@article {pmid41171075,
year = {2025},
author = {Cazzola, J and Talpo, F and Faravelli, G and Donati, C and Maramai, S and Saletti, M and Giuliani, G and Paolino, M and Cappelli, A and Anzini, M and Sommi, P and Vitali, A and Sala, A and Trucco, A and Biella, GR and Spaiardi, P},
title = {Evaluation of a New Riluzole-Based Compound VA945 on Sodium and Potassium Conductances Expressed by SH-SY5Y- Derived Neurons.},
journal = {Journal of neurochemistry},
volume = {169},
number = {11},
pages = {e70280},
pmid = {41171075},
issn = {1471-4159},
mesh = {*Riluzole/pharmacology/analogs & derivatives ; Humans ; *Neurons/drug effects/metabolism ; *Neuroprotective Agents/pharmacology ; Cell Line, Tumor ; Potassium/metabolism ; *Potassium Channels ; Sodium/metabolism ; Membrane Potentials/drug effects ; Patch-Clamp Techniques ; *Sodium Channels ; Dose-Response Relationship, Drug ; },
abstract = {Riluzole (Rilutek), a derivative of benzothiazole, acts as a neuroprotective agent by inhibiting voltage-dependent sodium (Na[+]) and delaying rectifier potassium (K[+]) currents. By doing so, it helps reduce excitotoxicity, a key pathogenetic mechanism in various neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Although riluzole is a clinically approved treatment for ALS, it is not fully effective, particularly in advanced stages of the disease. In this study, we functionally characterized a newly synthetized riluzole-based compound, VA945, with potentially enhanced neuroprotective effects. By means of SH-SY5Y human neuroblastoma cells differentiated into neurons, we assessed using whole-cell patch-clamp techniques the effects of VA945 on voltage-dependent Na[+] and K[+] currents at extracellular concentrations of 5, 50, and 100 μM. The compound reduced maximal activation and inactivation of Na[+] conductance, as well as maximal activation of K[+] conductance, across all tested concentrations. We also observed shifts of the activation and inactivation curves to more hyperpolarized potentials along with changes in the slope factor (k), indicating an altered voltage sensitivity of voltage-dependent K[+] and Na[+] channels. While the activation kinetics of both channels remained unaffected, and the inactivation kinetics of Na[+] were unchanged, we noted a slowdown in the deactivation kinetics of the K[+] channels. Altogether, these findings suggest that VA945 exerts multi-target pharmacological effects on neuronal voltage-dependent ion currents critically involved in excitotoxicity and neurodegeneration, across a wide range of concentrations. This warrants further ex vivo and/or in vivo studies to explore its potential as a neuroprotective agent.},
}

*Riluzole/pharmacology/analogs & derivatives
Humans
*Neurons/drug effects/metabolism
*Neuroprotective Agents/pharmacology
Cell Line, Tumor
Potassium/metabolism
*Potassium Channels
Sodium/metabolism
Membrane Potentials/drug effects
Patch-Clamp Techniques
*Sodium Channels
Dose-Response Relationship, Drug

@article {pmid41169216,
year = {2025},
author = {Chisholm, CG and McAlary, L and Lum, JS},
title = {From translation to stabilization and degradation: A multifaceted approach for the treatment of superoxide dismutase 1-associated amyotrophic lateral sclerosis.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00778},
pmid = {41169216},
issn = {1673-5374},
}

@article {pmid41165282,
year = {2025},
author = {Roedl, K and Genbrugge, C},
title = {Managing cardiac arrest in the intensive care unit.},
journal = {Current opinion in critical care},
volume = {},
number = {},
pages = {},
doi = {10.1097/MCC.0000000000001319},
pmid = {41165282},
issn = {1531-7072},
abstract = {PURPOSE OF REVIEW: This review aims to explore the distinct clinical characteristics, epidemiology, treatment approaches, and research needs concerning cardiac arrest in the intensive care unit (ICU-CA), a specific subset of in-hospital cardiac arrest (IHCA). While IHCA remains a major cause of mortality, recent data indicate improved outcomes, with a notable variation in incidence and survival depending on the location, particularly within the ICU setting.

RECENT FINDINGS: Recent studies underscore that ICU-CA differs significantly from general IHCA in etiology, monitoring, and treatment environment. Although incidence rates vary widely (4-78 per 1000 ICU admissions), recent data suggest a stabilization. Causes of ICU-CA often involve noncardiac factors such as septic shock and respiratory failure. Treatment is typically guided by general advanced life support (ALS) protocols, but ICU-specific resources such as real-time monitoring, invasive pressure measurements, transesophageal echocardiography, and the potential for extracorporeal cardiopulmonary resuscitation offer unique advantages. The COVID-19 pandemic highlighted the vulnerability of ICU patients, with respiratory causes dominating and extremely poor outcomes reported.

SUMMARY: In summary, ICU-CA represents a distinct clinical entity requiring tailored research. Future directions should prioritize international registries, validation of predictive models using artificial intelligence, and clarification of do-not-resuscitate practices to improve outcomes and resource allocation in this critically ill population.},
}

@article {pmid41155541,
year = {2025},
author = {Perez, DM},
title = {α1A-Adrenergic Receptor as a Target for Neurocognition: Cautionary Tale from Nicergoline and Quinazoline Non-Selective Blockers.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {10},
pages = {},
pmid = {41155541},
issn = {1424-8247},
support = {R01 AG066627/AG/NIA NIH HHS/United States ; RO1AG066627/GF/NIH HHS/United States ; },
abstract = {Decades ago, previous studies that used non-selective ergot derivatives suggested that blockage of the α1A-adrenergic receptor mildly increased cognition through increased blood flow to the brain due to vasodilation and, thus, could be used as a treatment for dementia. However, further studies indicated that nicergoline was non-specific and hit many different targets. Today, a similar scenario is developing with the use of non-selective α1-AR antagonists of the quinazoline class, referred to as "osins", as potential treatments for COVID-19/SARS, post-traumatic stress disorder, cancer, and neurodegenerative disorders, such as Parkinson's, Alzheimer's, and amyotrophic lateral sclerosis. While there is extensive evidence of neuroprotection from many clinical trials, the mechanism of action of quinazolines is often not α1-AR-mediated but keyed to its glycolysis-enhancing effects through activation of the enzyme phosphoglycerate kinase 1 (PGK1). These studies have incorrectly labeled the α1A-adrenergic receptor as an "old target" to treat Alzheimer's and other neurocognitive diseases, hampering drug development. This review will summarize these and other studies to indicate that activation, not blockage, of norepinephrine's actions, through α1A-AR, mediates cognitive, memory, and neuroprotective functions that may reverse the progression of neurocognitive diseases.},
}

