@article {pmid42070188,
year = {2026},
author = {Chambers, RL and Lahuerta-Martín, S and Greco, AM and Pattinson, R and Pickles, T and Hassan, J and Mokkink, LB},
title = {Assessing content validity: challenges of conducting systematic reviews of patient-reported outcome measures and recommendations to improve the application of COSMIN guidance.},
journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation},
volume = {35},
number = {6},
pages = {},
pmid = {42070188},
issn = {1573-2649},
abstract = {PURPOSE: Systematic reviews of Patient-Reported Outcome Measures (PROMs) are essential for selecting appropriate measures for research and clinical practice. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines provide a standardised framework for evaluating measurement properties of PROMs, with content validity considered to be the most important property, yet the most complex and poorly reported. This study aimed to report common challenges researchers face when evaluating content validity in systematic reviews on the quality of PROMs, and to provide clear, experience-informed recommendations to overcome them.

METHOD: A narrative synthesis of challenges in evaluating content validity in systematic reviews of PROMs is presented. Challenges were extracted from Elsman et al.’s umbrella review and from stakeholder consultations with the authors of this manuscript, providing practical recommendations and illustrative examples.

RESULTS: Seven challenges were identified: (1) feasibility of conducting a systematic review on the quality of PROMs, (2) identifying all articles describing PROM development for the target population, (3) managing different versions of PROMs, (4) poor reporting in primary studies (5) ambiguity in classifying studies as PROM development or content validity studies, (6) applying the criteria for content validity, specifically, to the results of development studies, and (7) accurately framing the scope of the PROM and the review. Recommendations include narrowing the scope of the review, conducting supplementary searches, treating PROM versions distinctly, and guidance on how to interpret poorly reported studies.

CONCLUSION: These insights support consistent application of COSMIN guidelines and improve PROM selection and use, complementing existing COSMIN materials.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11136-026-04261-5.},
}

@article {pmid42082278,
year = {2026},
author = {Zhu, Z and Yuan, L and Yang, J and Jiang, S and Cao, Y and Yang, J and Zhang, Y and Mo, Y and Chen, C and Zhang, H and Zhou, J and , },
title = {Healthcare burden of bronchopulmonary dysplasia among very preterm infants in China: a cohort study.},
journal = {BMJ paediatrics open},
volume = {10},
number = {1},
pages = {},
doi = {10.1136/bmjpo-2025-004259},
pmid = {42082278},
issn = {2399-9772},
mesh = {Humans ; *Bronchopulmonary Dysplasia/epidemiology/mortality/economics/therapy ; China/epidemiology ; Infant, Newborn ; Female ; Male ; Prospective Studies ; Intensive Care Units, Neonatal ; Length of Stay/statistics & numerical data ; Infant, Extremely Premature ; Severity of Illness Index ; Infant, Premature ; Gestational Age ; Infant ; Hospitalization/statistics & numerical data/economics ; *Cost of Illness ; },
abstract = {OBJECTIVE: To assess the healthcare burden of bronchopulmonary dysplasia (BPD) among very preterm infants in China.

DESIGN: A prospective cohort study between 2022 and 2023.

SETTING: Chinese Neonatal Network (CHNN) participating centres.

PATIENTS: Infants with gestational age <32 weeks admitted to CHNN neonatal intensive care units.

MAIN OUTCOME MEASURES: A composite rate of BPD or mortality at 36 weeks' postmenstrual age (PMA), major comorbidities, clinical resources utilisation and outcome at discharge. BPD severity was classified by Jensen et al's criteria.

RESULTS: Among 17 793 eligible infants, 568 (3.2%) infants died before 36 weeks' PMA, 1729 (9.7%) were discharged against medical advice before 36 weeks' PMA, 9895 (55.6%) were classified as no BPD, 2751 (15.5%) developed Grade 1 BPD, 2634 (14.8%) developed Grade 2 BPD and 216 (1.2%) developed Grade 3 BPD. Infants with BPD had significantly longer hospital stays than those without BPD (median (IQR), 67 (52-84) vs 44 (34-56) days) and incurred higher total hospitalisation charges (median (IQR), 127 (91-177) vs 73 (52-103) thousand CNY) and charge per day (median (IQR), 1975 (1638-2361) vs 1714 (1409-2048) CNY). Mortality at discharge increased with BPD severity, with rates of 0.2% (18/9895) for infants without BPD, 0.5% (15/2751) for Grade 1 BPD, 2.1% (56/2634) for Grade 2 and 26.9% (58/216) for Grade 3. Similarly, the rates of major comorbidities and the need for home oxygen therapy increased with BPD severity.

CONCLUSIONS: Greater BPD severity was associated with increased comorbidities, higher in-hospital mortality and greater utilisation of healthcare resources. These findings emphasised the ongoing need to develop cost-saving strategies to reduce the risk and severity of BPD in this vulnerable population and improve overall care.},
}

Humans
*Bronchopulmonary Dysplasia/epidemiology/mortality/economics/therapy
China/epidemiology
Infant, Newborn
Female
Male
Prospective Studies
Intensive Care Units, Neonatal
Length of Stay/statistics & numerical data
Infant, Extremely Premature
Severity of Illness Index
Infant, Premature
Gestational Age
Infant
Hospitalization/statistics & numerical data/economics
*Cost of Illness

@article {pmid42082894,
year = {2026},
author = {Kipourgos, G and Bakalis, N and Albani, E and Stefanopoulos, N and Lakoumentas, J and Tzenalis, A},
title = {Expert Consensus on Key Attributes of Nurses in Resuscitation Teams: Findings From a Delphi Study.},
journal = {Nursing in critical care},
volume = {31},
number = {3},
pages = {e70506},
doi = {10.1111/nicc.70506},
pmid = {42082894},
issn = {1478-5153},
mesh = {Humans ; Delphi Technique ; *Consensus ; *Clinical Competence ; *Patient Care Team ; *Heart Arrest/nursing/therapy ; Greece ; Female ; Male ; *Resuscitation/nursing ; *Cardiopulmonary Resuscitation/nursing ; Adult ; Middle Aged ; },
abstract = {BACKGROUND: In-hospital cardiac arrest (IHCA) requires coordinated interdisciplinary action. Nurses are often first responders and essential members of resuscitation teams, yet the attributes that define their effectiveness remain unclear. Although team performance has been widely studied, few works have systematically examined nursing competencies in this context. This is the first Delphi-based study in Greece defining key nursing attributes within in-hospital resuscitation teams.

AIM: To achieve expert consensus on the key attributes characterizing effective nursing participation in IHCA teams.

STUDY DESIGN: A two-round Delphi study was conducted with experts in resuscitation and critical care. Round one involved thematic analysis of semi-structured interviews. In round two, experts rated attributes on a 10-point Likert scale. Consensus was defined as mean (M) > 8 and coefficient of variation (CV) < 20%. Descriptive statistics and Kendall's W assessed agreement across domains.

RESULTS: Thirty-nine attributes were identified and grouped into seven domains: education, experience, physical condition, psychological resilience, technical skills and non-technical skills. Thirty-five attributes met the consensus criteria. Highest agreement was observed for ALS certification, stress resilience, closed-loop communication, adaptability and teamwork. Strongest consensus emerged in non-technical (M = 9.75, CV = 3.79%) and technical (M = 9.61, CV = 5.62%) domains.

CONCLUSIONS: This study provides an evidence-informed framework of competencies and personal qualities underpinning nurses' effectiveness in resuscitation teams, emphasizing both technical expertise and non-technical skills-especially closed-loop communication, composure and collaboration.

The framework supports clearer role delineation, structured competency development and enhanced team effectiveness in IHCA management.},
}

Humans
Delphi Technique
*Consensus
*Clinical Competence
*Patient Care Team
*Heart Arrest/nursing/therapy
Greece
Female
Male
*Resuscitation/nursing
*Cardiopulmonary Resuscitation/nursing
Adult
Middle Aged

@article {pmid42082968,
year = {2026},
author = {Terrin, F and Faggin, S and Bizzotto, E and Santinello, D and Cerantola, S and Borsato, G and Fabris, F and Scarso, A and Licitra, R and Guella, G and Sales, G and Cagnin, S and Treu, L and Bubacco, L and Giron, MC and Plotegher, N and Dalla Valle, L},
title = {β-Sitosterol β-D-glucoside (BSSG) triggers intestinal inflammation in zebrafish and mouse models prior to neurodegeneration onset.},
journal = {Journal of biomedical science},
volume = {33},
number = {1},
pages = {},
pmid = {42082968},
issn = {1423-0127},
support = {PhD Fellowship 2020//MUR/University of Padova/ ; PostDoc Fellowship 2024//Department of Biology/ ; PostDoc Fellowship ARD-B 2023//Department of Pharmaceutical and Pharmacological Sciences/ ; PostDoc Fellowship ARD-B 2020//Department of Pharmaceutical and Pharmacological Sciences/ ; Seed 2020//Department of Biology Intramural Grant/ ; Seed 2022//Department of Biology Intramural Grant/ ; Project ID: CN00000041 - SP. 3//National Center For Gene Therapy And Drugs Based On RNA Technology Neurodegeneration/ ; UNIPD-DSF-PRID-2023//San Camillo Hospital Grant, Treviso, Italy/ ; },
mesh = {Animals ; Zebrafish ; Mice ; *Sitosterols/adverse effects/toxicity ; Disease Models, Animal ; Gastrointestinal Microbiome/drug effects ; *Intestines/drug effects ; *Glucosides/adverse effects ; *Inflammation/chemically induced ; *Neurodegenerative Diseases/chemically induced ; },
abstract = {BACKGROUND: Glucosylated-sterols can be synthetized endogenously, absorbed through the diet or derive from bacterial infection. Their clinical relevance is currently underestimated, even though their imbalance has been associated with an increased risk of neurodegeneration over the lifespan. We studied the detrimental effects elicited by dietary consumption of the plant-derived β-sitosterol β-D-glucoside (BSSG), known to be associated with the occurrence of ALS-PDC, to elucidate its potential mechanism of action.

METHODS: Zebrafish larvae and adults, as well as mice, were treated with BSSG administered directly in the water or via customized food pellet, respectively. Since the intestine was identified as the primary target tissue, its morphological and functional characteristics were assessed, together with transcriptional profiling and gut microbiota sequencing. Ex vivo analysis of zebrafish gut contractility was applied to evaluate intestinal neuromuscular responses. Mutant and transgenic zebrafish lines were used to explore a potential BSSG mechanism of action.

RESULTS: BSSG induced intestinal inflammation in both zebrafish and mouse models. This previously unknown effect was evidenced by gut dysmotility and inflammatory response. Transcriptomic analyses revealed increased expression of inflammation-related genes in the intestine of both zebrafish and mice, while preliminary gut microbiota analyses suggested the onset of dysbiosis. Transgenic and mutant zebrafish lines, depleted of genes involved in glucocorticoids synthesis and activity, evidenced that BSSG likely interacts with the glucocorticoid receptor, potentially impairing its canonical anti-inflammatory activity.

CONCLUSIONS: We identified novel pathways altered by dietary BSSG exposure. This molecule appears to initially induce gut inflammation, leading to changes in intestinal morphology and function, and may contribute to neurodegeneration through disruption of the well-known gut-brain axis.},
}

Animals
Zebrafish
Mice
*Sitosterols/adverse effects/toxicity
Disease Models, Animal
Gastrointestinal Microbiome/drug effects
*Intestines/drug effects
*Glucosides/adverse effects
*Inflammation/chemically induced
*Neurodegenerative Diseases/chemically induced

@article {pmid42083136,
year = {2026},
author = {O'Reilly, ÉJ and Bjornevik, K and Furtado, JD and Patel, AV and Wang, Y and Kolonel, LN and Le Marchand, L and Ascherio, A},
title = {Pre-Diagnostic Plasma Carotenoids, Tocopherols and Retinol Levels, and Risk of Amyotrophic Lateral Sclerosis.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78240},
pmid = {42083136},
issn = {1531-8249},
support = {R01 NS045893/NS/NINDS NIH HHS/United States ; R01 CA49449//Common Fund/ ; U01 CA164973/CA/NCI NIH HHS/United States ; U01 CA167552/CA/NCI NIH HHS/United States ; UM1 CA186107/CA/NCI NIH HHS/United States ; },
abstract = {OBJECTIVE: Our goal was to examine whether pre-diagnostic plasma carotenoids and tocopherols are associated with amyotrophic lateral sclerosis (ALS).

METHODS: A nested case-control study within 4 United States cohorts, where 154 participants with pre-diagnostic blood-draw, were diagnosed during follow-up with amyotrophic lateral sclerosis (ALS). Controls were randomly selected from participants alive on the date a case was diagnosed, matched 2:1 by cohort, sex, age, race/ethnicity, fasting-status, time of blood-draw. Carotenoid and tocopherol levels were quantified by high-performance liquid-chromatography with diode array-detector. ALS incidence or death rate ratios (RR) were estimated using conditional logistic regression adjusting for body mass index, smoking status, physical activity, cholesterol, and urate levels.

RESULTS: The association between beta-carotene and ALS varied by sex (p-for-interaction = 0.007). After matched- and multivariable-adjustment, women with higher cis-, trans- and total beta-carotene had lower incidence of ALS (RR for 1-standard deviation [SD] increase in total beta-carotene: 0.68; 95% CI: 0.48-0.98; p = 0.038), whereas a positive association was seen in men (1-SD increase: RR = 1.44; 95% CI: 1.03-2.01; p = 0.033). However, after further adjustment for other correlated carotenoids, the association in men was attenuated, whereas it remained significant in women. Women with higher beta-cryptoxanthin, but not men, had a lower risk of ALS (1-SD increase: RR = 0.67; 95% CI: 0.48-0.94; p = 0.02; p-for-interaction = 0.12). Alpha-carotene, lutein-zeaxanthin, lycopene, retinol, and tocopherols were not associated with ALS, except for a borderline inverse association of gamma-tocopherol in men (RR = 0.74; 95% CI: 0.54-1.01; p = 0.059).

INTERPRETATION: Higher pre-diagnostic plasma levels of beta-carotene and beta-cryptoxanthin in women and gamma-tocopherol in men were suggestively associated with lower ALS risk. Other carotenoids or tocopherols were not clearly associated with ALS. ANN NEUROL 2026.},
}

@article {pmid42084465,
year = {2026},
author = {Farquharson, K and Macrae, T},
title = {Lexical Properties of Stimuli in Standardized Articulation and Phonology Tests: A Short Report.},
journal = {American journal of speech-language pathology},
volume = {},
number = {},
pages = {1-9},
doi = {10.1044/2026_AJSLP-25-00129},
pmid = {42084465},
issn = {1558-9110},
abstract = {PURPOSE: The purpose of the present study was to report the phonological neighborhood density, phonotactic probability, and word frequency of the stimuli in 12 commonly used articulation and/or phonological tests. We extend the work of Macrae (2017), who identified variability in stimulus items across consonant singletons, consonant clusters, vowels, phoneme complexity, and bound morpheme. This study sought to augment that work with a deeper analysis of lexical and sublexical features of these stimuli.

METHOD: The stimuli from 12 articulation and/or phonological tests were extracted, resulting in 667 stimuli. All stimuli were run through a phonological neighborhood density and phonotactic probability calculator. Word frequency was determined using Moe et al.'s (1982) database.

RESULTS: Means and ranges for all lexical characteristics were computed across each of the 12 tests. Most stimuli were from sparse phonological neighborhoods, and included common sound sequences. Although the average word frequency value was in the high range, overall, very few test stimuli were high-frequency words.

DISCUSSION: There was not one articulation and/or phonological test that considered or balanced these three lexical properties. We discuss the linguistic constraints surrounding developing such a test. We also discuss future research opportunities to examine if these lexical properties may result in over- and underidentification of children with speech sound disorders.},
}

@article {pmid42084479,
year = {2026},
author = {Liu, X and Dhakal, D and Gu, S and Li, G and Jing, M and Zhang, G and Wang, Y and Zhang, Z and Fan, D},
title = {Relationship between grip strength, functional outcome, and health-related quality of life measurements in amyotrophic lateral sclerosis patients.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/17582024.2026.2667425},
pmid = {42084479},
issn = {1758-2032},
abstract = {AIM: To explore how grip strength is related to functional status and health-related quality of life (HRQoL) in amyotrophic lateral sclerosis (ALS) patients.

METHODS: In the phase 2 trial of TBN for treatment of ALS, 148 patients in full analysis set received TBN (600 mg or 1200 mg) or a placebo for 180 days. Outcome measurements included ALS Functional Rating Scale-Revised (ALSFRS-R), 40-item ALS Assessment Questionnaire (ALSAQ-40), grip strength, and forced vital capacity (FVC). Spearman's rank correlation was used to examine associations between grip strength, ALSFRS-R and ALSAQ-40. A principal component analysis-ANCOVA model adjusted for sex was used to further explore the associations.

RESULTS: Grip strength was strongly correlated with ALSFRS-R fine motor function domain (rs = 0.740) and moderately correlated with ALSAQ-40 activities of daily living (ADL) domain (rs = -0.637) (p < 0.05). Weak correlations were observed between FVC and both ALSFRS-R total score (rs = 0.355) and respiratory domain (rs = 0.229) and ALSAQ-40 domains. Grip strength was a strong predictor of ALSFRS-R fine motor and ALSAQ-40 ADL domains.

CONCLUSION: Grip strength was associated with functional status and HRQoL, supporting its potential role as a meaningful clinical outcome measure in patients with ALS.},
}

@article {pmid42084503,
year = {2026},
author = {Shino, Y and Muraki, N and Kobatake, Y and Kamishina, H and Kosuge, H and Nakakido, M and Tsumoto, K and Furukawa, Y},
title = {Structural analysis of Cu/Zn-superoxide dismutase linked to neurodegenerative disease by antibody-guided cryo-EM.},
journal = {Protein science : a publication of the Protein Society},
volume = {35},
number = {6},
pages = {e70615},
doi = {10.1002/pro.70615},
pmid = {42084503},
issn = {1469-896X},
support = {19H05765//Ministry of Education, Culture, Sports, Science and Technology/ ; 22H02768//Ministry of Education, Culture, Sports, Science and Technology/ ; 22K19389//Ministry of Education, Culture, Sports, Science and Technology/ ; },
mesh = {Dogs ; Animals ; *Superoxide Dismutase-1/chemistry/metabolism/genetics ; Cryoelectron Microscopy ; *Antibodies, Monoclonal/chemistry/metabolism ; Humans ; *Neurodegenerative Diseases/enzymology ; Models, Molecular ; Dog Diseases/enzymology ; Amyotrophic Lateral Sclerosis ; },
abstract = {Accumulation of misfolded proteins is a hallmark of many neurodegenerative diseases. To characterize such misfolded species in vivo, conformation-specific antibodies are widely used; however, limited knowledge of antibody-epitope interactions often hampers mechanistic insight. To address this, we determined the cryo-electron microscopy structure of the complex between a monoclonal antibody, 19A9, and Cu/Zn-superoxide dismutase (SOD1), a protein associated with canine degenerative myelopathy (DM), which is related to human amyotrophic lateral sclerosis. Biochemical analyses confirmed that 19A9 specifically recognizes monomeric SOD1, and the structure revealed binding near the interface normally used for homodimerization in native SOD1, with steric hindrance preventing interaction when the protein is in its homodimeric form. Immunofluorescence staining of spinal cord sections revealed that 19A9 stained a subset of motoneurons in DM-affected dogs, but not in asymptomatic controls. Structural characterization of the 19A9-monomeric SOD1 complex enabled us to propose that SOD1 monomers can arise in vivo under pathological conditions.},
}

Dogs
Animals
*Superoxide Dismutase-1/chemistry/metabolism/genetics
Cryoelectron Microscopy
*Antibodies, Monoclonal/chemistry/metabolism
Humans
*Neurodegenerative Diseases/enzymology
Models, Molecular
Dog Diseases/enzymology
Amyotrophic Lateral Sclerosis

@article {pmid42084731,
year = {2026},
author = {Pendergast, TH and Maddali, S and Chaluvadi, SR and Qi, P and Vencill, WK and Bennetzen, JL and Devos, KM},
title = {Widespread non-target-site resistance in Setaria viridis to four classes of herbicide.},
journal = {TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik},
volume = {139},
number = {6},
pages = {},
pmid = {42084731},
issn = {1432-2242},
support = {0952177//Directorate for Biological Sciences/ ; },
mesh = {*Herbicide Resistance/genetics ; *Herbicides/pharmacology ; Acetyl-CoA Carboxylase/genetics ; *Setaria Plant/genetics/drug effects ; Acetolactate Synthase/genetics ; Genotype ; Mutation ; Plant Proteins/genetics ; Alleles ; 3-Phosphoshikimate 1-Carboxyvinyltransferase/genetics ; },
abstract = {Although herbicide resistance in Setaria is rampant and cosmopolitian across four herbicide families, we encountered little evidence of target-site resistance, indicating diverse non-target mechanisms of metabolizing, sequestering, and overwhelming herbicides. Setaria viridis is a cosmopolitan weed and model genetic system with increasing reports of resistance to multiple classes of herbicides. Our goal was to assess the herbicide resistance and allelic diversity in herbicide target genes in a collection of Setaria genotypes from North America and Eurasia, and identify the occurrence of novel and known target-site mutations that led to resistance. A total of 214 Setaria genotypes were exposed to commonly used herbicides that inhibit specific genes: herbicide action class (HRAC) group 1 herbicides targeting acetyl-CoA carboxylase (ACCase), HRAC 2 targeting acetolactate synthase (ALS), HRAC 9 targeting 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase, and HRAC 10 targeting glutamine synthetase. ACCase and ALS genes in 53 accessions were PCR-amplified and sequenced. Whole-genome sequencing reads covering the target genes were analyzed for an additional 98 genotypes. Herbicide trials showed that 30% of our accessions set seed following application of at least one herbicide, and 13 accessions were resistant to multiple classes of herbicides. Although there were numerous SNPs, including some known to lead to resistance, in our target genes, SNPs found predominantly in herbicide-resistant genotypes were largely intronic or synonymous. A small number of amino acid substitutions in ALS and ACCase indicated potential and incomplete resistance to HRAC 1 and 2 herbicides, but no SNPs putatively associated with herbicide resistance were identified in the other 6 target-site genes. The broader pattern of herbicide resistance in S. viridis is likely driven by non-target mutations that detoxify or compartmentalize applied herbicides.},
}

*Herbicide Resistance/genetics
*Herbicides/pharmacology
Acetyl-CoA Carboxylase/genetics
*Setaria Plant/genetics/drug effects
Acetolactate Synthase/genetics
Genotype
Mutation
Plant Proteins/genetics
Alleles
3-Phosphoshikimate 1-Carboxyvinyltransferase/genetics

@article {pmid42085565,
year = {2026},
author = {Singh, K and Ahmad, I and Jain, D and Mim, TJ and Noman, AA and Shihab, MPR and Kondaveeti, SB and Gupta, JK and Wal, P},
title = {Novel Cellular Signalling Axes in Neurodegenerative Diseases: From NLRP3 Inflammasome to Wnt/β-Catenin and Hippo-YAP Pathways.},
journal = {Journal of biochemical and molecular toxicology},
volume = {40},
number = {5},
pages = {e70880},
doi = {10.1002/jbt.70880},
pmid = {42085565},
issn = {1099-0461},
mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; *Inflammasomes/metabolism ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Wnt Signaling Pathway ; Animals ; Hippo Signaling Pathway ; *beta Catenin/metabolism ; YAP-Signaling Proteins ; *Adaptor Proteins, Signal Transducing/metabolism ; *Protein Serine-Threonine Kinases/metabolism ; *Transcription Factors/metabolism ; Signal Transduction ; },
abstract = {Neurodegenerative diseases (NDs), including Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and Parkinson's disease (PD), are characterised by impaired cellular homeostasis and progressive neuronal loss. Emerging evidence highlights the critical role of cellular signalling pathways in the progression and pathogenesis of these disorders. With a focus on the NLRP3 inflammasome, Wnt/β-catenin, and Hippo-YAP cascades, this review focuses on new signalling pathways linked to neurodegenerative disorders. Among them, the NLRP3 inflammasome is a crucial mediator of neuroinflammation, causing neuronal damage and persistent immune activation. In contrast, these pathways regulate neurogenesis, synaptic plasticity, and cell survival, offering potential neuroprotective functions. Dysregulation of these pathways disrupts cellular integrity, exacerbates disease progression, and represents a convergence point for therapeutic intervention. In NDs, knowing how these pathways interact offers fresh perspectives on disease processes and finds new targets for the creation of disease-modifying treatments.},
}

Humans
*Neurodegenerative Diseases/metabolism/pathology
*Inflammasomes/metabolism
*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
*Wnt Signaling Pathway
Animals
Hippo Signaling Pathway
*beta Catenin/metabolism
YAP-Signaling Proteins
*Adaptor Proteins, Signal Transducing/metabolism
*Protein Serine-Threonine Kinases/metabolism
*Transcription Factors/metabolism
Signal Transduction

