@article {pmid42281996,
year = {2026},
author = {Cooper-Knock, J and Bonsall, S and Kazu, R and King, M and Leung, D and Mahiddine, F and Highley, J and Strange, A and Chen, Y and Sassani, M and Eldahshoury, M and Boyne, J and Collins, M and Monte, E and Harvey, C and Gornall, S and Jangid, A and Treanor, C and Moll, T and van Dijk, C and Cabras, S and Urban, A and Bowden, K and Wareing, H and Huang, Y and Shaw, P and West, R and Kenna, K and Hornstein, E and Zhang, S and Zhou, J and Snyder, M},
title = {Single-nucleus multiomic atlas of ALS primary motor cortex nominates neuroprotective WDR49-expressing astrocytes.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-9853460/v1},
pmid = {42281996},
issn = {2693-5015},
abstract = {Amyotrophic lateral sclerosis (ALS) causes selective neurodegeneration in primary motor cortex, yet cell-type-specific molecular changes driving this vulnerability remain poorly understood. We present an integrated single-nucleus RNA- and ATAC-sequencing atlas of 778,330 nuclei from the primary motor cortex of 140 genetically characterised donors. ALS is associated with widespread transcriptional reprogramming driven by a common set of transcription factors (TFs) across multiple cell-types. Astrocytes harbour the most differentially expressed genes. Within astrocytes, a WDR49-expressing subpopulation is spatially associated with TDP-43 pathology, and genetic variants within WDR49 confer risk for both sporadic and monogenic autosomal dominant ALS. In patient-derived induced astrocytes, WDR49 protein abundance predicts the survival of co-cultured neurons. WDR49 localises to PML nuclear bodies, where it regulates astrocyte reactivity and secretion of EVs containing protein chaperones. Together, these in vivo and in vitro findings suggest that WDR49+ astrocytes mount a compensatory secretory response to extracellular protein aggregates, and that loss of this capacity lowers the threshold for ALS pathogenesis.},
}

@article {pmid42282536,
year = {2026},
author = {Cortez, JD and Avalos, JL},
title = {Heterologous iron-sulfur cluster biogenesis and delivery for cytosolic isobutanol and isopentanol production in Saccharomyces cerevisiae.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.05.29.728687},
pmid = {42282536},
issn = {2692-8205},
abstract = {Saccharomyces cerevisiae is an excellent microbial platform for sustainable production of next generation biofuels such as the branched chain higher alcohols (BCHAs) isobutanol and isopentanol. A cytosolic pathway for BCHA production is generated from expression of prokaryotic orthologs of branched-chain amino acid (BCAA) enzymes acetolactate synthase (ALS), mutant NADH-dependent ketol-acid reductoisomerase (KARI [P2D1-A1]), and dihydroxy-acid dehydratase (DHAD). The potential for this pathway has been hindered by the availability of iron-sulfur clusters, particularly the 2Fe-2S cluster, required for DHAD to function in the cytosol. ILV3 , the endogenous yeast DHAD located in the mitochondria, can be deleted to create a valine auxotroph. In this study we use bioinformatics, heterologous gene library synthesis, and a valine complementation assay to find prokaryotic iron-sulfur cluster biosynthetic gene clusters (BGC) and accessory genes that aid DHAD function in the yeast cytosol. This work presents, to our knowledge, the first functional BGC that enhances the cytosolic activity of prokaryotic DHADs in S. cerevisiae . The SUF BGC from Bacillus subtilis combined with a ferritin-like protein (FTNB) from Escherichia coli and the Lactococcus lactis DHAD enhanced the production of BCHAs. Combined expression gave an average isobutanol titer of 412mg/L, 1.8-fold greater than L. lactis DHAD expressed alone. This work establishes a blueprint for better biofuel production by improving iron-sulfur cluster dependent enzyme activity in the yeast cytosol.},
}

@article {pmid42282588,
year = {2026},
author = {Kochen, NN and Zafari, S and Renaud, A and Schneider, N and Vunnam, N and Liao, EE and Dutton, JR and Braun, AR and Sachs, JN},
title = {From anti-fungal to potential neurotherapeutic: Posaconazole as an effective inhibitor of cellular TDP-43 pathology.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.06.01.728552},
pmid = {42282588},
issn = {2692-8205},
abstract = {Recently, we showed that ketoconazole, a known anti-fungal inhibitor of CYP51, stabilized TAR DNA-binding protein 43 (TDP-43) native self-interactions, reduced TDP-43 pathology and rescued TDP-43-induced SREBP2 downregulation. Despite its promising effects, ketoconazole is not viable for repurposing for ALS due to liver toxicity side effects that occur when orally delivered. To address this, we tested the activities of seven additional known azole-based CYP51 inhibitors in order identify a viable alternative to ketoconazole. Using our established TDP-43 mislocalization and aggregation assay in HEK293T cells, we identified posaconazole, an FDA-approved, CNS-penetrant and orally delivered anti-fungal, as the strongest inhibitor of TDP-43 pathology. Posaconazole was able to reduce insoluble TDP-43 and restore SREBP2 levels, outperforming ketoconazole. Mechanism of action (MOA) experiments suggest posaconazole is able to outperform ketoconazole by inducing a significantly stronger activation of autophagy and upregulation of heat shock proteins known to clear TDP-43. Further MOA experiments show that the effects of posaconazole on TDP-43 are dependent on its known ability to lower cellular cholesterol levels. By correlating our experimental results on the eight CYP51 inhibitors tested, we show that predicted affinity towards human CYP51 strongly correlates with the inhibitors' ability to lower TDP-43 aggregation and mislocalization. Finally, we tested posaconazole in a low dose sodium arsenite ALS model in iPSC-derived motor neurons, showing that it is efficacious at inhibiting TDP-43 pathology in the nanomolar range. Altogether, these results support the repurposing of posaconazole for ALS/FTD as a means to prevent TDP-43 pathology.},
}

@article {pmid42274592,
year = {2026},
author = {Sgalletta, B and Agostini, F and Bisaglia, M},
title = {The Role of Iron in Neuronal Homeostasis: A Double-Edged Sword.},
journal = {Cells},
volume = {15},
number = {11},
pages = {},
pmid = {42274592},
issn = {2073-4409},
mesh = {Humans ; *Iron/metabolism ; *Homeostasis ; Animals ; *Neurons/metabolism ; Neurodegenerative Diseases/metabolism/pathology ; Neurogenesis ; Neurodevelopment ; Brain/metabolism ; },
abstract = {Iron is an essential micronutrient that plays a central role in numerous biological processes. Despite its relatively low abundance in the human body, iron is particularly critical for brain function. Systemic and cerebral iron homeostasis is tightly regulated through coordinated mechanisms involving absorption, transport, storage, and recycling. Within the brain, iron metabolism is further controlled by the blood-brain barrier and specialized neural cell populations, including neurons, astrocytes, oligodendrocytes, and microglia. Iron is indispensable for neurodevelopment, supporting neurogenesis, myelination, and neurotransmitter synthesis. However, both iron deficiency and iron overload have detrimental consequences. Early-life iron deficiency disrupts neural development and leads to long-lasting cognitive, motor, and behavioral impairments, whereas excessive iron accumulation promotes oxidative stress, ferroptosis, and neuroinflammation. These mechanisms have been described to contribute to the pathogenesis of major neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, neurodegeneration with brain iron accumulation, and amyotrophic lateral sclerosis. This review first outlines systemic and brain iron metabolism, highlighting how neural cells regulate homeostasis. Next, it examines iron's physiological roles, particularly in neurogenesis and neurodevelopment. Finally, it explores iron's involvement in neurodegenerative diseases, emphasizing neuroinflammation as a primary mechanism of iron toxicity.},
}

Humans
*Iron/metabolism
*Homeostasis
Animals
*Neurons/metabolism
Neurodegenerative Diseases/metabolism/pathology
Neurogenesis
Neurodevelopment
Brain/metabolism

@article {pmid42274906,
year = {2026},
author = {He, Y and Yi, T and Min, M and Xu, K and Lin, H and Xu, R and Deng, D and Xiao, X},
title = {Environmental Factors Drive Neurodegenerative Diseases Through Glutamate Excitotoxicity: A Convergent Mechanistic Pathway.},
journal = {Neuroscience bulletin},
volume = {},
number = {},
pages = {},
pmid = {42274906},
issn = {1995-8218},
abstract = {This review illustrates how environmental stressors disrupt glutamate homeostasis via specific mechanisms: lead-induced thiol modification, manganese mediated yin yang 1 (YY1)-histone deacetylases (HDAC) repression, PM2.5-triggered microglia-astrocyte crosstalk, and advanced glycation end products (AGEs)-receptor for advanced glycation end products (RAGE)-nuclear factor kappa-B (NF-κB) signaling from high-sugar diets. Together with genetic susceptibility and pigment epithelium-derived factor (PEDF), these factors impair astrocytic glutamate uptake, promoting synaptic glutamate accumulation. Subsequent N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor overactivation triggers calcium overload, mitochondrial dysfunction, oxidative stress, and neuroinflammation-termed "degenerative excitotoxicity". Excitotoxicity manifests in Alzheimer's disease (amyloid-beta-excitatory amino acid transporter 2 (EAAT2) interplay), Parkinson's disease (subthalamic nucleus-driven excitatory storm), and amyotrophic lateral sclerosis (astrocytic failure versus neuronal cell-autonomous mechanisms). Future interventions need multi-target strategies, emerging technologies, and lifestyle modifications. This convergent framework offers a unified understanding linking environmental exposure to neurodegeneration and charts a roadmap toward mechanism-based prevention and treatment.},
}

@article {pmid42274979,
year = {2026},
author = {Ojha, GJ and Talwar, T},
title = {Exploring the Role of Spirituality in Neuropalliative Care: An Integrative Review.},
journal = {Journal of religion and health},
volume = {},
number = {},
pages = {},
pmid = {42274979},
issn = {1573-6571},
abstract = {Neuropalliative care aims to address the physical, psychosocial and spiritual needs of persons with progressive and life-limiting neurological conditions, while spiritual care fosters hope and meaning in life. Progressive neurological disorders with an uncertain disease trajectory present a set of complex challenges that have far-reaching consequences on the patient's self-belief, questioning the very existence, self-identity, and belongingness. A typical neuropalliative care team consists of neurologists, nurses, psychologists, occupational therapists, and spiritual care providers. Previous research indicates that spiritual care improves coping and quality of life in persons with Parkinson's disease and Amyotrophic lateral sclerosis. This study aimed to explore how spiritual needs are addressed in the area of neuropalliative care, examining the theoretical frameworks and empirical studies that incorporate spirituality as a component of neuropalliative care. The databases PubMed, PsycINFO, Cochrane Library, Scopus and two peer-reviewed journals were searched using a strategy based on three sets of terms "spirituality," "progressive neurological conditions" and "neuropalliative care." Articles included were in the English language, and mentioned spirituality in the context of neuropalliative care or palliative care for neurological conditions. Initial screening yielded 744 articles, of which 29 were selected for synthesis. Results highlighted the various challenges in ascertaining and meeting the spiritual needs in neuropalliative care. The review concludes that palliative services should be initiated early following the diagnosis of a progressive neurological condition so that the patient and family have enough time to reflect, create memories, and prepare in advance for the inevitable through dignity and resilience.},
}

@article {pmid42275159,
year = {2026},
author = {Ito, D and Iida, M and Iguchi, Y and Hashizume, A and Yamada, S and Kishimoto, Y and Komori, S and Obara, K and Nishisaki, S and Yokoi, S and Shimamura, T and Takemoto, Y and Nakatochi, M and Akashi, T and Hinohara, K and Lee-Okada, HC and Okada, Y and Niwa, J and Sobue, G and Tanaka, S and Takashina, K and Yokomizo, T and Katsuno, M},
title = {Fatty acid amide hydrolase inhibition for treatment of amyotrophic lateral sclerosis.},
journal = {JCI insight},
volume = {},
number = {},
pages = {},
doi = {10.1172/jci.insight.198842},
pmid = {42275159},
issn = {2379-3708},
abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease caused by the selective loss of upper and lower motor neurons. There is a considerable variability in the disease progression of sporadic ALS, but the molecular basis for phenotypic heterogeneity remains largely unknown. ALS patients often manifest systemic metabolic abnormalities such as glucose intolerance and hypermetabolic state. We conducted reverse translational research to explore therapeutic targets in ALS based on the systemic metabolic alterations in patients and identified several metabolites associated with the disease progression, including metabolites involved in the expanded endocannabinoid system (ECS). In particular, the levels of N-acyl taurines (NATs) were correlated with the longitudinal change in the revised ALS functional rating scale and survival. Experiments with ALS cellular models, iPS cells derived from ALS patients and SOD1G93A transgenic mice revealed that PF-04457845, a fatty acid amide hydrolase inhibitor, upregulated the expanded ECS, particularly the levels of NATs and ameliorated motor neuron degeneration through the regulation of microglial environment, synapse plasticity, and neuronal development. These results collectively indicate that dysregulation of NATs is associated with ALS progression and PF-04457845 may represent a potential disease-modifying therapy for ALS.},
}

@article {pmid42276279,
year = {2026},
author = {Gurung, N and Choi, DY and Park, PH},
title = {Naringenin as a Multi-Target Neuroprotective Agent in Neurodegenerative Diseases.},
journal = {Neurochemistry international},
volume = {},
number = {},
pages = {106203},
doi = {10.1016/j.neuint.2026.106203},
pmid = {42276279},
issn = {1872-9754},
abstract = {Neurodegenerative diseases (ND) such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS) are characterized by progressive neuronal loss driven by complex and multifactorial pathogenic mechanisms. Naringenin (NAR), a citrus-derived flavanone, has attracted considerable interest as a neuroprotective molecule due to its pleiotropic pharmacological activities such as antioxidant, anti-inflammatory and ability to modulate multiple cellular targets. This review provides a comprehensive overview of NAR pharmacokinetic profile, mechanistic actions, and therapeutic potential across major ND. We highlight how NAR's multi-target effects-including redox homeostasis maintenance, suppression of neuroinflammation, protein aggregation inhibition, and modulation of signaling pathways-contribute to neuroprotection in various experimental models of AD, PD, HD, ALS, and MS. Preclinical studies demonstrate that NAR can ameliorate cognitive and motor deficits in toxin and transgenic models of neurodegeneration, attenuate pathological hallmarks such as amyloid-beta toxicity, dopaminergic neuronal loss, and neuroinflammation, and induce cytoprotective pathways including Nrf2-mediated antioxidant response and autophagy. However, NAR's clinical translation is challenged by poor bioavailability; thus, novel delivery systems are being explored to enhance brain uptake. NAR emerges as a promising multi-functional neuroprotective agent that can simultaneously target diverse pathogenic processes in ND. Further research including advanced formulation development and well-designed clinical trials is warranted to fully establish NAR's therapeutic efficacy and safety in humans.},
}

@article {pmid42276329,
year = {2026},
author = {Abzhanova, E and Kawae, Y and Mizuno, H and Umemoto, T and Ciftci, H and Tsuboi, M and Hirabayashi, Y and Mizuno, H},
title = {ALS-associated protein TDP-43 disturbs axonal projections in the somatosensory cortex.},
journal = {Neuroscience research},
volume = {},
number = {},
pages = {105079},
doi = {10.1016/j.neures.2026.105079},
pmid = {42276329},
issn = {1872-8111},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by loss of upper and lower motor neurons that gradually causes muscle weakness and paralysis, eventually resulting in death. While ALS was once believed to specifically target motor neurons, recent clinical studies have revealed sensory involvement. The pathological hallmark of ALS is TAR DNA-binding protein 43 (TDP-43) aggregation in cytoplasm, with increasing evidence of its presence in both motor and sensory neurons. However, sensory abnormalities remain poorly characterized. To address this research gap, we analyzed the effects of TDP-43 expression on layer 2/3 (L2/3) pyramidal neurons of the primary somatosensory cortex in mice projecting through corpus callosum. In utero electroporation (IUE) was performed to express GFP alone (control) or in combination with TDP-43. Compared with the control, mice co-expressing GFP and TDP-43 showed disturbed callosal axonal projections of L2/3 neurons. Mutant TDP-43 variants displayed a more pronounced phenotype, indicating pathogenic role during fetal cortical development. To distinguish developmental from maintenance effects, tamoxifen-inducible TDP-43 expression was used to initiate postnatal TDP-43 expression. Postnatal induction resulted in shorter axonal length and reduced branching rather than gross projections disturbance. Taken together, these results demonstrate that TDP-43 expression can disturb the integrity of axonal projections, such as callosal projections of L2/3 neurons in the somatosensory cortex.},
}

