesseling, H and Ramos, A and Woodworth, L and Taksir, TV and Ryan, SK and Wirak, G and Zhao, Z and Hammond, TR and Morel, C and Bangari, DS and Ofengeim, D and Rapino, F and Hagan, N},
title = {Targeting MAPK-dependent pathways to modulate reactive astrocyte pathology in neurodegeneration.},
journal = {Communications biology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s42003-026-10323-8},
pmid = {42225893},
issn = {2399-3642},
abstract = {Reactive astrocytes play a crucial role in the pathogenesis of neurodegenerative diseases; however, the mechanisms underlying glial cell interactions remain poorly understood. Here, we show that human primary astrocytes and iPSC-derived astrocytes in a tri-culture system adopt a reactive state with a distinct molecular phenotype overlapping with transcriptomic signatures observed in ALS astrocytes. Integrated proteomic and phosphoproteomic analyses revealed dysregulated cytoskeletal remodeling and kinase signaling in reactive astrocytes. Surface marker screening identified ICAM-1 as a novel in-vitro marker, validated in ALS spinal cord. Functionally, reactive astrocytes induced neurotoxicity and altered neuronal activity. To elucidate mechanisms regulating neurotoxicity, a phenotypic small molecule screen identified MAP kinase as a functional regulator, with subsequent single-nucleus RNA sequencing uncovering dysregulated signaling pathways modulated by MAPK inhibition in the tri-culture system. Together, these complementary approaches define the molecular landscape of reactive astrocytes, providing a systems-level framework for exploring disease mechanisms and therapeutic strategies in neurodegeneration.},
}

@article {pmid42226981,
year = {2025},
author = {Romina, A and Mohaddeseh, L and Mansour, B},
title = {Fabrication and Evaluation of PVA-NYS-THY Nanofiber Scaffolds as Antifungal Agents Against Fluconazoleresistant Candida glabrata.},
journal = {Archives of Razi Institute},
volume = {80},
number = {5},
pages = {1229-1238},
pmid = {42226981},
issn = {2008-9872},
abstract = {INTRODUCTION: The emergence of fluconazole-resistant Candida glabrata presents a significant challenge in antifungal therapy, necessitating the development of alternative treatment strategies. C. glabrata, an opportunistic yeast, is increasing resistance to common antifungals like fluconazole, often due to efflux pump overexpression, leading to compromised treatment efficacy, higher mortality, prolonged hospital stays, and increased healthcare costs. This study focused on fabricating and evaluating polyvinyl alcohol-nystatin-thymol (PVA-NYS-THY) nanofibrous scaffolds as a novel antifungal approach against fluconazole-resistant C. glabrata.

MATERIALS & METHODS: Clinical isolates were identified and assessed for resistance using culture methods, molecular assays, and antifungal susceptibility testing. PVA-NYS-THY nanofibers, produced via electrospinning, exhibited uniform fibers with an average diameter of ~100 nm as confirmed by scanning electron microscopy (SEM). Fourier transform infrared spectroscopy confirmed the successful incorporation of functional groups. Real-time polymerase chain reaction (PCR) was employed to evaluate the nanofibers' effect on the expression of secreted aspartyl proteinases (SAP) and agglutinin-like sequence (ALS) gene. Scaffold release kinetics were characterized, and antifungal efficacy was assessed using minimum inhibitory concentration (MIC) assays.

RESULTS: PVA-NYS-THY scaffolds showed favorable release profiles and significantly downregulated ALS and SAP gene expression. MIC values for PVA-NYS-THY, PVA-NYS, and PVA-THY were 7.81, 15.62, and 62.5 µg/mL, respectively, demonstrating superior antifungal activity of the PVA-NYS-THY formulation.

CONCLUSION: These findings suggest PVA-NYS-THY nanofibrous scaffolds offer a promising therapeutic strategy for combating fluconazole-resistant C. glabrata, providing a novel solution to overcome current limitations in antifungal treatment.},
}

@article {pmid42227145,
year = {2026},
author = {Kumar, V and Kashif, M and Singh, V and Rawat, RS and Khan, A and Sarkar, GC and Majood, M},
title = {Therapeutic targeting of DNA repair pathway dysregulation in aging, cancer, and neurodegeneration.},
journal = {Expert opinion on therapeutic targets},
volume = {},
number = {},
pages = {},
doi = {10.1080/14728222.2026.2683686},
pmid = {42227145},
issn = {1744-7631},
abstract = {INTRODUCTION: Genome maintenance is increasingly recognized as a shared vulnerability across aging, cancer, and neurodegeneration, yet the therapeutic implications of pathway-specific dysregulation of DNA repair remain incompletely defined.

AREAS COVERED: This review integrates recent mechanistic and translational literature on how base excision repair, nucleotide excision repair, mismatch repair, homologous recombination, canonical non-homologous end joining, and alternative end joining are remodeled across these conditions. We discuss how oxidative stress, replication stress, telomere dysfunction, mitochondrial injury, and persistent DNA damage response signaling drive senescence and inflammation; how tumor cells exploit repair rewiring to survive genotoxic stress and acquire resistance; and how post-mitotic neurons are limited by restricted repair redundancy. We also summarize biomarkers for repair-state stratification and emerging strategies targeting PARP, ATR, ATM, DNA-PK, POLQ, and cGAS-STING.

EXPERT OPINION: Clinical translation will depend less on single-gene alterations than on defining context-specific repair states and pathway dependencies. Such stratification should enable rational combinations that either restore repair fidelity in aging and neurodegeneration or exploit repair addiction in cancer.},
}

@article {pmid42227472,
year = {2026},
author = {Amin, MA and Zehravi, M and Sweilam, SH and Darwin, R and Gupta, JK and Bhargav, E and Dharmamoorthy, G and Kumar, VV and Rao, AA and Suliman, M and Periyasamy, T and Emran, TB},
title = {Fisetin and Neurodegeneration: From Preclinical Studies to Potential Clinical Applications.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273427644251204045253},
pmid = {42227472},
issn = {1996-3181},
abstract = {Neurodegenerative diseases (NDs), like Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis, pose significant challenges due to their gradual deterioration and limited available treatments. Fisetin, a naturally occurring flavonoid, has gained attention for its neuroprotective properties. This review explores the therapeutic potential of fisetin in NDs, focusing on its molecular processes and signaling pathways. Additionally, fisetin exhibits significant protective properties, particularly in reducing oxidative stress, neuroinflammation, and apoptosis. It enhances neuronal survival and reduces neuroinflammation by regulating key pathways, such as Nrf2/ARE, PI3K/Akt, and NF-κB. It also has anti-inflammatory, anti-apoptotic, and antioxidant actions. It stimulates autophagic processes, aiding in the removal of harmful protein aggregates, like tau tangles and amyloid plaques, which are hallmarks of NDs. Fisetin, as demonstrated through behavioral evaluations in animal models, has been found to improve motor coordination, synaptic plasticity, and cognitive function. Furthermore, fisetin's potential as a neuroprotective drug is emphasized by its role in enhancing autophagy and reducing tau and amyloid pathology. Research has shown its efficacy in enhancing neural resilience, synaptic plasticity, and cognitive function in both preclinical and in vitro settings. However, clinical translation remains limited due to challenges in pharmacokinetics and bioavailability, despite robust experimental evidence. Further clinical trials are needed to evaluate the safety and efficacy of fisetin, especially in early-stage NDs, explore potential synergistic effects, and understand the molecular interactions. The review demonstrates fisetin's therapeutic potential, recent research, and future strategies for NDs, highlighting bioavailability limitations and the need for new formulations or delivery systems.},
}

@article {pmid42227825,
year = {2026},
author = {Watson, MD and Lee, JC},
title = {Site-Specific Raman Probes Reveal Droplet Aging and Residue-Level Fibril Polymorphism in TDP-43CTD.},
journal = {Journal of the American Chemical Society},
volume = {},
number = {},
pages = {},
doi = {10.1021/jacs.6c07727},
pmid = {42227825},
issn = {1520-5126},
abstract = {The C-terminal domain of TAR DNA-binding protein 43 (TDP-43CTD) drives both liquid-liquid phase separation (LLPS) and amyloid formation. Understanding how TDP-43CTD droplets convert into amyloid aggregates, a process implicated in amyotrophic lateral sclerosis and frontotemporal dementia, requires methodology capable of site-specific structural characterization with spatial resolution. Here, we used confocal Raman spectroscopy in conjunction with an alkyne-modified amino acid (4-ethynyl-l-phenylalanine, FCC) to probe aging in individual TDP-43CTD droplets at seven aromatic sites. While nascent droplets are composed of disordered proteins, β-sheet conformers develop in aged droplets and amyloid aggregates. All three states are spectrally distinct via the alkyne stretching band, with sensitivity that varies depending on the aromatic site probed. C-terminal sites (Y374FCC, W385FCC, and F397FCC) are highly sensitive amyloid probes, revealing multiple polymorphs at the single-residue level that are not resolvable by global secondary structure or morphological characterization alone. Strikingly, while W334FCC abolishes β-sheet formation in droplets, de novo aggregation still occurs, demonstrating that droplet aging is not required for amyloid formation. Given its broad applicability to other proteins and compatibility with cellular imaging, this work establishes a generalizable approach for investigating conformational changes underlying LLPS and amyloid formation in cellulo.},
}

@article {pmid42216417,
year = {2026},
author = {Curman, P and Alam, U and Ludwig, RJ},
title = {Response to Meisenheimer et al's "Behind the data: Pitfalls and bias in database research".},
journal = {Journal of the American Academy of Dermatology},
volume = {94},
number = {2},
pages = {e135-e136},
doi = {10.1016/j.jaad.2025.09.108},
pmid = {42216417},
issn = {1097-6787},
}

@article {pmid42217760,
year = {2026},
author = {Jiang, Y and Hu, S and Yang, B and Zhang, L and Wang, Y and Yang, G and Zhang, H},
title = {Fluid-based biomarkers of amyotrophic lateral sclerosis: recent advances and future prospects.},
journal = {Brain research},
volume = {},
number = {},
pages = {150395},
doi = {10.1016/j.brainres.2026.150395},
pmid = {42217760},
issn = {1872-6240},
abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder with no definitive cure. The absence of specific diagnostic biomarkers leads to diagnostic delays, hindering early intervention and management. This review provides a critical appraisal of fluid-based biomarkers for ALS across multiple sources-cerebrospinal fluid (CSF), blood, urine, saliva, and tears-with emphasis on their diagnostic and prognostic potential, limitations, and readiness for clinical translation. While neurofilaments (NfL, pNfH) are well-established as sensitive indicators of neuroaxonal injury and are increasingly used as prognostic and pharmacodynamic markers in clinical trials, they lack disease specificity. Biomarkers reflecting ALS-specific pathology, such as TDP-43 species and C9orf72 dipeptide repeat proteins (DPRs), show promise but remain in early validation stages with limited multicenter data. Emerging markers from non-invasive sources (urine p75ECD, salivary chromogranin A, tear metabolomics) offer potential for repeated sampling but require rigorous external validation before clinical adoption. To address current gaps, we introduce a standardized evidence grading framework (Tier 1-3) and a comprehensive reporting template for biomarker studies, including explicit performance metrics (AUC, sensitivity, specificity, confidence intervals) and validation status. We also propose minimum reporting standards for study design, pre-analytical variables, and statistical rigor, modeled on REMARK guidelines. A roadmap for biomarker validation and a cross-fluid comparison matrix are provided to guide future research. Despite considerable progress, significant challenges remain, including biological heterogeneity, pre-analytical variability, and insufficient external validation. Future efforts should prioritize multicenter prospective studies, assay harmonization, ethical frameworks for early diagnosis, and integration of emerging technologies such as artificial intelligence and digital twins. Fluid-based biomarkers, while not yet replacing clinical evaluation, are essential tools for accelerating drug development, enabling patient stratification, and moving toward personalized medicine in ALS.},
}

@article {pmid42218400,
year = {2026},
author = {Abbasi, H and Shafaatdoost, M and Mohajerani, A and Asadollahi, M and Rashidi, M and Malekahmadi, M and Sarraf, P},
title = {Association between body composition and disease progression in adults with amyotrophic lateral sclerosis: a cross-sectional study.},
journal = {BMC neurology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12883-026-04971-w},
pmid = {42218400},
issn = {1471-2377},
support = {IR. TUMS.NI.REC.1401.059//Tehran University of Medical Sciences and Health Services/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron degeneration, muscle wasting, and respiratory failure, with a median survival of 30 months. Due to the strong link between dysphagia, weight loss, and disease progression, this study investigates the relationship between body composition and clinical outcomes in ALS adults. This cross-sectional study involved 93 ALS adults (29 females, 64 males) from Imam Khomeini Hospital in Tehran, selected based on EI Escorial criteria. Researchers assessed body composition, functional abilities, and disease progression using ALSFRS-R, MRC scores, and DPR, analyzing associations through linear regression models with RStudio in conjunction with R software. In this study, significant differences were found between the third and first tertiles for various measures. Significant associations were observed between body composition and ALSFRS-R for MAC (β: 3.0; P = 0.006), with underweight and moderately active adults exhibiting notable differences. The MRC score was positively associated with FFM (β: 5.8; P = 0.002), SLM (β: 5.6; P = 0.002), SMM (β: 3.8; P = 0.001), MAC (β: 3.2; P = 0.002), ICW (β: 2.7; P = 0.002), and ECW (β: 1.5; P = 0.003), while underweight and low-to-moderate physical activity adults indicated inverse associations. For DPR, significant relationships were noted for weight (β: 4.5; 95% CI: 0.02, 9.3; P = 0.002) and FFM (β: 11; P < 0.001), influenced by gender and physical activity. The findings highlight the role of gender, weight, and activity in ALS management, suggesting that maintaining a healthy weight along and muscle mass along with regular activity is associated with better outcomes. This can inform personalized treatment strategies for better patient care.},
}

@article {pmid42218846,
year = {2026},
author = {Bridge, F and Thevathasan, W and Schultz, D and Zhang, W and Wright, E and Yeh, WZ},
title = {Neurosymptomatic HIV CSF viral escape with parkinsonism and amyotrophic lateral sclerosis-like syndrome: a case report.},
journal = {Journal of neuroimmunology},
volume = {418},
number = {},
pages = {578992},
doi = {10.1016/j.jneuroim.2026.578992},
pmid = {42218846},
issn = {1872-8421},
abstract = {Human immunodeficiency virus (HIV) infection can lead to various neurologic complications affecting central and peripheral nervous systems. Rarely, patients on combined anti-retroviral therapy (CART) with peripheral virologic suppression may develop compartmentalised central nervous system infection with cerebrospinal fluid (CSF) viral escape. We report the case of a 42-year-old man with chronic HIV infection and a previous diagnosis of Parkinson's disease referred for neurologic evaluation with diffuse hyperreflexia including brisk jaw jerk. He was adherent to combined anti-retroviral therapy (CART). During follow-up, he developed mild upper and lower limb weakness and gait instability. Electromyography was consistent with a motor neuropathy or neuronopathy. Neuraxial MRI showed non-specific supratentorial white matter lesions. Plasma HIV viral load was suppressed (<20 copies/mL) whereas CSF viral load was 35 copies/mL, consistent with CSF viral escape. CSF neopterin level was elevated indicating neuroinflammation. HIV-associated neurological overlap syndrome, with parkinsonism and an amyotrophic lateral sclerosis-like syndrome, in the context of neurosymptomatic CSF escape was diagnosed. The patient's HIV CART regime was adjusted to improve CNS penetration. Neurosymptomatic HIV CSF escape is a rare and likely under-recognised complication which can occur despite compliance with CART. When suspected, CSF viral load should be tested. CART optimisation to improve CNS penetration may be potentially beneficial in neurosymptomatic CSF viral escape and to reduce HIV-associated neurotoxicity, but these require further study to confirm.},
}

@article {pmid42219148,
year = {2026},
author = {Martin, R and Beauchamp-Chalifour, P and Rayes, J and Matovinovic, K and Schneider, PS},
title = {Incidence and Strategies for Prevention of Adjustable Loop Suspensory Fixation Maldeployment in Multiligament Knee Reconstruction.},
journal = {Journal of ISAKOS : joint disorders & orthopaedic sports medicine},
volume = {},
number = {},
pages = {101151},
doi = {10.1016/j.jisako.2026.101151},
pmid = {42219148},
issn = {2059-7762},
abstract = {INTRODUCTION/OBJECTIVES: Adjustable loop suspensory (ALS) fixation offers the ability to re-tension grafts in complex multiligament knee reconstruction. A frequent complication of adjustable loop fixation is implant maldeployment. This study's primary objective was to determine the incidence of implant maldeployment associated with ALS fixation in a cohort of patients that underwent multiligament knee reconstruction and to identify the most at risk tunnel(s). Our secondary objective was to determine the clinical impact of implant maldeployment.