@article {pmid41155480,
year = {2025},
author = {Turpo-Peqqueña, AG and Valencia-Arce, RJ and Del-Carpio-Carrazco, FL and Quispe-Ppacco, DJ and Carbajal-Llerena, PF and Loza-Chipa, HR and Vásquez-Macedo, AS and Gómez, B},
title = {Inhibition of Casein Kinase 1δ as a Novel Therapeutic Strategy for Amyotrophic Lateral Sclerosis: A Theoretical Study.},
journal = {International journal of molecular sciences},
volume = {26},
number = {20},
pages = {},
pmid = {41155480},
issn = {1422-0067},
mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/enzymology ; *Casein Kinase Idelta/antagonists & inhibitors/chemistry/metabolism ; Molecular Docking Simulation ; Humans ; Molecular Dynamics Simulation ; *Protein Kinase Inhibitors/chemistry/pharmacology/therapeutic use ; Protein Binding ; },
abstract = {Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disease characterized by the degeneration of motor neurons and the pathological accumulation of phosphorylated TDP-43. Casein kinase one delta (CK1δ) has been identified as a key regulator of this aberrant phosphorylation, making it a promising therapeutic target. In this theoretical study, 26 structurally diverse compounds were evaluated against CK1δ using molecular docking, molecular dynamics simulations, and binding free energy calculations. Among them, BZH exhibited the most stable interaction with CK1δ (-46.53±1.94 kcal/mol). An inverse correlation was observed between theoretical affinity and experimental IC50 values, supporting the predictive validity of the computational approach. Pharmacokinetic analysis indicated that IMF and BIP show good oral absorption and the ability to cross the blood-brain barrier. At the same time, the toxicological profile classified all compounds in toxicity Class IV (moderate risk). Additionally, dynamic migration toward an alternative pocket was observed during simulation, highlighting the importance of considering protein flexibility in drug design. This study proposes BZH, IMF, and BIP as promising CK1δ inhibitors for future experimental validation in the treatment of ALS.},
}

*Amyotrophic Lateral Sclerosis/drug therapy/enzymology
*Casein Kinase Idelta/antagonists & inhibitors/chemistry/metabolism
Molecular Docking Simulation
Humans
Molecular Dynamics Simulation
*Protein Kinase Inhibitors/chemistry/pharmacology/therapeutic use
Protein Binding

@article {pmid41152189,
year = {2025},
author = {Snyder, A and Samra, K and Wu, T and Russell, LL and Farren, J and Crook, J and Haselhuhn, T and Porter, K and Szabo, M and Duckett, A and Lin, F and Danielian, L and Traynor, BJ and Scholz, SW and Boeve, BF and Rosen, HJ and Rohrer, JD and Kwan, JY},
title = {Integrating a motor domain enhances disease severity scales in an FTD-ALS spectrum cohort.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {10},
pages = {e70786},
pmid = {41152189},
issn = {1552-5279},
support = {U19 AG063911/AG/NIA NIH HHS/United States ; U19AG063911//The National Institute on Aging/ ; U01AG045390//The National Institute on Aging/ ; U54NS092089//The National Institute on Aging/ ; U01 AG045390/AG/NIA NIH HHS/United States ; //The Intramural Research Program of the National Institutes of Health/ ; U54 NS092089/NS/NINDS NIH HHS/United States ; },
mesh = {Humans ; Male ; *Severity of Illness Index ; Female ; *Frontotemporal Dementia/diagnosis/physiopathology ; Middle Aged ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; Aged ; Longitudinal Studies ; Cohort Studies ; Neuropsychological Tests ; },
abstract = {INTRODUCTION: The Genetic Frontotemporal Initiative (GENFI) and Advancing Research and Treatment in Frontotemporal Lobar Degeneration (ARTFL)-Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) Longitudinal Frontotemporal Lobar Degeneration Study (ALLFTD) consortia developed Clinical Dementia Rating (CDR)-derived scales with a motor domain to overcome systematic underestimation of disease severity by the CDR. We calculated disease severity scores using these scales in a mixed neurodegenerative cohort and correlated them with objective motor measures.

METHODS: The CDR plus National Alzheimer's Coordinating Center (NACC) Frontotemporal Lobar Degeneration (FTLD), CDR + NACC FTLD-M (Motor), and Multidomain Impairment Rating (MIR) scores and motor measures were determined and correlated in 242 participants.

RESULTS: Both CDR + NACC FTLD-M and MIR showed increased disease severity scores and correlated with motor measures. These findings were held in 81 amyotrophic lateral sclerosis (ALS) participants and correlated with the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale. Including a motor domain required fewer study participants in a simulated clinical trial sample size calculation.

DISCUSSION: With a motor domain, CDR + NACC FTLD-M and MIR improve disease severity classification and correlate with quantitative motor assessments. This addition more fully captures the extent of symptoms across the FTD-ALS spectrum and improves clinical trial efficiency.

HIGHLIGHTS: CDR + NACC FTLD-M and MIR strongly correlate with objective motor measures. The enhanced scales improve disease severity classification in FTD and ALS. Greater clinical trial efficiency is achieved using these enhanced scales.},
}

Humans
Male
*Severity of Illness Index
Female
*Frontotemporal Dementia/diagnosis/physiopathology
Middle Aged
*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology
Aged
Longitudinal Studies
Cohort Studies
Neuropsychological Tests

@article {pmid41149102,
year = {2025},
author = {Mauriello, L and Cuozzo, A and Pezzella, V and Isola, G and Spagnuolo, G and Iorio-Siciliano, V and Ramaglia, L and Blasi, A},
title = {Oral Health Status in Patients with Amyotrophic Lateral Sclerosis: A Scoping Review.},
journal = {Dentistry journal},
volume = {13},
number = {10},
pages = {},
pmid = {41149102},
issn = {2304-6767},
abstract = {Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative syndrome which often leads to progressive muscular dysfunction and therefore oral health deterioration. The aim of this scoping review is to evaluate oral health status in ALS patients focusing on the importance of dental care in improving patient's quality of life. Methods: A comprehensive literature search was conducted on PubMed, Scopus, Web of Science, and Embase databases until June 2025 using a combination of keywords and MeSH terms related to ALS and oral health. Studies were screened and selected based on inclusion and exclusion criteria, focusing on human clinical data reporting oral health outcomes in ALS. Results: Eight studies met the inclusion criteria. The findings showed a high prevalence of oral complications in bulbar-onset ALS patients. Common issues included reduced tongue mobility, poor oral hygiene, sialorrhea, and decreased masticatory function were evaluated. Conclusions: Oral health impairment in ALS patients frequently contributes to systemic risks and reduced quality of life. A dental expert may play an important role in multidisciplinary care teams in terms of early diagnosis and conservative treatment of oral diseases ranging from periodontal disease to temporomandibular disorders (TMD). Personalized oral hygiene strategies and adjunctive therapies may serve as key elements in maintaining overall health and patient comfort in ALS. Therefore, the objective of the following review was to evaluate oral health complication in patients with ALS, highlighting the impact of oral care on patients' quality of life.},
}