@article {pmid42086102,
year = {2026},
author = {Chen, M and Huang, X and Li, Y and Hu, L and Lu, R and Li, L},
title = {Microplastics as an emerging environmental pollutant potentially leading to neurodegenerative diseases.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2026.04.033},
pmid = {42086102},
issn = {1873-7544},
abstract = {Microplastics (MPs), defined as plastic fragments less than 5 mm in diameter, are ubiquitous in the environment. As an emerging environmental pollutant, MPs can infiltrate the human body through multiple pathways, including inhalation, ingestion, dermal contact and bloodborne transmission.Correspondingly, MPs, which can penetrate the blood-brain barrier and enter the central nervous system (CNS), have been linked to the development of neurodegenerative diseases (NDs).In this review, we provide a comprehensive analysis of the environmental distribution of MPs, the pathways of entry into the human body, and the distribution within the CNS. Furthermore, we explore intrinsic factors influencing the neurotoxicity of MPs and elucidate the mechanisms underlying MPs-induced NDs, including Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis. Beyond mechanistic insights, we offer a novel perspective by exploring the potential adaptation of emerging environmental MPs detection and removal technologies for CNS applications. Ultimately, elucidating these mechanisms positions the reduction of MPs accumulation as a critical intervention point, highlighting the adaptation of environmental technologies as a promising strategy for the prevention and management of NDs.},
}

@article {pmid42069601,
year = {2026},
author = {Robinson, L and Do-Ha, D and Cheng, F and Stevens, CH and Rosa Porto, R and Coles, M and Subachandran, J and Kalajdzic, P and Lui, J and Balez, R and Sanz Muñoz, S and Cabral-da-Silva, MC and Berg, T and Morsch, M and Lisowski, L and Tan, RH and Burgio, G and Karl, T and Lee, A and Chung, RS and Blair, I and Ooi, L},
title = {ALS-FTD-linked CCNF[S621G] drives increased hippocampal astrocyte ramification and mitochondrial dysfunction and impairs motor neuron excitability.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-026-03827-x},
pmid = {42069601},
issn = {1742-2094},
support = {APP1107644//National Health and Medical Research Council/ ; APP1135720//National Health and Medical Research Council/ ; CE230100021//Australian Research Council/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases with overlapping pathology. Mutations in CCNF, encoding the E3 ubiquitin ligase, Cyclin F, can cause ALS, FTD, or both, even within the same family. Most prior studies of CCNF[S621G] have relied on overexpression systems, potentially confounding outcomes through disruption of endogenous Cyclin F. Here, we generated the first knock-in mouse model of endogenous Ccnf[S621G] using CRISPR/Cas9. Heterozygous and homozygous Ccnf[S621G] mice showed no motor decline or neuronal loss after 18 months, however immunohistochemistry revealed increased hippocampal astrocyte ramification, with sex-, age, and subfield-dependent effects. These data indicate that endogenous Ccnf[S621G] may prime early astrocyte alterations in the absence of overt neurodegeneration. Similar astrocyte morphological changes were observed in canonically affected regions of sporadic ALS and FTD-ALS patients post mortem, as well as in CCNF[S621G] iPSC-derived astrocytes following inflammatory stimulation. Proteomics on Ccnf mice identified early dysregulation of pathways related to translation, mitochondrial function, cytoskeletal remodelling, synaptic transmission and neuroinflammation. Correspondingly, CCNF[S621G] iPSC-derived astrocytes displayed impaired mitochondrial membrane potential and altered network morphology under both basal and inflammatory stimuli. As altered neuronal excitability is a hallmark of ALS, we examined astrocyte-driven changes to neuronal excitability. CCNF[S621G] iPSC-derived motor neurons cultured alone were hyperexcitable, firing more action potentials than isogenic controls. Remarkably, co-culture with CCNF[S621G] astrocytes, but not isogenic control astrocytes, abolished repetitive firing, increased the proportion of neurons unable to generate action potentials, and reduced voltage-gated sodium currents in CCNF[S621G] and isogenic control neurons. Together, these findings identify astrocyte alterations as an early feature of CCNF[S621G]-mediated disease, in the absence of neuronal loss. Moreover, the combination of astrocytic mitochondrial dysfunction and the ability of CCNF[S621G] astrocytes to suppress repetitive neuronal firing suggests a critical astrocyte-driven non-cell autonomous mechanism that may contribute to an oligogenic role for CCNF in ALS/FTD pathogenesis.},
}

@article {pmid42070160,
year = {2026},
author = {Abdel Mageed, SS and Sayed, GA and Mahdy, A and El-Dakroury, WA and Abdulkader, AO and Moustafa, HAM and Mansour, RM and Mohammed, OA and Elballal, MS and Elesawy, AE and Doghish, AS},
title = {miRNAs in Amyotrophic Lateral Sclerosis: Tiny Molecules, Tremendous Impact.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42070160},
issn = {1559-1182},
mesh = {*Amyotrophic Lateral Sclerosis/genetics/therapy/diagnosis/metabolism ; Humans ; *MicroRNAs/genetics/metabolism ; Animals ; Biomarkers/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder distinguished by progressive motor neuron degeneration, with diverse clinical manifestations and complex genetic and environmental triggers. The variability in disease progression underscores the necessity for tailored diagnostic and therapeutic approaches. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, have emerged as promising biomarkers and therapeutic targets in ALS. Dysregulation of specific miRNAs has been linked to mechanisms of ALS, including neuromuscular dysfunction, neuroinflammation, and neuronal survival/apoptosis. The potential of miRNA-based therapies, such as mimics and inhibitors, offers a more integrated approach by modulating entire disease networks, rather than targeting isolated pathways. However, challenges persist, particularly in delivering these therapies efficiently across the blood-brain barrier and minimizing off-target effects. Current delivery strategies involving nanoparticles, viral vectors, and exosome-based approaches require optimization for clinical use. This review synthesizes the latest research on miRNA-mediated mechanisms in ALS, evaluating their diagnostic, prognostic, and therapeutic potential, while highlighting the current limitations in clinical validation. It underscores the importance of standardized methodologies, multi-omics integration, and rigorous validation to facilitate the clinical translation of miRNA-based strategies. Standardized protocols and multicenter validation in large cohorts are essential to confirm the diagnostic accuracy of miRNAs, paving the way for their clinical application in ALS precision medicine.},
}

*Amyotrophic Lateral Sclerosis/genetics/therapy/diagnosis/metabolism
Humans
*MicroRNAs/genetics/metabolism
Animals
Biomarkers/metabolism

@article {pmid42070757,
year = {2026},
author = {Liu, JY and Liu, SY and Ran, LX and Qiao, WH and Zhang, F and Zhang, KS and Liang, XX and Liu, MY and Yu, ZH and Wei, MJ and Zhong, X},
title = {Organelle-orchestrated cGAS-STING signaling and its role in neurodegeneration.},
journal = {Pharmacological research},
volume = {},
number = {},
pages = {108216},
doi = {10.1016/j.phrs.2026.108216},
pmid = {42070757},
issn = {1096-1186},
abstract = {The cGAS-STING signaling pathway serves as a central signalling axis of the innate immune system, and its aberrant activation plays a pivotal role in inflammatory responses. Recent studies have demonstrated that its regulation depends not only on individual organelles but also on a coordinated interorganelle network. This review systematically analyze how mitochondria, centrosomes, the endoplasmic reticulum (ER), membrane contact sites (MCSs), the Golgi apparatus, endosomes, and lysosomes collectively orchestrate cGAS-STING signaling. Mitochondria initiate signaling by releasing mitochondrial DNA; centrosomes serve as platforms for double-stranded DNA accumulation to potentiate cGAS activation; the ER anchors STING in a calcium homeostasis-dependent manner; mitochondrial-associated ER membranes (MAMs) integrate calcium and lipid signaling as regulatory checkpoints governing STING trafficking to the Golgi apparatus; the Golgi amplifies downstream signaling through site-specific post-translational modifications of STING; finally, the endosome-lysosome system, together with ER-lysosome MCSs, acts as a coordinated hub for STING sorting, lysosomal degradation and signal termination. Consequently, disruption of organelle homeostasis leads to persistent STING activation. In neurodegenerative conditions including Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis and Huntington's disease, organelle dysfunction resulting from calcium overload, impaired organelle clearance, proteolytic cleavage of tethering proteins or multi-source attacks drives aberrant STING signaling. Sustained STING activity exacerbates pathological cascades such as protein misfolding, chronic neuroinflammation, and progressive neuronal loss. Therefore, therapeutic strategies targeting key regulatory nodes of the STING pathway, from upstream organelle repair to direct pharmacological inhibition, offer significant potential to mitigate disease-associated pathological progression and constitute a promising foundation for precision therapeutics in neurodegenerative disorders.},
}

@article {pmid42071322,
year = {2026},
author = {Buttifant, E and Allogmanny, S and Probst, Y},
title = {Investigating Disordered Eating Behaviours Among Individuals Living With Neurodegenerative Disease: A Scoping Review.},
journal = {Journal of human nutrition and dietetics : the official journal of the British Dietetic Association},
volume = {39},
number = {3},
pages = {e70250},
doi = {10.1111/jhn.70250},
pmid = {42071322},
issn = {1365-277X},
mesh = {Humans ; *Feeding and Eating Disorders/etiology/epidemiology/complications ; *Neurodegenerative Diseases/complications/psychology ; *Feeding Behavior/psychology ; Hyperphagia ; Female ; Male ; Alzheimer Disease/complications ; },
abstract = {AIM: Neurodegenerative diseases and disordered eating have become rapidly expanding areas of research. However, research addressing the relationship between the two is lacking.

METHODS: A scoping review guided by the Joanna Briggs Institute methodological framework was completed to synthesise the evidence related to disordered eating behaviours among individuals living with neurodegenerative disease. A systematic search strategy was applied across four scientific databases. A narrative descriptive analysis was conducted to identify key patterns in the studies categorised by the type of eating behaviour. The types of tools used within studies were explored.

RESULTS: Thirty-six evidence sources were included in this review. Overeating-related issues such as hyperphagia were identified (n = 5, 25%) for dementia and Alzheimer's disease-related studies. Appetite-related changes were prevalent across amyotrophic lateral sclerosis (n = 1, 100%) and dementia and Alzheimer's disease-related studies (n = 6, 30%). Food addiction and binge eating were reported in all Parkinson's disease studies (n = 9, 100%), and in one case report for dementia. Eating disorders such as anorexia, bulimia and binge eating disorder were identified in all multiple sclerosis-related studies (n = 6, 100%). Validated and unvalidated tools (53%, n = 19) were used to identify eating behaviours.

CONCLUSIONS: This review revealed reports of disordered eating behaviours among various neurodegenerative disease types. Additional research is required to understand the aetiology and mechanisms behind disordered eating behaviours in these populations. Standardised tools to assess eating behaviours for people living with a neurodegenerative disease are needed. Eating behaviours should be screened upon neurodegenerative disease diagnosis and monitored as part of routine care.},
}

Humans
*Feeding and Eating Disorders/etiology/epidemiology/complications
*Neurodegenerative Diseases/complications/psychology
*Feeding Behavior/psychology
Hyperphagia
Female
Male
Alzheimer Disease/complications

@article {pmid42072614,
year = {2026},
author = {Ferreon, JC and Choi, KJ and Quan, MD and Tsoi, PS and Ferreon, CC and Coskun, U and Liao, SJ and Ferreon, ACM},
title = {Modulation of Biomolecular Aggregate Morphology and Condensate Infectivity.},
journal = {Biomolecules},
volume = {16},
number = {4},
pages = {},
doi = {10.3390/biom16040492},
pmid = {42072614},
issn = {2218-273X},
support = {R01 GM122763/GM/NIGMS NIH HHS/United States ; },
mesh = {Humans ; *Protein Aggregates ; *Heterogeneous Nuclear Ribonucleoprotein A1/chemistry/metabolism/genetics ; Amyloid/metabolism/chemistry ; Alzheimer Disease/metabolism/pathology ; Amyotrophic Lateral Sclerosis/metabolism/pathology ; *Biomolecular Condensates/chemistry/metabolism ; Prions/metabolism/chemistry ; *Protein Aggregation, Pathological/metabolism ; },
abstract = {Neurodegenerative diseases feature diverse pathological protein aggregates, including Lewy bodies in Alzheimer's disease (AD) and skein-like filaments in amyotrophic lateral sclerosis (ALS). The physical mechanisms underlying this morphological diversity remain unclear. Here, we demonstrate that aggregation of the prion-like domain of hnRNPA1 (A1PrD), implicated in AD and ALS, is driven by solution composition and phase transition dynamics. Utilizing 3D timelapse and fluorescence lifetime imaging microscopy, we show that solution conditions modulate phase separation, gelation, and fibrillation, resulting in distinct structures such as fibril, gel, and starburst morphologies. Homotypic and heterotypic interactions between A1PrD and RNA were observed to shift the balance between pathological and physiological condensates. Importantly, amyloid-rich starbursts displayed prion-like infection capabilities toward amyloid-poor condensates. Our findings highlight how the interplay between solution composition and kinetic balances of liquid-liquid phase separation, gelation, and fibrillation shapes the diverse pathological aggregate morphologies characteristic of neurodegenerative diseases.},
}

Humans
*Protein Aggregates
*Heterogeneous Nuclear Ribonucleoprotein A1/chemistry/metabolism/genetics
Amyloid/metabolism/chemistry
Alzheimer Disease/metabolism/pathology
Amyotrophic Lateral Sclerosis/metabolism/pathology
*Biomolecular Condensates/chemistry/metabolism
Prions/metabolism/chemistry
*Protein Aggregation, Pathological/metabolism

@article {pmid42072687,
year = {2026},
author = {Fiorucci, C and Rossi, MN and Santo, RD and Salvatori, I and Scaricamazza, S and Giuliani, S and Carletta, O and Filomena, E and Laurenti, D and Mattioli, R and Mosca, L and Valle, C and Ferri, A and D'Erchia, AM and Cervelli, M},
title = {Transcriptomic Analysis Reveals the Beneficial Effects of Spermidine in an ALS Mouse Model.},
journal = {Biomolecules},
volume = {16},
number = {4},
pages = {},
doi = {10.3390/biom16040566},
pmid = {42072687},
issn = {2218-273X},
support = {LSH-Puglia, T4-AN-01 H93C22000560003//INNOVA - Italian network of excellence for advanced diagnosis/ ; Grant Code IR0000010//ELIXIR-IT/ ; MAE0067342//Protocols of Scientific and Technological Bilateral Cooperation funded by the Ministry of Health/ ; L. 232/2016-art.1 cc. 314-337 awarded to the Department of Science of Roma Tre University (2023-2027)//MIUR-Italy Grants of Departments of Excellence/ ; CUP B83C22002820006//Progetto ECS 0000024 Rome Technopole/ ; },
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism/pathology ; Mice ; Disease Models, Animal ; *Spermidine/pharmacology/therapeutic use ; Muscle, Skeletal/metabolism/drug effects/pathology ; Gene Expression Profiling ; Spinal Cord/metabolism/drug effects ; Mitochondria/metabolism/drug effects/genetics ; Mice, Transgenic ; *Transcriptome/drug effects ; Humans ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics/metabolism ; Superoxide Dismutase-1/genetics ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease marked by progressive degeneration of motor neurons and skeletal muscle. Gene expression analysis of the spinal cord and gastrocnemius of the SOD1-G93A ALS mouse model revealed a strong increase in inflammatory pathways and, specifically in the ALS gastrocnemius, a decrease in mitochondrial transcription and an increase in ribosomal protein expression. Treatment of ALS mice with the polyamine spermidine (SPD), a promising molecule in combating neurodegeneration and muscle atrophy, is able to partially restore the expression of more than four thousand genes in gastrocnemius tissue, including the mitochondrial regulator Pgc1α, as well as all the mitochondrial encoded genes and a large class of ribosomal proteins. SPD enhanced mitochondrial bioenergetics, as evidenced by Seahorse experiments, and delayed muscle weakness in vivo, as shown by grip strength records. These findings suggest that SPD can act as a potential supplement in the therapeutic strategy for ALS, offering a foundation for further research to improve patient outcomes.},
}

Animals
*Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism/pathology
Mice
Disease Models, Animal
*Spermidine/pharmacology/therapeutic use
Muscle, Skeletal/metabolism/drug effects/pathology
Gene Expression Profiling
Spinal Cord/metabolism/drug effects
Mitochondria/metabolism/drug effects/genetics
Mice, Transgenic
*Transcriptome/drug effects
Humans
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics/metabolism
Superoxide Dismutase-1/genetics

@article {pmid42073390,
year = {2026},
author = {Hossain, R and Surinkaew, S and Sompol, P and Bastaki, NK and Jafrin, R and Sekeroglu, N and Tangpong, J},
title = {Mapping the Polar Neuro-Interactome of Garcinia mangostana Against the AD-PD-ALS Nexus.},
journal = {Life (Basel, Switzerland)},
volume = {16},
number = {4},
pages = {},
doi = {10.3390/life16040580},
pmid = {42073390},
issn = {2075-1729},
support = {WU69203//Walailak University under the New Researcher Development scheme/ ; },
abstract = {Background/Objectives: Neurodegenerative diseases like Alzheimer's, Parkinson's, and Amyotrophic lateral sclerosis (ALS) share common molecular pathways, including neuroinflammation and oxidative stress, which complicate the effectiveness of single-target treatments. Garcinia mangostana L. (mangosteen) has shown neuroprotective properties, but previous studies focused on lipophilic xanthones, which have poor bioavailability and uncertain blood-brain barrier permeability. Methods: In the current study, polar metabolites from G. mangostana peel aqueous extract (GMPE) were assessed for potential multi-target interactions via UHPLC-QTOF-MS-based metabolomics, systems pharmacology, and molecular docking analysis. Further, in silico ADMET screening and network-based analyses assessed for overlap between GMPE compounds and genes associated with neurodegeneration (AD, PD, ALS). Results: Analysis of genes linked to AD, PD, and ALS revealed 121 common molecular targets influenced by GMPE metabolites. Network and enrichment analyses indicated that the compounds derived from GMPE may be involved in common pathways related to oxidative stress, neuroinflammation, and neuronal survival. Molecular docking analyses suggest that selected metabolites are likely to exhibit moderate binding affinities to their respective protein targets. Conclusions: The results presented in this study provide evidence that GMPE may possess potential multi-target interactions within common neurodegenerative pathways. However, since the data are based on computational and predictive approaches, these results should be considered hypothesis-generating and warrant further experimental validation.},
}

@article {pmid42073963,
year = {2026},
author = {Aokalani, MC and Wisner, KL and Andescavage, NN and Limperopoulos, C and Stuart, BK},
title = {Implementing Outpatient Therapeutic Playgroups for NICU Families: A Quality Improvement Project.},
journal = {Behavioral sciences (Basel, Switzerland)},
volume = {16},
number = {4},
pages = {},
doi = {10.3390/bs16040600},
pmid = {42073963},
issn = {2076-328X},
support = {(HRSA-GPE)//Health Resources and Services Administration Graduate Psychology Education Program/ ; T32 HD098066/HD/NICHD NIH HHS/United States//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; },
abstract = {Therapeutic playgroups have shown promise in enhancing caregiver-infant mental health outcomes, yet tailored approaches for families following neonatal intensive care unit (NICU) admission remain limited. In this brief report on Quality Improvement, we evaluate key strategies and challenges in implementing an adapted therapeutic playgroup intervention designed for caregivers and infants with a history of NICU hospitalization at University of California, San Francisco and Zuckerberg San Francisco (UCSF) Zuckerberg San Francisco General Hospital (ZSFG) We conducted semi-structured interviews with NICU psychologists to assess local feasibility, barriers, and facilitators to implementation. Implementation science frameworks-the Consolidated Framework for Implementation Research (CFIR) and Proctor et al.'s implementation outcomes framework (acceptability, adoption, appropriateness, feasibility, and sustainability)-were used to guide data organization and interpretation. Qualitative reporting guidelines were followed to enhance transparency in describing interviews and analytic procedures. The psychologists emphasized the importance of embedding therapeutic playgroups within existing clinical workflows, providing flexible delivery models, and customizing curricula to meet cultural and family-specific needs. Multidisciplinary collaboration enhanced feasibility and parent engagement. Barriers included organizational constraints and variability in caregiver readiness. These findings inform local program development and highlight considerations for integrating dyadic mental health support into post-NICU care. Future work should incorporate caregiver perspectives and explore effective interventions across diverse settings.},
}

@article {pmid42073997,
year = {2026},
author = {Rafique, A and Junaid, A and Bakovic, M},
title = {Impact of Oxidative Stress-Driven Ferroptosis in Neurodegeneration.},
journal = {International journal of molecular sciences},
volume = {27},
number = {8},
pages = {},
doi = {10.3390/ijms27083353},
pmid = {42073997},
issn = {1422-0067},
support = {APP465536/CAPMC/CIHR/Canada ; },
mesh = {*Ferroptosis ; Humans ; *Oxidative Stress ; Animals ; *Neurodegenerative Diseases/metabolism/pathology ; Lipid Peroxidation ; Iron/metabolism ; Reactive Oxygen Species/metabolism ; },
abstract = {Ferroptosis is an iron-dependent cell death driven by lipid peroxidation and failure of cellular antioxidant defenses. It is triggered by oxidative stress and can be aggravated by aging, inflammation, and dysregulation of iron homeostasis. In the central nervous system, iron dyshomeostasis, mitochondrial dysfunction, and membrane lipid remodeling can amplify oxidative injury and increase susceptibility to ferroptotic damage, particularly in vulnerable neurons. There is growing evidence that ferroptosis-related processes are linked to Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis. This review addresses novel approaches to track ferroptosis in vivo, such as imaging and biomarker techniques, and important molecular mechanisms linking iron metabolism, reactive oxygen species, and PUFA-driven lipid peroxidation to neuronal damage. We also explore upstream transcriptional control via NRF2, iron chelation and iron-handling modulation, inhibition of lipid peroxidation, and reinforcement of the System Xc-GSH-GPX4 and CoQ10-linked defense pathways. Subsequently, we highlight translational issues that need attention to further progress ferroptosis-targeted therapies for neurodegenerative disease.},
}

*Ferroptosis
Humans
*Oxidative Stress
Animals
*Neurodegenerative Diseases/metabolism/pathology
Lipid Peroxidation
Iron/metabolism
Reactive Oxygen Species/metabolism

@article {pmid42074010,
year = {2026},
author = {Goloborshcheva, VV and Kostikova, YS and Kucheryanu, VG and Morozov, SG and Kokhan, VS},
title = {Insights into the Impact of Low-Dose Ionizing Radiation on Neurodegenerative Disease Progression in In Vivo Models.},
journal = {International journal of molecular sciences},
volume = {27},
number = {8},
pages = {},
doi = {10.3390/ijms27083368},
pmid = {42074010},
issn = {1422-0067},
support = {FGFU-2025-0004//Russian state contract/ ; },
mesh = {Animals ; Humans ; *Radiation, Ionizing ; *Neurodegenerative Diseases/radiotherapy/pathology/metabolism ; Disease Models, Animal ; Disease Progression ; Autophagy/radiation effects ; DNA Repair/radiation effects ; },
abstract = {The effective treatment of neurodegenerative diseases (NDDs), such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, remains a critical challenge in modern medicine. Given the limitations of current therapies, alternative strategies to slow neurodegeneration are urgently needed. This study presents a critical review of the current evidence regarding low-dose ionizing radiation (IR) as a promising modality for modulating neurodegenerative processes. This study examines current experimental data on the effects of low-dose IR (LDIR) on cellular protective and compensatory mechanisms, including evidence from in vivo models of NDDs. Our analysis demonstrates that LDIR enhances antioxidant activity and DNA repair, stimulates autophagy and neuroplasticity, and modulates neuroinflammatory signaling. Collectively, these findings support the hypothesis of the neuroprotective potential of LDIR, underscoring its translational viability provided that strict dosimetric guidelines are followed and individual biological responses are rigorously monitored.},
}

Animals
Humans
*Radiation, Ionizing
*Neurodegenerative Diseases/radiotherapy/pathology/metabolism
Disease Models, Animal
Disease Progression
Autophagy/radiation effects
DNA Repair/radiation effects

