@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.},
}

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

LEVEL OF EVIDENCE: IV.},
}