@article {pmid41148458,
year = {2025},
author = {Goel, F and Kumar, D and Singh, P and Rai, SN and Yadav, DK},
title = {Molecular crosstalk between miRNAs and lncRNAs in neurodegenerative disease pathways.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {16},
pmid = {41148458},
issn = {1573-4978},
mesh = {Humans ; *RNA, Long Noncoding/genetics/metabolism ; *MicroRNAs/genetics/metabolism ; *Neurodegenerative Diseases/genetics/metabolism/therapy ; Gene Expression Regulation ; Animals ; Signal Transduction ; Gene Regulatory Networks ; },
abstract = {Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS), are characterized by progressive neuronal degeneration and dysfunction. Of recent interest, a series of studies have been targeting the role of non-coding RNAs, particularly miRNAs and lncRNAs, in regulating gene expression and influencing cellular pathways that may play a critical role in the pathogenesis of these diseases. miRNAs regulate many biological processes by degrading or repressing the translation of target mRNAs, whereas lncRNAs act as scaffolds, sponges, and guides to control gene expression and cellular activities. Both miRNAs and lncRNAs participate in neurodegenerative mechanisms such as protein aggregation, inflammation, oxidative stress, and neuroinflammation. While targeting miRNAs and lncRNAs holds promise for potential therapeutic benefits, problems persist with their efficient delivery, specificity, and off-target effects. New techniques like viral vectors, lipid nanoparticles, and CRISPR-based gene editing will further enhance the development of therapies based on miRNA and lncRNA. Moreover, their interaction with regulatory networks may present new avenues toward understanding disease mechanisms and guiding therapeutic design. This review covers the role of miRNAs and lncRNAs in neurodegenerative disorders, their therapeutic potential, challenges, and future directions in ncRNA-based treatment approaches.},
}

Humans
*RNA, Long Noncoding/genetics/metabolism
*MicroRNAs/genetics/metabolism
*Neurodegenerative Diseases/genetics/metabolism/therapy
Gene Expression Regulation
Animals
Signal Transduction
Gene Regulatory Networks

@article {pmid41146348,
year = {2025},
author = {Khizar, M and Alokozay, E and Junaid, M and Alokozay, N},
title = {Critical appraisal of progress and challenges in tuberculosis preventive treatment in the Western Pacific Region: a situational analysis of seven high tuberculosis burden countries.},
journal = {Tropical medicine and health},
volume = {53},
number = {1},
pages = {143},
pmid = {41146348},
issn = {1348-8945},
abstract = {We commend Oh et al.'s recent analysis of TB preventive treatment (TPT) in the Western Pacific Region, but note important gaps and ways forward. We first caution that reliance on routine program data may overestimate gains. For example, China's passive surveillance misses ≈20% of cases [1]. Prospective cohorts or integrated surveillance including clinical databases could validate coverage estimates. We also urge attention to overlooked risk groups beyond children and PLHIV (as highlighted by Oh et al. [2]), groups like healthcare workers, prisoners, and people with diabetes warrant targeted TPT pilots (e.g., occupational health or prison-based programs). In the Philippines, ~ 36% of TB patients first seek private care [3], so partnering with private clinics and pharmacies is essential to reach all contacts. Likewise, MDR-TB contacts were underemphasized; WHO now strongly recommends a 6-month levofloxacin regimen for MDR contacts [4]. We encourage pilot studies of this regimen (as in Mongolia [5]) and operational research on MDR-TPT. Finally, policy does not guarantee practice as Cambodia and Lao PDR have guidelines, yet stockouts and training gaps persist [6, 7]. Embedding TPT in universal health insurance and conducting cost effectiveness studies will support sustainable scale-up. In sum, by suggesting concrete examples and research strategies for each country, we aim to refine Oh et al.'s insights into actionable steps for TPT acceleration.},
}

@article {pmid41144002,
year = {2025},
author = {Vidovic, M and Lapp, HS and Dittes, I and Leuchten, N and Aringer, M and Günther, C and Günther, R},
title = {Methotrexate therapy as a promising long-term treatment approach for immune-mediated adverse reactions of tofersen in SOD1-ALS: a case report.},
journal = {Journal of neurology},
volume = {272},
number = {11},
pages = {732},
pmid = {41144002},
issn = {1432-1459},
}

@article {pmid41143669,
year = {2025},
author = {Morley, M and Aurora, M and Gustafson, K and Seals, CS and Feuer, A and Datar, S and Parvanta, S and Thakur, N and Dave, KD},
title = {Medicare expenditures in the first year of amyotrophic lateral sclerosis diagnosis.},
journal = {The American journal of managed care},
volume = {31},
number = {10},
pages = {e308-e312},
doi = {10.37765/ajmc.2025.89813},
pmid = {41143669},
issn = {1936-2692},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/economics/drug therapy/diagnosis ; United States ; *Health Expenditures/statistics & numerical data ; Aged ; Male ; Female ; *Medicare/economics/statistics & numerical data ; Aged, 80 and over ; Fee-for-Service Plans/economics/statistics & numerical data ; Cohort Studies ; },
abstract = {OBJECTIVES: To determine Medicare expenditures and potential beneficiary out-of-pocket liability for Medicare beneficiaries with amyotrophic lateral sclerosis (ALS), including costs related to drug treatments.

STUDY DESIGN: This cohort study utilized the 100% Medicare fee-for-service claims for 2017-2021, including Part A and Part B medical claims and Part D prescription drug event data.

METHODS: Eligible Medicare beneficiaries with ALS were identified based on 1 or more inpatient or 2 or more outpatient claims with an International Statistical Classification of Diseases, Tenth Revision diagnosis code for ALS (G12.21) between 2017 and 2020. Health care expenditures and beneficiary liability were assessed for the 12-month study period.

RESULTS: At 1 year post index, Medicare beneficiaries with ALS had more than 3 times the Medicare expenditures of beneficiaries without ALS ($47,450 vs $13,889, respectively). Similar patterns were observed for beneficiary liability. Approximately one-third of Medicare beneficiaries used either edaravone or riluzole in the first 12 months following ALS diagnosis. The cost of care for beneficiaries using these drugs was notably higher than for beneficiaries with ALS overall.