@article {pmid42074053,
year = {2026},
author = {Ribeiro, GD and Queiroz, DD and Monteiro-Neto, JR and Gerhardt, E and de Souza, GF and Albino, PCSC and Paranhos, LH and Outeiro, TF and Eleutherio, ECA},
title = {Molecular Modulation of the Crosstalk Between TDP-43 and SOD1.},
journal = {International journal of molecular sciences},
volume = {27},
number = {8},
pages = {},
doi = {10.3390/ijms27083409},
pmid = {42074053},
issn = {1422-0067},
support = {CNE 201.174/2022//FAPERJ/ ; PROBRAL 88881.986154/2024-01//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; PQ 309635/2023-3//National Council for Scientific and Technological Development/ ; CNPq Universal 401780/2023-6//National Council for Scientific and Technological Development/ ; 210.034/2026//FAPERJ/ ; },
mesh = {*Superoxide Dismutase-1/metabolism/genetics ; *DNA-Binding Proteins/metabolism/genetics ; Humans ; Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Phosphorylation/drug effects ; Pyruvaldehyde/pharmacology ; Mutation ; Cytosol/metabolism ; Protein Binding ; Glycosylation ; },
abstract = {Glycation of superoxide dismutase 1 (SOD1) has been shown to modulate the cytosolic levels of phosphorylated TAR DNA-binding protein 43 (TDP-43), a hallmark of amyotrophic lateral sclerosis (ALS) pathology. In this study, we investigated the interaction between TDP-43 and SOD1 and assessed how methylglyoxal (MGO)-induced glycation and the ALS-associated G93A SOD1 mutation affect this interplay in H4 cells. MGO exposure reduced SOD1 activity and TDP-43 phosphorylation in cells expressing WT SOD1, but not in those expressing G93A SOD1. Both WT and mutant SOD1 interacted with TDP-43 in the nucleus and cytosol; however, cytosolic interactions were more prevalent in G93A-expressing cells. Although MGO did not significantly alter the overall interaction between TDP-43 and WT SOD1, it induced cytosolic inclusion formation at 0.4 mM, a concentration associated with reduced cell viability. These inclusions did not colocalize with stress granules, indicating alternative aggregation pathways. Treatment with cyclosporin A, which inhibits the phosphatase calcineurin, decreased both TDP-43-WT SOD1 inclusions and cytosolic interactions between TDP-43 and G93A SOD1. Together, these findings suggest that SOD1 damage, induced by glycation or ALS-linked mutation, may affect TDP-43 phosphorylation status and promote its cytosolic mislocalization and aggregation, providing new insights into ALS-associated proteinopathy.},
}

*Superoxide Dismutase-1/metabolism/genetics
*DNA-Binding Proteins/metabolism/genetics
Humans
Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology
Phosphorylation/drug effects
Pyruvaldehyde/pharmacology
Mutation
Cytosol/metabolism
Protein Binding
Glycosylation

@article {pmid42074133,
year = {2026},
author = {Meltzer, M and Zamir, MS and Tzuri, N and Tan, AM and Geva, M and Hayden, MR and Lichtenstein, RG},
title = {Pridopidine Protects ALS Patient-Derived Neural Progenitor Cells via Sigma-1 Receptor Activation.},
journal = {International journal of molecular sciences},
volume = {27},
number = {8},
pages = {},
doi = {10.3390/ijms27083489},
pmid = {42074133},
issn = {1422-0067},
mesh = {*Receptors, sigma/metabolism/agonists ; Sigma-1 Receptor ; Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/drug therapy ; *Neural Stem Cells/metabolism/drug effects/pathology ; Endoplasmic Reticulum Stress/drug effects ; *Piperidines/pharmacology ; Induced Pluripotent Stem Cells/metabolism/drug effects ; Cell Survival/drug effects ; Membrane Potential, Mitochondrial/drug effects ; Mitochondria/metabolism/drug effects ; Apoptosis/drug effects ; *Neuroprotective Agents/pharmacology ; Tunicamycin/pharmacology ; Transcription Factor CHOP/metabolism ; },
abstract = {The sigma-1 receptor (S1R) is an endoplasmic reticulum (ER)-resident protein enriched at the mitochondria-associated ER membranes (MAMs) that supports ER homeostasis, preserves mitochondrial function, and enhances cell survival under stress. Disruptions of MAM integrity and prolonged ER stress are well-recognized pathological features of amyotrophic lateral sclerosis (ALS), contributing to motor neuron dysfunction and degeneration. In this study, we evaluated the protective effects of pridopidine, a highly selective and potent S1R agonist currently in clinical development for Huntington's disease (HD) and ALS, using neural progenitor cells (NPCs) derived from induced pluripotent stem cells (iPSCs) from a patient with sporadic ALS. Exposure of ALS NPCs to the ER stressor tunicamycin increased the ER stress markers binding immunoglobulin protein (BiP) and C/EBP homologous protein (CHOP), disrupted mitochondrial membrane potential, upregulated expression of the mitochondrial apoptotic marker, BAX, increased caspase-3 activation, and reduced cell viability. Pridopidine significantly attenuated tunicamycin-induced BiP and CHOP expression in a biphasic, dose-dependent manner (with maximal efficacy at 1 µM), consistent with the typical pharmacology of S1R agonists. Pridopidine restored mitochondrial membrane potential, reduced mitochondrial apoptotic signaling, shown by decreased BAX expression and caspase-3 activation, and improved survival of ALS-NPCs under ER stress. Co-treatment with the selective S1R antagonist, NE-100, attenuated these effects, supporting an S1R-mediated mechanism of action for pridopidine. Together, these results demonstrate that S1R activation by pridopidine mitigates ER-stress-induced mitochondrial dysfunction and cell loss in ALS-NPCs, resulting in enhanced survival of NPCs supporting the therapeutic potential of pridopidine in ALS.},
}

*Receptors, sigma/metabolism/agonists
Sigma-1 Receptor
Humans
*Amyotrophic Lateral Sclerosis/metabolism/pathology/drug therapy
*Neural Stem Cells/metabolism/drug effects/pathology
Endoplasmic Reticulum Stress/drug effects
*Piperidines/pharmacology
Induced Pluripotent Stem Cells/metabolism/drug effects
Cell Survival/drug effects
Membrane Potential, Mitochondrial/drug effects
Mitochondria/metabolism/drug effects
Apoptosis/drug effects
*Neuroprotective Agents/pharmacology
Tunicamycin/pharmacology
Transcription Factor CHOP/metabolism

@article {pmid42074537,
year = {2026},
author = {Yesbek Kaymaz, A and Bora-Akoğlu, G and Erdem Yurter, H and Grunseich, C},
title = {Gene Targeted Therapies for Neurodegenerative Disorders: Strategies and Implications in ALS and SMA.},
journal = {Genes},
volume = {17},
number = {4},
pages = {},
doi = {10.3390/genes17040419},
pmid = {42074537},
issn = {2073-4425},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/genetics ; *Genetic Therapy/methods ; *Muscular Atrophy, Spinal/therapy/genetics ; Gene Editing/methods ; Animals ; *Neurodegenerative Diseases/therapy/genetics ; Genetic Vectors/genetics ; },
abstract = {Advances in technology have provided a better understanding of the genetic basis of neurodegenerative disorders and their underlying molecular pathophysiology. However, treating these disorders with conventional strategies is a major challenge. The approval of gene targeted therapy for spinal muscular atrophy (SMA) has laid the foundation for developing highly personalized therapies for other neurodegenerative disorders. As intensive research and efforts to advance gene targeted therapies continue, this review provides an overview of viral and non-viral vectors and delivery methods, as well as treatment strategies, including gene addition, replacement, editing, silencing, and splice modulation. Gene targeted approaches and clinical trials for SMA and amyotrophic lateral sclerosis (ALS) have demonstrated success, and additional studies are in progress. The design of efficient clinical trials which facilitate successful translation into clinical practice is of critical importance. Key considerations include the selection of appropriate disease models, understanding the natural history of the disease, and establishing well-defined outcome measures to assess prognosis of the disease and therapeutic efficacy. Finally, the precision of CRISPR-based gene editing offers the potential for one-time corrective therapies for monogenic disorders like SMA and SOD1-ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/genetics
*Genetic Therapy/methods
*Muscular Atrophy, Spinal/therapy/genetics
Gene Editing/methods
Animals
*Neurodegenerative Diseases/therapy/genetics
Genetic Vectors/genetics

@article {pmid42074613,
year = {2026},
author = {Quak, ZX and Wang, F and Tay, SKH and Koh, PL and Yap, ES and Ng, KWP},
title = {Thrombosis in Neuromuscular Medicine: Current Evidence, Unmet Needs, and Future Directions.},
journal = {Journal of clinical medicine},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/jcm15082810},
pmid = {42074613},
issn = {2077-0383},
abstract = {Venous thromboembolism (VTE), comprising deep vein thrombosis and pulmonary embolism, is an important but under-recognised complication in neuromuscular diseases. In adults, emerging epidemiological data suggests increased VTE occurrence in conditions such as Amyotrophic Lateral Sclerosis, myotonic dystrophy, myasthenia gravis, inflammatory neuropathies, inflammatory myopathies, and POEMS syndrome. This heightened risk reflects not only disease-related immobility but also disorder-specific biological mechanisms, including inflammation, endothelial dysfunction and cardiomyopathy-related stasis. Therapies such as corticosteroids, IVIG-related hyperviscosity, long-term central venous access, perioperative immobility, critical illness, and complex orthopaedic procedures have prothrombotic effects. Despite this multifactorial risk profile, disease-specific guidance for thromboprophylaxis is lacking, and current practice relies heavily on extrapolation from general medical and surgical recommendations rather than data derived from neuromuscular cohorts. In children and adolescents, the VTE burden is less well-characterised, but events have been reported in Duchenne and Becker muscular dystrophy, congenital myopathies, and spinal muscular atrophy particularly with advanced motor impairment, severe cardiomyopathy, ventilatory insufficiency, and prolonged hospitalisation. Beyond venous events, selected neuromuscular disorders also exhibit increased arterial thrombosis risk. Myotonic dystrophy and dystrophinopathies are associated with cardiomyopathy and arrhythmia that predispose to systemic embolism and stroke, while inflammatory myopathies may demonstrate arterial events related to vasculitic or endothelial processes, although overall evidence remains limited. This review summarises available empirical and epidemiological evidence on venous and arterial thrombosis across adult and paediatric neuromuscular disorders, outlines disease-specific mechanistic pathways, examines treatment-related contributors, and highlights key evidence gaps that must be addressed to guide rational and targeted prophylaxis strategies in this complex, heterogeneous population.},
}

@article {pmid42074898,
year = {2026},
author = {Shovman, Y and Lerner, Y and Gotkine, M},
title = {Slower Progression Rates in Lower Limb-Onset ALS.},
journal = {Journal of clinical medicine},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/jcm15083096},
pmid = {42074898},
issn = {2077-0383},
support = {//Perner Yaacov memorial fund/ ; },
abstract = {Objectives: The aim of this study was to assess the differences in diagnostic delay and disease progression in people with ALS (PALS) based on site of onset. Methods: A retrospective analysis of prospectively collected data was performed, including all PALS seen in the ALS clinic in the Hadassah Medical Center between January 2009 and March 2022. PALS were divided to three groups based on site of onset (upper limb onset-ULO, lower limb onset-LLO, or bulbar onset-BO). A linear mixed-effects model was constructed with the following variables: diagnostic delay, site of onset, age of onset and time since the initial visit. The model was applied to the ALSFRS-R total score and the bulbar and motor subscales. Results: Data from 1255 visits of 281 PALS were included in the study. PALS with LLO had longer diagnostic delays than PALS in the BO group. Slower decline of total ALSFRS-R score was observed in younger PALS, and in PALS with LLO when compared with PALS with BO or ULO. The slower decline of ALSFRS-R in PALS with LLO was due to a slower decline in the motor subscale. Longer diagnostic delays were associated with lower total ALSFRS-R scores at the initial visit and with slower rates of decline. Conclusions: Comparison among PALS with ULO, LLO and BO revealed differences in the diagnostic delay and in the rate of functional decline, suggesting that differentiating between ULO and LLO ALS may be useful in the stratification of PALS in clinical trials.},
}

@article {pmid42076023,
year = {2026},
author = {Rodkin, S and Gasanov, M and Tushev, A and Belousova, E and Gordeeva, Y and Nwosu, C and Tolmacheva, A},
title = {The Dual Role of Connexins in Stroke, Neurotrauma, Neurodegenerative and Psychiatric Disorders: A Global Systematic Review.},
journal = {Molecules (Basel, Switzerland)},
volume = {31},
number = {8},
pages = {},
doi = {10.3390/molecules31081341},
pmid = {42076023},
issn = {1420-3049},
support = {25-75-10137//Russian Science Foundation/ ; },
mesh = {Humans ; *Connexins/metabolism/genetics ; *Mental Disorders/metabolism ; Animals ; *Neurodegenerative Diseases/metabolism ; *Stroke/metabolism ; Gap Junctions/metabolism ; *Brain Injuries, Traumatic/metabolism ; Spinal Cord Injuries/metabolism ; },
abstract = {Background: Connexins (Cx) are a family of transmembrane proteins that form gap junctions and connexin hemichannels (HCs), enabling direct intercellular communication within the nervous system. Connexin 43 (Cx43), the principal astrocytic connexin, exhibits a context-dependent dual role: under physiological conditions it maintains tissue homeostasis and metabolic support, whereas under pathological conditions excessive activation of Cx43 hemichannels promotes neuroinflammation, excitotoxicity, blood-brain barrier disruption, and secondary neural tissue damage. Other connexin isoforms also contribute to the pathogenesis of neurological and psychiatric disorders through alterations in neuronal synchronization, glial signaling, and myelin integrity. Objective: To systematize current evidence on the role of key connexin isoforms in acute nervous system injuries-including stroke, traumatic brain injury, spinal cord injury, and peripheral nerve injury-as well as chronic disorders such as neurodegenerative diseases, epilepsy, and psychiatric disorders, with particular emphasis on the functional duality of connexin channels and the therapeutic potential of their selective modulation. Methods: A systematic literature search was conducted in the PubMed, Scopus, and Web of Science databases in accordance with the PRISMA framework and the PRISMA Extension for Scoping Reviews guidelines. The review included data from experimental models, postmortem brain studies, genetic association analyses, and pharmacological intervention studies. The retrieved studies were screened, assessed for eligibility, and integrated using a qualitative narrative synthesis approach. Results: In acute neural injuries, hyperactivation of Cx43 hemichannels amplifies inflammatory signaling, edema formation, and neuronal death, whereas selective HCs inhibitors reduce lesion volume and improve functional outcomes in experimental models. Connexin 36 (Cx36) contributes to cortical spreading depolarization and seizure propagation, while Connexin 32 (Cx32) and Connexin 47 (Cx47) are critically involved in oligodendrocyte function and white-matter demyelination. In PNI, Cx43 upregulation contributes to neuropathic pain, whereas mutations in Cx32 cause hereditary demyelinating neuropathies. In neurodegenerative diseases-including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis-Cx43 hemichannel activity promotes neuroinflammation and pathological protein accumulation, while reduced Cx32/Cx47 expression disrupts metabolic support of axons. In psychiatric disorders such as major depressive disorder, bipolar disorder, and schizophrenia, decreased astrocytic connexin expression (Cx43 and Cx30) has been associated with impaired glial-neuronal communication and cognitive-emotional dysfunction. In epilepsy, increased Cx43/Cx30 expression contributes to neuronal hypersynchronization and blood-brain barrier dysfunction, whereas selective hemichannel blockade suppresses seizure activity. Conclusions: Cx-particularly Cx43-occupies a central position in the molecular mechanisms of secondary neural injury and network dysfunction. The dual functional properties of gap junctions and hemichannels determine their context-dependent effects across neurological and psychiatric diseases. Selective inhibition of pathological HCs activity shows significant neuroprotective and anticonvulsant potential and represents a promising direction for the development of targeted therapeutic strategies. Further studies are required to determine optimal therapeutic time windows, tissue-specific effects, and the long-term safety of Cx modulation.},
}

Humans
*Connexins/metabolism/genetics
*Mental Disorders/metabolism
Animals
*Neurodegenerative Diseases/metabolism
*Stroke/metabolism
Gap Junctions/metabolism
*Brain Injuries, Traumatic/metabolism
Spinal Cord Injuries/metabolism

@article {pmid42076656,
year = {2026},
author = {Manavalan, G and Arnon, Y and Nithyaa, AN and Arnon, S},
title = {Smart Sensor-Driven Gait Rehabilitation Walker Using Machine Learning for Predictive Home-Based Therapy.},
journal = {Sensors (Basel, Switzerland)},
volume = {26},
number = {8},
pages = {},
doi = {10.3390/s26082547},
pmid = {42076656},
issn = {1424-8220},
mesh = {Humans ; *Machine Learning ; *Gait/physiology ; Electromyography ; Male ; Female ; *Walkers ; Middle Aged ; Aged ; Biomechanical Phenomena ; Pilot Projects ; },
abstract = {Abnormal gait associated with neuromuscular and musculoskeletal disorders represents a growing clinical burden, particularly in aging populations. This study presents a modular, low-cost Smart Rehabilitation Walker (SRW) that integrates multimodal sensing and real-time haptic feedback to enable simultaneous gait monitoring and corrective intervention in both clinical and home environments. The system combines force-sensing resistors for bilateral load symmetry assessment, inertial measurement units for fall detection, and surface electromyography (sEMG) for neuromuscular activity monitoring within a closed-loop assistive feedback architecture. A 15-day pilot study involving ten individuals with rheumatoid arthritis and clinically observed neurological gait abnormalities demonstrated measurable improvements in gait biomechanics. The Force Symmetry Index (FSI), calculated using the Robinson symmetry metric, decreased from an average of 0.9691 to 0.2019, corresponding to a 79.26% average reduction in inter-limb load asymmetry. Concurrently, sEMG measurements showed a substantial increase in neuromuscular activation (ΔEMG = 4.28), with statistical analysis confirming a significant improvement across participants (paired t-test: t(9) = 13.58, p < 0.001). To model rehabilitation trajectories, a nonlinear predictive framework based on Gaussian Process Regression achieved high predictive accuracy (R[2] ≈ 0.9, with a mean RMSE of 0.0385), while providing uncertainty-aware trend estimation. Validation using an independent amyotrophic lateral sclerosis gait dataset further demonstrated the transferability of the analytical pipeline. These results highlight the potential of sensor-enabled assistive walkers as scalable platforms for quantitative gait rehabilitation, adaptive feedback, and long-term mobility monitoring.},
}

Humans
*Machine Learning
*Gait/physiology
Electromyography
Male
Female
*Walkers
Middle Aged
Aged
Biomechanical Phenomena
Pilot Projects

@article {pmid42076823,
year = {2026},
author = {Petrozziello, T and Mizerak, E and Krishnamoorthy, A and Donahue, RA and Castillo Torres, AL and Monsanto, RZB and Hammerschlag, BL and Webster, HA and Fillingham, B and Kivisäkk, P and Timmons, J and Fox, K and Arnold, SE and Cohen, J and Klee, J and Paganoni, S and Cudkowicz, ME and Chibnik, LB and Berry, JD and Sadri-Vakili, G},
title = {Phosphorylated Tau at Threonine 181 Is Elevated in Amyotrophic Lateral Sclerosis Plasma.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70266},
pmid = {42076823},
issn = {1097-4598},
support = {//Linda and Mike Mussallem Foundation/ ; //Andre Family/ ; P30AG062421//National Institute of Aging (NIA)/ ; },
abstract = {INTRODUCTION/AIMS: Reliable biomarkers for amyotrophic lateral sclerosis (ALS) remain limited. Although previous studies have shown altered cerebrospinal fluid (CSF) tau measures in ALS, the clinical relevance of plasma tau species as biomarkers remains unclear. Here, we sought to determine whether total tau, tau phosphorylated at T181 (pTau-T181), and their ratio are altered in ALS and whether these measures correlate with disease progression.

METHODS: Plasma samples were obtained from two independent cohorts from the Northeast ALS Consortium (NEALS) Biofluid Repository (cohort 1: n = 76 ALS and n = 52 healthy controls [HC]; cohort 2: n = 98 ALS and n = 90 HC). Cohort 1 (mean age ALS 61.8 years; 63% male) included longitudinal samples; cohort 2 (mean age ALS 45.8 years; 51% male) was cross-sectional. Tau measures were quantified using Quanterix Simoa (cohort 1) and Meso Scale Discovery (MSD) (cohort 2) platforms.

RESULTS: In cohort 1, total tau was lower in ALS versus HC (0.88 vs. 1.49 pg/mL), whereas pTau-T181 (30.29 vs. 12.97 pg/mL) and pTau-T181:tau ratio (52.07 vs. 13.18 pg/mL) were higher. In cohort 2, total tau (40.07 vs. 25.85 pg/mL), pTau-T181 (6.77 vs. 2.18 pg/mL), and their ratio (0.37 vs. 0.098 pg/mL) were elevated in ALS. Plasma measures in cohort 1 did not correlate with decline on the revised ALS Functional Rating Scale (ALSFRS-R). Brain-derived tau (BD-tau) was elevated in ALS (10.07 vs. 5.65 pg/mL) in a subset of samples from cohort 1.

DISCUSSION: Collectively, plasma pTau-T181 levels are consistently elevated in ALS, supporting future studies to define its potential utility as an ALS biomarker.},
}

@article {pmid42077117,
year = {2026},
author = {Chambers, KL},
title = {Enhancement, Autonomy, and the Limits of Beneficence.},
journal = {Bioethics},
volume = {},
number = {},
pages = {},
doi = {10.1111/bioe.70113},
pmid = {42077117},
issn = {1467-8519},
abstract = {Procreative enhancement involves someone making a choice about what genetic trait(s) another person will have. Such control over the body (and mind) of another person, even if done for the recipient's benefit, threatens to overstep the moral boundary between persons. The use of genetic interventions to "enhance" one's offspring without their consent may violate that person's future autonomy. Schaefer, Kahane, and Savulescu argue, however, that the value of autonomy supports at least one class of procreative enhancements: those aimed at enhancing a future person's autonomy by improving their cognitive functioning. I argue that Schaefer et al.'s case for enhancing autonomy rests on a mistaken view about how autonomy bears on our moral obligations. They collapse the value of autonomy into the value of beneficence, or the value of promoting a person's well-being. I will show that while so-called autonomy enhancements may promote a future person's well-being, they cannot make a person more autonomous. Attempts to enhance a future person's autonomy by way of genetic modification instead constitute a violation of that person's autonomy.},
}

@article {pmid42079033,
year = {2026},
author = {Tsai, AC},
title = {What breaks when federal commitments break: comment on Beccia et al.},
journal = {SSM. Mental health},
volume = {9},
number = {},
pages = {},
pmid = {42079033},
issn = {2666-5603},
abstract = {In this commentary on Beccia et al.'s mapping of the 2025 first-wave mental health and substance use-related federal grant terminations, I interpret what happened as a stress test of the U.S. postwar research funding compact. The damage was amplified because the U.S. scientific research enterprise is structurally fragile, characterized by debt-financed institutional growth premised on ever-rising federal budgets; heavy reliance on "soft money" salaries; an oversupplied trainee pipeline; and hypercompetitive, winner-take-all funding dynamics. The damage from the grant terminations has radiated, or will radiate, outward in concentric circles of harm: disrupted research studies and abandoned participants; layoffs, fear, and self-censorship among scientists; scarring of early-career trajectories; institutional and regional capacity loss; and future downstream harms to population mental health and public trust. Even if these grant awards are reinstated, political control, administrative delays and payline squeezes, and indirect cost pressures can and likely will operate as durable de facto defunding.},
}

@article {pmid42079104,
year = {2026},
author = {Kaye, J and Amirani, N and Chan, Ú and Al Bistami, N and Faghihmonzavi, Z and Ahirwar, M and Thomas, R and Robinson, W and Vertudes, E and Raja, K and Barch, M and Linsley, D and Jovicic, A and Finkbeiner, S},
title = {Predictive Cellular Signatures from Live Human Motor Neurons Distinguish TDP-43 ALS and Enable ALS Subtype Stratification.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.04.22.719920},
pmid = {42079104},
issn = {2692-8205},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive, rapid deterioration of motor neurons (MNs). Rare mutations in a handful of genes are sufficient to cause ALS; however, 90% of ALS cases are not linked to these genes and their underlying cause remains unknown. Abnormal subcellular distribution, structure or aggregation of the TDP-43 protein are nearly universal hallmarks of the disease, suggesting a shared molecular mechanism across both genetic and sporadic ALS (sALS). However, the heterogeneity of the ALS clinical syndrome suggests that the underlying mechanisms culminating in ALS and TDP-43 pathology may partly differ among individuals and may need to be understood to develop successful therapies that target subgroups of patients. Here, we harnessed the power of machine learning (ML) to begin to decode, in a systematic and unbiased fashion, the cellular signatures of ALS. We used high-content imaging of live, human iPSC-derived motor neurons (iMNs) from ALS patients or gene-edited and gene-corrected TDP-43 mutant lines to train shallow connected ML algorithms (SMLs) and deep convolutional neural networks (DNNs). Our models identified and distinguished mutant and control iMNs with moderately high accuracy. We then used explainability methods to uncover the discriminating cellular signals and found that the strongest ones mapped to the nuclear area, suggesting underlying alterations within the nucleus. We validated this finding by revealing that TDP-43 mutant iMNs display alterations in nucleocytoplasmic shuttling and cellular integrity. Further, a time-interaction ML model uncovered dynamic morphological transitions preceding degeneration, offering a window into early pathogenic events as well as neurodevelopmental changes. Extending our ML pipeline to iMNs with mutations in the ALS gene C9orf72 or derived from sALS revealed both overlapping and distinguishable signatures, suggesting shared yet distinct mechanistic pathways. Together, these findings establish ML-driven phenotypic profiling as a powerful approach to stratify people with ALS, help disentangle the molecular heterogeneity of ALS and produce a more holistic phenotypic definition in cell-based models, and ultimately find causes and treatments. This strategy offers a scalable and innovative paradigm for uncovering early disease mechanisms not only in ALS but potentially across a spectrum of neurodegenerative and sporadic disorders.},
}

@article {pmid42079349,
year = {2026},
author = {Hoshino, A and Nagata, S and Asakura, T and Tamura, H},
title = {Support-receiving networks and the isolation in schizophrenia: A preliminary study toward recovery-oriented occupational therapy.},
journal = {The British journal of occupational therapy},
volume = {89},
number = {5},
pages = {354-363},
pmid = {42079349},
issn = {1477-6006},
abstract = {INTRODUCTION: Social isolation is a major barrier to recovery for individuals with schizophrenia. Although prior studies examined social networks in relation to symptom severity and quality of life, few have integrated structural and relational dimensions of connectedness within a framework relevant to occupational therapy. This study investigated factors associated with social networks among individuals with schizophrenia in Japan, using Wang et al.'s conceptual framework and social network analysis.