METHODS: Demographic, radiological, and clinical data were collected from adult patients who underwent multiligament knee reconstruction using ALS fixation, between January 1, 2018, and January 1, 2020. The primary outcome measure was the incidence of implant maldeployment, as defined by radiologic soft-tissue interposition of >5 mm or radiologic intraosseous button flip. Secondary outcomes were the rate of reoperation, postoperative Lysholm and Tegner scores and postoperative knee range of motion. Statistical analyses were conducted using univariate logistic regression, and Odds Ratio (OR) with 95% confidence interval (CI) were reported.

RESULTS: A total of 241 ALS buttons were included in 56 patients, predominantly male patients (N=39, 70%), with a median age of 32 [26.0-42.0] years. The incidence of ALS implant maldeployment was 5% (N=11/241). Soft-tissue interposition maldeployment only occurred for the femoral medial collateral ligament (MCL) and the femoral posterior cruciate ligament posteromedial bundle fixation (PCL PM). Reoperation occurred in five out of nine (56%) patients with maldeployment, and six out of 34 (18%) in patients with well deployed implants (OR 6.8, 95% CI 1.1 to 49, p=0.022). Maldeployment did not appear to impact postoperative knee patient reported outcomes or range of motion (p≥0.05). The median follow-up duration was 9.1 [7.4-13.6] months.

CONCLUSION: This cohort demonstrates a 5% incidence of maldeployment when using ALS fixation. Despite maldeployment, ALS fixation demonstrated similarly favorable clinical outcomes, but higher rate of reoperation. In multiligament reconstructions, surgeons should be particularly attentive with femoral ALS button deployment for PCL and MCL grafts.

LEVEL OF EVIDENCE: IV.},
}

@article {pmid42219616,
year = {2026},
author = {Busi, R and Goggin, D and Eyres, N and Runge, F and Porri, A and Flower, K},
title = {A Trp574-Leu substitution confers resistance to three classes of acetolactate synthase inhibitors in Australian brome grass (Bromus diandrus).},
journal = {Pest management science},
volume = {},
number = {},
pages = {},
doi = {10.1002/ps.70979},
pmid = {42219616},
issn = {1526-4998},
support = {UWA2007-002RTX//Grains Research and Development Corporation/ ; },
abstract = {BACKGROUND: Brome grass (Bromus diandrus) is a prevalent weed in southern Australian cropping regions which causes significant economic damage in crops and pastures. Before harvest 2023, two populations (named 6-24 and 7-24) suspected of resistance to imidazolinone herbicides were collected from separate fields. Preliminary screening indicated that these populations were resistant to several different acetolactate synthase (ALS)-inhibiting herbicides. Therefore, further characterisation of the level and mechanism of resistance was carried out.

RESULTS: There was high survival of the resistant populations at the maximum tested rates of sulfometuron (600 g ha[-1]) and imazamox + imazapyr (74 + 34 g ha[-1], 2× the label rate for use in imidazolinone-tolerant crops). All examined individuals (15 from each population) carried the same point mutation causing a tryptophan-to-leucine substitution at position 574 in the ALS protein. Application of the cytochrome P450 inhibitor malathion prior to herbicide treatment did not affect survival rates.

CONCLUSIONS: This is the first study reporting a Trp574-Leu mutation as the basis for cross-resistance to ALS-inhibiting herbicides (sulfonylureas, imidazolinones and triazolopyrimidines) in Australian populations of B. diandrus. Control of these populations will require strategic use of pre-emergence herbicides and herbicide-tolerant crops in combination with harvest weed seed control. © 2026 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.},
}

@article {pmid42219776,
year = {2026},
author = {Patera, E and Avilova, O and Choudhury, B and Burns, D},
title = {Empowering anatomists at all career stages: The vital role of reflective practice for professional growth.},
journal = {Anatomical sciences education},
volume = {},
number = {},
pages = {},
doi = {10.1002/ase.70271},
pmid = {42219776},
issn = {1935-9780},
abstract = {Supporting the growth of anatomy educators is both an investment in individuals and in the future of anatomy education. Anatomy educators come from diverse academic and professional backgrounds and hold varied teaching portfolios. Consequently, their professional needs differ depending on their training, qualifications, and roles. Empowering anatomy educators requires a long-term commitment that combines personal development, institutional initiatives, and a culture of reflection. A cornerstone of this process is reflective practice, which enables anatomy educators to strengthen their teaching, refine their professional identity, and adapt to evolving educational needs. In this viewpoint commentary, we recommend three practical strategies for getting started with critical reflection: (a) writing a teaching philosophy statement (TPS), (b) adopting the Teaching Squares approach, and (c) developing a teaching portfolio, each providing structured opportunities for educators to critically examine and enhance their practice. Established reflective models such as Gibbs' Reflective Cycle, Rolfe et al.'s Reflective Model, and Brookfield's Four Lenses of Reflection can help guide anatomy educators in structuring their critical reflection. Finally, we emphasize that engaging in critical self-reflection is not a tick-box exercise but a deliberate and ongoing practice essential for the professional growth of anatomy educators, as well as the cultivation of a reflective academic culture.},
}

@article {pmid42221419,
year = {2019},
author = {Kocia, L and Love, P},
title = {The non-disjoint ontic states of the Grassmann ontological model, transformation contextuality, and the single qubit stabilizer subtheory.},
journal = {Journal of physics. A, Mathematical and theoretical},
volume = {52},
number = {9},
pages = {},
pmid = {42221419},
issn = {1751-8113},
abstract = {We show that it is possible to construct a preparation non-contextual ontological model that does not exhibit 'transformation contextuality' for single qubits in the stabilizer subtheory. In particular, we consider the 'blowtorch' map and show that it does not exhibit transformation contextuality under the Grassmann Wigner-Weyl-Moyal (WWM) qubit formalism. Furthermore, the transformation in this formalism can be fully expressed at order ℏ 0 , where it satisfies all of Kolmogorov's axioms of classical probability theory, and so does not qualify as a candidate quantum phenomenon. In particular, we find that the Grassmann WWM formalism at order ℏ 0 corresponds to an ontological model governed by an additional set of constraints arising from the relations defining the Grassmann algebra. Due to this additional set of constraints, the allowed probability distributions in this model do not form a single convex set when expressed in terms of disjoint ontic states and so cannot be mapped to models whose states form a single convex set over disjoint ontic states. However, expressing the Grassmann WWM ontological model in terms of non-disjoint ontic states corresponding to the monomials of the Grassmann algebra results in a single convex set. We further show that a recent result by Lillystone et al that proves a broad class of preparation and measurement non-contextual ontological models must exhibit transformation contextuality lacks the generality to include the ontological model considered here; Lillystone et al's result is appropriately limited to ontological models whose states produce a single convex set when expressed in terms of disjoint ontic states. Therefore, we prove that for the qubit stabilizer subtheory to be captured by a preparation, transformation and measurement non-contextual ontological theory, it must be expressed in terms of non-disjoint ontic states, unlike the case for the odd-dimensional single-qudit stabilizer subtheory.},
}

@article {pmid42221822,
year = {2026},
author = {Sreeram, A and Baron, DM and Brusati, A and Stallworth, K and Humphrey, J and Landers, JE},
title = {Global transcriptional changes across multiple isogenic C9orf72 patient iPSC-derived neurons.},
journal = {iScience},
volume = {29},
number = {6},
pages = {116054},
pmid = {42221822},
issn = {2589-0042},
abstract = {Hexanucleotide repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD); yet, mechanisms underlying selective neuronal vulnerability remain unclear. A major challenge in identifying consistent transcriptomic changes across C9orf72 patient-derived neuron lines has been heterogeneous differentiations, lack of isogenic controls and low sequencing depth. To overcome these challenges, we generated homogeneous cortical neuron (iCNs) cultures from multiple isogenic C9orf72 patient iPSC pairs and performed RNA deep sequencing. We identified robust and reproducible gene expression and splicing alterations in pathways related to cytoskeletal organization, extracellular matrix adhesion and synaptic signaling. Notably, we observed exon 30 skipping in the cytoskeletal regulator filamin B (FLNB), resulting in loss of its hinge domain. This was accompanied by altered FLNB localization, disrupted actin crosslinking, and mechanotransduction signaling. These findings reveal convergent transcriptomic and functional disruptions across multiple isogenic C9orf72 patient-derived iCNs offering insights into ALS/FTD pathogenesis.},
}

@article {pmid42222887,
year = {2026},
author = {Michels, S and Chen, C and Ruf, WP and Garcia Garcia, MM and Arnold, FJ and Wu, Z and Bennett, CL and Shams, D and Thompson, LM and Walker, AC and Dickson, DW and Petrucelli, L and Dorst, J and Prudencio, M and Li, W and La Spada, AR},
title = {Multimodal analysis of cell-free DNA identifies epigenetic biomarkers for amyotrophic lateral sclerosis diagnosis and progression.},
journal = {The Journal of clinical investigation},
volume = {136},
number = {11},
pages = {},
doi = {10.1172/JCI191508},
pmid = {42222887},
issn = {1558-8238},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis/blood ; *Cell-Free Nucleic Acids/genetics/blood/cerebrospinal fluid ; Female ; *Epigenesis, Genetic ; *DNA Methylation ; Male ; Biomarkers/blood/cerebrospinal fluid ; C9orf72 Protein/genetics ; Disease Progression ; Middle Aged ; Aged ; Neurofilament Proteins/cerebrospinal fluid ; Adult ; },
abstract = {The role of the epigenome in age-related neurodegenerative disorders remains understudied. Here, we analyzed circulating cell-free DNA (cfDNA) from blood to detect methylation changes as a liquid biopsy for Amyotrophic Lateral Sclerosis (ALS). Our study included 20 patients with sporadic ALS, 10 patients with C9orf72-associated ALS, 10 asymptomatic carriers of the C9orf72 repeat expansion mutation, and 21 nondisease control individuals. Following targeted enzymatic methyl-sequencing (EM-seq) of approximately 4 million CpG sites, we detected numerous differentially methylated genes, including several implicated in ALS disease risk and pathogenesis. By integrating multiple epigenetic features, we delineated a distinct epigenetic signature, which achieved an average area under the curve (AUC) of 0.91 ± 0.10 upon receiver operator characteristic (ROC) analysis, which enabled detection of approximately 70% of patients with ALS with close to 100% specificity. Furthermore, we also identified a set of genes whose methylation status significantly correlated with clinical disease progression and cerebrospinal fluid (CSF) neurofilament levels. Our results reveal the potential of cfDNA-based biomarkers to accurately diagnose ALS and potentially predict disease progression.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/diagnosis/blood
*Cell-Free Nucleic Acids/genetics/blood/cerebrospinal fluid
Female
*Epigenesis, Genetic
*DNA Methylation
Male
Biomarkers/blood/cerebrospinal fluid
C9orf72 Protein/genetics
Disease Progression
Middle Aged
Aged
Neurofilament Proteins/cerebrospinal fluid
Adult

@article {pmid42222897,
year = {2026},
author = {Inoue, H and Horimoto, Y and Tsuda, Y and Madokoro, Y and Kawashima, S and Akagi, A and Iwasaki, Y and Matsukawa, N},
title = {Visible Tongue Fasciculations With Electromyographic Denervation in Autopsy-Proven Progressive Supranuclear Palsy Mimicking Amyotrophic Lateral Sclerosis.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70308},
pmid = {42222897},
issn = {1097-4598},
}

@article {pmid42222958,
year = {2026},
author = {Zeigler-Hill, V},
title = {Desperate to connect: Men's dependence on romantic relationship in a competitive mating landscape.},
journal = {The Behavioral and brain sciences},
volume = {49},
number = {},
pages = {e130},
doi = {10.1017/S0140525X25102483},
pmid = {42222958},
issn = {1469-1825},
mesh = {Humans ; Male ; *Competitive Behavior ; *Sexual Partners/psychology ; *Interpersonal Relations ; Emotions ; },
abstract = {This commentary builds on Wahring et al.'s model of male emotional dependency by integrating mating market dynamics. It argues that men's reliance on romantic partners, combined with competitive pressures and limited emotional networks, creates a volatile psychological landscape. Romantic failure, in this context, can deeply threaten self-worth - fueling distress, behavioral issues, and, in extreme cases, ideological radicalization.},
}

Humans
Male
*Competitive Behavior
*Sexual Partners/psychology
*Interpersonal Relations
Emotions