CONCLUSIONS: Approximately one-third of people with ALS on Medicare receive disease-modifying medication. ALS is a burdensome disease with significant financial implications for people with ALS and the Medicare program. Treatment for ALS presents affordability challenges, and policy makers must consider how current Medicare policy addresses the costs of care.},
}

Humans
*Amyotrophic Lateral Sclerosis/economics/drug therapy/diagnosis
United States
*Health Expenditures/statistics & numerical data
Aged
Male
Female
*Medicare/economics/statistics & numerical data
Aged, 80 and over
Fee-for-Service Plans/economics/statistics & numerical data
Cohort Studies

@article {pmid41141812,
year = {2025},
author = {Cobos, SN and Fisher, RMA and Bennett, SA and Janani, C and Dansu, DK and Cleere, MM and Yeasmin, A and Cruz, G and Qureshi, S and Villasi, W and Frederic, R and Chen, K and Mirzakandova, M and Angelakakis, G and Son, E and Elgendy, A and Torrente, MP},
title = {C9orf72 Dipeptide Repeat Proteinopathy Is Linked to Increased Histone H3 Phosphorylation on Serine 10.},
journal = {ACS omega},
volume = {10},
number = {41},
pages = {48395-48411},
pmid = {41141812},
issn = {2470-1343},
abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal illnesses forming a neurodegenerative disease continuum. While most ALS/FTD cases are sporadic, a small proportion of cases are linked to mutations in many genes. Among these, hexanucleotide repeat expansions in the C9orf72 gene are the most common and lead to the formation of dipeptide repeat proteins (DPRs), including a proline-arginine dipeptide (PR), which aggregate in the cytoplasm of decaying neurons. As genetics alone fails to explain the etiology of ALS/FTD, it is possible that epigenetic mechanisms - such as histone post-translational modifications (PTMs) - are involved in disease processes. A Saccharomyces cerevisiae (PR)50 overexpression model displays overt growth suppression and aggregation. Here, we exploit this model as a discovery platform to comprehensively characterize changes in the levels of PTMs on Histones H3 and H4. We find that overexpression of (PR)50 is associated with increased levels of phosphorylation on Histone H3 at Serine 10 (H3S10ph). Furthermore, (PR)50 overexpression revealed modest increases in the levels of other marks associated with increased gene expression. Remarkably, decreased abundance of Ipl1, the kinase responsible for phosphorylating H3S10 in yeast, leads to amelioration of the growth suppression phenotype and restores H3S10ph levels even in the context of (PR)50 overexpression. Recapitulating our results in yeast, several c9orf72 ALS patient-derived fibroblasts and induced pluripotent stem cell (iPSCs) lines display similar increases in H3S10ph levels. Altogether, these findings reveal a previously undiscovered connection between H3S10ph and c9 ALS/FTD proteinopathy that could reveal novel targets for the treatment of this disease.},
}

@article {pmid41141079,
year = {2025},
author = {Jeong, E and Li, D},
title = {Antisense Oligonucleotide Therapy for Amyotrophic Lateral Sclerosis (ALS): An Umbrella Review.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e93140},
pmid = {41141079},
issn = {2168-8184},
abstract = {Amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig's disease, is a fatal neurodegenerative disease prominent in the elderly population. To this point, no completely effective treatments have been procured; however, antisense oligonucleotide therapies, or ASOs, are a promising venue. In order to investigate the efficacy of ASOs in the treatment of ALS by targeting specific genetic mutations, we conducted an umbrella review utilizing keywords such as "ALS" and "ASO" in the PubMed database, excluding sources published more than 10 years ago for relevance. Results revealed that of multiple tentative ASO treatments, for multiple specific gene mutations, only one, Tofersen, was approved for the wider population. The main cause of failure was an inability to meet efficacy endpoints, resulting in the discontinuation of the product. Tofersen is able to treat mutations in the SOD1 gene, but not any others. While initially discouraging, the production of ASOs is a relatively new and advanced process, and slow progress is expected. However, there remains the problem of identifying and treating the much more prevalent sporadic ALS, which is much more common compared to familial ALS.},
}

@article {pmid41137739,
year = {2025},
author = {van Wijk, IF and Kraneburg, L and van Eijk, RPA and Veldink, JH and van Es, MA and Westeneng, HJ and van den Berg, LH},
title = {Prodromal symptoms in amyotrophic lateral sclerosis from the perspective of the patient and of the caregiver.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/21678421.2025.2574687},
pmid = {41137739},
issn = {2167-9223},
abstract = {OBJECTIVE: Clinically manifest ALS is preceded by a prodromal phase in gene mutation carriers, characterized by mild motor impairment. A well-defined prodromal phase could enable earlier diagnosis and treatment. We investigated the presence of a prodromal phase in sporadic ALS, from the perspective of patients and caregivers.

METHODS: A survey was conducted of symptom onset in 279 ALS patients from a population-based registry and 150 caregivers. 244 patients and 123 caregivers were included in the primary qualitative analysis, followed by quantitative analysis of identified themes. A prodromal phase was defined as symptoms, in response to open-ended questions, before onset of recorded weakness, bulbar complaints or shortness of breath. Mild motor symptoms were defined as fasciculations, cramps, stiffness, atrophy, reduced sports performance, or mobility issues.

RESULTS: 26.6% of patients and 17.5% of caregivers reported a prodromal phase, primarily with mild motor symptoms (patients 23.0%; caregivers 11.4%). Prodromal symptoms occurred a median of 6.0 months (IQR 2.8-11.8 months) before recorded disease onset. In closed-ended questions, 19.2% of patients and 22.2% of caregivers reported cognitive or behavioral symptoms before weakness onset, compared to only 0.6% and 1.8% in open-ended questions.

CONCLUSIONS: In sporadic ALS, approximately a quarter of patients report a prodromal phase characterized primarily by mild motor symptoms. However, mild motor symptoms alone are unlikely to contribute to earlier disease recognition. Cognitive or behavioral symptoms are often not recognized as part of the clinical spectrum. These findings emphasize the need for reliable biomarkers to detect ALS pathology at an early stage.},
}