METHOD: A cross-sectional study was conducted with 31 individuals attending a psychiatric day-service center. Social isolation was assessed across four domains: network quantity, network quality, emotional appraisal (mattering and loneliness), and resource appraisal (helping and being helped). Multiple regression analysis identified factors related to network size, with significance set at p < 0.05.

RESULTS: Participants had extremely small networks, averaging fewer than one close contact. Regression analysis showed that only being helped by others was significantly associated with larger network size (β = 0.214, p < 0.01). Loneliness, helping others, and mattering were not significant predictors.

CONCLUSION: Individuals with schizophrenia may experience profound social isolation, with networks limited to relationships where they are recipients of help. Occupational therapy should promote opportunities for reciprocal, empowering connections to support recovery and community integration.},
}

@article {pmid42080410,
year = {2026},
author = {Kasper, E and Lehto, A and Nordmann, N and Peters, O and Hellmann, J and Priller, J and Spruth, EJ and Petzold, GC and Vogt, I and Weydt, P and Bernsen, S and Dinter, E and Falkenburger, B and Günther, R and Düzel, E and Glanz, W and Synofzik, M and Beichert, L and Spottke, A and Wagner, M and Brosseron, F and Schmid, MC and Schneider, A and Teipel, S and Prudlo, J and Hermann, A},
title = {Impact of Plasma p-tau181 on Cognition, Motor Phenotypes, and Disease Course in ALS.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.70423},
pmid = {42080410},
issn = {2328-9503},
abstract = {Phosphorylated tau181 (p-tau181), an Alzheimer's disease biomarker, was recently evaluated in amyotrophic lateral sclerosis (ALS). We investigated plasma p-tau181 in 202 ALS/ALS-FTD patients and 94 healthy controls, assessing cognitive performance, motor function, and longitudinal dynamics. Plasma p-tau181 and NfL were significantly elevated in ALS, with p-tau181 increasing over 1 year while NfL remained stable. Neither marker correlated with cognitive performance, and only NfL was associated with disease severity and progression. Plasma p-tau181 was higher in patients with predominant lower motor neuron involvement. The results indicate that p-tau181 reflects peripheral processes in ALS, providing a complementary, mechanistically distinct biomarker from NfL.},
}

@article {pmid42081010,
year = {2026},
author = {Li, J and Yang, X and Liu, J and Zhao, K},
title = {Unraveling the Pathophysiological Link Between ALS and SCA: The Role of Ischemic Cerebral Vascular Dissection and the Efficacy of Endovascular Therapy.},
journal = {Cerebellum (London, England)},
volume = {25},
number = {3},
pages = {},
pmid = {42081010},
issn = {1473-4230},
support = {YXJL-2022-00351-0183//Neuroscience Innovation Development Research Project/ ; PW2022A-28//Pudong New Area Health Commission/ ; },
mesh = {Humans ; Male ; *Amyotrophic Lateral Sclerosis/complications/diagnostic imaging/physiopathology ; *Spinocerebellar Ataxias/complications/diagnostic imaging/physiopathology ; *Endovascular Procedures/methods ; Young Adult ; *Brain Ischemia/complications/diagnostic imaging/surgery ; *Aortic Dissection/complications/diagnostic imaging/surgery ; Treatment Outcome ; },
abstract = {To explore the role of ischemic cryptogenic vascular dissection (CVD) in a patient presenting with overlapping symptoms of amyotrophic lateral sclerosis (ALS) and spinocerebellar ataxia (SCA), and the impact of endovascular treatment on posterior circulation hypoperfusion, cerebellar atrophy, and clinical symptoms. A 22-year-old male patient with progressive neurological symptoms underwent MRI, CTA, and genetic testing, revealing cerebellar atrophy, a novel TGM6 gene variation associated with SCA type 35, and SETX gene deletions linked to ALS type 4. Ischemic CVD was diagnosed via dynamic contrast-enhanced CT (DCE-CT) and treated with endovascular stent repair followed by dual antiplatelet therapy. Following endovascular treatment, posterior circulation hypoperfusion and cerebellar atrophy were significantly improved. MRI follow-up showed increased cerebellar size and reduced interlobar spacing, with cerebellar dimensions expanding by up to 26.98% and interlobar spacing narrowing by up to 27.14%. Concurrently, the patient experienced marked improvement in clinical symptoms. At the 21-month follow-up, the patient's Modified Rankin Scale (MRS) score was rated as favorable. Ischemic CVD may underlie overlapping ALS and SCA symptoms, suggesting a genetic-vascular link. Endovascular treatment of CVD led to improvements in posterior circulation hypoperfusion, cerebellar atrophy, and clinical symptoms, supporting further investigation into this potential pathogenic nexus.},
}

Humans
Male
*Amyotrophic Lateral Sclerosis/complications/diagnostic imaging/physiopathology
*Spinocerebellar Ataxias/complications/diagnostic imaging/physiopathology
*Endovascular Procedures/methods
Young Adult
*Brain Ischemia/complications/diagnostic imaging/surgery
*Aortic Dissection/complications/diagnostic imaging/surgery
Treatment Outcome

@article {pmid42081784,
year = {2026},
author = {Zhu, RH and Kalra, S and Dobrowolski, P and Fok, D and DuVal, M and Putko, BN and Johnston, W and Beecher, G},
title = {Medical Assistance in Dying in ALS: Frequency, Survival, and Associations With Patient Characteristics in a Canadian Clinic.},
journal = {Neurology},
volume = {106},
number = {10},
pages = {e218032},
doi = {10.1212/WNL.0000000000218032},
pmid = {42081784},
issn = {1526-632X},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/therapy ; Female ; Male ; Aged ; Canada/epidemiology ; Middle Aged ; Retrospective Studies ; *Suicide, Assisted/statistics & numerical data ; Gastrostomy/statistics & numerical data ; },
abstract = {OBJECTIVES: Medical assistance in dying (MAiD) has been available across Canada since 2016 for patients with amyotrophic lateral sclerosis (ALS). We aimed to characterize MAiD use, identify associated factors, and compare survival and location of death in a Canadian ALS cohort.

METHODS: We retrospectively reviewed patients with ALS followed at a Canadian multidisciplinary clinic who died between January 1, 2019 and December 31, 2024. Patient characteristics were described by MAiD status. Factors associated with MAiD utilization were evaluated using regression analyses, and survival and location of death were compared between patients who did and did not pursue MAiD.

RESULTS: Of 255 patients (median age 67 years [IQR 60-75]; 42% female), 55 (21.6%) underwent MAiD. Percutaneous endoscopic gastrostomy (PEG) use was inversely associated with MAiD utilization (OR 0.34, 95% CI 0.15-0.78), whereas demographic and disease characteristics were not associated with MAiD. Survival from diagnosis to death was shorter among patients who underwent MAiD (median 12 vs 14 months; p = 0.019), with no difference from symptom onset. Death at home was more frequent with MAiD (62% vs 35%; p < 0.001).

DISCUSSION: MAiD is a common end-of-life option in ALS, reflecting patient values and is associated with lower PEG use, shorter postdiagnosis survival, and more frequent death at home.},
}

Humans
*Amyotrophic Lateral Sclerosis/mortality/therapy
Female
Male
Aged
Canada/epidemiology
Middle Aged
Retrospective Studies
*Suicide, Assisted/statistics & numerical data
Gastrostomy/statistics & numerical data

@article {pmid42081880,
year = {2026},
author = {Schnieders, C and Scholl, C and Hoeflich, A and Schmicke, M},
title = {A pilot study on the influence of early pregnancy interferon τ to the expression of IGF-binding proteins in primary bovine hepatocytes.},
journal = {Domestic animal endocrinology},
volume = {96},
number = {},
pages = {107018},
doi = {10.1016/j.domaniend.2026.107018},
pmid = {42081880},
issn = {1879-0054},
abstract = {The implantation period is crucial for the establishment of pregnancies in cows. Interferon τ (IFNτ) is produced during early implantation and acts in autocrine, paracrine and endocrine fashions on other endocrine systems. One of these is the insulin-like growth factor 1 (IGF-1) system, which is important for cell growth, proliferation, and therefore pregnancy establishment. This study investigated the effect of IFNτ on the expression of hepatic IGF-binding proteins (IGFBPs) in vitro. Primary bovine hepatocytes in a 2D sandwich culture model were stimulated with recombinant bovine IFNτ (rbIFNτ; 0.1-10.0 ng/mL) for six hours. The mRNA expression of IGFBP-1 to -7 and acid labile subunit (ALS) was measured using qRT‒PCR, and protein production was confirmed using western ligand blotting. All the IGFBPs (1-7) and ALS were expressed at basal levels in primary bovine hepatocytes, with IGFBP-2 to -4 secreted at appreciable concentrations in the medium. The expression of IGFBP-2 to -6 was stimulated by IFNτ, (treatment with rbIFNτ vs. control; IGFBP-2: for 0.5 ng/mL rbIFNτ, p = 0.0166; IGFBP-3: for 0.5 ng/mL, 5.0 ng/mL, and 10.0 ng/mL rbIFNτ, p = 0.0293, p = 0.0252, and p = 0.0099; IGFBP-4: for 0.5 ng/mL rbIFNτ, p = 0.0024; IGFBP-5: for 0.5 ng/mL and 10 ng/mL rbIFNτ, p = 0.0008 and p = 0.0421; IGFBP-6: for 0.1-10.0 ng/mL rbIFNτ, p = 0.0498-0.0022). These results indicate modulation of the IGF-system through IFNτ, which may contribute to adaptations supporting the early establishment of pregnancies in cattle.},
}

@article {pmid42067481,
year = {2026},
author = {Adhyapak, SU and Mishra, P and Basavaraj, M},
title = {Comment on "Improving care for amyotrophic lateral sclerosis with artificial intelligence and affective computing".},
journal = {Journal of the neurological sciences},
volume = {},
number = {},
pages = {125886},
doi = {10.1016/j.jns.2026.125886},
pmid = {42067481},
issn = {1878-5883},
}

@article {pmid42067845,
year = {2026},
author = {Sawada, J and Nakayama, Y and Shimatani, K and Matsuda, C and Haraguchi, M and Itagaki, Y and Bokuda, K and Hayashi, K and Morishima, R and Shinba, T and Fukui, S and Shimizu, T},
title = {Cluster analysis of heart rate variability reveals subgroups with preserved and early-impaired autonomic regulation in amyotrophic lateral sclerosis.},
journal = {BMC neurology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12883-026-04901-w},
pmid = {42067845},
issn = {1471-2377},
support = {Grant-in-Aid for Scientific Research [B] 22H03398 and 23K24656//Japan Society for the Promotion of Science/ ; },
abstract = {BACKGROUND: Patients with amyotrophic lateral sclerosis (ALS) occasionally exhibit autonomic nervous system dysregulation. We examined whether autonomic regulation differed across patients with ALS with varying severity and progression.

METHODS: A total of 45 patients with ALS were enrolled and classified into three subgroups using cluster analysis. Heart rate variability was assessed using the maximum entropy method. The low-frequency (LF) and high-frequency (HF) components, LF/HF ratio (LF/HF), and heart rate (HR) were measured. Temporal changes in each parameter during rest, mental tasks, and post-task rest were evaluated. The values for all patients and subgroups were compared with those of 11 healthy control subjects. Between-group differences were evaluated at rest and using the Task/Rest and After/Task ratios, and within-group changes across the three phases were also analyzed, with non-parametric statistical tests applied.

RESULTS: Cluster analysis classified the patients into three groups: "Group 1: early-preserved group", "Group 2: late-preserved group", and "Group 3: late-impaired group". Overall, the patients showed lower HF and higher LF/HF at rest than the controls, indicating parasympathetic hypoactivity and sympathetic predominance. Abnormalities were more prominent in Groups 1 and 3 than in Group 2. The former two groups showed blunted HF, LF/HF and HR responses during the tasks. The late-preserved group (Group 2) showed no difference in the Task/Rest ratios of HF, LF/HF and HR compared with the controls.

CONCLUSION: Autonomic regulatory functions differ depending on the severity and progression of ALS. The presence of HRV abnormalities in early-preserved patients suggests that autonomic dysregulation in ALS may not be limited to a late-stage secondary complication but may also be present earlier stages. Recognizing HRV abnormalities from early stages may help identify patients at risk of faster progression. Future longitudinal studies in larger cohorts are needed to establish the pathophysiological significance of HRV abnormalities.},
}

@article {pmid42068122,
year = {2026},
author = {Spataro, E},
title = {Invited Commentary on: Brownlee et al.'s "Effect of an Enhanced Recovery after Surgery (ERAS) Protocol in Post-Operative Pain and Opioid Consumption after Rhinoplasty".},
journal = {Facial plastic surgery & aesthetic medicine},
volume = {},
number = {},
pages = {26893614261447768},
doi = {10.1177/26893614261447768},
pmid = {42068122},
issn = {2689-3622},
}

@article {pmid42068244,
year = {2026},
author = {Chevet, E},
title = {Exploring the role of phase separation in TDP-43 pathogenesis with ArtiTDP43.},
journal = {The FEBS journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/febs.70577},
pmid = {42068244},
issn = {1742-4658},
abstract = {TDP-43 is a nuclear RNA-binding protein implicated in neurodegenerative diseases such as ALS and FTLD, where it becomes mislocalized to the cytoplasm and forms pathological aggregates. These aggregates are thought to arise through liquid-liquid phase separation, a process by which proteins form dynamic, membrane-less condensates that can mature into solid structures. To better understand this process, the authors developed ArtiTDP43, a chemically controllable system that enables reversible formation of TDP-43 condensates in cells. Using this tool, they showed that TDP-43 forms different structures depending on its concentration: small liquid-like puncta, intermediate condensates associated with stress granules, and large solid aggregates resembling disease pathology. These transitions are reversible at early stages but become irreversible as aggregates solidify. The study by Combe et al. demonstrates that increasing cytoplasmic TDP-43 concentration drives a liquid-to-solid transition, while oxidative stress accelerates this process and promotes pathological features such as phosphorylation and p62 recruitment. Importantly, formation of cytoplasmic aggregates leads to depletion of nuclear TDP-43 and increased cell death, indicating toxicity. Overall, the findings establish a mechanistic link between phase separation, aggregation, and cytotoxicity in TDP-43 proteinopathies. ArtiTDP43 provides a powerful tool to study early disease mechanisms and explore therapeutic strategies aimed at preventing pathological aggregation or maintaining normal TDP-43 dynamics.},
}

@article {pmid42069087,
year = {2026},
author = {Zecca, C and Urso, D and Dell'Abate, MT and Borlizzi, F and Rollo, E and Logroscino, G},
title = {Neurofilament light and GFAP predict survival in frontotemporal dementia spectrum: A population-based study.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107421},
doi = {10.1016/j.nbd.2026.107421},
pmid = {42069087},
issn = {1095-953X},
abstract = {BACKGROUND: Survival estimates for frontotemporal lobar degeneration (FTLD)-related syndromes by incorporating fluid biomarkers are essential to better assess their prognostic value and explore how they might inform long-term outcomes in FTLD. Population-based registries provide valuable data for these predictions. The aim of the present study was to assess whether NfL and GFAP levels correlate with mortality risk in a population-based registry of incident FTLD.

METHODS: Incident cases with FTLD-spectrum, occurring between 2018 and 2020, were followed for up to six years. Survival and hazard analysis according to biomarkers levels were conducted.

RESULTS: Median survival was 6 years from symptom onset and 3 years from diagnosis. While FTD-ALS phenotype showed significantly shorter survival, no differences were observed among bvFTD, PPAs, and CBS/PSP. Biomarkers were significantly associated with survival. Higher plasma GFAP (HR = 1.006, 95%CIs 1.001-1.012; p = 0.026) and plasma NfL (HR = 1.027, 95%CIs 1.003-1.053; p = 0.025) were associated with increased mortality risk in bvFTD, PPAs, and CBS/PSP.

CONCLUSIONS: These results highlight the potential of NfL and GFAP as valuable biomarkers for assessing prognosis in FTLD and underscore the importance of incorporating biomarker analysis into clinical practice for more accurate patient management. Further studies are needed to refine prognostic models for FTLD.},
}

@article {pmid42069088,
year = {2026},
author = {Senerchia, G and Iuzzolino, VV and Spisto, M and Panico, F and Polito, C and Aruta, L and Fiorenza, M and Sirica, R and Terracciano, D and Dubbioso, R},
title = {Elevated plasma sTREM2 reflects microglial activation but lacks diagnostic and clinical relevance in amyotrophic lateral sclerosis.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107430},
doi = {10.1016/j.nbd.2026.107430},
pmid = {42069088},
issn = {1095-953X},
abstract = {Microglial activation contributes to the neuroinflammatory response in amyotrophic lateral sclerosis. Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) reflects microglial activity in several neurodegenerative disorders, but its role in amyotrophic lateral sclerosis remains unclear. We evaluated plasma sTREM2 as a marker of microglial activation in amyotrophic lateral sclerosis (ALS) and compared its diagnostic performance with established blood biomarkers of neurodegeneration. Plasma sTREM2, neurofilament light chain (NfL), phosphorylated tau181 (Ptau181), and glial fibrillary acidic protein (GFAP) were measured in 100 patients with ALS, 30 healthy controls, and 30 disease mimics. Group differences were assessed using general linear models adjusted for age and sex. Associations with clinical variables and inflammatory markers were tested using Spearman correlation, and diagnostic performance was evaluated using receiver operating characteristic curves. Plasma sTREM2 differed across groups (p = 0.016), with higher levels in ALS compared with healthy controls (p = 0.013) and in mimics compared with healthy controls (p = 0.007), but no difference between ALS and mimics (p = 0.394). Discrimination between ALS and controls was modest (area under the curve 0.677), with no discrimination between ALS and mimics (area under the curve 0.512). No association was found between sTREM2 and disease severity or inflammatory markers (all p > 0.10). Plasma sTREM2 increases in ALS but lacks diagnostic specificity and clinical associations, supporting its role as a nonspecific marker of neuroimmune activation rather than a biomarker of disease-related neurodegeneration.},
}

@article {pmid42069252,
year = {2026},
author = {Zi, X and Li, H and Fan, H},
title = {Considerations on Sayed et al.'s Bimekizumab Trial: Definitions, Bias, and Risk.},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.04.1974},
pmid = {42069252},
issn = {1097-6787},
}

@article {pmid42065104,
year = {2025},
author = {Doherty, AJ and Howarth, JL},
title = {The Simplified BrainTower and Pipe Cleaners: Model Building as a Learning Tool in Neuroscience.},
journal = {Journal of undergraduate neuroscience education : JUNE : a publication of FUN, Faculty for Undergraduate Neuroscience},
volume = {24},
number = {1},
pages = {27-37},
pmid = {42065104},
issn = {1544-2896},
abstract = {Models have a long history of use in helping students to understand the three-dimensional organisation of biological structures. This is particularly true of neuroanatomical teaching where it is often difficult to distinguish grey and white matter in the fixed prosections often used in dissection rooms. A model system designed to help medical students understand the anatomy of the ascending and descending white matter tracts through the brain and spinal cord had the opposite effect: it made the task of learning these tracts more difficult. The model was complex and difficult for students to engage with. The aim of this study was to introduce a simplified version of this modelling system that was interactive and intuitive, to enable students to build a model in a single workshop session and to assess how the modeling activity impacted on students' learning. Students were asked to build a model of either the anterolateral/spinothalamic tracts (ALS), the dorsal column/medial lemniscus tract (DCML) or the corticospinal tracts (CST) using pipe-cleaners to represent the route of the pathway, including the number of neurons. We found that students were easily able to build a representation of one of these tracts and that they could answer questions on the structure and function of the tract they built significantly better than similar questions related to the other tracts. This enhancement in knowledge was maintained through to end of unit exams eleven weeks after the modelling activity, demonstrating that actively building a model contributes to deep rather than superficial learning.},
}

@article {pmid42061283,
year = {2026},
author = {Banerjee, S and Panjwani, D and Singh, S and Singh, TG},
title = {TGR5 and FXR receptors in motor degeneration: Molecular mechanism, crosstalk pathways and therapeutic prospects.},
journal = {Journal of neuroimmunology},
volume = {417},
number = {},
pages = {578942},
doi = {10.1016/j.jneuroim.2026.578942},
pmid = {42061283},
issn = {1872-8421},
abstract = {Motor neuron degeneration in disorders such as amyotrophic lateral sclerosis, spinal muscular atrophy, and Parkinson's disease is increasingly recognized as a consequence of disrupted metabolic, mitochondrial, and inflammatory balance. There is emerging data that bile acid receptors - Takeda G-protein-coupled receptor 5 (TGR5) and Farnesoid X receptor (FXR) are key regulators that combine systemic metabolism with neuronal survival. These receptors modulate the mitochondrial biogenesis, oxidative stress responses, and glial inflammatory signaling and coordinate gut-liver-brain crosstalk. Their malfunction leads to an unaffected energy metabolism, increased reactive oxygen species, and neuroinflammation, thereby accelerating the death of motor neurons. Their dysfunction results in impaired energy metabolism increased reactive oxygen species and neuroinflammation, accelerating motor neuron death. Pharmacological activation of TGR5 and FXR improves mitochondrial integrity reduces cytokines driven toxicity and preserves neuromuscular junction stability in preclinical models. However, translational opportunities are dampened by some factors such as restriction of bioavailability of the central nervous system, receptor variation and metabolic systemic interactions. To clarify, the TGR5 -FXR signaling axis would provide a mechanistic model of how to develop metabolism-based therapeutics that can simultaneously supplement mitochondrial protection, immunologic mangling, and neuro-specific to energetic homeostasis in motor neuron disease.},
}

@article {pmid42061810,
year = {2026},
author = {Arasmou-Idrovo, MS and Marín-Rodríguez, B and Gironda-Martínez, A and García, AG and León, R and Pascual-Guerra, J and Torres-Rico, M},
title = {UNEXPECTED MECHANISMS OF REPURPOSED DRUGS IN THE PATHOGENIC PATHWAYS OF NEURODEGENERATIVE DISEASES. DISCOVERING NEW NEUROPROTECTIVE THERAPIES IN CELLULAR MODELS.},
journal = {Neuropharmacology},
volume = {},
number = {},
pages = {110994},
doi = {10.1016/j.neuropharm.2026.110994},
pmid = {42061810},
issn = {1873-7064},
abstract = {Advances in biomedicine have increased life expectancy, leading to a growing prevalence of age-related neurodegenerative diseases such as Alzheimer's and Parkinson's disease, alongside disorders of genetic or environmental origin including multiple sclerosis, Huntington's disease, and amyotrophic lateral sclerosis. Despite their diverse etiologies, these conditions share convergent pathogenic mechanisms-calcium overload, neuroinflammation, and oxidative stress-that drive neuronal apoptosis and progressive neurodegeneration. Developing therapies that effectively target these interconnected pathways remains a major challenge. Here, we applied a drug-repurposing pipeline integrating computational chemistry, calcium channel affinity prediction, and in vitro validation in SH-SY5Y and HEK293 cells. Eight clinically approved CNS drugs were screened for activity against Caᵥ1, Orai1, and P2X7 channels, and subsequently evaluated in neuroprotection assays. Several compounds demonstrated significant efficacy, with chlorpromazine showing broad-spectrum activity (neuroprotection, Caᵥ1.2 and P2X7 antagonism, anti-inflammatory effects), trimipramine emerging as a potent antioxidant, and vilazodone displaying synergistic neuroprotection in combination with procyclidine. These findings reveal multi-target pharmacological profiles in well-tolerated drugs not currently used for neurodegenerative indications. By highlighting both individual and combinatorial strategies, this work provides a foundation for translational studies aimed at repurposing approved agents for complex neurological disorders, with particular relevance to Parkinson's disease.},
}

@article {pmid42062527,
year = {2026},
author = {Azzolino, D and Zulueta, A and Piras, R and Mariani, P and Sideri, R and Lucchi, T and Lunetta, C},
title = {Agreement between bioimpedance-measured and calf-derived appendicular skeletal muscle mass in amyotrophic lateral sclerosis patients.},
journal = {European journal of clinical nutrition},
volume = {},
number = {},
pages = {},
pmid = {42062527},
issn = {1476-5640},
support = {Ricerca Corrente//Ministero della Salute (Ministry of Health, Italy)/ ; Ricerca Corrente//Ministero della Salute (Ministry of Health, Italy)/ ; Ricerca Corrente//Ministero della Salute (Ministry of Health, Italy)/ ; Ricerca Corrente//Ministero della Salute (Ministry of Health, Italy)/ ; Ricerca Corrente//Ministero della Salute (Ministry of Health, Italy)/ ; Ricerca Corrente//Ministero della Salute (Ministry of Health, Italy)/ ; Ricerca Corrente//Ministero della Salute (Ministry of Health, Italy)/ ; },
abstract = {BACKGROUND: Over time, amyotrophic lateral sclerosis (ALS) has been considered an accelerated model of sarcopenia. However, muscle mass is rarely assessed in ALS patients. The aim of this study was to explore the agreement between bioelectrical impedance analysis (BIA)-measured and calf circumference (CC)-derived appendicular skeletal muscle mass index (ASMMI) in ALS patients.