@article {pmid42276614,
year = {2026},
author = {Karthikeyan, K and Velmurugan, G and Upadhyay, R and Sevanan, M and Chinnathambi, S},
title = {Glutamate and glutamine metabolism in neurodegenerative diseases.},
journal = {International review of neurobiology},
volume = {186},
number = {},
pages = {1-24},
doi = {10.1016/bs.irn.2026.01.008},
pmid = {42276614},
issn = {2162-5514},
mesh = {Humans ; *Glutamic Acid/metabolism ; *Glutamine/metabolism ; *Neurodegenerative Diseases/metabolism/drug therapy ; Animals ; },
abstract = {Glutamate is known as the most important excitatory neurotransmitter in brain. Glutamate and glutamine recycling is very essential to maintain the nitrogen metabolism. Despite of its major functions, its dysregulation is a basic pathology which is common to neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), and Amyotrophic lateral sclerosis (ALS). Amyloid-β and Tau in AD disrupt glutamate uptake and the glutamate-glutamine cycle, accelerating synaptic failure, whereas loss of astrocytic EAAT2 in ALS generates unrelenting excitotoxicity and motor neuron demise. Toxic α-synuclein aggregation in PD exacerbates dopamine-glutamate imbalance through destabilizing corticostriatal transmission. This review explores on the key mechanisms by which glutamate impairment leads to the pathogenies of neurogenerative disorders and also about current medications like amantadine, memantine, and riluzole which are glutamate antagonists, are shown to partially alleviative but cannot halt the advancement of the disease. One of the potential targets for disease-modifying treatments could be the receptor modulation, astrocytic function, and elimination of excess glutamate.},
}

Humans
*Glutamic Acid/metabolism
*Glutamine/metabolism
*Neurodegenerative Diseases/metabolism/drug therapy
Animals

@article {pmid42276630,
year = {2026},
author = {McRae, M and Hart, L and Wolf, L},
title = {Accreditation as opportunity: Preparing future nursing leaders through faculty collaboration and succession planning.},
journal = {Journal of professional nursing : official journal of the American Association of Colleges of Nursing},
volume = {65},
number = {},
pages = {137-141},
doi = {10.1016/j.profnurs.2026.04.007},
pmid = {42276630},
issn = {1532-8481},
abstract = {Preparing for Commission on Collegiate Nursing Education (CCNE) accreditation requires extensive faculty engagement, yet the literature offers limited guidance on operational strategies to cultivate collaboration and mentorship during this process. This article describes the Keigwin School of Nursing's adaptation of Benner's novice to expert framework and Haverkamp et al.'s (2018) "map for accreditation" to design a collaborative approach for developing the self-study report and preparing for a site visit. Junior faculty were paired with experienced mentors in dyads, assigned to analyze key elements of the CCNE Standards, and reported findings back to cross-program Standard Teams. This structure fostered faculty development, enhanced understanding of accreditation processes, and promoted succession planning. Standardized meeting minutes, end-of-year committee reports, and the use of stoplight tracking tools provided systematic evidence of continuous quality improvement. Faculty-wide meetings and individualized support further strengthened readiness and confidence for site visit engagement. The outcome was full faculty participation, successful alignment of undergraduate and graduate program reaccreditation cycles, and no accreditation compliance concerns reported for any program. These results underscore the value of mentorship, collaboration, and succession planning in accreditation preparation and highlight the potential to address national challenges in faculty shortages, destabilization of higher education, and the need for a unified nursing faculty voice in academic advocacy.},
}

@article {pmid42276908,
year = {2026},
author = {Covas Moschovas, M and Falagario, U and Pellegrino, F and Wiklund, P and Patel, V},
title = {Reply to Alexander Light, Max Peters, Manit Arya, et al's Salvage Focal Therapy vs Radical Prostatectomy for Localized Radiorecurrent Prostate Cancer. JAMA Oncol 2026;12:364-73. https://doi.org/10.1001/jamaoncol.2025.6448.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2026.05.031},
pmid = {42276908},
issn = {1873-7560},
}

@article {pmid42279231,
year = {2026},
author = {Mesches, MH and Granholm, AC and Paredes, D and Mesches, K and Oguma, Y and Dezawa, M},
title = {Stem Cell Therapy for Parkinson's Disease: A Mechanistically Distinct Role for Muse Cells.},
journal = {Journal of clinical medicine},
volume = {15},
number = {11},
pages = {},
doi = {10.3390/jcm15114370},
pmid = {42279231},
issn = {2077-0383},
abstract = {Cell replacement therapy is a promising investigational approach for Parkinson's disease (PD), a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra. Although current PD therapies provide symptomatic relief, none halt or reverse disease progression. Early transplantation studies using fetal dopaminergic neurons provided proof of concept for PD cell replacement, with recent efforts focusing on pluripotent stem cell-derived dopaminergic progenitors that are now entering clinical testing. These strategies face challenges, however, including immune compatibility, tumorigenic risk, and the need for controlled differentiation and functional integration. Multi-lineage differentiating stress-enduring (Muse) cells are endogenous, non-tumorigenic pluripotent-like stem cells that home to sites of tissue injury and differentiate in response to the host microenvironment. A targeted literature search of PubMed and Scopus, however, did not identify prior reviews specifically addressing Muse cells in the context of PD, highlighting a gap in the literature. Here, we examine current limitations of established cell-replacement approaches and consider whether Muse cells may represent a mechanistically distinct cell source. Early clinical studies of Muse cell therapy in stroke and amyotrophic lateral sclerosis suggest an encouraging safety profile and preliminary signals of potential therapeutic benefit, although these findings are based on small, early-stage trials and require confirmation. The evidence supporting Muse cell therapy in PD is currently limited to a single preclinical animal study, supported by mechanistic in vitro findings and indirect evidence from other neurologic disease models; therefore, its relevance to PD remains to be established, and current evidence is insufficient to support conclusions regarding clinical efficacy. Together, these observations provide a rationale for further targeted preclinical investigation and support the systematic evaluation of Muse cells as a mechanistically distinct candidate for regenerative therapy in PD.},
}

@article {pmid42280649,
year = {2026},
author = {Liu, Q and Zhang, R and Sun, L and Lu, X and Xu, G and Tong, H and Zhang, B and Liu, X and Du, S},
title = {Mechanism of Echinochloa crus-galli Resistance to the ALS-Inhibiting Herbicide Pyrazosulfuron-ethyl in China.},
journal = {Plants (Basel, Switzerland)},
volume = {15},
number = {11},
pages = {},
doi = {10.3390/plants15111611},
pmid = {42280649},
issn = {2223-7747},
abstract = {Rice (Oryza sativa L.) is a staple food crop, feeding more than 3.5 billion people. With the increasing demand for food in the 21st century, weed infestation poses the most significant biotic threat to global food security, and herbicides remain the most effective and economic way to manage it in field. However, weeds can rapidly adapt under herbicide selection pressure due to their high competitiveness, rapid growth, and reproductive capacity. Hence, we collected Echinochloa crus-galli populations from Heilongjiang and Hebei provinces in China and investigated their resistance mechanisms to pyrazosulfuron-ethyl (PSE), a sulfonylurea herbicide that inhibits acetolactate synthase (ALS). Dose-response experiments confirm that the resistant (R) population exhibits 52.9-fold resistance to PSE compared with the susceptible (S) population. Inhibitor bioassays with malathion and NBD-Cl, together with ALS activity assays, ALS gene sequencing, and molecular docking, collectively suggest that resistance is strongly associated with the ALS Trp-574-Leu target-site substitution, with a possible additional contribution from enhanced herbicide metabolism. However, because the S and R populations originate from geographically distinct locations, some of the observed physiological and molecular differences may also reflect inherent population variation. Specifically, the ALS W574L substitution is predicted to reduce key interactions between ALS and PSE. This study provides valuable evidence for the risk of PSE resistance evolution in E. crus-galli and elucidates the molecular mechanism conferring resistance to ALS inhibitors.},
}

@article {pmid42281786,
year = {2026},
author = {Tsai, AC},
title = {Defining a shift estimand on forgivingness without domesticating forgiveness: Comment on Cowden et al.},
journal = {SSM. Mental health},
volume = {9},
number = {},
pages = {},
pmid = {42281786},
issn = {2666-5603},
abstract = {This commentary responds to Cowden et al.'s (2026) careful epidemiologic study of the population-wide changes in well-being that might follow from two explicitly defined "shift" scenarios applied to a three-item forgivingness measure. I value the paper's candor about its counterfactual aim: it is not asking whether forgiveness is good in the abstract, but what could plausibly happen if the distribution of measured forgivingness were moved in specified ways. I argue that Cowden et al.'s (2026) methodological clarity surfaces what remains ethically and theologically decisive. In Christian thought, forgiveness is not simply an emotion-regulation technique or a general prosocial disposition; it is a demanding practice formed by grace and ordered toward truth, justice, mercy, and (where possible) repair. When we compress that "thick" practice into a several-item scale for administration in population surveys, we risk treating qualitatively different moral realities as interchangeable. This thinning is subject to the same critique when applied to intervention: a shift estimand tells us what might follow from a distributional change but not how to bring it about; and different ways of cultivating forgiveness may not be morally or practically interchangeable, even if they produce the same numerical shift. While the rigor Cowden et al. (2026) bring to this literature is commendable, the remaining challenge is to connect distributional shifts in forgivingness scores to the concrete practices and communal disciplines that form forgiveness as a moral reality rather than a psychological technique.},
}

@article {pmid42265995,
year = {2026},
author = {Ozlu, C and Schwaede, A and McGowan, B and Zhang, L and Finch, M and Wolfe, LF and Ajroud-Driss, S and Franz, C and Kuntz, N},
title = {Two Patients With Juvenile-Onset, Rapidly Progressive Amyotrophic Lateral Sclerosis Associated With an SOD1 Variant (p.Asp125Gly) With Incomplete Penetrance.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70314},
pmid = {42265995},
issn = {1097-4598},
abstract = {INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) patients are rarely encountered before age 25 years, often associated with genetic variants. SOD1 gene variants are well-known to account for a subset of adult-onset ALS but have only been described in a handful of early onset patients. Variants affecting residue 125 in SOD1 have been described in adult-onset ALS patients with a rapid progression. Here we report two such patients.

METHODS: The clinical, genetic, and electrodiagnostic findings of two unrelated adolescents with juvenile onset rapidly progressive SOD1-ALS are described.

RESULTS: Patient 1 presented at 16 and patient 2 at 15 years-of-age with lower limb onset of weakness, lower motor neuron examination findings, and rapid progression over months to involve all body regions. Both patients underwent extensive laboratory, electrophysiologic, and radiologic testing ruling out any alternate etiologies. For both patients, whole-exome sequencing revealed the pathogenic variant p.Asp125Gly in the SOD1 gene inherited from asymptomatic fathers.

DISCUSSION: These two patients expand the phenotypic spectrum of SOD1-ALS, demonstrating a rapidly progressive juvenile lower limb onset phenotype associated with the p.Asp125Gly variant inherited with incomplete penetrance. Recognition and further characterization of juvenile SOD1-ALS are important in light of the advances in targeted therapies.},
}

@article {pmid42266360,
year = {2026},
author = {Ilczak, T and Ćwiertnia, M and Sumera, K and Babik, P and Białoń, P and Dutka, M and Malinowska-Lipień, I and Augustyn, M and Majewski, M and Lis, A and Leszczyński, P and Stasicki, A and Abramczyk, P and Kukla, P and Pollok-Waksmańska, W and Trojak-Piętka, J and Kawecki, M},
title = {Nontechnical Skills (NTS) and the Quality of Conducting Prehospital Advanced Cardiopulmonary Resuscitation Among Paramedics.},
journal = {Emergency medicine international},
volume = {2026},
number = {},
pages = {2207053},
pmid = {42266360},
issn = {2090-2840},
abstract = {INTRODUCTION: It is common knowledge that the correct application of cardiopulmonary resuscitation (CPR) requires technical skills such as defibrillation, high-quality chest compressions, and efficient airway management. However, scientific research is increasingly underlining the role of appropriate training in nontechnical skills (NTS).

RESEARCH AIM: This exploratory study aimed to assess the relationship between NTS and the quality of advanced CPR among paramedics.

MATERIALS AND METHODS: The research involved 51 paramedics randomly assigned to 17 three-person teams. Each team participated in a 15-min cardiac arrest scenario. After the first session, the teams were divided into two groups: the intervention group (Group 1), which underwent specialized NTS training, and the control group (Group 2), which did not receive the initial training. Directly after the training phase, all teams from both groups carried out a second attempt during a simulated sudden cardiac arrest (SCA) scenario identical to the first one.

RESULTS: The lowest CPR result in the intervention group (Group 1) was Min = -3.00, and the highest Max = 13.00, while in the control group (Group 2), the lowest result was Min = -42.00, and the highest Max = 8.00 (p < 0.05). In Group 1, a statistically significant correlation (p < 0.05) was noted between the change in the NTS score and the change in the CPR result. A higher NTS score was accompanied by a higher CPR score.

CONCLUSIONS: A short NTS training session was associated with improved NTS application by paramedic resuscitation teams. Furthermore, higher chest compression quality positively correlated with NTS proficiency.},
}

@article {pmid42267592,
year = {2026},
author = {Malik, MMUD},
title = {Moral Injury, Peer Support and Allied Health Integration: Three Extensions to Gilmore et al.'s Account of Mental Health Crisis Care in Homelessness.},
journal = {Journal of psychiatric and mental health nursing},
volume = {},
number = {},
pages = {},
doi = {10.1111/jpm.70156},
pmid = {42267592},
issn = {1365-2850},
}

@article {pmid42267597,
year = {2026},
author = {Held-Bradford, EC and DeMarco, E and Zocher, S and Weaver, K and Forsman, K and Hayat, G and Subramaniam, DS and Doherty, M},
title = {Functional Motor Change Across Time and Phenotypes in Patients With Amyotrophic Lateral Sclerosis: A Descriptive Study.},
journal = {Neurorehabilitation and neural repair},
volume = {},
number = {},
pages = {15459683261445435},
doi = {10.1177/15459683261445435},
pmid = {42267597},
issn = {1552-6844},
abstract = {PURPOSE: Progressive disability occurs in persons with amyotrophic lateral sclerosis (pALS), but change over time across phenotypes remains understudied, limiting clinical decision-making. This descriptive study describes functional motor change with detailed measures across ALS phenotypes to enhance clinical decision making.

MATERIALS AND METHODS: Electronic health record data from an interdisciplinary ALS clinic (n = 109 pALS, 2018-2022) including demographics, disability (ALS Functional Rating Scale-[ALSFRS-R]), and functional motor scores (10 m Walk, Handheld dynamometry [grip and ankle]) was utilized. Phenotype groups were defined by site of onset (bulbar, limb onset; upper limb or lower limb). Analysis was conducted using R and included changes scores and measures of central tendency in 3-month intervals.

RESULTS: PALS included n = 43 bulbar, n = 32 upper limb, n = 34 lower limb onset, age 65, 60 to 71 (median, interquartile range). ALFSRS-R decline was greatest in bulbar, and similar in upper and lower limb. Patterns of change within motor scores suggest greatest loss of grip strength in bulbar and upper limb, ankle strength in upper limb, walking speed in lower limb, and preservation of community ambulation in upper limb.

CONCLUSION: While ALSFRS-R scores were similar in upper and lower limb, detailed functional motor measures indicated differences in groups. These patterns provide insight to guide clinical decision making and future research to enhance care in pALS.},
}

@article {pmid42267908,
year = {2026},
author = {Donati Della Lunga, I and Cerutti, L and Barabino, V and Figus, GG and Callegari, F and Oneto, L and Tedesco, M and Bacchetti, F and Milanese, M and Massobrio, P and Brofiga, M},
title = {Developmental circuit instability in amyotrophic lateral sclerosis: from hyperexcitability to network collapse.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag185},
pmid = {42267908},
issn = {1460-2156},
abstract = {Amyotrophic lateral sclerosis (ALS) is traditionally viewed as a late-onset motor neuron disease, yet how cortical dysfunction originates and contributes to pathogenesis remains unresolved. In this study, we reconstruct the developmental trajectory of cultured cortical networks derived from SOD1G93A mouse embryos using a multimodal approach, by combining morphometric, electrophysiological, pharmacological, molecular, computational, and machine-learning techniques. We prove that ALS neurons fail to acquire mature polarization and connectivity, displaying a transient phase of hyperexcitability that precedes a progressive collapse of network organization. Astrocytic dysfunction emerges early and impairs synchronization, establishing a causal link between glial dysfunction and neuronal instability. The analysis of synaptic transmission reveals an excitatory bias followed by maladaptive inhibitory recruitment and GABA/glutamate co-release, causing fragmented and inefficient network topologies. Finally, in silico modelling identified deficient intrinsic adaptation as a key driver of hyperexcitability. Together, our findings position ALS as a developmentally rooted disorder of cultured cortical network homeostasis, driven by glial, synaptic, and intrinsic adaptation failures. By demonstrating that cortical dysfunction is embedded before degeneration, this work provides a unifying framework connecting early network instability to disease progression and establishes electrophysiological network signatures, detected by machine learning classifiers, as candidate biomarkers for early diagnosis and therapeutic screening.},
}

@article {pmid42268433,
year = {2026},
author = {Sytwu, HP and Jih, KY and Tsai, YS and Fang, SY and Liao, YC and Lee, YC},
title = {FUS-associated ALS in Taiwan: genetic spectrum, clinical features, and a founder haplotype of p.H517D.},
journal = {Journal of neurology},
volume = {273},
number = {7},
pages = {},
pmid = {42268433},
issn = {1432-1459},
support = {112-2314-B-075-034-MY3//National Science and Technology Council/ ; 114-2314-B-075-021-MY3//National Science and Technology Council/ ; 113-2314-B-075-018-MY3//National Science and Technology Council/ ; },
abstract = {OBJECTIVE: To characterize the genetic spectrum and clinical features of FUS-associated amyotrophic lateral sclerosis (ALS) in a Taiwanese cohort and to investigate whether the recurrent p.H517D variant represents a founder mutation.