@article {pmid41136425,
year = {2025},
author = {Vokali, E and Chevalier, E and Dreyfus, N and Charmey, D and Melly, T and Kocher, J and Ratnam, M and Serra, AM and Jaquier, T and Delgado, C and Ravache, M and Scialò, C and Cappelli, S and Kroth, H and Capotosti, F and Luthi-Carter, R and Afroz, T and Derouazi, M and Constantinescu, CC and Seelaar, H and Buratti, E and Nelson, PT and Polymenidou, M and Pfeifer, A and Kosco-Vilbois, M and Seredenina, T},
title = {Development of [[18]F]ACI-19626 as a first-in-class brain PET tracer for imaging TDP-43 pathology.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {9358},
pmid = {41136425},
issn = {2041-1723},
support = {P01 AG019724/AG/NIA NIH HHS/United States ; P30 AG028383/AG/NIA NIH HHS/United States ; P50 AG023501/AG/NIA NIH HHS/United States ; },
mesh = {*Positron-Emission Tomography/methods ; *Brain/diagnostic imaging/metabolism/pathology ; Humans ; *DNA-Binding Proteins/metabolism ; Animals ; *Radiopharmaceuticals/pharmacokinetics/chemistry ; Fluorine Radioisotopes ; *TDP-43 Proteinopathies/diagnostic imaging/metabolism/pathology ; Mice ; Male ; Frontotemporal Dementia/diagnostic imaging/metabolism/pathology ; Amyotrophic Lateral Sclerosis/diagnostic imaging/metabolism/pathology ; Female ; },
abstract = {Aggregated TDP-43 is a hallmark of frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and limbic-predominant age-related TDP-43 encephalopathy (LATE), and a common co-pathology in other neurodegenerative diseases. Currently, no specific biomarkers exist to assess TDP-43 pathology in vivo. We developed two small-molecule radiopharmaceuticals, [[18]F]ACI-19278 and [[18]F]ACI-19626, for visualizing TDP-43 inclusions by positron emission tomography (PET). Both ligands bind with high affinity to aggregated, but not soluble, TDP-43 in patient brain samples from diverse TDP-43 proteinopathies, including frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP), ALS, and LATE, and in cell models. Both compounds display excellent selectivity for TDP-43 over Aβ, Tau, and α-synuclein aggregates. In non-human primates, [[18]F]ACI-19278 and [[18]F]ACI-19626 show a pharmacokinetic profile suitable for brain PET imaging (rapid brain uptake; fast and complete washout). ACI-19278 and ACI-19626 are promising first-in-class TDP-43 PET tracers with the potential to revolutionize the diagnosis and treatment of neurodegenerative proteinopathies, enabling a precision medicine approach.},
}

*Positron-Emission Tomography/methods
*Brain/diagnostic imaging/metabolism/pathology
Humans
*DNA-Binding Proteins/metabolism
Animals
*Radiopharmaceuticals/pharmacokinetics/chemistry
Fluorine Radioisotopes
*TDP-43 Proteinopathies/diagnostic imaging/metabolism/pathology
Mice
Male
Frontotemporal Dementia/diagnostic imaging/metabolism/pathology
Amyotrophic Lateral Sclerosis/diagnostic imaging/metabolism/pathology
Female

@article {pmid41135742,
year = {2025},
author = {Hu, T and Xi, J and Xie, N and Zhang, X and Huang, N and Cheng, Y},
title = {Multi-Omics Analysis Reveals the Protective Role of Transcriptional Enhancer Factor and the Pathogenic Mechanism of Monocytes in Parkinson's Disease.},
journal = {Brain research bulletin},
volume = {},
number = {},
pages = {111594},
doi = {10.1016/j.brainresbull.2025.111594},
pmid = {41135742},
issn = {1873-2747},
abstract = {Parkinson's disease (PD) is a multifactorial neurodegenerative disorder whose pathogenic mechanisms remain incompletely elucidated. This study aimed to systematically identify key regulatory factors involved in PD at the genetic, cellular, and molecular levels. Using univariate Mendelian randomization (UVMR), we identified plasma proteins and genes associated with Alzheimer's disease (AD), PD, and amyotrophic lateral sclerosis (ALS), and validated their causal relationships through colocalization analysis. Cross-validation across multi-omics datasets revealed transcriptional enhancer factor (TEF) as a protective factor for PD, whereas increased counts of CD14[+]CD16[+] monocytes were identified as a risk factor. Single-cell analysis and multivariate Mendelian randomization (MVMR) further suggested potential mediating roles of these factors in PD pathogenesis. In vitro experiments demonstrated that TEF overexpression significantly enhanced the resistance of neuroblastoma cells to rotenone-induced damage, inhibited apoptosis, and preserved tyrosine hydroxylase (TH) expression. In vivo, TEF notably improved motor coordination and exploratory behavior in PD mouse models. Collectively, these findings suggest that TEF may exert neuroprotective effects by modulating immune and neuronal pathways, offering a novel therapeutic target for the prevention and treatment of Parkinson's disease.},
}

@article {pmid41135686,
year = {2025},
author = {Columbro, SF and Tortarolo, M and Re Cecconi, AD and Piccirillo, R and Bendotti, C and Biasini, E and Pasetto, L and Bonetto, V},
title = {Beneficial effects of synthetic torpor in a fast-progressing mouse model of amyotrophic lateral sclerosis.},
journal = {Experimental neurology},
volume = {396},
number = {},
pages = {115521},
doi = {10.1016/j.expneurol.2025.115521},
pmid = {41135686},
issn = {1090-2430},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron loss, muscle atrophy, and progressive paralysis. Currently approved treatments provide only limited benefits. Due to the complex and multifactorial nature of ALS pathology, therapies targeting multiple pathways may prove more effective. Synthetic torpor, a state that mimics natural hibernation, has shown promise in promoting neuroprotection by modulating metabolism, reducing inflammation, and preserving both neurons and muscles. In this study, synthetic torpor was induced using 5'AMP combined with environmental cooling in the fast-progressing SOD1[G93A] ALS mouse model on the 129SvHsd genetic background, known for its aggressive disease course, early metabolic dysfunction and unresponsiveness to treatments. Synthetic torpor was highly effective in preserving motor neurons. The treatment significantly delayed disease onset and extended survival, although mildly, without altering overall disease duration. In the spinal cord, synthetic torpor increased glucose transporters, reduced markers of oxidative stress, decreased glial activation and sustained upregulation of neuroprotective proteins, such as RBM3 and PPIA. This occurred despite an increased SOD1 aggregation in a later phase of the disease. Muscles display clear protective effects across disease progression with preservation of mass, reduced atrogin-1, lower PDK4 and oxidative stress markers, associated with improvements in markers of axonal integrity and muscle denervation. This study provides proof-of-concept that activating multiple protective molecular pathways, particularly those involved in glucose metabolism and protein folding, can mitigate the pathological processes in ALS, especially in rapidly progressing forms of the disease.},
}

@article {pmid41132886,
year = {2025},
author = {Agüera-Morales, E and Fernández-Sánchez, VE and Navarro-Mascarell, G and Cabezas-Rodríguez, JA and Peña-Toledo, MÁ and Reyes-Rodríguez, V and Postigo-Pozo, MJ and Patrignani-Ochoa, G and Geniz-Clavijo, MÁ and Márquez-Infante, C and Tallon-Aguilar, L and Tinoco-González, J and Padillo-Ruiz, J and Valladares-Sánchez, A and Caballero-Eraso, C and López-Ramírez, C and Mata Alcázar-Caballero, R and Leyva-Fernández, L and Rodríguez-Acosta, A and Maldonado-Sánchez, R and García-Martín, ML and Somoza-Ramírez, M and Quijano-Ruiz, B and Macías-Sánchez, MDM and Carmona-Sánchez, G and Fernández-López, O and Fernández-Fernández, Ó},
title = {Adipose-derived mesenchymal stem cells for the treatment of Amyotrophic Lateral Sclerosis. A phase I/II safety and efficacy clinical trial.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1655124},
pmid = {41132886},
issn = {1664-2295},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease with few treatments available. Mesenchymal stem cells have arisen as a potential treatment option for ALS due to their immune system modulation and their neuroprotective effects. This clinical trial aimed to evaluate the safety, efficacy and feasibility of three intravenous doses of autologous adipose-derived mesenchymal stem cells (AdMSC) in ALS patients.