METHODS: Body composition was assessed using anthropometric measures and BIA. Pearson analyses were used to assess correlations and Kappa (κ) statistics were used to evaluate agreement between BIA-measured and CC-derived ASMMI. CC predictive ability was assessed through the area under the receiver operating characteristic curve.

RESULTS: A total of 61 ALS patients were included. The CC-ASMM was highly correlated with the BIA-ASMM (r = 0.830, p < 0.001) and CC-ASMMI was moderately correlated with BIA-ASMMI (r = 0.62, p < 0.001). Low CC-derived and BIA-derived ASMMI presented a moderate degree of agreement in the overall sample (k = 0.546, 95% CI 0.325-0.767) and in men (k = 0.432, 95% CI 0.056-0.809), while a substantial agreement was observed in women (k = 0.613, 95% CI 0.344-0.883). The optimal cut-off values for CC in identifying low ASMMI from the ROC analysis, were 34 cm for both sexes with an area under the curve (AUC) of 0.818 for men (sensitivity 80%, specificity 78.3%) and of 0.841 (sensitivity 83.3%, specificity 72.7%) for women.

CONCLUSION: Our preliminary study showed a good predictive ability of the CC, an anthropometric parameter significantly associated with sarcopenia, in reflecting the ASMM. The best performance was found for a CC cut-off point of ≤34 cm in both sexes.},
}

@article {pmid42063547,
year = {2026},
author = {Demaegd, KC and Kool, L and Baindoor, S and Donovan, PD and Su, J and Westeneng, HJ and van Eijk, RPA and Geoghegan, G and Perez Morrissey, E and Halang, L and Poesen, K and Masrori, P and Gibriel, HAY and Jirström, E and Venø, MT and Kjems, J and Hardiman, O and Veldink, JH and Kenna, K and van den Berg, LH and Van Damme, P and Prehn, JHM and van Es, MA},
title = {Small RNA sequencing identifies serum tDR-1:34-Gly-GCC tiRNA levels as a biomarker for survival in amyotrophic lateral sclerosis.},
journal = {iScience},
volume = {29},
number = {5},
pages = {115636},
pmid = {42063547},
issn = {2589-0042},
abstract = {Survival is highly variable in amyotrophic lateral sclerosis (ALS), complicating prognosis and clinical trial design. Despite advances in biomarker development, accessible prognostic tools are limited. Small non-coding (snc) RNAs are a recently discovered biomarker class showing differential regulation across neurodegenerative diseases, including ALS. Here, we explored changes in sncRNAs over time in ALS. We performed small RNA sequencing in a discovery cohort of 116 longitudinal serum samples from ALS 40 patients collected at 3- to 4-month intervals and identified tRNA-derived stress-induced RNA (tiRNA) tDR-1:34-Gly-GCC as the top sncRNA to increase over time. The finding was validated using TaqMan PCR and replicated in an independent cohort of 35 patients. Both univariate and joint model analyses showed that higher tDR-1:34-Gly-GCC levels correlated with shorter survival. Given that the translation of mRNAs and stress-induced translation inhibition are dysregulated in ALS and linked to familial ALS genes, combined with these findings, serum tDR-1:34-Gly-GCC tiRNA levels hold potential as a prognostic biomarker and outcome measure in clinical trials.},
}

@article {pmid42063613,
year = {2025},
author = {van der Putten, TAW and Verhees, JJF and Koma, Z and van Hoof, PH and Heijkers, D and de Boer, WF and Esser, HJ and Hoogerwerf, G and Lemmers, P},
title = {Insights into the fine-scale habitat use of Eurasian Water Shrew (Neomys fodiens) using radio tracking and LiDAR.},
journal = {Journal of mammalogy},
volume = {106},
number = {3},
pages = {549-560},
pmid = {42063613},
issn = {0022-2372},
abstract = {The Eurasian Water Shrew (Neomys fodiens) is one of the largest shrew (Soricidae) species in Eurasia. In Western Europe, this semiaquatic species often occurs in riparian and marshland habitats that have a high degree of naturalness, but is being threatened by habitat degradation and other anthropogenic factors. The species mostly occurs in low abundance and is elusive. Therefore, understanding its habitat use is challenging, yet imperative for establishing species-specific conservation measures. Technological developments in radio tracking and high-resolution remote sensing such as Light Detection And Ranging (LiDAR) now enable the quantification of ecological niches and provide insight into habitat requirements for a species. Here, we combined radio tracking and LiDAR to quantify habitat use by Eurasian water shrews. Alongside a lowland brook in the Netherlands, 20 individuals were tracked between September and October 2022, resulting in 332 unique locations of Eurasian water shrews. For each of these locations, 11 LiDAR-derived variables were calculated and subsequently analyzed in a species distribution model (SDM). The SDM yielded a model with a high accuracy (predictive performance AUC = 0.93). The variable of highest importance was dense and relatively short vegetation <1 m, which had a positive effect on Eurasian Water Shrew occurrence. Open areas seem to be avoided. Vegetation of heights between 1 and 15 m were found to be less important for the occurrence. The probability of occurrence decreased with increasing distance to water, indicating that the species occurs in the proximity of water, although vegetation-related variables were more important. The obtained detailed knowledge of fine-scale habitat use can be used to improve habitat conservation, restoration, and management for the species. Combining radiotelemetry data with LiDAR data is a promising approach to identifying species-habitat relationships of elusive species such as the Eurasian Water Shrew.},
}

@article {pmid42064053,
year = {2026},
author = {Chen, Y and Kang, Q and Nie, D and Zhang, P and Zhou, X and Li, Z and Hu, Y and Xin, T and Gong, H},
title = {Combination of albumin-lymphocyte score and skeletal muscle index predicts prognosis of patients with ovarian cancer after primary debulking surgery.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1781291},
pmid = {42064053},
issn = {1664-3224},
mesh = {Humans ; Female ; Middle Aged ; *Ovarian Neoplasms/surgery/mortality/blood/pathology/diagnosis ; Prognosis ; *Cytoreduction Surgical Procedures ; Retrospective Studies ; *Muscle, Skeletal/pathology ; Aged ; Adult ; *Lymphocytes ; Lymphocyte Count ; },
abstract = {PURPOSE: Accumulating evidence underscores the significance of inflammation and nutrition in tumor progression. Although low albumin-lymphocyte score (ALS) and skeletal muscle index (SMI) are known to be associated with negative outcomes in patients with ovarian cancer (OC) undergoing primary debulking surgery, the usefulness for predicting prognosis remains unclear. We aimed to assess the relevant preoperative prognostic variables and their combined impact on patients with OC.

METHODS: This retrospective study included 347 patients with primary OC from multiple medical centers. The patients were divided into discovery (237 patients) and validation (110 patients) cohorts. Serological tests and plain computed tomography were performed to quantify the ALS and SMI. We investigated the preoperative prognostic ability of a unique index based on a combination of ALS and SMI, the CAS grade.

RESULTS: Patients with a lower ALS and a higher SMI showed improved overall survival (OS) and recurrence-free survival (RFS). Upon stratification by CAS grade, grade 1 patients demonstrated the highest body mass index and the most favorable survival prognosis, whereas grade 3 patients demonstrated the poorest OS and RFS. The independent variables for OS and RFS included residual disease and elevated CAS grade. These findings were validated in an independent cohort study.

CONCLUSION: The CAS grade, a combination of ALS and SMI, is a meaningful and independent predictor of prognosis in patients with OC.},
}

Humans
Female
Middle Aged
*Ovarian Neoplasms/surgery/mortality/blood/pathology/diagnosis
Prognosis
*Cytoreduction Surgical Procedures
Retrospective Studies
*Muscle, Skeletal/pathology
Aged
Adult
*Lymphocytes
Lymphocyte Count

@article {pmid42064717,
year = {2026},
author = {Chikamura, K and Yoshida, W and Tsurumi, S and Kawahara, J},
title = {Rightward shift of self-face representation.},
journal = {i-Perception},
volume = {17},
number = {2},
pages = {20416695261444892},
pmid = {42064717},
issn = {2041-6695},
abstract = {Self-face representation refers to an internal image of one's own face that does not necessarily match its physical properties. A previous study showed that remembered facial features located centrally or on the right side, such as the nose and right eye, tend to shift rightward. However, this rightward bias may result from using the right index finger to report locations. The present study examined whether the bias would occur when participants used the left index finger, following Mora et al.'s procedure in which participants, with their eyes closed, pointed to locations on a transparent acrylic board as if the designated facial features were projected in parallel in front of the board. Twenty-eight participants pointed to designated facial features using either their right or left index finger. The reported locations were recorded digitally and compared with the actual feature locations. When using the right finger, a rightward bias appeared for all central and right-side facial features. When using the left finger, all left-side facial features shifted leftward, indicating a leftward bias. Importantly, the rightward bias remained for all right-side facial features. These results suggest that the bias reflects both a general tendency toward rightward shifting and an artifact related to the side of the reporting finger.},
}

@article {pmid42055290,
year = {2026},
author = {Gaillard, SL and Meisenheimer, J and Hou, J and Dellavalle, RP},
title = {Response to Jin et al.'s "Global, regional, and National burden of pruritus: A comprehensive study from the Global Burden of Disease, 1992-2021.".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.03.116},
pmid = {42055290},
issn = {1097-6787},
}

@article {pmid42055490,
year = {2026},
author = {Banerjee, C and Singh, RK and Mehan, S},
title = {Raloxifene Beyond Osteoporosis: Unlocking Neurorestoration Through Remyelination, Inflammatory Regulation, and Neuroimmune Modulation in CNS Pathologies.},
journal = {International immunopharmacology},
volume = {181},
number = {},
pages = {116668},
doi = {10.1016/j.intimp.2026.116668},
pmid = {42055490},
issn = {1878-1705},
abstract = {Raloxifene, a selective estrogen receptor modulator (SERM), has emerged as a promising candidate for repurposing in neurodegenerative and neuropsychiatric disorders. Traditionally approved for osteoporosis and breast cancer prevention, its tissue-selective estrogen receptor modulation underpins its potential therapeutic applications. This review critically examines the pharmacological, preclinical, and clinical evidence supporting raloxifene's neuroprotective and neuropsychiatric effects, as well as its mechanisms of action, safety profile, and clinical limitations. Raloxifene exerts neuroprotective effects by targeting estrogen receptors, including ERα, ERβ, and GPER, modulating genomic and non-genomic pathways. These pathways regulate oxidative stress, mitochondrial stability, neuroinflammation, and apoptosis-core features of neurological disorders such as Alzheimer's (AD), Parkinson's (PD), Multiple sclerosis (MS), and Amyotrophic lateral sclerosis (ALS). Preclinical studies demonstrate raloxifene's ability to reduce amyloid-β aggregation in AD, protect dopaminergic neurons in PD, mitigate demyelination in MS, and decrease protein aggregation in ALS. Additionally, raloxifene exhibits positive effects on memory, attention, and negative symptoms in schizophrenia, alongside antidepressant and anxiolytic properties. Although promising, raloxifene's clinical translation faces challenges. Existing trials are limited by small sample sizes, heterogeneous designs, and a lack of long-term data. Most studies focus on postmenopausal women, leaving gaps regarding effects in men, premenopausal women, and younger populations. Furthermore, discrepancies between preclinical and clinical dosing complicate its therapeutic optimization. Future research should explore sex-specific effects, optimize CNS-targeted dosing strategies, and employ biomarkers for neuroprotection and inflammation. Long-term trials are essential to evaluate its disease-modifying potential. Raloxifene represents a promising repurposing candidate for CNS disorders, however, its therapeutic role remains to be established through robust clinical validation.},
}

@article {pmid42055632,
year = {2026},
author = {Alhadidy, MM and Hinton, TV and Ernst, KN and Yang, Y},
title = {Amyloid extraction from neurodegenerative disease tissues for structural studies.},
journal = {Methods in enzymology},
volume = {729},
number = {},
pages = {1-33},
doi = {10.1016/bs.mie.2026.01.032},
pmid = {42055632},
issn = {1557-7988},
mesh = {Humans ; Cryoelectron Microscopy/methods ; *Neurodegenerative Diseases/metabolism/pathology ; *Brain/metabolism/pathology ; *Amyloid beta-Peptides/isolation & purification/chemistry/ultrastructure ; alpha-Synuclein/isolation & purification/chemistry ; tau Proteins/isolation & purification/chemistry ; DNA-Binding Proteins/isolation & purification/chemistry ; },
abstract = {Amyloid aggregates are hallmarks of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). Yet structural analysis of these brain-extracted filaments requires specialized extraction protocols that minimize structural perturbation while removing tissue matrix components. This chapter focuses on amyloid-β (Aβ) filaments, the primary component of senile plaques in AD, and presents three complementary methods for isolating these filaments from human brain tissues suitable for cryo-electron microscopy analysis. These methods have enabled high-resolution structural studies reaching 2.0-3.5 Å resolution and revealed distinct conformational polymorphs in AD and other neurodegenerative diseases. Method selection depends on tissue type, target filaments, and downstream analysis requirements, with comprehensive guidance provided for optimal protocol choice and implementation. The protocols demonstrate broad applicability beyond Aβ extraction, with successful adaptations provided for tau, α-synuclein, and TDP-43 extraction. Understanding these filamentous structures extracted with minimal perturbation is essential for developing targeted therapeutics and advancing structure-based drug design approaches for AD, PD, ALS, FTD, and other neurodegenerative diseases.},
}

Humans
Cryoelectron Microscopy/methods
*Neurodegenerative Diseases/metabolism/pathology
*Brain/metabolism/pathology
*Amyloid beta-Peptides/isolation & purification/chemistry/ultrastructure
alpha-Synuclein/isolation & purification/chemistry
tau Proteins/isolation & purification/chemistry
DNA-Binding Proteins/isolation & purification/chemistry

@article {pmid42057546,
year = {2026},
author = {Jha, NK and Chauhan, P and Abomughaid, MM and Avinash, D and Almutary, AG and Lakhanpal, S and Singh, A and Sulaimani, GM and Al-Kuraishy, HM and Mohammed, HA and Misra, J and Thakur, K and Kumar, D},
title = {mTOR Signalling in Neurodegenerative Disorders: Unveiling Key Factors, Mechanistic Insights, and Possible Therapeutic Interventions.},
journal = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology},
volume = {60},
number = {2},
pages = {136-174},
doi = {10.33594/000000858},
pmid = {42057546},
issn = {1421-9778},
mesh = {*TOR Serine-Threonine Kinases/metabolism/antagonists & inhibitors ; Humans ; *Signal Transduction/drug effects ; *Neurodegenerative Diseases/metabolism/pathology/drug therapy ; Animals ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; AMP-Activated Protein Kinases/metabolism ; Alzheimer Disease/metabolism/pathology/drug therapy ; Autophagy ; },
abstract = {Neurodegenerative diseases (NDDs) are defined by the gradual degeneration of neuronal cells, wherein the accumulation of misfolded proteins can lead to memory impairments, motor dysfunctions, and other deteriorations. Despite the widespread impact, there are currently no viable pharmaceuticals to treat these disorders. The mTOR protein is a crucial regulator of cell survival, growth, autophagy, and apoptosis. Targeted modulation of mTOR signaling holds promise for mitigating neurodegeneration in Alzheimer's, Huntington's, ALS, and Parkinson's disease. Understanding its interactions with pathways such as PI3K/Akt, AMPK, and SIRT1 is essential for developing effective therapeutics.},
}

*TOR Serine-Threonine Kinases/metabolism/antagonists & inhibitors
Humans
*Signal Transduction/drug effects
*Neurodegenerative Diseases/metabolism/pathology/drug therapy
Animals
Phosphatidylinositol 3-Kinases/metabolism
Proto-Oncogene Proteins c-akt/metabolism
AMP-Activated Protein Kinases/metabolism
Alzheimer Disease/metabolism/pathology/drug therapy
Autophagy

@article {pmid42057560,
year = {2026},
author = {Turner, N and Wilson, E and Faull, C and Palmer, J and Davidson, S and Turner, MR},
title = {A qualitative exploration of how people with motor neurone disease who use tracheostomy ventilation understand and experience quality of life.},
journal = {Disability and rehabilitation},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/09638288.2026.2658439},
pmid = {42057560},
issn = {1464-5165},
abstract = {PURPOSE: This qualitative study aimed to increase awareness of how people with motor neurone disease (pwMND) who use tracheostomy ventilation (TV) understand quality of life.

METHODS: Semi-structured interviews were conducted with 14 pwMND (age 36-76 years) who had used TV for 3 months-12 years.

RESULTS: Five themes were identified following thematic analysis. PwMND who use TV associated quality of life with: i) Extending life; ii) Improving symptom management; iii) Adapting to living with MND; iv) Finding purpose; v) Staying positive. TV extended survival and improved management of symptoms such as breathlessness and secretions. Psychological adaptation and acceptance supported pwMND to focus on remaining abilities and sources of enjoyment, whilst the pursuit of meaning and purpose sustained a positive outlook.

CONCLUSIONS: Quality of life for pwMND who use TV is multidimensional, encompassing physical, psychological, and existential domains. Findings underscore the value of a person-centred approach, recognising that pwMND can maintain a positive outlook despite significant limitations. A holistic assessment of quality of life is recommended, addressing not only physical health but also psychological and social well-being. Effective communication is required to ensure pwMND consider all implications of TV, including costs of adapting the home and demands of living with paid carers.},
}

@article {pmid42058164,
year = {2026},
author = {Park, S and Song, Y},
title = {Development and implementation of a student-led, project-based, community health nursing clinical placement focused on health promotion for nursing students in Korea.},
journal = {Journal of research in nursing : JRN},
volume = {},
number = {},
pages = {17449871261427312},
pmid = {42058164},
issn = {1744-988X},
abstract = {PURPOSE: This study aimed to develop and implement a community health nursing clinical placement focused on a health promotion project for nursing students in Korea.

METHODS: This quantitative descriptive study developed and implemented a community health nursing clinical placement curriculum based on a health promotion project.

RESULTS: In this study, Jalinus et al's seven steps for project-based learning were applied: formulation of expected learning outcomes through community health promotion projects, understanding the concept of teaching materials, skill training, designing the community health promotion project theme, developing the community health promotion project proposal, executing the community health promotion project, and presenting the community health promotion project outcomes. Nursing students demonstrated positive satisfaction scores with the clinical placement.

CONCLUSIONS: The community health nursing clinical placement focused on a health promotion project demonstrated a high level of student satisfaction. The nursing students actively engaged in the clinical placement and expressed strong satisfaction with the acquisition of new knowledge and the development of competencies to assess community health issues. Locally co-designed clinical placements that reflect regional characteristics may contribute to improved student satisfaction, and there is a need to include student participation in the future design of learner-driven, problem-solving-oriented curriculum.},
}

@article {pmid42058282,
year = {2026},
author = {Kalyani, A and Northall, A and Schreiber, S and Brüggemann, J and Vielhaber, S and Al Dubai, M and Bin Ramadan, A and Mattern, H and Speck, O and Reichert, C and Kuehn, E},
title = {Individualized phenotyping of functional amyotrophic lateral sclerosis pathology in sensorimotor cortex.},
journal = {Brain communications},
volume = {8},
number = {2},
pages = {fcag127},
pmid = {42058282},
issn = {2632-1297},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of motor neurons in primary motor cortex, leading to muscle weakness, atrophy and death within a median of 3 years. Even though ALS is characterized by different disease subtypes affecting different body parts, individualized phenotyping of functional ALS pathology has so far not been achieved. We recorded 7 Tesla functional MRI data while ALS patients and matched controls moved affected and non-affected body parts in the MR scanner. We applied robust Shared Response Modelling for capturing ALS-specific shared responses for group classification, and Partial Least Squares regression for relating the latent variables to clinical subtypes and the degree of disease progression. We show that disease onset and severity can be best modelled by functional connectivity rather than local activation changes. We also show that functional disease-defining information in primary motor cortex is not the strongest in the area that is behaviourally first-affected, deviating from the behavioural phenotype of the patients. When computing the model's weight distribution of the King stage classification and projecting them back into voxel space, the highest mean weights are present in the foot and tongue/face regions. Our data highlight the importance of 7 Tesla functional MRI task-based functional connectivity measures for classifying ALS patients in addition to structural readouts and provides evidence that a 7 Tesla functional MRI can be used for identifying a disease signature of each individual ALS patient.},
}

@article {pmid42058985,
year = {2026},
author = {Balusamy, S and Sivalingam, R and Rooben, S and Helen, S},
title = {RES-MND: Motor neuron disease detection using Res4Net-convolutional block attention module.},
journal = {Turkish journal of medical sciences},
volume = {56},
number = {2},
pages = {426-438},
pmid = {42058985},
issn = {1303-6165},
mesh = {Humans ; *Motor Neuron Disease/diagnostic imaging/diagnosis ; Magnetic Resonance Imaging/methods ; *Multimodal Imaging/methods ; *Neural Networks, Computer ; Algorithms ; },
abstract = {BACKGROUND/AIM: Motor neuron diseases (MNDs) are progressive neurological disorders that cause muscle weakness and wasting as a result of ongoing neurodegeneration. MNDs require comprehensive diagnostic approaches that integrate clinical symptoms, laboratory findings, and multimodal imaging data.

MATERIALS AND METHODS: In this study, a novel residual network for motor neuron disease detection (RES-MND) framework is proposed for detecting MNDs using multimodal imaging data. Initially, the input multimodal images, including MRI, CT, PET, and DTI, are preprocessed using adaptive dynamic histogram equalization and the total variation bilateral filter. The preprocessed multimodal images are processed through Res4Net-CBAM for feature extraction to enhance image recognition performance. A dove swarm optimization algorithm is employed to select the most relevant features from the multimodal images. Finally, the deep belief network (DBN) classifies five categories, including one control group (normal) and four MND types: ALS, PLS, PBP, and PMA.

RESULTS: The performance of the proposed RES-MND method is evaluated using standard metrics such as accuracy, precision, recall, and F1-score. According to the results, the proposed RES-MND method achieved the highest accuracy rate of 99.65%, outperforming existing methods.

