@article {pmid41655843,
year = {2026},
author = {Mulla, Z and Coupe, N},
title = {Halal and Healthy: A Qualitative Study of British Muslim Perspectives on Meat Consumption and Plant-based Diets.},
journal = {Appetite},
volume = {},
number = {},
pages = {108496},
doi = {10.1016/j.appet.2026.108496},
pmid = {41655843},
issn = {1095-8304},
abstract = {Reducing meat consumption has the potential to improve both population and planetary health, however approaches to this have not been fully explored, particularly in the British Muslim community. British Muslims consume more meat than the average British person and face disproportionate diet related health risks. Although reducing meat consumption and eating more plant-based is known to reduce such health risks, there is limited understanding of British Muslim perceptions of this dietary transition. This study explored the barriers and facilitators towards British Muslims reducing meat consumption by increasing consumption of plant-based foods. The qualitative study involved semi-structured interviews with 15 British Muslims from Greater Manchester. Interviews were inductively analysed using reflexive thematic analysis and then deductively mapped to Michie et al.'s (2014) COM-B model. Two themes were identified. "Islamic Teachings and Food Choices" highlighted how Islamic teachings and practices gave religious significance to meat and taught foundational ethics that could encourage plant-based diets identified as reflective motivation influences. "The Value of Meat" explored perceptions of the elevated status of meat, influenced by beliefs about health, socio-economic status, and sociocultural norms. Social opportunity and reflective motivation were key influences identified in this theme. This study emphasised the importance of culturally relevant dietary interventions considering religious beliefs and community norms.},
}

@article {pmid41655130,
year = {2026},
author = {Xiang, Q and Liu, Y and Wang, J},
title = {Golgi fragmentation driven by the USP11-ITCH axis triggers autolysosomal failure in neurodegeneration.},
journal = {Autophagy},
volume = {},
number = {},
pages = {},
doi = {10.1080/15548627.2026.2629295},
pmid = {41655130},
issn = {1554-8635},
abstract = {Golgi fragmentation is a prominent early hallmark of neurodegenerative diseases such as Alzheimer disease (AD) and amyotrophic lateral sclerosis (ALS), yet the shared molecular mechanisms underlying this phenomenon remain poorly understood. Here we identify the E3 ubiquitin ligase ITCH as a central regulator of Golgi integrity and proteostasis. Elevated ITCH disrupts both cis- and trans-Golgi networks, dislocates lysosomal hydrolase sorting factors, and impairs maturation of hydrolases. The ensuing lysosomal dysfunction leads to autophagosome accumulation and defective clearance of accumulated cytoplasmic toxic proteins like TARDBP/TDP-43. Genetic and pharmacological inhibition of ITCH restores autolysosomal degradation and protects neurons in both mammalian and Drosophila models. Aberrant buildup of the deubiquitinase USP11 drives ITCH accumulation, intensifying neuronal proteotoxic stress in individuals with AD and ALS. These findings reveal a mechanistic pathway connecting Golgi disorganization, autolysosomal impairment, and proteotoxic stress in neurodegeneration.},
}

@article {pmid41654110,
year = {2026},
author = {Shen, Y and Shen, S and Luo, ZG},
title = {Gene-targeted versus broad-spectrum therapies in ALS: comparative lessons and strategic outlook.},
journal = {Journal of genetics and genomics = Yi chuan xue bao},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jgg.2026.01.012},
pmid = {41654110},
issn = {1673-8527},
abstract = {Amyotrophic lateral sclerosis (ALS) is a relentless and fatal neurodegenerative disorder characterized by the progressive loss of motor neurons, leading to muscle weakness, paralysis, and ultimately, respiratory failure. Despite a growing understanding of its complex pathophysiology, therapeutic options remain limited. This review critically analyzes recent clinical advances by comparing two divergent strategies, including precision gene-targeted therapies for monogenic ALS subtypes and broad-spectrum agents for the wider sporadic population. While gene therapies like tofersen demonstrate clear molecular target engagement, their translation to robust clinical benefit remains a challenge. In contrast, broad-spectrum agents have faced consistent late-stage failures, often due to the disease's underlying diversity, which undermines a one-size-fits-all approach. We argue that this heterogeneity, coupled with a lack of predictive biomarkers and the difficulty of late-stage intervention, represents the core barrier to progress. The future of ALS therapeutics therefore depends on a strategic pivot toward personalized medicine. This requires prospectively stratifying patients, developing rational combination therapies, and intervening earlier in the disease course, ultimately treating ALS as a syndrome of distinct molecular diseases rather than a single entity.},
}

@article {pmid41654003,
year = {2026},
author = {Sia, T and Sheehy, TP and Morgan, P and Wools, CA and Zhao, Y and Gibbs, R and Mathieson, S and Smith, AA},
title = {Trajectory of Mobility Fuction Decline for People with Motor Neuron Disease.},
journal = {Archives of physical medicine and rehabilitation},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.apmr.2026.01.028},
pmid = {41654003},
issn = {1532-821X},
abstract = {OBJECTIVE: The primary aim of this study was to explore factors that may influence the rate of mobility function decline. A secondary aim was to identify the impact of neck weakness on mobility decline in people living with motor neuron disease (MND).

DESIGN: Retrospective, longitudinal observational study design.

SETTING: This study was undertaken at a State-wide Progressive Neurological Disease Service (SPNDS) in the inpatients, outpatients and community-based services. The SPNDS clinic treats adults with MND from both metropolitan and rural settings.

PARTICIPANTS: Adults with motor neuron disease attending the Statewide Progressive Neurological Disease Service were recruited to participate in the study.

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: categorical data relating to mobility function (walking endurance, gait aid used and level of assistance required) was recorded. Neck weakness was measured as present or absent based on participant subjective report and/or objective observation of head position when upright.

RESULTS: Results from the 358 participants recruited showed that the median time to loss of independent gait was 30.5 months (range 4-239; IQR 26), full time wheelchair use was 34 months (IQR 35; range 5-238) and median time to becoming housebound was 28 months from MND symptom onset (IQR 24.5; range 5-219 months). 141 (39.4%) participants had neck weakness. The presence of neck weakness resulted in earlier loss of independent gait and quicker to become housebound. There was no significant difference in time to full time wheelchair use between participants with or without neck weakness.

CONCLUSION: There was an effect of both phenotype and neck weakness on the trajectory of mobility function decline in people with MND. Overall, people with amyotrophic lateral sclerosis (ALS) phenotype (bulbar, cervical or lumbar onset) experienced a more rapid rate of decline in mobility function than those with flail limb and primary lateral sclerosis (PLS) phenotypes. Additionally, those demonstrating neck weakness were quicker to decline in mobility than those without neck weakness.},
}

@article {pmid41653702,
year = {2026},
author = {Sebastianelli, L and Versace, V and Ferrazzoli, D and Ortelli, P and Trinka, E and Sellner, J and Nardone, R},
title = {Neurophysiology in the mirror: A tri-layer model of mirror movements informed by TMS evidence.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {184},
number = {},
pages = {2111692},
doi = {10.1016/j.clinph.2026.2111692},
pmid = {41653702},
issn = {1872-8952},
abstract = {OBJECTIVE: Mirror movements are involuntary, task-coupled contractions in contralateral homologous muscles during unilateral movement. While often described as a developmental remnant or rare clinical sign, mirror movements offer insight into the physiological mechanisms that underlie motor lateralization and interhemispheric balance. This review aimed to synthesize the available neurophysiological evidence-primarily from transcranial magnetic stimulation (TMS)-and propose a structured, mechanism-based framework for interpreting mirror movements across neurological conditions.

METHODS: A structured narrative review was conducted of studies published between 1966 and November 2025 using TMS in individuals with congenital, developmental, or acquired mirror movements. Studies using neuroimaging or peripheral electrophysiology were included selectively to support anatomical or functional interpretation of TMS findings. Data were organized into three mechanistic layers based on prevailing neurophysiological signatures rather than etiology alone.

RESULTS: Three non-mutually exclusive mechanisms were identified: (I) persistent fast-conducting ipsilateral corticospinal projections, primarily in congenital mirror movement syndromes and early brain injury; (II) deficient transcallosal inhibition, observed in conditions affecting interhemispheric balance such as amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, and callosal agenesis; and (III) bilateral overactivation of premotor and supplementary motor areas, especially under conditions of impaired motor program selection or increased task demands.

CONCLUSIONS: Mirror movements can be interpreted within a tri-layer model reflecting distinct disruptions in corticospinal connectivity, interhemispheric inhibition, and supraspinal motor control.

SIGNIFICANCE: This framework provides an integrative model for interpreting neurophysiological findings in mirror movements, offering insight into hierarchical motor control without implying specific diagnostic or therapeutic applications.},
}

@article {pmid41653524,
year = {2026},
author = {Kim, SH and Roh, YS},
title = {Effects of a theory-based advanced life support booster training program on competency retention in nursing students: A randomized controlled trial.},
journal = {Nurse education in practice},
volume = {92},
number = {},
pages = {104754},
doi = {10.1016/j.nepr.2026.104754},
pmid = {41653524},
issn = {1873-5223},
abstract = {AIM: This study evaluated the effectiveness of a theory-based advanced life support (ALS) booster training program on six-month retention of knowledge, skills performance and teamwork.

BACKGROUND: Retention of ALS competencies is vital for nursing students, yet skills and knowledge often decline within months of initial training.

DESIGN: A randomized controlled trial was conducted.

METHODS: A convenience sample of 65 fourth-year nursing students were randomly assigned to an experimental group (n = 33) receiving a two-hour booster session based on mastery learning and deliberate practice theories or to a control group (n = 32). ALS knowledge, skills and teamwork were measured at baseline and six months post-training. Data were analyzed using non-parametric tests and generalized estimating equation.

RESULTS: Both groups experienced declines over time. However, the experimental group showed significantly better retention in skills performance (p < .001) and teamwork (p = .025). Knowledge retention was higher but not statistically significant (p = .116).

CONCLUSIONS: A brief, theory-based booster session effectively improved long-term retention of ALS skills and teamwork, supporting its integration into nursing education.},
}

@article {pmid41653014,
year = {2026},
author = {Abrahao, A and Ciepielewska, M and Zinman, L},
title = {Value of Clinical Evidence and Health Economics and Outcomes Research (HEOR) Studies.},
journal = {Muscle & nerve},
volume = {73 Suppl 1},
number = {Suppl 1},
pages = {S7-S12},
pmid = {41653014},
issn = {1097-4598},
support = {//Mitsubishi Tanabe Pharma America, Inc./ ; },
mesh = {Humans ; *Outcome Assessment, Health Care/economics ; *Economics, Medical ; Randomized Controlled Trials as Topic ; Amyotrophic Lateral Sclerosis/therapy/economics ; *Evidence-Based Medicine/economics ; Cost-Benefit Analysis ; },
abstract = {Randomized controlled trials (RCTs) remain the gold standard for establishing the efficacy and safety of new treatments. However, clinical evidence derived from the systematic analysis of real-world data generated through routine clinical practice can complement RCT data by offering insights into treatment performance in broader, more heterogeneous patient populations and clinical care settings. The integration of high-quality clinical evidence into health economics and outcomes research (HEOR) is increasingly important, as it supports healthcare decision-making across multiple stakeholders, including regulatory agencies, payers, clinicians, and patients. Multiple study designs, such as pragmatic trials, hybrid RCTs, external control arms, and observational studies, can provide valuable clinical evidence beyond the controlled trial setting. These data can enhance understanding of comparative effectiveness, patient-reported outcomes, treatment safety, and healthcare utilization and costs. The field of amyotrophic lateral sclerosis offers a compelling example of how clinical evidence derived from global registries and clinical studies has advanced understanding of disease epidemiology, treatment patterns, and the effectiveness of therapies, including riluzole and edaravone. Consequently, this review and the associated supplementary articles are meant to serve as a primer to inform clinicians of the potential contribution of clinical evidence to HEOR studies.},
}

Humans
*Outcome Assessment, Health Care/economics
*Economics, Medical
Randomized Controlled Trials as Topic
Amyotrophic Lateral Sclerosis/therapy/economics
*Evidence-Based Medicine/economics
Cost-Benefit Analysis

@article {pmid41653010,
year = {2026},
author = {Abrahao, A and Zinman, L and Apple, S},
title = {Current and Ongoing Clinical Studies.},
journal = {Muscle & nerve},
volume = {73 Suppl 1},
number = {Suppl 1},
pages = {S26-S28},
pmid = {41653010},
issn = {1097-4598},
support = {//Mitsubishi Tanabe Pharma America, Inc./ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Edaravone/therapeutic use ; *Clinical Trials as Topic ; *Free Radical Scavengers/therapeutic use/administration & dosage ; },
abstract = {This article provides a comprehensive overview of current and ongoing studies evaluating intravenous (IV) edaravone and edaravone oral suspension in the treatment of amyotrophic lateral sclerosis (ALS). In addition to data from clinical practice and post hoc analyses, multiple observational and interventional studies are underway to better understand the efficacy, safety, and biological impact of edaravone in clinical settings. Key studies include SUNRISE Japan, a long-term postmarketing surveillance study of IV edaravone in Japanese patients with ALS; the ALS/Motor Neuron Disease Natural History Study, a longitudinal registry designed to inform clinical trial design and track ALS progression; and the REFINE-ALS study, which is actively collecting biomarker data to elucidate the pathophysiologic mechanisms influenced by edaravone. For edaravone oral suspension, United States Food and Drug Administration approval was supported by Study MT-1186-A01, a phase 3 trial assessing safety and tolerability over 48 weeks, with extension Study MT-1186-A03. Study MT-1186-A02, conducted as an FDA postmarketing commitment, and its extension, Study MT-1186-A04, evaluated whether investigational once daily dosing showed superior efficacy vs. the approved on/off dosing regimen. Collectively, these studies contribute to a growing body of evidence supporting the use of edaravone as a therapeutic option for ALS. They also underscore the importance of continued data collection from both clinical trials and clinical settings to inform optimal treatment strategies and combination therapy approaches as more agents become available in an evolving ALS treatment landscape.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy
*Edaravone/therapeutic use
*Clinical Trials as Topic
*Free Radical Scavengers/therapeutic use/administration & dosage

@article {pmid41653008,
year = {2026},
author = {Brooks, BR and Ennist, DL and Beaulieu, D and Apple, S},
title = {Generalizability of Edaravone Efficacy.},
journal = {Muscle & nerve},
volume = {73 Suppl 1},
number = {Suppl 1},
pages = {S16-S18},
pmid = {41653008},
issn = {1097-4598},
support = {//Mitsubishi Tanabe Pharma America, Inc./ ; },
mesh = {Humans ; *Edaravone/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy/physiopathology ; Male ; Female ; Middle Aged ; *Free Radical Scavengers/therapeutic use ; Treatment Outcome ; Aged ; Disease Progression ; Retrospective Studies ; Vital Capacity/drug effects ; Machine Learning ; },
abstract = {The pivotal phase 3 trial MCI186-19 (Study 19) demonstrated the efficacy of intravenous edaravone in slowing functional decline in patients with amyotrophic lateral sclerosis (ALS), leading to United States Food and Drug Administration approval. Study 19 utilized a targeted enrollment enrichment strategy based on post hoc analyses from earlier trials, selecting patients with higher baseline function, more rapid disease progression, and better respiratory status. To evaluate the generalizability of Study 19 results, subsequent post hoc analyses assessed the efficacy of edaravone in broader ALS populations. One machine learning-based analysis retrospectively applied a validated model to Study 16 data, stratifying patients by predicted risk of respiratory decline. This detectable effect cluster analysis suggested that up to 70% of Study 16 participants may have benefited from edaravone. A second analysis investigated edaravone efficacy in patients from Study 19 with forced vital capacity (FVC) < 80% predicted (%p) at the start of treatment, since FVC ≥ 80%p was one of the Study 19 inclusion criteria. Both high- and low-FVC subgroups demonstrated reduced ALS functional rating scale-revised decline at 48 weeks when treated continuously with edaravone. These findings support the potential benefit of edaravone in a wider range of patients with ALS than those enrolled in Study 19, providing important insights into how clinical trial enrichment strategies may influence perceived efficacy, and underscoring the need for future prospective studies in more diverse ALS populations.},
}

Humans
*Edaravone/therapeutic use
*Amyotrophic Lateral Sclerosis/drug therapy/physiopathology
Male
Female
Middle Aged
*Free Radical Scavengers/therapeutic use
Treatment Outcome
Aged
Disease Progression
Retrospective Studies
Vital Capacity/drug effects
Machine Learning

@article {pmid41653006,
year = {2026},
author = {Gwathmey, KG and Apple, S},
title = {Introduction to the Supplement.},
journal = {Muscle & nerve},
volume = {73 Suppl 1},
number = {Suppl 1},
pages = {S3-S6},
pmid = {41653006},
issn = {1097-4598},
support = {//Mitsubishi Tanabe Pharma America, Inc./ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Edaravone/therapeutic use ; *Neuroprotective Agents/therapeutic use ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease with marked phenotypic and clinical heterogeneity. Three active pharmaceutical agents are currently approved by the United States Food and Drug Administration (FDA) for ALS: riluzole, edaravone (including intravenous [IV] and oral suspension formulations), and tofersen. Study MCI186-19 (Study 19) was a pivotal, phase 3 randomized controlled trial that demonstrated a significant reduction in physical functional decline vs. placebo in Japanese patients with ALS and contributed to FDA approval of IV edaravone in 2017. Edaravone oral suspension was FDA-approved in May 2022 following the results of Study MT-1186-A01, which showed it was well tolerated with a safety profile consistent with IV edaravone. Following Study 19, the clinical benefit of edaravone has remained an active area of investigation. This supplement presents data from clinical trials, post hoc analyses, and clinical studies that expand understanding of the use of edaravone in broader ALS populations. Topics include safety in clinical practice, generalizability of efficacy, clinical treatment outcomes, and health economics and outcomes research studies. Together, these findings aim to inform clinicians, researchers, and stakeholders regarding the evolving evidence base for edaravone in the management of ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy
*Edaravone/therapeutic use
*Neuroprotective Agents/therapeutic use

@article {pmid41653005,
year = {2026},
author = {Genge, A and Apple, S},
title = {Safety of Intravenous Edaravone in Clinical Practice.},
journal = {Muscle & nerve},
volume = {73 Suppl 1},
number = {Suppl 1},
pages = {S13-S15},
pmid = {41653005},
issn = {1097-4598},
support = {//Mitsubishi Tanabe Pharma America, Inc./ ; },
mesh = {Humans ; Edaravone/adverse effects/administration & dosage ; *Amyotrophic Lateral Sclerosis/drug therapy ; Male ; Female ; *Free Radical Scavengers/adverse effects/administration & dosage ; Middle Aged ; Administration, Intravenous ; Pharmacovigilance ; Aged ; *Antipyrine/analogs & derivatives/adverse effects/administration & dosage ; Adult ; Product Surveillance, Postmarketing ; },
abstract = {This article summarizes the post-marketing pharmacovigilance safety data of intravenous (IV) edaravone during the 1- and 3-year periods following its launch for amyotrophic lateral sclerosis (ALS) in the United States. The most frequently reported adverse events (AEs) and serious AEs (SAEs) included those consistent with ALS disease progression, such as fatigue and muscular weakness, and were not qualitatively different from those reported in previous ALS trials. There were AEs and SAEs associated with IV administration, such as administration site reactions, and five non-fatal anaphylaxis SAEs were reported. No new safety signals were identified, and IV edaravone continues to demonstrate a favorable safety profile. These insights are especially useful as treatment transitions to edaravone oral suspension, which avoids IV-related complications. These findings underscore the importance of ongoing clinical safety assessments in informing ALS treatment decisions.},
}

Humans
Edaravone/adverse effects/administration & dosage
*Amyotrophic Lateral Sclerosis/drug therapy
Male
Female
*Free Radical Scavengers/adverse effects/administration & dosage
Middle Aged
Administration, Intravenous
Pharmacovigilance
Aged
*Antipyrine/analogs & derivatives/adverse effects/administration & dosage
Adult
Product Surveillance, Postmarketing

@article {pmid41653004,
year = {2026},
author = {Brooks, BR and Berry, JD and Ciepielewska, M},
title = {Survival of Intravenous Edaravone-Treated Patients With ALS: Evidence From Administrative Claims Analyses.},
journal = {Muscle & nerve},
volume = {73 Suppl 1},
number = {Suppl 1},
pages = {S23-S25},
pmid = {41653004},
issn = {1097-4598},
support = {//Mitsubishi Tanabe Pharma America, Inc./ ; },
mesh = {Humans ; *Edaravone/administration & dosage/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy/mortality ; Female ; Male ; Middle Aged ; Retrospective Studies ; Aged ; *Free Radical Scavengers/administration & dosage/therapeutic use ; Administration, Intravenous ; Adult ; Neuroprotective Agents ; Databases, Factual ; United States ; Treatment Outcome ; },
abstract = {Randomized controlled trials remain the cornerstone of evidence generation in amyotrophic lateral sclerosis (ALS), yet their inherent challenges, including disease rarity, heterogeneity, and limited validated biomarkers, highlight the need for complementary clinical evidence. This exploratory, retrospective study assessed overall survival in patients with ALS treated with intravenous (IV) edaravone using data from a large United States administrative claims database of patients enrolled from August 2017 to March 2020. Patients receiving IV edaravone (n = 318) were propensity score matched 1:1 with controls not treated with IV edaravone (n = 318), adjusting for 11 covariates. Median overall survival was 29.5 versus 23.5 months for the edaravone-treated group compared to controls, with a 27% reduced risk of death observed in the treated cohort (p = 0.005). These findings, together with existing data from the pivotal phase 3 Study MCI186-19 of IV edaravone, contribute to the growing body of literature suggesting a dual benefit of edaravone on both function and survival in ALS, offering critical insights for clinicians, patients, and payers navigating ALS treatment decisions.},
}

Humans
*Edaravone/administration & dosage/therapeutic use
*Amyotrophic Lateral Sclerosis/drug therapy/mortality
Female
Male
Middle Aged
Retrospective Studies
Aged
*Free Radical Scavengers/administration & dosage/therapeutic use
Administration, Intravenous
Adult
Neuroprotective Agents
Databases, Factual
United States
Treatment Outcome

@article {pmid41653003,
year = {2026},
author = {Brooks, BR and Shefner, J and Apple, S},
title = {Study 19 (MCI186-19) Post Hoc Analyses.},
journal = {Muscle & nerve},
volume = {73 Suppl 1},
number = {},
pages = {S19-S22},
doi = {10.1002/mus.70039},
pmid = {41653003},
issn = {1097-4598},
support = {//Mitsubishi Tanabe Pharma America, Inc./ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Edaravone/therapeutic use ; Treatment Outcome ; Disease Progression ; Male ; Female ; *Free Radical Scavengers/therapeutic use ; Randomized Controlled Trials as Topic ; Middle Aged ; *Neuroprotective Agents/therapeutic use ; },
abstract = {While randomized controlled trials (RCTs) are the gold standard for evaluating the efficacy of therapies in amyotrophic lateral sclerosis (ALS), post hoc analyses can provide critical insights into clinical effectiveness, treatment durability, and subpopulation responses. Several post hoc analyses of Study MCI186-19 (Study 19), the pivotal phase 3 RCT that supported the United States Food and Drug Administration approval of intravenous edaravone, have been performed to explore the broader clinical impact of this therapy. These analyses assessed the long-term treatment efficacy, changes in individual ALS Functional Rating Scale-Revised item scores, survival and additional milestone events, and the impact of edaravone in patient subgroups defined by disease progression trajectories using latent class analysis. Collectively, these findings reinforce the long-term clinical benefit of edaravone and demonstrate that edaravone may offer benefits across a spectrum of ALS disease trajectories, beyond those defined in the original study criteria. These studies help address questions not captured in the original RCT and may inform future trial design and treatment decisions.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy
*Edaravone/therapeutic use
Treatment Outcome
Disease Progression
Male
Female
*Free Radical Scavengers/therapeutic use
Randomized Controlled Trials as Topic
Middle Aged
*Neuroprotective Agents/therapeutic use

@article {pmid41652471,
year = {2026},
author = {Scekic-Zahirovic, J and Antonucci, S and Wiesner, D and Ebner, C and El Hajj, H and Aousji, O and Halablab, K and Fan, Y and Zelaya, A and Yartas, G and Baskar, K and Çakmak, EA and Bayer, D and Sung, HK and Dupuis, L and Park, J and Roselli, F},
title = {Large-scale mapping of the MCH network in ALS mice reveals the vulnerability of dopaminergic and GABAergic neurons in zona incerta.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-026-02231-z},
pmid = {41652471},
issn = {2051-5960},
}

@article {pmid41652348,
year = {2026},
author = {Johansen, H and Nakken, O and Holmøy, T and Fredheim, OMS},
title = {Disease trajectories and end of life care in a Norwegian ALS cohort.},
journal = {BMC neurology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12883-026-04698-8},
pmid = {41652348},
issn = {1471-2377},
abstract = {OBJECTIVE: This retrospective cohort study aims to provide comprehensive data on the disease trajectory and end-of-life care in patients dying from ALS.