@article {pmid42214970,
year = {2026},
author = {Franzoia, B and de Diego-Balaguer, R},
title = {The beat in speech: A window into the attentional mechanisms supporting the detection of non-adjacent dependencies.},
journal = {Cognition},
volume = {274},
number = {},
pages = {106596},
doi = {10.1016/j.cognition.2026.106596},
pmid = {42214970},
issn = {1873-7838},
abstract = {Converging evidence suggests that musical training can elicit positive transfer effects across multiple domains of language processing, including grammar. In humans, exposure to musical rhythm induces beat and meter perception, which has been shown to enhance attentional allocation and temporal prediction. Theories hypothesize that the predictive gains intrinsic to music rhythmicity may exert cascading effects on syntactic processing by modulating sensitivity to speech prosody. From this perspective, learning should also be boosted insofar as prosody tends to align with grammatical structure. In the present study, we introduce a novel behavioural paradigm to investigate the link between rhythmicity and grammar learning by testing whether the rhythmic beat facilitates the detection of grammar-like structures in artificial languages (ALs), implemented as non-adjacent dependencies (NADs) between variable syllables forming a speech stream (e.g., PU reliably predicts KI in PUlaruKI). A total of 147 participants were exposed to four ALs that varied in rhythmic, grammatical structure, and the alignment between the two: (i) a beat-inducing rhythm with no NADs; (ii) a beat-hindering rhythm with NADs; (iii) a beat-inducing rhythm with embedded NADs temporally misaligned, and (iv) NADs aligned with beat time-points. Results of the implicit and, after exposure, explicit learning measures demonstrate enhanced learning when NADs are embedded within beat-inducing rhythmic structures. Together, these findings suggest that rhythm enhances predictive and attentional mechanisms implicated in grammar learning, underscoring their role in its acquisition.},
}

@article {pmid42215498,
year = {2026},
author = {Viuff, JH},
title = {Immortal time bias from conditioning on future events in Parkinson's disease survival analysis.},
journal = {NPJ Parkinson's disease},
volume = {12},
number = {1},
pages = {},
pmid = {42215498},
issn = {2373-8057},
abstract = {This comment highlights potential immortal time bias in Brakedal et al.’s study of Parkinson’s disease (PD) survival. Because PD status and exclusion criteria rely on future prescription patterns, individuals classified as having PD are, by design, unable to die during early follow-up. This likely inflates survival estimates, particularly among the oldest patients. Aligning eligibility criteria with the start of follow-up and avoiding conditioning on future events would reduce this bias in future research.},
}

@article {pmid42215790,
year = {2026},
author = {Li, S and Xu, S and Li, F and Zhao, Q and Zhang, P and Guan, Q and Sun, X and Bi, J and Xiao, H and Tang, Y and Peng, C and Chen, Q and Wang, Y and Yang, M},
title = {The C9orf72/SMCR8 complex maintains microglial homeostasis via RAB8A ESCRT-mediated lysosomal repair.},
journal = {The EMBO journal},
volume = {},
number = {},
pages = {},
pmid = {42215790},
issn = {1460-2075},
support = {32070743//MOST | National Natural Science Foundation of China (NSFC)/ ; 32560156//MOST | National Natural Science Foundation of China (NSFC)/ ; 202401BF070001-015//Yunnan Provincial Science and Technology Department ()/ ; 202401AS070131//Yunnan Provincial Science and Technology Department ()/ ; C619300A142//Yunnan Provincial Science and Technology Department ()/ ; C1762201000139//Yunnan University (YNU)/ ; KC-242410334//Yunnan University (YNU)/ ; },
abstract = {Microglia are critical regulators of neuroinflammation and neurodegeneration. Haploinsufficiency of C9orf72, the most frequently mutated gene in amyotrophic lateral sclerosis and frontotemporal dementia, has been linked to autophagy-lysosomal pathway defects, but the role of C9orf72 in microglia remains unclear. Here, we identify the C9orf72/SMCR8 complex as a key regulator of microglial homeostasis through promoting lysosomal membrane repair. Loss of C9orf72 and SMCR8 in mice causes age‑dependent neuroinflammation and microgliosis, with microglia adopting a disease-associated state. In aged brain and spinal cord tissue, microglia display lysosomal damage marked by galectin‑3 accumulation. Using a lysosomotropic agent to induce lysosomal damage in microglia, we find that C9orf72/SMCR8-deficient cells accumulate damaged lysosomes and show defective recruitment of phosphorylated RAB8A and the Endosomal Sorting Complexes Required for Transport (ESCRT) machinery to damaged lysosomes. Notably, mutant microglia accumulate GTP‑bound RAB8A, which becomes hyperphosphorylated and mislocalized to RAB7-positive, LAMP1-negative vesicles. The GTPase-activating activity of the C9orf72/SMCR8 complex is essential for lysosomal repair. Our findings reveal that the C9orf72/SMCR8 complex coordinates RAB8A-ESCRT-mediated lysosomal repair to safeguard microglial homeostasis and limit neuroinflammation.},
}

@article {pmid42215819,
year = {2026},
author = {Ream, A and Woodcock, A and Zlatkovic, S and Pedersen, RM and Bonilla, A and Middleton, H and Hernandez, PR and Schultz, PW},
title = {Implementing multiple implicit association tests in Qualtrics: A guide and demonstration using balanced identity design theory.},
journal = {Behavior research methods},
volume = {58},
number = {7},
pages = {},
pmid = {42215819},
issn = {1554-3528},
mesh = {Humans ; *Association ; Software ; Surveys and Questionnaires ; Attitude ; },
abstract = {Interest in implicit processes, such as attitudes and identities, has grown in behavioral sciences since Greenwald and colleagues (1998) developed and introduced the Implicit Association Test (IAT). The IAT was developed to measure these processes, which has become more accessible with the popularity of Qualtrics as a data collection tool, especially through methods and code provided by Carpenter et al. (2019). They demonstrated how to construct a single IAT for use on the Qualtrics platform, providing research resources for creating IATs to examine concept-pair associations. However, there is no guidance on constructing multiple IATs on survey software platforms for research that requires two or more IATs in a single study. This paper extends Carpenter et al.'s (2019) work by outlining the process of developing, implementing, and utilizing multiple IATs within a single Qualtrics survey. We provide a tutorial using examples from our research using the Balanced Identity Design (BID) framework, including step-by-step written and visual instructions and templates, instructions for planning and building multiple IATs and dynamically presenting them in a single Qualtrics survey and code for processing IAT data. We also demonstrate the utility of the multiple IAT approach by reporting a short study utilizing BID theory wherein we measure implicit racial/ethnic identity, STEM identity, and race/ethnicity-STEM associations in a single study via three IATs.},
}

Humans
*Association
Software
Surveys and Questionnaires
Attitude

@article {pmid42215859,
year = {2026},
author = {La Cognata, V and Gentile, G and Morello, G and Guarnaccia, M and Cavallaro, S},
title = {RNA-centric approaches in amyotrophic lateral sclerosis: prospects for future therapeutics.},
journal = {Expert opinion on therapeutic targets},
volume = {},
number = {},
pages = {},
doi = {10.1080/14728222.2026.2682782},
pmid = {42215859},
issn = {1744-7631},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by profound clinical and molecular heterogeneity, which has substantially hindered the development of effective therapies. Significant advances in ALS research have been driven by the study of RNA biology, together with the implementation of advanced transcriptomic technologies and artificial intelligence - based algorithms, which are assuming a transformative role in reshaping the field.

AREAS COVERED: We discuss how genome-wide expression profiling enables the identification of molecular signatures for drug discovery and repurposing, facilitates the stratification of patients into biologically distinct subtypes for more refined clinical trials, and guides the development of novel nucleic acid-based therapies. Furthermore, we explore the potential of transcriptomics to identify molecular vulnerabilities during pre-symptomatic stages, paving the way for early intervention.

EXPERT OPINION: The convergence of transcriptomics and artificial intelligence is poised to fundamentally redefine ALS, transforming it from a single clinical entity into a spectrum of molecularly defined disorders, each potentially amenable to targeted therapeutic intervention. While challenges in translating high-dimensional data into clinical practice remain, the integration of transcriptomics with advanced computational tools promises to accelerate the transition toward a new era of personalized medicine in ALS.},
}

@article {pmid42214472,
year = {2026},
author = {Garrett, TL and Wintermute, L and Armitage, M and Ward, S and Gerber, K and Elbasiouny, SM},
title = {Optimized multiplex immunofluorescent protocols for simultaneous in situ identification of α-motoneuron subtypes.},
journal = {Journal of neuroscience methods},
volume = {},
number = {},
pages = {110815},
doi = {10.1016/j.jneumeth.2026.110815},
pmid = {42214472},
issn = {1872-678X},
abstract = {BACKGROUND: Accurate identification of α-motoneuron (α-MN) subtypes - slow (S), fast fatigue-resistant (FR), fast fatigue-intermediate (FI), and fast fatigable (FF) - is essential for studying motor circuit organization and selective vulnerability in neurodegenerative disease. While electrophysiological approaches can distinguish these subtypes, existing immunohistochemical (IHC) methods lack the ability to simultaneously identify all four α-MN classes in situ, particularly the FI subtype, limiting their utility for large-scale or tissue-based analyses.

NEW METHOD: Here, we present novel multiplex immunofluorescent strategies that enables simultaneous in situ identification of S, FR, FI, and FF α-MN subtypes, including intermediate populations, within single sections of mouse lumbar spinal cord. This approach integrates a combinatorial marker framework with optimized co-labeling conditions to resolve subtype-specific molecular signatures, including FI MNs, which have not been previously distinguishable using standard IHC methods.

RESULTS: We establish a systematic validation pipeline demonstrating robust and reproducible subtype classification across multiple protocols, sexes, mouse strains, and disease conditions, including the G93A-SOD mouse model of amyotrophic lateral sclerosis. Labeled populations recapitulate known size distributions and exhibit consistent subtype-specific patterns across lumbar segments, supporting both the accuracy and reproducibility of the method.

CONCLUSIONS: By enabling comprehensive in situ classification of all major α-MN subtypes, this approach represents a substantive refinement of multiplex IF, overcoming key limitations of existing IF methods and enabling analyses of α-MN subtype organization and selective vulnerability that were previously not feasible with standard histological techniques. This framework is broadly applicable to studies of motor system organization, aging, and neurodegenerative disease.},
}

@article {pmid42204729,
year = {2026},
author = {Pasetto, L and Callegaro, S and Corbelli, A and Fiordaliso, F and Ferrara, D and Brunelli, L and Sestito, G and Pastorelli, R and Bianchi, E and Cretich, M and Chiari, M and Potrich, C and Moglia, C and Corbo, M and Sorarù, G and Lunetta, C and Calvo, A and Chiò, A and Mora, G and Pennuto, M and Quattrone, A and Rinaldi, F and D'Agostino, VG and Basso, M and Bonetto, V},
title = {Correction: Decoding distinctive features of plasma extracellular vesicles in amyotrophic lateral sclerosis.},
journal = {Molecular neurodegeneration},
volume = {21},
number = {1},
pages = {},
doi = {10.1186/s13024-026-00955-z},
pmid = {42204729},
issn = {1750-1326},
}

@article {pmid42205021,
year = {2026},
author = {Sun, QH and Xuan, X and Du, YG and Zhai, YC and Ma, T and Duan, F and Xia, CQ and Huang, XS and Huang, YH and Wang, HF},
title = {APOE ε4 Allele is Associated with Cognitive Impairment in Chinese Sporadic ALS: A Retrospective Cohort Study.},
journal = {Biomedical and environmental sciences : BES},
volume = {39},
number = {5},
pages = {564-571},
doi = {10.3967/bes2026.038},
pmid = {42205021},
issn = {2214-0190},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Alleles ; *Amyotrophic Lateral Sclerosis/genetics/complications ; *Apolipoprotein E4/genetics/blood ; China ; *Cognitive Dysfunction/genetics/etiology ; Genotype ; Retrospective Studies ; East Asian People/genetics ; },
abstract = {OBJECTIVE: To evaluate the effects of apolipoprotein E (APOE) genotype and serum APOE levels on cognitive and motor phenotypes in Chinese patients with sporadic amyotrophic lateral sclerosis (ALS).

METHODS: APOE genotypes were determined in 289 patients with sporadic ALS, and serum APOE levels were measured in a subset of 222 patients. Cognitive function was assessed using the Edinburgh Cognitive and Behavioural ALS Screen. We examined the association of APOE genotype and serum levels with age at onset, site of onset, disease progression rate (DPR), time to generalization of symptoms (TTG), and cognitive performance.

RESULTS: No significant differences were observed in sex, age at onset, site of onset, DPR, or TTG among patients with different APOE genotypes. Similarly, serum APOE levels did not correlate with these clinical variables. However, the APOE-ε4 allele was associated with lower ALS-specific cognitive scores, particularly in the domain of verbal fluency.

CONCLUSION: Our study provides preliminary evidence linking the APOE-ε4 allele to cognitive impairment, particularly in language fluency, among Chinese patients with ALS. These findings support the hypothesis that APOE genotype contributes to ALS etiology and suggest its role in shaping distinct cognitive phenotypes in the disease.},
}

Adult
Aged
Female
Humans
Male
Middle Aged
Alleles
*Amyotrophic Lateral Sclerosis/genetics/complications
*Apolipoprotein E4/genetics/blood
China
*Cognitive Dysfunction/genetics/etiology
Genotype
Retrospective Studies
East Asian People/genetics

@article {pmid42206537,
year = {2026},
author = {Pulecio, J and Parra, S and Quiroz, W and Bravo, MA},
title = {Chemometric-Assisted Determination of Benzo[a]pyrene (BaP) and Benzo[a]anthracene (BaA) in Water Samples Using Fluorescence and Commercial Membranes: A White Analytical Chemistry Approach.},
journal = {Luminescence : the journal of biological and chemical luminescence},
volume = {41},
number = {6},
pages = {e70523},
doi = {10.1002/bio.70523},
pmid = {42206537},
issn = {1522-7243},
support = {Fondecyt Regular 1240296//Agencia Nacional de Investigación y Desarrollo, ANID/ ; ANID-PFCHA/Doctorado nacional/2024-21242116//Agencia Nacional de Investigación y Desarrollo, ANID/ ; },
mesh = {*Benzo(a)pyrene/analysis ; *Benz(a)Anthracenes/analysis ; *Water Pollutants, Chemical/analysis ; Spectrometry, Fluorescence ; *Membranes, Artificial ; Fluorescence ; },
abstract = {This study evaluates different solid membranes to develop an analytical method for the immobilization of two priority PAHs, benzo[a]pyrene (BaP) and benzo[a]anthracene (BaA), followed by the measurement of excitation-emission fluorescence matrices (directly measured over the membrane) coupled to second-order multivariate calibration. Commercially available membranes, such as nylon and C18, proved to be suitable supports for these purposes, especially for aqueous samples. The multivariate curve resolution-alternating least squares (MCR-ALS) algorithm showed adequate flexibility to fit the data and achieve the second-order advantage, even in the presence of unmodeled interferences. Even though both membranes showed different selectivity, the developed method allows quantification of PAH at ng L[-1] levels with a prediction error below 10%. The proposed methodology was successfully applied to spiked real water samples, demonstrating its suitability for detecting PAHs at trace levels. Finally, the proposed method was evaluated and compared with reported analytical approaches based on white analytical chemistry principles, showing remarkable analytical performance for monitoring PAHs in natural water samples.},
}