METHODS: All coding exons and flanking intronic regions of FUS were analyzed by Sanger sequencing in 650 unrelated Taiwanese patients with ALS. Clinical characteristics of patients carrying FUS variants were evaluated. Haplotype analysis using polymorphic microsatellite markers flanking FUS was performed to assess a potential founder effect of the p.H517D variant.

RESULTS: Eight distinct heterozygous pathogenic FUS variants were identified in 11 probands and five affected relatives, including six missense and two frameshift variants. The most frequent variant was p.H517D, detected in four probands. A novel frameshift variant, p.G499Vfs*30, was identified as a de novo mutation in a juvenile-onset ALS patient. Compared with the non FUS-associated ALS cohort, patients with FUS-associated ALS had a significantly younger mean age at onset (40.1 vs 56.6 years) and more frequent bulbar onset (50% vs 19%). Haplotype analysis suggested a common founder for the p.H517D variant.

CONCLUSIONS: FUS mutations accounted for 1.7% of ALS cases in this Taiwanese cohort. The recurrent p.H517D variant appears to represent a population-specific founder mutation. Patients with FUS variants presented with earlier disease onset and heterogeneous clinical phenotypes, and de novo variants contributed to juvenile-onset disease.},
}

@article {pmid42268660,
year = {2026},
author = {Roy, É and Blais, M and Dion, P and Rouleau, GA and Dupré, N and Picher-Martel, V},
title = {Oligogenic variants in NEK1 and ATXN2 in amyotrophic lateral sclerosis: report of two cases and review of the literature.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/21678421.2026.2685158},
pmid = {42268660},
issn = {2167-9223},
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that affects the upper and lower motor neurons and leads to progressive paralysis. More than 40 genes have been implicated in familial ALS, which represents about 10% of ALS cases. Some genes, including C9orf72, SOD1, FUS and TARDBP are undoubtedly considered causative, but many others have uncertain pathogenicity and low penetrance. Here, we described the cases of two siblings affected by ALS and carrying both an ATXN2 heterozygous 32 CAG trinucleotide repeat expansion and a novel NEK1 heterozygous c.1674_1677dup. The segregation of both variants in this large family with thirteen siblings may support a role for these variants as susceptibility alleles within an oligogenic model. Our review of the literature suggests that NEK1 variants are frequently found in combination with other variants and repeats expansion in the ATXN2 gene appears to be more associated with monogenic ALS, but also frequently combined with C9orf72 repeat expansion.},
}

@article {pmid42269975,
year = {2026},
author = {Ma, M and Cui, B and Sun, X and Liu, S and Shao, K and Liu, F and Lin, P and Li, W and Zhao, Y and Yu, D and Lou, J and Yun, Y},
title = {Progressive choroid plexus enlargement across disease stages in patients with sporadic amyotrophic lateral sclerosis.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107481},
doi = {10.1016/j.nbd.2026.107481},
pmid = {42269975},
issn = {1095-953X},
abstract = {BACKGROUND: The choroid plexus (CP), a key structure involved in cerebrospinal fluid homeostasis and glymphatic function, is increasingly recognized as an interface for neuroimmune communication. Recent studies have identified CP abnormalities as potential neuroimaging markers in several neurodegenerative disorders, including sporadic amyotrophic lateral sclerosis (sALS). However, whether CP enlargement occurs early and progresses across clinical stages or over time in patients with sALS remains unclear. Given the role of the CP in peripheral-central nervous system immune crosstalk, the association between neuroinflammation and CP abnormalities in sALS also requires clarification. In this prospective study, we used structural MRI to examine cross-sectional and longitudinal CP volume changes in patients with sALS and to evaluate their associations with CSF inflammatory markers.

METHODS: This prospective study included 161 newly diagnosed patients with sALS who underwent genetic testing and structural MRI, and 64 healthy controls (HCs) who underwent structural MRI. Disease stage in patients with sALS was assessed using the King's staging system. Longitudinal MRI was performed in a subset of 42 patients, of whom 38 also underwent baseline CSF inflammatory protein assessment.

RESULTS: Compared with HCs, patients with sALS at all King's stages showed significantly larger CP volumes after Bonferroni correction (all p < 0.05). CP volumes were significantly greater in patients at King's stage 3 than in those at King's stage 1 or stage 2 after Bonferroni correction (all p < 0.05). In the longitudinal subgroup, CP volume increased significantly from baseline to follow-up. Multivariable analysis showed that higher CSF CHIT1 and IL-6 levels were independently associated with larger CP volume in patients with sALS (β = 0.348-0.456; p < 0.01).

CONCLUSIONS: Our findings provide evidence that CP enlargement occurs early and progresses across disease stages and over time in patients with sALS. Higher CSF CHIT1 and IL-6 levels were associated with larger CP volume, supporting a potential link between neuroinflammation and CP abnormalities in sALS. These findings support CP enlargement as a promising neuroimaging marker for monitoring disease progression and neuroinflammatory processes in patients with sALS.},
}

@article {pmid42270846,
year = {2026},
author = {Wood, H and Hamdi, N},
title = {Advancing amyotrophic lateral sclerosis research in Egypt.},
journal = {Nature reviews. Neurology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41582-026-01230-x},
pmid = {42270846},
issn = {1759-4766},
}

@article {pmid42271582,
year = {2026},
author = {Ito, M},
title = {[Re-evaluating ALS Medical Care in Japan: An International Comparison of Japan, Europe, the United States, and Canada-Insights from Mechanical Ventilation, Support for Social Participation, End-of-Life Care Options, Approved Drugs, and Precision Medicine].},
journal = {Brain and nerve = Shinkei kenkyu no shinpo},
volume = {78},
number = {6},
pages = {654-657},
doi = {10.11477/mf.188160960780060654},
pmid = {42271582},
issn = {1881-6096},
abstract = {Amyotrophic lateral sclerosis (ALS) care in Japan should be re-evaluated not simply as a matter of clinical choice but as a function of the public support system structure. In Japan, care is distinguished by a publicly funded model that supports home-based living and social participation following tracheostomy invasive ventilation. In contrast, Europe reflects a model centered on non-invasive ventilation and palliative care, and the United States reflects a system in which precision therapies are approved earlier but access remains highly unequal. Further, Canada reflects a model integrating multidisciplinary ALS clinics with Medical Assistance in Dying within a shared policy framework. These differences extend beyond treatment preferences and instead reflect broader social, institutional, and ethical configurations that shape the future of individuals with ALS. As access to emerging disease-modifying therapies increasingly depends on genetic testing, the central challenge in ALS care is shifting from end-of-life decision-making to the equitable distribution of precision medicine. Comparative reappraisal of national care models is therefore critical for understanding ALS not only as a neurological disease but also as a condition shaped by welfare systems, care infrastructure, and policy design.},
}

@article {pmid42271589,
year = {2026},
author = {Kunieda, K},
title = {[Clinical Management of Dysphagia and Nutritional Disorders in Neurodegenerative Diseases].},
journal = {Brain and nerve = Shinkei kenkyu no shinpo},
volume = {78},
number = {6},
pages = {695-700},
doi = {10.11477/mf.188160960780060695},
pmid = {42271589},
issn = {1881-6096},
abstract = {Dysphagia is common in patients with neuro degenerative diseases. It is associated with aspiration pneumonia, malnutrition, and reduced quality of life. Swallowing assessment should incorporate therapeutic perspectives, including the use of compensatory strategies. In conditions such as amyotrophic lateral sclerosis, weight loss is associated with a poor prognosis, and nutritional therapy may function as a disease-modifying intervention. Clinical ethical issues may arise, including decisions regarding gastrostomy or care for patients with impaired decision-making capacity. A multidisciplinary team approach is essential for managing dysphagia and nutritional problems in these patients.},
}

@article {pmid42272352,
year = {2026},
author = {Lizio, A and Farè, M and Gerardi, F and Collesi, M and Sansone, VA and Lunetta, C and Diamanti, L and Cerri, F},
title = {Impact of treatment burden on medication adherence and quality of life in amyotrophic lateral sclerosis: a prospective multicentre study.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/21678421.2026.2683691},
pmid = {42272352},
issn = {2167-9223},
abstract = {BACKGROUND: Patients with amyotrophic lateral sclerosis (ALS) face substantial barriers to medication adherence as disease progression necessitates complex drug formulation adjustments, such as crushing tablets, mixing with liquids, or delivering via feeding tubes. These modifications may not only increase the time and effort required but could also impact drug efficacy and safety.

OBJECTIVE: To evaluate the prevalence and the impact of treatment burden on medication adherence and patient-reported quality of life (QoL) in ALS.

METHODS: This prospective multicenter study enrolled ALS patients across three Italian reference centers, with assessments at baseline, 6, and 12 months. Key measures included the Multimorbidity Treatment Burden Questionnaire (MTBQ), ALSFRS-R, DYALS (dysphagia), Morisky Medication Adherence Scale, SSS-8 (somatic symptoms), INQoL (QoL), SWAMECO (swallowing/medication difficulties), alongside comorbidities and current therapies. Associations between treatment burden, QoL, and adherence were analyzed using multivariable models.

RESULTS: A total of 114 consecutive ALS patients were enrolled. Clinically significant treatment burden was observed in 69.3% of patients, with over half reporting moderate-to-high levels according to the MTBQ classification. Elevated burden was independently related to greater somatic symptom severity and formulation modification needs. Moreover, higher burden associated with poorer QoL and diminished adherence after confounder adjustment. Longitudinally, patients experiencing worsening burden over 1 year showed accelerated QoL decline compared to those remaining stable, though adherence trajectories were unaffected.

CONCLUSION: Treatment burden, particularly driven by drug formulation complexities and somatic symptoms, emerges as a pivotal, modifiable determinant of adherence and QoL in ALS. Targeted interventions to alleviate modifiable burden components hold promise for optimizing clinical outcomes and enhancing patient-centred care.},
}

@article {pmid42272365,
year = {2025},
author = {Mishra, V and Shekhar, S and Bisht, S and Chatterjee, R and Pandey, L and Pandey, A},
title = {Incidental Radiation Exposure to the Internal Mammary Lymph Nodes in Breast Cancer Patients Undergoing Intensity-Modulated Radiation Therapy: A Retrospective Analysis.},
journal = {The Gulf journal of oncology},
volume = {1},
number = {49},
pages = {16-21},
pmid = {42272365},
issn = {2521-3881},
mesh = {Humans ; Female ; *Radiotherapy, Intensity-Modulated/methods/adverse effects ; Retrospective Studies ; Middle Aged ; Adult ; *Breast Neoplasms/radiotherapy/pathology ; *Lymph Nodes/radiation effects/pathology ; *Radiation Exposure ; Radiotherapy Planning, Computer-Assisted/methods ; Radiotherapy Dosage ; },
abstract = {BACKGROUND: Breast cancer (BC) remains the most common malignancy among Indian women, with Stage III being the most frequent at diagnosis. While radiation therapy (RT) plays a pivotal role in the adjuvant treatment of breast cancer, the inclusion of internal mammary lymph nodes (IMLNs) in the radiation field remains controversial due to potential cardiopulmonary toxicity. However, the extent of incidental radiation to the IMLNs, especially with forward planning intensity-modulated radiation therapy (IMRT), remains under-explored.

OBJECTIVE: This study aimed to evaluate the incidental radiation dose received by the IMLNs in patients with leftsided breast cancer treated with forward planning IMRT.

MATERIALS AND METHODS: A total of 36 left-sided breast cancer patients, aged 35-60 years, who underwent modified radical mastectomy followed by adjuvant RT using IMRT, were retrospectively analyzed. CT-based planning and contouring were performed according to RTOG guidelines, with IMLNs contoured retrospectively using Jetwa et al.'s method. Dosimetric parameters for the planning target volume (PTV) and IMLNs were extracted and analyzed using dose-volume histograms. Statistical comparisons were made using the dependent Student's t-test.

RESULTS: The PTV received effective radiation coverage with a mean D95 of 38.47 Gy and a mean Dmean of 40.10 Gy. The IMLNs, although not directly targeted, received significant incidental radiation, with a mean D95 of 8.49 Gy, D50 of 21.59 Gy, and Dmean of 21.40 Gy. The maximum dose to the IMLNs (Dmax) reached 38.14 Gy. Comparative analysis revealed statistically significant differences in both Dmax and Dmean between PTV and IMLNs (p = 0.004 and p < 0.001, respectively).

CONCLUSION: Forward planning IMRT provides substantial incidental radiation exposure to the IMLNs, which may have therapeutic implications in reducing recurrence risk. However, this exposure also necessitates careful consideration of potential long-term toxicities to adjacent organs. Further prospective studies are warranted to evaluate the clinical outcomes associated with incidental IMLN irradiation.},
}

Humans
Female
*Radiotherapy, Intensity-Modulated/methods/adverse effects
Retrospective Studies
Middle Aged
Adult
*Breast Neoplasms/radiotherapy/pathology
*Lymph Nodes/radiation effects/pathology
*Radiation Exposure
Radiotherapy Planning, Computer-Assisted/methods
Radiotherapy Dosage

@article {pmid42274555,
year = {2026},
author = {Khan, MS and Zafar, I and Noman, M and Yang, G and Kang, KS and Bopassa, JC},
title = {Polypharmacology of Pathway Crosstalk in Neurodegenerative Diseases: Chemical Modulation of Interconnected Signaling Networks.},
journal = {Cells},
volume = {15},
number = {11},
pages = {},
pmid = {42274555},
issn = {2073-4409},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology ; *Signal Transduction/drug effects ; *Polypharmacology ; Animals ; Oxidative Stress ; Mitochondria/metabolism ; },
abstract = {Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), arise from highly interconnected molecular and cellular abnormalities that progressively lead to neuronal dysfunction, synaptic failure, and cell death. This review provides a unified framework to understand the interrelated molecular mechanisms driving these diseases, with a focus on identifying key disease-specific intervention nodes. Core contributors include oxidative stress, mitochondrial dysfunction, protein aggregation, neuroinflammation, and emerging roles of peroxisomal dysfunction in redox imbalance, lipid dysregulation, and inflammatory amplification. Single-target therapies often show limited efficacy due to the complex, interconnected nature of these pathways. In contrast, polypharmacology, which targets multiple disease-relevant mechanisms simultaneously, offers a more promising therapeutic strategy. This review critically examines how pathway crosstalk drives neurodegenerative progression, with particular emphasis on mitochondrial-ROS-inflammatory signaling, aggregation-proteostasis failure, synaptic-neuroimmune dysfunction, and gut-brain communication. It evaluates various multi-node intervention strategies, including multi-target-directed ligands (MTDLs), molecular hybrids, natural products, drug repurposing, and nanocarrier-based delivery systems. Advances in network pharmacology, artificial intelligence (AI), bioinformatics, and multi-omics have enhanced the identification of actionable therapeutic nodes, candidate compounds, and brain-targeted delivery platforms. Notably, the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathways-play distinct roles in neuroinflammation, amplifying neuronal damage by releasing inflammatory cytokines and inducing mitochondrial dysfunction. However, successful translation into clinical practice remains constrained by challenges such as blood-brain barrier penetration, patient heterogeneity, and biomarker limitations. The review advocates for a shift towards mechanism-informed, patient-stratified polypharmacological strategies to better address the network pathology of neurodegeneration, despite significant translational hurdles.},
}

Humans
*Neurodegenerative Diseases/drug therapy/metabolism/pathology
*Signal Transduction/drug effects
*Polypharmacology
Animals
Oxidative Stress
Mitochondria/metabolism

@article {pmid42274577,
year = {2026},
author = {Schuldt, ON and Leitch, SR and Jones, LK and Buckley, PR and Morrison, BE},
title = {Neuroinflammatory Remodeling by Type 2 Immune Pathways Links Allergic Signaling to Neurodegenerative Disease.},
journal = {Cells},
volume = {15},
number = {11},
pages = {},
pmid = {42274577},
issn = {2073-4409},
support = {R15HL165397//National Heart Lung and Blood Institute/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/immunology/pathology ; Animals ; *Signal Transduction/immunology ; *Hypersensitivity/immunology ; *Neuroinflammatory Diseases/immunology ; },
abstract = {The hallmarks of allergic diseases are Type 2 immunity, including IL-4 and IL-13 production, IgE antibody generation, mast cell and basophil activation, histamine release, and eosinophil activation. There are many routes by which such mediators can influence CNS biology, including cytokine entry or signaling via brain barrier receptors; leukocyte trafficking across activated barriers; cytokine signaling via circumventricular organ sites or dural immune compartments; vagus nerve afferent signaling; mast cell degranulation; and histamine neuromodulation. Neuroinflammation is a common hallmark of many neurodegenerative diseases, but whether and to what degree allergic/type 2 immune biology may be involved depends on the specific disease stage and pathology. Here, we assess studies connecting the roles of IL-4/IL-13 signaling, IgE/mast cell activation, eosinophil-attractive chemokines, and histamines in Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, dementia with Lewy bodies, Huntington's disease, prion disease, and tauopathy/atypical parkinsonism. Mechanisms appear most clear in the case of Parkinson's disease, where epidemiology suggests an important role in dementia/Alzheimer's disease, while for other neurodegenerative conditions the evidence is less compelling and may be either mechanistic or modulatory. Confounding issues include sex differences, drug exposures, comorbid conditions, socioeconomic factors, and coexisting inflammatory diseases. Finally, we suggest a strategy based on longitudinal immune phenotyping, CNS biomarkers, and pathway manipulation to assess the relationship between allergic immune signaling and neurodegeneration.},
}