METHODS: The study presents detailed information on a cohort dying from ALS in the area served by Akershus University Hospital from 2011 to 2022. Data was obtained from the patient medical records.

RESULTS: 118 patients were included. 65 patients (55%) were referred to the Department of Palliative medicine for specialist palliative care, with a median duration from referral to death of two months and one third of patients not being able to communicate verbally at the time of referral. The most common life-sustaining treatment was non-invasive ventilation and percutaneous endoscopic gastrostomy, whereas most prevalent limitation of life-sustaining treatment was withholding of tracheostomy with invasive ventilation. Hospital was the most common place of death with 54 (46%) of all deaths. For in-hospital-deaths, the most common place of death was the palliative care ward, with 21 patients (39%), but a substantial proportion (17%) died at intensive or intermediate care units. Overall, 37% of in-hospital deaths had been admitted to either intensive or intermediate care units during their last week of life, which may suggest these patients deteriorated rapidly without having documented advanced care planning and therefore received resource demanding and futile treatment during the last week of life.

CONCLUSION: Many patients lived in their own homes until admitted to their last hospital stay in life. However, these last hospital stays were frequently characterized by insufficient advanced care planning, leading to futile overtreatment.

TRIAL REGISTRATION: Retrospectively registered.},
}

@article {pmid41651385,
year = {2026},
author = {Raina, GS and Mehan, S and Das Gupta, G},
title = {Neuroprotection via IGF-1 Neuronal Signaling Activation by Melatonin and Edaravone Synergy in Methylmercury-Induced ALS-like Neurotoxicity: Comprehensive Analysis of Brain Regions, Spinal Cord, CSF, and Blood Plasma.},
journal = {Neurotoxicology},
volume = {},
number = {},
pages = {103398},
doi = {10.1016/j.neuro.2026.103398},
pmid = {41651385},
issn = {1872-9711},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron degeneration, oxidative stress, neuroinflammation, and neurotransmitter imbalances. This study explored the neuroprotective potential of melatonin (MLT), alone and in combination with edaravone (EDR), in a methylmercury (MEME)-induced ALS rat model. MEME exposure effectively replicated ALS pathology, causing behavioral deficits, oxidative stress, neuroinflammation, apoptosis, and widespread structural damage in critical brain regions and the spinal cord. MLT administration at 5mg/kg (MLT5) and 10mg/kg (MLT10) significantly mitigated MEME-induced neurotoxicity in a dose-dependent manner. MLT improved motor function, reduced depressive-like behavior, and restored body weight. Biochemically, MLT enhanced antioxidant defenses, including superoxide dismutase (SOD) and catalase (CAT), reduced pro-inflammatory cytokines, interleukin-1 beta (IL-1β), increased anti-inflammatory cytokines, interleukin-10 (IL-10), and restored neurotransmitter balance like dopamine and Gamma-Aminobutyric Acid (GABA). Mechanistically, MLT activated the IGF-1 signaling pathway, promoting neuronal survival and reducing apoptosis (Caspase-3 expression). Histopathological analyses confirmed that MLT preserved neuronal and glial integrity, reduced demyelination, and restored myelin basic protein (MBP) levels in brain and cerebrospinal fluid. The combination of MLT and EDR exhibited synergistic neuroprotective effects, surpassing the efficacy of individual treatments in reducing oxidative stress, inflammation, and neuronal damage. Behavioral and biochemical improvements were paralleled by systemic recovery, as evidenced by normalized hematological parameters and reduced methylmercury accumulation in brain tissues. These findings underscore MLT, particularly in combination with EDR, as a potent therapeutic agent for ALS, offering multi-targeted neuroprotection. Future studies should explore its translational potential in clinical settings for the treatment of neurodegenerative diseases.},
}

@article {pmid41651252,
year = {2026},
author = {Hnath, B and Ekambaram, S and Dokholyan, NV},
title = {Novel extracellular vesicle release pathway facilitated by toxic superoxide dismutase 1 oligomers.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107309},
doi = {10.1016/j.nbd.2026.107309},
pmid = {41651252},
issn = {1095-953X},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that results in paralysis and death within three to five years. Mutations in over forty different proteins have been linked to ALS, raising debate over whether ALS is a single disease or multiple disorders with similar symptoms. Mutations in Cu,Zn superoxide dismutase 1 (SOD1) are found in only 2-3% of ALS cases, yet misfolded SOD1 appears in both sporadic (sALS) and familial (fALS) patients. Furthermore, mutations in TDP-43 or FUS increase levels of misfolded SOD1 on extracellular vesicles (EVs). Small EVs isolated from ALS patient samples have been shown to cause death of wild-type motor neurons and myotubes, supporting the theory that EVs play a role in spreading disease. We hypothesize that the previously identified toxic trimeric SOD1 spreads via EVs in ALS and influences the distribution of other ALS-related proteins, suggesting a common mechanism. To test this, we isolate EVs from motor neuron-like cells expressing mutations that stabilize trimers. We then perform a sandwich enzyme-linked immunosorbent assay (ELISA) using a CD9 capture antibody to measure whether misfolded SOD1 and 17 other ALS-related proteins increase or decrease on EVs with trimer stabilization. We identify which EV release pathway is affected by trimeric SOD1 using endocytosis and exocytosis inhibitors and analyze altered protein interaction pathways through co-immunoprecipitation and mass spectrometry proteomics. Our results show that VAPB, VCP, and Stathmin-2 increase on EVs when trimers are stabilized. The common pathway linking these ALS-associated proteins and SOD1 appears to involve multiple mechanisms, including the Caveolae endocytosis pathway, pointing to a novel hybrid EV release pathway in ALS. Overall, our findings show that trimeric SOD1 influences EV cargo and spread in ALS.},
}

@article {pmid41649950,
year = {2026},
author = {Komori, S and Ito, D and Hashizume, A and Yamada, S and Kishimoto, Y and Kawase, T and Kondo, A and Suzuki, M and Hatanaka, M and Oba, C and Katsuno, M},
title = {Characteristics of muscle cramps as a prodromal symptom of sporadic amyotrophic lateral sclerosis.},
journal = {Journal of neuromuscular diseases},
volume = {},
number = {},
pages = {22143602261422971},
doi = {10.1177/22143602261422971},
pmid = {41649950},
issn = {2214-3602},
abstract = {BACKGROUND: Prodromal symptoms of sporadic amyotrophic lateral sclerosis (SALS) including muscle cramps were reported; however, their detailed characteristics have not been sufficiently studied.

OBJECTIVES: To clarify the detailed profiles of prodromal symptoms in SALS.

METHODS: Patients with SALS (n = 47) and healthy controls (n = 25) were enrolled. A questionnaire-based survey was conducted to investigate symptoms before and after disease onset, including sensory, autonomic, sleep, cognitive disturbances, and frequent muscle cramps. Frequent muscle cramps were defined as those occurring at least twice per month in the lower limbs, or at least once per month in the upper limbs or trunk. We evaluated the relationship between surveyed symptoms and clinical characteristics.

RESULTS: Prodromal frequent muscle cramps were observed in 29.8% of SALS patients, most frequently in the lower limbs. With disease progression, the sites with cramps increased, and the frequency of cramps during awakening also increased. The SALS patients with prodromal cramps had greater lean mass than those without (p = 0.023). Multivariate analysis showed that the presence of cramps after disease onset was associated with a slower longitudinal decline in the ALSFRS-R score (p = 0.048). Upper limb-onset SALS patients experienced cramps more frequently before onset than bulbar-onset patients did (p = 0.033).

CONCLUSIONS: Frequent muscle cramps often precede muscle weakness during the prodromal phase of limb-onset SALS. The frequency of cramps increased with disease progression. Prodromal cramps were associated with lean mass, whereas cramps after disease onset were associated with a slower rate of disease progression.},
}

@article {pmid41649614,
year = {2026},
author = {Mukherjee, R and Mehan, S and Choudhary, D and Rana, R and Das Gupta, G and Samant, R and Tongra, M},
title = {Sulforaphane-Mediated Multitarget Therapeutic Effects in Methylmercury-Induced ALS-Like Pathology: Comparative Analysis and Multifaceted Approach to Neuroprotection and Systemic Recovery.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {422},
pmid = {41649614},
issn = {1559-1182},
mesh = {Animals ; *Isothiocyanates/pharmacology/therapeutic use ; Sulfoxides ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Methylmercury Compounds/toxicity ; *Amyotrophic Lateral Sclerosis/drug therapy/pathology/chemically induced/physiopathology ; Female ; Rats ; Rats, Sprague-Dawley ; *Recovery of Function/drug effects ; *Neuroprotection/drug effects ; Male ; Oxidative Stress/drug effects ; Apoptosis/drug effects ; Antioxidants/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by motor neuron loss driven by oxidative stress, neuroinflammation, and dysregulated survival signaling. The objective of this study was to evaluate the neuroprotective efficacy and safety of sulforaphane (SUFP) in a methylmercury (MMHg[+])-induced preclinical rat model of ALS, with comparison to omaveloxolone (OVX) and dimethyl fumarate (DIMT). SUFP treatment, particularly at 4 mg/kg, significantly restored antioxidant defense mechanisms through upregulation of Nrf2, HO-1, and SIRT1 while suppressing pro-inflammatory cytokines (IL-1β, TNF-α), apoptotic markers (Bax, caspase-3), and stress-related signaling pathways including p75NTR, PI3K/Akt, and MAPKs. These molecular effects translated into meaningful functional recovery, as evidenced by improvements in grip strength, locomotor performance, spatial memory, and depressive-like behavior. Histopathological evaluation demonstrated attenuation of demyelination and preservation of neuronal architecture in cortical, hippocampal, and cerebellar regions. Beyond central neuroprotection, SUFP exerted systemic benefits by normalizing hepatic enzymes, improving skeletal muscle integrity, restoring redox balance, stabilizing neurofilament and myelin-associated proteins, and correcting hematological alterations. Comparative analysis revealed that SUFP conferred superior neuroprotection with a favorable safety profile relative to OVX and, although slightly less efficacious than DIMT, exhibited reduced systemic toxicity. Molecular docking further supported SUFP's interaction with Nrf2-Keap1 targets, reinforcing its antioxidant and anti-inflammatory mechanisms. Collectively, these findings identify SUFP as a multifaceted and well-tolerated therapeutic candidate for ALS, supporting its further translational and clinical evaluation.},
}

Animals
*Isothiocyanates/pharmacology/therapeutic use
Sulfoxides
*Neuroprotective Agents/pharmacology/therapeutic use
*Methylmercury Compounds/toxicity
*Amyotrophic Lateral Sclerosis/drug therapy/pathology/chemically induced/physiopathology
Female
Rats
Rats, Sprague-Dawley
*Recovery of Function/drug effects
*Neuroprotection/drug effects
Male
Oxidative Stress/drug effects
Apoptosis/drug effects
Antioxidants/metabolism

@article {pmid41647790,
year = {2025},
author = {Raymond, J and Larson, T and Nair, T and Kaufman, J and Horton, DK and Weisskopf, M and Mohidul, S and Mehta, P},
title = {Age-period-cohort effect on motor neuron disease mortality in the United States, 2001-2020.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1751690},
pmid = {41647790},
issn = {1664-2295},
abstract = {INTRODUCTION: Motor neuron diseases (MND) are progressively fatal diseases causing loss of motor neurons throughout the body. Recent studies have suggested an increase in prevalence and mortality of amyotrophic lateral sclerosis (ALS), the most common adult-onset MND. It is unclear whether the increase is because of earlier diagnosis or potentially new exposures. Age-period-cohort (APC) analysis can help identify contributors to temporal disease trends by differentiating impacts of biological aging, historical time period, and birth cohort. The aim of this study is to evaluate APC effects on MND mortality in the United States from 2001 to 2020.

METHODS: We analyzed deaths by MND for the period 2001-2020 in subjects aged 40-84 years. We used APC modeling to compute net drift, local drift, longitudinal age curve, rate ratios (RR), and confidence intervals (CI) for each period and cohort. Analysis used the APC Web Tool provided by the United States' National Cancer Institute.

RESULTS: Over the 20-year period, there were 119,890 MND deaths. Men consistently had higher mortality compared to women. Analysis yielded noteworthy birth cohort effects for men. For men, the cohort RR decreased from 1919 to 1953 and peaked again between 1959 and 1963. Men born after 1973 had a reduced RR = 0.77 (95% CI = 0.63-0.94). Women born after 1973 had a cohort RR = 1.00 (95% CI = 0.75-1.34).

CONCLUSION: APC analysis revealed potentially impactful age, period, and cohort effects in U.S. MND mortality between 2001 and 2020, with higher mortality among men and evidence of sex-specific cohort patterns. Cohort effects suggest potential generational differences in risk. Further investigation is needed to disentangle ascertainment effects from true etiologic influences.},
}

@article {pmid41647265,
year = {2026},
author = {Kim, H},
title = {Task-invariant networks interfere with and task-specific networks support memory formation: An fMRI meta-analysis.},
journal = {Imaging neuroscience (Cambridge, Mass.)},
volume = {4},
number = {},
pages = {},
pmid = {41647265},
issn = {2837-6056},
abstract = {Why do some moments imprint themselves in memory while others vanish without a trace? This meta-analysis identifies a dissociation in large-scale brain networks during encoding: networks associated with impairing encoding are task-invariant, whereas those supporting it are task-specific. Drawing on 56 functional magnetic resonance imaging (fMRI) studies employing the subsequent memory paradigm, the analysis contrasted neural activity for later-remembered versus later-forgotten trials across verbal and pictorial tasks. Using Yeo et al.'s 17-network parcellation, the results show that encoding-impairing effects consistently recruit specific subsystems within the default mode, frontoparietal, and ventral attention networks-a pattern consistent with distraction or mind-wandering. Conversely, encoding-supporting effects diverge by task: verbal encoding engages language-related networks, whereas pictorial encoding activates visuo-perceptual systems. This asymmetry suggests that encoding failure may arise from similar attentional lapses across contexts, whereas successful encoding requires precise, context-sensitive neural engagement. Taken together, these findings provide a network-level perspective on how the brain shifts between states conducive to remembering and states conducive to forgetting.},
}

@article {pmid41646446,
year = {2026},
author = {Donkin, A and Rodseth, R and Giddy, J},
title = {FDNHSA's response to KL Dunkle et al.'s 'Upholding clinical integrity and South African relevance: A defence of the SASOP position statement on the care of transgender and non-binary youth'.},
journal = {The South African journal of psychiatry : SAJP : the journal of the Society of Psychiatrists of South Africa},
volume = {32},
number = {},
pages = {2602},
pmid = {41646446},
issn = {1608-9685},
}

@article {pmid41646374,
year = {2026},
author = {Cropper, H and Mir, F and Liu, J and Srivastava, V and Ramizuddin, M and Kopecky, K and Mocanu, E and Dachet, F and Jiang, QL and Soni, M and Valyi-Nagy, T and Mnatsakanova, D and Abrams, C and Song, F and Loeb, J},
title = {Axonal dying back of upper motor neurons in human ALS.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-8545414/v1},
pmid = {41646374},
issn = {2693-5015},
abstract = {Patients with amyotrophic lateral sclerosis (ALS) present with arm, leg, or bulbar weakness with or without spasticity. While genetics plays a clear role in a subset of cases, it cannot explain why symptoms start focally or how upper (UMN) and lower motor neuron (LMN) systems are linked. Here, we examined the clinicopathological relationships between UMN and LMN disease in ten ALS patients. Detailed clinical assessments were obtained and tissues from the motor cortex, brainstem, and spinal cord were collected via a rapid autopsy protocol. Tissues were stained for UMN/LMN, myelin, axons, microglia, and pTDP43. Total RNA-sequencing was performed in the medulla, cervical, and lumbar spinal cords from each patient to identify pathways enriched at sites of disease onset. None of the patients had symptoms of frontotemporal dementia (FTD), but all had focal sites of clinical onset and spasticity, indicating both UMN and LMN involvement. Postmortem examination showed LMN degeneration and microglial activation were highest at sites of disease onset. In contrast, UMN degeneration of the corticospinal tract (CST) was present equally at all levels of the spinal cord up through the medulla, regardless of the site of disease onset. Surprisingly, there was no evidence of UMN degeneration of cortical motor neurons or their projecting axons above the brainstem. Similarly, while extensive pTDP43 aggregates were seen in degenerating LMNs, no pTDP43 aggregates were seen in UMN cell bodies or their axons. Mechanistically, RNA-sequencing implicated inflammatory pathways, especially at sites of disease onset. Our findings suggest that many ALS patients without FTD have a dying back of UMN axons, independent of the site of disease onset, which stops in the brainstem with preservation of cortical motor neurons and their proximal axons. Our findings suggest that UMN axonal degeneration can be directly triggered by LMN degeneration and inflammation.},
}

@article {pmid41646275,
year = {2025},
author = {Naddaf, R and Shmilovich, H and Carasso, S and Keshet-David, R and Herren, R and Gefen, T and Goshen-Lago, T and Zwang, Y and Livyatan, I and Shental, N and Haberfeld, O and Straussman, R and Markar, SR and Nilsson, M and Kashtan, H and Ben-Aharon, I and Geva-Zatorsky, N},
title = {Esophageal microbiome correlates with post-esophagectomy anastomotic leak in cancer patients.},
journal = {ESMO gastrointestinal oncology},
volume = {8},
number = {},
pages = {100172},
pmid = {41646275},
issn = {2949-8198},
abstract = {BACKGROUND: Despite continuous improvement in long-term survival after esophagectomy, potential serious post-operative complications, such as anastomotic leaks (ALs), still occur. Several risk factors for ALs have been proposed, including environmental factors. Our main objective was to examine the correlation of esophageal tumor microbiome composition and functional profile with ALs. Additionally, we analyzed the microbiome of esophageal tumors and their potential correlation with clinical features of the patients.

MATERIALS AND METHODS: Surgical specimens of esophageal tumors and adjacent normal tissues were collected from consecutive patients who underwent an esophagectomy. Formalin-fixed paraffin-embedded (FFPE) tissue samples were processed using 16S ribosomal DNA multiple fragments amplicon sequencing to characterize bacterial microbiome composition. The tumor and normal tissue microbiome and bacterial functional profile were analyzed based on the clinical outcome of ALs.

RESULTS: Out of 60 patients who met the inclusion criteria, 52 (86.7%) patients had both normal adjacent tissue (NAT) and tumor (T) FFPE samples included with sufficient bacterial DNA extracted for analysis. A total of 28% of participants had esophageal ALs. Proportion tests [P < 0.05, false discovery rate (FDR) < 0.25] revealed operational taxonomic units (OTUs) significantly present in T samples as opposed to NAT samples, as well as significantly present OTUs in patients with AL as opposed to patients without AL complication.

CONCLUSIONS: In this study, we provide a profile of the understudied esophageal microbiome and its connection to ALs. Our results can provide potential clues on how to avoid ALs by considering a patient's personal microbiome when providing perioperative care.},
}

@article {pmid41646005,
year = {2026},
author = {Peng, J and Fan, T and Wang, J and Deng, Y and Xu, R},
title = {Current potential biomarkers for Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis: review of literature.},
journal = {Dialogues in clinical neuroscience},
volume = {28},
number = {1},
pages = {17-39},
doi = {10.1080/19585969.2026.2622722},
pmid = {41646005},
issn = {1958-5969},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/blood/metabolism ; *Biomarkers/cerebrospinal fluid/blood ; *Alzheimer Disease/diagnosis/blood/metabolism/cerebrospinal fluid ; *Parkinson Disease/diagnosis/blood/metabolism/cerebrospinal fluid ; },
abstract = {INTRODUCTION: Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) are several common neurodegenerative diseases (NDs). At present, is the lack of effective diagnosis, progression, prognosis and therapeutic biomarkers. it is a urgent demand to search the relevant confident biomarkers.