*Benzo(a)pyrene/analysis
*Benz(a)Anthracenes/analysis
*Water Pollutants, Chemical/analysis
Spectrometry, Fluorescence
*Membranes, Artificial
Fluorescence

@article {pmid42206648,
year = {2026},
author = {Pupillo, E and Bianchi, E and Diamanti, L and Bergamaschi, R and Pisoni, E and Riva, N and Lunetta, C and Filosto, M and Padovani, A and Tremolizzo, L and De Lodovici, ML and Leone, MA and , },
title = {Air pollutants and amyotrophic lateral sclerosis in a population-based registry: investigating disease susceptibility, progression and survival.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/21678421.2026.2677537},
pmid = {42206648},
issn = {2167-9223},
abstract = {Objective: to investigate the association between long-term exposure to fine particulate matter (PM2.5) and nitrogen oxides (NOx) with ALS risk, progression, and survival. Methods: We conducted a population-based study in Lombardy, Italy. A case-control analysis included 161 incident ALS cases (2011-2014) and 161 age-, sex-, and province-matched controls. Average residential exposures to PM2.5 and NOx over the 20 years before diagnosis were estimated using European Monitoring and Evaluation Programme data and analysed with conditional logistic regression. A retrospective cohort of 135 ALS cases was used to assess associations with disease progression (ΔFS) and mortality using logistic and Cox regression models, adjusting for demographic and lifestyle factors. Results: Higher PM2.5 exposure in the 20 years preceding diagnosis was associated with increased ALS risk (adjusted OR per 5 µg/m[3] increase 1.19; 95% CI 1.01-1.40), with consistent findings across sensitivity analyses. NOx was not associated with ALS incidence. In contrast, NOx exposure in the 5 years before diagnosis was marginally associated with increased mortality (adjusted HR 1.12; 95% CI 1.00-1.26), whereas PM2.5 was not. Neither pollutant was significantly associated with disease progression rate. Conclusions: Long-term PM2.5 exposure was associated with higher ALS risk, while NOx showed a modest association with mortality. These findings support a role of air pollution in ALS susceptibility and highlight the need for integrated environmental prevention strategies to mitigate the burden of neurodegenerative diseases.},
}

@article {pmid42207242,
year = {2026},
author = {Alarcan, H and Veyrat-Durebex, C and Pradat, PF and Cassereau, J and Destee, A and Couratier, P and Camu, W and Neau, JP and Fleury-Lesaunier, MC and Emond, P and Dufour, D and Al Ojaimi, Y and Lefèvre, A and Vourc'h, P and Corcia, P and Andres, CR and Blasco, H},
title = {Anchoring ALS Prognosis: Neurofilament Light Chain Outperforms Inflammatory, Metabolic, and CNS Barrier Biomarkers in the METABALS Cohort.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42207242},
issn = {1559-1182},
mesh = {Humans ; *Neurofilament Proteins/blood/metabolism/cerebrospinal fluid ; Biomarkers/metabolism/blood ; *Amyotrophic Lateral Sclerosis/metabolism/blood/diagnosis/pathology ; Female ; Male ; Prognosis ; Middle Aged ; Cohort Studies ; *Inflammation/metabolism/blood ; *Blood-Brain Barrier/metabolism ; *Blood-Spinal Cord Barrier/metabolism ; *Metabolomics/methods ; Aged ; Kynurenine/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder with marked biological heterogeneity. Despite extensive research, reliable prognostic biomarkers remain limited, with neurofilament light chain (NfL) being the only marker increasingly implemented in clinical practice. The objective of this study is to assess and compare the prognostic value of NfL, circulating markers of central nervous system (CNS) barrier dysfunction, inflammatory mediators, kynurenine pathway metabolites, and global metabolomic profiles in patients with ALS. Seventy-two patients with ALS from the prospective multicenter METABALS cohort were included. Serum, cerebrospinal fluid (CSF), and urine samples were collected at diagnosis. NfL concentrations, markers of blood-brain and blood-spinal cord barrier permeability (albumin quotient, S100B, neuron-specific enolase [NSE]), 48 inflammatory mediators, kynurenine pathway metabolites, and untargeted metabolomic profiles were measured. Associations with clinical features, disease progression, and survival were investigated using univariate analyses and multivariate models. Serum and CSF NfL concentrations were strongly associated with ALS Functional Rating Scale-Revised scores, respiratory function, diagnostic delay, and survival. Higher serum NfL concentrations at diagnosis predicted shorter survival (ROC AUC = 0.86). In all multivariate and multi-block models, serum NfL was the only biomarker independently associated with survival. Markers of CNS barrier integrity, inflammatory mediators, and metabolomic signatures showed limited prognostic value but provided insights into metabolic remodeling and barrier dysfunction. In this integrated multi-omics study, serum NfL clearly outperformed inflammatory, metabolic, and CNS barrier markers as a prognostic biomarker in ALS, supporting its central role in clinical stratification while complementary biological markers highlighted several relevant pathophysiological mechanisms.},
}

Humans
*Neurofilament Proteins/blood/metabolism/cerebrospinal fluid
Biomarkers/metabolism/blood
*Amyotrophic Lateral Sclerosis/metabolism/blood/diagnosis/pathology
Female
Male
Prognosis
Middle Aged
Cohort Studies
*Inflammation/metabolism/blood
*Blood-Brain Barrier/metabolism
*Blood-Spinal Cord Barrier/metabolism
*Metabolomics/methods
Aged
Kynurenine/metabolism

@article {pmid42207631,
year = {2026},
author = {Valenti, D and Joshi, V and Pankivskyi, S and Cai, HH and Hamon, L and Desforges, B and Molliex, A and Duez, J and Bursztyka, J and Davignon, L and Maucuer, A and Bollot, G and Pastré, D},
title = {RNA-binding protein diversity and NLS arginines regulate FUS mixing in mRNA-rich compartments.},
journal = {Cell reports},
volume = {45},
number = {6},
pages = {117430},
doi = {10.1016/j.celrep.2026.117430},
pmid = {42207631},
issn = {2211-1247},
abstract = {Despite being prone to condensation, many RNA-binding proteins (RBPs) do not form large condensates in cells. This issue is still widely researched, particularly because aggregation of RBPs, such as FUS, is the hallmark of some neurodegenerative diseases. Elevated RNA levels and protein chaperone activity have already emerged as key factors preventing aberrant phase separation. Here, we explored the role of RBP diversity in mRNA-rich condensates. While FUS and its partners form distinct compartments when probed one by one, increasing RBP diversity buffers FUS spatial segregation. In addition, we found that frequently mutated arginine residues in the nuclear localization signal (NLS) at the C-terminal end promote FUS mixing with multiple RBPs. Therefore, we anticipate that pathological NLS mutations in FUS not only alter its active nuclear import but also regulate FUS interactions with its partners in mRNA-rich compartments with putative consequences for the onset and progression of FUS-related neurodegenerative diseases.},
}

@article {pmid42207731,
year = {2026},
author = {Queiroz, EM and Couto, CM and Ferreira, AR and de Souza, LC and Caramelli, P},
title = {Clinical presentation and diagnostic challenges of frontotemporal dementia in Brazil: A 15-year cohort study.},
journal = {Neuroepidemiology},
volume = {},
number = {},
pages = {1-23},
doi = {10.1159/000552730},
pmid = {42207731},
issn = {1423-0208},
abstract = {INTRODUCTION: Frontotemporal dementia (FTD) comprises heterogeneous neurodegenerative syndromes with limited data from low- and middle-income countries, where diagnostic delay and misdiagnosis are common.

METHODS: A retrospective cohort study was conducted of 190 patients with FTD meeting criteria for behavioral variant FTD (bvFTD), primary progressive aphasia (PPA), or FTD-amyotrophic lateral sclerosis (FTD-ALS) who were evaluated at a publicly-funded Brazilian tertiary referral center (2009-2024). Clinical features, diagnostic trajectories, neuroimaging, genetic testing, and survival outcomes were analyzed. Standardized mortality ratios (SMRs) were calculated using IBGE 2017 life tables as a reference.

RESULTS: The cohort comprised 95 bvFTD (50.0%; 73 probable and 22 possible), 79 PPA (41.6%), and 16 FTD-ALS (8.4%) patients. Accurate initial diagnosis was achieved in only 15.8% of bvFTD patients and 17.7% of PPA patients, with Alzheimer's disease being the most common misdiagnosis (36.8% and 34.2%, respectively). Survival differed significantly between subtypes (p < 0.001), with FTD-ALS having the shortest median survival (79.0 months) compared with PPA (119.0 months) and bvFTD (144.0 months). Compared with PPA, FTD-ALS was associated with increased mortality risk (HR: 4.01; 95% CI: 1.94-8.31; p < .001). FTD patients had approximately twice the expected mortality for age- and sex-matched individuals in the general population (SMR: 1.97; 95% CI: 1.59-2.38), with the highest excess mortality in FTD-ALS patients (SMR: 4.08).

DISCUSSION: This Brazilian hospital-based cohort reveals alarming diagnostic delays despite typical clinical phenotypes and high mortality across all FTD subtypes relative to the general population. These findings highlight the need for improved FTD awareness and specialized training among healthcare providers in Brazil and similar Latin American countries, underscoring the value of hospital-based cohort studies in characterizing FTD in low- and middle-income countries.},
}

@article {pmid42210215,
year = {2026},
author = {Paley, CA and Henderson, M and Freeman, S and Acosta, CR and Ziegler, L and Chapman, EJ},
title = {Adapting a brief mindful breathing intervention for self-management of distress in advanced cancer patients: the RESOLVE-i study.},
journal = {BMC palliative care},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12904-026-02148-3},
pmid = {42210215},
issn = {1472-684X},
support = {L412/YCR_/Yorkshire Cancer Research/United Kingdom ; L412/YCR_/Yorkshire Cancer Research/United Kingdom ; L412/YCR_/Yorkshire Cancer Research/United Kingdom ; L412/YCR_/Yorkshire Cancer Research/United Kingdom ; L412/YCR_/Yorkshire Cancer Research/United Kingdom ; L412/YCR_/Yorkshire Cancer Research/United Kingdom ; },
abstract = {BACKGROUND: Psychological distress is common among patients with advanced cancer and can be a barrier to effective symptom management. Despite national guidance, psychological support in UK palliative care remains limited. Existing interventions are frequently delivered by untrained staff lacking confidence. Adapting evidence-based interventions offers an efficient strategy to improve care. This study describes the adaptation of a brief mindful breathing intervention, originally developed in Malaysia, for self-management of distress by patients with advanced cancer in the UK.

METHODS: Using Moore et al.'s ADAPT framework, we followed four stages: Step 1: A systematic review (PROSPERO: CRD42022311729) established a rationale for adapting a brief mindful breathing intervention for distress in advanced cancer. Step 2: Semi-structured interviews with healthcare professionals (HCPs) explored acceptability, perceived utility, and integration into routine care. Step 3: A series of interviews with patients and carers informed the cultural and contextual iterative adaptation of the mindful breathing intervention and the development of accessible self-management resources. Step 4: A feasibility study was designed to assess acceptability, implementation, and to generate pilot data.

RESULTS: The systematic review supported the effectiveness of mindful breathing, though evidence found was context-specific to Malaysian clinical settings. HCPs endorsed integration into routine care but noted time constraints and concerns about information accessibility. Feedback from patients and carers informed several adaptations for self-management, including simplified language, inclusive imagery, removal of prescriptive instructions (e.g., breathing through the nose), and development of low-literacy resources. A video animation, infographic, and HCP training package were created to support implementation.

CONCLUSIONS: This stakeholder-informed adaptation resulted in a self-management mindful breathing intervention tailored for patients with advanced cancer in the UK. The intervention is now ready for feasibility testing and represents a scalable, resource-efficient strategy to enhance psychological support in palliative care, in line with NHS goals for community-based self-management.},
}

@article {pmid42210413,
year = {2026},
author = {Tripathi, P and Guo, H and Yamoah, A and Mathur, R and Doukas, P and Dreser, A and Jesse, CM and Aronica, E and Hermann, A and Steinbusch, H and Brook, GA and Weis, J and Goswami, A},
title = {VAPB confers selective neuroprotection by driving autophagic degradation of pathogenic aggregates in ALS.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-026-02298-8},
pmid = {42210413},
issn = {2051-5960},
abstract = {During the progression of amyotrophic lateral sclerosis (ALS), only specific motor neurons (MNs) preferentially deteriorate, while others are spared until the disease reaches its end stage. Resilient MNs possess several protective factors, yet the precise molecular mechanism(s) underlying selective neuronal vulnerability remains poorly understood. Vesicle-associated membrane protein (VAMP)-binding protein B (VAPB) is an endoplasmic reticulum (ER) protein involved in protein quality control (PQC) mechanisms, including unfolded protein response (UPR) as well as autophagy. A dominantly inherited P56S mutation in the VAPB gene has been linked to ALS8, atypical ALS, and late-onset spinal muscular atrophy (SMA). The P56S VAPB mutation causes ER-associated inclusions, disorganization, and ER stress, contributing to MN degeneration through toxic gain and loss of function. Over-expression of VAPB protein confers neuroprotection in a mouse model of ALS, and increased levels of neuronal VAPB inversely correlate with the absence of pathological aggregates. We hypothesize that VAPB is crucial for motor neuron survival by promoting autophagic degradation of ALS-associated aggregates, while lack of VAPB confers neuronal vulnerability. We analyzed the brain and spinal cord from sporadic (s) and familial (f) ALS patients, comparing patterns of VAPB immunoreactivity using immunohistochemistry, complemented by Western and dot blot analysis. Pathophysiological insights from these studies were further explored using cell culture models, including MNs derived from induced pluripotent stem cells (iPSCs). Consistent with our hypothesis we observed that MNs/neurons resistant to ALS exhibited elevated levels of VAPB and were devoid of pathogenic aggregates. Similarly, ALS-resistant oculomotor neurons showed increased VAPB immunoreactivity compared to normal controls. VAPB was often found to be sequestered within toxic aggregates alongside autophagy-related proteins in the lumbar spinal cord MNs. Notably, a compensatory increase in VAPB immunoreactivity was observed at the C-bouton synapse, suggesting a potential alternative mechanism of neuroprotection. Supporting these findings, in vitro experiments indicated that VAPB overexpression promoted autophagy and assisted in clearing ALS-associated RNA-binding protein aggregates. In summary, VAPB promotes selective neuronal survival by facilitating the autophagic clearance of toxic aggregates. Abnormal VAPB accumulations likely disrupt these neuroprotective processes.},
}