METHODS: A multicentre, randomized, parallel group, placebo-controlled, double-blinded clinical trial (EudraCT: 2011-006254-85) was conducted in 40 patients with ALS in treatment with riluzole. Patients were randomized 1:1:1:1 into the following treatment groups: 1 × 10[6] cells/kg, 2 × 10[6] cells/kg, 4 × 10[6] cells/kg and placebo. After a 6 month follow-up, patients in the placebo group were randomized 1:1:1 to receive one of the three doses of AdMSC and they were followed up for another 6 months. Lastly, all patients were followed-up in a 36-month open-label extension. Safety was mainly assessed through the evaluation of adverse events and their relationship with the medicinal product. Several variables were measured to assess efficacy, such as ALS Functional Rating Scale, Ashworth spasticity scale, neurophysiological and neuropsychological parameters and overall survival. The feasibility of the procedure was assessed through the evaluation of the extraction and infusion of AdMSC.

RESULTS: Safety of AdMSC was observed through all follow-up periods, with similar percentages of adverse events between groups and no significant differences between groups in the rate of adverse events related to treatment. The administration procedure was feasible for all patients. Across all analyzed measures, we observed the expected progressive decline characteristic of ALS, with no statistically significant between-group differences in the rate of change.

DISCUSSION: The results obtained in this study are consistent with the ones obtained in other clinical trials using similar doses of MSC, where safety was demonstrated and efficacy results were inconclusive, due to not reaching statistical significance. Larger studies with an increased sample size, different doses and route of administration or combination of routes, repeated dosing or larger duration and comprehensive assessment of immunological effect would be needed to analyze the efficacy of AdMSC in the treatment of ALS.

CLINICAL TRIAL REGISTRATION: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2011-006254-85.},
}

@article {pmid41117572,
year = {2025},
author = {Soar, J and Böttiger, BW and Carli, P and Jiménez, FC and Cimpoesu, D and Cole, G and Couper, K and D'Arrigo, S and Deakin, CD and Ek, JE and Holmberg, MJ and Magliocca, A and Nikolaou, N and Paal, P and Pocock, H and Sandroni, C and Scquizzato, T and Skrifvars, MB and Verginella, F and Yeung, J and Nolan, JP},
title = {European Resuscitation Council Guidelines 2025 Adult Advanced Life Support.},
journal = {Resuscitation},
volume = {215 Suppl 1},
number = {},
pages = {110769},
doi = {10.1016/j.resuscitation.2025.110769},
pmid = {41117572},
issn = {1873-1570},
mesh = {Humans ; *Advanced Cardiac Life Support/standards/methods ; *Cardiopulmonary Resuscitation/standards/methods ; Adult ; Europe ; *Heart Arrest/therapy ; *Out-of-Hospital Cardiac Arrest/therapy ; },
abstract = {These European Resuscitation Council (ERC) Guidelines 2025 Adult Advanced Life Support (ALS) are based on the International Liaison Committee on Resuscitation (ILCOR) Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations (CoSTR). The evidence informing the ALS Guidelines is also included. When ILCOR has not addressed a specific topic, the ERC ALS Writing Group has provided its own guidance and the evidence supporting it. This section provides recommendations for ALS for adults with in- or out-of-hospital cardiac arrest. The ERC Guidelines 2025 ALS emphasise providing early and effective ALS interventions to improve survival from cardiac arrest in adults.},
}

Humans
*Advanced Cardiac Life Support/standards/methods
*Cardiopulmonary Resuscitation/standards/methods
Adult
Europe
*Heart Arrest/therapy
*Out-of-Hospital Cardiac Arrest/therapy

@article {pmid41117139,
year = {2025},
author = {Pedro, KM and Alvi, MA and Goulart, GR and Fehlings, MG},
title = {Riluzole as a pharmacological therapy for spinal cord injury: where does this therapy stand?.},
journal = {Current opinion in neurology},
volume = {},
number = {},
pages = {},
doi = {10.1097/WCO.0000000000001434},
pmid = {41117139},
issn = {1473-6551},
abstract = {PURPOSE OF REVIEW: Spinal cord injury (SCI) remains a disabling condition associated with long term neurological impairment, functional disability, and reduced quality of life. Despite decades of research, pharmacological interventions with proven clinical efficacy remain limited. This review critically evaluates the current evidence supporting riluzole as a neuroprotective agent for acute traumatic and nontraumatic SCI. We synthesize findings from preclinical and clinical studies, assess the progress towards clinical translation, and outline key challenges and research opportunities for future implementation.

RECENT FINDINGS: Riluzole, an FDA-approved agent for amyotrophic lateral sclerosis (ALS), inhibits voltage-gated sodium channels and modulates glutaminergic transmission, two mechanisms central to the pathogenesis of secondary injury in SCI and in nerve cell degeneration in nontraumatic forms of SCI, including degenerative cervical myelopathy (DCM). Preclinical studies consistently demonstrate functional and histopathological improvements following riluzole administration. Phase I/II trials have provided evidence for its safety and tolerability in acute SCI patients, while the RISCIS and CSM-PROTECT trials, two landmark multicenter randomized controlled studies, along with their secondary analyses, revealed promising multidomain improvements in motor function, independence, and quality of life indices. Sub-studies have also established pharmacokinetic and pharmacodynamic frameworks for individualized dosing, and early biomarker analysis suggests potential for predictive stratification.