AREA COVERED: This review systematically analysed the potential biomarkers of blood, cerebrospinal fluid, neuroimaing and emerging non-invasive indicators, and synthesises current evidences on the biomarkers of AD, PD and ALS about diagnosis, progression, prognosis and therapeutic, especially diagnosis biomarkers.

EXPERT COMMENTARY: In this review, we focus on discussing relevant diagnosis, progression, prognosis and therapeutic biomarkers for AD, PD and ALS in recent years, and prospecting the possible future directions of relevant biomarkers.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/blood/metabolism
*Biomarkers/cerebrospinal fluid/blood
*Alzheimer Disease/diagnosis/blood/metabolism/cerebrospinal fluid
*Parkinson Disease/diagnosis/blood/metabolism/cerebrospinal fluid

@article {pmid41645941,
year = {2026},
author = {Iammeechai, W and Srikulmontri, T and White, BAA},
title = {Emotional intelligence development in medical education: A scoping review of educational interventions.},
journal = {Medical teacher},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/0142159X.2026.2621214},
pmid = {41645941},
issn = {1466-187X},
abstract = {Background and aims: Emotional intelligence (EI) is an essential competency for physicians. Medical educators seek educational interventions to cultivate EI in their learners. This scoping review aimed to conceptualize current knowledge about educational interventions for developing EI in medical education. Methods: This study adopted the first five stages of Levac et al.'s scoping review framework, which builds on Arksey and O'Malley's scoping review methodology. The authors accessed three databases-PubMed, CINAHL, and PsycINFO-to review the literature from 2014 to February 2025. Two authors (WI and TS) independently screened the literature for eligibility. A third author (BAAW) resolved any discrepancies. Two authors (WI and BAAW) charted the eligible articles. Results: Of the 638 studies, 64 were eligible. Approximately one-third of eligible studies focused on interventions for medical students. Stress management, leadership, communication, and professionalism were key topics integrated into EI development interventions. Various methods were employed, such as small-group discussions, case-based discussions, and simulations. Most studies used self-rating questionnaires as assessment tools. Half of the studies (56.25%) reported positive impacts from their interventions. Conclusions: The findings could serve as a guide for educators and researchers seeking to implement or study such interventions.},
}

@article {pmid41645155,
year = {2026},
author = {McDonald, DW and Chugh, N and Sava, R and Duennwald, ML},
title = {FUS and TDP-43 aggregation are uncoupled from toxicity in ageing yeast models.},
journal = {BMC biology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12915-026-02537-3},
pmid = {41645155},
issn = {1741-7007},
support = {RGPIN-2024-05867//Natural Sciences and Engineering Research Council of Canada/ ; },
abstract = {BACKGROUND: Protein aggregation is indicative of the loss of proteostasis associated with neurodegenerative diseases, including Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). Proteins like Fused in sarcoma (FUS) and Tar DNA-binding protein 43 (TDP-43) accumulate and aggregate in the cytosol of neurons in ALS/FTD. Yet, it remains unclear how ageing affects FUS and TDP-43 aggregation, and how these aggregates in turn influence neurodegeneration in ALS/FTD. In addition, mistranslation can reduce longevity, challenge proteostasis, and modulate protein aggregation. To investigate how ageing and mistranslation modulate FUS and TDP-43 aggregation and toxicity, we enlist tractable and reliable yeast models.

RESULTS: Using optimized low-expression FUS and TDP-43 yeast models, we demonstrate that chronological ageing antagonizes proteostasis, the steady state levels and solubility of molecular chaperones, and aggregation of FUS and TDP-43. In addition, mistranslation caused by tRNA variants further antagonize FUS and TDP-43 aggregation and synergize to exacerbate FUS and TDP-43 cytotoxicity.

CONCLUSIONS: Our work provides new insights into factors that uncouple FUS and TDP-43 aggregation from toxicity and support a rather protective role for FUS and TDP-43 aggregates in promoting longevity.},
}

@article {pmid41643661,
year = {2026},
author = {Liu, H and Liu, M and Liu, Y and Gui, G and Paul, T and Lu, YN and Huang, Z and Wang, H and Xiao, Y and Zheng, Z and Periz, G and Shi, Y and Ichida, JK and Myong, S and Ji, H and Wang, J},
title = {C9orf72 hexanucleotide repeat RNA drives transcriptional dysregulation through genome-wide DNA:RNA hybrid G-quadruplexes.},
journal = {Neuron},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuron.2025.12.005},
pmid = {41643661},
issn = {1097-4199},
abstract = {A hexanucleotide repeat expansion in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. While repeat RNAs are implicated in disease pathogenesis, their mechanisms of action remain incompletely understood. Here, we show that GGGGCC repeat RNA engages chromatin genome-wide preferentially at promoter regions in patient cells. This interaction obstructs RNA polymerase II and transcription factors with GC-rich motifs, leading to broad transcriptional repression. Biochemical assays, single-molecule imaging, and native bisulfite sequencing analyses demonstrate that GGGGCC repeat RNA intrinsically forms DNA:RNA hybrid G-quadruplexes (HQs) with cognate DNA, providing a structural basis for transcriptional interference. Stabilization of these G-quadruplex structures exacerbates neuronal vulnerability to metabolic stress in patient-derived motor neurons and cortical organoids, whereas restoring key gene dysregulation improves resistance. These findings uncover a previously unrecognized trans-acting mechanism whereby repetitive RNAs form hybrid structures with genomic DNA, disrupt gene regulation, and contribute to neurodegeneration.},
}

@article {pmid41643607,
year = {2026},
author = {Cásedas, G and Rojas-Márquez, H and Ventura, L and Moliner, C and Maggi, F and Rubio-Castellanos, A and López, V},
title = {Involvement of Keap1/Nrf2 and the antioxidant defence in cytoprotective effects induced by cannabis polyphenols in SH-SY5Y neuronal cells.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {196},
number = {},
pages = {119048},
doi = {10.1016/j.biopha.2026.119048},
pmid = {41643607},
issn = {1950-6007},
abstract = {Oxidative stress (OS) is widely recognized as a central promoter to the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). Cannabis sativa L. synthesizes a complex array of bioactive compounds that extends well beyond the well-known cannabinoids to include a diverse suite of polyphenols, terpenes, fatty acids, tocopherols, and proteins. The non-cannabinoid polyphenolic fraction is composed primarily of flavonoids, stilbenoids, lignans, and lignanamides, which contribute substantially to the plant's antioxidant, anti-inflammatory, and neuroprotective properties. This study investigates the redox-modulating and cytoprotective properties of a polyphenolic fraction derived from Cannabis sativa L. in SH-SY5Y neuroblastoma cells. Neurons were treated with various concentrations of the aqueous polyphenolic cannabis extract and exposed to oxidative stress using hydrogen peroxide (100 µM). Protein and gene expression related to redox signalling were analyzed via Western blot and qPCR, and molecular docking studies were performed in silico. Furthermore, antioxidant enzymes activity was measured by spectrophotometry. Results revealed that the phenolic fraction significantly activated the Keap1/Nrf2 pathway, increased expression of PRDX1 and PRDX3, and enhanced endogenous antioxidant defences. Simultaneously, it reduced endoplasmic reticulum stress-induced apoptosis (via Bax/Bcl-2 modulation) and attenuated inflammatory markers, including NO, NF-κB2, IL-6, and IL-8. In silico docking studies identified Leu583 as a key residue in Nrf2-ligand interactions. These findings suggest that Cannabis sativa L. polyphenols are key bioactive compounds modulating redox homeostasis and inflammation, and offering neuroprotective benefits with potential relevance in diseases involving mitochondrial dysfunction and oxidative damage.},
}

@article {pmid41643564,
year = {2026},
author = {Ma, Z and Zheng, J and Wang, H and Chen, C and Yue, J and Duan, X and Jiang, H},
title = {A Novel Classification of Esophageal Anastomotic Leaks and Its Impact on Healing Time After Esophagogastrostomy.},
journal = {Cancer research and treatment},
volume = {},
number = {},
pages = {},
doi = {10.4143/crt.2025.1029},
pmid = {41643564},
issn = {2005-9256},
abstract = {PURPOSE: Anastomotic leakage (AL) is a severe complication after esophagogastrostomy, yet the classifications of AL and their associated healing times are poorly understood.

MATERIALS AND METHODS: This study retrospectively analyzed 117 cases of AL among 2,728 patients who underwent esophagectomy with circular stapled esophagogastric anastomosis at Tianjin Medical University Cancer Institute and Hospital from January 1, 2019, to March 31, 2024. AL cases were categorized into four types based on the direction of leakage (anterior, right, posterior, and left). The differences in healing times among these four types were analyzed using the log-rank test. A multivariable Cox model was used to identify factors associated with healing time.

RESULTS: The incidence of AL was 4.3% (117/2728), with a median occurrence time of 9 days (Interquartile Range[IQR]: 5) and a median healing time of 56 days (IQR:64). Single cervical ALs accounted for 17.5%, with significantly shorter healing times compared to intrathoracic leaks (33 days vs. 61 days, p=0.018). Right-sided leaks were the most common (49.6%), while left-sided leaks healed faster than right- and posterior-sided leaks (42 days vs. 63 days vs. 70 days, p<0.05). Body Mass Index (BMI), diabetes, and neoadjuvant therapy did not influence healing time. In 117 AL patients, the occurrence of tracheoesophageal fistula (p=0.004) and the placement of trans-fistula reverse drainage tubes (p=0.002) were associated with healing time.

CONCLUSION: These findings provide valuable insights for clinicians to better understand the mechanisms of AL development and predict the healing times.},
}

@article {pmid41643078,
year = {2026},
author = {Fernandez, R and Sívori, M},
title = {[Clinical scale of ventilatory failure risk in patients with amyotrophic lateral sclerosis].},
journal = {Medicina},
volume = {86},
number = {1},
pages = {60-72},
pmid = {41643078},
issn = {1669-9106},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/mortality/physiopathology ; Male ; Retrospective Studies ; Female ; Middle Aged ; *Hypercapnia/etiology ; *Respiratory Insufficiency/etiology/mortality ; Aged ; Risk Factors ; Risk Assessment/methods ; Prognosis ; Respiration, Artificial ; Dyspnea/etiology ; },
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that causes atrophy and paralysis of skeletal muscles, including respiratory muscles. The development of ventilatory failure determines the prognosis. The primary outcome was to determine which common clinical variables can be predictors of daytime hypercapnia and develop a risk model of ventilatory failure. Secondary outcome was to determinate the survival rate of high-risk patients with and without hypercapnia.

MATERIALS AND METHODS: Retrospective study. Patients with ALS without mechanical ventilation were selected and followed from June 2015 to May 2024. They underwent arterial blood carbon dioxide measurement and classified into two groups: hypercapnic (pCO2 ≥45 mmHg) and normocapnic (pCO2 <45 mmHg). Different predictive models for hypercapnia were constructed.

RESULTS: An association between orthopnea (p=0.0001), dyspnea (p=0.02) and FVC <50% (p=0.04) was found. The predictive model constructed with the following variables: orthopnea, dyspnea and ALSFRS-R score ≤21, presented a good performance on the detection hypercapnia risk. A score > 23 points had a sensitivity of 80.6% and a specificity of 72.8% for detecting patients at high risk of hypercapnia. Normocapnic patients at high risk who start mechanical ventilation before developing hypercapnia improve their survival rate by 6 months (p=0.17).

DISCUSSION: The risk score includes easily obtained clinical variables and is effective in detecting patients at risk for hypercapnia. Initiating mechanical ventilation in at-risk patients who have not yet developed hypercapnia has a clinically significant impact on survival.},
}

Humans
*Amyotrophic Lateral Sclerosis/complications/mortality/physiopathology
Male
Retrospective Studies
Female
Middle Aged
*Hypercapnia/etiology
*Respiratory Insufficiency/etiology/mortality
Aged
Risk Factors
Risk Assessment/methods
Prognosis
Respiration, Artificial
Dyspnea/etiology

@article {pmid41643021,
year = {2026},
author = {Jiang, X and Schaeffer, L and Patni, D and Russo, T and Lee, CZ and Aguilar, C and Marques, C and Jansen-West, K and Hruska-Plochan, M and Ray-Soni, A and Lim, SM and Held, A and Yue, M and Castellanos Otero, P and Aryal, S and Beaussant, HDAM and Basu, H and Takakuwa, H and Daughrity, LM and Ramesh, N and Da Costa, P and A A Quadros, AR and Nolan, M and Reyes, CJF and Wheeler, H and Moran, LC and Griesman, G and Wymann, B and Trombetta, BA and Lopez-De-Silanes, ES and Canori, M and Krishnan, G and Vieira Souza Da Silva, Y and Eriani, G and Albers, MW and Arnold, SE and Song, Y and Jain, A and Chiu, IM and Zhang, YJ and Gao, FB and Wainger, BJ and Polymenidou, M and Petrucelli, L and Martin, F and Lagier-Tourenne, C},
title = {Blocking RAN translation without altering repeat RNAs rescues C9ORF72-related ALS and FTD phenotypes.},
journal = {Science (New York, N.Y.)},
volume = {391},
number = {6785},
pages = {eadv2600},
doi = {10.1126/science.adv2600},
pmid = {41643021},
issn = {1095-9203},
mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology/therapy ; *Frontotemporal Dementia/genetics/pathology/therapy ; *C9orf72 Protein/genetics ; Animals ; Mice ; Humans ; *Protein Biosynthesis ; DNA Repeat Expansion ; Phenotype ; Induced Pluripotent Stem Cells ; Motor Neurons/pathology ; DNA-Binding Proteins/metabolism ; *RNA/genetics/metabolism ; Disease Models, Animal ; *ran GTP-Binding Protein/genetics ; Dipeptides/genetics ; Codon ; Mutation ; },
abstract = {GGGGCC (G4C2) repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Toxicity is thought to result from the accumulation of either repeat RNAs and/or dipeptide repeat proteins (DPRs) translated from repeat-containing transcripts through repeat-associated non-AUG (RAN) translation. To disentangle RNA from DPR toxicity, we mutated a CUG codon predominantly used to initiate DPR translation from all three reading frames. This mutation disrupted DPR synthesis while preserving the expression of repeat-containing RNAs. Despite the accumulation of RNA foci, behavioral deficits and pathological abnormalities, including p-TDP-43 inclusions, STING activation, motor neuron loss, neuroinflammation, and increased plasma neurofilament concentration, were alleviated in C9ORF72 mice. Base editing of the CUG codon also improved molecular phenotypes and survival in patient induced pluripotent stem cell-derived neurons, which highlights the potential of therapeutically targeting DPR production rather than repeat RNAs.},
}

*Amyotrophic Lateral Sclerosis/genetics/pathology/therapy
*Frontotemporal Dementia/genetics/pathology/therapy
*C9orf72 Protein/genetics
Animals
Mice
Humans
*Protein Biosynthesis
DNA Repeat Expansion
Phenotype
Induced Pluripotent Stem Cells
Motor Neurons/pathology
DNA-Binding Proteins/metabolism
*RNA/genetics/metabolism
Disease Models, Animal
*ran GTP-Binding Protein/genetics
Dipeptides/genetics
Codon
Mutation

@article {pmid41642988,
year = {2026},
author = {Wells, TL and Galani, M and Popoli, R and Zagoraiou, L and Akay, T},
title = {Compensatory scaling of modulatory neural populations in response to motor challenges.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {6},
pages = {e2519741123},
doi = {10.1073/pnas.2519741123},
pmid = {41642988},
issn = {1091-6490},
mesh = {Animals ; Mice ; *Motor Neurons/physiology/metabolism ; *Interneurons/physiology/metabolism ; Spinal Cord/physiology/metabolism ; Serotonin/metabolism ; Brain Stem/physiology/metabolism ; Muscle, Skeletal/physiology ; Locomotion/physiology ; Cholinergic Neurons/physiology/metabolism ; Male ; Electromyography ; },
abstract = {Precise and adaptable movements are achieved by well-regulated muscle contractions, which are mainly governed by the excitability of motor neurons. Several neuromodulatory systems originating in the motor cortex, brainstem, and spinal cord regulate motor neuron excitability via the release of neurotransmitters such as acetylcholine and serotonin. However, these systems can have seemingly similar effects on motor neuron output, raising questions about interaction during movement. To address this, we investigated two modulatory systems in mice: the cholinergic V0c interneurons in the spinal cord and the serotonergic system in the brainstem. Electromyographic and behavioral recordings revealed that, when compared to control mice, mice whose V0c interneuron cholinergic output was genetically inactivated failed to display speed-dependent modulation of the gastrocnemius muscle, and exhibited lower amplitude bursting in the gastrocnemius muscle during swimming. c-Fos expression in this population during locomotion also indicated that they are active in a speed-dependent manner. Relative to control mice, those mice whose V0c interneurons had their cholinergic output inactivated showed upregulated activity in motor-related serotonergic populations while trotting at higher speeds but not while walking at lower speeds, indicating that serotonin plays a compensatory role in the absence of functional V0c interneurons. Last, we observed a progressive recruitment of these two populations in mice with amyotrophic lateral sclerosis, and the recruitment of serotonergic neurons is hastened in those mice whose V0c interneurons had their cholinergic output inactivated. These findings highlight that modulatory systems scale their activity to match motor demand across various circumstances.},
}

Animals
Mice
*Motor Neurons/physiology/metabolism
*Interneurons/physiology/metabolism
Spinal Cord/physiology/metabolism
Serotonin/metabolism
Brain Stem/physiology/metabolism
Muscle, Skeletal/physiology
Locomotion/physiology
Cholinergic Neurons/physiology/metabolism
Male
Electromyography

@article {pmid41642483,
year = {2026},
author = {Alhajeri, MM and Abukhaled, Y and Alkhanjari, RR and Bassiouni, W and Al-Ali, H and Baig, A and Sembaij, SH and Al Muhairi, FA and Dimassi, Z and Hamdan, H and Abd-Elrahman, KS},
title = {Neuroglial Function and Hormonal Modulation in Neurodegenerative Diseases: The Influence of Sex Hormones.},
journal = {Cellular and molecular neurobiology},
volume = {},
number = {},
pages = {},
doi = {10.1007/s10571-026-01674-1},
pmid = {41642483},
issn = {1573-6830},
abstract = {Astrocytes, microglia, and oligodendrocytes, key neuroglial cell types, are essential for central nervous system (CNS) homeostasis, immune regulation, and neuronal support. In neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), glial dysfunction contributes to pathogenesis via chronic inflammation, synaptic disruption, oxidative stress, and impaired myelination. Growing evidence highlights the regulatory influence of sex hormones on glial function. These hormones modulate inflammatory tone, synaptic remodeling, and remyelination, potentially contributing to sex-based differences in disease incidence, progression, and treatment response. This review synthesizes current understanding of glial involvement in neurodegeneration and examines how gonadal hormones interact with astrocytes, microglia, and oligodendrocytes. By integrating glial biology with neuroendocrinology, we propose that hormone-glia interactions represent promising, personalized targets for sex-informed therapies in CNS disorders.},
}

@article {pmid41642424,
year = {2026},
author = {Sun, Y and Huang, C and Pan, Y and Zhang, H and He, X},
title = {Correction: Muscle Fibrosis in Amyotrophic Lateral Sclerosis: Molecular Mechanisms, Diagnostic Advances, and Therapeutic Strategies.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {418},
doi = {10.1007/s12035-026-05721-2},
pmid = {41642424},
issn = {1559-1182},
}

@article {pmid41641857,
year = {2026},
author = {Marcinkowska, K and Wrzesińska-Krupa, B and Obrępalska-Stęplowska, A},
title = {Insights Into Sequences of Viral and Bacterial Origin in the Metatranscriptome of Centaurea cyanus L. Susceptible and Resistant to Acetolactate Synthase (ALS)-Inhibiting Herbicides.},
journal = {Environmental microbiology reports},
volume = {18},
number = {1},
pages = {e70287},
doi = {10.1111/1758-2229.70287},
pmid = {41641857},
issn = {1758-2229},
support = {2020/04/X/NZ9/01767//National Science Centre/ ; },
mesh = {*Herbicides/pharmacology ; *Acetolactate Synthase/antagonists & inhibitors ; *Bacteria/genetics/classification/isolation & purification/drug effects ; *Herbicide Resistance ; *Centaurea/microbiology/virology ; Arylsulfonates/pharmacology ; Transcriptome ; Poland ; Plant Weeds/virology/microbiology ; *Plant Viruses/genetics/classification/isolation & purification ; Phylogeny ; },
abstract = {Cornflower (Centaurea cyanus L.) is a widespread weed in cereal crops and is commonly controlled with sulfonylurea herbicides. In Poland, populations of cornflower resistant to acetolactate synthase inhibiting herbicides, such as tribenuron-methyl, have been increasingly reported. Both target-site and non-target-site resistance mechanisms may contribute to this phenomenon. Plant-associated microorganisms are known to play essential roles in alleviating abiotic stress. Moreover, weeds are considered reservoirs of plant pathogenic viruses. Since bacteria and viruses associated with cornflower have not been analysed to date, data mining was undertaken to identify viral and bacterial sequences in metatranscriptome datasets obtained from plant biotypes that are both susceptible and highly resistant to tribenuron-methyl. Using MEGAN6 and Kraken2, taxonomic classification revealed the presence of sequences of two double-stranded RNA viruses belonging to the family Partitiviridae, which have not been described before. For bacterial sequences, 19 genera were identified, including Bacillus, Mesorhizobium and Acinetobacter, some of which are associated with plant growth promotion or xenobiotic degradation. Although the presence of partitiviruses was unrelated to herbicide resistance status, some bacterial genera (e.g., Rothia) were more abundant in resistant than in susceptible plants. These results suggest that those bacterial genera present in weeds may be involved in counteracting ALS-inhibiting herbicides.},
}