Humans
*Neurodegenerative Diseases/immunology/pathology
Animals
*Signal Transduction/immunology
*Hypersensitivity/immunology
*Neuroinflammatory Diseases/immunology

@article {pmid42261159,
year = {2026},
author = {Shirbhate, E and Singh, V and Mishra, OK and Koch, B and Tiwari, AK and Yasin, HKA and Rajak, H},
title = {The Pivotal Role of HDAC6 in Amyotrophic Lateral Sclerosis: Neuroprotective Protagonist or Degenerative Adversary?.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X462214260429080002},
pmid = {42261159},
issn = {1875-6190},
abstract = {The review specifically examines the pivotal role of HDAC6 in the pathophysiological pathway of Amyotrophic Lateral Sclerosis (ALS), an escalating neurodegenerative ailment marked by the discerning damage to motor neurons. Several lines of evidence implicate inadequate proteostasis in significantly influencing neuronal degeneration. The accumulation of misfolded proteins and proteotoxicity are highlighted as significant factors in ALS pathophysiology. Key pathological hallmarks include ubiquitin-positive inclusions, disrupted RNA metabolism, cytoskeletal perturbations, and compromised axonal transport systems. HDAC6 dysregulation disrupts axonal transport, impairing mitochondrial function and increasing oxidative stress, leading to rapid motor neuron damage and cell death. The enzyme's aberrant deacetylation of α-tubulin destabilizes microtubules and impairs intracellular trafficking. Despite HDAC6's participation in these unfavorable processes, it also exerts neuroprotective properties. It deacetylates tubulin, promoting efficient axonal transport and autophagic clearance. HDAC6 helps form aggresomes and stress granules, which are essential for cellular defence against proteotoxic stress. Through its zinc finger ubiquitin-binding domain, HDAC6 interacts with polyubiquitinated proteins, facilitating their autophagic degradation. HDAC6 inhibition can boost autophagic flux and reduce protein aggregation, while its activation may amplify the protective effects. This dichotomous behaviour of HDAC6 may pose an obstacle to the design of targeted therapy. Illuminating the complex mechanisms through which HDAC6 influences neurodegeneration and neuroprotection is important before constructing effective treatments for ALS. The review provides a clear understanding of the complex role of HDAC6 in ALS pathogenesis and highlights potential strategies to improve the prognosis of people affected by this neurological illness.},
}

@article {pmid42262533,
year = {2026},
author = {Korade, G and Kharat, S and Rathi, K},
title = {Nitric oxide in neuroinflammation and neurodegeneration: dual roles, inflammasome crosstalk, and biomarker opportunities.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {42262533},
issn = {1432-1912},
abstract = {Nitric oxide is a short-lived gas that plays a critical role in numerous physiological processes, including vascular regulation, neurotransmission, and immune responses. In the CNS NO's role is complex, as it can both protect and damage neurons. Microglia, the brain's resident macrophages, produce excessive NO in response to stimuli like endotoxins and cytokines, leading to chronic inflammation and neuronal damage associated with neurodegenerative diseases such as Alzheimer's, Parkinson's, multiple sclerosis, and amyotrophic lateral sclerosis. NO's dual role as a pro-inflammatory and anti-inflammatory mediator is intricately linked to its impact on neuronal health and disease progression. This review is aimed at summarizing and critically discussing the roles of NO in neuroinflammation, neurodegeneration, inflammasome regulation, and related therapeutic perspectives. A narrative literature review was conducted using electronic databases (e.g. PubMed and Google Scholar) to identify experimental and clinical studies on NO, neuroinflammation, neurodegenerative diseases, inflammasomes, and related biomarkers and therapies, with emphasis on mechanistic and translational work. Research into NO's effects on inflammasomes, key components of the innate immune system, reveals that NO can inhibit inflammasome activation, influencing inflammatory responses. Despite progress, challenges remain, including the need for cell-type-specific models, advanced technological approaches, and the development of selective NO modulators. Overall, current evidence indicates that NO exerts both neuroprotective and neurotoxic effects in the CNS, mediated by its complex interactions with neural, glial, and immune pathways. Future research should focus on the dual nature of NO, explore lesser-known inflammasomes, and incorporate human-centric models to develop targeted therapies.},
}

@article {pmid42262640,
year = {2026},
author = {Tavassoli, T and Marco, EJ and Puts, N},
title = {Sensory Reactivity in Autism: Integrating Behavioural, Affective, Physiological, and Neural Dimensions.},
journal = {Current psychiatry reports},
volume = {28},
number = {1},
pages = {},
pmid = {42262640},
issn = {1535-1645},
abstract = {PURPOSE OF REVIEW: The goal of this paper is to synthesise recent research on sensory reactivity differences in autism across the lifespan, using He et al.'s sensory taxonomy as an organising framework. The review aims to address how behavioural, affective, perceptual, physiological, and neural levels of processing contribute to sensory reactivity differences, and how these differences relate to broader outcomes such as mental health, adaptive functioning, and quality of life.

RECENT FINDINGS: Across behavioural studies, autistic youth show elevated and variable sensory responsivity, with hypersensitivity predicting internalising symptoms and sensory seeking linked to externalising behaviours. Affective reactivity is consistently elevated across cultures, associated with anxiety and caregiver stress, and sensory seeking may function as a coping mechanism. Psychophysical research reveals domain‑specific perceptual differences-such as reduced tactile adaptation, altered motion noise exclusion, and enhanced pitch discrimination-rather than overarching hyper‑ or hyposensitivity. These perceptual findings often show limited correspondence with questionnaire‑based measures. Physiologically, autonomic dysregulation is implicated, or pharmacological approaches show emerging promise. Neuroimaging evidence highlights excitation-inhibition imbalance and altered connectivity, including dissociations between exogenous and endogenous networks in sensory‑reactive autistic children. Across multiple levels of processing, sensory reactivity differences in autism are robust, heterogeneous, and meaningfully linked to mental health and daily functioning. Key conclusions include: • Sensory hyperreactivity predicts internalising challenges, while sensory seeking may reflect regulatory strategies. • Perceptual differences are domain‑specific • Physiological and neural evidence converges on autonomic dysregulation and differences in connectivity patterns.},
}

@article {pmid42262849,
year = {2026},
author = {Deleu, B and Dupont, P and Bracaval, K and Ombelet, F and Hobin, F and Lamaire, N and Van Laere, K and Van Damme, P and De Vocht, J},
title = {[18]F FDG-PET correlates of motor neuron disease motor variants.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-5},
doi = {10.1080/21678421.2026.2682820},
pmid = {42262849},
issn = {2167-9223},
abstract = {While [18]F-fluorodeoxyglucose positron emission tomography (FDG-PET) is an established biomarker in amyotrophic lateral sclerosis (ALS), the metabolic correlates of motor neuron disease (MND) motor variants remain poorly defined. This is why we investigated patterns of cerebral glucose metabolism across the spectrum of MNDs, including progressive muscular atrophy (PMA), primary lateral sclerosis (PLS), and ALS. We retrospectively included 18 PMA, 25 PLS, and 43 matched non-hereditary ALS patients according to most recent diagnostic criteria. FDG-PET imaging revealed similar widespread hypometabolism in PMA, as in ALS, whereas PLS showed a more focal motor cortical pattern of hypometabolism. Despite clinical differences between MND subtypes, PMA and ALS showed similar FDG-PET metabolic patterns, whereas PLS exhibited a more restricted cortical signature in this retrospective study.},
}

@article {pmid42262924,
year = {2026},
author = {Mastromarco, GJ and Earnshaw, R and Moore, G and Xu, XYS and Sadek, NH and Cui, F and Lo, N and Lee, HO},
title = {Human J-domain proteins promote stress granule disassembly and suppress neurodegeneration-linked protein aggregation.},
journal = {Cell reports},
volume = {45},
number = {6},
pages = {117326},
doi = {10.1016/j.celrep.2026.117326},
pmid = {42262924},
issn = {2211-1247},
abstract = {Stress granules are conserved biomolecular condensates that form under stress and rapidly disassemble during recovery. Stress granules have been linked to pathological protein aggregation and their impaired disassembly reduces cell viability, yet the mechanisms governing their clearance and protein aggregation remain unclear. We find that human HSP70 and a subset of J-domain proteins (JDPs) localize to stress granules and that chemical or genetic inhibition of these chaperones markedly slows granule disassembly. Conversely, overexpressing these JDPs, particularly DNAJB1, accelerates disassembly without altering assembly. In vitro, HSP70 and DNAJB1 partition into G3BP1 condensates and reduce their size in an ATP-dependent manner. In cells expressing amyotrophic lateral sclerosis (ALS)-linked mutant FUS, DNAJB1 depletion further impairs stress granule clearance and promotes pre-amyloid accumulation, while depleting a non-stress granule JDP has no effect. Our findings demonstrate that specific JDP chaperones enhance stress granule disassembly and help limit aberrant protein aggregation.},
}

@article {pmid42263252,
year = {2025},
author = {Bétourné, A and Texakalidis, P and Raheb Khelo, R and Campbell, M and Sadiq, SA and Boulis, NM},
title = {Intrathecal Administration of Riluzole in Amyotrophic Lateral Sclerosis.},
journal = {Neurosurgery},
volume = {},
number = {},
pages = {},
doi = {10.1227/neu.0000000000003859},
pmid = {42263252},
issn = {1524-4040},
abstract = {BACKGROUND AND OBJECTIVES: Riluzole is the only treatment known to improve survival in amyotrophic lateral sclerosis (ALS) patients. However, its efficacy and dosing are limited by hepatic toxicity and interindividual pharmacokinetic variability. Recent experimental studies in hounds have shown that continuous intrathecal (IT) administration of riluzole is well tolerated and achieves significantly higher spinal cord tissue levels. We report the first 2 human ALS cases treated with IT riluzole.

METHODS: A catheter was inserted into the lumbar cistern and advanced to the midcervical region under fluoroscopic guidance and connected to a subcutaneous pump. Therapy was initiated at 0.1 mg/h of riluzole. The infusion rate was gradually increased until it reached a maximum of 4.8 mg/d.

RESULTS: The 2 patients tolerated dose escalation and treatment for over 2 years without apparent motor or sensory complications. Patients reported no asthenia, a central side effect often reported as a reason to abandon oral therapy.

CONCLUSION: This is the first report of chronic IT riluzole infusion in humans at a dose found to be safe in canines. A phase 1 study is planned to establish the maximum tolerated human dose, followed by a randomized placebo-controlled trial to determine the safety and tolerability of IT riluzole in patients with ALS.},
}

@article {pmid42263370,
year = {2026},
author = {Deveci, Ş and Matur, Z and Erzurumluoğlu, SS},
title = {Sensory abnormalities and entrapment neuropathies identified by nerve conduction studies in patients with amyotrophic lateral sclerosis.},
journal = {Neuromuscular disorders : NMD},
volume = {64},
number = {},
pages = {106463},
doi = {10.1016/j.nmd.2026.106463},
pmid = {42263370},
issn = {1873-2364},
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder primarily affecting motor neurons; however, non-motor symptoms, including sensory and autonomic disturbances, are increasingly recognized. This retrospective cross-sectional study evaluated the frequency of sensory and entrapment neuropathies in 114 patients with ALS using electrodiagnostic (EDX) studies. Demographic characteristics, comorbidities, and sensory and autonomic symptoms were documented. Electrophysiological evidence of sensory neuropathy was identified in 20 patients overall (20/114, 17.5%), including 10 patients without diabetes mellitus (DM), whereas entrapment neuropathy was detected in 28 patients overall (28/114, 24.6%), including 16 of those without DM or hypothyroidism. Sensory neuropathy was significantly associated with both DM and a history of chronic disease. In contrast, these comorbid conditions were not significantly associated with entrapment neuropathy. Furthermore, patient-reported symptoms showed no correlation with electrophysiological evidence of sensory involvement on EDX. Sensory neuropathy was more frequent in patients with spinal-onset than bulbar-onset disease, although the difference was not statistically significant. This study confirms that sensory involvement is not uncommon in ALS. Although clinical symptoms are poor predictors, electrophysiological abnormalities consistent with sensory and entrapment neuropathies are common. A significant proportion of these abnormalities are idiopathic and may directly reflect the disease process itself, particularly in spinal-onset cases.},
}

@article {pmid42263417,
year = {2026},
author = {Chung, J},
title = {A two-continua model of sleep health and sleep disorders: Why framework proliferation is a feature.},
journal = {Sleep medicine reviews},
volume = {88},
number = {},
pages = {102320},
doi = {10.1016/j.smrv.2026.102320},
pmid = {42263417},
issn = {1532-2955},
abstract = {Multi-dimensional sleep health (MDSH) frameworks emerged in the 2010s to articulate positive sleep health beyond the absence of sleep disorders. Meng et al. (2026) [1] provide the first systematic review directly comparing the two leading instruments, the Ru-SATED scale (Buysse, 2014; Ravyts et al., 2021) [2, 3] and the Sleep Health Index (SHI) (Knutson et al., 2017) [4], and surface two unresolved tensions: a conceptual question (what is the relationship between sleep health and sleep disorders?) and an operational question (will sleep science converge on a single MDSH framework?). This perspective elaborates Meng et al.'s brief observation that MDSH is orthogonal to sleep disorders into a Two-Continua Model (TCM), drawing on the dual-continua model of mental health. The TCM defines a sleep disorder continuum (X-axis) and an orthogonal sleep health continuum (Y-axis), generating a four-quadrant typology. Implications: the typology identifies under-attended populations for surveillance; MDSH complements rather than replaces disorder-focused science; joint-axis modeling integrating disorder and health information yields more powerfully predictive frameworks; and a proliferation of tailored MDSH frameworks is a feature of a maturing research program, not a defect.},
}

@article {pmid42263783,
year = {2026},
author = {Lai, TF and Liao, Y and Tzeng, PL and Wen, CJ and Chan, DC},
title = {Association of Brief Bouts of Vigorous Physical Activity and Frailty in Older Adults With Regular and Irregular Exercise Habits.},
journal = {Journal of aging and physical activity},
volume = {},
number = {},
pages = {1-7},
doi = {10.1123/japa.2024-0332},
pmid = {42263783},
issn = {1543-267X},
abstract = {Brief bouts of vigorous physical activity such as vigorous intermittent lifestyle physical activity (VILPA) have emerged as a flexible alternative to traditional structured exercise, requiring less time commitment, preparation, and access to facilities. This study explored the association between VILPA and the odds of prefrailty or frailty in 195 older adults aged 65 and above at National Taiwan University Hospital. Frailty status was evaluated using Fried et al.'s criteria, which include slowness, weakness, weight loss, exhaustion, and low physical activity. VILPA was measured using a waist-worn accelerometer. Multivariate binary logistic regression models revealed that meeting the VILPA duration or bouts thresholds was linked to lower odds of prefrailty or frailty. These associations were significant in those with irregular exercise habits, with adherence to VILPA duration or bouts thresholds correlating with reduced prefrailty or frailty likelihood (odds ratio = 0.21, 95% confidence interval [0.05, 0.89]). However, no significant associations were observed in individuals with regular exercise habits. Adhering to VILPA thresholds may be associated with lower frailty odds, particularly in older adults with irregular exercise habits. These findings suggest that promoting brief bouts of vigorous physical activity in daily life may have potential implications for frailty reduction in older adults, especially those who do not engage in regular exercise. This approach offers a potentially accessible and flexible alternative to structured exercise programs for maintaining health in aging populations.},
}

@article {pmid42264115,
year = {2026},
author = {Pynn, SR and Jørgensen, H and Vanstone, C and Mosewich, AD and Holt, NL and , },
title = {A narrative scoping review exploring parents' emotion knowledge and abilities in youth sport.},
journal = {Psychology of sport and exercise},
volume = {},
number = {},
pages = {103187},
doi = {10.1016/j.psychsport.2026.103187},
pmid = {42264115},
issn = {1878-5476},
abstract = {The purpose of this narrative scoping review was to explore how parents identify, express, use, understand, and manage their own and others' emotions in the context of youth sport. Mikolajczak's (2009) tripartite model of emotional intelligence (EI) was used as the conceptual lens for this review. Using Levac et al.'s (2010) framework for conducting scoping reviews, we reviewed 87 relevant sport parenting studies and conducted consultation focus groups with 10 sport parents and six former youth athletes. Qualitative data analysis techniques were used to map the findings into themes based on the dimensions of EI (i.e., identification and expression of emotions, using emotions, understanding emotions, and managing emotions). Findings indicated that parents identified and articulated their own emotions and empathised with their children in the sport context. This emotional awareness informed their emotionally supportive behaviours, such as providing encouragement and comfort. Parents' understanding of their children and sport shaped how and when they provided appropriate support in emotional situations. Parents also engaged in efforts to manage their own emotional reactions, drawing on self-awareness and knowledge of the sport environment to regulate their behaviour during competition. These findings provide insight into the specific aspects of youth sport parents' emotional competencies and can be used to inform sport parent education initiatives.},
}

@article {pmid42264185,
year = {2026},
author = {Baker, A and Okorie, M},
title = {UK Foundation Programme training needs a national minimum standard for advanced life support.},
journal = {Clinical medicine (London, England)},
volume = {},
number = {},
pages = {100605},
doi = {10.1016/j.clinme.2026.100605},
pmid = {42264185},
issn = {1473-4893},
abstract = {Since 2021, Advanced Life Support (ALS) has no longer been a mandatory requirement of the UK Foundation Programme. Although the shift towards capability rather than certification was educationally defensible, in practice it has created marked national variation in how resuscitation preparedness is developed, evidenced and signed off. Foundation doctors now enter emergencies with unequal access to funded ALS training, simulation and supervised assessment, while supervisors are left to judge equivalence without a consistent national threshold. This matters not because patient-level harm has been neatly proven, but because high-stakes clinical capability should not depend on local opportunity or variable interpretation. A capability-based curriculum and a national minimum standard are not mutually exclusive. The Foundation Programme should therefore restore a national ALS requirement, or a formally recognised equivalent standard, alongside funded access, blended delivery and transparent national evaluation of uptake, exemptions and outcomes.},
}

@article {pmid42264545,
year = {2026},
author = {Vishwakarma, H and Chauhan, A and Kaur, L and Awasthi, A},
title = {Nanotechnology-enabled targeting strategies for neurodegenerative disorders: role of functionalized nanoparticles.},
journal = {The Journal of pharmacy and pharmacology},
volume = {78},
number = {6},
pages = {},
doi = {10.1093/jpp/rgag060},
pmid = {42264545},
issn = {2042-7158},
abstract = {BACKGROUND: Neurodegenerative disorders comprise a diverse group of progressive neurological diseases characterized by the gradual loss of neuronal structure and function. Conditions such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis arise from multifactorial mechanisms involving genetic susceptibility, environmental factors, and age-related cellular decline.