@article {pmid42211895,
year = {2026},
author = {Yang, X and Yang, J and Li, R and Dong, H and Liu, Y},
title = {Peripheral immune cells and glycation indices as potential diagnostic biomarkers in amyotrophic lateral sclerosis.},
journal = {Experimental biology and medicine (Maywood, N.J.)},
volume = {251},
number = {},
pages = {10987},
pmid = {42211895},
issn = {1535-3699},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/blood/immunology ; *Biomarkers/blood ; Female ; Male ; Glycosylation ; Retrospective Studies ; Middle Aged ; Glycated Hemoglobin/analysis ; ROC Curve ; Monocytes ; Aged ; Leukocytes ; },
abstract = {The diagnosis of amyotrophic lateral sclerosis (ALS) mainly relies on clinical symptoms and the exclusion of other diseases, with a lack of specific biomarkers, leading to delayed diagnosis and a high rate of misdiagnosis. This study aims to explore the utility of peripheral immune cells and glycosylation indices as potential diagnostic biomarkers for ALS to enhance the accuracy and efficiency of early ALS diagnosis. This retrospective study included 54 ALS patients diagnosed in our hospital from June 2023 to October 2024, along with 54 healthy controls. Blood samples and laboratory data, including levels of peripheral immune cells and glycosylation indices, were collected from both groups. Through logistic regression, random forest models, receiver operating characteristic (ROC) curve analysis, and SHAP interpretability analysis, the predictive abilities and clinical significance of each candidate indicator were screened and evaluated. Notable disparities were detected in age, leukocyte count, monocyte levels, glycated haemoglobin A1c (HbA1c), and haemoglobin glycation index (HGI) between the control and ALS groups (all P < 0.05). Logistic regression analysis revealed that age (OR = 1.114) and monocyte (OR = 3.174) were risk factors for ALS, while leukocyte (OR = 0.533) and HbA1c (OR = 0.069) were protective factors. The random forest algorithm, ranked by decreasing importance, showed that leukocyte, HGI, monocyte, and HbA1c level all influenced ALS. Using these indicators to predict ALS resulted in a false-positive rate of 18% and a false-negative rate of 6%. ROC curve analysis indicated that the combined use of leukocyte, monocyte, HbA1c level, and HGI provided the highest diagnostic value for ALS (AUC = 0.774), which was higher than that of any individual indicator (all P < 0.05). SHAP analysis visualization demonstrated that increased monocyte and decreased leukocyte, HGI, and HbA1c level were all associated with an increased risk of ALS onset, ranked in descending order of feature importance as monocyte, leukocyte, HGI, and HbA1c. Peripheral blood white blood cells, monocytes, HbA1c, and HGI can serve as potential diagnostic biomarkers for ALS. Combined detection can improve the diagnostic accuracy of ALS, facilitating early diagnosis and intervention, and ultimately improving patient prognosis. Further validation in cohorts including disease controls is required to confirm specificity.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/blood/immunology
*Biomarkers/blood
Female
Male
Glycosylation
Retrospective Studies
Middle Aged
Glycated Hemoglobin/analysis
ROC Curve
Monocytes
Aged
Leukocytes

@article {pmid42212627,
year = {2026},
author = {Raymond, J and Larson, T and Mohidul, S and Martin-Greene, D and Love, K and Mehta, V and Wymer, J and Howard, I and Horton, DK and Mehta, P},
title = {Diagnostic differences between military veterans and non-veterans: data from the United States National ALS Registry.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/21678421.2026.2677528},
pmid = {42212627},
issn = {2167-9223},
abstract = {Background and Aim: Veterans in the U.S. have been reported to have a higher risk of developing amyotrophic lateral sclerosis (ALS) than the general population. However, it is unclear whether veterans experience differences in symptom recognition, diagnostic timing or access to care. This study examined differences reported in clinical characteristics and diagnostic trajectories between male veteran (MV) and non-veteran male (NVM) ALS patients enrolled in the U.S. National ALS Registry. Methods: We conducted a propensity score-matched analysis using self-administered military and clinical surveys from 2014 to 2024. Among 2,891 male ALS patients, MV were matched 1:1 with NVM on smoking history, birth year, head injury history, and region of residence at diagnosis. Outcomes included reported symptoms, time from symptom onset to diagnosis, and time to selected interventions. Results: Overall, 802 MV were matched to 802 NVM. Veterans were older at and reported longer intervals from symptom onset to ALS diagnosis (20.8 vs 16.7 months, p = 0.0004). MV were more likely to report difficulty swallowing and falls. Veterans were also more likely to use noninvasive breathing equipment (p = 0.0322). Findings from time-to-event analyses showed MV received wheelchairs or scooters statically earlier than NMV (log-rank p = 0.0028). Conclusions: Among participants in the Registry, MV reported differences in diagnostic timing, symptoms, and the use of supportive interventions compared to NVM. These findings may reflect differences in healthcare access, care pathways, and disease recognition over intrinsic differences in ALS biology. Because Registry participation is voluntary and data are self-reported, the result may not be generalizable to the broader ALS population.},
}

@article {pmid42212756,
year = {2026},
author = {Zhou, L and Li, M and Dai, Q and Liu, X and Li, C and Jiao, H and Pan, H and Xu, R},
title = {5-Hydroxytryptamine Distribution Alteration in Both Neuron and Synapse of Tg(SOD1*G93A)1gur Mice: A Potential Intervention Candidate Strategy for Amyotrophic Lateral Sclerosis.},
journal = {CNS neuroscience & therapeutics},
volume = {32},
number = {6},
pages = {e70946},
doi = {10.1002/cns.70946},
pmid = {42212756},
issn = {1755-5949},
support = {30560042//National Natural Science Foundation of China/ ; 81160161//National Natural Science Foundation of China/ ; 81360198//National Natural Science Foundation of China/ ; 82160255//National Natural Science Foundation of China/ ; GJJ13198//Education Department of Jiangxi Province/ ; GJJ170021//Education Department of Jiangxi Province/ ; 20142BBG70062//Jiangxi Provincial Department of Science and Technology/ ; 20171BAB215022//Jiangxi Provincial Department of Science and Technology/ ; 20192BAB205043//Jiangxi Provincial Department of Science and Technology/ ; 20212BAB216026//Jiangxi Provincial Department of Science and Technology/ ; 20181019//Health and Family Planning Commission of Jiangxi Province/ ; 202110016//Health and Family Planning Commission of Jiangxi Province/ ; 202310119//Health and Family Planning Commission of Jiangxi Province/ ; 2024SSY06081//Jiangxi Province Key Laboratory of Neurology/ ; 2024A0159//Science and Technology Plan Project of Jiangxi Provincial Administration of Traditional Chinese Medicine/ ; 20243BBI91030//Key Research and Development Project of Jiangxi Provincial Department of Science and Technology/ ; },
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *Serotonin/metabolism ; *Synapses/metabolism/pathology ; *Spinal Cord/metabolism/pathology ; Mice, Transgenic ; Mice ; *Neurons/metabolism/pathology ; Brain Stem/metabolism/pathology ; Receptor, Serotonin, 5-HT2A/metabolism ; Superoxide Dismutase-1/genetics ; Tryptophan Hydroxylase/metabolism ; Male ; Receptor, Serotonin, 5-HT1A/metabolism ; Disease Models, Animal ; Female ; Superoxide Dismutase/genetics/metabolism ; Mice, Inbred C57BL ; },
abstract = {AIMS: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease; the precise pathogenesis of sporadic ALS (sALS) has not yet been elucidated up to now. Previous studies revealed that the abnormal alterations of some non-motor neurons (non-MN) were a potential pathogenesis of sALS. Therefore, this study aims to search the potential evidences of non-MN in the pathogenesis of ALS via exploring potential relationships between 5-hydroxytryptamine (5-HT) neurons and the development of ALS.

METHODS: We employed fluorescent immunohistochemistry to investigate the altered distribution patterns of 5-HT and tryptophan hydroxylase 2 in the spinal cord and brainstem of Tg(SOD1*G93A)1Gur (TG) and wild-type (WT) mice. Additionally, we used western blot to analyze the expression levels of 5-hydroxytryptamine receptor 1A (5-HTR1A) and 5-HTR2A.

RESULTS: Our findings revealed that 5-HT synapses were primarily distributed in the funiculus lateralis, anterior horn, posterior horn, central lateral column, and the area around the central canal of cervical, thoracic, and lumbar segments, and raphe nucleus as well as lateral paragigantocellular nucleus, and gradually reduced following age increase in WT mice. However, 5-HT synapses in the spinal cord and 5-HT neurons in the brainstem gradually increased following the progression of disease and presented a significantly negative correlation between the increased distribution of 5-HT synapses and neurons and the reduction of neural cell number (positively correlated with the increase in neural cell death) at the onset and/or progression stage of TG mice. 5-HTR1A significantly increased, while 5-HTR2A significantly decreased at the onset stage of TG mice.

CONCLUSION: Our study speculated that the distribution changes of 5-HT synapses in the spinal cord and 5-HT neurons in the brainstem play a potential protective role in the pathogenesis of sALS through a compensatory 5-HT increase.},
}

Animals
*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics
*Serotonin/metabolism
*Synapses/metabolism/pathology
*Spinal Cord/metabolism/pathology
Mice, Transgenic
Mice
*Neurons/metabolism/pathology
Brain Stem/metabolism/pathology
Receptor, Serotonin, 5-HT2A/metabolism
Superoxide Dismutase-1/genetics
Tryptophan Hydroxylase/metabolism
Male
Receptor, Serotonin, 5-HT1A/metabolism
Disease Models, Animal
Female
Superoxide Dismutase/genetics/metabolism
Mice, Inbred C57BL

@article {pmid42212889,
year = {2026},
author = {Sommers-Spijkerman, M and Müller, F and Kruitwagen-Van Reenen, E and Visser-Meily, JMA and Uitslag, R and Beelen, A},
title = {Understanding psychological adjustment in patients with amyotrophic lateral sclerosis and their caregivers: a scoping review.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/21678421.2026.2671166},
pmid = {42212889},
issn = {2167-9223},
abstract = {OBJECTIVE: Psychological adjustment is a major focus in the care of people with amyotrophic lateral sclerosis (ALS) and their caregivers, given its critical role in maintaining quality of life (QoL). This scoping review aimed to gain a better understanding of ALS patients' and caregivers' psychological adjustment, to inform future care and research.

METHODS: PubMed, Web of Science, PsycINFO, Embase and CINAHL were searched for peer-reviewed studies reporting associations of psychological factors with patient/caregiver QoL. Psychological factors were categorized by type (cognitive, emotional or behavioral responses), and by strength (weak, moderate, strong) and direction (positive, negative) of their association with patient/caregiver QoL.

RESULTS: Twenty-nine studies were included, identifying twelve cognitive responses (hope, positive thinking/reframing, psychological flexibility, resilience, coping/pain self-efficacy, helplessness, hopelessness, pain catastrophizing, rumination, self-perceived burden, self-stigma), two emotional responses (emotional support, venting) and three behavioral responses (independence, positive action, substance use) associated with patient QoL. Five cognitive responses (resilience, mindfulness, hopelessness, passive reaction coping, psychological inflexibility) and one behavioral response (positive action) were found associated with caregiver QoL.

CONCLUSIONS: A range of cognitive, emotional and behavioral responses, most notably cognitive responses, were found to shape patient and/or caregiver psychological adjustment, hence may serve as potential targets in ALS clinical practice. Nonetheless, empirical evidence is limited by heterogeneity in outcomes and measures and a lack of longitudinal, multivariable, and caregiver-oriented research. More systematic, standardized and longitudinal data collection is needed to clarify how psychological adjustment processes evolve throughout the disease trajectory and to identify modifiable targets for psychological supportive care.},
}

@article {pmid42212970,
year = {2026},
author = {Kallambettu, V and Maureen, F and Chapin, J and Hutcheson, K and Plowman, E},
title = {DIGEST Grades Remain Stable With Inclusion of Moderately Thickened Liquids in the Videofluoroscopic Examination in Individuals With Amyotrophic Lateral Sclerosis.},
journal = {Journal of speech, language, and hearing research : JSLHR},
volume = {},
number = {},
pages = {1-6},
doi = {10.1044/2026_JSLHR-25-00478},
pmid = {42212970},
issn = {1558-9102},
abstract = {PURPOSE: The Dynamic Imaging Grade of Swallowing Toxicity (Version 2; DIGESTV2) is a videofluoroscopy (VF) scale that measures pharyngeal swallowing severity based on functional measures of swallowing safety and efficiency. Original validation is based on a standard VF testing protocol including thin liquid, puree, and solid consistencies. Given that thickened liquid bolus trials are common in VF clinical testing protocols, we sought to determine the agreement in DIGESTV2 grades with and without the inclusion of moderately thick liquid bolus trials on DIGESTV2 outcomes in people with amyotrophic lateral sclerosis (pALS).

METHOD: This study represents a secondary analysis of VF examinations from a prospective longitudinal study conducted in 109 pALS. VF evaluations contained 10 barium trials spanning three International Dysphagia Diet Standardisation Initiative (IDDSI) levels (0-7). Duplicate, independent, and blinded ratings were completed. DIGESTV2 Efficiency and Safety grading was then completed under two conditions-with and without the inclusion of moderately thick liquid bolus trials into DIGESTV2 grading-to produce two sets of DIGESTV2 ratings for each VF study. Descriptives, percent agreement, and a weighted Cohen's kappa were performed on DIGESTV2 grades.

RESULTS: A total of 373 VF examinations were included in this analysis. DIGESTV2 grade percent agreement with and without IDDSI Level 3 was excellent for Safety (98.1%), Efficiency (93.8%), and Total (94.1%) grades. Kappa values for Safety, Efficiency, and Total grades were .96, .89, and .91, respectively, indicating excellent agreement across bolus trial inclusion methods.