CONCLUSION: The proposed DBN achieved 0.68%, 0.41%, and 0.9% higher accuracy than SNN, DNN, and CNN, respectively. The proposed RES-MND method achieved 1.08%, 2.18%, and 1.7% higher overall accuracy compared to existing methods such as miRNA, vGRF, and SVM-RFE, respectively.},
}

Humans
*Motor Neuron Disease/diagnostic imaging/diagnosis
Magnetic Resonance Imaging/methods
*Multimodal Imaging/methods
*Neural Networks, Computer
Algorithms

@article {pmid42059647,
year = {2026},
author = {Ma, X and Jiang, Z and Yang, T and Zhang, H and Lu, W and Liu, K and Fan, X and Yang, G and Wu, S},
title = {Integrated multi-omics analysis reveals gut dysbiosis and altered energy metabolism in Chinese ALS patients.},
journal = {Microbiology spectrum},
volume = {},
number = {},
pages = {e0060926},
doi = {10.1128/spectrum.00609-26},
pmid = {42059647},
issn = {2165-0497},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with a complex etiology. Emerging evidence implicates gut microbiota dysbiosis in ALS pathology via the gut-brain axis, yet the specific integrative profile of the gut microbiome, virome, and metabolome, particularly in Chinese patients, remains incompletely characterized. Although global diversity indices showed no significant differences, taxonomic analysis revealed distinct compositional shifts. The ALS microbiome was characterized by a significant depletion of beneficial anti-inflammatory genera, specifically Akkermansia and Faecalibacterium, and an expansion of opportunistic pathogens such as Escherichia and oral-associated taxa (e.g., Streptococcus). We also observed a specific alteration in the gut virome, with viral genera including Puppervirus and Donellivirus enriched in ALS patients. Functionally, the ALS microbiome exhibited a marked upregulation of pathways involved in L-ascorbate (vitamin C) degradation and fatty acid biosynthesis, suggesting a microbial contribution to systemic oxidative stress. Metabolomic analysis corroborated these findings, identifying 271 differentially expressed metabolites. ALS patients showed elevated levels of inflammatory lipids (e.g., LysoPC) and metabolic intermediates of the tricarboxylic acid (TCA) cycle, alongside a downregulation of antioxidants. Integrative analysis highlighted profound dysregulation in porphyrin metabolism, oxidative phosphorylation, and energy homeostasis. Our findings demonstrate that ALS is associated with a specific dysbiotic gut ecosystem characterized by the loss of protective commensals, unique viral signatures, and functional metabolic reprogramming that exacerbates host oxidative stress and energy deficits. These results provide new insights into gut-brain interactions and highlight microbial antioxidant depletion as a potential therapeutic target.IMPORTANCEAmyotrophic lateral sclerosis (ALS) is a devastating disease with no cure. While gut bacteria are known to influence brain health, we still do not understand exactly how they contribute to ALS progression. In this study, we used advanced DNA sequencing and chemical analysis to deeply examine the gut ecosystem of ALS patients. Beyond just cataloging which bacteria are present, we discovered what they are doing: the ALS microbiome actively breaks down vitamin C (a critical antioxidant) and disrupts energy metabolism. We also found a loss of protective bacteria that maintain the gut barrier. These findings are significant because they suggest that the gut microbiome in ALS patients may be actively fueling the disease by depleting the body's antioxidant reserves. This points to a new potential treatment strategy: targeting these specific bacterial functions or replenishing specific metabolites to protect motor neurons.},
}

@article {pmid42059992,
year = {2026},
author = {Ghiyamihoor, F and Asemi Rad, A and Hassanifar, P and Kaur, R and Patel, JH and Kim, I and Marzban, A and Mehdizadeh, M and Levin, DB and Ghavami, S and Toncheva, A and Benali, S and Dubois, P and Balci, F and Habibi, HR and Manto, M and Marzban, H},
title = {Micro- and Nanoplastics in the Human Brain: Mechanistic Plausibility, Translational Challenges, and Links to Neurological Disease Trends.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42059992},
issn = {1559-1182},
mesh = {Humans ; *Brain/pathology/metabolism/drug effects ; *Nervous System Diseases/metabolism/pathology ; *Translational Research, Biomedical/trends ; *Microplastics/adverse effects/toxicity ; Animals ; Blood-Brain Barrier/metabolism ; },
abstract = {The exponential growth in plastic production since the mid-twentieth century has led to the pervasive presence of micro- and nanoplastics (MNPs) across ecosystems and human exposure pathways, coinciding with a rising global burden of neurological disorders. Increasing evidence demonstrates that MNPs are not confined to peripheral tissues but can accumulate even in the human brain, raising concerns about their potential contribution to neurological disease. This structured review synthesizes global trends in plastic production, environmental MNP burden, and human exposure, together with emerging data on brain accumulation, entry pathways, neurotoxic mechanisms, and key translational challenges. We present evidence showing that MNPs may cross brain barriers via multiple routes, including the blood-brain barrier, blood-cerebrospinal fluid barrier, olfactory, and circumventricular pathways, particularly under conditions of barrier vulnerability. Experimental studies reveal that once in neural tissue, MNPs may disrupt synaptic function, mitochondrial homeostasis, autophagy, and redox balance, while activating neuroinflammatory and gut-brain axis-mediated pathways. These mechanisms intersect with disease-relevant processes implicated in multiple neurological disorders whose global prevalence and societal burden have sharply increased over recent decades, including stroke, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, mood disorders, and neurodevelopmental conditions. Despite growing mechanistic plausibility, translational and human epidemiological evidence remains limited by methodological heterogeneity, a lack of standardized detection methods, and the absence of longitudinal clinical data/studies. We highlight critical analytical and translational gaps, public health implications, and priorities for longitudinal, biomarker‑driven studies needed to rigorously test whether MNPs may contribute to population‑level risk of neurological disease.},
}

Humans
*Brain/pathology/metabolism/drug effects
*Nervous System Diseases/metabolism/pathology
*Translational Research, Biomedical/trends
*Microplastics/adverse effects/toxicity
Animals
Blood-Brain Barrier/metabolism

@article {pmid42060866,
year = {2026},
author = {Kiernan, MC and Genge, A and Grosskreutz, J and Kuwabara, S and Lillo, P and Rosenfeld, J and Cummings, C},
title = {The World Federation of Neurology Specialty Group in ALS/MND: toward strategic partnership and new frontiers.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/21678421.2026.2663915},
pmid = {42060866},
issn = {2167-9223},
abstract = {A memorandum of understanding was recently established between the World Federation of Neurology Specialty Group and the International Alliance of ALS/MND Associations. This new strategic partnership brings together leading clinicians and researchers with national and regional organizations dedicated to supporting ALS patients, their families, and caregivers. The purpose of partnership is to strengthen global coordination in research, education, advocacy, and clinical care for people living with MND. The agreement outlines shared priorities, including promoting equitable access to diagnosis and treatment, supporting capacity building in low- and middle-income regions, and facilitating the exchange of scientific knowledge and best practice. Both parties commit to joint initiatives such as international meetings, guideline development, clinical trials and data-sharing efforts that advance understanding of disease mechanisms and therapeutic approaches. Together, these organizations represent the scientific and human dimensions of the ALS challenge. Through partnership, the WFN Specialty Group and the International Alliance aim to accelerate progress toward improved outcomes and, ultimately, effective treatments for MND worldwide.},
}

@article {pmid42060880,
year = {2026},
author = {, },
title = {Retirement of Guidelines: Practice Parameter Update: The Care of the Patient With Amyotrophic Lateral Sclerosis: Drug, Nutritional, and Respiratory Therapies (An Evidence-Based Review): Report of the Quality Standards Subcommittee of the American Academy of Neurology.},
journal = {Neurology},
volume = {106},
number = {10},
pages = {e218083},
doi = {10.1212/WNL.0000000000218083},
pmid = {42060880},
issn = {1526-632X},
}

@article {pmid42060881,
year = {2026},
author = {Nolano, M and Provitera, V and Caporaso, G and Areniello, AR and Borreca, I and Stancanelli, A and Senerchia, G and Iuzzolino, VV and Fasolino, I and Vitale, F and Ciccarelli, G and Dell'Aversana, D and Masciarelli, F and Tozza, S and Iodice, R and Santoro, L and Manganelli, F and Dubbioso, R},
title = {Phosphorylated TDP-43 Pathology in Skin and Muscle Tissue of Patients With Amyotrophic Lateral Sclerosis.},
journal = {Neurology},
volume = {106},
number = {10},
pages = {e214940},
doi = {10.1212/WNL.0000000000214940},
pmid = {42060881},
issn = {1526-632X},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/metabolism ; Female ; Middle Aged ; Male ; *DNA-Binding Proteins/metabolism ; Aged ; Cross-Sectional Studies ; *Skin/pathology/metabolism ; Case-Control Studies ; Phosphorylation ; *Tongue/pathology/metabolism ; Biomarkers/metabolism ; },
abstract = {BACKGROUND AND OBJECTIVES: Phosphorylated TAR DNA-binding protein 43 (pTDP-43) is the pathologic hallmark of amyotrophic lateral sclerosis (ALS), yet no peripheral premortem biomarker is available. We evaluated pTDP-43 distribution in skin and tongue tissues and its association with ALS and clinical stage.

METHODS: This cross-sectional case-control study included patients with ALS meeting revised El Escorial criteria who underwent skin and tongue biopsies. Control groups included healthy controls (HC), patients with non-ALS neuropathy or neuronopathy (NANN), and patients with burning mouth syndrome (BMS). pTDP-43 was quantified in Meissner corpuscles (MC) and keratinocytes using standardized immunofluorescence. In MC, PGP (%), pTDP-43 (%), and the pTDP-43/PGP ratio were assessed. A subset of skin samples underwent western blot analysis. ALS severity was classified using King's staging system. Diagnostic performance was evaluated using receiver operating characteristic analysis.

RESULTS: Fifty patients with ALS were included, median age 66.5 years, 36% female. Control groups included 20 HC, median age 60 years, 20% female, and 20 patients with NANN, median age 60 years, 50% female. Tongue biopsy was performed in 10 patients with ALS and 10 patients with BMS. pTDP-43 deposits were detected in ALS across epidermis and dermis structures, whereas they were almost absent in HC and low in NANN. Accordingly, MC pTDP-43% differed across groups (H = 53.30; p < 0.001), with median values of 0.35 (interquartile range [IQR] 0.39) in ALS, 0.04 (IQR 0.03) in NANN, and 0.00 in HC. The pTDP-43/PGP ratio increased with clinical stage at subject level (Z = 2.20, p = 0.028) and single-corpuscle level (H = 21.72, p < 0.001). Western blot showed higher pTDP-43/GAPDH ratio in ALS skin than in HC (median 3.45, IQR 7.23 vs 1.30, IQR 0.80; p = 0.007). Nonphosphorylated TDP-43 did not differ across groups. In keratinocytes, pTDP-43 was higher in ALS than in NANN and HC (median 0.047, IQR 0.023; 0.019, IQR 0.049; and 0.005, IQR 0.047; p < 0.001). Combined cutaneous pTDP-43 measures discriminated ALS from HC (area under the curve [AUC] 0.94, p < 0.001) and from NANN (AUC 0.90, p < 0.001). Tongue biopsies showed pTDP-43 aggregates in intramuscular nerves, denervated endplates, and muscle fibers.

DISCUSSION: Peripheral pTDP-43 deposition distinguishes ALS from controls and reflects disease stage, supporting its potential role as a biomarker of ALS and disease severity. Larger and longitudinal studies are required for validation.},
}

Humans
*Amyotrophic Lateral Sclerosis/pathology/metabolism
Female
Middle Aged
Male
*DNA-Binding Proteins/metabolism
Aged
Cross-Sectional Studies
*Skin/pathology/metabolism
Case-Control Studies
Phosphorylation
*Tongue/pathology/metabolism
Biomarkers/metabolism

@article {pmid42043709,
year = {2026},
author = {Umar, M and Franjieh, K and White, AL and Ward-Dones, E and Ismael, S and Roskey, RC and Courseault, J and Bix, GJ},
title = {Role of Folate Metabolism in Neurodegenerative Diseases: Insight from Experimental and Clinical Studies.},
journal = {Current nutrition reports},
volume = {15},
number = {1},
pages = {},
pmid = {42043709},
issn = {2161-3311},
abstract = {PURPOSE OF REVIEW: Folate is a key regulator of one-carbon metabolism (OCM), which supports essential physiological processes, including DNA synthesis, repair, methylation, amino acid homeostasis, and redox balance. It is also crucial for brain health throughout life, from neural tube formation during early development to neurotransmitter synthesis, myelination, neuronal development, synaptic plasticity and cognitive function during later stages of life. Disruption of folate-mediated OCM (FOCM) can adversely affect brain health and contribute to neurodegeneration. In this review, we summarize current evidence linking FOCM dysregulation to neurodegenerative diseases, emphasizing disease-specific mechanisms and the therapeutic potential of modulating folate metabolism, as evidenced by experimental and clinical studies.

RECENT FINDINGS: Disruption of FOCM can lead to oxidative stress, impaired methylation, excitotoxicity, and neuroinflammation, thereby contributing to neurodegenerative diseases. In Alzheimer’s disease, impaired FOCM promotes amyloid-β accumulation, tau pathology, cognitive decline, and vascular dysfunction, consistent with low folate and elevated homocysteine observed clinically, though supplementation outcomes remain mixed. In Parkinson’s disease, folate deficiency and hyperhomocysteinemia exacerbate motor deficits and dopaminergic neurodegeneration via oxidative stress, mitochondrial dysfunction, and NLRP3-mediated inflammation and combined folate and vitamin B12 supplementation may reduce levodopa-associated risks. Elevated homocysteine and aberrant FOCM have also been reported in Amyotrophic Lateral Sclerosis, Multiple Sclerosis, and Huntington’s disease and are associated with neuroinflammation, demyelination, neuronal loss, and severe disease phenotypes in these conditions.

SUMMARY: Overall, maintaining optimal folate levels may be a promising strategy to support brain health and reduce the risk of neurodegenerative disorders.},
}

@article {pmid42049669,
year = {2026},
author = {Vrana, KE},
title = {Are Cannabis and/or Cannabinoids a Potential Therapy for ALS?.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70262},
pmid = {42049669},
issn = {1097-4598},
support = {R01 AT012053/GF/NIH HHS/United States ; },
}

@article {pmid42050008,
year = {2026},
author = {Gascón, E and Calvo, AC and Zaragoza, P and Osta, R},
title = {Unveiling an ALS Blood Transcriptomic Signature: A Machine Learning Classifier Distinct from Neurodegenerative Controls.},
journal = {Neuroinformatics},
volume = {24},
number = {2},
pages = {},
pmid = {42050008},
issn = {1559-0089},
}

@article {pmid42051098,
year = {2026},
author = {Khan, N and Doshi, G},
title = {Zebrafish (Danio rerio) as a Model for Neurodegenerative Disease Research: Mechanisms, Biomarkers, and Translational Promise.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273442688260330060220},
pmid = {42051098},
issn = {1996-3181},
abstract = {Zebrafish (Danio rerio) have gained prominence as a versatile vertebrate model for studying neurodegenerative disorders due to their genetic similarity to humans, rapid development, transparency, and suitability for high-throughput drug screening. The usefulness of zebrafish in modelling human neurological disorders is supported by the similarity of their brains' anatomical and neurochemical characteristics, including comparable divisions of the forebrain, midbrain, and hindbrain, as well as dopaminergic, serotonergic, glutamatergic, and GABAergic pathways. Zebrafish have been used to successfully model several neurodegenerative diseases, including Alzheimer's disease (via tau phosphorylation and amyloid-beta aggregation), Parkinson's disease (via dopaminergic neuronal loss and alpha-synuclein pathology), Huntington's disease (via polyglutamine-expanded huntingtin), and amyotrophic lateral sclerosis (via mutant SOD1 and TDP- 43 transgenes). They have also been used to study multiple sclerosis, spinocerebellar ataxias, and Rett syndrome, enabling mechanistic exploration and preclinical drug discovery. This review crucially depicts how zebrafish models provide an affordable, morally acceptable, and scalable platform for early-stage neurodegeneration research. These models complement, rather than replace, rodent- and human-derived systems. Additionally, we will review how to bridge the gap between therapeutic screening and basic mechanistic findings, highlighting their increasing significance in the neuroscience research continuum.},
}

@article {pmid42051550,
year = {2026},
author = {Chakraborty, DK and Roy, T and Ngo, ST and Al-Chalabi, A and Al Khleifat, A},
title = {Gut microbiota and ALS: cause, consequence or correlation? - a systematic review.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1774417},
pmid = {42051550},
issn = {1662-4548},
abstract = {BACKGROUND: Gut microbiome disturbances have been proposed as contributors to amyotrophic lateral sclerosis (ALS), a multisystem neurodegenerative disorder characterised by motor neuron loss, extra-motor symptoms, and rapid progression. Mechanistic links between dysbiosis, epithelial and blood-brain barrier dysfunction, metabolic imbalance, and immune activation have been suggested, but causality remains unresolved. We conducted a systematic review to evaluate the evidence supporting microbiome involvement in ALS pathogenesis.

METHODS: We searched PubMed, Medline, Embase, Scopus, Semantic Scholar, and Google Scholar (Nov 23, 2025) for human and ALS-relevant animal studies assessing bacterial microbiota, gut or blood-brain barrier integrity, microbial metabolites, or immune pathways. No language or date restrictions were applied. Studies were screened according to predefined criteria, and quality was assessed using QUADAS-2. Owing to the heterogeneity of study designs and sequencing approaches, findings were synthesised narratively.

FINDINGS: 61 of 2,397 studies met inclusion criteria. Across human cohorts, ALS was consistently associated with reduced microbial diversity, shifts in key taxa, and disruption of microbial pathways regulating short-chain fatty acids, nicotinamide metabolism, and inflammatory signalling. Several mechanistic animal studies demonstrated that microbiota manipulation, through antibiotics, faecal microbiota transfer, or supplementation with protective taxa, modulated motor function, microglial activation, gut permeability, and survival, indicating that dysbiosis can influence disease trajectories. Conversely, longitudinal human data showed that dysbiosis often emerged alongside worsening physical function, gastrointestinal dysmotility, weight loss, and changes in dietary intake, suggesting secondary effects of disease progression. Integrative multi-omics studies linked microbial alterations with systemic cytokine profiles, metabolic stress pathways, and CNS immune phenotypes, reinforcing a bidirectional gut-brain axis. However, the predominance of cross-sectional designs and small sample sizes substantially limits causal inference.

INTERPRETATION: Current evidence supports a model in which gut dysbiosis interacts with ALS via barrier failure, metabolic disruption, and immune dysregulation, but does not establish dysbiosis as a primary cause of disease. Preclinical findings highlight microbiome-derived mechanisms with disease-modifying potential, yet human data largely indicate association rather than initiation. Clarifying temporal relationships will require longitudinal, multi-modal studies, integration with pre-symptomatic cohorts, and controlled interventional trials. Microbiome-targeted therapies remain a promising but unproven avenue for ALS.},
}

@article {pmid42051853,
year = {2026},
author = {Eissazade, N and Nazemi, L and Haghi Ashtiani, B and Moradi-Lakeh, M},
title = {Neutrophil-to-lymphocyte ratio in amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {Brain communications},
volume = {8},
number = {2},
pages = {fcag132},
pmid = {42051853},
issn = {2632-1297},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited diagnostic and prognostic biomarkers. The neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, has been proposed as a potential indicator. This systematic review and meta-analysis assesses the diagnostic and prognostic value of NLR in ALS. We searched PubMed, Scopus, Embase and Web of Science through June 2025 for peer-reviewed studies evaluating NLR in adults with ALS diagnosed by established criteria. Eligible studies reported validated measurements of NLR and diagnostic or prognostic outcomes. Two reviewers independently extracted data and assessed quality. Random-effects meta-analyses were performed, with heterogeneity, publication bias, evidence certainty and sources of heterogeneity evaluated using meta-regression. Sixteen studies from 12 countries including 357 044 participants met inclusion criteria, comprising 8710 ALS patients (mean age 60.3 years; 59.1% male) and 348 334 controls (mean age 57.8 years; 47.6% male). Meta-analysis of 11 studies showed a pooled mean NLR of 2.74 in ALS patients [95% CI (2.42, 3.10); I [2] = 95.4%], while three control studies yielded a pooled mean NLR of 1.94 [95% CI (1.55, 2.43); I [2] = 94.7%]. Comparison of three studies demonstrated a 35% higher NLR in ALS patients than controls [95% CI (1.03, 1.76); I [2] = 88.3%], with low certainty according to GRADE due to observational design and substantial heterogeneity. Elevated NLR was consistently associated with worse clinical outcomes, including faster disease progression, lower ALSFRS-r scores, reduced forced vital capacity, shorter survival and increased mortality. Pooled univariate analyses from four studies showed that higher NLR predicted mortality [HR = 1.16; 95% CI (1.04, 1.29); I [2] = 93.8%]. Multivariable-adjusted analyses from six studies confirmed NLR as an independent predictor of poorer survival (HR = 1.13; 95% CI (1.06, 1.21); I [2] = 86.5%), with heterogeneity modestly reduced after adjustment for age and sample size. Certainty of evidence for prognostic outcomes was rated low to moderate. Associations between higher NLR and age at onset, sex and classical ALS phenotype were inconsistent. NLR correlated with inflammatory markers and gut microbiota features, supporting a potential mechanistic link between systemic inflammation and ALS disease progression. Elevated NLR is associated with ALS diagnosis and poorer prognosis, including faster disease progression and reduced survival. Despite heterogeneity and potential bias, NLR appears to be a readily accessible biomarker for disease monitoring and risk stratification in ALS, warranting validation in large, longitudinal studies.},
}

@article {pmid42051912,
year = {2026},
author = {File, C and Price, AM and Ahmad, R and Shanina, E and Sun, RL},
title = {Amyotrophic lateral sclerosis and chronic inflammatory demyelinating polyneuropathy coexistence in a patient with a C9orf72 variant: case report.},
journal = {Frontiers in dementia},
volume = {5},
number = {},
pages = {1785124},
pmid = {42051912},
issn = {2813-3919},
abstract = {BACKGROUND: The C9orf72 variation has been strongly implicated in the inheritance of familial ALS, frontotemporal dementia (FTD), and combined ALS-FTD cases. Increasing evidence implicates immune changes and inflammation in some ALS patients. Several studies demonstrated that ALS coexists with CIDP or polyneuropathy. Mouse models of C9orf72 loss-of-function mutations exhibit fatal immune dysregulation.

CASE SUMMARY: A 62-year-old Caucasian man developed right foot drop, and he underwent fibular nerve release without significant improvement. At the same time, he developed progressive weakness and numbness in his bilateral hands. MRI revealed cervical canal stenosis and neuroforaminal narrowing that prompted neurosurgical decompression without clinical improvement. Subsequently, he developed left foot drop. At the clinic presentation, he exhibited dysarthria, tongue fasciculations, weakness in all extremities, muscle atrophy, widespread fasciculations, and upper extremity hyperreflexia, meeting clinical criteria for ALS. Genetic testing identified a pathogenic variant in the C9orf72 gene, confirming a C9orf72 variant, commonly linked to familial ALS. Brain MRI demonstrated the motor band sign. Although EMG/NCS findings were consistent with lower motor neuron disease, he also had signs of demyelinating polyneuropathy based on conduction parameters. Neuromuscular ultrasound showed significant multifocal nerve enlargement typical of immune-mediated neuropathy. CSF studies revealed albuminocytologic dissociation (protein: 112 mg/dL, with normal cell count) and high albumin quotient and index. He fulfilled the 2021 EAN/PNS criteria for possible typical CIDP. He was treated with intravenous immunoglobulin in addition to riluzole with temporary improvement.

CONCLUSION: This is the first case of the co-existence of CIDP and ALS in the setting of a pathogenic C9orf72 variant.},
}

@article {pmid42052844,
year = {2026},
author = {Chen, W and Wang, J and Li, Q and Zhang, L and Wu, X and Luo, S and Xie, Y and Guo, P},
title = {Keap1-Nrf2 Signaling Pathway-Mediated Antioxidant Defense in Neurodegenerative Diseases: Mechanisms and Traditional Chinese Medicine Therapeutic Strategies.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {31},
number = {4},
pages = {45233},
doi = {10.31083/FBL45233},
pmid = {42052844},
issn = {2768-6698},
support = {81660671//National Natural Science Foundation of China/ ; 202101AZ070001-172//Yunnan Provincial Science and Technology Department-Applied Basic Research Joint Special Funds of Chinese Medicine/ ; 202105AG070014//Yunnan Provincial Key Laboratory of Formula Granules/ ; zyzdxk-2023192//High-level Discipline Construction Project of Dai Medicine, National Administration of Traditional Chinese Medicine/ ; 2024SS24045//Yunnan Key Laboratory for Dai and Yi Medicines/ ; },
mesh = {Humans ; *NF-E2-Related Factor 2/metabolism ; *Signal Transduction/drug effects ; *Kelch-Like ECH-Associated Protein 1/metabolism ; *Neurodegenerative Diseases/metabolism/drug therapy ; *Medicine, Chinese Traditional/methods ; *Antioxidants/metabolism/therapeutic use ; Oxidative Stress/drug effects ; Animals ; Drugs, Chinese Herbal/therapeutic use ; },
abstract = {Neurodegenerative diseases (NDs) are incurable, progressively disabling disorders marked by sustained neuronal degeneration and loss. Their molecular basis involves intricate regulatory networks, while current therapeutic strategies remain inadequate. Oxidative stress (OS) constitutes a major driver in the initiation and progression of age-related pathologies. Kelch-like enoyl-CoA hydratase-associated protein-1 (Keap1)-Nuclear factor Erythroid 2-related factor 2 (Nrf2) signaling pathway, an essential antioxidant system, exerts protective effects by limiting OS-mediated cellular injury. Extensive evidence demonstrates a close association between Nrf2 signaling and the pathological processes of NDs, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Traditional Chinese medicine, characterized by multi-target and multi-pathway regulatory actions of its bioactive constituents, offers distinctive therapeutic potential for NDs. This review provides an integrated analysis of current advances of Nrf2 involvement in NDs and evaluates therapeutic strategies based on traditional Chinese medicine and its active components, with the aim of guiding future clinical translation.},
}

Humans
*NF-E2-Related Factor 2/metabolism
*Signal Transduction/drug effects
*Kelch-Like ECH-Associated Protein 1/metabolism
*Neurodegenerative Diseases/metabolism/drug therapy
*Medicine, Chinese Traditional/methods
*Antioxidants/metabolism/therapeutic use
Oxidative Stress/drug effects
Animals
Drugs, Chinese Herbal/therapeutic use

@article {pmid42053396,
year = {2026},
author = {Russell, C and Walz, T and Manzo, L and Mueller, S and Messina, S and Arana, S and Feng, K and Harner, H},
title = {"It's My Dark Secret": A Qualitative Study on the Abortion Experiences of US Active-Duty Servicewomen.},
journal = {Perspectives on sexual and reproductive health},
volume = {},
number = {},
pages = {},
doi = {10.1111/psrh.70064},
pmid = {42053396},
issn = {1931-2393},
abstract = {INTRODUCTION: The Hyde Amendment limits US military abortion care and coverage for active-duty servicewomen (ADSW). ADSW face numerous barriers to care when seeking an abortion. The purpose of this study was to explore the lived experiences of US servicewomen who had an abortion while serving on active duty.