*Herbicides/pharmacology
*Acetolactate Synthase/antagonists & inhibitors
*Bacteria/genetics/classification/isolation & purification/drug effects
*Herbicide Resistance
*Centaurea/microbiology/virology
Arylsulfonates/pharmacology
Transcriptome
Poland
Plant Weeds/virology/microbiology
*Plant Viruses/genetics/classification/isolation & purification
Phylogeny

@article {pmid41641779,
year = {2026},
author = {Varderidou-Minasian, S and Jakobs, CE and Pasteuning-Vuhman, S and Gal, L and Timmers, A and Altelaar, M and Lorenowicz, MJ and Pasterkamp, RJ},
title = {Mesenchymal stem cell-derived extracellular vesicle treatment of induced pluripotent stem cell-derived motor neurons with different amyotrophic lateral sclerosis genetic backgrounds.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-01790},
pmid = {41641779},
issn = {1673-5374},
abstract = {Motor neurons derived from induced human pluripotent stem cells offer a powerful model to study motor neuron diseases, such as amyotrophic lateral sclerosis. While widely used, our knowledge of the proteomic changes in these models is rather rudimentary. In this study, we conducted a comparative proteomic analysis of induced pluripotent stem cell-derived motor neurons carrying amyotrophic lateral sclerosis-associated mutations in C9ORF72, TARDBP, or FUS. This revealed both mutation-specific and shared proteomic signatures, unveiling common and divergent disease mechanisms. Using these new insights, we then evaluated the therapeutic potential of mesenchymal stem cell-derived extracellular vesicles. These experiments showed a functional effect of mesenchymal stem cell-derived extracellular vesicles in amyotrophic lateral sclerosis-FUS motor neurons in vitro and their ability to reverse proteomic changes more generally in motor neurons with different amyotrophic lateral sclerosis genetic backgrounds. These findings highlight key molecular pathways involved in amyotrophic lateral sclerosis at the protein level and support the potential of mesenchymal stem cell-derived extracellular vesicles as a versatile therapeutic approach.},
}

@article {pmid41641215,
year = {2026},
author = {Zhang, Y and Wang, JJ and Xing, HY and Yan, J},
title = {Neurofeedback for autism spectrum disorder: Current evidence, challenges, and future directions.},
journal = {World journal of psychiatry},
volume = {16},
number = {2},
pages = {114358},
pmid = {41641215},
issn = {2220-3206},
abstract = {Neurofeedback therapy (NFT) has emerged as a promising noninvasive intervention for autism spectrum disorder (ASD), targeting core symptoms such as social communication deficits and emotional dysregulation. This editorial synthesizes findings from recent studies, including Wang et al's retrospective analysis (2025), which reported improvements in Social Responsiveness Scale and Aberrant Behavior Checklist scores following NFT combined with conventional therapy. Mechanistically, NFT may modulate prefrontal gamma-band activity, enhances neuroplasticity in social brain networks (e.g., default mode network, a brain network involved in social cognition), and optimizes cognitive processing via event-related potential changes (e.g., shortened P300 latency). Emerging trends include hybrid approaches (e.g., NFT with repetitive transcranial magnetic stimulation and artificial intelligence-driven protocols). However, challenges persist in protocol standardization, long-term efficacy validation, and biomarker identification. Future research must prioritize large-scale randomized trials, neuromarker discovery, and individualized protocols to establish NFT as a viable component of precision psychiatry for ASD.},
}

@article {pmid41640951,
year = {2026},
author = {Cui, X and Yin, BQ and Chen, L},
title = {Remote telerehabilitation for frailty management in liver transplant candidates: A feasible yet underutilized strategy.},
journal = {World journal of hepatology},
volume = {18},
number = {1},
pages = {114880},
pmid = {41640951},
issn = {1948-5182},
abstract = {This letter reviews Loschi et al's study evaluating structured telerehabilitation for frail cirrhotic liver transplant candidates, which fills a critical pre-transplant care gap. The video-based program, using low-cost tools and asynchronous sessions, improved liver frailty index reduction and function in adherent patients (29.8%) although a high attrition rate (70%) highlighted engagement challenges. Limitations include a small, non-randomized sample, mixed frailty subgroups, and unexplored long-term effects. Future directions emphasize hybrid models, patient-centered barrier analysis, and policy-driven frailty screening. This work advances digital health for cirrhosis; however, larger trials are needed to optimize outcomes.},
}

@article {pmid41640615,
year = {2026},
author = {Wang, G and Pan, SJ},
title = {Integrative acupoint stimulation within enhanced recovery after endoscopic procedures: Harnessing the neuroimmune axis for enhanced gastrointestinal recovery.},
journal = {World journal of gastroenterology},
volume = {32},
number = {3},
pages = {114048},
pmid = {41640615},
issn = {2219-2840},
mesh = {Humans ; *Acupuncture Points ; Recovery of Function ; *Enhanced Recovery After Surgery ; *Gastrointestinal Tract/innervation/surgery/immunology ; Neuroimmunomodulation ; Randomized Controlled Trials as Topic ; *Perioperative Care/methods ; Hypothalamo-Hypophyseal System/immunology ; *Transcutaneous Electric Nerve Stimulation/methods ; Pituitary-Adrenal System ; *Endoscopy, Gastrointestinal/adverse effects ; Treatment Outcome ; },
abstract = {Enhanced recovery after surgery (ERAS) programs have transformed perioperative care, yet delayed gastrointestinal function and excessive neuroendocrine stress remain major obstacles to optimal recovery. Hong et al's randomized controlled trial embedded acupoint-based neuromodulation - meridian-timed acupoint application combined with transcutaneous electrical acupoint stimulation - within an ERAS framework and demonstrated accelerated gastrointestinal recovery accompanied by endocrine attenuation. This article offers a structured critical appraisal of the trial, emphasizing methodological rigor, mechanistic plausibility, and alignment with ERAS core principles of stress mitigation, functional restoration, and patient experience. The observed reductions in norepinephrine, cortisol, and aldosterone suggest modulation of the hypothalamic-pituitary-adrenal axis as a key mediator of benefit. Future research priorities include multicenter, sham-controlled validation; integration of autonomic and inflammatory biomarkers (heart rate variability, interleukin-6, tumor necrosis factor-α, C-reactive protein); and pragmatic evaluation of cost-effectiveness and acceptability. Positioning acupoint stimulation within precision-integrative perioperative care could advance ERAS from a recovery protocol to a system of host-response modulation. Integrative acupoint neuromodulation thus represents a biologically coherent, low-risk, and scalable strategy for enhancing resilience, accelerating gastrointestinal recovery, and improving surgical outcomes worldwide.},
}

Humans
*Acupuncture Points
Recovery of Function
*Enhanced Recovery After Surgery
*Gastrointestinal Tract/innervation/surgery/immunology
Neuroimmunomodulation
Randomized Controlled Trials as Topic
*Perioperative Care/methods
Hypothalamo-Hypophyseal System/immunology
*Transcutaneous Electric Nerve Stimulation/methods
Pituitary-Adrenal System
*Endoscopy, Gastrointestinal/adverse effects
Treatment Outcome

@article {pmid41640493,
year = {2025},
author = {Li, SC},
title = {Evolving target: A 16-year progressive framework for shifting the rubric of scientific publishing toward transparency, artificial intelligence, and the Economic Impact Factor for impact that matters.},
journal = {World journal of stem cells},
volume = {17},
number = {12},
pages = {111748},
pmid = {41640493},
issn = {1948-0210},
abstract = {Reflecting on 16 years of continuous evolution at the World Journal of Stem Cells, this editorial offers a forward-looking vision for redefining the framework of scientific publishing. With the emergence of artificial intelligence, open science, and the growing need for translational value, we propose shifting from traditional citation-based assessments toward an impact and progress framework, anchored by the Economic Impact Factor. The World Journal of Stem Cells experience, grounded in metrics and milestones, supports this evolution: Among the more than 1200 published articles since inception, our top 10 cited works have collectively accrued over 2475 citations, led by Kyurkchiev et al (398 citations) and Casteilla et al (392 citations). Emerging scholars such as Ann De Becker and Nipha Chaicharoenaudomrung have shaped the next generation of research, as seen in our top 10 junior authors table. Clinically, World Journal of Stem Cells has supported critical translational work, such as Tsang et al's mesenchymal stem cell stroke trial (27 citations), illustrating real-world impact. Thematic breadth remains a cornerstone, with 22 focus areas including artificial intelligence-integrated programming, spatial single-cell biology, CRISPR-based gene editing, and bench-to-bedside translation. As Nature and other leading publishers move toward transparent peer review, World Journal of Stem Cells embraces editorial co-creation, recognizing peer reviewers and editors as contributors with "10000-foot eagle views" by publishing peer-review reports side-by-side with the related manuscripts since its inception. Together, these shifts signify a call to recalibrate what we value in science - not just what is cited, but what truly counts.},
}

@article {pmid41640104,
year = {2026},
author = {Karros, M and DiFulco, M and Nogid, A},
title = {Tofersen: A Novel Option for the Treatment of Amyotrophic Lateral Sclerosis.},
journal = {The Annals of pharmacotherapy},
volume = {},
number = {},
pages = {10600280251408862},
doi = {10.1177/10600280251408862},
pmid = {41640104},
issn = {1542-6270},
abstract = {OBJECTIVE: This review summarizes current evidence on the efficacy and safety of tofersen (Qalsody) in treating amyotrophic lateral sclerosis (ALS).

DATA SOURCES: PubMed, MEDLINE, Google Scholar, and ClinicalTrials.gov were searched using the keywords: Qalsody, BIIB067, antisense oligonucleotides, SOD1, and amyotrophic lateral sclerosis. Articles published from inception to November 2025 were included.

English-language studies assessing the pharmacokinetics, pharmacology, efficacy, and safety of tofersen were included. Prescribing information and real-world evidence were also reviewed.

DATA SYNTHESIS: Tofersen is an intrathecally administered antisense oligonucleotide targeting superoxide dismutase 1 (SOD1) mRNA. Early trials demonstrate dose-dependent reductions in cerebrospinal fluid (CSF) SOD1 protein levels of -33% and slower ALS Functional Rating Scale (ALSFRS-R) decline compared to placebo (-1.19 vs -5.63 points). In Phase 3 trials, tofersen reduced CSF SOD1 by 29% and plasma neurofilament light chain (NfL) by 60%, while biomarkers increased in the placebo group. There was no significant difference in ALSFRS-R decline between tofersen and placebo (-6.98 vs -8.14; P = 0.97). Real-world data show favorable patient-related outcomes and improvement in ALSFRS-R. Adverse effects are primarily lumbar puncture related with serious neurologic events documented in 7% of tofersen recipients.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:As the first Food and Drug Administration (FDA)-approved gene-directed therapy for SOD1 ALS, tofersen directly targets the underlying genetic cause. Barriers include the need for genetic confirmation and intrathecal administration.

CONCLUSION: Tofersen provides a promising targeted treatment option for pathogenic SOD1 ALS. Ongoing studies will clarify its long-term clinical impact.},
}

@article {pmid41640102,
year = {2026},
author = {Ross, D and Lewis, O and McLean, O and Bhanot, S and Donahue, S and Baker, R and Dias, R and Eagerton, D and Mohanty, V and Mohanty, BK},
title = {Thermally activated history-dependent homogenization of G-quadruplexes in an ALS/FTD-associated gene.},
journal = {Biophysical journal},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.bpj.2026.01.054},
pmid = {41640102},
issn = {1542-0086},
abstract = {A significant proportion of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) cases exhibit a substantial copy number expansion of the hexanucleotide GGGGCC/GGCCCC sequence in the C9ORF72 gene. The GGGGCC sequence forms a non-canonical DNA structure called a G-quadruplex (G4) which has been associated with the disease states and with nucleic acid condensate formation. G4s can fold into various topologies, which can differentially impact fidelity of DNA synthesis. However, how G4 conformational heterogeneity and its regulation impact hexanucleotide repeat expansion is unclear, and important clues may lie in the thermodynamic properties of different G4 topologies. Here, we use temperature-swept CD spectroscopy to observe configurational homogenization of an initially heterogeneous population of G4s over a small range of temperatures, demonstrating thermally activated behavior. The G4s adopt the parallel configuration after the temperature sweep, and subsequent temperature sweeps show little to no reversal back to non-parallel topologies, suggesting the homogenization is history-dependent. Finally, we provide an analytical theory based on a two-state thermodynamic model which is compatible with experimental evidence, and we discuss alternate mechanisms for the homogenization transition. These findings suggest that kinetic regulation of non-canonical DNA structures may play a role in cellular homeostasis or disease pathogenesis.},
}

@article {pmid41639687,
year = {2026},
author = {Zhang, N and Su, WM and Chen, T and Zhang, Q and Cao, B and Wang, Y and Chen, YP},
title = {From pathogenesis to therapy: the emerging role of regulatory T cells in amyotrophic lateral sclerosis.},
journal = {Journal of neuroinflammation},
volume = {23},
number = {1},
pages = {50},
pmid = {41639687},
issn = {1742-2094},
support = {82371422//National Natural Science Fund of China/ ; 2022YFC2703101//National Key Research and Development Program of China/ ; 2023HXFH032//1·3·5 project for disciplines of excellence Clinical Research Fund, West China Hospital, Sichuan University/ ; },
}

@article {pmid41639347,
year = {2026},
author = {Tosi, M and Favero, F and Zuccalà, M and Visha, E and Caushi, F and Barizzone, N and Pomella, N and Follia, L and Corrado, L and Corà, D and Martignetti, L and Leone, M and D'Alfonso, S},
title = {A multi-omics study on monozygotic twins discordant for amyotrophic lateral sclerosis and literature review underline a potential role for innate immunity and epigenetic dysregulation in disease mechanisms.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {3},
pages = {230},
pmid = {41639347},
issn = {1590-3478},
support = {DIG-ALS//AriSLA/ ; PRIN project GENIALS//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron degeneration. Although genetic contributions to both familial and sporadic ALS (sALS) cases are well established, a substantial portion of ALS heritability remains unexplained, suggesting the involvement of other genetic and epigenetic factors.

METHODS: To address this gap, we have devised a comprehensive multi-omics approach in a pair of Italian monozygotic twins discordant for ALS, performing DNA methylation, transcriptomic, and whole exome sequencing (WES). We then conducted a structured literature research on ALS-discordant monozygotic twins (n = 45) and on case-control sALS (~ 7000 patients and ~ 3000 controls), investigated for at least one of the omics approaches.

RESULTS: Our exploratory analysis reveals distinct transcriptomic and epigenetic profiles underlying the discordant disease phenotypes in genetically identical individuals, particularly implicating immune system functions and brain development pathways. Notably, a comprehensive comparison of our results with existing literature underlined the involvement of pathways related to NK cell activation, chemokine production, and signal transduction, suggesting potential shared disease associated mechanisms across ALS cases.

CONCLUSIONS: This hypothesis-generating study, although limited by the sample size, demonstrates the utility of multi-omics approaches in uncovering broader pathological insights into ALS, speculating on the possible contribution of innate immunity and epigenetic dysregulation in disease processes. This work provides a foundation for future research aimed at identifying disease-associated processes and biomarkers.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10072-026-08813-y.},
}

@article {pmid41639245,
year = {2026},
author = {Fernandes, AR and Owen, AP and Faroqi, AH and Lee, J and Sachdeva, GS and Morderer, D and Hoffmann, C and Madden, B and Zhang, S and Ren, Y and Boschen, SL and Pandey, A and Rossoll, W and McLean, PJ},
title = {A split biotin ligase approach reveals proteins associated with oligomeric alpha-synuclein during aggregation.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-37551-6},
pmid = {41639245},
issn = {2045-2322},
support = {U01CA271410/BC/NCI NIH HHS/United States ; RF1AG076122/GF/NIH HHS/United States ; A2021615S//BrightFocus Foundation/ ; 23A04//Florida Department of Health Ed and Ethel Moore Alzheimer's Disease Research Grant/ ; 024079//Michael J. Fox Foundation for Parkinson's Research/ ; 24A10//Florida Department of Health Ed and Ethel Moore AD Research Program/ ; U54 NS110435/NS/NINDS NIH HHS/United States ; APDA#11-08//Mayo Clinic American Parkinson's Disease Association Center for Advanced Research/ ; },
abstract = {Lewy pathology can form over decades in patients with Lewy body diseases, but the causal cellular mechanisms associated with this process remain unclear. This project aims to discover proteins that associate with monomeric and/or oligomeric alpha-synuclein during early stages of the aggregation process. To mimic aggregation processes, cells expressing a synuclein-biotin ligase fusion protein were treated with human recombinant pre-formed fibrils and subjected to BioSITe and mass spectrometry. Using a novel split biotin ligase fused to alpha-synuclein facilitated the identification of proteins specifically associated with multimeric alpha-synuclein. A total of 581 proteins were differentiated into potential interactors of monomeric versus multimeric alpha-synuclein in physiological versus aggregated conditions. The data reveal potentially relevant phosphorylation mechanisms, connections to insulin processing, and a potential interaction with ALS/FTD-associated FUS. Interestingly, we propose that loss of specific interactions may contribute to pathology in patients with sporadic onset of Lewy body diseases. Future studies will validate both true interaction of highlighted proteins with alpha-synuclein, and the impact of such proteins on alpha-synuclein aggregation.},
}

@article {pmid41639167,
year = {2026},
author = {Jansén-Storbacka, LR and Honasoge, KS and Molnárová, E and Soboleva, A and Agema, BC and Paats, MS and Moes, DJAR and Veerman, GDM and Barbaro, ABT and Dobbe, R and Grossmann, I and Azimi, S and Mathijssen, RHJ and Dingemans, AC and Staňková, K},
title = {Can evolutionary therapy be applied in non-small cell lung cancer?.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-36712-x},
pmid = {41639167},
issn = {2045-2322},
support = {VI.Vidi.213.139//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 955708//European Commission/ ; },
abstract = {Evolutionary therapy (ET) applies principles of evolutionary biology to steer tumour dynamics and forestall or delay treatment resistance, typically guided by data-driven mathematical models. Our aim is to assess whether ET protocols, and specifically Zhang et al.'s protocol proposed for metastatic castrate-resistant prostate cancer, can be theoretically effective for fast-growing metastatic cancers such as stage IV non-small-cell lung cancer (NSCLC). Using longitudinal tumour-burden data from NSCLC patients treated with erlotinib, we systematically evaluate 26 two-population differential-equation models based on classical tumour-growth dynamics, with varying assumptions about density- and frequency-dependent interactions, pharmacokinetics, and treatment-induced death. Previous work by Yin et al. on the same dataset employed an exponential model that omitted density- and frequency-dependent interactions; although it provided a good fit to tumour-burden data, its structure would theoretically lead to poorer outcomes under ET protocols. In contrast, our analysis identifies the minimal model structure required to reproduce the resistance-driven regrowth observed in NSCLC, with the Gompertzian model featuring log-kill dynamics and both density- and frequency-dependent interactions providing the best fit. In this model, Zhang et al.'s protocol prolonged median time-to-progression to 42.3 months compared with 24.8 months under maximum tolerated dose. These results indicate that ET is theoretically a viable treatment strategy for NSCLC. This study offers a practical framework for assessing ET feasibility using clinical data and supports future clinical translation of ET in NSCLC.},
}

@article {pmid41638908,
year = {2026},
author = {Villarroel-Campos, D and Vargas, JNS and Wallace, M and Sun, K and Sleigh, JN and Fratta, P and Schiavo, G},
title = {TBK1 activity regulates the directionality of axonal transport of signalling endosomes.},
journal = {Life science alliance},
volume = {9},
number = {4},
pages = {},
pmid = {41638908},
issn = {2575-1077},
mesh = {*Protein Serine-Threonine Kinases/metabolism/genetics ; *Endosomes/metabolism ; *Axonal Transport/physiology ; Humans ; Signal Transduction ; Phosphorylation ; Animals ; rab GTP-Binding Proteins/metabolism/genetics ; rab7 GTP-Binding Proteins ; Amyotrophic Lateral Sclerosis/metabolism ; Mice ; Axons/metabolism ; Motor Neurons/metabolism ; Lysosomes/metabolism ; Protein Transport ; Neurons/metabolism ; },
abstract = {The polarised and complex morphology of neurons poses massive challenges for efficient cargo delivery between the axon and soma, a process termed axonal transport. We have previously shown that the retrograde axonal transport of pro-survival, neurotrophic signalling endosomes relies on Rab7 in motor neurons, and that their trafficking is impaired in the early stages of amyotrophic lateral sclerosis (ALS) pathogenesis. Here, we report the effect of Rab7 phosphorylation on the transport of these signalling endosomes. We show that the ALS-linked kinase TBK1 phosphorylates Rab7 at S72 in neurons, altering its binding to cytoplasmic dynein adaptors. Accordingly, both TBK1 knockdown and the expression of a loss-of-function Rab7 mutant (S72E) induce aberrant bidirectional movement of signalling endosomes without modifying neuronal polarity or endosomal sorting. This alteration is specific for signalling endosomes, as axonal transport of lysosomes and mitochondria remains unaffected. We have therefore discovered a new TBK1 function that ensures the unidirectional transport of signalling endosomes, suggesting that reduced TBK1 activity determines retrograde transport dysfunctions and long-range signalling impairments.},
}

*Protein Serine-Threonine Kinases/metabolism/genetics
*Endosomes/metabolism
*Axonal Transport/physiology
Humans
Signal Transduction
Phosphorylation
Animals
rab GTP-Binding Proteins/metabolism/genetics
rab7 GTP-Binding Proteins
Amyotrophic Lateral Sclerosis/metabolism
Mice
Axons/metabolism
Motor Neurons/metabolism
Lysosomes/metabolism
Protein Transport
Neurons/metabolism