CONCLUSIONS: Standard inclusion of moderately thick liquid bolus trials did not significantly impact DIGESTV2 grading in this data set. These results add to the preliminary but growing evidence suggesting stability of DIGEST grading with alternate bolus protocols in another patient population.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.32348451.},
}

@article {pmid42213237,
year = {2026},
author = {Leboeuf, M and Nijssen, J and Comley, LH and Aguila Benitez, JC and Mei, I and Gómez Alcalde, S and Muñoz de Bustillo-Alfaro, RA and Radoi, V and Nichterwitz, S and Schweingruber, C and Acevedo Arozena, A and Hedlund, E and Cullheim, S},
title = {Reevaluating the role of beta2-microglobulin: new insights on selective vulnerability in ALS pathology.},
journal = {Acta neuropathologica},
volume = {151},
number = {1},
pages = {},
pmid = {42213237},
issn = {1432-0533},
mesh = {*Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics ; *beta 2-Microglobulin/metabolism/genetics ; Animals ; Humans ; *Motor Neurons/pathology/metabolism ; Mice ; Female ; Spinal Cord/pathology/metabolism ; Male ; Mice, Transgenic ; Superoxide Dismutase-1/genetics ; HLA Antigens/metabolism/genetics ; Disease Models, Animal ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by the selective loss of motor neurons (MNs). Why these neurons are particularly vulnerable in ALS remains unclear, as does why certain MN groups remain resistant throughout the disease course. We investigated the role of the human leukocyte antigens (HLAs) and beta2-microglobulin (β2m) in MN susceptibility to ALS, given their reported involvement in both prolonging and shortening disease progression. Loss of HLAs in ALS has also been shown to increase MNs vulnerability to toxicity exerted by activated astrocytes. RNA sequencing of control tissues demonstrated that disease-resistant oculomotor neurons (OMNs) and Onuf's MNs exhibited β2m and HLA mRNA levels comparable to those of vulnerable spinal MNs, suggesting that baseline differences in these transcripts do not explain the differential vulnerabilities of these MN groups. However, HLA protein levels showed an inverse correlation with spinal MN size, with the large MNs, those lost early in ALS, displaying the lowest HLA expression. HLA protein levels were also reduced in spinal MNs from end-stage ALS patient tissues, while remaining relatively unchanged in OMNs. In contrast, spinal MNs uniquely exhibited significant upregulation of β2m and HLA-C transcripts during disease, likely reflecting a protective compensatory response. Together, these findings suggest that β2m and HLAs may contribute to spinal MN vulnerability in ALS. To assess their functional role, β2m knockout mice were crossbred with SOD1G93A ALS mice. Loss of β2m did not alter life span of the ALS mice, but led to partial preservation of lumbrical muscle innervation that was insufficient to maintain motor function. Analysis of GFAP immunoreactivity revealed marked neuroinflammation activation in the spinal cords of β2m knockout mice. As these mice retain normal MN numbers and life-span, this indicates that loss of functional MHC-I, even in the presence of astrocyte activation, is insufficient to cause MN disease. Furthermore, β2m knockout significantly increased GFAP activation in SOD1G93A mice, but did not further exacerbate disease progression, suggesting that loss of functional MHC-I does not necessarily render MNs more vulnerable to astrocyte toxicity. Overall, these findings indicate that β2m and HLAs are dynamically regulated in ALS, and may influence MN vulnerability, but they are not major disease modifiers in ALS.},
}

*Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics
*beta 2-Microglobulin/metabolism/genetics
Animals
Humans
*Motor Neurons/pathology/metabolism
Mice
Female
Spinal Cord/pathology/metabolism
Male
Mice, Transgenic
Superoxide Dismutase-1/genetics
HLA Antigens/metabolism/genetics
Disease Models, Animal

@article {pmid42214007,
year = {2026},
author = {Bracaval, K and De Vocht, J and Ombelet, F and Den Bulcke, LV and Peeters, AM and Deleu, B and Vrijsen, B and Kalkanis, A and Buyse, B and Testelmans, D and Van Den Bossche, M and Van Damme, P},
title = {Sleep disturbances and respiratory dysfunction in amyotrophic lateral sclerosis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/21678421.2026.2671162},
pmid = {42214007},
issn = {2167-9223},
abstract = {OBJECTIVE: To investigate how respiratory dysfunction and site of onset influences changes in sleep architecture in people with ALS (pwALS).

METHODS: We conducted a retrospective observational study, analyzing demographic data, lung function tests, and polysomnography (PSG) measures. Descriptive statistics, correlation analyses, and survival analyses were performed.

RESULTS: Our cohort had 240 pwALS, 63% male, median age at onset 59.3 (IQR 16.5) years. Median time from onset to PSG was 27.5 (IQR 25) months. Most pwALS had spinal onset (79%). Spirometry at time of PSG showed a reduced Forced Vital Capacity (FVC) (58; (IQR 26) %). We saw a significant FVC decline (3.9; (IQR 4) % per month) in the months before PSG. The sleep quality assessment in pwALS revealed a reduced total sleep time (339; (IQR 144.7) minutes), diminished sleep efficiency (62.8; (IQR 26.5)%) and increased wake after sleep onset (172; (IQR 130.2) minutes) when compared to normal values of healthy age-matched adults. The spinal onset group had a higher number of arousals. In the multivariate linear regression model adjusted for age and sex, FVC is a significant predictor for sleep efficiency (β = 3.359, p = 0.0059). Spinal onset, a slower rate of FVC decline in the months preceding PSG and a preserved FVC (≥ 70%) at the time of PSG were associated with improved survival.

CONCLUSION: We observed substantial sleep disturbances in our cohort overall with substantially increased arousals in the spinal group. FVC is a significant predictor for sleep efficiency and the decline in FVC is linked to survival.},
}

@article {pmid42214042,
year = {2026},
author = {de Boer, EMJ and Willemse, SW and Veldink, JH and Goedee, HS and Vrancken, AFJE and van Rheenen, W and Westeneng, HJ and van den Berg, LH and van Es, MA},
title = {Diagnostic Revision From Primary Lateral Sclerosis to Amyotrophic Lateral Sclerosis: A Cohort Study.},
journal = {Neurology},
volume = {106},
number = {12},
pages = {e218055},
doi = {10.1212/WNL.0000000000218055},
pmid = {42214042},
issn = {1526-632X},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; Female ; *Motor Neuron Disease/diagnosis/physiopathology/epidemiology ; Male ; Middle Aged ; Aged ; Disease Progression ; Cohort Studies ; Retrospective Studies ; Registries ; Netherlands ; Electromyography ; },
abstract = {BACKGROUND AND OBJECTIVES: Primary lateral sclerosis (PLS) is defined as a pure upper motor neuron syndrome and is a diagnosis of exclusion, amyotrophic lateral sclerosis (ALS) being the most likely alternative diagnostic consideration. A minimum disease duration of 2 years is required for the diagnosis of PLS, after which patients are classified as probable PLS (P-PLS) and subsequently as definite PLS (D-PLS) after 4 years. Our aim is to apply the current diagnostic criteria to a population-based cohort and investigate which clinical characteristics are associated with a diagnostic revision to ALS.

METHODS: This cohort study included patients meeting the current diagnostic criteria for PLS retrospectively from the Dutch Motor Neuron Disease Registry. Diagnostic revision to ALS was based on clinical assessment, EMG findings according to the revised El Escorial Criteria, or if patients had died from disease progression within 4 years of disease onset. Clinical characteristics were compared for patients who underwent diagnostic revision with ALS vs true PLS. Subdistribution hazard ratios (SHRs) for characteristics associated with diagnostic revision were determined using Fine-Gray regression.

RESULTS: We included 478 patients (median age of onset 59.3 years, interquartile range 50.8-67.0, 47.9% female), of whom 311 (65.1%) met criteria for P-PLS and 167 (34.9%) for D-PLS at diagnosis. Eighty-eight patients (18%) underwent diagnostic revision to ALS, 76 cases (86%) before 4 years of disease duration. Patients whose diagnosis was revised to ALS had higher median age at onset (63.4 vs 58.0 years, p = 5.20 × 10[-4]), more often had bulbar onset (38.6% vs 19.7%, p = 6.19 × 10[-4]), and faster progression (median ALS Functional Rating Scale-revised slope 0.43 vs 0.18, p = 6.05 × 10[-11]). The risk of diagnostic revision increased if progression rate was faster (SHR 3.08 95% CI 1.69-5.60, p = 2.35 × 10[-4]) and if diagnosis was P-PLS compared with D-PLS (SHR 3.08, 95% CI 1.65-5.74, p = 3.96 × 10[-4]).

DISCUSSION: In our cohort, most diagnostic revisions from PLS to ALS were in patients with a disease duration of less than 4 years. Besides disease duration, a faster progression rate was associated with diagnostic revision from PLS to ALS. Adding progression rate to the current diagnostic criteria could increase accuracy and help identify patients at higher risk of developing ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology
Female
*Motor Neuron Disease/diagnosis/physiopathology/epidemiology
Male
Middle Aged
Aged
Disease Progression
Cohort Studies
Retrospective Studies
Registries
Netherlands
Electromyography

@article {pmid41987206,
year = {2026},
author = {Zheng, M and Li, M and Liu, S and Guan, R and Liu, X},
title = {RNA-binding proteins: a comprehensive review of multifaceted regulatory mechanisms in neuroinflammation and implications in the pathogenesis of neurological disorders.},
journal = {Journal of neuroinflammation},
volume = {23},
number = {1},
pages = {},
pmid = {41987206},
issn = {1742-2094},
support = {82230063//National Natural Science Foundation of China/ ; },
abstract = {Neuroinflammation stands as a cornerstone pathological hallmark across a spectrum of neurological disorders, drawing intensified scientific scrutiny owing to its profoundly intricate and multi-layered regulatory networks. At the heart of this complexity, RNA-binding proteins (RBPs) emerge as masterful post-transcriptional orchestrators, exerting precise control over a vast array of neuroinflammatory cascades. Mounting evidence underscores that RBPs transcend their classical roles in RNA sensing and innate immune recognition, actively shaping pivotal biological pathways—ranging from inflammatory signal transduction and programmed cell death to metabolic reprogramming, epigenetic remodeling and dynamic crosstalk with non-coding RNAs. Furthermore, the functional versatility of RBPs is amplified by nuanced alterations in their nucleocytoplasmic trafficking, stress granule formation, post-translational modifications, and RNA-binding specificities, all of which intricately fine-tune their regulatory impact within the neuroinflammatory milieu. Strikingly, the cell type-specific actions of RBPs in neurons, microglia, and astrocytes unveil a sophisticated tapestry of molecular specialization, offering transformative insights into their context-dependent functions. Abnormal function of RNA-binding proteins is closely related to neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis. In addition, RNA-binding proteins are involved in various pathological processes, including central nervous system infections, stroke, high-altitude cerebral hypoxia, and traumatic brain injury. This review systematically organizes the multifaceted regulatory mechanisms of RNA-binding proteins in neuroinflammation. It deeply explores their key roles in the occurrence and development of nervous system diseases. The review aims to construct a comprehensive theoretical framework and provide a scientific basis for developing new diagnostic methods and targeted therapeutic strategies.},
}

@article {pmid42203747,
year = {2026},
author = {Esch, T},
title = {What's love got to do with it? The formula for love needs psychological and motivational neurobiological components.},
journal = {The Behavioral and brain sciences},
volume = {49},
number = {},
pages = {e7},
doi = {10.1017/S0140525X25102227},
pmid = {42203747},
issn = {1469-1825},
mesh = {*Love ; Humans ; *Motivation/physiology ; *Brain/physiology ; },
abstract = {Kruglanski et al.'s love model rightly highlights motivation and meaning as core to love, aligning with current research. However, this commentary expands the view, emphasizing love's biological basis in brain systems and evolving different types of motivation. Love fulfills both individual and species-level needs, promoting health, connection, and generativity. True love transcends ego, growing into unconditional, spiritually rich connectedness over time.},
}

*Love
Humans
*Motivation/physiology
*Brain/physiology

@article {pmid42203750,
year = {2026},
author = {Van Dessel, P and Boddez, Y},
title = {Extending the motivational model of love: A Goal-Directed Predictive Processing perspective.},
journal = {The Behavioral and brain sciences},
volume = {49},
number = {},
pages = {e19},
doi = {10.1017/S0140525X25102161},
pmid = {42203750},
issn = {1469-1825},
mesh = {*Love ; Humans ; *Goals ; *Motivation ; *Models, Psychological ; },
abstract = {We extend Kruglanski et al.'s model by embedding it within a Goal-Directed Predictive Processing framework. This perspective conceptualizes romantic love as arising from self-referential inferences tied to personal goals and reveals that love may include merit, appreciation, and significance, but is not defined or limited by them. It also explains love experiences that exceed the scope of the authors' model.},
}

*Love
Humans
*Goals
*Motivation
*Models, Psychological

@article {pmid42203757,
year = {2026},
author = {Lucchi Basili, L and Sacco, PL},
title = {Significance is not enough: The biopsychological foundations of romantic love.},
journal = {The Behavioral and brain sciences},
volume = {49},
number = {},
pages = {e2},
doi = {10.1017/S0140525X25102318},
pmid = {42203757},
issn = {1469-1825},
mesh = {Humans ; *Love ; Female ; Male ; Emotions/physiology ; },
abstract = {Kruglanski et al.'s significance-based model overlooks fundamental biopsychological mechanisms driving romantic love. The Tie-Up Theory reveals how women's subconscious biological compatibility assessments through physical, chemical, and behavioral signals operate independently of conscious significance calculations. Their gender-neutral framework ignores how men's receptive emotional orientation differs from women's active emotional competence. By reducing love to significance enhancement, the model cannot explain irrational attractions, persistent relationships despite low "merit," or gendered dissolution patterns determined by reward cycle breakdowns.},
}

Humans
*Love
Female
Male
Emotions/physiology

@article {pmid42204151,
year = {2026},
author = {Jia, Q and Zhu, L and Li, D and Nan, Z and Hou, J and Zhao, Y and Zhu, G and Ou, K and Guo, M and Dui, H and Liu, X and Yan, XX and Yang, S and Huang, L and Fan, D and Li, S and Li, XJ and Yin, P},
title = {Caspase-4 transgenic mice exhibit cytoplasmic TDP-43 accumulation and age-dependent neuropathology.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-73724-7},
pmid = {42204151},
issn = {2041-1723},
support = {32270564//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {TAR DNA-binding protein (TDP-43) is a multifunctional protein that binds DNA and RNA within the nucleus. In neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS), TDP-43 is mislocalized to the cytoplasm, forming inclusions. Current TDP-43 transgenic mouse models generally fail to exhibit significant cytoplasmic accumulation and loss of nuclear TDP-43, which hampers the investigation of cytoplasmic TDP-43 pathology. We previously discovered that primate-specific caspase-4 (CASP4) can cleave TDP-43, producing truncated fragments that are mislocalized to the cytoplasm. Here we show that a transgenic mouse model that expresses human CASP4 and recapitulates the cytoplasmic mislocalization of endogenous TDP-43 and motor dysfunction in an age-dependent manner. Moreover, CASP4 mice exhibited gene expression changes and neuropathology similar to patients with sporadic ALS. Inhibition of CASP4 by its antisense oligonucleotide ameliorated TDP-43 pathology and subsequent neurotoxicity in CASP4 mice. Thus, CASP4 mice present a valuable animal model for exploring endogenous TDP-43-mediated pathogenesis and therapeutics.},
}