PATHOPHYSIOLOGY: Key pathogenic processes include oxidative stress, mitochondrial dysfunction, protein misfolding and aggregation, impaired axonal transport, Golgi fragmentation, and chronic neuroinflammation, all of which disrupt neuronal homeostasis and synaptic communication, ultimately leading to neuronal death. Hormonal imbalances further exacerbate these effects by promoting oxidative damage, inflammation, and metabolic dysfunction.

CHALLENGES IN THERAPY: Despite advances in understanding disease mechanisms, effective drug delivery remains challenging due to the restrictive nature of the blood-brain barrier.

Recent developments highlight the potential of nanoparticle-based drug delivery systems to overcome these limitations. Functionalized nanoparticles enhance blood-brain barrier penetration, improve targeting specificity, and enable controlled drug release. These systems can deliver neuroprotective agents, antioxidants, peptides, and gene therapies directly to affected brain regions. Thus, integrating disease pathophysiology with nanotechnology-based strategies offers a promising approach for improving therapeutic outcomes and advancing precision treatment in neurodegenerative disorders.},
}

@article {pmid42264722,
year = {2026},
author = {He, S and Yu, H and Li, X and Chen, J and Liu, Z and Miao, D and Ren, M and Cui, H},
title = {Distribution of resistant Aegilops tauschii populations across China and its target-site resistance mechanism.},
journal = {Pesticide biochemistry and physiology},
volume = {221},
number = {},
pages = {107181},
doi = {10.1016/j.pestbp.2026.107181},
pmid = {42264722},
issn = {1095-9939},
abstract = {Aegilops tauschii is a notorious weed that poses a severe threat to wheat production. Recently, its resistance to mesosulfuron-methyl has been increasingly documented in some provinces of China. With Ae. tauschii rapidly expanding its distribution range throughout China, however, its nationwide resistance distribution and the underlying resistance molecular mechanisms remain poorly understood. To address this knowledge gap, 305 populations of Ae. tauschii were collected from eight major wheat-growing provinces of China to characterize their nationwide resistance profiles and target-site resistance mechanisms. Of the populations examined, 83 populations from Shanxi, Shaanxi, Henan, Hebei, Shandong, and Jiangsu provinces exhibited varying levels of resistance to mesosulfuron-methyl. Resistant populations were particularly widespread in Shanxi and Shaanxi compared with other regions. Forty-seven resistant populations were then selected for target-site mutation analysis. A Pro-197-Leu substitution in the acetolactate synthase (ALS) gene was identified in 14 resistant populations, whereas no known resistance-conferring amino acid alteration was detected in the remaining 33 populations. Resistant populations carrying the Pro-197-Leu mutation displayed a higher resistance level than resistant populations without ALS gene mutations. Furthermore, in vitro ALS activity assays showed that populations with the Pro-197-Leu substitution were highly resistant to mesosulfuron-methyl, with resistance index (RI) ranging from 32.95 to 33.12. In contrast, the RI values of resistant populations lacking target-site mutations were below 2.90. To the best of our knowledge, this study represents the first report of a target-site mutation (Pro-197-Leu) conferring resistance to mesosulfuron-methyl in Ae. tauschii.},
}

@article {pmid42264735,
year = {2026},
author = {Rojano-Delgado, AM and Sohrabi, S and Santana, APDS and Palma-Bautista, C and Domínguez-Valenzuela, JA and Gherekhloo, J and Alcántara-de la Cruz, R and De Prado, R},
title = {Herbicide metabolism and EPSPS Pro-106-Ser substitution confer multiple resistance in Chenopodium spp. from Southern Spain.},
journal = {Pesticide biochemistry and physiology},
volume = {221},
number = {},
pages = {107132},
doi = {10.1016/j.pestbp.2026.107132},
pmid = {42264735},
issn = {1095-9939},
abstract = {Long-term herbicide programs in Mediterranean perennial systems have imposed sustained selection pressure on weed populations, promoting the evolution of multiple resistance. We investigated resistance mechanisms in Chenopodium album (Ca) and C. vulvaria (Cv) from southern Spain following more than two decades of glyphosate-based management. We aimed to (i) confirm resistance to atrazine, tribenuron-methyl (TM), glyphosate, and 2,4-D; (ii) distinguish between target-site and metabolic resistance; and (iii) characterize the biochemical and molecular basis of cross- and multiple-herbicide resistance. Screening assays revealed high survival (78-100%) of resistant (R) populations to acetolactate synthase (ALS)-, photosystem II (PSII)-, auxinic-, and 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS)-inhibiting herbicides. Dose-response assays confirmed resistance, with resistance indices (RI) of 6.7 and 5.1 for atrazine, 19.0 and 17.3 for TM, 7.0 and 13.9 for glyphosate, and 6.0 and 6.9 for 2,4-D in CaR and CvR, respectively. Radiolabelled and analytical metabolism assays demonstrated enhanced herbicide metabolism in R populations: atrazine (94-95% vs. 13-16% in S), TM (68-69% vs. 24-25%), 2,4-D (64-65% vs. 2-4%), and glyphosate (39-43% vs. 8-9%). Malathion partially reversed resistance to atrazine, TM, and 2,4-D, supporting cytochrome P450 (CYP450) involvement. In contrast, glyphosate metabolism was independent of CYP450 or glutathione S-transferases inhibition. Biochemical assays showed no differences in PSII or ALS sensitivity (I50 RI ≈ 1), whereas EPSPS inhibition assays revealed a tenfold increase in I50 in CvR. Sequencing identified a Pro-106-Ser substitution in EPSPS exclusively in CvR. Enhanced metabolism predominates in the R Chenopodium spp. populations, with coexistence of metabolic and target-site mechanisms in CvR, increasing the risk of further cross-resistance under continued herbicide reliance.},
}

@article {pmid42265364,
year = {2026},
author = {Treittinger, K and Yang, S and Fischer, R and Dreisbach, G},
title = {The asymmetric list shift effect - flexible adaptation to new context demands?.},
journal = {Attention, perception & psychophysics},
volume = {88},
number = {5},
pages = {},
pmid = {42265364},
issn = {1943-393X},
abstract = {The list-wide proportion congruency effect describes how the congruency effect varies depending on the frequency of incongruent trials within a block. Specifically, the congruency effect is larger in mostly congruent (MC) blocks compared to mostly incongruent (MI) blocks. Research has shown that adaptation to these blocks does not change symmetrically when transitioning between them: moving from MC to MI leads to a rapid decrease in the congruency effect while transitioning from MI to MC results in little or no increase (Abrahamse et al., 2013). We aimed to investigate this asymmetric list shift (ALS) effect in a within-participants design where all participants experienced both transitions (MC-MI and MI-MC). Throughout Experiments 1-3 using a color-word Stroop task, we identified various forms of practice - including trial-type, stimulus-specific learning, general RT decrease, and a decrease in congruency effects over time (see Schmidt, 2016) - that can either facilitate or obscure the ALS effect, depending on the order in which participants experienced the transitions. In Experiment 4, using a face-name version of the Stroop task, where we minimized practice-related confounding factors by employing more complex stimuli and used a new stimulus set in the second transition, an ALS effect was observed regardless of the order of transition and for frequency-unbiased (i.e., 50% congruent) items. The role of practice effects and implications for the (in)-flexibility of control adaptations will be discussed.},
}

@article {pmid42265426,
year = {2026},
author = {Johannsen, L and Koger, A and Straub, ER and Stephan, DN and Kiesel, A and Koch, I and Müller, H},
title = {Contrasting cognitive control in the Simon and spatial Stroop tasks regarding their interference with the control of standing balance.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {42265426},
issn = {2045-2322},
abstract = {The scientific understanding of any interaction between cognition and balance control is advanced by methods that capture event-related effects of cognitive processes on balance with high temporal resolution and precision. We developed such an approach to examine how cognitive conflict interferes with the control of body balance during upright standing. Participants stood on a force plate while performing two cognitive conflict paradigms: a Simon task, which according to Kornblum et al.'s dimensional overlap model[41] mainly induces spatial stimulus-response conflict during response selection, and a Spatial Stroop task, which additionally elicits a stimulus-stimulus conflict during stimulus encoding. By aligning force plate time series data to the onset events of target and response across all trials, we assessed the temporal dynamics of spatial congruency effects on force moment variability as a marker of balance control activity. Across both experimental cognitive tasks, we observed strong congruency effects in cognitive task performance, when considering trials after previous congruent trials. Further, incongruent trials were associated with systematic transient reductions in force moment variability along the mediolateral axis in balance control. These observations are in line with the assumption that the recruitment of cognitive processes for conflict resolution temporarily inhibits, suppresses, or postpones balance adjustments. Importantly, regarding the impact of cognitive interference on body balance, data confirm our previous observations using improved methods and demonstrate that reduction in balance control activity during resolution of cognitive conflict generalizes to a task with multiple conflict loci (Spatial Stroop task). Thereby, this extended range of conflict does not result in correspondingly stronger interference effects in balance control. From a theoretical perspective, the results align with predictive models of postural regulation and intermittent, event-driven accounts of balance control.},
}

@article {pmid42265532,
year = {2026},
author = {Ella, A and Bar-Kalifa, E},
title = {Relational Memory Reconsolidation: A New Lens on Change Mechanisms in EFT for Couples.},
journal = {Family process},
volume = {65},
number = {2},
pages = {e70172},
doi = {10.1111/famp.70172},
pmid = {42265532},
issn = {1545-5300},
abstract = {This paper presents a new framework to account for change mechanisms in Emotion-Focused Therapy for Couples (EFT). Building on Lane et al.'s (2015) integrated memory model, the Relational Memory Reconsolidation model described here posits that EFT reshapes partners' relational memory structures through emotionally intense moments of expressed vulnerability and responsiveness. These vulnerability-responsiveness events allow partners to access and transform memories of past relational experiences (i.e., episodic memory) as well as associated beliefs about themselves and the relationship (i.e., semantic memory). This process of emotional activation and reconsolidation allows maladaptive interaction patterns, which are rigid and stressful, to evolve into more adaptive, emotionally responsive exchanges. These emotional moments activate and transform relational self-states that are responsive to interpersonal cues and can shape partners' self-concepts in a relational context. As therapy progresses and emotionally significant interactions are repeated, the coactivation of adaptive and maladaptive self-states updates neocortical memory traces, leading to changes in higher-order relational semantic structures (i.e., the relational self). These moments foster alignment in partners' perceptions of their shared reality, characterized by mutuality in feelings, practices, memories, goals, and identity. Clinically, the framework highlights the need to elicit one partner's core vulnerable emotions and, within the reconsolidation window, disconfirm related expectations (e.g., rejection) through the other partner's empathic and supportive response. This process may transform key components of partners' relational memory, including relational episodic memories, semantic structures, and procedural emotional responses.},
}

@article {pmid42265600,
year = {2026},
author = {Jiang, S and Chen, F and Ma, H and Wu, S and Tang, X and Pan, X and Li, Q and Tao, A and Xu, J and Qi, J and Fang, P and Chen, J and Zhang, L},
title = {Cloning and functional verification of endogenous U6 promoters for developing an efficient CRISPR/Cas9-mediated genome editing system in kenaf (Hibiscus cannabinus L.).},
journal = {BMC plant biology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12870-026-09228-9},
pmid = {42265600},
issn = {1471-2229},
support = {32472219//the National Natural Science Foundation of China/ ; 2023J01443//Fujian Provincial Natural Science Foundation of China/ ; CARS-16//China Agricultural Research System of MOF and MARA/ ; KFB23001//Science and Technology Innovation Project of Fujian Agriculture and Forestry University/ ; ASTIP-IBFC-01//Agriculture Science and Technology Innovation Program/ ; },
abstract = {BACKGROUND: The U6 promoter is a critical component of the CRISPR/Cas9 system, as it drives the transcription of single-guide RNAs (sgRNAs) to enable precise genome editing. Endogenous promoters typically exhibit higher transcriptional activity than their exogenous counterparts, which can significantly enhance editing efficiency. However, the endogenous U6 promoter in kenaf (Hibiscus cannabinus L.), an important fiber crop, has not yet been characterized.

METHODS: Using the Arabidopsis U6-26 (AtU6-26) promoter as a reference, we performed a homologous sequence search and identified two candidate U6 promoters in kenaf, designated HcU6-1 and HcU6-14. Promoter fragments were amplified from the kenaf cultivar 'Fuhong 952' and cloned into a β-glucuronidase (GUS) reporter vector. Histochemical GUS staining assays revealed that both HcU6 promoters were transcriptionally active, with HcU6-14 showing significantly stronger expression levels compared to HcU6-1.

RESULTS: To further evaluate the utility of these promoters for genome editing, we constructed CRISPR/Cas9 vectors targeting the kenaf acetolactate synthase (ALS) gene, driven by either HcU6-14P or the exogenous cotton GbU6-9P promoter. Agrobacterium rhizogenes K599-mediated transformation was used to induce hairy roots, and mutation analysis of the ALS gene was performed via Sanger sequencing. Notably, targeted mutations in the ALS gene were detected in hairy roots transformed with the HcU6-14P-driven CRISPR/Cas9 vector, whereas no mutations were observed in roots transformed with the exogenous GbU6-9P promoter. These results demonstrate that the endogenous HcU6-14 promoter confers superior genome editing efficiency compared to the heterologous promoter, which facilitates the development of improved varieties with enhanced agronomic traits.},
}

@article {pmid42256556,
year = {2026},
author = {Xiao, X and Hao, G and Wan, P and Hou, W},
title = {Safety evaluation of Tofersen in amyotrophic lateral sclerosis based on the FAERS database.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1843630},
pmid = {42256556},
issn = {1664-2295},
abstract = {BACKGROUND: This study utilizes data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) to conduct a post-marketing safety evaluation of Tofersen.

METHODS: A systematic search of the FAERS database was performed to identify adverse event (AE) reports from Q1 2023 to Q4 2025 was performed. Multi-dimensional disproportionality analyses were conducted using the ROR, PRR, BCPNN, and MGPS method.

RESULTS: A total of 409 Tofersen-related reports were identified, revealing significant signals across 22 System Organ Class (SOC) categories and 369 Preferred Terms (PTs). At the SOC level, the most prominent safety signals were observed in injury, poisoning and procedural complications, nervous system disorders, and musculoskeletal and connective tissue disorders. In contrast, ear and labyrinth disorders, as well as respiratory, thoracic and mediastinal disorders, were not listed in the current product labeling and may warrant further investigation. At the PT level, neurological procedural complication, CSF red blood cell count positive, CSF white blood cell count increased, and CSF cell count increased exhibited the strongest signals, primarily reflecting cerebrospinal fluid cytological and biochemical abnormalities, as well as procedural-related adverse events such as post-lumbar puncture syndrome, procedural pain, and procedural headache. Although central nervous system-related events (e.g., increased intracranial pressure, peroneal nerve palsy, papilloedema, and facial paralysis) and infectious or inflammatory events (e.g., radiculopathy, myelitis, aspiration pneumonia, and meningitis) were less frequently reported, their relatively high disproportionality signals warrant clinical attention and systematic monitoring. Notably, a newly identified signal of pulmonary embolism suggests a potential thromboembolic risk in specific patient populations.