@article {pmid41638429,
year = {2026},
author = {Madsen, M and Rønne, ME and Petersen, AB and Tandrup, T and Pilgaard, B and Holck, J and Aachmann, FL and Wilkens, C and Klau, LJ and Svensson, B},
title = {Dissecting a two-domain alginate lyase of family PL6 reveals a mechanistic basis for substrate specificity and enzyme activity.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {111227},
doi = {10.1016/j.jbc.2026.111227},
pmid = {41638429},
issn = {1083-351X},
abstract = {Alginate lyases (ALs) cleave 4-O-glycosidic linkages in alginate, composed of mannuronate (M) and guluronate (G) residues via β-elimination with preference for either one or several M-M, M-G, G-M, G-G linkages. ALs in polysaccharide lyase family 6 (PL6), present different specificities and modes of action, contain either one or two parallel β-helix domains. About half of almost 600 PL6 sequences are of the two-domain type, all located in the phyla Pseudomonadota and Bacteroidota. Here, functional roles are described for the N- and C-terminal domains (NTD and CTD) using BoPL6, a two-domain AL from the human gut bacterium Bacteroides ovatus CP926, which is specific for G in subsite +1. The NTD contains the catalytic site, but BoPL6-NTD markedly preferred the model substrate polyMG and cleaved M-G bonds in endo-mode, whereas the NTD + CTD mixture, similarly to BoPL6, acted with highest activity on model substrate polyG in exo-mode, verified by time-resolved [1]H-NMR. CTD was not catalytically active but bound polyguluronate and, when mixed with BoPL6-NTD, promoted activity on polyG, yielding products of DP 1‒3, similarly to BoPL6. This defines a crucial role of CTD in shaping the active site in BoPL6, as validated by substrate docking. The BoPL6 E634A mutant in the conserved CTD DEST loop, interacting with the active site in two-domain PL6 enzymes, was inactive, while the corresponding CTD mutant mixed with the NTD did not form the WT structure and had highly reduced activity on polyG, but acted on polyMG in endo-mode with improved rate and conversion.},
}

@article {pmid41638255,
year = {2026},
author = {Yeh, CH and Chen, SC},
title = {Comments on Huang et al.'s "Proteomic profiling reveals distinct inflammatory and neurogenic endotypes in rosacea".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.12.114},
pmid = {41638255},
issn = {1097-6787},
}

@article {pmid41637622,
year = {2026},
author = {Du, C and Li, Y and Wu, R and Shen, Y and Yang, J and Xiao, X and Zhou, Y},
title = {Aberrant Splicing Signatures Underpin Oligodendrocyte Damage in ALS and Neuron Loss in FTD.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e14886},
doi = {10.1002/advs.202514886},
pmid = {41637622},
issn = {2198-3844},
support = {2023YFC2307802//National Key R&D Program of China/ ; 2042022dx0003//Fundamental Research Funds for the Central Universities/ ; 2025AFA051//Hubei Provincial Natural Science Foundation of China/ ; 2023AFB182//Hubei Provincial Natural Science Foundation of China/ ; 2023KFZZ007//Open Project of Hubei Key Laboratory/ ; 32525018//National Natural Science Foundation of China/ ; 82341023//National Natural Science Foundation of China/ ; 324B2009//National Natural Science Foundation of China/ ; 82401650//National Natural Science Foundation of China/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two severe diseases sharing similar genetic, pathological, and clinical features, including TDP-43 pathology. However, differences in molecular changes between ALS and FTD remain elusive. Here, integrating large sets of bulk and single-nucleus RNA-seq from ALS/FTD patients revealed expression and splicing changes indicating more severe oligodendrocyte damage in ALS than FTD, and more significant neuron loss in FTD. Specifically, we identified 31 oligodendrocyte-specific and 507 neuron-specific aberrant splicing junctions as potential biomarkers with robust classification performance, and experimentally validated a novel target in patient tissues. Moreover, we found that abnormally spliced transcripts produced de novo peptides in patients' cerebrospinal fluids. Importantly, we further identified the targets of TDP-43 in glial cells and decoded the differential RNA-binding protein (RBP) contexts of TDP-43-regulated aberrant splicing. These findings uncover that ALS and FTD patients have distinct dysfunctional cell populations harboring specific aberrant splicing signatures, suggesting varying cellular impacts and providing potential biomarkers and insights into molecular mechanisms underlying ALS/FTD.},
}

@article {pmid41635876,
year = {2025},
author = {Elsawah, HK and Elmarawany, MN},
title = {Letter regarding Pereira et al.'s SAH-VP score: Methodological and statistical considerations.},
journal = {Brain & spine},
volume = {5},
number = {},
pages = {104294},
pmid = {41635876},
issn = {2772-5294},
}

@article {pmid41635251,
year = {2026},
author = {Li, X and Ding, W and Lu, Y and Sun, M and Xu, E},
title = {Nocturnal Hypoxia and Sleep-Disordered Breathing as Potential Early Biomarkers of Respiratory Progression in Mild ALS.},
journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques},
volume = {},
number = {},
pages = {1-20},
doi = {10.1017/cjn.2026.10557},
pmid = {41635251},
issn = {0317-1671},
}

@article {pmid41635249,
year = {2026},
author = {Ponikiewska, K and Strus, W and Cieciuch, J},
title = {The Temperament Metadimensions Model: A Complex Framework for Formal Characteristics of Behavior as Composed of Energetic, Temporal, and Autoregulatory Facets of Reactivity and Activity.},
journal = {Journal of personality},
volume = {},
number = {},
pages = {},
doi = {10.1111/jopy.70054},
pmid = {41635249},
issn = {1467-6494},
abstract = {OBJECTIVE: The paper presents the Temperament Metadimensions Model (TMM), which extends the integrative model of temperament structure proposed by Strus et al. (2022). This extension adds four autoregulatory trait-facets to the originally proposed four energetic and four temporal ones, enhancing the theoretical comprehensiveness of the model in terms of regulatory function of temperament and coverage of crucial constructs postulated in other well-established temperament theories. The autoregulatory trait-facets were conceptually introduced and subsequently empirically tested within the whole expanded 12 trait-facet model of bipolar and orthogonal Reactivity and Activity metadimensions, verifying its synthesizing and predictive potential.

METHOD: The empirical verification of the TMM model was performed throughout three subsequent studies, with a joint sample of 1756 participants (52.0% females; Mage = 34.68). We examined the TMM's: (1) internal structure, (2) relationships with constructs from other established theories of temperament, and (3) predictive capabilities in relation to mental health-related variables.

RESULTS AND CONCLUSIONS: The obtained results confirmed the validity of the 12-facet TMM as an integrative and comprehensive framework for formal characteristics of behavior, possessing evident functional significance and indicating its superiority over the eight-facet Strus et al.'s (2022) model. Theoretical implications of the TMM were discussed.},
}

@article {pmid41635116,
year = {2026},
author = {Wang, Y and Lipton, SA},
title = {Aberrant Protein S-Nitrosylation Mimics the Effect of Rare Genetic Mutations in Neurodegenerative Diseases.},
journal = {Journal of neurochemistry},
volume = {170},
number = {2},
pages = {e70365},
doi = {10.1111/jnc.70365},
pmid = {41635116},
issn = {1471-4159},
support = {DP1 DA041722/DA/NIDA NIH HHS/United States ; R01 DA048882/DA/NIDA NIH HHS/United States ; ReMIND-L DISC4 16292//California Institute for Regenerative Medicine/ ; R01 AG056259/AG/NIA NIH HHS/United States ; R01 AG078756/AG/NIA NIH HHS/United States ; R35 AG071734/AG/NIA NIH HHS/United States ; R56 AG065372/AG/NIA NIH HHS/United States ; RF1 AG057409/AG/NIA NIH HHS/United States ; U01 AG088679/AG/NIA NIH HHS/United States ; /NH/NIH HHS/United States ; /NH/NIH HHS/United States ; },
mesh = {Humans ; *Neurodegenerative Diseases/genetics/metabolism ; Animals ; *Mutation/genetics ; *Protein Processing, Post-Translational/genetics ; },
abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease/Lewy body dementia (PD/LBD), and amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) are driven by complex interactions of genetic and environmental factors. While genome wide association studies (GWAS) have uncovered a number of risk gene variants (e.g., APOE, SNCA [encoding α-synuclein], and protein disulfide isomerase [PDI]), these genetic factors alone cannot fully explain disease onset or progression. Emerging evidence suggests that post-translational modifications of proteins, particularly S-nitrosylation (SNO), act as a critical link between environmental stress and neurodegenerative pathology. Here, we review data showing that while physiological protein SNO regulates diverse neuronal processes, aberrant SNO, occurring very commonly in the diseased brain, can disrupt protein function in ways that mimic the deleterious effects of rare genetic mutations. We advance the concept of "mutational mimicry," whereby aberrant SNO of key neuronal or glial proteins reproduces the functional consequences of known specific genetic mutations, ultimately converging on common pathways of synaptic dysfunction emanating from mitochondrial and metabolic impairment, proteostasis, neuroinflammation, and so on. Supporting this framework, proteomic analyses show significant overlap between abnormally S-nitrosylated proteins in diseased brains and known genetic risk factors in AD and PD/LBD as well as in ALS. By linking redox biology to human genetics, this review highlights how environmental factors can phenocopy or enhance genetic susceptibilities. Understanding this convergence not only provides novel insight into disease mechanisms but also suggests new therapeutic targets to intervene in these convergent pathways with the goal of halting neurodegenerative processes.},
}

Humans
*Neurodegenerative Diseases/genetics/metabolism
Animals
*Mutation/genetics
*Protein Processing, Post-Translational/genetics

@article {pmid41634873,
year = {2026},
author = {Garrigos, D and Martinez-Morga, M and Pombero, A and García-Lopez, R and Pastor, D and Riquelme, D and Blanquer, M and Iniesta, F and Valdor, R and Geijo-Barrientos, E and Hargus, G and Moraleda, JM and Martínez, S},
title = {Chaperone mediated autophagy is deficient in spinal motoneurons of ALS patients with TDP-43 proteinopathy.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-026-02238-6},
pmid = {41634873},
issn = {2051-5960},
support = {Grant Numbers SEV-2017-0723//Spanish State Research Agency, through the "Severo Ochoa" Programme for Centres of Excellence in R&D/ ; Grant Numbers SEV-2017-0723//Spanish State Research Agency, through the "Severo Ochoa" Programme for Centres of Excellence in R&D/ ; Grant Numbers SEV-2017-0723//Spanish State Research Agency, through the "Severo Ochoa" Programme for Centres of Excellence in R&D/ ; Grant Numbers SEV-2017-0723//Spanish State Research Agency, through the "Severo Ochoa" Programme for Centres of Excellence in R&D/ ; Grant Numbers SEV-2017-0723//Spanish State Research Agency, through the "Severo Ochoa" Programme for Centres of Excellence in R&D/ ; Grant Numbers SEV-2017-0723//Spanish State Research Agency, through the "Severo Ochoa" Programme for Centres of Excellence in R&D/ ; Grant Numbers SEV-2017-0723//Spanish State Research Agency, through the "Severo Ochoa" Programme for Centres of Excellence in R&D/ ; SAF2017-83702-R and PID2020-11817RB-I00//Spanish Ministerio de Ciencia e Innovación/ ; SAF2017-83702-R and PID2020-11817RB-I00//Spanish Ministerio de Ciencia e Innovación/ ; SAF2017-83702-R and PID2020-11817RB-I00//Spanish Ministerio de Ciencia e Innovación/ ; SAF2017-83702-R and PID2020-11817RB-I00//Spanish Ministerio de Ciencia e Innovación/ ; SAF2017-83702-R and PID2020-11817RB-I00//Spanish Ministerio de Ciencia e Innovación/ ; SAF2017-83702-R and PID2020-11817RB-I00//Spanish Ministerio de Ciencia e Innovación/ ; SAF2017-83702-R and PID2020-11817RB-I00//Spanish Ministerio de Ciencia e Innovación/ ; SAF2017-83702-R and PID2020-11817RB-I00//Spanish Ministerio de Ciencia e Innovación/ ; Grant Number 2018/041//Generalitat Valenciana (program Prometeo II)/ ; Grant Number 2018/041//Generalitat Valenciana (program Prometeo II)/ ; Grant Number 2018/041//Generalitat Valenciana (program Prometeo II)/ ; Grant Number 2018/041//Generalitat Valenciana (program Prometeo II)/ ; Grant Number 2018/041//Generalitat Valenciana (program Prometeo II)/ ; Grant Number 2018/041//Generalitat Valenciana (program Prometeo II)/ ; Grant Number 2018/041//Generalitat Valenciana (program Prometeo II)/ ; RD21/0017/0017; RD21/0017/0001//Instituto de Salud Carlos III (ISCIII) through the RICORS Project TERAV/ ; RD21/0017/0017; RD21/0017/0001//Instituto de Salud Carlos III (ISCIII) through the RICORS Project TERAV/ ; RD21/0017/0017; RD21/0017/0001//Instituto de Salud Carlos III (ISCIII) through the RICORS Project TERAV/ ; RD21/0017/0017; RD21/0017/0001//Instituto de Salud Carlos III (ISCIII) through the RICORS Project TERAV/ ; RD21/0017/0017; RD21/0017/0001//Instituto de Salud Carlos III (ISCIII) through the RICORS Project TERAV/ ; Ramon y Cajal (RYC) 2019-027520-I//Ministerio de Ciencia e Innovación/ ; },
}

@article {pmid41633676,
year = {2025},
author = {Šoša, I and Sergi, CM},
title = {Genomics for Sudden Cardiac Death: A Review of the Topic and Call for Increased Professionalism in Clinico-Molecular Autopsy and Forensic Laboratory Sciences.},
journal = {Annals of clinical and laboratory science},
volume = {55},
number = {6},
pages = {859-868},
pmid = {41633676},
issn = {1550-8080},
mesh = {Humans ; *Death, Sudden, Cardiac/pathology ; *Genomics/methods ; Autopsy ; *Professionalism ; Gene Frequency ; *Forensic Genetics ; Genome, Human/genetics ; },
abstract = {In 2001, the first draft sequence of the human genome was released, the culmination of a decade-long, multibillion-dollar effort. Since then, an OMICs platform has been proposed to further evaluate and edit the human genome for diagnostic and therapeutic purposes. The Human Genome Project opened a Pandora's box, expanding the forensic laboratory physicians' toolbox. Kinship analysis has been used extensively for parentage testing and identifying cases of human remains and missing persons. The Combined DNA Index System has played a significant role in forensic DNA databases. Nanopore sequencing and improved genomic tools aid enormously in identifying amplicons from degraded samples. The application of genomics in determining the potential channelopathies of sudden cardiac death (SCD) has been an enormous step forward in recent years in forensic histopathology. We reviewed the literature. Kong et al.'s meta-analysis of the mean allele frequencies of SCN5A, NOS1AP, KCNH2, KCNE1, and KCNQ1 genes across Black, Caucasian, Asian, and Hispanic ethnicities has been pivotal to forensic science in the last decade. The authors used sequenced genomic data from the Exome Aggregation Consortium to compare allele frequencies between different ethnicities. They found that Asians had the highest overall mean allele frequencies for NOS1AP and SCN5A, Caucasians had the highest KCNH2 frequency, and Hispanics had the highest KCNQ1 frequency. In 2026, the call for increased professionalism in clinico-molecular autopsy and forensic laboratory sciences is driven by rapid technological advancements (e.g., forensic molecular genomic autopsies), critical workforce shortages in some geographical areas, and the increasing complexity of death investigations. This professionalization focuses on standardizing molecular protocols, enhancing ethical frameworks, and addressing the need for specialized interdisciplinary expertise.},
}

Humans
*Death, Sudden, Cardiac/pathology
*Genomics/methods
Autopsy
*Professionalism
Gene Frequency
*Forensic Genetics
Genome, Human/genetics

@article {pmid41633603,
year = {2026},
author = {Tian, X and Song, Z and Huang, Y and Yao, W},
title = {[Analysis of early complications and risk factors in patients with amyotrophic lateral sclerosis after percutaneous endoscopic gastrostomy].},
journal = {Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences},
volume = {58},
number = {1},
pages = {190-195},
pmid = {41633603},
issn = {1671-167X},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/surgery ; *Gastrostomy/adverse effects/methods ; Male ; Middle Aged ; Risk Factors ; Female ; Retrospective Studies ; *Postoperative Complications/etiology/epidemiology ; Aged ; Adult ; Enteral Nutrition/adverse effects/methods ; *Gastroscopy/adverse effects ; },
abstract = {OBJECTIVE: To explore risk factors of early complications (≤14 days) and the clinical characteristics in patients with amyotrophic lateral sclerosis (ALS) after percutaneous endoscopic gastrostomy (PEG).

METHODS: Patients diagnosed with ALS who underwent first PEG insertion between January 2011 and December 2020 were eligible. Medical records were retrospectively reviewed to determine clinical characteristics and outcomes (≤14 days) of patients who underwent the pull type PEG. Grouping was performed based on the presence and severity of complications, and SPSS 27.0 statistical software was used for data analysis. Finally, Logistic regression model was applied for multivariate factor analysis of risk factors related to complications.

RESULTS: In the study, 192 cases of PEG were all successfully completed, with 97 (51%) males, mean age of ALS onset disease (55±11) years and 93 (48%) bulbar onset symptoms included. Complications occurred in 40 (21%) cases after PEG within 14 days, all of which had fever, including 16 cases without clear infection focus, 18 cases of respiratory tract infections, and 6 cases of fistula site infections. In the study, 13 (7%) cases had major complications, including 11 cases of respiratory tract infection and 2 cases of stoma infection. Two cases of respiratory tract infection died due to respiratory failure, and the remaining 11 cases recovered after upgraded antibiotic. No complications, such as tube dislodgement, benign pneumoperitoneum, hemorrhage or buried bumper syndrome occurred. The operation time and postoperative hospital stay were longer in the complication group than in the non-complication group [(16±5) min vs. (13±5) min, P < 0.001; 6 (5, 9) d vs. 5 (3, 7) d, P=0.009]. Compared with the mild complication group, the creatinine and triglyceride in the major complication group were significantly lower [(46.5±16.2) μmol/L vs.(66.8±16.4) μmol/L, P＜0.001; (1.1±0.5) mmol/L vs.(1.6±0.7) mmol/L, P=0.038], and the operation time was significantly longer [(20±5) min vs. (15±5) min, P=0.002]. Further, Logistic regression model analysis revealed that the operation time was also independent associated with complications (OR=1.132, 95%CI: 1.051-1.220, P=0.001).

CONCLUSION: PEG was a reliable method for ALS patients to put nutrition tube. Postoperative fever was the most common complications. Long surgical duration was an independent risk factor for the occurrence of complications (≤14 d).},
}

Humans
*Amyotrophic Lateral Sclerosis/surgery
*Gastrostomy/adverse effects/methods
Male
Middle Aged
Risk Factors
Female
Retrospective Studies
*Postoperative Complications/etiology/epidemiology
Aged
Adult
Enteral Nutrition/adverse effects/methods
*Gastroscopy/adverse effects

@article {pmid41633359,
year = {2026},
author = {Xie, X and Liu, J and Liang, W and Zhang, Y and Gong, X and Yuan, S and Qi, C and Huang, M and Shi, L and Hou, M and Zhang, M and Liu, W and Sun, W and Wu, Y and Li, C and Cao, Z and Jing, H and Qian, L and Liu, J and Yuan, S and Wang, Q and Shen, Y and Liu, Z and Li, Y and Pan, H and Zhu, B and Shan, B and He, K and Wang, W and Zou, C and Li, Y and Chou, JJ and Yuan, J},
title = {Repression of RIPK1 kinase by INPP5D inhibits expression of diverse proinflammatory mediators and late-onset Alzheimer's disease risk factors.},
journal = {Immunity},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.immuni.2026.01.014},
pmid = {41633359},
issn = {1097-4180},
abstract = {Genome-wide association studies strongly implicate neuroinflammation in late-onset Alzheimer's disease (LOAD). Genetic risk loci for LOAD are enriched for genes expressed in microglia, but the relationship among microglial LOAD risk genes has been unclear. We found that the N-terminal SH2 domain of INPP5D, an important LOAD risk gene, directly interacted with the cell death regulator RIPK1 at p-Y383 to suppress RIPK1 kinase activation. Microglial INPP5D deficiency cell-autonomously promoted RIPK1-mediated transcriptional induction of diverse LOAD risk genes, proinflammatory cytokines, complements, and ROS mediators, as well as proinflammatory signaling mediators such as Toll-like receptors (TLRs), MyD88, Nlrp3, gasdermin D, and Zbp1. RIPK1-regulated microglial transcriptomic signatures were found in microglial subtypes implicated in human Alzheimer's disease (AD) pathogenesis. Furthermore, microglial INPP5D deficiency promoted aging-dependent RIPK1-mediated development of neuronal TDP-43 pathology, neuronal loss, and motor dysfunction in a non-cell-autonomous manner. Our data suggest that INPP5D functions as an intracellular rheostat in regulating RIPK1-mediated neuroinflammation for promoting aging-related neurodegenerative diseases, including LOAD and AD-amyotrophic lateral sclerosis comorbidity.},
}

@article {pmid41633321,
year = {2026},
author = {Di Gennaro, G and Grammaldo, LG and Tomasini, A},
title = {Toward a multidimensional understanding of internalized epilepsy stigma.},
journal = {Epilepsy & behavior : E&B},
volume = {177},
number = {},
pages = {110899},
doi = {10.1016/j.yebeh.2026.110899},
pmid = {41633321},
issn = {1525-5069},
abstract = {This letter responds to Prieto et al.'s discussion of our article Rethinking epilepsy stigma: the uncanny, the emotional, and the structural. We clarify that our original framework was primarily theoretical, aiming to illuminate the multifaceted mechanisms sustaining internalized epilepsy stigma, including the "uncanny" experience of seizures, ambivalent emotional responses, and structural inequities. We highlight how third-generation psychotherapeutic approaches, emphasizing psychological flexibility, mindfulness, and emotional acceptance, complement cognitive-behavioral strategies by enhancing individuals' capacity to relate adaptively to stigma-related distress. We propose that integrating behavioural, emotional, and structural perspectives offers a multidimensional framework to better understand and address internalized epilepsy stigma, guiding interventions that promote psychological well-being, social inclusion, and empowerment for people living with epilepsy.},
}

@article {pmid41631638,
year = {2026},
author = {Allen, S and Howard, J and McDermott, CJ and Boardman, F and McNeill, A},
title = {Limited data capture on reproductive medicine use in amyotrophic lateral sclerosis: implications for monitoring access.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/21678421.2026.2618124},
pmid = {41631638},
issn = {2167-9223},
abstract = {There is very limited evidence around the use of reproductive genetic testing in individuals with amyotrophic lateral sclerosis (ALS)-linked gene variants. This study aimed to identify the use of reproductive genetic testing in these individuals to understand patterns of (under)utilization and to identify barriers to equitable access. Freedom of information requests were sent in January 2025 to the 22 regional clinical genetics centers across the UK around reproductive services for individuals with, or at risk for, ALS and Huntington's disease. Limited data were available with only six trusts answering in full. The data that our study yielded raises significant concerns and inconsistencies regarding clinical recording and reporting of reproductive genetic counseling and testing. The absence of standardized retrievable data limits the ability to assess utilization and may point toward a systemic issue in data capture of reproductive genetic services for individuals at risk of ALS, and by extension, those affected by other genetic conditions.},
}

@article {pmid41630926,
year = {2026},
author = {Saucier, J and Al-Qadi, M and Allain, EP and Robichaud, PP and Chamard-Witkowski, L and Alvarez, M and Dion-Côté, AM and Richard, L and Crapoulet, N and Ben Amor, M},
title = {Expanding the Genetic Landscape of ATXN2 Variants: Insights From a Biallelic Trinucleotide Repeat Expansion in an Acadian Family.},
journal = {Neurology. Genetics},
volume = {12},
number = {1},
pages = {e200345},
pmid = {41630926},
issn = {2376-7839},
abstract = {BACKGROUND AND OBJECTIVES: Spinocerebellar ataxias are a diverse group of autosomal dominant cerebellar ataxias. SCA2 is a complex ataxia with various extracerebellar symptoms, including parkinsonism, dystonia, hyporeflexia, and cognitive impairment. ATXN2 is a modulator of neurologic disease: Expansions of at least 37 CAG (glutamine) repeats are pathogenic for SCA2, while expansions in the intermediate range (30-32) convey risk for the development of neurodegenerative disorders including Parkinson disease and amyotrophic lateral sclerosis. Homozygous variants are exceedingly rare. This study describes a novel ATXN2 presentation identified in an Acadian family from New Brunswick, Canada: a CAG repeat expansion within the fully penetrant range of SCA2, asymptomatic in the heterozygous state and resulting in a neurodegenerative disorder in homozygous patients.