@article {pmid42204279,
year = {2026},
author = {Fowler, M and Carr, JM and Gold, J and Walker, A and Rogers, ML},
title = {Evaluation of triumeq treatment on a TDP-43 mouse model of amyotrophic Lateral sclerosis.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-55433-9},
pmid = {42204279},
issn = {2045-2322},
support = {DIS-202303-00932//FightMND/ ; DIS-202303-00932//FightMND/ ; IG1950//Motor Neurone Disease Research Australia/ ; IG1950//Motor Neurone Disease Research Australia/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterised by the accumulation of TAR DNA Binding Protein (43 kDa; TDP-43) within the cytoplasm of neurons. Endogenous retroviruses (ERVs) have been implicated in ALS pathology and the application of antiretroviral therapy, specifically Triumeq, has been proposed for treatment of ALS. However, evidence to support the actions of Triumeq in ALS is lacking. This study investigates the effects of the antiretroviral treatment Triumeq on ALS disease that occurs through TDP-43 pathology by utilising the doxycycline (Dox)-suppressible rNLS8 TDP-43 expression mouse model. In this model, TDP-43 accumulation in the cytoplasm is induced after removal of Dox. Disease was assessed through measures of body weight, neurological score, motor function, urinary p75[ECD] and inflammatory marker expression. Mice were treated with Triumeq and TDP-43 pathology and inflammatory marker expression examined. Triumeq treatment significantly improved motor function early on in the disease course but did not impact other disease progression markers or disease endpoint. In this TDP-43 ALS mouse model, there was a positive association of TDP-43 mRNA levels with transcription factor ATF4, and inflammatory markers CXCL10 and IRF-1, and Triumeq treatment negated this association. Triumeq treatment transiently and modestly improved motor function and influenced TDP-43 associated inflammatory gene expression in an ALS mouse model. These findings support the potential use of Triumeq in treating TDP-43-associated ALS and supports further investigation to better understand if the beneficial actions of Triumeq are via disruption of TDP-43-driven inflammation in ALS.},
}

@article {pmid42204548,
year = {2026},
author = {Jin, X and Fu, Y and Qiu, T and Li, J and Zhang, H and Chen, Y and Chen, K and Zhang, Y and Wang, J and Yi, X and Palaniyappan, L and Braden, BB},
title = {Putative glymphatic dysfunction links extracellular fluid dysregulation to white matter degeneration and clinical impairment in amyotrophic lateral sclerosis.},
journal = {BMC medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12916-026-04948-z},
pmid = {42204548},
issn = {1741-7015},
support = {No. 2022LNJJ09//Project Program of National Clinical Research Center for Geriatric Disorders/ ; 2024ZZTS0954//Fundamental Research Funds for the Central Universities of Central South University/ ; U22A20377//National Natural Science Foundation of China/ ; No.2024PT5109//Scientific Research Program of FuRong Laboratory/ ; CB-C2022//Santé/ ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron degeneration and prominent extra-motor involvement. Impaired clearance of neurotoxic proteins has led to increasing interest in the brain glymphatic system; however, its in vivo associations with brain microstructure and clinical heterogeneity remain incompletely understood.

METHODS: One hundred forty-six patients with ALS and 149 demographically matched healthy controls (HCs) underwent multimodal MRI and comprehensive clinical assessments. Putative glymphatic function was quantified using diffusion tensor imaging along perivascular space (DTI-ALPS). Extracellular free water fraction (FWF) and free-water-corrected fractional anisotropy (fwcFA) were derived to characterize extracellular fluid and white matter microstructure. Group differences were assessed using vertex-wise and voxel-wise analyses with correction for multiple comparisons. Associations among imaging metrics and clinical measures were evaluated using correlation and serial mediation analyses.

RESULTS: Compared with HCs, patients with ALS exhibited significantly reduced DTI-ALPS index, widespread increases in cortical FWF, bidirectional alterations in white matter FWF, and extensive reductions in fwcFA across major white matter tracts. Reduced DTI-ALPS was associated with changes in extracellular free water and white matter microstructural integrity, whereas FWF and fwcFA measures were associated with functional, cognitive, and emotional outcomes. Mediation analyses identified significant indirect associations between DTI-ALPS and both functional and cognitive measures through a pathway involving cortical FWF, white matter FWF, and fwcFA, although direct associations were not observed.

CONCLUSIONS: These findings provide in vivo evidence that putative glymphatic dysfunction co-occurs with extracellular fluid alterations, white matter microstructural changes, and clinical impairment in ALS. Multi-compartment diffusion imaging may offer complementary markers for characterizing brain microstructure and its clinical relevance in ALS.},
}

@article {pmid42190754,
year = {2026},
author = {Wu, X and Wang, X and Zhang, Z},
title = {Response to Chen et al., "Comments on Wu et al's "The efficacy and adverse reactions of 755 nm picosecond alexandrite laser on the treatment of nevus of Ota at different endpoints".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.05.061},
pmid = {42190754},
issn = {1097-6787},
}

@article {pmid42190894,
year = {2026},
author = {Oriquat, G and Abdulqader, AF and Farid, H and Ashurov, Z and Sottarov, A and Ghafl, NY and Bainsal, N and Singh, R},
title = {From protector to perpetrator: The cGAS-STING pathway at the intersection of neurodegeneration and neuroinflammation.},
journal = {Brain research bulletin},
volume = {241},
number = {},
pages = {111963},
doi = {10.1016/j.brainresbull.2026.111963},
pmid = {42190894},
issn = {1873-2747},
abstract = {The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, a cornerstone of the innate immune system designed to combat pathogens, is now implicated as a critical driver of sterile inflammation in the brain. This review synthesizes compelling evidence that in the aging and diseased central nervous system, endogenous cytosolic DNA, sourced from genomic instability, mitochondrial dysfunction, and activated retrotransposons, hijacks this pathway. Chronic cGAS-STING activation transforms microglia into inflammatory amplifiers, instigates neurotoxic astrocyte programs, and directly compromises neuronal health, creating a self-perpetuating cycle of neuroinflammation. We dissect the cell-type specific consequences within the neurovascular unit and establish the pathway's role in the pathogenesis of ALS/FTD, Alzheimer's, Parkinson's, and Huntington's diseases. Crucially, we evaluate the therapeutic potential of targeting this axis, discussing small-molecule inhibitors, oligonucleotide therapies, and upstream interventions to quell the source of immunogenic DNA. We also explicitly examine contradictory preclinical data, including the retracted PINK1-Parkin-STING report and context-dependent neurovascular findings, to provide a balanced appraisal of STING biology in the CNS. By reconciling its dual protective and pathogenic roles, this review posits cGAS-STING as a pivotal mechanism-based therapeutic node for halting the progression of neurodegenerative disorders.},
}

@article {pmid42191539,
year = {2026},
author = {Pérez-Bonilla, M and Díaz-Borrego, P and Mora-Ortiz, M and Mayordomo-Riera, FJ and Girela-López, E},
title = {Discovering Hidden Vocal Subtypes: An Unsupervised Acoustic-Biomechanical Exploration of Voice Profiles.},
journal = {Journal of voice : official journal of the Voice Foundation},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jvoice.2026.05.002},
pmid = {42191539},
issn = {1873-4588},
abstract = {OBJECTIVE: This study aims to explore latent acoustic-biomechanical patterns of voice production using an unsupervised multivariate approach, and to identify data-driven vocal profiles across individuals with amyotrophic lateral sclerosis (ALS) and nonneurological dysphonia.

METHODS: A cross-sectional sample of 100 individuals, including patients with ALS and individuals with nonneurological dysphonia, was analyzed. Sustained vowel phonation was recorded and characterized using 26 variables, including standard acoustic measures (fundamental frequency -fo-, jitter, shimmer, and harmonics-to-noise ratio (HNR)) and 22 biomechanical parameters. Principal component analysis was applied to investigate relationships among variables and reduce dimensionality. Unsupervised clustering was performed at both the variable level to identify functional groupings and the participant level to derive data-driven voice profiles. Cluster validity was assessed using internal indices. Post hoc statistical comparisons and chi-square tests were used descriptively to characterize between-cluster differences and their relationship with clinical categories.

RESULTS: The first five principal components explained 70.7% of the total variance, revealing structured relationships between acoustic and biomechanical features. Participant level clustering consistently supported a two-profile solution. Fifteen voice parameters differed significantly between profiles after false discovery rate correction, with the largest effects observed for shimmer, HNR, and the biomechanical parameter Pr11, reflecting differences in vocal stability and noise-related characteristics. The identified profiles were not significantly associated with clinical diagnostic categories.

CONCLUSIONS: An unsupervised multimodal analysis of sustained phonation revealed two coherent vocal profiles that transcend traditional diagnostic labels. These data-driven voice phenotypes may capture functional patterns of voice production and support future efforts toward more refined and personalized characterization of voice disorders.},
}

@article {pmid42191846,
year = {2026},
author = {Zhang, J and Tian, M and Niu, T and Li, R and Liu, Q and Liu, M and Zhou, X and Dong, H and Liu, Y},
title = {The role of adiponectin and cytokines in Amyotrophic lateral sclerosis: assessment of disease progression and survival status.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-54291-9},
pmid = {42191846},
issn = {2045-2322},
support = {H2023206055//Key Project of Natural Science Foundation of Hebei Province/ ; 20240391//Scientific Research Foundation of Health Commission of Hebei Province/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disorder. ALS typically progresses rapidly, leading to respiratory failure within 3 to 5 years of symptom onset. Identifying risk factors that influence disease progression and survival is critical for enhancing management strategies. The present study therefore investigated the roles of inflammatory factors and adipokines (especially adiponectin) in the progression and prognosis of ALS. The study included 80 ALS patients, with a follow-up period of 1.5 years. Survival analysis was performed using a Cox regression, with hazard ratios (HR) and 95% confidence intervals (CI) presented via forest plots. Our results indicated that ALS patients in the fast-progressing group exhibited lower levels of adiponectin (p < 0.001) and IL-10 (p < 0.001). The Cox regression and forest plot results suggest the potential of adiponectin (HR = 0.905, 95%CI: 0.866-0.946, p < 0.001), IL-10 (HR = 0.968, 95%CI: 0.951-0.986, p < 0.001), δFS (HR = 1.234, 95%CI: 1.065-1.430, p = 0.005) and ALSFRS-R (HR = 0.820, 95%CI: 0.765-0.878, p < 0.001) as potential risk factors. In addition, these risk factors are significantly associated with poor survival prognosis in high-risk populations (all p < 0.001). This study identifies adiponectin, IL-10, ALSFRS-R, and δFS as key risk factors influencing ALS progression and prognosis.},
}

@article {pmid42191932,
year = {2026},
author = {Heckmann, JM and Floudiotis, N and Makanjuola, A and Ogunniyi, A and Mochan, A and Mongwe, RR and Sokhi, DS and Nel, M},
title = {Motor neuron disease in Africa: a critical appraisal of the literature.},
journal = {Nature reviews. Neurology},
volume = {},
number = {},
pages = {},
pmid = {42191932},
issn = {1759-4766},
abstract = {Motor neuron disease (MND) refers to a group of neurodegenerative diseases that cause motor neuron degeneration and death. The most common subtype, amyotrophic lateral sclerosis (ALS), is characterized by both upper and lower motor neuron impairment, which can manifest clinically in the bulbar region or asymmetrically in a limb. Typically, the disease progresses over several months, and death from respiratory failure occurs within 2-5 years of onset. As we highlight in this Review, data on MND in Africa are sparse, although common observations in this region - and in other populations with relatively low life expectancy - include apparent earlier disease onset and lower disease incidence compared with the rest of the world. In view of the HIV epidemic in Africa, we critically examine the evidence for an association between ALS and HIV infection. We briefly discuss conditions that might be regarded as ALS mimics and summarize the limited data on MND genetics in this region. Other issues pertinent to people living with MND in Africa include the absence of cognitive and behavioural data and the limited access to multidisciplinary clinics, therapies and palliative care. We share our perspective on how the ALS Africa Network is coordinating a shift in the African MND landscape to improve patient care.},
}

@article {pmid42192558,
year = {2026},
author = {Aggad, WS and Ghosh, R and Almohaimeed, HM and Mohammedsaleh, ZM and Saleh, FM and Almars, AI and Jyothi, SR and Panigrahi, R and Kumer, A and Dhara, B},
title = {Exosome-mediated gut-brain axis signaling in neurodegenerative diseases: Mechanisms, experimental evidence, and therapeutic perspectives-A narrative review.},
journal = {Animal models and experimental medicine},
volume = {},
number = {},
pages = {},
doi = {10.1002/ame2.70226},
pmid = {42192558},
issn = {2576-2095},
support = {PNURSP2026R213//Princess Nourah Bint Abdulrahman University/ ; },
abstract = {The stomach and the brain are connected by a sophisticated two-way communication mechanism called the gut-brain axis. Extracellular vesicles, particularly exosomes, that move bioactive substances between the stomach and the brain, such as proteins, lipids, metabolites, and microRNAs, may improve the gut-brain axis. In the past years, the role of exosome-mediated communication has been recognized as significant in relation to the etiology, continued progression, and potential treatment of neurodegenerative disorders. The authors of this review article present a summary of the current understanding of the relationship of gut microbiome, exosome biogenesis, and the pathophysiological development of neurodegenerative diseases. Evidence from laboratory studies, animal studies, and newly emerging human studies suggests that microbiome-based metabolites and inflammatory mediators may modulate how exosomes are produced, what they carry, and how they interact with the blood-brain barrier. These exosomal signals may impact neuroinflammation, neuronal signaling, and the spread of pathological proteins of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. In addition, they examine some possible ways to target the gut-brain axis from a therapeutic perspective, including manipulating the gut microbiome, providing probiotics and/or prebiotics, performing fecal microbiota transplantation, and/or using engineered extracellular vesicles as vehicles for drug delivery. The authors also outline some of the methodological differences that make it difficult to assess the effects of exosomes.},
}

@article {pmid42192595,
year = {2026},
author = {Liu, Y and Wu, W},
title = {Clinical Value and Research Prospects of 1024 Matrix Optimization in 64-Slice Cerebral CTA for Perforating Artery Visualisation.},
journal = {Journal of medical radiation sciences},
volume = {},
number = {},
pages = {},
doi = {10.1002/jmrs.70101},
pmid = {42192595},
issn = {2051-3909},
abstract = {This letter comments on Nagumo et al.'s study evaluating 1024-matrix reconstruction for intracranial perforating artery visualisation in 64-slice cerebral CTA, affirming its cost-effective value for standard CT scanners (https://doi.org/10.1002/jmrs.70055). We endorse the key finding that 1024-matrix improves small artery detection via higher sampling density, while highlighting the need for cross-vendor validation, workflow impact quantification, and clinical outcome assessment. This simple post-processing strategy is highly scalable, and further multicentre studies are warranted to confirm its universal utility.},
}