METHODS: Researchers conducted a qualitative secondary analysis of free-text response data using thematic analysis. We developed the codebook using a modified version of Coast et al.'s (2018) framework for Trajectories of women's abortion related care. Data were collected between December 2021 to June 2022 and included N = 178 participants who self-reported having an abortion while serving on active duty in the US military.

RESULTS: Most participants (n = 122, 62%) cited unplanned pregnancy as their reason for having an abortion. Some participants (n = 22, 12%), identified as having a "medically necessary" abortion (i.e., miscarriage, ectopic pregnancy). Emergent themes included lack of understanding about abortion care, financial and logistical barriers to accessing abortion care often exacerbated by military policies, lack of medical privacy, and subpar care received from military treatment facilities during pregnancy options counseling or TRICARE covered abortion care.

DISCUSSION: ADSW experience systemic barriers to care and often seek care outside of the military medical system to protect their privacy. Military healthcare professionals do not provide adequate pregnancy options counseling or patient education regarding pregnancy loss. The US Department of Defense should enact policies ensuring access to abortion care to maintain the physical well-being and mission readiness of servicewomen.},
}

@article {pmid42053785,
year = {2026},
author = {Fernandes, JMA and Dutra Junior, AM and Thomas, FP and Gondim, FAA},
title = {Evolving 10-year epidemiological landscape of amyotrophic lateral sclerosis (ALS) in Ceará, Brazil.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/21678421.2026.2663916},
pmid = {42053785},
issn = {2167-9223},
abstract = {Objective: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that affects upper and lower motor neurons with variable cognitive impairment. Despite its rarity, ALS has a major social and economic impact and increasing incidence worldwide. There are few population-based studies of ALS in Brazil. Methods: We present a descriptive and quantitative study, with a retrospective and prospective design, of patients with ALS followed at the Walter Cantídio University Hospital (HUWC) from January 2013 to December 2023, with the aim of describing the clinical, epidemiological, and genetic aspects of ALS in this population, as well as the ALS epidemiology within the state of Ceará, Brazil. Results: Two hundred and forty patients had their medical records analyzed. One hundred and thirty-four (55.8%) cases were male, with a male to female ratio of 1.3:1. The mean age of symptom onset was 56.39 ± 13.05 years. 92.1% (221) of cases were sporadic, 7.9% (19) were familial. Spinal onset was most common (72.1%). Genetic mutations were found in 10 patients, with SOD1 mutations (variant: c.358G > C; p.Val120Leu) being the most common. Using riluzole prescription data, the prevalence and incidence of ALS in 2022 were estimated at 2.32 and 0.8/100.000/inhabitants, respectively. Conclusion: The epidemiology of ALS in the state of Ceará is similar to what has been reported in prior studies from Brazil and other developing countries; SOD1 mutations were the most prevalent genetic subtype.},
}

@article {pmid42054542,
year = {2026},
author = {Gu, T and Xue, J and Zhang, Z and Cao, J and Song, J and Li, G and Ming, L and Zhu, Z and Wang, H},
title = {Mechanisms of Resistance to ALS Inhibitors and Bentazone in Fimbristylis littoralis and Rapid Identification of the ALS Trp-574-Leu Mutation Using LAMP-CRISPR/Cas12a.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c17149},
pmid = {42054542},
issn = {1520-5118},
abstract = {Fimbristylis littoralis Gaudich., a harmful sedge weed in Chinese rice paddy, impairs rice productivity and quality. In this study, we identified a resistant population (FL2) displaying multiple resistance to pyrazosulfuron-ethyl and bentazone, alongside cross-resistance to other acetolactate synthase (ALS)-inhibiting herbicides. The other population (FL6) showed exclusive resistance to bensulfuron-methyl. Sequencing demonstrated that FL2 carried a Trp-to-Leu mutation at codon 574 of ALS, whereas no mutations were detected in the psbA gene of bentazone-resistant FL2 or the ALS gene of bensulfuron-methyl-resistant FL6. Studies on nontarget-site resistance (NTSR) mechanisms indicated that FL2's resistance to pyrazosulfuron-ethyl was associated with neither PBO-inhibited P450s nor NBD-Cl-inhibited GSTs. In contrast, FL6's resistance to bensulfuron-methyl and FL2's resistance to bentazone were linked to P450 activity. A loop-mediated isothermal amplification (LAMP) coupled with CRISPR/FnCas12a assay was established for rapid detection of the Trp-574-Leu mutation, facilitating resistance management. These findings provide insights for managing resistant F. littoralis populations.},
}

@article {pmid42054734,
year = {2026},
author = {Hussein, MA and Saad, H and Eltabaa, A and Abdelnaser, A and Abdelrazek, A},
title = {Can PEEK cage replace bone graft in calcaneal lengthening osteotomy in treatment of pediatric pes planovalgus?.},
journal = {Foot (Edinburgh, Scotland)},
volume = {67},
number = {},
pages = {102226},
doi = {10.1016/j.foot.2026.102226},
pmid = {42054734},
issn = {1532-2963},
abstract = {BACKGROUND: Flatfoot deformity can cause significant functional impairment, often necessitating surgical correction. Calcaneal lengthening osteotomy is a well-established procedure; however, traditional bone grafts have limitations such as donor site morbidity and nonunion risk. Polyether ether ketone (PEEK) cages offer a novel alternative, potentially enhancing surgical outcomes through improved biomechanical properties and bone incorporation.

PURPOSE: To evaluate the efficacy of PEEK cages in lateral calcaneal lengthening osteotomy in adolescent patients.

METHODS: This prospective study included 41 adolescent patients with symptomatic flatfoot undergoing lateral calcaneal lengthening osteotomy using PEEK cages. Radiographic parameters, including calcaneal inclination angle (CIA) and talo-first metatarsal angles (TFA), were assessed preoperatively and postoperatively. Functional incorporation was evaluated using Worth et al.'s classification. Patients were followed for at least one year.

RESULTS: Postoperative radiographic assessments showed significant improvement. The median CIA increased from 3° (0°-7°) to 17° (12°-20°) (P < 0.001). TFA lateral decreased from 20° (11°-26°) to 2° (0°-8°) (P < 0.001), and TFA anteroposterior reduced from 22° (14°-28°) to 3° (0°-9°) (P < 0.001). At one-year follow-up, 92.7% of 41 patients demonstrated satisfactory incorporation (Grades III-IV). Complications included cage subsidence (7.3%) and pseudoarthrosis (2.4%).

CONCLUSIONS: PEEK cages in calcaneal lengthening osteotomy demonstrated excellent radiographic and clinical outcomes, with high incorporation rates and minimal complications.},
}

@article {pmid42054746,
year = {2026},
author = {Biscetti, L and Gambuzza, ME and Princiotto, M and Sabbatinelli, J and Olivieri, F and Fiorillo, M and Chinigò, C and Muglia, L and Cozza, A and Beccacece, A and Gembillo, G and Bruschetta, G and Villalta Savedra, E and Lattanzio, F and Corsonello, A and Soraci, L},
title = {From necroptosis to neuroinflammation: Unraveling mechanisms and therapeutic targets in age-related cognitive decline.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {199},
number = {},
pages = {119326},
doi = {10.1016/j.biopha.2026.119326},
pmid = {42054746},
issn = {1950-6007},
abstract = {Aging is the major risk factor for several chronic conditions, including cognitive decline and dementia. It is accompanied by profound immune alterations characterized by a progressive decline in immune competence, a process known as immunosenescence. The resulting dysregulation of immune function leads to the overproduction of proinflammatory cytokines and fuels a persistent, low-grade inflammatory state termed inflammaging. This chronic inflammation contributes to dysfunction across the central and peripheral nervous systems, promoting neuronal damage and accelerating neurodegenerative processes such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and other age-related cognitive disorders. Within this framework, prolonged activation of inflammatory pathways can trigger regulated forms of cell death. Among these, necroptosis has recently emerged as a potential mediator linking inflammaging to neurodegeneration. Its core molecular effectors, including the receptor-interacting protein kinases RIPK1 and RIPK3 and the mixed-lineage kinase domain-like protein (MLKL), are increasingly expressed in aged neural tissues, promoting the release of damage-associated molecular patterns (DAMPs) that amplify glial activation, oxidative stress, and blood-brain barrier disruption. Growing evidence suggests that necroptotic signaling may be upregulated in the aging brain and in neurodegenerative disorders, where it could contribute to neuronal loss and cognitive impairment. This review discusses the potential role of necroptosis in the continuum between inflammation and neurodegeneration, highlighting emerging diagnostic and therapeutic perspectives. Epigenetic and circulating biomarkers, such as phosphorylated MLKL and specific microRNAs, may support early detection, while pharmacological and nutraceutical strategies targeting necroptosis show promising neuroprotective effects in preclinical studies.},
}

@article {pmid42055109,
year = {2026},
author = {Zhu, Y and Zhang, H and Zhang, Z and Song, G and Fu, J and Wang, H},
title = {The role of ultrasound in addressing neurodegenerative diseases: A review of mechanisms, applications, and challenges.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2026.04.024},
pmid = {42055109},
issn = {1873-7544},
abstract = {With the aging of the global population, neurodegenerative diseases have become a major public health challenge. Currently, there are many limitations in the traditional treatment of neurodegenerative diseases, such as medicine, deep brain stimulation, transcranial magnetic stimulation, and transcranial direct current stimulation, including the inability to penetrate the blood-brain barrier (BBB) accurately and challenges in achieving precise and quantitative control during the treatment process. Ultrasound is an emerging neural modulation technology that stands out for its non-invasive nature, precise targeting, and unique ability to penetrate the BBB, demonstrating tremendous application potential. In this review, we summarized the common types of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS), and the limitations of traditional treatments. It delves into the physical principles, classification, mechanisms, and unique advantages of ultrasound therapy in neuromodulation. It provides a detailed account of the current status of application of ultrasound in neurodegenerative diseases, and represents the advantages and challenges currently faced by ultrasound therapy, which offers insights into future research directions and technological improvements.},
}

@article {pmid42045773,
year = {2026},
author = {Rana, R and Mehan, S and Mukherjee, R and Khan, MDN and Das Gupta, G and Narula, AS},
title = {Caffeic Acid Phenethyl Ester Enhanced the Klotho/SIRT1/Nrf2/HO-1 Axis to Protect Against Methylmercury-Induced ALS-Like Neurodegeneration.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42045773},
issn = {1559-1182},
support = {DST-SERB, Govt. of India (Grant Number: CRG/2021/001009).//Science and Engineering Research Board/ ; },
mesh = {Animals ; *Caffeic Acids/pharmacology/therapeutic use ; *Phenylethyl Alcohol/analogs & derivatives/pharmacology/therapeutic use ; Klotho Proteins ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy/chemically induced/pathology ; *NF-E2-Related Factor 2/metabolism ; *Sirtuin 1/metabolism ; Male ; *Heme Oxygenase-1/metabolism ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Glucuronidase/metabolism ; Oxidative Stress/drug effects ; *Signal Transduction/drug effects ; Apoptosis/drug effects ; Mice ; *Nerve Degeneration/drug therapy/pathology/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by motor neuron degeneration, oxidative stress, and neuroinflammation. This study evaluated the neuroprotective potential of caffeic acid phenethyl ester (CAPE) against MTME + 5-induced neurotoxicity in an ALS-like pathology model. CAPE (50 and 100 mg/kg., p.o.) demonstrated significant therapeutic efficacy by improving motor and cognitive deficits, restoring oxidative balance, and mitigating neuroinflammatory and apoptotic pathways. Behavioral assessments, including the open field, grip strength, forced swim, and Morris water maze, highlighted CAPE's ability to restore neuromuscular coordination and cognitive function in a dose-dependent manner. Cellular and Molecular analyses revealed that MTME[+]5 exposure significantly disrupted Klotho/SIRT-1/Nrf2/HO-1 antioxidant signaling, increased pro-inflammatory cytokines (TNF-α, IL-1β), and elevated apoptotic markers (Bax, caspase-3) while depleting anti-inflammatory cytokines (IL-10) and neuroprotective proteins. Furthermore, CAPE treatment restored these parameters, reduced oxidative stress, and enhanced antioxidant defenses (SOD, CAT, r-GSH). Furthermore, CAPE normalized neurotransmitter imbalances, including acetylcholine, dopamine, GABA, serotonin, and glutamate, alleviating excitotoxicity. Histopathological and gross morphological analyses confirmed CAPE50 and CAPE100 ability to preserve neuronal and myelin integrity across key brain regions, including the cerebral cortex, hippocampus, striatum, midbrain, and cerebellum. CAPE also reduced methylmercury accumulation in the brain and cerebrospinal fluid, indicating detoxifying effects. Co-administration of vitamin B1 (VTB1(200)) further amplified CAPE's therapeutic efficacy. Complete blood count (CBC) analysis demonstrated MTME[+]5-induced hematological abnormalities, including reduced RBCs, hemoglobin, WBCs, and platelets, alongside elevated eosinophils and basophils. CAPE treatment normalized these parameters, indicating systemic recovery. These findings establish CAPE as a promising neuroprotective agent for ALS, capable of targeting neurocomplications.},
}

Animals
*Caffeic Acids/pharmacology/therapeutic use
*Phenylethyl Alcohol/analogs & derivatives/pharmacology/therapeutic use
Klotho Proteins
*Amyotrophic Lateral Sclerosis/metabolism/drug therapy/chemically induced/pathology
*NF-E2-Related Factor 2/metabolism
*Sirtuin 1/metabolism
Male
*Heme Oxygenase-1/metabolism
*Neuroprotective Agents/pharmacology/therapeutic use
*Glucuronidase/metabolism
Oxidative Stress/drug effects
*Signal Transduction/drug effects
Apoptosis/drug effects
Mice
*Nerve Degeneration/drug therapy/pathology/metabolism

@article {pmid42046818,
year = {2026},
author = {Modi, RD and Rossi, P and Brennan, HB and Ton, LT and Patel, A and Kidd, M and White, SM and Ring, M and Schwartz, ER and Glynn, T and Redwine, LS},
title = {Feasibility of Creating a Teaching and Learning Kitchen for an Interdisciplinary Group of Medical Professional Students While Creating a Bridge With an Inner-City Miami Community.},
journal = {Global advances in integrative medicine and health},
volume = {15},
number = {},
pages = {27536130261442566},
pmid = {42046818},
issn = {2753-6130},
abstract = {OBJECTIVE: While obesity is a public health threat, many providers feel ill-prepared to advise patients on diet and nutrition for disease prevention. Miami, Florida, has a unique mix of ethnicities and cultures, and more than half of its residents are born outside the US, which creates additional barriers to providing adequate dietary advice. This study aimed to develop and refine a "food-as-medicine" and community service program in this culturally diverse region to improve future health care providers' knowledge, skills, and self-care practices.

METHODS: Feasibility was assessed using Bowen et al.'s framework, examining demand, acceptability, practicality, and implementation. Preliminary efficacy was determined by assessing student learning. A panel of four medical students provided consultation for developing this course. Twenty-four medical and six physical therapy (PT) students attended, and 21 completed both the pre- and post-surveys. The course consisted of four 2.5-hour classes, including lectures on diet/nutrition, social drivers of health, case studies, and chef-led cooking activities. Attendees subsequently provided diet/nutrition workshops to children in the community.

RESULTS: Most students (87%) attended at least three class sessions and the community service activity. Nutrition subscales, knowledge (P = 0.018), health equity awareness (P < 0.05), and dietary advice confidence (P < 0.05) improved. PT and medical students did not differ in attitudes toward the importance of nutrition for disease prevention or the survey subscales.

CONCLUSIONS: Strong participation, improved understanding, and confidence in dietary advice confirmed the feasibility and preliminary effectiveness of integrating a "food-as-medicine" program into medical and PT curricula, enhancing nutrition awareness and developing referral competencies for obesity-related chronic disease prevention.},
}

@article {pmid42046889,
year = {2026},
author = {Martinez-Gonzalez, L and Sanchez-Santos, C and Huang, CS and Gil, C and Martinez, A},
title = {Innovative therapies under clinical development for ALS treatment: Small molecules.},
journal = {Expert opinion on investigational drugs},
volume = {},
number = {},
pages = {},
doi = {10.1080/13543784.2026.2667249},
pmid = {42046889},
issn = {1744-7658},
abstract = {INTRODUCTION: The clinical trial landscape for Amyotrophic Lateral Sclerosis (ALS) is a rapidly evolving field, characterized by significant obstacles but also by an increasing volume of novel therapeutics entering clinical research. Expanding on our 2022 work, this review examines the current state of the ALS clinical pipeline. Given the high volume of ongoing trials, the diversity of their biological targets and the nature of their therapeutic approaches, we focus this comprehensive update in providing a comprehensive overview of the current state of small-molecule development, focusing on agents that have entered or progressed through clinical evaluation since 2022 to the end of 2025.

AREAS COVERED: Clinical trials for ALS registered within the United States (ClinicalTrials.gov) and European Union (EU Clinical Trials Register/CTIS) databases have been systematically reviewed and are detailed in this report.

EXPERT OPINION: The implementation of advanced clinical trial platforms has introduced more efficient, adaptive strategies, leading to a significant increase in the breadth of explored therapies for ALS. Furthermore, the advent of precision medicine, powered by Artificial Intelligence (AI) for enhanced patient selection and stratification, offers a critical pathway toward overcoming the challenges posed by this severe and heterogeneous disease.},
}

@article {pmid42047551,
year = {2026},
author = {Zeng, Y and Qian, H and Zhao, H and Fu, M and Pan, L and Liu, M},
title = {LrGSTU181 Contributes to Glufosinate Resistance in the Multiple Resistant Lolium rigidum Populations.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c17635},
pmid = {42047551},
issn = {1520-5118},
abstract = {Glufosinate is increasingly applied alongside glyphosate to control glyphosate-resistant weeds, a practice that has led to emerging resistance issues. Here, glufosinate resistance was confirmed in two multiple-resistant Lolium rigidum (glyphosate, ALS- and ACCase inhibitors) populations, NLR70 and WALR70 (RIs of 4.47 and 2.17, respectively), with no target-site GS resistance mutations. GST and P450 inhibitor studies identified distinct mechanisms: NBD-Cl reversed glufosinate resistance in both populations, while malathion reversed resistance only in population NLR70. Resistance in population NLR70 involved both the overexpression of LrGS1-2 and LrGS2 and the upregulation of LrGSTU181, CYP94B3, and possibly other GSTs and P450s. Whereas in population WALR70, resistance likely involved LrGSTU181 and possibly other GSTs. Transgenic validation demonstrated that LrGSTU181 contributes to glufosinate resistance and clodinafop-propargyl. These findings suggest a possible preadaptation scenario wherein detoxification genes selected under long-term herbicide pressure contribute to the evolution of resistance to chemically distinct herbicides.},
}

@article {pmid42047858,
year = {2026},
author = {Hu, N and Liu, M and Cui, L},
title = {Slowly progressive amyotrophic lateral sclerosis associated with a rare SOD1 Pro67Arg mutation: a case report.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {5},
pages = {},
pmid = {42047858},
issn = {1590-3478},
}

@article {pmid42048042,
year = {2026},
author = {Keha, E and Bugg, JM},
title = {Item-specific control of word reading as evidenced by a novel proportion wordness effect.},
journal = {Memory & cognition},
volume = {},
number = {},
pages = {},
pmid = {42048042},
issn = {1532-5946},
abstract = {Jacoby and colleagues demonstrated that control processes can adapt at the level of individual stimuli, giving rise to the item-specific proportion congruence (ISPC) effect, whereby items that frequently appear as incongruent produce a smaller Stroop effect. Prior research has focused exclusively on informational conflict (competition between word meaning and ink color), leaving open whether item-specific control mechanisms also affect task conflict (competition between the task sets of word reading and color naming). Across two experiments, we addressed this question. In Experiment 1, using an ISPC manipulation, we replicated the classic reduction of informational conflict for mostly incongruent items but found no evidence of item-specific control of task conflict. In Experiment 2, we introduced a novel item-specific proportion wordness (ISPW) manipulation to vary the likelihood of task conflict at the item level, by presenting items mostly with neutral words or neutral nonwords. Results revealed robust item-specific effects on task conflict and informational conflict, with reductions in both types of conflict for items that were mostly neutral words. These findings clarify the scope of item-specific control: while manipulations of reactive informational control selectively influence informational conflict, manipulations of reactive task control can regulate not only task conflict but additionally informational conflict. Our results refine and extend Jacoby et al.'s original insight, providing initial evidence for item-specific control of word reading, and demonstrating the operation of item-specific control at multiple levels of conflict via an ISPW manipulation that modulated the likelihood of word reading.},
}

@article {pmid42049092,
year = {2026},
author = {Liu, C and Meng, L and Zhang, Z},
title = {Physiological and pathological functions of TAF15 in neurodegenerative diseases and cancers.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2026.04.066},
pmid = {42049092},
issn = {2090-1224},
abstract = {BACKGROUND: TATA-box binding protein associated factor 15 (TAF15) is a multifunctional DNA/RNA-binding protein that plays pivotal roles in transcription regulation, precursor mRNA splicing, and cellular stress responses. Accumulating evidence demonstrates that TAF15 is strongly implicated in two distinct pathological classes: neurodegenerative diseases and cancers. In neurodegenerative diseases including frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), TAF15 undergoes abnormal cytoplasmic aggregation and mislocalization in neurons and glia, and TAF15 has been established as a candidate disease gene for ALS. In a wide range of cancers, TAF15 drives oncogenic transcriptional dysregulation either via wild-type protein dysfunction or the formation of oncogenic fusion proteins derived from chromosomal translocations.