METHODS: Three individuals, 2 siblings and their cousin, were investigated for a neurodegenerative disorder with overlapping phenotypes. The affected individuals and their 5 immediate family members underwent whole-genome sequencing analyzed by ExpansionHunter, repeat-primed PCR and Sanger sequencing.

RESULTS: Sequencing revealed a homozygous 39/39 CAG repeat expansion with 4 CAA interruptions in ATXN2 across all 3 affected individuals. After experiencing childhood intellectual or learning difficulties, the patients developed a pyramidal syndrome with spastic gait and a major neurocognitive disorder characterized by prominent frontal signs during their late twenties. Within a decade, all patients completely lost their autonomy. Shared phenotypic features included ataxia, spasticity, aphasia, dysphagia, myoclonus, atypical parkinsonism, incontinence, diffuse cortical atrophy with frontal predominance, and cerebellar atrophy. The same 39 CAG repeat allele with 4 CAA interruptions was identified in heterozygous state in 4 asymptomatic parents (age 65+) and 1 sibling in their thirties. Three carriers consented to further investigation with a neurologic examination, neuropsychological assessment, and cerebral MRI. Clinical and radiologic signs of disease were absent, despite the carriers' ages and their heterozygous expansion in the fully penetrant range of SCA2.

DISCUSSION: This study describes a novel ATXN2 expansion within the classic pathogenic range for SCA2 that manifests as an early-onset neurodegenerative disorder in the homozygous state, while being asymptomatic into late adulthood in the heterozygous state.},
}

@article {pmid41630851,
year = {2026},
author = {Appel, M and Jubel, A and Antoni, M},
title = {Interobserver reliability of the AO/OTA and Luo three-column classification systems for tibial plateau fractures and their impact on surgical approach selection.},
journal = {Journal of orthopaedics},
volume = {74},
number = {},
pages = {234-238},
pmid = {41630851},
issn = {0972-978X},
abstract = {PURPOSE: This study aims to compare the interobserver reliability of the traditional two-dimensional AO/OTA classification with the more recent three-dimensional Luo three-column classification for tibial plateau fractures. Furthermore, it evaluates the impact of both systems on the surgical approach selection, particularly examining Luo et al.'s hypothesis that the three-column classification encourages increased consideration of the posterior column during preoperative planning. However, this hypothesis has not been evaluated yet, leaving a research gap regarding its influence in practice on surgical approach selection.

METHODS: Fifteen cases of tibial plateau fractures were retrospectively analyzed by nine trauma surgeons using radiographs and CT scans. Fractures were classified according to the AO/OTA and Luo classifications, and preferred surgical approaches for definitive fixation were determined. Interobserver reliability was assessed using Fleiss' kappa and interpreted according to the categorical rating by Landis and Koch. Additionally, a chi-square test was performed to evaluate statistical significance in the surgical approach selection.

RESULTS: Both classification systems showed overall substantial reliability (kAO = 0.63; kLuo = 0.67). The difference in agreement for surgical approach groups between the two classifications was 0.11 (kAO_approach = 0.37; kLuo_approach = 0.48). The posterior approach group was not selected significantly more often using the Luo three-column classification compared to the AO/OTA classification (p = 0.543).

CONCLUSION: No significant difference in interobserver reliability or in the choice of surgical approach was observed between the AO/OTA and Luo classifications.},
}

@article {pmid41630787,
year = {2026},
author = {Mukai, T and Kanbayashi, T and Kobayashi, M and Okano, MP and Tachiyama, K and Miyaji, Y and Hatanaka, Y and Kobayashi, S and Sonoo, M},
title = {Discrimination of spontaneous activity in needle EMG based on the quantitative assessment of the discharge rhythm using "Random Index".},
journal = {Clinical neurophysiology practice},
volume = {11},
number = {},
pages = {65-71},
pmid = {41630787},
issn = {2467-981X},
abstract = {OBJECTIVE: Discrimination between EMG activity such as fibrillation potentials/positive sharp waves (Fib/PSW), end plate spikes (EPS), fasciculation potentials (FP), and contaminating voluntary motor unit potentials (MUP) is mandatory for EMG diagnosis. Discharge rhythm is the key for discrimination. We devised a new parameter, Random Index (RI), which quantifies the rhythm and takes a value from 0 to 1, smaller for regular trains of discharges. This study evaluated the utility of RI as well as modified versions of the regularity indices proposed in past reports.

METHODS: EMG records of patients with amyotrophic lateral sclerosis were retrospectively reviewed. EPS were collected also from a healthy volunteer. The EMG activity was classified by an expert. RI and other regularity indices as well as the median instantaneous firing rate (IFRm) were calculated.

RESULTS: Analyzed sequences were 73 Fib/PSW, 27 EPS, 24 FP, and 36 MUP. The four types were clearly separated over the 2-dimensional plots of regularity indices vs. IFRm. Especially, Fib/PSW and EPS were far separated in these plots. RI achieved significantly better discrimination between Fib/PSW and MUP than other indices.

CONCLUSION: RI is a robust tool for discriminating EMG activity.

SIGNIFICANCE: RI and other regularity indices would be useful for educational purpose.},
}

@article {pmid41629214,
year = {2026},
author = {Malard, F},
title = {Transcript-Level Modulation of O-GlcNAc Transferase for Aging-Related Neurodegenerative Diseases.},
journal = {Chembiochem : a European journal of chemical biology},
volume = {27},
number = {2},
pages = {e202500774},
pmid = {41629214},
issn = {1439-7633},
mesh = {Humans ; *N-Acetylglucosaminyltransferases/genetics/metabolism ; *Neurodegenerative Diseases/metabolism/genetics/drug therapy ; *Aging/metabolism/genetics ; RNA, Messenger/metabolism/genetics ; RNA Splicing ; Animals ; },
abstract = {The O-GlcNAc Transferase (OGT) is responsible for the addition of β-O-linked N-acetyl-D-glucosamine (O-GlcNAc) to serine and threonine residues, thereby regulating more than 8000 human proteins through O-GlcNAcylation. In the brain, reduced O-GlcNAc levels, which can arise from insufficient OGT activity, have been increasingly linked to aging-related neurodegenerative diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. While current strategies focus on restoring O-GlcNAc levels via O-GlcNAcase (OGA) inhibition, recent discoveries highlight transcript-level regulation of OGT as a direct and promising therapeutic target. This concept article explores the role of intron detention and decoy exon-mediated splicing repression in limiting OGT pre-mRNA maturation and proposes the use of antisense oligonucleotides or selective splicing factor degraders to promote productive splicing and nuclear export of OGT mRNA. By enhancing OGT expression independently of O-GlcNAc feedback, these approaches aim to restore proteostasis and improve resilience to neurodegeneration, offering a novel therapeutic approach for aging-related neurodegenerative diseases.},
}

Humans
*N-Acetylglucosaminyltransferases/genetics/metabolism
*Neurodegenerative Diseases/metabolism/genetics/drug therapy
*Aging/metabolism/genetics
RNA, Messenger/metabolism/genetics
RNA Splicing
Animals

@article {pmid41629165,
year = {2026},
author = {Zermeño, NA and Godde, K},
title = {Patterns in the Phenice (1969) and Klales et al. (2012) methods of sex estimation using forensic casework from the United States.},
journal = {Journal of forensic sciences},
volume = {},
number = {},
pages = {},
doi = {10.1111/1556-4029.70279},
pmid = {41629165},
issn = {1556-4029},
abstract = {Sex estimation methods from the pelvis have been well-studied in research settings to estimate accuracy, error, and bias. However, patterns in casework are minimally described. We uniquely examine forensic anthropology casework in the United States retrospectively for the Phenice and Klales et al.'s sex estimation methods. Our hypothesis is that casework patterns will reflect the greater literature derived from research settings that show Phenice's method is more accurate and has lower error and sex bias. We use the publicly available Forensic Anthropology Database for Assessing Methods Accuracy. A sample of 229 cases from the United States reported the outcomes of applying these methods. McNemar's tests evaluate whether estimated sex is consistent with documented sex, and a Fisher's exact test compared the performance of the two methods. We further calculated accuracy, error, and sex biases of the methods. The McNemar's and Fisher's exact tests were not statistically significant, which indicates that both methods estimated sex at a rate close to the documented sex and to each other. Phenice's method displayed an accuracy of 99.4%, an error of 0.6%, and a sex bias of -2.4%. Alternatively, the Klales et al.'s method performed slightly lower with a 97.5% accuracy, 2.5% error, and 3.5% sex bias. Forensic anthropology casework in the United States reflects broader patterns in accuracy, error, and bias in the research setting literature, where Phenice outperforms the Klales et al.'s method, despite the values from casework probably reflecting practitioners using information beyond the method reported to make a final sex estimate.},
}

@article {pmid41629112,
year = {2026},
author = {Kuzmanova, BR and Kuzmanova, MR and Elgizouli, M and Tatrai, B and Möller, JC},
title = {Novel KIF5A variant in a patient with early-onset levodopa-responsive Parkinson's syndrome.},
journal = {BMJ case reports},
volume = {19},
number = {2},
pages = {},
doi = {10.1136/bcr-2025-267762},
pmid = {41629112},
issn = {1757-790X},
mesh = {Humans ; Male ; *Kinesins/genetics ; *Levodopa/therapeutic use ; Adult ; *Parkinson Disease/genetics/drug therapy ; Mutation ; *Parkinsonian Disorders/genetics/drug therapy ; Antiparkinson Agents/therapeutic use ; },
abstract = {We present the case of a male in his mid-30s with a progressive complex neurological phenotype primarily characterised by levodopa-responsive parkinsonism with motor fluctuations as well as gait ataxia, peripheral neuropathy and finally also spastic paraplegia. Genetic analysis identified a novel heterozygous variant in the KIF5A gene: c.937G>A (p.Glu313Lys). This variant is genetically classified as likely pathogenic. Other pathogenic mutations in the KIF5A gene are associated with hereditary spastic paraplegia type 10, Charcot-Marie-Tooth disease type 2 and amyotrophic lateral sclerosis. We discuss the clinical, genetic and prognostic implications of this finding.},
}

Humans
Male
*Kinesins/genetics
*Levodopa/therapeutic use
Adult
*Parkinson Disease/genetics/drug therapy
Mutation
*Parkinsonian Disorders/genetics/drug therapy
Antiparkinson Agents/therapeutic use

@article {pmid41628987,
year = {2026},
author = {Xue, X and Cui, H and Hu, S and Ma, H and Wei, S and Huang, H and Li, X and Huang, Z},
title = {Both target-site and non-target-site resistance mechanisms confer mesosulfuron-methyl resistance in Silene conoidea L.},
journal = {Pesticide biochemistry and physiology},
volume = {218},
number = {},
pages = {106905},
doi = {10.1016/j.pestbp.2025.106905},
pmid = {41628987},
issn = {1095-9939},
mesh = {*Sulfonylurea Compounds/pharmacology ; Acetolactate Synthase/genetics/metabolism/antagonists & inhibitors ; *Herbicide Resistance/genetics ; *Herbicides/pharmacology ; *Silene/drug effects/genetics ; Plant Proteins/genetics/metabolism ; Molecular Docking Simulation ; Mutation ; },
abstract = {Silene conoidea L., a common weed in wheat fields, is mainly controlled by acetolactate synthase (ALS)-inhibiting herbicides such as mesosulfuron-methyl. In this study, we investigated a mesosulfuron-methyl resistant population to elucidate the resistance mechanisms. The resistant (R) population displayed a high level of resistance to mesosulfuron-methyl, with the resistance index (RI) of 18.87. It also exhibited cross-resistance to halosulfuron-methyl, florasulam, flumetsulam, and flucarbazone‑sodium. In vitro ALS enzyme activity in the R population was 22.85-fold higher than in the susceptible (S) population. A W574L mutation (leucine replaced tryptophan) was identified in the ALS gene of the R population. Through molecular docking, this substitution of amino acid weakened the π-π stacking interaction between mesosulfuron-methyl molecule and the non-mutated ALS enzyme. The R population also showed significantly higher ALS expression than the S population, while the ALS gene copy number did not differ between the two populations. Pretreatment with malathion (cytochrome P450 inhibitor) and NBD-Cl (glutathione S-transferases inhibitor) reduced mesosulfuron-methyl resistance by 43.92 % and 29.20 %, respectively. Indicating that CYP450s and GSTs are involved in resistance. Transcriptome and qPCR analyses identified significant upregulation of three ABC transporter genes, three CYP450 genes, and one GST gene in the R population. Meanwhile, KEGG pathway analysis indicated that the photosynthetic pathways were significantly affected after mesosulfuron-methyl treatment. This is the first report of mesosulfuron-methyl resistance in S. conoidea, involves both target site resistance and non-target site resistance mechanisms.},
}

*Sulfonylurea Compounds/pharmacology
Acetolactate Synthase/genetics/metabolism/antagonists & inhibitors
*Herbicide Resistance/genetics
*Herbicides/pharmacology
*Silene/drug effects/genetics
Plant Proteins/genetics/metabolism
Molecular Docking Simulation
Mutation

@article {pmid41628199,
year = {2026},
author = {Hasan, MM and Mostaid, MS and Bepari, AK and Reza, HM and Hossain, M},
title = {Discovery of a novel Keap1 inhibitor for neurodegeneration through virtual screening and molecular dynamics simulations.},
journal = {PloS one},
volume = {21},
number = {2},
pages = {e0341965},
pmid = {41628199},
issn = {1932-6203},
mesh = {*Kelch-Like ECH-Associated Protein 1/antagonists & inhibitors/metabolism/chemistry ; Molecular Dynamics Simulation ; Humans ; NF-E2-Related Factor 2/metabolism/chemistry/antagonists & inhibitors ; Molecular Docking Simulation ; Protein Binding ; Drug Discovery ; Drug Evaluation, Preclinical ; *Neurodegenerative Diseases/drug therapy/metabolism ; Biological Products/chemistry/pharmacology ; *Neuroprotective Agents/pharmacology/chemistry ; },
abstract = {Oxidative stress is a key feature of Alzheimer's disease (AD) and other neurodegenerative disorders. The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway controls redox balance, and disrupting the Keap1-Nrf2 protein-protein interaction (PPI) has become a promising therapeutic approach. Marine natural products (MNPs), because of their structural diversity and bioactivity, are an underexplored source of potential neuroprotective compounds. This study aimed to identify novel marine-derived inhibitors of the Keap1-Nrf2 interaction using a comprehensive in silico pipeline. A total of 14,492 compounds from an open-access MNP database were virtually screened against the Keap1 Kelch domain through molecular docking. The top 1,329 candidates exhibited strong binding affinities, with several reaching scores comparable to the co-crystallized reference ligand L5F. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling was employed to assess pharmacokinetic properties, brain penetration, and safety, leading to the identification of compound 145398-61-4 as the most promising hit. Molecular dynamics (MD) simulations verified the structural stability of the Keap1-145398-61-4 complex, while binding free energy calculations indicated energetically favorable interactions. Additional validation using principal component analysis (PCA) and highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy analysis further confirmed the stability of this interaction. Overall, our in silico study identified compound 145398-61-4 as a novel Keap1-Nrf2 inhibitor, highlighting its potential as a lead candidate for developing treatments for Alzheimer's disease and other neurodegenerative disorders, such as amyotrophic lateral sclerosis and multiple sclerosis.},
}

*Kelch-Like ECH-Associated Protein 1/antagonists & inhibitors/metabolism/chemistry
Molecular Dynamics Simulation
Humans
NF-E2-Related Factor 2/metabolism/chemistry/antagonists & inhibitors
Molecular Docking Simulation
Protein Binding
Drug Discovery
Drug Evaluation, Preclinical
*Neurodegenerative Diseases/drug therapy/metabolism
Biological Products/chemistry/pharmacology
*Neuroprotective Agents/pharmacology/chemistry

@article {pmid41626491,
year = {2026},
author = {Akimoto, Y and Miyamae, Y and Shigemori, H},
title = {Effects of Cyanidin Derivatives for the Aggregation of Cu/Zn Superoxide Dismutase 1.},
journal = {ACS omega},
volume = {11},
number = {3},
pages = {3849-3865},
pmid = {41626491},
issn = {2470-1343},
abstract = {Cu/Zn superoxide dismutase 1 (SOD1), whose aggregation is considered cytotoxic, is implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Therefore, inhibiting SOD1 aggregation may represent a promising strategy for the treatment and prevention of this disease. We first screened seven polyphenols using an optimized thioflavin T (Th-T) assay and found that cyanidin exhibited the strongest inhibitory activity among the seven polyphenols. We then compared cyanidin with its derivatives(?)delphinidin, petunidin, malvidin, and cyanidin-3-glucoside (C3G). In this study, we concluded that delphinidin had the strongest antifibrillation activity among the five cyanidin derivatives. Turbidity, transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS), circular dichroism (CD) spectroscopy, and Fourier transform infrared (FT-IR) spectroscopy indicated that the inhibitory activity was influenced by the number of phenolic hydroxyl groups on the B-ring of the cyanidin derivatives. Based on the LDH assay, delphinidin was the most effective compound in preventing the formation of cytotoxic SOD1 aggregates in the cells. Furthermore, we found that the compounds also interfered with the SOD1 cross-linking. Finally, we transfected GFP-SOD1A4 V into Neuro2a cells and observed that the compounds' inhibitory activity on intracellular aggregation was limited.},
}

@article {pmid41625796,
year = {2025},
author = {Jagannathan, A and Al-Bayati, R and Clarke, KM and Micallef, J and Willett, T and Wattie, N and Dubrowski, A},
title = {Developing and Validating a Competency Framework for Non-clinical Simulation Operations Specialists.},
journal = {Cureus},
volume = {17},
number = {12},
pages = {e100408},
pmid = {41625796},
issn = {2168-8184},
abstract = {BACKGROUND: Simulation-based education (SBE) is essential for developing and maintaining clinical skills, yet its effectiveness is partially contingent on simulation operations specialists (SOS) who provide technical, pedagogical, and safety support. Traditionally, SOS roles have been filled by clinicians, but healthcare workforce shortages have prompted simulation centres to rely on informal, on-the-job pathways to train non-clinicians as SOS. This approach has raised concerns regarding workforce readiness and highlights the absence of structured training pathways. To address this gap, we developed and validated a competency framework explicitly tailored to entry-level, non-clinical SOS to inform the development of structured training pathways.

METHODS: A mixed-methods design guided by participatory action research (PAR) was used to guide this work. This study followed Batt et al.'s six-step model to develop and validate the competency framework. Methods included a narrative review, artificial intelligence (AI)-supported competency generation, semi-structured interviews, a card-sorting exercise, survey-based validation, and focus groups.  Results: This study produced a validated competency framework for non-clinical SOS training consisting of 36 competencies across three technical pillars: (i) Simulation Technology (SIMTECH); (ii) Educational Principles (EDUPRI); and (iii) Safety (SAFE), plus a General Competencies (GEN) pillar aligned with transferable knowledge, skills, and attitudes (KSAs).  Conclusion: This study provides the first validated competency framework tailored for entry-level, non-clinical SOS, grounded in both theory and real-world perspectives. The final framework offers a foundation for curriculum developers, employers, and certification bodies, and informs the development of accessible training pathways for non-clinicians entering the simulation operations field.},
}

@article {pmid41625676,
year = {2025},
author = {Ghasemi, S and Imani, B and Torabi, M and Ayubi, E},
title = {The effects of team-based and mastery-based learning on the student's clinical competence and the results of clinical evaluation: A quasi-experimental study among operating room nursing students.},
journal = {Journal of education and health promotion},
volume = {14},
number = {},
pages = {537},
pmid = {41625676},
issn = {2277-9531},
abstract = {BACKGROUND: Clinical education is a crucial component of the medical education system, providing essential opportunities to enhance students' clinical competence and skills. In light of the numerous challenges in the clinical environment of the operating room, this study was conducted to compare the impact of team-based and mastery-based learning methods on the student's clinical competence and their evaluation.

MATERIALS AND METHODS: This quasi-experimental study was conducted on 6[th]-semester operating room technology students at Hamadan University of Medical Sciences in 2023. In this study, students were selected by the convenience sampling method and were placed in two educational groups (team-based and mastery-based) of 31 people by the matching method. After implementing the training process in the operating room environment, the data related to the study were collected from Liu et al.'s clinical competence questionnaire and clinical assessment checklist of operating room nursing students.