CONCLUSION: These findings provide real-world evidence to inform the balance between the therapeutic potential and safety profile of Tofersen. Future clinical strategies should focus on mitigating central nervous system-related and procedure-related adverse events. Further mechanistic studies are crucial.},
}

@article {pmid42257176,
year = {2026},
author = {Villasi, W and Frederic, R and Qureshi, S and Zheng, B and Torrente, MP and Fisher, RMA},
title = {Histone H3 Post-Translational Modification Changes are Linked to Manganese and Copper Exposure in Saccharomyces cerevisiae.},
journal = {microPublication biology},
volume = {2026},
number = {},
pages = {},
pmid = {42257176},
issn = {2578-9430},
abstract = {Prolonged exposures to heavy metals are risk factors for chronic diseases, such as Amyotrophic Lateral Sclerosis and Frontotemporal dementia (ALS/FTD). ALS/FTD comprises a fatal neurodegenerative disease continuum and is linked to disruptions in the levels of histone post-translational modifications (PTMs). Epigenetic mechanisms can connect environmental exposures to disease occurrences. Here, we examine the effects of manganese and copper exposure on the H3 PTM landscape in yeast. Manganese exposure decreases H3K9ac, H3K14ac, and H3S10ph levels. Copper exposure increases H3S10ph and H3K14ac levels and decreases H3K36me3 levels. This provides a basis for linking environmental exposure to biological mechanisms of disease.},
}

@article {pmid42257870,
year = {2026},
author = {Nguyen, N and Lauinger, AR and Naik, A and Liu, R and Yolcu, Y and Arnold, PM},
title = {Clinical Research for the Use of 7 T Magnetic Resonance Imaging for Spinal Pathologies: a Scoping Review.},
journal = {Clinical neuroradiology},
volume = {},
number = {},
pages = {},
pmid = {42257870},
issn = {1869-1447},
abstract = {PURPOSE: Magnetic resonance imaging (MRI) at 7 T (7T) offers higher signal-to-noise ratio and improved spatial resolution compared to lower magnetic field strengths such as 1.5T and 3T, which may improve lesion detection and anatomical visualization for spinal cord pathology. This review summarizes current techniques and achievements in 7T spinal imaging and outlines associated technical barriers and future directions.

METHODS: A scoping review in accordance with PRISMA extension for scoping reviews guidelines was performed utilizing PubMed, Scopus, and Web of Science. Only studies related to 7T MRI of human subjects were included, after removing unrelated studies and those of non-human subjects.

RESULTS: Twenty-nine studies were included. Current literature supports 7T's superior resolution and signal-to-noise ratio in comparison to 1.5T and 3T MRI. These studies reported improved lesion detection and staging in multiple sclerosis (MS), spinal cord injury (SCI), and amyotrophic lateral sclerosis (ALS); however, the implications of results are limited by small sample sizes, technical heterogeneity, and inconsistent outcome measures. Additionally, the use of 7T spinal imaging remains limited by radiofrequency coil design, susceptibility artifacts, physiological noise, lack of FDA-clearance for spinal indications, and an absence of standardized imaging protocols. Future research aims to address these limitations.

CONCLUSION: Spinal cord imaging at 7T is challenging due to technical constraints and higher susceptibility to artifacts as a result of physiological noise (respiration, swallowing, and bulk movement). However, early studies' results using 7T imaging support improved ability, compared to 3T, to provide enhanced visualization of fine anatomical structures, such as nerve roots, and to improve spinal cord lesion detection.},
}

@article {pmid42257902,
year = {2026},
author = {Horiuchi, K and Nakamura, S and Ishikawa, K and Nunomura, S and Yamada, K and Inoue, T and Oiwa, K and Fujii, S and Oshima, Y and Kudo, A and Yabe, I},
title = {Early respiratory decline around diagnosis and short-term post-landmark outcomes in amyotrophic lateral sclerosis: a 6-month landmark cohort study.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {7},
pages = {},
pmid = {42257902},
issn = {1590-3478},
abstract = {BACKGROUND: In amyotrophic lateral sclerosis (ALS), respiratory decisions rely on serial trends rather than a single value. We evaluated whether early respiratory decline around diagnosis provides prognostic information in a real-world landmark framework.

METHODS: This single-center retrospective cohort screened 94 consecutive patients diagnosed between April 2019 and December 2025. A 6-month landmark was used. Early decline was estimated from %FVC values between - 30 and + 180 days around diagnosis. The primary model included age and early %FVC decline; robustness analyses included time-varying Cox, piecewise Cox, RMST, included-vs-excluded comparison, death-only analysis, and slope-quality filtering.

RESULTS: Of 94 screened patients, 62 met baseline eligibility, 56 had calculable early slope, and 45 entered the landmark cohort; 28 post-landmark composite events occurred. In the Cox model, faster early %FVC decline was associated with higher hazard of death or invasive mechanical ventilation via tracheostomy (HR 1.33 per 1%/month faster decline, 95% CI 1.14-1.55, p < 0.001). PH diagnostics suggested non-proportionality (%FVC p = 0.031; NIV p = 0.034 in the expanded model), so this HR was interpreted as an average follow-up association and complemented by PH-robust analyses. The signal was stronger early than late, remained consistent in a death-only analysis, and favored the slower-decline group by RMST at 24 and 36 months.

CONCLUSIONS: In this selected measurement-capable landmark cohort, early respiratory decline provided a clinically meaningful short-to-medium term prognostic signal for post-landmark adverse outcomes. External validation is required before broader generalization beyond measurement-capable landmark populations.},
}

@article {pmid42259179,
year = {2026},
author = {Nakasako, J and Yaguchi, R and Terayama, A and Kuwahara, M and Nishimoto, Y},
title = {Association of anti-glycolipid IgG with respiratory function decline in amyotrophic lateral sclerosis.},
journal = {Journal of the neurological sciences},
volume = {488},
number = {},
pages = {126039},
doi = {10.1016/j.jns.2026.126039},
pmid = {42259179},
issn = {1878-5883},
abstract = {OBJECTIVE: Effective treatments for amyotrophic lateral sclerosis (ALS) remain limited, underscoring the need to identify robust biomarkers associated with disease severity and prognosis. This study investigated whether immunoglobulin G (IgG) and immunoglobulin M (IgM) anti-glycolipid antibodies are associated with clinical manifestations of ALS, particularly decline in respiratory function.

METHODS: This was a retrospective observational cohort study of the patients with ALS. Among patients with definite or probable limb-onset ALS, 11 patients in the glycolipid IgG-positive group were compared with 15 patients in the IgG-negative group, and 5 patients in the glycolipid IgM-positive group were compared with 9 patients in the IgM-negative group, with adjustment for age. Associations between anti-glycolipid antibody status and respiratory function were assessed using Kaplan-Meier survival analysis and Cox proportional hazards models.

RESULTS: The time to decline of percent forced vital capacity (%FVC) below 80% and 60% was significantly shorter in the IgG-positive group than in the IgG-negative group (p = 0.002 and p = 0.025, respectively). Cox proportional hazards analysis demonstrated that IgG antibody positivity was an independent risk factor for earlier decline in %FVC to 80%.

INTERPRETATION: These findings suggest that anti-glycolipid IgG antibodies may be associated with respiratory function decline in ALS. Larger comprehensive studies will be required to validate these results and to elucidate the underlying pathophysiological mechanisms.},
}

@article {pmid42259250,
year = {2026},
author = {Creel, SC},
title = {A note of caution on tone language advantages for music.},
journal = {Current biology : CB},
volume = {36},
number = {11},
pages = {R467-R469},
doi = {10.1016/j.cub.2026.04.009},
pmid = {42259250},
issn = {1879-0445},
abstract = {Liu et al.[1] reported recently in Current Biology a large-scale citizen science replication of the tone-language advantage for musical pitch perception. Their 493,100 volunteers spoke 54 languages, including 19 tone languages, those in which a word's pitch pattern contributes to its meaning. For example, Mandarin ma with high pitch means 'mother', while ma with dipping pitch means 'horse'. Previous studies reported tone language advantages, but with far smaller and less linguistically diverse samples (mostly East Asian tone languages). I applaud the authors' exploration of diverse tone languages with disparate tonal properties, including varying numbers, types, and linguistic uses of tones, plus varying cultural factors. While I do not dispute the overall tone language advantage, I take issue with Liu et al.'s[1] inference that the effect is consistent across the varied tone languages tested: because of the properties of the models they used to estimate individual-language effects, their more-diverse tone languages spuriously appear to pattern consistently, when in actuality the data are too noisy to draw strong conclusions about tone languages as a unified group.},
}

@article {pmid42259394,
year = {2026},
author = {Zhang, K and Kong, S and Ma, Y and Kan, C and Zheng, T and Sun, X},
title = {Natural Monomer Compounds in Neurodegenerative Diseases: Targeting Ferroptosis and Neuroinflammation.},
journal = {Behavioural brain research},
volume = {},
number = {},
pages = {116319},
doi = {10.1016/j.bbr.2026.116319},
pmid = {42259394},
issn = {1872-7549},
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss driven by oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation. Ferroptosis, an iron-dependent and lipid peroxidation-associated form of regulated cell death, has recently been identified as a key contributor to neuronal vulnerability. Emerging evidence demonstrates that purified natural monomer compounds derived from medicinal plants exert potent neuroprotective effects by targeting ferroptosis and neuroinflammatory pathways. Representative agents such as curcumin, baicalin, resveratrol, and ginsenoside Rg1 activate nuclear factor E2-related factor-2 and glutathione peroxidase 4 signaling to preserve redox balance, while suppressing microglia-mediated inflammation through inhibition of toll-like receptor 4 pathways. This review highlights the interplay between ferroptosis and neuroinflammation in NDDs, summarizes the regulatory effects of bioactive herbal monomer compounds, and discusses recent advances in multi-omics profiling, nano-delivery strategies, and translational research. By modulating the ferroptosis-neuroinflammation axis, these compounds may represent promising therapeutic candidates for NDDs.},
}

@article {pmid42260601,
year = {2026},
author = {Yoshida, M},
title = {Development and validation of the creative personality and thinking styles scale: a multifaceted measure for assessing creativity-related individual differences.},
journal = {BMC psychology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40359-026-04959-8},
pmid = {42260601},
issn = {2050-7283},
abstract = {BACKGROUND: Creativity is the process of generating contextually useful novel outcomes by uniquely reconfiguring existing knowledge and information. While various measures examine specific aspects of creativity, multifaceted measures that holistically assess creativity as a domain-general factor are still needed. This study developed the Creative Personality and Thinking Styles Scale (C-PETS), which measures personality, thinking styles, and creativity-related motivation based on Plucker et al.'s theory of creativity.

METHODS: The initial C-PETS item pool was developed by referencing existing scales, followed by a qualitative screening process to ensure theoretical consistency. Exploratory factor analysis involving 572 participants was conducted to examine the underlying factor structure. Subsequently, confirmatory factor analysis and a higher-order model analysis involving 943 participants were performed to verify the model fit.

RESULTS: Exploratory factor analysis identified a five-factor, 16-item scale comprising Broad Thinking, Thorough Thinking, Information Manipulation, Challenge-Seeking, and Ambiguity Tolerance. The higher-order CFA model demonstrated an excellent fit (GFI = .97, CFI = .98, RMSEA = .02). Criterion-related validity was supported by significant correlations with the Short Scale of Creative Self-Efficacy (r = .75), Aesthetic Experiences Scale (r = .30), and Divergent Association Task (r = .18). Test-retest reliability after two weeks was strong (r = .87). Additionally, a positive correlation was observed with educational attainment.

CONCLUSIONS: The C-PETS represents a valuable contribution to creativity assessment by providing a multifaceted measure of creativity-related personality, thinking styles, and motivation.},
}

@article {pmid42261056,
year = {2026},
author = {Bromberg, MB},
title = {The Flail Limb Syndrome.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70307},
pmid = {42261056},
issn = {1097-4598},
abstract = {The flail limb syndrome is primarily a lower motor neuron disorder that initially affects proximal arm muscles (flail arm syndrome-FAS) or distal leg muscles (flail leg syndrome-FLS). Both were recognized early on (1886 for FAS and 1918 for FLS) as somewhat distinct from classic amyotrophic lateral sclerosis (ALS). Descriptions in the literature are case series with limited information on electrophysiologic features (central and peripheral), cognitive involvement, and genetic mutations. What follows is a compilation of these features. The flail limb syndromes are rare, representing ~7%-8% of ALS. They have a higher ratio of males to females compared to classic ALS. Both are defined by predominant focal arm or leg weakness for ~2 years before progression to other regions, although there can be early and mild clinical or electrophysiologic evidence for denervation and reinnervation in other regions during the initial period. Ultimately, there is progression to respiratory failure, but at a slower rate compared to classic ALS. Upper motor neuron clinical signs are variable, but transcortical magnetic stimulation paradigms and magnetic resonance imaging tractography support upper motor neuron loss. Tests of the split hand pattern show it is rare compared to ALS. Dementia is also rare. Genetic testing supports a spectrum of ALS-related gene mutations but at a lower frequency than with classic ALS, and no gene mutation is predominant. Diagnosis requires ~2 years of regional stability to predict the better prognosis for the flail limb syndromes.},
}

@article {pmid42248993,
year = {2026},
author = {Gad, AG and Kelani, KM and Mahmoud, AM and Arafa, RM and Abbas, AEF},
title = {Fedorov algorithm-optimized chemometric spectrophotometry for cefepime-tazobactam microanalysis in plasma and pharmaceuticals with integrated MA and NQS sustainability assessment.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {42248993},
issn = {2045-2322},
abstract = {A green, sustainability-oriented chemometric-assisted UV spectrophotometric platform was developed for the simultaneous determination of Cefepime (CFPM) and Tazobactam (TAZO) in pharmaceutical formulations and human plasma. Water served as the sole diluent, eliminating hazardous organic solvents and substantially reducing the environmental impact of the analytical procedure. Calibration and validation sets were efficiently constructed using the Fedorov exchange algorithm within Brereton's multilevel design framework, yielding 25 calibration and 13 validation mixtures and reducing experimental workload by approximately 70% compared with conventional designs. Three complementary chemometric models were evaluated: Principal Component Regression (PCR), Firefly Algorithm-assisted Partial Least Squares (FA-PLS), and Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS). Among them, MCR-ALS demonstrated superior predictive performance, with correlation coefficients exceeding 0.9998 for both analytes, minimal systematic bias confirmed by Elliptical Joint Confidence Region analysis, and high robustness across pharmaceutical and plasma matrices. Limits of detection were 0.0487 and 0.0396 µg mL[-1], while limits of quantification were 0.1476 and 0.1200 µg mL[-1] for CFPM and TAZO, respectively. The method was validated in accordance with ICH guidelines and successfully applied to CEFE-MAX™ powder for injection and fortified human plasma. Matrix effect evaluation showed negligible signal suppression (- 2.35% to - 1.27%), indicating strong matrix tolerance and calibration transferability. Comparative benchmarking against reported HPLC-UV, LC-MS/MS, capillary zone electrophoresis, and UV spectrophotometric methods demonstrated that the proposed approach achieves an optimal balance of sensitivity, simplicity, and environmental sustainability. Sustainability assessment using the Multi-Color Assessment (MA), carbon footprint analysis, and the Need-Quality-Sustainability (NQS) index yielded a Whiteness Score of 83.6%, an NQS score of 90, and a low carbon footprint of 0.032 kg CO2-eq per analysis. Overall, the developed platform provides a rapid, cost-effective, and environmentally responsible alternative for routine quality control and preliminary therapeutic monitoring of the CFPM-TAZO combination.},
}

@article {pmid42250142,
year = {2026},
author = {Jalaiei, A and Kiani Darabi, AH and Sakkaki, E and Rezazadeh, M and Ghafouri-Fard, S},
title = {Molecular interplay between Non-coding RNAs and BDNF in Neurodegenerative Disorders: a systematic review.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {},
pmid = {42250142},
issn = {1573-4978},
abstract = {Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays essential roles in nervous system development, neuronal maintenance, and neurogenesis. Aberrant BDNF concentrations, observed both peripherally and within the central nervous system (CNS), have been consistently implicated in the pathogenesis of a spectrum of neurodegenerative disorders (NDDs), including Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Huntington's disease, and Multiple sclerosis. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), regulate gene expression and are critical factors in cellular processes relevant to neurodegenerative disease pathobiology. Consequently, ncRNAs are posited as promising biomarkers and potential therapeutic modalities for CNS-related pathologies. However, robust empirical evidence substantiating ncRNA-mediated, post-transcriptional regulation of BDNF expression in the context of neurodegeneration remains relatively scarce. The objective of this systematic review is to provide a critical synthesis of the current literature on the diagnostic and prognostic utility of ncRNAs that modulate BDNF expression, specifically within the scope of neurodegenerative disorders. Furthermore, we will explore innovative therapeutic strategies centered on targeting BDNF-associated miRNAs for the treatment of these disorders.},
}

@article {pmid42250707,
year = {2026},
author = {Hosseinpoor, Z and Seyedalipour, B and Behjou, NK and Hosseinkhani, S and Baziyar, P},
title = {Inhibitory effect of silymarin on amyloid formation in ALS-associated hSOD1 P66R mutant.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {152922},
doi = {10.1016/j.ijbiomac.2026.152922},
pmid = {42250707},
issn = {1879-0003},
abstract = {The aberrant aggregation of human superoxide dismutase 1 (hSOD1) into β-sheet-rich amyloid fibrils is a crucial process in the pathogenesis of amyotrophic lateral sclerosis (ALS), enhancing motor neuron degeneration and disease progression. The P66R mutation in SOD1 destabilizes local structure and promotes β-sheet-driven fibrillation, which makes it a suitable model for exploring approaches for reducing pathogenic aggregation. Here, we evaluate silymarin, a polyphenolic compound with known antioxidant and neuroprotective properties, for its potential to inhibit P66R-hSOD1 aggregation. ThT fluorescence and transmission electron microscopy analyses demonstrate a significant decrease in amyloid fibril formation in the presence of silymarin; in addition, FTIR spectroscopy confirms the suppression of β-sheet formation. Fluorescence quenching and ANS binding assays indicate a moderate-affinity binding between silymarin and the mutant protein, along with a reduction in surface hydrophobicity. Hemolysis assays confirm its protective effect against membrane damage induced by aggregates, while molecular docking and dynamic simulations indicate that silymarin stabilizes aggregation-prone areas with hydrogen bonding and hydrophobic interactions, thereby promoting compact conformations and reducing solvent-exposed surfaces. The findings identified silymarin as an effective anti-amyloidogenic agent that reduces β-sheet accumulation and fibril formation while also decreasing cytotoxicity, highlighting its potential as a therapeutic candidate for ALS.},
}