AIM OF REVIEW: A central unresolved question is how TAF15 contributes to two mechanistically distinct disease entities. This review aims to provide a mechanistically integrated analysis of the physiological and pathological functions of TAF15. We use TAF15's intrinsic molecular properties as a unifying framework to connect its roles in neurodegeneration and cancer. We also summarize key pathogenic mechanisms and emerging therapeutic strategies targeting TAF15, with the goal of proposing a novel conceptual perspective to guide future research. Key scientific concepts of review. TAF15 may act as a biologically relevant molecular link between neurodegeneration and cancer through its intrinsic molecular characteristics, such as nucleic acid binding, phase separation, and nucleocytoplasmic shuttling. The "localization determines outcome" hypothesis offers a unifying framework to explain the connection between the two diseases. TAF15 holds promise as a target for novel biomarkers and precision therapeutics across both disease areas. Deepening mechanistic studies of TAF15 will not only advance understanding of its dual pathological roles but also illuminate the largely unexplored molecular link between neurodegenerative diseases and cancers.},
}

@article {pmid42049146,
year = {2026},
author = {Senerchia, G and Iuzzolino, VV and Spisto, M and Panico, F and Polito, C and Aruta, L and Fiorenza, M and Sirica, R and Terracciano, D and Dubbioso, R},
title = {Plasma NfL, GFAP and pTau181 define distinct biological axes in amyotrophic lateral sclerosis.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107415},
doi = {10.1016/j.nbd.2026.107415},
pmid = {42049146},
issn = {1095-953X},
abstract = {Amyotrophic lateral sclerosis is biologically heterogeneous, and blood biomarkers may reflect distinct pathological mechanisms. We investigated whether plasma neurofilament light chain (NfL), phosphorylated tau at threonine 181 (pTAU181), and glial fibrillary acidic protein (GFAP) capture non-overlapping biological domains in amyotrophic lateral sclerosis. Plasma biomarkers were measured using a fully automated chemiluminescent immunoassay platform in patients with amyotrophic lateral sclerosis and control groups. Upper motor neuron burden was quantified using transcranial magnetic stimulation and the Penn Upper Motor Neuron Score. Lower motor neuron involvement was assessed by electromyography and Medical Research Council strength scores. Associations were tested using multivariable models adjusted for age, sex, disease progression rate, and phenotype. Latent profile analysis was applied to identify biomarker-defined subgroups. NfL levels increased with greater upper motor neuron burden across both neurophysiological and clinical measures. In contrast, pTAU181 selectively reflected lower motor neuron degeneration, particularly chronic denervation severity. GFAP levels were strongly associated with age and showed no relationship with motor neuron involvement. After adjustment for age and other covariates, higher GFAP levels were independently associated with behavioural lability. Biomarker levels did not differ across cognitive classes. Latent profile analysis identified three biologically distinct clusters characterized by selective pTAU181 elevation, progressive NfL increase, or prominent glial activation. Cluster membership independently predicted disease aggressiveness. These findings demonstrate that plasma NfL, pTAU181, and GFAP capture complementary biological processes in amyotrophic lateral sclerosis and support combined biomarker profiling for mechanistically informed patient stratification.},
}

@article {pmid42036719,
year = {2026},
author = {Lin, CY and Hsieh, WC and Wang, SM},
title = {Poly-GR promotes ferroptosis-associated vulnerability in C9orf72-ALS.},
journal = {Cell & bioscience},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13578-026-01574-3},
pmid = {42036719},
issn = {2045-3701},
support = {MOST 111-2628-B-039- 006-MY3//National Science and Technology Council/ ; CMU114-MF-04//China Medical University, Taiwan/ ; },
abstract = {Ferroptosis, an iron-dependent form of oxidative cell death driven by uncontrolled lipid peroxidation, has been increasingly implicated in neurodegeneration. However, its involvement and the underlying regulatory mechanism in C9orf72-linked amyotrophic lateral sclerosis (ALS), the most common genetic form of the disease, remain incompletely understood. Here, we show that the arginine-rich dipeptide repeat protein poly-GR promotes ferroptosis-associated molecular and biochemical features in motor neuron-like NSC34 cells. Poly-GR expression significantly increased lipid peroxidation, intracellular ferrous iron, and reactive oxygen species, indicating a cellular environment permissive for ferroptotic vulnerability. Mechanistically, poly-GR suppresses the Nrf2/Slc7a11 antioxidant defense axis by reducing Nrf2 nuclear localization and its occupancy at the Slc7a11 promoter, resulting in decreased Slc7a11 transcription. Restoration of Nrf2 or Slc7a11 expression attenuated lipid peroxidation and oxidative stress, while the iron chelator deferiprone effectively reduced Fe[2+] accumulation and ferroptosis-associated injury. Functionally, poly-GR sensitized neuronal cells to erastin-induced ferroptotic stress-associated cell death, an effect reversed by Nrf2 or Slc7a11 overexpression and iron chelation. Together, these findings indicate that poly-GR disrupts redox homeostasis and iron metabolism to increase susceptibility to ferroptosis, highlighting the Nrf2/Slc7a11 pathway and labile iron regulation as potential therapeutic targets in C9orf72-associated ALS.},
}

@article {pmid42037134,
year = {2026},
author = {Classen, S and Del Mundo, J and Kulkarni, D and Prabhakar, S and Hicks, A and Hammel, M},
title = {BilboMD: a web-accessible SAXS and AlphaFold-guided modeling pipeline.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkag377},
pmid = {42037134},
issn = {1362-4962},
support = {//Office of Biological and Environmental Research/ ; P30 GM124169/NH/NIH HHS/United States ; CA92584/CA/NCI NIH HHS/United States ; //Advanced Research Projects Agency for Health/ ; //National Energy Research Scientific Computing Center/ ; DDR-ERCAP0031203//Department of Energy User Facility/ ; },
abstract = {BilboMD is a web-accessible platform that facilitates integrative modeling of flexible macromolecules using experimental small-angle X-ray and neutron scattering data. BilboMD combines a browser-based interface with high-performance back-end services hosted locally at the SIBYLS beamline and at the National Energy Research Scientific Computing Center (NERSC). BilboMD guides users through a workflow that includes preparing compatible input files, conformational sampling through molecular dynamics (MD) simulations, small-angle X-ray scattering (SAXS) fitting with FoXS, and establishing multi-state models with MultiFoXS. Input assistants (Inp Jiffy and PAE Jiffy) streamline the process of defining rigid and flexible regions for conformational sampling, including automatic inference from AlphaFold PAE matrices. All analyses are containerized to ensure reproducibility, with job metadata and provenance stored in a central database. By leveraging GPU-enabled MD engines, such as OpenMM (on NERSC resources), BilboMD significantly accelerates conformational sampling and expands the set of models used for SAXS fitting. The platform reduces technical barriers for non-specialists while providing API access for advanced users to automate and integrate with custom workflows. Thus, BilboMD democratizes ensemble-based SAXS modeling, accelerates high-throughput SAXS/small-angle neutron scattering analysis, and lays the groundwork for future integration of AI-driven structure prediction with experimental scattering data. It is freely available without a login requirement at https://bilbomd.bl1231.als.lbl.gov.},
}

@article {pmid42037681,
year = {2026},
author = {Wölk, SA and Prudlo, J and Walter, U and Patejdl, R},
title = {Augmented and prematurely occurring H-reflex recovery curve shows enhanced spinal network excitability in ALS patients when employing the double stimulation paradigm.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1790581},
pmid = {42037681},
issn = {1664-2295},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder in which motoneuron loss in the brain and spinal cord induces complex neuroplastic changes. Although these alterations hold considerable potential for clinical diagnosis and disease monitoring, they remain underutilized due to the lack of sensitive and non-invasive assessment methods. The H-reflex is a monosynaptic spinal reflex arc and represents the neurophysiological analog of the Achilles tendon reflex. A modified H-reflex double-stimulation paradigm enables differentiation of the temporal dynamics of spinal inhibitory and excitatory mechanisms. In ALS, this approach may provide clinically relevant insights into motor system dysfunction. Furthermore, this approach may contribute to a better understanding of the pathophysiology of spinal network plasticity associated with this disease, reflecting the complex interplay between spinal and supraspinal pathways. We assessed H-reflex recovery in 15 ALS patients and 82 non-ALS subjects, including 12 age-matched healthy controls (HC). The protocol included 14 interstimulus intervals (ISI) within a timeframe of up to one second. In contrast to the HCs, ALS patients exhibited recovery at ISIs of 30 or 50 ms. At interstimulus intervals ranging from 50 to 200 ms, the extent of recovery was significantly elevated in the ALS group compared to the age-matched HCs. ALS patients thus demonstrate heightened spinal network excitability as evidenced by an augmented and prematurely occurring H-reflex recovery measurement. These alterations likely reflect changes in neuronal network activity and can be attributed to modifications in both segmental spinal circuits and supraspinal regulatory pathways.},
}

@article {pmid42037767,
year = {2026},
author = {McGee, SB and Stanisheuski, S and Mehl, RA and Cooley, RB},
title = {Efficient and Site-Specific Incorporation of 3-Nitro-Tyrosine Into Recombinant Proteins in Escherichia coli.},
journal = {Bio-protocol},
volume = {16},
number = {8},
pages = {e5674},
pmid = {42037767},
issn = {2331-8325},
abstract = {3-nitro-tyrosine (nitroTyr) is one of numerous oxidative protein modifications implicated in diseases such as cardiovascular disease, cancer, and amyotrophic lateral sclerosis (ALS). Because of this, the ability to site-specifically encode nitroTyr into recombinant proteins is a powerful approach for studying these disease pathways. However, producing proteins with defined nitration sites is technically challenging due to the limitations of traditional chemical nitration via peroxynitrite, which lacks residue and site-specificity. Genetic code expansion (GCE) offers a solution by enabling precise incorporation of nitroTyr at designated TAG codons using engineered aminoacyl-tRNA synthetase/tRNA pairs from Methanocaldococcus jannaschii and Methanomethylophilus alvus. This protocol provides a reliable, optimized workflow for incorporating nitroTyr into proteins in E. coli using GCE. It guides users through key considerations in selecting cell lines, media conditions, and GCE systems to minimize off-target effects such as release factor 1 competition, near-cognate suppression, and chemical reduction of nitroTyr. The method is demonstrated using wild-type and TAG-containing superfolder GFP but is broadly applicable to other proteins of interest. Key features • This protocol offers a practical guide for the recombinant expression of proteins containing site-specific 3-nitro-tyrosine in E. coli. • These methods should be used to characterize the functional and structural consequences of site-specific tyrosine nitration on proteins without having to modify any other residues. • This protocol avoids the use of peroxynitrite as a method to nitrate proteins, which modifies all solvent accessible tyrosine residues to different extents. • Users are guided through the advantages and disadvantages of using different expression strains and genetic code expansion systems depending on specific needs.},
}

@article {pmid42038083,
year = {2026},
author = {MacMillan, C and Gogtay, N and Gibson, D and Qian, JJ and Sauve, WM and Shih, E},
title = {Psychometric evaluation of the DSM-5-TR-Level 1 Cross-Cutting Symptom Measure: transdiagnostic factor analysis in a real-world psychiatric outpatient sample.},
journal = {Frontiers in psychiatry},
volume = {17},
number = {},
pages = {1680352},
pmid = {42038083},
issn = {1664-0640},
abstract = {BACKGROUND: Dimensional approaches to psychiatric assessment are increasingly used to complement categorical diagnoses. The DSM-TR Level 1 Cross-Cutting Symptom Measure (DSM-XC) assesses symptoms across psychopathology domains, but its latent structure remains unexplored in large, real-world psychiatric outpatient populations, limiting guidance on how clinicians interpret and apply results.

METHODS: We analyzed real-world data from patients (N = 3,101) using the Osmind platform who completed the DSM-XC as part of measurement-based care (the systematic collection of patient-reported outcomes to guide clinical decision-making). Exploratory factor analysis was conducted in half of the sample, and confirmatory factor analysis tested two models in the remaining half: a 6-factor general model, a 5-factor bifactor model with a general psychopathology factor. A third confirmatory model based on Caspi et al's framework was also evaluated using the full sample.

RESULTS: The 6-factor general model identified domains of 'Mood', 'Anxiety', 'Depression', 'Psychosis', 'Substance Use', and 'Distress and Disconnection'. The 5-factor bifactor model demonstrated a strong general psychopathology factor. The Caspi-inspired model showed acceptable fit but weaker support for the specific dimensions. These results underscore the DSM-XC's capacity to capture both shared and domain-specific dimensions of psychopathology, highlighting its relevance for dimensional assessment.

CONCLUSION: By clarifying its latent structure, this study identified clinically meaningful symptom dimensions which helps facilitate interpretation and application of the DSM-XC in the real-world. As dimensional and measurement-based approaches continue to expand in psychiatry, clearer understanding of tools such as the DSM-XC may support their integration into clinical practice and future research.},
}

@article {pmid42038869,
year = {2025},
author = {Behroozinia, M and Khosrawi, S},
title = {Rehabilitation Interventions in Adults with Amyotrophic Lateral Sclerosis: A Review :.},
journal = {Galen medical journal},
volume = {14},
number = {},
pages = {e3708},
pmid = {42038869},
issn = {2322-2379},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is the most common and rapidly devastating neurodegenerative disease, which causes impairment of motor neurons in the upper and lower limbs, as well as in the bulbar muscles among adults. This leads to progressive weakness of voluntary muscles. The median survival after the emergence of initial symptoms is typically three years. During this period, due to the worsening of general well-being and independence, patients and their caregivers experience significant emotional stress. Furthermore, there is currently no definitive treatment for ALS. Consequently, patients face various challenges associated with motor impairment, including mobility disturbances, respiratory dysfunction, speech difficulties, and limitations in activities of daily living. Therefore, rehabilitation plays a vital role as a component of multidisciplinary care for managing these issues and reducing the impact of the disease on patients and their families. It is considered the optimal choice for alleviating the discomfort of ALS patients until a curative treatment is discovered.This narrative review aims to provide an overview of different aspects of rehabilitation, including physical therapy, occupational therapy, speech therapy, and respiratory strategies focused on enhancing independence, functional abilities, and overall quality of life while minimizing disabilities and complications in patients coping with this debilitating condition.},
}

@article {pmid42039076,
year = {2026},
author = {Tao, Y and Xiao, M and Mofreh, SAM and Salem, S},
title = {The effect of EFL learners' identity on English speaking proficiency and autonomous learning skills among university students: the mediating role of speaking anxiety.},
journal = {Frontiers in psychology},
volume = {17},
number = {},
pages = {1773756},
pmid = {42039076},
issn = {1664-1078},
abstract = {INTRODUCTION: As a Foreign Language (EFL) learner identity constitutes a pivotal sociopsychological factor in higher education; however, empirical research on how learner identity relates to speaking proficiency (SP) and autonomous learning skills (ALS) remains limited, particularly regarding the affective mechanism through speaking anxiety (SA).

METHODS: Drawing on Identity Theory and the Affective Filter Hypothesis, the present study examined the effect of EFL learner identity, modeled as a second order latent construct indicated by identity belongingness (IDB) and identity expectations (IDE), on SP and ALS among 392 Chinese non-English major sophomores, and tested speaking anxiety (SA) as a mediator using structural equation modeling (SEM).

RESULTS: The results showed that overall learner identity significantly predicted both SP and ALS, and that SA served as a meaningful affective pathway, accounting for approximately 36% of the total effects on learning outcomes.

DISCUSSION: These findings highlight the importance of fostering an identity-supportive learning environment that reduces the "affective filter" and strengthens university students' oral communication and learner autonomy in EFL contexts.},
}

@article {pmid42039423,
year = {2026},
author = {Rout, SR and Kulke, M and Droemer, MA and Wendel, M and Cheng, TC and Mauck, TA and Asgari, S and Nemec, AA and Shein, M and Sato, Y and Fukai, S and Witte, G and Tomko, RJ and Stengel, F and Zacharias, M and Schuetz, AK and Sakata, E},
title = {The vacuolar tauopathy-associated mutation D395G confers redox sensitivity to p97/VCP.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.04.16.718620},
pmid = {42039423},
issn = {2692-8205},
abstract = {The multifunctional AAA+ ATPase p97/VCP is a pivotal regulator of cellular proteostasis, extracting polyubiquitinated substrates from protein complexes or organelle membranes for proteasomal degradation. Mutations in p97 are linked to a broad spectrum of neurodegenerative disorders, including multisystem proteinopathy and amyotrophic lateral sclerosis. Here, we provide insights into the basis of dysfunction in p97 [D] [395] [G] , implicated in vacuolar tauopathy, using an integrated structural approach. The mutation destabilizes the interaction network in the transient ADP.P i state previously identified in p97 [WT] and alters the dynamics of the linker between the tandem ATPase domains, resulting in decreased ATPase activity. We further demonstrate that the D395G mutation sensitizes p97 to oxidative stress by enhancing C522 oxidation, thereby perturbing nucleotide binding in D2, and define the functional basis of this oxidative inactivation of p97. These findings reveal redox control as a key regulatory layer of the p97 ATPase cycle and provide a mechanistic framework for how oxidative stress contributes to p97-associated neurodegeneration.},
}

@article {pmid42039583,
year = {2026},
author = {Sowoidnich, L and Norman, AL and Gerstner, F and Siemund, JK and Buettner, JM and Pagiazitis, JG and Dreilich, V and Pilz, K and Tian, D and Sumner, CJ and Paradis, A and Mentis, GZ and Simon, CM},
title = {A standardized framework resolves ambiguity in motor neuron loss across neurodegenerative diseases.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.04.15.718647},
pmid = {42039583},
issn = {2692-8205},
abstract = {UNLABELLED: Motor neuron (MN) loss is a hallmark of neurodegenerative disorders, yet its assessment remains variable, confounding mechanistic and therapeutic interpretation. To address this, we conducted a systematic review and meta-analysis of spinal muscular atrophy (SMA) mouse studies, revealing 60% variability in reported MN loss, largely attributable to nonspecific spinal cord sampling. Using a whole-segment approach with tissue clearing, MN tracing, and multimodal imaging, we confirmed segment-dependent differences in MN counts. Common MN markers (SMI-32, Nissl) lacked specificity, whereas choline acetyltransferase (ChAT) provided robust labeling in murine and human spinal cords. Deep learning-based whole-mount segmentation enabled unbiased MN quantification and validated manual counts. Integrating analysis with computational modeling established segment sampling as a key driver of variability and revealed degeneration patterns: widespread MN loss in amyotrophic lateral sclerosis (ALS), selective MN loss in severe SMA, and preservation in mild SMA models. These findings establish a framework for reproducible MN quantification.

HIGHLIGHTS: Spinal cord segment-specific analysis reduces variability and allows accurate MN quantificationChAT is the most reliable MN marker in murine and human spinal cordsDeep learning-based segmentation enables unbiased MN quantification in intact spinal cordsMN degeneration is widespread in ALS but restricted to pools innervating proximal muscles in severe SMA.},
}

@article {pmid42040341,
year = {2026},
author = {Rong, P and Heidrick, L and Pattee, G},
title = {Translation of surface electromyography into a clinically applicable objective bulbar assessment tool to improve measurement-based care in amyotrophic laterals sclerosis.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1784520},
pmid = {42040341},
issn = {1662-4548},
abstract = {OBJECTIVE: This study aims to translate surface electromyography (sEMG) into a clinically applicable, objective tool for assessing bulbar involvement in amyotrophic lateral sclerosis (ALS).

METHODS: A clinically grounded sEMG framework was developed, integrating a standardized, repeatable protocol with a novel analytic pipeline, to automatically extract 60 features from six craniofacial muscle groups during a set of motorically demanding but cognitively and linguistically less challenging oral diadochokinetic (DDK) tasks. Using this framework, 104 oral DDK recordings were acquired from 16 individuals with ALS-nine with overt bulbar symptoms (ALS+B) and seven without (ALS-B)-and 10 healthy controls (HCs). The sEMG features were clustered into 10 interpretable composite measures and validated by evaluating their (1) internal consistency using Cronbach's α ; (2) associations with standardized functional outcomes and a biomechanical metric-stiffness-via mediation analysis; (3) discriminatory efficacy in distinguishing ALS+B and ALS-B from HC, as well as from each other, using machine learning classifications; and (4) robustness to common nonmotor confounders, including age, sex, and cognitive-linguistic impairments, through a comparison of discriminatory performance before and after adjustment for these factors.

RESULTS: All composite measures exhibited (1) high internal consistency (Cronbach's α = 0.89 ± 0.071), (2) significant (or marginally significant) direct or stiffness-mediated indirect associations with the functional outcomes, and (3) consistently high discriminatory accuracy (0.82-0.85), both before and after adjustment for confounders.

CONCLUSION: The sEMG framework demonstrates strong potential as a reliable, valid, and robust objective tool to detect subclinical neuromuscular changes throughout the prodromal and symptomatic phases of bulbar involvement in ALS, while remaining resistant against disease-related cognitive-linguistic impairments and disease-unrelated confounders. This tool may augment standard clinical evaluations, enabling earlier detection of bulbar involvement and measurement-based care in ALS.},
}

@article {pmid42040397,
year = {2026},
author = {Maia, ME and Carvalho, M and Sousa Gomes, C and Arruda, M and Antunes de Magalhães, AJ and Farias, D},
title = {Plant-Derived Peptides with Neuroprotective Activity: Advances and Perspectives in the Prevention of Neurodegenerative Diseases.},
journal = {ACS omega},
volume = {11},
number = {15},
pages = {22458-22478},
pmid = {42040397},
issn = {2470-1343},
abstract = {Neurodegenerative diseases, such as Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis, represent an increasing global public health challenge, driven by population aging and the lack of effective curative therapies. In this context, plant-derived peptides have emerged as promising bioactive compounds due to their multitarget neuroprotective properties and favorable safety profiles. This review provides a comprehensive overview of plant peptides with reported activity against neurodegeneration, highlighting their natural sources, biological activities, and mechanisms of action. Evidence from in vitro and in vivo models indicates that these peptides act through multiple complementary pathways, including attenuation of oxidative stress, modulation of neuroinflammation, regulation of apoptosis, preservation of mitochondrial function, and inhibition of toxic protein aggregation. Additionally, several peptides have been shown to enhance synaptic plasticity, modulate neurotransmission, and regulate ion channel activity, suggesting beneficial effects on neuronal communication and cognitive function. Some studies explored structural modifications, such as the introduction of specific residues or glycosylation, which have resulted in greater stability and enhanced efficacy against oxidative insults. Overall, plant-derived peptides demonstrate consistent neuroprotective effects and low toxicity; however, challenges related to the blood-brain barrier, bioavailability, and the understanding of molecular mechanisms must still be overcome to enable their clinical application.},
}

@article {pmid42041525,
year = {2026},
author = {Bertoni, G and Ristori, S and Monti, D},
title = {Immunosenescence and Inflammaging as Drivers of Neurodegeneration: Cellular Mechanisms, Neuroimmune Crosstalk, and Therapeutic Implications.},
journal = {Cells},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/cells15080657},
pmid = {42041525},
issn = {2073-4409},
support = {DM 1557 11.10.2022//Next Generation EU/ ; },
mesh = {Humans ; *Immunosenescence/immunology ; *Neurodegenerative Diseases/immunology/pathology/therapy ; *Inflammation/immunology/pathology ; Animals ; *Aging/immunology ; *Neuroimmunomodulation ; },
abstract = {Aging is accompanied by profound alterations in immune function, termed immunosenescence, and by a chronic, low-grade inflammatory state known as inflammaging. These processes are increasingly recognized as central drivers of age-related neurodegenerative diseases, including Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis and Multiple Sclerosis. In the central nervous system, senescent microglia and astrocytes lose their homeostatic and neuroprotective functions, while systemic immune aging and blood-brain barrier dysfunction further amplify neuroinflammation and impair protein aggregate clearance. This sustained pro-inflammatory environment promotes synaptic dysfunction, neuronal loss and cognitive decline. Here, we synthesize current knowledge of the mechanistic links among immunosenescence, inflammaging, and neurodegeneration, highlighting innate and adaptive immune dysregulation, mitochondrial impairment, and failed resolution pathways. We further discuss emerging therapeutic strategies, including senolytics, immunoceuticals, microbiome-based interventions and advanced drug delivery systems, aimed at restoring immune homeostasis and enhancing brain resilience. By integrating mechanistic and translational insights, this review provides a framework for developing novel interventions to target immune aging in neurodegenerative diseases.},
}

Humans
*Immunosenescence/immunology
*Neurodegenerative Diseases/immunology/pathology/therapy
*Inflammation/immunology/pathology
Animals
*Aging/immunology
*Neuroimmunomodulation

@article {pmid42041567,
year = {2026},
author = {Auburger, G and Kandi, AR and Vutukuri, R and Almaguer-Mederos, LE and Gispert, S and Sen, NE and Key, J},
title = {Astro-Versus Microglia-Enriched Transcriptomes from Aged Atxn2-CAG100-Knockin Mice Suggest Underlying Pathology of RNA Processing at Ribosomes, and Possibly at U-Bodies.},
journal = {Cells},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/cells15080699},
pmid = {42041567},
issn = {2073-4409},
support = {AU96/21-1//Deutsche Forschungsgemeinschaft/ ; SFB1039//Deutsche Forschungsgemeinschaft/ ; },
mesh = {Animals ; *Microglia/metabolism/pathology ; *Ataxin-2/genetics/metabolism ; Mice ; *Transcriptome/genetics ; *Ribosomes/metabolism/genetics ; Amyotrophic Lateral Sclerosis/genetics/pathology ; *Astrocytes/metabolism/pathology ; *RNA Processing, Post-Transcriptional/genetics ; Gene Knock-In Techniques ; *Aging/genetics ; Spinocerebellar Ataxias/genetics/pathology ; },
abstract = {Spinocerebellar Ataxia type 2 (SCA2) and Amyotrophic Lateral Sclerosis type 13 (ALS13) are triggered by polyglutamine expansion in Ataxin-2 (ATXN2). To understand these neurodegenerative disorders at the molecular level, the brains of 10-month-old Atxn2-CAG100-knockin mice were analyzed as microglial, astroglial and neuronal fractions via global RNA sequencing. Data were validated by comparison with the spinal cord oligonucleotide microarray profile or filtered by RNA-seq consistency. Here, we show that the mutation causes a massive inflammatory response in microglia and a reciprocal loss of neuronal transcripts in glial fractions, suggesting severe synapse loss. Beyond these general neurodegenerative signs, we identify pathognomonic changes in the machinery for protein translation and RNA splicing. Glial fractions showed upregulation of Gpnmb (to 2082%), Cst7, Clec7a, Axl, Csf1, Lgals3, Lgals3bp, Slc11a1, and Usp18 as an unspecific neuroinflammatory signature, versus downregulation of axonal Nefh (to <19%), and synaptic Scn4b, Camk2b, Rab15, and Grin1 mRNAs correlating with circuit disconnection. In all fractions, reductions in Kif5a, Rph3a, and Cplx1 were noted versus disease-specific inductions of ribosomal subunits, presumably mirroring the partial loss-of-function of ATXN2 as RNA translation modulator. Selective accumulations of embryonic factors Rnu1b2 and Eef1a1 versus downregulation of adult Eef1a2 specify the mutation impact on splicing and translation elongation. As a potential underpinning of toxic gain-of-function, the proteostasis transcript Rnf213 appeared increased in astroglial and microglial fractions. These transcriptome data suggest altered ribosomal and spliceosome machinery, with massive microgliosis versus mild astrogliosis, at the core of SCA2 and ALS13.},
}

Animals
*Microglia/metabolism/pathology
*Ataxin-2/genetics/metabolism
Mice
*Transcriptome/genetics
*Ribosomes/metabolism/genetics
Amyotrophic Lateral Sclerosis/genetics/pathology
*Astrocytes/metabolism/pathology
*RNA Processing, Post-Transcriptional/genetics
Gene Knock-In Techniques
*Aging/genetics
Spinocerebellar Ataxias/genetics/pathology