RESULTS: Findings showed that implementing the team-based learning method significantly affected students' clinical competence (P value = 0.012). Also, utilizing a mastery-based learning method compared to a team-based one had a significantly greater impact on the level of clinical skills and evaluation of students (P value = 0.007).

CONCLUSION: The results of this study have practical implications for clinical instructors and higher education institutions. Clinical instructors are advised to adopt a team-based learning method to enhance the student's clinical competence in the operating room. Furthermore, higher education institutions are encouraged to provide adequate resources and make essential efforts to modernize educational methods in clinical environments, thereby empowering students and improving the quality of healthcare.},
}

@article {pmid41626035,
year = {2025},
author = {Jackson, MC and Azarraga, RB and Fraix, MP and Agrawal, DK},
title = {Stage-Based Communication Rehabilitation in Amyotrophic Lateral Sclerosis (ALS): A Review of Strategies for Enhancing Quality of Life.},
journal = {Archives of internal medicine research},
volume = {8},
number = {4},
pages = {359-371},
pmid = {41626035},
issn = {2688-5654},
support = {R25 AI179582/AI/NIAID NIH HHS/United States ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) is an incurable progressive degenerative neuromuscular disease. One way ALS affects patients is through dysarthria significantly impacting a patient's quality of life by affecting their ability to communicate. This makes maintaining relationships, identity and autonomy difficult, all of which affect psychological wellbeing - a determinant of the quality of life. Dysarthria makes communication difficult, and because the regions affected by ALS first are different for each patient, creating strategies for rehabilitating communication can be challenging. In this review we explore the different communication rehabilitation options available and organize them based on if they are usable based on the onset of intelligibility and locked in state. Interventions before the onset of intelligibility in the early stage are proactive measures such as voice banking and education which empower patient autonomy and a sense of control. Interventions between onset of intelligibility and the locked-in state in the middle stage are alternative and augmentative communication strategies varied in accessibility and usability in patients based on their preferences and functional ability. Late-stage interventions which work after a patient with ALS has entered a locked-in state, are the most technologically advanced alternative and augmentative communication devices and rehabilitate function inaccessible by other methods in this disease stage. While assessing patient values and recommending interventions which meet patient needs is most important in rehabilitation of communication in patient with ALS, using a stage-based approach to evaluate and recommend the treatment of dysarthria and communication rehabilitation will optimize quality of life throughout the progression of disease.},
}

@article {pmid41625544,
year = {2025},
author = {Douglas, H and Di Vincenzo, M and Dossa, RFJ and Nunziante, L and Sujit, S and Arulkumaran, K},
title = {Levels of shared autonomy in brain-robot interfaces: enabling multi-robot multi-human collaboration for activities of daily living.},
journal = {Frontiers in human neuroscience},
volume = {19},
number = {},
pages = {1718713},
pmid = {41625544},
issn = {1662-5161},
abstract = {Individuals with ALS and other severe motor impairments often rely on caregivers for daily tasks, which limits their independence and sense of control. Brain-robot interfaces (BRIs) have the potential to restore autonomy, but many existing systems are task-specific and highly automated, which reduces the users' sense of empowerment and limits opportunities to exercise autonomy. In particular, shared autonomy approaches hold promise for overcoming current BRI limitations, by balancing user control with increased robot capabilities. In this work, we introduce a collaborative BRI that integrates non-invasive EEG, EMG, and eye tracking to enable multi-user, multi-robot interaction in a shared kitchen environment with mobile manipulators. Our system modulates assistance through three levels of autonomy-Assisted Teleoperation, Shared Autonomy, and Full Automation-allowing users to retain meaningful control over task execution while reducing effort for routine operations. We conducted a controlled user study comparing autonomy conditions, evaluating performance, workload, ease of use, and agency. Our results show that, while Full Automation was generally preferred by users due to lower workload and higher usability, Shared Autonomy provided higher reliability and preserved user agency, especially in the presence of noisy EEG decoding. Although there was significant individual variability in EEG decoding performance, our post-hoc analysis revealed the potential benefits of customizing pipelines for each user. Finally, we note that our findings are specific to the multi-modal configuration tested and should not be interpreted as a universal claim about the superiority of any autonomy level, and, furthermore, our user study was limited by the use of healthy adults rather than target population (e.g., individuals with ALS), gender imbalance, and a relatively small sample size, which may affect generalizability. Project website: https://coopopen.github.io/.},
}

@article {pmid41625181,
year = {2026},
author = {Zhen, J and Liu, Q and Xue, X and Hao, F and Zhang, S and Liu, N and Li, Z and Chen, J and Cheng, J},
title = {The Application Value of Nursing Interventions Based on the Chronic Illness Trajectory Framework in Patients With Amyotrophic Lateral Sclerosis.},
journal = {Neurology research international},
volume = {2026},
number = {},
pages = {1280057},
pmid = {41625181},
issn = {2090-1852},
abstract = {This prospective study evaluated the impact of nursing interventions based on the Chronic Illness Trajectory Framework (CITF) on anxiety, depression, mental toughness, sleep quality, and ALSFRS-R scores in amyotrophic lateral sclerosis (ALS) patients to enhance care strategies. Eighty ALS patients were enrolled from the Department of Neurology at the First Hospital of Shanxi Medical University between February 2023 and March 2024. Participants were randomly assigned to an intervention group (CITF-based nursing interventions) or a control group (standard care). Over an 8-week period, the intervention group demonstrated significantly lower anxiety and depression scores, higher mental toughness, and improved sleep quality compared to the control group (p < 0.05). Additionally, the intervention group achieved higher ALSFRS-R scores (31.63 ± 3.54 vs. 29.58 ± 3.38) (p < 0.05). These findings indicate that CITF-based nursing interventions effectively reduce negative emotional states, enhance mental resilience, improve sleep quality, and boost overall quality of life in ALS patients. Based on this study, nurses can integrate CITF-based interventions into standard ALS care to enhance patients' emotional well-being and functional outcomes. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2500108691.},
}

@article {pmid41624110,
year = {2026},
author = {Debernard, S and Gassias, E and Aguilar, P and Maria, A and Fuentes, A and Couzi, P and Bozzolan, F and Durand, N and Force, E},
title = {Involvement of Taiman in juvenile hormone signaling controlling sexual maturation in a male moth.},
journal = {Current research in insect science},
volume = {9},
number = {},
pages = {100122},
pmid = {41624110},
issn = {2666-5158},
abstract = {In insects, juvenile hormone (JH) is essential for orchestrating reproductive events. For example, in the male moth Agrotis ipsilon, the behavioral response to female sex pheromone is linked to neuronal sensitivity in the primary olfactory centers (antennal lobes, ALs), and the maturation of accessory sex glands (ASGs) are known to be age- and JH-dependent. The molecular basis of this regulatory action of JH is not fully deciphered, and we show here that the heterodimerizing partner of Methoprene-tolerant called Taiman (Tai) is essential for the sexual maturation of male A. ipsilon. Tai expression in ALs and ASGs is elevated from the third day of adult life and is responsible for the acquisition of behavioral responsiveness to the sex pheromone and ASG maturation. Tai-deficient old males exhibited altered sexual behavior and delayed ASG maturation. Moreover, the expression levels of Tai and Krüppel homolog 1 (Kr-h1), an early JH-induced transcription factor, were reduced in ALs and ASGs of JH-deprived and Tai-deficient old males, respectively. Exogenous JH injection into young males resulted in precocious sexual maturation and this JH induction was suppressed by Tai silencing. Our results demonstrate that Tai is an actor of the JH signaling pathway that operates in ALs and ASGs to promote pheromone information processing and consequently the display of sexual behavior in synchrony with ASG maturation, ultimately optimizing male reproductive success. Thus, this study provides additional insights into the molecular mechanisms underlying hormonal regulation of sexual maturation in insects.},
}

@article {pmid41623730,
year = {2026},
author = {Surtees, JE and Lambert, CV},
title = {Maintenance of competence in rarely performed clinical skills by advanced life support providers in Gauteng, South Africa: A mixed-methods study.},
journal = {African journal of emergency medicine : Revue africaine de la medecine d'urgence},
volume = {16},
number = {1},
pages = {100932},
pmid = {41623730},
issn = {2211-4203},
abstract = {INTRODUCTION: Advanced Life Support (ALS) providers are highly trained emergency care professionals with a broad range of clinical skills. Confidence and competence to perform a clinical skill or intervention has been linked to frequency of application. Differences in training, caseloads, and the context in which ALS providers operate can influence how often they get to perform different skills. Although the Health Professions Council of South Africa (HPCSA) mandates Continuing Professional Development (CPD), there is no requirement for ALS providers to demonstrate maintenance of procedural competence. In this study we investigated approaches to the maintenance of competency in rarely performed clinical skills among a sample of Gauteng-based ALS providers.

METHODS: An exploratory, descriptive mixed-methods design was employed. A quantitative survey of 41 ALS providers assessed frequency of performance and self-reported confidence across 55 clinical skills was performed in March 2023. This was followed by two focus group discussions to explore in greater depth participant's experiences with regard to maintenance of clinical skills.

RESULTS: More than half of the 55 skills we assessed were reported to be "rarely" performed. Confidence to perform a particular skill generally mirrored the frequency with which the skill was performed. Focus group participants identified valuable strategies for maintaining skills that included clinical rotations across diverse work environments, peer discussions, instructional videos, and CPD-accredited courses that included a practical component. Limitations were identified in the current CPD system with regard to maintenance of clinical skills.

CONCLUSION: Skill decay and a reduction in confidence among ALS providers can be linked to infrequent performance of certain clinical skills and interventions. A more purposeful coordinated strategy involving education and training providers, employers and practitioners is required to better support the maintenance of clinical skills that are infrequently performed.},
}

@article {pmid41623487,
year = {2026},
author = {Lian, L and Robinson, H and Daniels, N and Prieto, GA and Poplawski, GHD and Lopez-Gonzalez, R},
title = {Aberrant CDK4/6-driven cell-cycle reentry drives neuronal loss and defines a therapeutic target in C9orf72 ALS/FTD.},
journal = {iScience},
volume = {29},
number = {2},
pages = {114596},
pmid = {41623487},
issn = {2589-0042},
abstract = {The C9orf72 hexanucleotide repeat expansion (G4C2) is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), yet targeted therapies remain unavailable. Here, we show that induced pluripotent stem cell (iPSC)-derived post-mitotic neurons from C9orf72 carriers exhibit age-dependent cell-cycle reentry, increased S-phase entry, and elevated cyclin and CDK expression. Mechanistically, arginine-containing dipeptide repeat proteins (poly-GR and poly-PR) translated from G4C2 repeats drive this aberrant activation through stimulation of the CDK4/6 pathway, whereas poly-GP and C9orf72 loss-of-function show no effect. Importantly, the FDA-approved CDK4/6 inhibitor palbociclib normalizes cell-cycle progression, reduces S-phase entry, decreases motor neuron death, and restores synaptic proteins PSD95 and synapsin-1. Single-nucleus RNA sequencing from C9orf72 patient cortex reveals cell-cycle activation within excitatory neuron subclusters and alterations in DNA repair and cell-cycle regulation pathways, supporting our in vitro findings. These findings establish cell-cycle dysregulation as a central pathogenic mechanism in C9orf72 ALS/FTD and highlight CDK4/6 signaling as a promising therapeutic target.},
}

@article {pmid41622476,
year = {2026},
author = {Liu, J and Zhou, L and Deng, Y and Xu, R},
title = {Amyotrophic lateral sclerosis: Neural repair strategies based on multi-target synchronous interventions.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00221},
pmid = {41622476},
issn = {1673-5374},
abstract = {Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disease that targets motor neurons in the cerebral cortex, medulla oblongata, and spinal cord. This review focuses on the current concepts in the aetiopathogenesis and diagnosis of amyotrophic lateral sclerosis, aiming to explore potential neural repair strategies (curative and/or progression-retarding therapeutics). Recent studies have highlighted that the complex pathogenesis of amyotrophic lateral sclerosis is related to its multifactorial aetiology, including proteostasis disruption, impaired RNA metabolism and DNA repair, cytoskeletal and axonal transport defects, excitotoxicity, neuroinflammation, mitochondrial dysfunction, oligodendrocyte dysfunction, nucleocytoplasmic transport deficits, lipid dyshomeostasis, and autophagy. Several approved drugs are currently used to treat patients with amyotrophic lateral sclerosis; however, their curative efficacy is limited. Thus, the search for effective therapeutic strategies for amyotrophic lateral sclerosis requires a comprehensive understanding of its pathogenesis. Current evidence indicates that a single drug cannot provide a satisfactory therapeutic effect. Additionally, multiple pathophysiological processes and related targets are involved in the pathogenesis of amyotrophic lateral sclerosis. Therefore, research on multi-target synchronous interventions may be the path forward for discovering and developing potential neural repair strategies.},
}

@article {pmid41622459,
year = {2026},
author = {Diaz, G and Hetz, C},
title = {Protein disulfide isomerases in amyotrophic lateral sclerosis: Endoplasmic reticulum proteostasis and neuromuscular function.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-01874},
pmid = {41622459},
issn = {1673-5374},
}

@article {pmid41622338,
year = {2026},
author = {Salehcheh, M and Nikravesh, M and Aghebat-Bekheir, S and Matin, M},
title = {Manganese concentrations in biological matrices and amyotrophic lateral sclerosis (ALS): a systematic review and meta-analysis.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {2},
pages = {216},
pmid = {41622338},
issn = {1590-3478},
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/blood ; Humans ; *Manganese/blood/metabolism/analysis ; },
abstract = {BACKGROUND: Manganese (Mn) is an essential but neurotoxic trace element implicated in neurodegenerative disorders. Its association with amyotrophic lateral sclerosis (ALS) remains uncertain. We conducted a systematic review and meta-analysis to evaluate whether Mn concentrations differ between ALS patients and healthy controls.

METHODS: We systematically searched PubMed, EMBASE, Web of Science, and Scopus for observational studies comparing Mn concentrations between ALS patients and healthy controls. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Heterogeneity was assessed with the I² statistic, and publication bias was evaluated by Egger's test.

RESULTS: Twelve studies (446 ALS cases, 652 controls) measuring Mn in blood, serum, cerebrospinal fluid (CSF), hair, urine, toenail, plasma, or tissue were included. The pooled SMD was 0.05 (95% CI: - 0.20 to 0.30; p = 0.68; I² = 71.7%), indicating no significant difference in Mn concentrations. Subgroup analyses by biological matrix and analytical method showed no consistent pattern; meta-regression identified analytical method as a significant source of heterogeneity.

CONCLUSION: No publication bias was detected (Egger's p = 0.53). Peripheral Mn concentrations do not differ significantly between ALS patients and controls. Future research should employ longitudinal and CNS-targeted approaches, incorporating occupational exposure assessment and standardized analytical protocols.},
}

*Amyotrophic Lateral Sclerosis/metabolism/blood
Humans
*Manganese/blood/metabolism/analysis

@article {pmid41621861,
year = {2026},
author = {Loan, A and D'Mello, R and Li, Y and Nurkan, T and Minic, Z and Wang, J and Man Chan, H},
title = {Prenatal low-dose MeHg exposure leads to proteomic and transcriptomic alterations consistent with neurodegenerative disease in the cerebellum of C57BL/6 mice.},
journal = {The Journal of toxicological sciences},
volume = {51},
number = {2},
pages = {89-100},
doi = {10.2131/jts.51.89},
pmid = {41621861},
issn = {1880-3989},
mesh = {Animals ; *Methylmercury Compounds/toxicity/administration & dosage ; Female ; Pregnancy ; Mice, Inbred C57BL ; *Cerebellum/metabolism/drug effects/pathology ; *Prenatal Exposure Delayed Effects/genetics/metabolism/chemically induced ; *Transcriptome/drug effects ; Proteomics ; *Neurodegenerative Diseases/genetics/chemically induced/metabolism ; Male ; Oxidative Stress/drug effects ; Mice ; },
abstract = {Methylmercury (MeHg) is a global pollutant that readily crosses the blood-brain barrier and placenta, posing significant risks to fetal neurodevelopment. While the cerebellum is a recognized target of MeHg toxicity in adults, the effect of fetal exposure remains poorly defined. In this study, we investigated the neurotoxic effects of low-dose MeHg exposure (0.2 ppm via drinking water) on the cerebellums of prenatal C57BL/6 mice using integrated transcriptomic and proteomic analyses. Cerebellar tissues collected from postnatal day 90-120 (P90-120) mice (n = 3/group) were processed for RNA sequencing and proteomics analysis. Differentially expressed genes (DEGs) and proteins (DEPs) revealed significant changes (n = 4/group) in multiple pathways associated with neurodegeneration, including Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Overlapping transcriptomic and proteomic findings identified potential underlying mechanisms such as chemical carcinogenesis driven by reactive oxygen species and retrograde endocannabinoid signaling, underscoring the central role of oxidative stress in MeHg-induced neurotoxicity. Collectively, these results indicate that prenatal MeHg exposure induces persistent molecular alterations consistent with neurodegenerative processes and synaptic dysfunction, despite the absence of overt behavioral changes at the time of sacrifice. The long-term consequences for delayed symptom onset and the potential contribution of these changes to the etiology of neurodevelopmental disorders warrant further investigation.},
}

Animals
*Methylmercury Compounds/toxicity/administration & dosage
Female
Pregnancy
Mice, Inbred C57BL
*Cerebellum/metabolism/drug effects/pathology
*Prenatal Exposure Delayed Effects/genetics/metabolism/chemically induced
*Transcriptome/drug effects
Proteomics
*Neurodegenerative Diseases/genetics/chemically induced/metabolism
Male
Oxidative Stress/drug effects
Mice

@article {pmid41621376,
year = {2026},
author = {Luthfiyah, S and Triwiyanto, T and Rusyadi, L and Ismath, M},
title = {Letter to Editor: Correlation between MRI-derived and biopsy-confirmed liver iron concentration in patients with chronic liver disease.},
journal = {European journal of radiology},
volume = {196},
number = {},
pages = {112701},
doi = {10.1016/j.ejrad.2026.112701},
pmid = {41621376},
issn = {1872-7727},
abstract = {We comment on Ba-Ssalamah et al.'s study comparing MRI-derived and biopsy-confirmed liver iron concentration in chronic liver disease. The strong agreement between two R2*-based methods supports the robustness of relaxometry-based LIC estimation in the low-mild iron range. We discuss physics-related considerations, including R2* nonlinearity, spatial sampling, signal modeling, and calibration dependence, and outline future directions toward volumetric mapping and cross-platform harmonization for quantitative liver MRI.},
}

@article {pmid41621017,
year = {2026},
author = {Aynaashe, A and Kursula, P},
title = {Genetic commonalities between rare subtypes of ALS and CMT: insights into molecular mechanisms of neurodegeneration.},
journal = {Amino acids},
volume = {},
number = {},
pages = {},
doi = {10.1007/s00726-026-03500-w},
pmid = {41621017},
issn = {1438-2199},
abstract = {Amyotrophic lateral sclerosis (ALS) and Charcot-Marie-Tooth disease (CMT) are two distinct neurodegenerative disorders. While ALS is characterised by rapidly progressive motor neuron degeneration, leading to severe complications and death, CMT as a peripheral neuropathy is less severe, and patients have a longer life span, although with a compromised quality of life. Despite their clinical differences, current knowledge suggests that familial ALS (fALS) and CMT may share common genetic and molecular mechanisms. We aimed to identify shared genes mutations and molecular pathways between fALS and CMT through a literature and database search. Thirteen genes were identified, involved in distinct cellular processes: axonal transport (DYNC1H1, KIF5A, SPG11, DCTN1), protein homeostasis (NEFH, VCP, SOD1), RNA metabolism (GARS, SETX), cellular stress response (HSPB1, FIG4), and mitochondrial function (MFN2, CHCHD10). While these linkages to the two diseases are rare for each gene, understanding possible mechanistic commonalities at the molecular level can initiate new research directions, help in identifying additional common genes between neurodegenerative disorders, and improve diagnostics.},
}

@article {pmid41620396,
year = {2026},
author = {Carroll, E and Scaber, J and Pasniceanu, IS and Dafinca, R and Gordon, D and Candalija, A and Talbot, K},
title = {Mutant TDP-43 drives impairments in axonal transport and glycolysis in a mouse stem-cell-derived motor neuron model of amyotrophic lateral sclerosis (ALS).},
journal = {Cell death & disease},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41419-026-08437-2},
pmid = {41620396},
issn = {2041-4889},
abstract = {TDP-43 dysfunction is thought to be central to ALS pathogenesis. Studying mutations in the gene which encodes TDP-43, TARDBP, provides a valuable opportunity to gain insight into how TDP-43 dysfunction alters cellular homoeostasis. Our group has previously developed a TDP-43[M337V] mouse embryonic stem cell-derived motor neuron (mESC-MN) model, which expresses a single copy of the human TARDBP gene expressing the pathogenic M337V mutation at low levels. Here, we perform extensive phenotypic characterisation of this model, and show that TDP-43[M337V] leads to reduced MN viability, impaired axonal transport and reduced basal glycolysis compared to TDP-43[WT] controls. Altered neuronal viability and function occurs in the absence of TDP-43 mislocalisation or aggregation, suggesting 'proteinopathy' is downstream of these ALS-relevant phenotypes. These findings provide further support for a link between TDP-43 dyshomeostasis, cellular bioenergetics and axonal transport and suggest these pathways warrant further investigation as targets for therapeutic intervention.},
}

@article {pmid41619791,
year = {2026},
author = {Yazdani, S and Seitz, C and Andersson, J and Ingre, C and Fang, F and Lovik, A},
title = {Methodological considerations in the analysis of survival data in amyotrophic lateral sclerosis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/21678421.2026.2615111},
pmid = {41619791},
issn = {2167-9223},
abstract = {Survival outcomes are commonly analyzed in studies with data from patients with progressive, neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). Given the fast progression of ALS, survival analyses are, however, often difficult to perform and interpret. In this methodological article we demonstrate on real-world data how the choices we make in the study design, data collection, and analysis could influence the results. The factors we consider in this study are length of follow-up, sample size, timing of sample collection, and choice of covariables adjusted for in the models. We further discuss the importance of each of these contributing factors and about how to avoid mistakes in interpreting and reporting survival data in ALS and other rare, progressive diseases.},
}