@article {pmid42193936,
year = {2026},
author = {Sepehrimanesh, M and Melen, SV and Yeasmin, F and Ojo, VA and Walden, F and Urmee, H and Etheridge, J and Nasu, AK},
title = {Emerging Therapeutic Strategies for Neurodegenerative Diseases: A Comprehensive Review of Recent Advances and Future Directions.},
journal = {Cells},
volume = {15},
number = {10},
pages = {},
doi = {10.3390/cells15100928},
pmid = {42193936},
issn = {2073-4409},
mesh = {Humans ; *Neurodegenerative Diseases/therapy ; Animals ; Neuroprotective Agents/therapeutic use ; Genetic Therapy ; },
abstract = {Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS; Lou Gehrig's disease), represent a growing global health burden characterized by progressive neuronal loss and functional decline. Despite decades of intensive research, effective disease-modifying therapies remain limited, underscoring the urgent need for innovative therapeutic strategies. This review highlights recent advances in the understanding of disease etiology and emerging treatment approaches, with a particular focus on modalities with translational potential. We discussed novel disease-modifying interventions, including gene and cell therapies, RNA-targeting strategies, and immunotherapies aimed at clearing misfolded proteins such as amyloid-β, tau, and α-synuclein. In parallel, we examined the evolving recognition of neuroinflammation and mitochondrial dysfunction as actionable therapeutic targets, alongside progress in precision medicine and biomarker-guided approaches that enable early diagnosis and individualized treatment. Additionally, we summarized developments in repurposed pharmacological agents, neuroprotective compounds, and lifestyle interventions, emphasizing the importance of integrative, multimodal strategies. Across AD, PD, and ALS, convergent molecular mechanisms, including protein misfolding, oxidative stress, and disrupted proteostasis, present opportunities for cross-disease therapeutic targeting. Finally, we addressed key challenges and future directions, including translating preclinical efficacy into clinical success, optimizing CNS-targeted delivery systems, and navigating ethical considerations surrounding gene editing and stem cell therapies.},
}

Humans
*Neurodegenerative Diseases/therapy
Animals
Neuroprotective Agents/therapeutic use
Genetic Therapy

@article {pmid42194069,
year = {2026},
author = {Malá, P and Váňová, N and Malý, O and Vyšata, O},
title = {Oxidative-Nitrosative Stress and Routine Biochemical Parameters in Amyotrophic Lateral Sclerosis: Associations with Clinical Status and Disease Duration-A Pilot Study.},
journal = {Biomolecules},
volume = {16},
number = {5},
pages = {},
doi = {10.3390/biom16050721},
pmid = {42194069},
issn = {2218-273X},
support = {Cooperatio Program, research area NEUR//Charles University/ ; Grant No. DRO-UHHK 00179906//Ministry of Health of the Czech Republic/ ; },
mesh = {Humans ; Pilot Projects ; *Amyotrophic Lateral Sclerosis/blood/metabolism/pathology ; *Nitrosative Stress ; *Oxidative Stress ; Female ; Biomarkers/blood ; Middle Aged ; Male ; Tyrosine/analogs & derivatives/blood ; Aged ; 8-Hydroxy-2'-Deoxyguanosine/blood ; Glutathione/blood ; Malondialdehyde/blood ; },
abstract = {BACKGROUND: This pilot study examined whether oxidative-nitrosative stress is associated with clinical status in amyotrophic lateral sclerosis (ALS). We analyzed associations between plasma markers of oxidative-nitrosative imbalance and ALSFRS-R, disease duration, survival, and routine biochemical parameters.

METHODS: Twenty-nine ALS patients fulfilling the Gold Coast diagnostic criteria were enrolled. Plasma levels of 3-nitrotyrosine (3-NT), 8-oxo-2'-deoxyguanosine (8-oxodG), malondialdehyde (MDA), glutathione (GSH), non-protein thiols (NP-SH), and non-protein disulfides (NP-SS-NP), as well as creatinine, urea, uric acid and BMI, were measured. Associations with ALSFRS-R and disease duration were evaluated using non-parametric correlation analyses and second-order polynomial regression (adjusted R[2]), while survival was explored using Kaplan-Meier analysis and multivariable Cox regression. Given the modest sample, we considered statistical power and applied Benjamini-Hochberg false discovery rate (FDR) correction within marker families.

RESULTS: At the uncorrected significance level, 3-NT showed a positive correlation with ALSFRS-R and a negative correlation with disease duration, and NP-SH correlated negatively with disease duration; however, these associations did not remain significant after FDR correction (FDR-adjusted p ≥ 0.099). Other oxidative-nitrosative markers and biochemical parameters showed no robust relationships with clinical measures. In Cox models, 3-NT was not significantly associated with survival (HR 3.44 per 1 nM, 95% CI 0.25-47.97, p = 0.358), whereas older age predicted higher mortality (HR 1.05 per year, 95% CI 1.00-1.10, p = 0.036).

CONCLUSIONS: 3-NT and NP-SH exhibited the strongest trends among the investigated markers, but their clinical associations in this small cross-sectional cohort remain exploratory and require confirmation in larger longitudinal studies.},
}

Humans
Pilot Projects
*Amyotrophic Lateral Sclerosis/blood/metabolism/pathology
*Nitrosative Stress
*Oxidative Stress
Female
Biomarkers/blood
Middle Aged
Male
Tyrosine/analogs & derivatives/blood
Aged
8-Hydroxy-2'-Deoxyguanosine/blood
Glutathione/blood
Malondialdehyde/blood

@article {pmid42194544,
year = {2026},
author = {Nord-Bronzyk, A and Ng, B and Lan, T and Schaefer, GO and Takahashi, S},
title = {Guiding Policymakers Toward Better AI Ethics Integration in Healthcare Regulation-Lessons from Singapore.},
journal = {Journal of clinical medicine},
volume = {15},
number = {10},
pages = {},
doi = {10.3390/jcm15103576},
pmid = {42194544},
issn = {2077-0383},
support = {MOH-000951-00//Ministry of health singapore/ ; },
abstract = {In terms of rollout, comprehensiveness, and strategy, Singapore's regulatory landscape governing the ethical use of Artificial Intelligence (AI) in healthcare has generally kept pace with other global leaders in AI advancement. However, establishing a robust and holistic regulatory framework that evolves along with emerging technologies is not easy-especially in healthcare, where the stakes are high and resources may be limited. We conducted a structured scoping analysis of key AI regulatory and professional documents in Singapore, selected using predefined inclusion criteria. Documents were systematically mapped against Savulescu et al.'s nine categories of ethical risk, followed by cross-document comparison to identify integration gaps and inconsistencies, and benchmarking against international AI governance frameworks. These recommendations are generalizable beyond Singapore for developers, implementers, healthcare professionals and patients and include dealing with bias in AI, enhancing human productivity without deskilling, facilitating more informed decision-making, and cultivating greater knowledge exchange between clinicians and patients, to name a few.},
}

@article {pmid42195033,
year = {2026},
author = {Richard, E and Al-Hajj Vourc'h, S and Marouillat, S and Beltran, S and Blasco, H and Corcia, P and Vourc'h, P},
title = {From Mutation to Manifestation: Penetrance in Amyotrophic Lateral Sclerosis.},
journal = {Genes},
volume = {17},
number = {5},
pages = {},
doi = {10.3390/genes17050576},
pmid = {42195033},
issn = {2073-4425},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *Penetrance ; *Mutation ; Superoxide Dismutase-1/genetics ; RNA-Binding Protein FUS/genetics ; C9orf72 Protein/genetics ; Genetic Counseling ; DNA-Binding Proteins/genetics ; Genetic Predisposition to Disease ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by progressive loss of motor neurons in the brain and spinal cord. While most cases are sporadic, around 10% are familial. Recent genetic studies show that many apparently isolated cases carry pathogenic mutations, highlighting the importance of penetrance, the probability that a causal mutation manifests clinically. This review focuses on mutation penetrance in ALS (C9orf72, SOD1, TARDBP, FUS genes), its variability across genes, age, and environmental or genetic modifiers, and its implications for genetic counseling. Identification of pathogenic mutations informs the monitoring of relatives and, in some cases, gives access to targeted therapies or clinical trials. Counseling of asymptomatic relatives must consider incomplete penetrance, which can lead to delayed or absent disease manifestation. ALS exists on a clinical and genetic continuum including related disorders, such as frontotemporal dementia, further influencing risk interpretation. Advances in panel, whole-exome and whole-genome sequencing refine our understanding of penetrance and enable precise diagnostics, and potential tailored therapies. Understanding penetrance is therefore essential to translate mutation discovery into informed clinical decisions and genetic counseling in ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/pathology
*Penetrance
*Mutation
Superoxide Dismutase-1/genetics
RNA-Binding Protein FUS/genetics
C9orf72 Protein/genetics
Genetic Counseling
DNA-Binding Proteins/genetics
Genetic Predisposition to Disease

@article {pmid42196191,
year = {2026},
author = {Giordano, A and Mandrioli, J and Cerri, F and Lunetta, C and Saebfar, H and Catania, M and Battipaglia, C and Leone, L and Trojsi, F and Vizziello, M and Gerardi, F and Farè, M and Zulueta, A and Piras, R and Giacchino, M and Gianferrari, G and Dalla Bella, E and Domi, T and Bonanomi, D and Ganci, G and Lombardi, R and Lauria, G and Riva, N},
title = {Longitudinal CSF and Serum Biomarker Dynamics in Tofersen-Treated SOD1-ALS: A Real-World Multicentre Cohort Study.},
journal = {International journal of molecular sciences},
volume = {27},
number = {10},
pages = {},
doi = {10.3390/ijms27104208},
pmid = {42196191},
issn = {1422-0067},
support = {IDEALS//AriSLA/ ; RF-2021-12373036//Ministero della salute Ricerca Finalizzata bando 2021/ ; Neurobiobanca di Modena//Fondazione Cassa di Risparmio di Modena/ ; Giovanni Marazzina Project//Giovanni Marazzina Foundation/ ; },
mesh = {Humans ; *Biomarkers/blood/cerebrospinal fluid ; *Superoxide Dismutase-1/genetics ; Female ; *Amyotrophic Lateral Sclerosis/drug therapy/blood/cerebrospinal fluid/genetics ; Longitudinal Studies ; tau Proteins/blood/cerebrospinal fluid ; Ubiquitin Thiolesterase/blood/cerebrospinal fluid ; Male ; Glial Fibrillary Acidic Protein/blood/cerebrospinal fluid ; Middle Aged ; Neurofilament Proteins/blood/cerebrospinal fluid ; Retrospective Studies ; Aged ; },
abstract = {Tofersen is a gene-targeted therapy for superoxide dismutase 1 (SOD1)-associated amyotrophic lateral sclerosis (ALS), but neurofilament light chain (NfL) may not fully capture the biological response to treatment. We performed a multicentre retrospective longitudinal study including 24 patients with SOD1-ALS treated with intrathecal tofersen at four Italian referral centres between 2022 and 2025. Cerebrospinal fluid (CSF) and serum biomarkers were assessed at baseline, month 3, month 6, and last available administration using single-molecule array assays to quantify NfL, glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCHL-1), and total Tau. NfL decreased after treatment initiation in both CSF and serum, providing the clearest pharmacodynamic signal. In contrast, CSF GFAP increased progressively over follow-up, while CSF total Tau and UCHL-1 rose mainly at later timepoints; serum GFAP, total Tau, and UCHL-1 also showed increases during follow-up. ALS Functional Rating Scale-Revised trajectories were broadly stable, whereas disease progression rate was lower at last follow-up than at baseline. Greater reductions in CSF NfL were observed in pathogenic versus uncertain SOD1 variants, and early serum NfL and UCHL-1 changes were associated with longer-term changes in disease progression. These findings suggest that longitudinal multi-analyte profiling may refine biological response stratification beyond NfL alone in tofersen-treated SOD1-ALS.},
}

Humans
*Biomarkers/blood/cerebrospinal fluid
*Superoxide Dismutase-1/genetics
Female
*Amyotrophic Lateral Sclerosis/drug therapy/blood/cerebrospinal fluid/genetics
Longitudinal Studies
tau Proteins/blood/cerebrospinal fluid
Ubiquitin Thiolesterase/blood/cerebrospinal fluid
Male
Glial Fibrillary Acidic Protein/blood/cerebrospinal fluid
Middle Aged
Neurofilament Proteins/blood/cerebrospinal fluid
Retrospective Studies
Aged

@article {pmid42196458,
year = {2026},
author = {Prodromos, CC and Del Villar, R and Striegel, A and Pena, G and Dixit, R},
title = {The Molecular Basis of Partial Reversal or Significant Slowing of ALS, Parkinson's Disease, and Lewy Body Dementia by Mesenchymal Exosomes/Secretome.},
journal = {International journal of molecular sciences},
volume = {27},
number = {10},
pages = {},
doi = {10.3390/ijms27104483},
pmid = {42196458},
issn = {1422-0067},
mesh = {Humans ; *Exosomes/metabolism/transplantation ; *Amyotrophic Lateral Sclerosis/therapy/metabolism ; *Parkinson Disease/therapy/metabolism ; Female ; Male ; *Lewy Body Disease/therapy/metabolism ; Aged ; *Mesenchymal Stem Cells/metabolism ; Middle Aged ; *Secretome/metabolism ; Case-Control Studies ; Administration, Intranasal ; },
abstract = {Neuromuscular and neurodegenerative (NMND) disorders are diseases that cause progressive damage to the central nervous system leaving patients with symptoms that negatively affect everyday living with death almost inevitable. These include amyotrophic lateral sclerosis (ALS), Lewy body dementia (LBD), and Parkinson's disease (PD) with cases expected to increase in the future. Intranasally administered stem cell-derived exosomes/secretome have been seen as potential therapeutic options for these disorders in preclinical animal models. This study sought to observe the efficacy of mesenchymal stem cell-derived exosomes/secretome in patients with ALS, LBD, and PD. Based off these preclinical studies, we conducted a case-controlled series experiment with 86 patients with ALS, LBD, or PD, with the independent variable being the treatment and the dependent variable being the clinical response. These patients were recruited and given intranasal instillations of various MSC-derived exosome/secretome products. Subsequent treatments were given to patients who did not have a response to one product. Patients were followed up at one week, one, two, three, and six months post-treatment. Historical external controls were used for comparison to clinical outcomes. There were no serious adverse events in any patient. A total of 67 of 86 (77%) patients showed a positive clinical response to at least one product. Outcomes were strongly associated with greater treatment frequency for ALS and LBD. Intranasal administration of MSC-derived exosome/secretome products were safe, and most patients showed overall improvement with at least one product. Some patients also saw a substantial decrease in the rate of decline compared to historical controls. These results also give rise to the hypothesis: do MSC-derived exosomes/secretome treatments show efficacy in other NMND disorders? The primary limitation of this study is the 6-month follow-up.},
}

Humans
*Exosomes/metabolism/transplantation
*Amyotrophic Lateral Sclerosis/therapy/metabolism
*Parkinson Disease/therapy/metabolism
Female
Male
*Lewy Body Disease/therapy/metabolism
Aged
*Mesenchymal Stem Cells/metabolism
Middle Aged
*Secretome/metabolism
Case-Control Studies
Administration, Intranasal