SUMMARY: Riluzole represents a promising candidate for neuroprotection in traumatic and nontraumatic SCI. The consistency of favorable trends across multiple domains and strong support from preclinical studies highlight riluzole's value in orphan diseases such as SCI. Future directions should focus on refining the therapeutic window, optimizing PK/PD modeling, and identifying patient subgroups most likely to benefit. Its implementation in a multimodal treatment paradigm for acute SCI will be crucial for optimizing management protocols in this highly disabling condition.},
}

@article {pmid41117127,
year = {2025},
author = {Kim, H and Uhm, JE and Park, J and Kim, YS and Sung, W and Lee, S and Kim, SH and Oh, KW},
title = {Monoclonal Gammopathy in Amyotrophic Lateral Sclerosis: No Impact on Clinical Progression and Immunotherapy Outcomes.},
journal = {European journal of neurology},
volume = {32},
number = {10},
pages = {e70376},
pmid = {41117127},
issn = {1468-1331},
support = {RS-2023-00265515//K-Brain Project of the National Research Foundation(NRF) Korean government (MSIT) (RS-2023-00265515)./ ; RS-2024-00348451//Korea Dementia Research Project through the Korea Dementia Research Center (KDRC), funded by the Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea (RS-2024-00348451)./ ; },
mesh = {Humans ; Male ; *Amyotrophic Lateral Sclerosis/epidemiology/therapy/complications ; Female ; Disease Progression ; Aged ; *Immunotherapy/methods ; Middle Aged ; *Paraproteinemias/epidemiology/therapy/complications ; Republic of Korea/epidemiology ; Registries ; Prevalence ; Treatment Outcome ; Adult ; Aged, 80 and over ; },
abstract = {BACKGROUND: The association between amyotrophic lateral sclerosis (ALS) and monoclonal gammopathy has been proposed, but evidence on its prevalence, clinical relevance, and treatment response remains limited, especially in Asian populations. This study aimed to investigate the prevalence of monoclonal gammopathy in Korean patients with ALS and evaluate the impact of immunotherapy.

METHODS: This registry-based study analyzed Korean patients with ALS at a tertiary referral hospital (2005-2023). All patients underwent electrophoresis and immunofixation electrophoresis to detect monoclonal gammopathy. Clinical progression was assessed using ALSFRS-R scores, disease progression rate (ΔFS), survival analysis, and electrophysiological evaluations.

RESULTS: Among 2400 patients with ALS, monoclonal gammopathy was identified in 1.0% (25/2400). Prevalence increased with age, 1.9% in patients aged ≥ 65 years and 0.7% (13/1755) aged < 65 years. Patients with ALS and monoclonal gammopathy were older (63.2 vs. 57.1; p = 0.01) and predominantly male (7.3:1 vs. 1.5:1; p < 0.01). Immunotherapy targeting monoclonal gammopathy did not significantly affect disease progression (pre-treatment ΔFS 1.00 ± 1.23 vs. post-treatment ΔFS 0.94 ± 0.86; p = 0.46) or survival outcomes (median survival 55.0 vs. 57.0 months; log-rank p = 0.93). Nerve conduction study did not correlate with clinical outcomes. IgM monoclonal gammopathy demonstrated later slower disease progression (initial ΔFS, overall ΔFS; p < 0.05) compared to IgA and IgG subtypes.

CONCLUSION: Monoclonal gammopathy in Korean patients with ALS was not more prevalent than in the general population, and immunotherapy did not impact ALS progression or survival. Clinical features may vary by immunoglobulin subtype. This collectively suggests minimal clinical significance of monoclonal gammopathy in ALS.},
}

Humans
Male
*Amyotrophic Lateral Sclerosis/epidemiology/therapy/complications
Female
Disease Progression
Aged
*Immunotherapy/methods
Middle Aged
*Paraproteinemias/epidemiology/therapy/complications
Republic of Korea/epidemiology
Registries
Prevalence
Treatment Outcome
Adult
Aged, 80 and over

@article {pmid41114109,
year = {2025},
author = {Zhou, QQ and Ren, YM and Shi, SM and Liu, TF},
title = {Microenvironmental code of pancreatic ductal adenocarcinoma: The prognostic symphony of budding, matrix and lymphocytes.},
journal = {World journal of gastrointestinal oncology},
volume = {17},
number = {10},
pages = {110523},
pmid = {41114109},
issn = {1948-5204},
abstract = {This editorial discusses Alpsoy et al's significant study of prognosis of pancreatic ductal adenocarcinoma (PDAC), which lacks histopathological markers. This study evaluated the synergistic prognolymphocytes. Peritumoral budding is significantly correlated with tumor volume, while intratumoral budding is closely related to lymph node metastasis. Peritumoral budding and intratumoral budding are confirmed as independent adverse prognostic factors, and their high levels of expression are associated with immature stromal phenotypes, suggesting the key role of epithelial-mesenchymal transition. These breakthrough findings provide a new multidimensional biomarker system for the prognostic assessment of PDAC, and promote the clinical transformation process of incorporating tumor budding indicators into the pathological reporting process. However, the complexity and spatiotemporal heterogeneity of the tumor microenvironment require us to go beyond traditional morphological analysis and move towards multiomics integration and dynamic monitoring. Through standardized pathological assessment, innovative treatment strategies and interdisciplinary collaboration, it is expected to transform tumor microenvironment-related markers into clinically applicable indicators, ultimately improving the treatment predicament of PDAC. This editorial intended to summarize relevant studies and share some of our views, in order to offer perspectives for future research.},
}

@article {pmid41107100,
year = {2025},
author = {Palomeque, S and Loguercio, AD and Arrais, CAG and Sánchez, C and Pulido, C},
title = {Three-dimensionally printed and milled composite materials for definitive restorations. Part 2: Effect of surface treatment on the bond strength of light-polymerized resin cement and surface morphology.},
journal = {The Journal of prosthetic dentistry},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.prosdent.2025.09.033},
pmid = {41107100},
issn = {1097-6841},
abstract = {STATEMENT OF PROBLEM: Evidence regarding the effect of surface treatment on the bond strength and surface morphology of 3-dimensionally (3D) printed and computer-aided design and computer-aided manufacturing (CAD-CAM) composite materials is sparse. Enhancing the bond strength to these materials and their surface modifications is essential for ensuring clinical success.

PURPOSE: The purpose of this in vitro study was to evaluate the microshear bond strength (µSBS) of light-polymerized resin cement and the surface morphology of composite materials for definitive indirect restorations after different pretreatments.

MATERIAL AND METHODS: Specimens (6×7×9 mm) from composite CAD-CAM materials were fabricated: 5 by 3D printing (Varseosmile Crown Plus - BEGO (VSC), Crowntec - Saremco Print (CWT), Biocrown - Prizma (BCN), Ceramic Crown - SprintRay (CCN), and Voxel Print - FGM (VXP) and 3 by milling: Cerasmart - GC (CSM), Brilliant Crios - Coltène (BCR), and Enamic - Vita (ENA). Thirteen specimens of each material were selected: 10 for μSBS and 3 for scanning electron microscopy (SEM). Two surface pretreatment protocols were applied: Airborne-particle abrasion with aluminum oxide followed by silane (AL+S), and 5% hydrofluoric acid followed by silane (HF+S). For µSBS testing, transparent cylindrical matrices were filled with light-polymerized resin cement. After 24-hour storage, the specimens were subjected to shear testing (crosshead speed of 1.0 mm/minute). The data were analyzed by 2-way variance analysis and the Bonferroni post hoc test (α=.05).