@article {pmid41619170,
year = {2026},
author = {Steffke, C and Brenner, D and Catanese, A},
title = {Reply to "Extending the Interpretation of Biomarker Dynamics in SOD1-ALS Proteomics".},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78090},
pmid = {41619170},
issn = {1531-8249},
}

@article {pmid41619021,
year = {2026},
author = {Dressler, D and Frevert, J and Johnson, EA and Fink, K and Pellett, S and Pandey, S and Walter, U and Tacik, P and Kanovsky, P and Shahidi, GA and Brüggemann, N and Rosales, RL and Relja, M and Jin, L and Rodriguez, JAS and Pan, L and Francisco, GE and Shang, H and Bai, X and Adib Saberi, F},
title = {Iatrogenic botulism: a risk for botulinum toxin's medical use?.},
journal = {Journal of neural transmission (Vienna, Austria : 1996)},
volume = {},
number = {},
pages = {},
pmid = {41619021},
issn = {1435-1463},
abstract = {Botulinum toxin (BT) is infamous for its extreme toxicity. If it enters the bloodstream, it can cause botulism presenting with a typical pattern of motor and autonomic dysfunction. An international expert panel organised by IAB-Interdisciplinary Working Group for Movement Disorders explored iatrogenic botulism after BT's medical use (IB), reached conclusions and formulated recommendations. When injected into its target tissue, BT binds to gangliosides on cholinergic nerve terminals before it is internalised permanently. Small amounts of BT, however, are circulating within the bloodstream. When BT type B is applied, IB-B occurs frequently, typically affecting the autonomic nervous system. When BT type A is applied, IB-A only occurs in special circumstances, even when high doses are used. We identified 236 patients with IB-A in the literature. All IB-A was mild or moderate and fully reversible. In 212 patients, it occurred with unapproved BT use. In 116 of them, unapproved BT preparations were used, in 81, unapproved indications were treated and in 15, underlying neuromuscular impairment including myasthenia gravis, Lambert-Eaton myasthenic syndrome, amyotrophic lateral sclerosis and spinal muscle atrophy were contraindications for BT use. In 24 patients, IB-A occurred in approved BT use. Their evaluation was frequently incomplete, so that causes for IB-A often remain unclear. They may include presence of differential diagnosis, subclinical neuromuscular impairment and interference with additional diseases. When IB is suspected, proper evaluation is necessary to verify it and to identify its causes. Off-label use is common in BT therapy. However, it should be performed with caution, especially in children and when high doses are applied. High BT doses should not be applied to low volumes of target tissues, in order not to exceed the BT binding capacity.},
}

@article {pmid41618645,
year = {2026},
author = {Verhoeff, MC and van Selms, MKA and Lobbezoo, F},
title = {A Personal Exploration of Oral Health in Amyotrophic Lateral Sclerosis (ALS) Through the Eyes of a Multifaceted Authority.},
journal = {Journal of oral rehabilitation},
volume = {},
number = {},
pages = {},
doi = {10.1111/joor.70157},
pmid = {41618645},
issn = {1365-2842},
abstract = {BACKGROUND AND OBJECTIVE: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that impairs motor function, including oral musculature, complicating oral hygiene and care. Despite its impact, oral health in ALS patients remains under-addressed. This personal scoping review explores oral health in ALS through the dual lens of Dr. Maurits K.A. van Selms-a dental researcher and ALS patient-highlighting care, research, and education priorities.

METHODS: Semi-structured interviews were conducted via email with Dr. van Selms, using a topic guide adapted from a prior personal scoping review. The interview covered personal experiences and professional insights into oral health care, research, and education in ALS. Responses were analysed and synthesised into thematic agendas.

RESULTS: Dr. van Selms emphasised the neglect of oral hygiene in ALS care. He advocated for patient-informed, tailored guidelines based on functional capacity, interdisciplinary collaboration, and improved accessibility to dental services. In research, he called for ethically sensitive, patient-centered studies that reduce the burden of oral care. Educationally, he stressed the need for inclusive training across disciplines and stakeholder levels, promoting self-advocacy and awareness. Instructional materials, such as videos, were recommended to support caregivers and patients.

CONCLUSION: This personal scoping review underscores the importance of integrating oral health into ALS management. Dr. van Selms' unique perspective reveals gaps in care delivery, research ethics, and education, advocating for interdisciplinary collaboration and proactive guideline development. His insights offer a roadmap for improving oral health outcomes and quality of life in ALS and similar neurodegenerative conditions.},
}

@article {pmid41618386,
year = {2026},
author = {Omranikhoo, H and Rezaee, M and Verdizadeh, A and Goudarzi, Z and Jafari, M and Gholami, A and Poursadeghfard, M and Keshavarz, K},
title = {Cost-utility analysis of Edaravone compared to Riluzole in patients with amyotrophic lateral sclerosis (ALS) in Iran.},
journal = {Cost effectiveness and resource allocation : C/E},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12962-025-00697-7},
pmid = {41618386},
issn = {1478-7547},
}

@article {pmid41618385,
year = {2026},
author = {Koyama, T and Tsumura, H and Okita, R and Yamazaki, K and Hasegawa, A and Imamura, K and Kato, T and Iwata, H and Kojima, R and Inoue, H and Matsumoto, S and Okuno, Y},
title = {Chemical genomics language model toward reliable and explainable compound-protein interaction exploration.},
journal = {Journal of cheminformatics},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13321-026-01155-z},
pmid = {41618385},
issn = {1758-2946},
support = {JP24KJ1510//Japan Society for the Promotion of Science/ ; 22K06112//Japan Society for the Promotion of Science/ ; JP24H01771//Grant-in-Aid for Transformative Research Areas (A) "Latent Chemical Space"/ ; JP22bm0804034//Japan Agency for Medical Research and Development/ ; },
abstract = {Accurate prediction of compound-protein interactions (CPIs) is crucial for chemical biology and drug discovery. Despite recent advancements, existing deep learning (DL)-based CPI models often struggle to simultaneously achieve high generalization performance, quantify prediction confidence, and ensure explainability. Here, we propose ChemGLaM, a chemical genomics language model designed to address these three crucial challenges, thereby enabling reliable and explainable CPI predictions. ChemGLaM integrates independently pre-trained chemical and protein language models through an interaction block with a cross-attention mechanism, achieving near state-of-the-art performance in predicting novel CPIs at a low computational cost. Incorporating uncertainty estimation and attention visualization enables ChemGLaM to enhance the success rate of virtual screening and to provide molecular insights into CPIs. To demonstrate the practical impact of ChemGLaM, we constructed a publicly available database containing large-scale CPI predictions for every possible pairing between all 20,434 human proteins and all 11,455 drugs and validated its practical applicability in a case study on amyotrophic lateral sclerosis. ChemGLaM marks an important step forward in addressing the challenges of AI-driven CPI exploration and drug discovery.Scientific ContributionThis study established a unified CPI prediction framework that simultaneously achieves high generalization performance, confidence quantification, and explainability. We leveraged this framework to create a community resource by constructing a comprehensive CPI database and demonstrated its practical utility by successfully prioritizing hit compounds and deconvoluting their targets in a phenotypic screening for amyotrophic lateral sclerosis.},
}

@article {pmid41618346,
year = {2026},
author = {Öijerstedt, L and Mravinacová, S and Olofsson, J and Azizi, L and Bergström, S and Yazdani, S and De Vita, N and Aksoylu, IS and Foucher, J and Juto, A and Kläppe, U and Nilsson, P and Månberg, A and Ingre, C},
title = {Ratios of CSF proteins reflect cognitive function in ALS.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-01976-y},
pmid = {41618346},
issn = {1758-9193},
}

@article {pmid41617608,
year = {2026},
author = {Tankéré, P and Bernard, E and Herquelot, E and Denis, H and Sfeir, L and Saint-Raymond, C and Mallaret, M and Lavergne, F and Baillieul, S and Peter-Derex, L and Tamisier, R and Pépin, JL},
title = {Health trajectories of patients with amyotrophic lateral sclerosis before and after initiation of non-invasive ventilation: a French nationwide database analysis.},
journal = {Thorax},
volume = {},
number = {},
pages = {},
doi = {10.1136/thorax-2025-223974},
pmid = {41617608},
issn = {1468-3296},
abstract = {BACKGROUND: Management of amyotrophic lateral sclerosis (ALS) is complicated by heterogeneous presentation and unpredictable disease course. This study described disease trajectories before and after initiation of non-invasive ventilation (NIV) therapy in individuals with ALS, examined the relationship between NIV initiation timing and survival and analysed health trajectory clusters.

METHODS: Data were extracted from the French national health insurance reimbursement system database for individuals with ≥1 reimbursement for NIV from January 2015 to December 2019, and ≥1 ALS disease code. Health trajectory clusters were determined using time sequence analysis through K-clustering.

RESULTS: We analysed data from 3443 individuals with ALS (58% male, median age 67 years). The median (IQR) time from ALS diagnosis to NIV initiation was 10.8 (4.5-22.2) months and death occurred 21.5 (12.8-33.9) months after diagnosis. Tracheostomy/gastrostomy was performed in 3.9%/33.4% of patients, respectively. Unsupervised machine learning clustering identified four distinct patient groups. NIV initiation was late in two Clusters (A and B); these individuals were younger, had fewer comorbidities and more physiotherapy sessions before/after NIV. Survival after NIV initiation was longer in Clusters B and C; these individuals had lower rates of depression/anxiety, more prescription of mechanical in/exsufflation therapy and fewer home and emergency hospitalisations. Cluster B was unique, showing late NIV initiation and long post-NIV survival. This cluster was more likely to have spinal onset, a higher rate of obstructive sleep apnoea and fewer comorbidities.

CONCLUSIONS: There was marked heterogeneity between patients with ALS and their care trajectories. Our data do not support a universal benefit for early initiation of NIV therapy.},
}

@article {pmid41616251,
year = {2026},
author = {Sang, Y and Ren, J and Aballay, A},
title = {A gut-activated NHR-86-CYP pathway mediates the neuroprotective effects of Enterococcus faecium probiotics in a nematode model of amyotrophic lateral sclerosis.},
journal = {PLoS biology},
volume = {24},
number = {1},
pages = {e3003627},
doi = {10.1371/journal.pbio.3003627},
pmid = {41616251},
issn = {1545-7885},
abstract = {Neurodegenerative diseases are often associated with oxidative stress, and while probiotics may influence neuronal health, the underlying mechanisms remain poorly understood. Using the sod-1 A4VM amyotrophic lateral sclerosis (ALS) model in Caenorhabditis elegans, we investigated the protective effects of the probiotic Enterococcus faecium against oxidative stress-induced neurodegeneration. Animals fed E. faecium showed reduced motor neuron degeneration under oxidative stress compared to those maintained on a standard Escherichia coli diet. Transcriptome analysis revealed a significant enrichment of oxidoreductase genes, including cytochrome P450 (cyp) genes. RNAi-mediated knockdown of cyp genes impaired E. faecium-mediated neuroprotection, and this loss correlated with increased reactive oxygen species (ROS) levels. We identified the conserved nuclear hormone receptor NHR-86 as a key regulator of cyp gene expression and neuroprotection. Loss of nhr-86 abolished the probiotic's protective benefits, while transgenic expression of nhr-86 restored cyp induction and neuronal resilience. Importantly, intestinal expression of NHR-86 was sufficient to restore CYP induction and neuronal resilience, whereas neuronal knockdown had no effect, indicating that gut NHR-86 activity is essential for this protective pathway. These findings reveal a previously uncharacterized NHR-CYP regulatory axis activated by an intestinal probiotic, highlighting a mechanistic link between microbial signals and host neuroprotection.},
}

@article {pmid41616079,
year = {2026},
author = {Steenkjaer, CH and Storgaard, JH and Levison, L and Blicher, JU},
title = {A national survey of pseudobulbar affect and symptomatic treatment in Amyotrophic Lateral Sclerosis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/21678421.2026.2620448},
pmid = {41616079},
issn = {2167-9223},
abstract = {OBJECTIVE: We aimed to determine diagnostic prevalence and symptom burden of pseudobulbar affect (PBA) in patients with Amyotrophic Lateral Sclerosis (ALS) in Denmark and differences in ongoing symptomatic treatment.

METHODS: In this national cross-sectional survey study, participants with ALS completed an online survey regarding PBA and PBA symptoms, which were quantified through the Center for Neurologic Study Lability Scale (CNS-LS). A CNS-LS score ≥ 13 served as a threshold indicative of PBA.

RESULTS: 157 participants with ALS were recruited. 12.1% were diagnosed with PBA and were more likely to receive antidepressant medication compared to those not diagnosed with PBA (47.4% compared to 15.2%, p = 0.002). 30.6% scored ≥13 in the CNS-LS; however, the proportion of participants treated with antidepressants was similar compared to those scoring below the ≥13 threshold (25% compared to 16.5%, p = 0.27). Of those not diagnosed with PBA, 23.2% scored ≥13 in the CNS-LS. This PBA symptomatic, but undiagnosed group was less likely to receive symptomatic treatment compared to patients with diagnosed PBA (12.5% compared to 47.4%, p = 0.009). No differences were seen in CNS-LS score between these groups.

CONCLUSIONS: The proportion of diagnosed PBA among the study population was low compared to previous studies; however, the proportion of patients with symptoms of possible PBA was markedly higher. Patients with known PBA were more likely to receive recommended symptomatic treatment compared to patients not diagnosed with PBA, despite symptoms indicative of PBA. These findings highlight the potential underrecognition of PBA in ALS and concurrent absence of symptomatic treatment.},
}

@article {pmid41615807,
year = {2026},
author = {Azizzadeh, M and Pirker-Kees, A and Wouters, EFM and Janssen, DJA and Spaetgens, B and Breyer-Kohansal, R and Breyer, MK},
title = {Association of allostatic load with frailty trajectories and the mediating role of depressive symptoms.},
journal = {The Journal of frailty & aging},
volume = {15},
number = {2},
pages = {100132},
doi = {10.1016/j.tjfa.2026.100132},
pmid = {41615807},
issn = {2260-1341},
abstract = {BACKGROUND: Frailty is a dynamic, age-related condition marked by progressive loss of resilience. Its risk factors include socioeconomic status and physiological stress burden, such as allostatic load score (ALS), remain unclear. This study aims to examine the role of depression in the association between ALS and frailty trajectories.

METHODS: We analyzed data from 5885 LEAD cohort participants aged 25-82 years at baseline and from 3564 participants with follow-up data. Frailty status (robust, pre-frail, frail) was defined using the Fried phenotype, and transitions between visits were assessed. ALS was calculated from 14 parameters spanning cardiovascular, metabolic, and body composition measures. Associations of ALS with frailty status at baseline and with frailty transitions at follow-up were examined, and depressive symptoms were tested as a mediator.

RESULTS: At baseline, 62.3% of participants were robust, 36.2% pre-frail, and 1.5% frail. Between visits, 16.3% transitioned to a worse frailty stage, while 17.7% improved. Higher ALS was linked to increased odds of being pre-frail/frail at baseline (OR 1.11; 95% CI: 1.08-1.15), and to a higher risk of transitioning from robust to pre-frail/frail (RRR 1.06; 95% CI: 1.02-1.09). Depressive symptoms mediated 35% (95% CI: 25-47%) of the cross-sectional and 17% (95% CI: 6.6-43%) of the longitudinal association between ALS and frailty.

CONCLUSIONS: Socioeconomic factors influenced frailty onset but not its progression, whereas depressive symptoms mediated approximately 17% of the effect of ALS on frailty development over time. These findings highlight the importance of exploring the effect of interventions for depression on frailty progression.},
}

@article {pmid41614607,
year = {2026},
author = {Combe, P and Subecz, C and Le Goff, G and Plamont, MA and Bohl, D and Gueroui, Z},
title = {Concentration-dependent cytoplasmic phase separation of TDP-43 drives aggregation and proteinopathy.},
journal = {The FEBS journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/febs.70429},
pmid = {41614607},
issn = {1742-4658},
support = {MND202003011470//Fondation pour la Recherche Médicale/ ; },
abstract = {TDP-43 mislocalization and aggregation are common features of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). However, the mechanisms underlying the transition of nuclear TDP-43 to cytoplasmic aggregates, and their contribution to disease pathogenesis, remain poorly understood. To address this gap, we present a methodology to chemically control the assembly and disassembly of cytoplasmic TDP-43 condensates. By fusing TDP-43 to a phase separation-prone protein scaffold, we can induce the formation of cytoplasmic TDP-43 condensates or, conversely, promote nuclear localization upon addition of a disassembly molecule. TDP-43 accumulates into various assemblies, ranging from submicrometric puncta to larger aggregate-like structures that display hallmarks of proteinopathy in a concentration-dependent manner. Furthermore, oxidative stress drives the maturation of TDP-43 assemblies from puncta into aggregates through interactions with stress granule components. Finally, we show that cytoplasmic TDP-43 aggregates deplete nuclear endogenous TDP-43 and induce cytotoxicity. Collectively, these findings highlight the local cytoplasmic concentration of TDP-43 and stress exposure as key determinants in the onset of TDP-43 proteinopathy, providing a relevant model to study pathological TDP-43 aggregation.},
}

@article {pmid41614057,
year = {2025},
author = {Subramani, NK and Venugopal, S and Rajan, AP},
title = {An integrated subtractive genomics and immunoinformatic approach for designing a multi-epitope peptide vaccine against methicillin-resistant Staphylococcus aureus.},
journal = {Frontiers in bioinformatics},
volume = {5},
number = {},
pages = {1745495},
pmid = {41614057},
issn = {2673-7647},
abstract = {INTRODUCTION: MRSA is a multi-drug-resistant bacteria responsible for severe infections that has become a major health concern. Due to constraints of traditional methods, there is a need for developing a new approach to prevent the MRSA-related infections by targeting key pathogens.

METHODS: Initially, the subtractive genomics was applied to the MRSA proteome to identify non-homologous, essential, and virulence targets using comparative BLAST-based screening. Further, immunoinformatic tools were employed for B- and T-cell epitope prediction and vaccine construction with appropriate adjuvants and linkers, followed by immune simulation and molecular docking with immune receptors.

RESULTS: Comparative metabolic pathway analysis identified 294 MRSA pathway proteins, with acetolactate synthase (ALS) as a non-homologous, essential, and virulent protein that is involved in the branched amino acid biosynthesis pathway. The constructed ALS vaccine consists of 3 B-cell and 19 T-cell epitopes exhibited stable immunological features with 97.55% global population coverage. Molecular docking revealed that ALS exhibited a superior binding affinity with the TLR4 receptor (-1,438.7 kcal/mol) than the TLR2 receptor (-1,103.5 kcal/mol), which was further confirmed by high structural stability and compactness analysis. Immune simulations also exhibited elevated IgM, IgG subtypes, and cytokine productions, suggesting a robust humoral and cellular immunity.

DISCUSSION: Identified ALS highlights its biological relevance in MRSA survival. The stability predictions with TLR4 suggested effective activation of innate immunity that may enhance antigen presentation and downstream adaptive immunity. The validation of the ALS vaccine's safety and immunogenicity further requires comprehensive in vitro and in vivo examinations.

CONCLUSION: Thus, ALS is recognized as a promising MRSA vaccine candidate and has the potential to activate immune responses effectively.},
}

@article {pmid41613680,
year = {2025},
author = {Yamazaki, J and Hideyama, T and Teramoto, S and Kato, H and Aizawa, H and Kwak, S and Terashi, H},
title = {Age-Related Changes in Matrix Metalloproteinase-9 Expression in Spinal Motor Neurons of Normal Mice.},
journal = {Cureus},
volume = {17},
number = {12},
pages = {e100305},
pmid = {41613680},
issn = {2168-8184},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder involving the degeneration of upper motor neurons (UMNs) and lower motor neurons (LMNs). Although the cause of motor neuron (MN) degeneration in patients with ALS remains unknown, certain MN types (such as oculomotor neurons) and MNs within the Onuf (Onuf-Mannen) nucleus are preserved until the terminal stage. We previously generated mice with a selective knockout of adenosine deaminase acting on RNA 2 (ADAR2) in cholinergic neurons (ADAR2[flox/flox] /vesicular acetylcholine transporter (VAChT)-Cre.Fast; AR2). AR2 mice exhibit slow progressive loss of LMNs accompanied by TAR DNA-binding protein 43 (TDP-43) pathology against a background of insufficient editing at the GluA2 glutamine/arginine (Q/R) site due to ADAR2 deficiency. This model confirmed that insufficient editing at the GluA2 Q/R site, due to reduced ADAR2 activity, contributes to the pathogenesis of ALS. Furthermore, in AR2 mice, more frequent death of fast-fatigable motor neurons (FF MNs) was observed owing to differences in vulnerability under ADAR2-deficient conditions. Similar changes were observed during normal aging in the control mice. These findings suggest that investigating the characteristics of FF MNs may be useful for analyzing neuronal death in ALS. Recently, matrix metalloproteinase-9 (MMP-9), a marker of FF MNs, was reported to induce neurodegeneration. However, the distribution of MMP-9 in normal spinal MNs and its age-related changes remain unclear. Therefore, we investigated the MMP-9 expression patterns in normal mice at six and 12 months of age. In the present study, the number of MNs in the anterior horn (AH) decreased with age, as did the number of MMP-9-positive MNs. Furthermore, as aging has been shown to induce the abnormal localization of TDP-43 in MMP-9-positive MNs, these MNs were considered vulnerable to degeneration. These findings suggest that MMP-9 not only functions as a marker for FF MNs but may also act as a potentially useful marker for MNs prone to degeneration with TDP-43 pathology, or for early degeneration in both physiological aging and age-related diseases, including ALS. Future investigations of MMP-9 expression in patients with ALS and in ALS mouse models are considered useful for elucidating ALS pathogenesis.},
}

@article {pmid41613245,
year = {2026},
author = {Aronsen, J},
title = {You have ALS: a nurse's revolt against despair.},
journal = {Journal of research in nursing : JRN},
volume = {},
number = {},
pages = {17449871251407834},
doi = {10.1177/17449871251407834},
pmid = {41613245},
issn = {1744-988X},
}