@article {pmid42251349,
year = {2026},
author = {Masrori, P and Amado, DA},
title = {RAN translation as a dominant pathogenic axis in C9ORF72-associated ALS and FTD models.},
journal = {Molecular neurodegeneration},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13024-026-00959-9},
pmid = {42251349},
issn = {1750-1326},
}

@article {pmid42251967,
year = {2026},
author = {Manchinu, MF and Congiu, M and Massidda, M and Borghero, G and Marongiu, J and Marzi, I and Maschio, A and Rallo, V and Serra, M and Porcedda, C and Etzi, M and Palmas, MF and Angius, A and Sogos, V and Pateri, MI and Steri, M and Coroneo, V and de Simone, A and Cossu, G and Chiti, F and Carta, AR},
title = {PBMC DEG/miRNA biomarkers of TDP-43 pathology in ALS.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107473},
doi = {10.1016/j.nbd.2026.107473},
pmid = {42251967},
issn = {1095-953X},
abstract = {Amyotrophic lateral sclerosis (ALS) lacks reliable, disease-specific, and minimally invasive biomarkers, representing a major barrier to early diagnosis and patient stratification. The primary aim of this translational pilot study was to identify a disease-specific, TDP-43-related, gene-microRNA (miRNA) signature in peripheral blood mononuclear cells (PBMCs) of ALS patients with potential diagnostic value. To this end, we first identified differentially expressed disease-specific genes (dsDEGs) using a TDP-43-based rat model of ALS, generated by stereotaxic infusion of full-length (FL) TAR DNA-binding protein 43 (TDP-43) into the motor cortex. Transcriptomic profiling of the motor cortex revealed candidate dsDEGs, which were subsequently validated by RT-qPCR in motor cortex, spinal cord, and PBMCs from the same animals. To assess translational relevance, expression levels of these dsDEGs were analyzed in PBMCs from early- to mid-stage ALS patients and matched healthy controls, while disease specificity was evaluated using Parkinson's disease (PD) samples. In parallel, conserved miRNAs predicted to target the identified dsDEGs were examined in both rat and human PBMCs. Five dsDEGs, Mctp1, Penk, Mt2A, Drd1, and Rasgrp2, were consistently dysregulated across central and peripheral tissues in the TDP-43 rat model. RT-qPCR analysis of human PBMCs confirmed significant and selective dysregulation of these genes in ALS, but not in PD, supporting disease specificity. Moreover, exposure of human neuroblastoma cells and healthy PBMCs to TDP-43 recapitulated the ALS-like expression changes. Computational and experimental analyses identified seven conserved miRNAs targeting these dsDEGs, of which four were significantly downregulated in ALS PBMCs, supporting a coordinated regulatory network. Receiver operating characteristic (ROC) analyses demonstrated strong discriminative performance for both the gene signature (AUC 0.87-1.00) and the associated miRNAs (AUC 0.95-1.00). Together, these findings define a novel PBMC-based gene-miRNA signature that mirrors central ALS pathology and shows high diagnostic accuracy and disease specificity, highlighting its potential as a minimally invasive biomarker for ALS.},
}

@article {pmid42252093,
year = {2026},
author = {Arlt, FA and Miske, R and Appeltshauser, L and Zinnow, V and Borowski, K and Stenzel, W and Radbruch, H and Meisel, A and Ruprecht, K and Endres, M and Blau, I and Kirchner, M and Mertins, P and Sanchez-Sendin, E and Wernick, S and Pressler, H and Stascheit, F and Linke, J and Hümmert, S and Werner, HB and Wibisono, EA and Doppler, K and Komorowski, L and Spiliotis, ET and Dubey, D and Zeckeridou, A and Pittock, SJ and Mills, JR and McKeon, A and Scharf, M and Prüss, H},
title = {Septin multimer autoantibodies in severe motor neuropathy mimicking lower motor neuron disease.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag183},
pmid = {42252093},
issn = {1460-2156},
abstract = {Severe neuropathies with predominant involvement of motor fibers can resemble lower motor neuron disease (LMND) phenotypes. Given the fatal prognosis of LMND, identifying underlying autoimmune syndromes is crucial to provide treatment options to patients. We investigated a novel autoantibody binding pattern observed on murine teased sciatic nerve fibers. Target antigens were identified using immunoprecipitation combined with mass spectrometry. Target specificity of these autoantibodies was validated in cell-based assays, neutralization assays, and knock-out models. A retrospective study cohort consisting of different neuropathies (chronic inflammatory demyelinating polyradiculopathy n=86, Guillain-Barré syndrome n=37, multifocal motor neuropathy n=18, diabetic neuropathy n=30, other inflammatory neuropathies n=10), amyotrophic lateral sclerosis (n=50), multiple sclerosis (n=50), and healthy controls (n=50) was negative for septin multimer autoantibodies. Histopathological analysis of skin and sural nerve including electron microscopy was performed in one seropositive patient, and autoantibody binding was characterized in vitro. Extensive immunotherapy was initiated in one patient, with clinical and serological follow-up over four years. Among 3,543 total samples tested, three patients (two male, one female) - diagnosed with the LMND variant of amyotrophic lateral sclerosis (ages 65, 72, and 79, respectively) - showed a novel and distinct autoantibody binding pattern of indirect immunofluorescence staining on peripheral nerves, targeting Schmidt-Lanterman incisures (SLIs), paranodes, and the abaxonal myelin. Target identification and validation revealed septin multimers as autoantibody epitopes. Despite the primarily intracellular location of septins, autoantibody binding was evident in living myelinated dorsal root ganglia, primarily at SLIs ("incisuropathy"). Septin multimer autoantibodies further initiated complement deposition on fixed and permeabilized cell-based assays. Sural nerve and skin biopsies showed inflammation, myelin and axonal pathology. Extensive immunotherapy in one patient was followed by disease stabilization over three years. The other two patients died of rapid disease progression: One of them received no immunotherapy while the other had ineffective treatments with single administrations of IVIG and rituximab. Our data suggest that septin multimer autoimmunity occurs in severe motor predominant neuropathies which can clinically resemble a neurodegenerative LMND. Screening for septin multimer autoantibodies should be considered in patients presenting with this phenotype. Follow-up studies need to determine the direct pathogenicity of septin multimer autoantibodies, their potential as a biomarker of an autoimmune syndrome, and responses to immunotherapy in larger cohorts.},
}

@article {pmid42252583,
year = {2026},
author = {Melone, M and Di Palma, M and Scimemi, A and Conti, F},
title = {Organization of Astrocytic GLT-1 at Cortical Inhibitory Synapses.},
journal = {Glia},
volume = {74},
number = {8},
pages = {e70180},
doi = {10.1002/glia.70180},
pmid = {42252583},
issn = {1098-1136},
support = {PRIN2022BZWEKA//Italian Ministry of University and Reearch/ ; R56NS12955601/NH/NIH HHS/United States ; },
mesh = {*Astrocytes/metabolism/ultrastructure ; Animals ; *Excitatory Amino Acid Transporter 2/metabolism ; *Synapses/metabolism/ultrastructure ; Humans ; *Cerebral Cortex/metabolism/ultrastructure/cytology ; Rats ; Male ; Female ; Rats, Sprague-Dawley ; Glutamic Acid/metabolism ; *Neural Inhibition/physiology ; },
abstract = {Glutamate spillover from excitatory synapses modulates neighboring inhibitory synapses, yet the ultrastructural organization of the major glutamate transporter GLT-1 at these sites remains poorly defined. Using quantitative pre-embedding electron microscopy in rat and human cortex, we found that GLT-1-positive astrocytic leaflets (ALs) were frequently juxtaposed to morphologically identified symmetric synapses, with similar prevalence across axo-somatic, proximal axo-dendritic, and distal axo-dendritic subtypes. Because inhibitory synapses are embedded in a dense excitatory neuropil, we applied distance-based phenotyping relative to the nearest asymmetric synapse to define symmetric-associated GLT-1+ ALs. Within this population, distal axo-dendritic symmetric synapses showed shorter AL-to-synaptic-edge distances and were embedded in a tighter local excitatory microenvironment. Post-embedding immunogold further showed that GLT-1 was enriched at the plasma membranes of ALs and localized extrasynaptically relative to symmetric synapses. Consistently, symmetric-associated membrane GLT-1 and closely spaced GLT-1/α2 couples (with an interdistance ≤ 50 nm) were preferentially localized within 1000 nm of distal symmetric synapses compared to proximal. Similar organizational features of membrane GLT-1/α2 couples were observed in human cortex. These findings identify a subtype-dependent extrasynaptic astrocytic GLT-1 organization at cortical inhibitory synapses and provide a morphological framework for glutamate-dependent modulation of inhibitory signaling.},
}

*Astrocytes/metabolism/ultrastructure
Animals
*Excitatory Amino Acid Transporter 2/metabolism
*Synapses/metabolism/ultrastructure
Humans
*Cerebral Cortex/metabolism/ultrastructure/cytology
Rats
Male
Female
Rats, Sprague-Dawley
Glutamic Acid/metabolism
*Neural Inhibition/physiology

@article {pmid42252587,
year = {2026},
author = {Jin, H},
title = {PET Molecular Probes for Neuroinflammation in Neurodegenerative Diseases: Progress and Prospects.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.6c00338},
pmid = {42252587},
issn = {1948-7193},
abstract = {Neuroinflammation is a central pathological process underlying neurodegenerative diseases, including Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis. Positron emission tomography (PET) molecular probes now enable the noninvasive, quantitative visualization of neuroinflammatory processes in the living brain. This review surveys recent advances in PET probes targeting microglial activation markers─including the 18 kDa translocator protein (TSPO), the purinergic P2X7 receptor (P2X7R), colony-stimulating factor 1 receptor (CSF1R), and sphingosine-1-phosphate receptor 1 (S1PR1)─as well as astrocyte reactivity markers such as monoamine oxidase B (MAO-B) and imidazoline-2 binding sites (I2BS). I discuss the evolution from first-generation TSPO ligands to polymorphism-insensitive third-generation tracers, highlight emerging targets beyond TSPO, and evaluate the translational value of these probes for early diagnosis, disease staging, treatment monitoring, and drug development. Current challenges-including limited cellular specificity, genetic polymorphism effects, quantification difficulties, and clinical accessibility barriers─are analyzed alongside promising solutions. Integrating neuroinflammation PET into multimodal biomarker frameworks will be essential for advancing precision medicine in neurodegenerative diseases.},
}

@article {pmid42253115,
year = {2026},
author = {Orzechowski, K and Wasiluk, M and Milewska, W and Kowalska, N and Chuang, YT and Cao, JY and Wang, CT and Neumann, A and Strzeżysz, O and Kozanecka-Szmigiel, A and Konieczkowska, J and Schab-Balcerzak, E and Lewandowski, W and Woliński, TR},
title = {Synergistic Effects of Nanoparticles and Surface Anchoring on Fine-Tuning the Photonic Bandgap in Blue Phase Liquid Crystals.},
journal = {ACS nano},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsnano.6c01127},
pmid = {42253115},
issn = {1936-086X},
abstract = {Precise control over the photonic bandgap in Blue Phase Liquid Crystals (BPLCs) remains challenging due to the inherent limitations of existing tuning methods. Here, we present a 2-fold approach that synergistically combines internal and external effectors to enable controlled, fine modulation of the photonic bandgap across a wide spectral range of 200 nm. Internally, nanoparticles (NPs) embedded within the BPLC lattice enhance the thermal stability of the blue phase and reduce the cubic unit cell size, thereby shifting the reflection bandgap toward shorter wavelengths. Externally, the chemical structure of homogeneous alignment layers (ALs) affects the spectral position of the Bragg reflection. By systematically varying four ALs and three NP doping levels (0, 0.5, and 2 wt %), a cooperative influence of both effectors on spectral tuning is observed. These interactions are qualitatively explained by contact-angle measurements and chemical interactions at the LC-AL and LC-NP interfaces. Kossel diagram analysis, together with a factor based on the total tuning range and associated statistical descriptors, is used to confirm and quantify Bragg wavelength shifts. The results demonstrate that combined internal and external control provides an effective strategy for adjusting the optical response and thermal behavior of BPLCs, supporting their application in photonic devices.},
}

@article {pmid42253371,
year = {2026},
author = {Chen, X and Mo, Y and Jiang, H},
title = {NEK1 variants and reduced protein levels in Chinese ALS patients: a descriptive study.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1831861},
pmid = {42253371},
issn = {1663-4365},
abstract = {OBJECTIVE: NIMA-related kinase 1 (NEK1) have been implicated in amyotrophic lateral sclerosis (ALS). But genetic spectrum and clinical presentation have not been systematically defined.

METHODS: We screened 378 ALS patients and identified NEK1 variant carriers. Clinical records were reviewed retrospectively to characterise phenotypes. Leukocytes were isolated after routine testing and NEK1 protein abundance was quantified by western blot to assess the relationship between NEK1 protein levels and the rate of clinical progression. In parallel, we conducted a structured narrative review of published NEK1-ALS cases based on a systematic search of PubMed, Embase, and Web of Science. We extracted genetic and clinical information to summarise the variant spectrum, co-mutation profiles, and phenotype differences across populations.

RESULTS: NEK1 variants were identified in 8 of 378 patients (2.12%). Protein analysis showed lower peripheral NEK1 levels among carriers than among controls in this small exploratory sample. An exploratory analysis further suggested that lower systemic NEK1 protein levels may be associated with faster disease progression; however, because these measurements were obtained from peripheral leukocytes at highly heterogeneous sampling times and without adjustment for major clinical confounders, they should be interpreted strictly as descriptive observations and do not support biomarker claims. While phenotypic heterogeneity and population-specific variant distributions were observed, these findings remain descriptive due to the small sample size.

CONCLUSION: This regional case series provides a descriptive overview of NEK1 variants in a Chinese ALS cohort and offers preliminary exploratory evidence consistent with reduced peripheral NEK1 protein levels in variant carriers. The observed inverse relationship between lower measured protein levels and faster clinical decline should be regarded as hypothesis-generating only. Given the small sample size, highly heterogeneous sampling times, use of peripheral leukocytes, and lack of adjustment for major clinical confounders, these protein data do not support biomarker claims at this stage. Validation in larger, prospective multi-center cohorts with standardized longitudinal sampling is required.},
}

@article {pmid42253609,
year = {2026},
author = {Lajoie, I and Kalra, S and Dadar, M},
title = {Data-driven subtyping and staging of ALS: A multicenter, longitudinal, deformation-based morphometry study.},
journal = {Imaging neuroscience (Cambridge, Mass.)},
volume = {4},
number = {},
pages = {},
pmid = {42253609},
issn = {2837-6056},
abstract = {Amyotrophic lateral sclerosis (ALS) is clinically and biologically heterogeneous, yet data-driven imaging subtyping approaches have rarely been validated longitudinally or linked to clinical and survival outcomes. We aimed to identify and validate distinct ALS subtypes and disease stages using deformation-based morphometry (DBM) and the Subtype and Stage Inference (SuStaIn) model, and to characterize their cross-sectional and longitudinal imaging, clinical, cognitive, and survival profiles. Data from 198 ALS patients and 144 healthy controls in the Canadian ALS Neuroimaging Consortium (CALSNIC) multicenter cohort were analyzed. Baseline regional DBM w-scores from 14 ALS-relevant regions served as input to SuStaIn to infer subtypes and stages. Longitudinal consistency of subtype and stage assignments (e.g. adherence to the expected disease evolution) was assessed using follow-up visits. Imaging and clinical trajectories were compared across subtypes using linear mixed-effects models incorporating stage and elapsed time. Associations between longitudinal variables and SuStaIn stage were estimated using mixed models, while baseline clinical and cognitive differences were assessed with ordinary least squares regression. Survival differences were evaluated using Kaplan-Meier curves and log-rank tests. SuStaIn identified one normal-appearing group (S0) and three ALS atrophy subtypes. S0 showed no baseline atrophy but exhibited longitudinal motor decline and the most favorable survival (log-rank p < 0.05 to p < 0.01). S1 exhibited classical motor/corticospinal tract-dominant degeneration, greater lower motor neuron burden, and intermediate survival. S2 showed limbic-onset atrophy progressing toward motor pathways, with preserved cognition and a milder course. S3 demonstrated extensive fronto-parietal and striatal atrophy, longitudinal motor-thalamic degeneration, and the shortest survival. Subtype and stage assignments demonstrated high longitudinal consistency (>90%). SuStaIn stage was strongly associated with widespread brain atrophy (and ventricular expansion), with the strongest effects in limbic-subcortical regions. Stage also correlated with ALS Functional Rating Scale-Revised (ALSFRS-R) decline and forced vital capacity (FVC) reduction, indicating that stage reflects disease-linked progression. This study establishes a robust, longitudinally validated model of ALS heterogeneity, showing that SuStaIn-derived subtypes define distinct disease trajectories, whereas the normal-appearing group reflects an early, structurally preserved state with a more favorable survival profile. By integrating probabilistic staging with longitudinal modeling, these findings clarify dynamic subtype-specific progression patterns and support the use of SuStaIn for biologically informed patient stratification, prognostication, and clinical trial enrichment in ALS.},
}

@article {pmid42253794,
year = {2026},
author = {Melby, SR and Asok Kumar, JN and Bigus, ER and Kellis, S},
title = {Clinical evaluation of communication brain computer interfaces in amyotrophic lateral sclerosis: a landscape analysis.},
journal = {Frontiers in human neuroscience},
volume = {20},
number = {},
pages = {1771146},
pmid = {42253794},
issn = {1662-5161},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease that leads to severe motor impairment, including loss of communication ability, and ultimately death. Communication brain computer interfaces (cBCIs) have the potential to restore communication without reliance on motor function, thereby improving quality of life, independence, and palliative care. However, standardized methods to evaluate cBCI efficacy necessary for clinical implementation are not yet established.

METHODS: We conducted a systematic literature review, semi structured interviews with key opinion leaders (KOLs), and a clinical assessment review panel to (1) identify clinical outcome assessments (COAs) relevant to cBCIs in ALS, (2) obtain expert feedback, and (3) synthesize the current clinical and scientific landscape.

RESULTS: A total of 21 COAs were identified as potentially relevant and may serve as a foundation for cBCI specific measures. However, no existing COA was found to comprehensively capture the clinical benefit or functional impact of cBCIs in ALS.

DISCUSSION: Current COAs are insufficient to evaluate cBCIs in ALS, highlighting a critical gap. Development of cBCI specific outcome measures is needed to support clinical validation, regulatory evaluation, and adoption.},
}

@article {pmid42253845,
year = {2026},
author = {Maslać, I and Palić, B and Kljakić, M and Puljić, M and Opančar, M and Kljakić, M and Opančar, B},
title = {Impact of dispatcher-assisted cardiopulmonary resuscitation, advanced life support training, and physician experience on out-of-hospital cardiac arrest outcomes in Mostar: a 10-year retrospective cohort study.},
journal = {Resuscitation plus},
volume = {28},
number = {},
pages = {101253},
pmid = {42253845},
issn = {2666-5204},
abstract = {BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a major public health challenge, with survival to hospital discharge rarely exceeding 10%. This study evaluated the association of dispatcher-assisted CPR (DA-CPR), advanced life support (ALS) training, and physician experience with OHCA outcomes in Mostar, Bosnia and Herzegovina, a resource-limited emergency medical service (EMS) system.

METHODS: We conducted a retrospective cohort study encompassing all OHCA cases recorded in the Mostar region between 2013 and 2022. Dispatcher-assisted CPR was formally implemented in early 2018. Accordingly, patients were stratified into two groups: the pre-implementation period (2013-2017) and the post-implementation period (2018-2022). The primary outcome was return of spontaneous circulation (ROSC) and the secondary outcome was survival to hospital discharge.

RESULTS: A total of 308 OHCA cases were included. ROSC was achieved in 88 patients (28.6%), and 14 patients (4.5%) survived to hospital discharge. Following DA-CPR implementation, ROSC increased from 22.7% to 33.5%. In adjusted logistic regression DA-CPR (OR = 1.857, 95% CI 1.075-3.208) and ALS-trained physician involvement (OR = 1.802, 95% CI 1.045-3.105) were independently associated with ROSC. Physician experience was not associated with ROSC or survival to hospital discharge, and no examined exposures were associated with survival to hospital discharge.

CONCLUSIONS: Dispatcher-assisted CPR and ALS-trained physician involvement were associated with higher odds of ROSC, while none of the examined variables showed an association with survival to hospital discharge. Early resuscitation gains did not translate into final outcomes in this resource-limited EMS system. Improving survival will require coordinated system strengthening, particularly public-access defibrillation and standardized post-resuscitation care.},
}

@article {pmid42254255,
year = {2026},
author = {Beniwal, SS and Rawat, A and Sharma, N and Calderón, DC and Mwaanga, C and Mora, VA and Saini, P and da Costa, REAR and Mushir Ali, AS and Kumar, A and Dwivedi, A and Mehta, SP and Patel, DR and Danda, P},
title = {Translating potential into practice: the evolving landscape of neural stem cell therapeutics in clinical applications.},
journal = {Annals of medicine and surgery (2012)},
volume = {88},
number = {6},
pages = {3284-3295},
pmid = {42254255},
issn = {2049-0801},
abstract = {BACKGROUND: Neural stem cell (NSC) therapeutics have emerged as a promising approach for addressing neurological disorders due to their inherent ability to self-renew, differentiate into neural lineages, and secrete neurotrophic factors.

METHODS: This narrative review explores the evolving clinical landscape of NSC applications, highlighting their therapeutic potential in neurodegenerative diseases, ischemic stroke, and spinal cord injuries.

FINDINGS: Recent clinical advancements demonstrate the safety and preliminary efficacy of NSC-based therapies in conditions like Parkinson's disease and amyotrophic lateral sclerosis. NSCs' capacity to promote neuroplasticity and tissue restoration underscores their potential in reversing synaptic and neuronal damage. Despite these advancements, significant challenges remain. Ethical considerations, particularly concerning cell sourcing and patient consent, must be carefully navigated. Technical barriers, including cell delivery, survival, and long-term integration, require innovative solutions. Furthermore, safety concerns such as tumor formation and immune rejection necessitate rigorous preclinical and clinical assessments. Regulatory challenges, including the standardization of manufacturing processes and international harmonization, are essential for widespread adoption.

CONCLUSION: Looking ahead, the integration of precision medicine, advanced biomaterials, and patient-specific-induced pluripotent stem cells offers promising approaches to enhance NSC therapeutics. Collaborative efforts between researchers, clinicians, and regulatory agencies are crucial for overcoming existing barriers and translating NSC research into clinical practice, offering new hope for patients with complex neurological conditions.},
}

@article {pmid42254864,
year = {2026},
author = {Yokoi, S and Iguchi, Y and Katsuno, M},
title = {Human iPSC-derived motor neurons as a platform for elucidating TDP-43-related amyotrophic lateral sclerosis pathogenesis: a mini review.},
journal = {Frontiers in molecular neuroscience},
volume = {19},
number = {},
pages = {1864964},
pmid = {42254864},
issn = {1662-5099},
abstract = {TAR DNA-binding protein 43 (TDP-43) is a major pathogenic RNA-binding protein associated with amyotrophic lateral sclerosis (ALS). Heterozygous mutations in TDP-43 cause familial ALS, known as ALS10. TDP-43 is predominantly localized in the nucleus under physiological conditions. Not only ALS patients with TARDBP mutations but also the majority of sporadic ALS patients exhibit TDP-43 pathology, which is defined by nuclear clearance and cytoplasmic aggregation. The inclusion of cryptic exons in genes such as STMN2 and UNC13A has emerged as a hallmark of TDP-43 loss of function, as demonstrated in TDP-43 knockdown models and postmortem analyses. However, it is not yet clear how TDP-43 levels and location change from healthy to pathological conditions in ALS. Motor neurons derived from induced pluripotent stem cells (iPSCs) have been widely used in ALS research and provide a promising platform to investigate early-stage disease mechanisms. However, challenges remain in generating models that faithfully recapitulate ALS pathogenesis. In this review, we summarize recent advances in TDP-43-related iPSC-derived motor neuron models and discuss future perspectives for elucidating ALS pathogenesis. We propose that longitudinal analyses of TDP-43 dynamics and co-culture systems will be essential to better model early ALS pathogenesis.},
}

@article {pmid42255170,
year = {2026},
author = {Gurumurthy, NP and Hurley, L and Nezami, BT and Gottfredson O'Shea, N},
title = {Behavior change techniques in mobile health interventions promoting recovery from substances: A synthesis of reviews and meta-analyses.},
journal = {Digital health},
volume = {12},
number = {},
pages = {20552076261458891},
pmid = {42255170},
issn = {2055-2076},
abstract = {OBJECTIVE: This synthesis of reviews and meta-analyses delves into the landscape of behavior change techniques (BCTs) employed in digital interventions designed to help individuals abstain from or reduce consumption of substances (including alcohol, tobacco, and illicit drugs). This review considers the "black box" problem in mHealth programs by using Michie et al.'s BCT taxonomy to describe BCTs that have been used in intervention literature and to explore potential active ingredients that may contribute to intervention effectiveness.

METHODS: We synthesize findings from 49 systematic reviews and meta-analyses. While individual studies often express inconclusiveness for the effectiveness of specific BCTs, this review uncovers promising avenues for future research. Our analysis focuses on mobile health (mHealth) just-in-time adaptive interventions (JITAIs), with a specific emphasis on substance use reduction.

RESULTS: Eleven BCTs were studied extensively in these reviews, including self-monitoring of behavior, feedback on behavior, goal setting, social support, prompts/cues, and behavior substitution. Our synthesis of evidence points to prompts/cues as particularly promising and highlights a handful of BCTs that demand further investigation, including self-monitoring, goal setting, and feedback on behavior.

CONCLUSIONS: This review identifies specific limitations in each step of review formulation and provides nuanced suggestions to enhance the efficacy of future research endeavors.},
}

@article {pmid42255926,
year = {2026},
author = {},
title = {Correction to: C9orf72 poly(glycine-alanine) knock-in mice exhibit mild rotarod and proteomic changes consistent with amyotrophic lateral sclerosis/frontotemporal dementia.},
journal = {Brain communications},
volume = {8},
number = {3},
pages = {fcag208},
doi = {10.1093/braincomms/fcag208},
pmid = {42255926},
issn = {2632-1297},
abstract = {[This corrects the article DOI: 10.1093/braincomms/fcag087.].},
}

@article {pmid42247870,
year = {2026},
author = {Aprile, FA and Pastore, A},
title = {Ribonucleic acid as an active driver of protein aggregation in neurodegeneration.},
journal = {Current opinion in structural biology},
volume = {99},
number = {},
pages = {103298},
doi = {10.1016/j.sbi.2026.103298},
pmid = {42247870},
issn = {1879-033X},
abstract = {Neurodegeneration has traditionally been largely attributed to protein aggregation, yet ribonucleic acid (RNA) has emerged as an active driver of pathology. Expanded repeat RNAs, misregulated RNA-binding proteins, and aberrant RNA-protein interactions can directly or indirectly trigger neuronal dysfunction, although the distinction between the two mechanisms might, in some cases, be loose. RNA modulates prion-like aggregation, scaffolds liquid-liquid phase separation, and either promotes or inhibits protein assembly, depending on RNA sequence and structure. The aim of this review is to discuss our current understanding of RNA's dual role-as a facilitator of aggregation or as a potential therapeutic target-revealing new mechanistic insights into diseases such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and spinocerebellar ataxias. We highlight RNA metabolism as a central determinant of neuronal vulnerability.},
}

@article {pmid42248860,
year = {2026},
author = {Ball, HE and Woods, AC and Wong, YC},
title = {TDP-43 oxidation and PP1 crosstalk at RNA granule-mitochondria contact sites.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-74009-9},
pmid = {42248860},
issn = {2041-1723},
support = {DP2GM146322//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; },
abstract = {Inter-organelle contact sites are key hubs for organelle bidirectional crosstalk. However, how mitochondria and RNA granules interact at contact sites and its regulation by mitochondrial oxidative phosphorylation (OXPHOS) remain unclear. Here, using Super-Resolution live microscopy, we identify RNA granule-mitochondria contact site formation in OXPHOS conditions. Reactive oxygen species (ROS) generated by mitochondrial OXPHOS promotes TDP-43 localization to cytoplasmic RNA granules via TDP-43 cysteine oxidation at Cys173/Cys175. Mechanistically, RNA granule-mitochondria contact tethering is mediated by TDP-43 on RNA granules binding to GADD34 on mitochondria, while contact untethering is regulated by TDP-43 oxidation. Functionally, this allows for GADD34 and its binding partner PP1 to regulate TDP-43 RNA granule dynamics, and conversely, for TDP-43 oxidation to regulate the ability of the phosphatase PP1 to form granules. Finally, disease-associated mutant TDP-43 misregulates this pathway, ultimately leading to PP1 granules lacking TDP-43. This dynamic crosstalk between TDP-43 oxidation and PP1 has significant consequences for TDP-43-associated diseases including Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD).},
}

@article {pmid42015194,
year = {2026},
author = {Luo, J and Li, K and Yang, R and Tang, M and Ge, J},
title = {Whole-exome sequencing identifies PRSS56 variants in Chinese patients with microphthalmia.},
journal = {BMC medical genomics},
volume = {19},
number = {1},
pages = {},
pmid = {42015194},
issn = {1755-8794},
support = {A1515010914//Guangdong Basic and Applied Basic Research Foundation/ ; 82271083//National Natural Science Foundation of China/ ; 2018YFA0108304//National Key Research and Development Program of China/ ; 2025QZSPT46//State Key Laboratory of Ophthalmology/ ; },
abstract = {PURPOSE: This study aimed to elucidate the genetic and clinical profiles of Chinese patients with microphthalmia harbouring PRSS56 variants and investigate the genotype‒phenotype correlation.

METHODS: Whole-exome sequencing (WES) was performed in patients with microphthalmia and available family members to assess coding regions and adjacent intronic splice boundaries for variant detection and downstream interpretation. The axial lengths (ALs) of all the probands and available family members were measured. The genotype‒phenotype correlation was explored by statistical analysis, and protein structure prediction was analysed in silico.

RESULTS: Seven PRSS56 variants were detected across four of the seven families, including two novel candidate variants (c.175G > A:p.E59K and c.1030 C > A:p.P344T) and five previously reported variants. Variant p.Q356Pfs152 was found in two unrelated families and was the most frequent. The mutational spectrum frequency in the Chinese population differed from that in other ethnic groups worldwide. The average AL was 17.82 ± 1.51 mm. In an exploratory pooled analysis combining the current cohort with previously published cases, eyes with biallelic LoF variants showed shorter ALs than eyes with missense variants. Variants p.G107V and p.E396K, which were reported exclusively in Chinese microphthalmia cases, were predicted to destabilize the PRSS56 protein.

CONCLUSIONS: Among nine individuals from seven families, seven PRSS56 variants were identified in four families, underscoring the significant genetic diversity within the Chinese population. The reported variant p.Q356Pfs*152 had the highest frequency in our cohort. Our findings expand current understanding of PRSS56-associated microphthalmia and provide valuable information for prenatal diagnosis and future therapeutic strategies.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-026-02376-9.},
}

@article {pmid42245509,
year = {2026},
author = {Wang, Z and Li, L and Dong, Y and Zhang, Y},
title = {The microbiota-tryptophan-brain axis in neurodegenerative diseases: pathogenic mechanisms, disease-specific roles, and translational therapeutics.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1820111},
pmid = {42245509},
issn = {1664-302X},
abstract = {The pathogenesis of neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD) and Parkinson's disease (PD) is very complex. Recent studies have shown that gut microbiota and their metabolites play a key role in the progression of these diseases. Tryptophan (Trp) is an essential amino acid, which mainly produces a variety of biologically active compounds in the intestine through the metabolism of indole pathway, Kynurenine pathway (KP) and serotonin pathway, including indole derivatives, Kynurenine (KYN) and serotonin (5-HT). These metabolites affect the central nervous system (CNS) through the Microbiota-gut-brain axis (MGBA) and affect CNS in a variety of mechanisms, including immune regulation, neuroprotection and maintenance of intestinal barrier function. They are involved in key pathological processes such as neuroinflammation, oxidative stress and pathological protein aggregation. This paper systematically reviews the mechanism of the role of Trp metabolites derived from gut microbiota in NDDs, and explores their specific roles in AD, PD, Amyotrophic Lateral Sclerosis (ALS) and Huntington's disease (HD), and summarizes the potential therapeutic value of the current pathway strategy. These strategies include nutritional intervention, targeted microbiome therapy [such as probiotic and fecal microbiota transplantation (FMT)], and metabolite-derived drugs. Future research must clarify its dynamic mechanism in the human body, develop relevant biomarkers, and promote personalized prevention and treatment strategies through clinical transformation, so as to provide a new direction for early intervention and treatment of NDDs.},
}

@article {pmid42246025,
year = {2026},
author = {Pu, H},
title = {Editorial: Regulated cell death and neurological diseases.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1842251},
pmid = {42246025},
issn = {1662-4548},
}

@article {pmid42246871,
year = {2026},
author = {Wang, Q and Zhou, X and Zhao, W and Du, H and Zhu, P},
title = {Three Unaddressed Methodological Concerns in Chen Et al.'s Sarcopenia Study: Physical Activity Weighting, Muscle Mass Estimation, and Time-Varying Exposure.},
journal = {Geriatrics & gerontology international},
volume = {26},
number = {6},
pages = {e70587},
doi = {10.1111/ggi.70587},
pmid = {42246871},
issn = {1447-0594},
}

@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.},
}