RESULTS: Within the HF+S groups, ENA exhibited the highest µSBS values (18.47 ±1.0 MPa), although no significant differences were found with VXP (16.12 ±1.4 MPa). The highest µSBS mean value was observed on the CCN surface after AL+S (19.49 ±2.8 MPa), followed by VSC (18.74 ±2.2 MPa) and CSM (18.45 ±1.1 MPa). The surface pattern with AL+S presented more evident irregularities on both printable and machinable materials.

CONCLUSIONS: Airborne-particle abrasion with aluminum oxide was found to be appropriate for both milled and printed materials. Hydrofluoric acid etching was not recommended for all types of CAD-CAM resin ceramics, even when followed by silane application.},
}

@article {pmid41103971,
year = {2025},
author = {Arachchige, ASPM},
title = {Rethinking ALS: Current understanding and emerging therapeutic strategies.},
journal = {AIMS neuroscience},
volume = {12},
number = {3},
pages = {391-405},
pmid = {41103971},
issn = {2373-7972},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive degeneration of the upper and lower motor neurons, which leads to muscle atrophy, spasticity, and ultimately respiratory failure. The etiology of ALS remains unclear, though a combination of genetic and environmental factors is suspected. Advances in understanding ALS pathophysiology, including the role of RNA metabolism, mitochondrial dysfunction, and glutamate toxicity, have paved the way for new research directions. While Riluzole offers limited survival benefits, there is no cure, and treatment remains mostly supportive. This article summarizes the current understanding of ALS in terms of its pathophysiology, epidemiology, risk factors, clinical presentation, and treatment strategies.},
}

@article {pmid41101465,
year = {2025},
author = {Veenstra, J and Ozog, D and Stephens, A},
title = {Response to Bunick et al, "Response to Veenstra et al.'s 'Benzoyl Peroxide Acne Treatment Shows No Significant Association with Benzene-Related Cancers: A Multicenter Retrospective Analysis' on Statistical Design".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.09.104},
pmid = {41101465},
issn = {1097-6787},
}

@article {pmid41101301,
year = {2025},
author = {Sasidharan, A and Somayaji, Y and Fernandes, R},
title = {Shifting Microglial Phenotypes: Targeting Disease-Associated Microglia in Neurodegeneration.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.5c00159},
pmid = {41101301},
issn = {1948-7193},
abstract = {Neurodegenerative disorders are marked by the gradual degeneration of neurons and deterioration of cognitive function. One key underlying factor in these diseases is neuroinflammation. An essential component of this process is microglia, which are the innate immune cells that maintain homeostasis in the brain. A common outcome of microglial dysregulation in neurodegenerative diseases is chronic neuroinflammation, which exacerbates neuronal damage and impairs synaptic function. This review focuses on the dual roles that disease-associated microglia (DAMs) play in neural inflammation and neuroprotection as well as their distinct transcriptional profile in neurodegenerative diseases. DAMs engage in phagocytosis to remove debris, in addition to releasing cytokines that promote inflammation. To create an effective medicine, it is imperative to comprehend these dual functions. The roles of DAMs in Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are discussed, along with the mechanisms (such as the TREM2-APOE pathway) causing their activation. This review attempts to highlight the important aspects that could direct future investigations and treatment development by clarifying the interactions between DAMs and neurodegenerative diseases.},
}

@article {pmid41097004,
year = {2025},
author = {Daponte, A and Koros, C and Skarlis, C and Siozios, D and Rentzos, M and Papageorgiou, SG and Anagnostouli, M},
title = {Neurofilament Biomarkers in Neurology: From Neuroinflammation to Neurodegeneration, Bridging Established and Novel Analytical Advances with Clinical Practice.},
journal = {International journal of molecular sciences},
volume = {26},
number = {19},
pages = {},
pmid = {41097004},
issn = {1422-0067},
mesh = {Humans ; *Biomarkers/metabolism/blood ; *Neurofilament Proteins/metabolism/blood ; *Neurodegenerative Diseases/metabolism/diagnosis ; *Neuroinflammatory Diseases/metabolism/diagnosis ; Animals ; },
abstract = {Neuroaxonal damage underlies permanent disability in various neurological conditions, both neuroautoimmune and neurodegenerative. It is crucial to accurately quantify and monitor axonal injury using biomarkers to evaluate disease progression and treatment effectiveness and offer prognostic insights. Neurofilaments (NFs), and especially neurofilament light chain (NfL), show promise for this purpose, as their levels increase with neuroaxonal damage in both cerebrospinal fluid and blood, independent of specific causal pathways. Recent advances in ultrasensitive immunoassays enable the reliable detection of NFs in blood, transforming them from research tools into clinically applicable measures. In multiple sclerosis (MS), serum NfL correlates with disease activity, treatment response, and long-term disability, and may complement MRI in monitoring subclinical progression. In MS, NfL is primarily emerging as a marker of disease activity and treatment response; in amyotrophic lateral sclerosis (ALS), it has progressed further, being integrated into clinical trials as a pharmacodynamic endpoint and considered by regulatory agencies as a drug development tool. Additionally, NFs are increasingly being investigated in Alzheimer's disease, frontotemporal dementia, and other neurodegenerative disorders, though their disease specificity is limited. Ongoing challenges include older and novel assay harmonization, normative range interpretation, biological and analytical variability, and integration with other molecular and imaging biomarkers. This critical narrative review synthesizes the existing literature on NFs as diagnostic, prognostic, predictive, and pharmacodynamic biomarkers and discusses their role in therapeutic development and precision medicine in neuroautoimmune and neurodegenerative diseases.},
}

Humans
*Biomarkers/metabolism/blood
*Neurofilament Proteins/metabolism/blood
*Neurodegenerative Diseases/metabolism/diagnosis
*Neuroinflammatory Diseases/metabolism/diagnosis
Animals

@article {pmid41096667,
year = {2025},
author = {Skarlis, C and Angelopoulou, E and Rentzos, M and Papageorgiou, SG and Anagnostouli, M},
title = {Monoclonal Antibodies as Therapeutic Agents in Autoimmune and Neurodegenerative Diseases of the Central Nervous System: Current Evidence on Molecular Mechanisms and Future Directions.},
journal = {International journal of molecular sciences},
volume = {26},
number = {19},
pages = {},
pmid = {41096667},
issn = {1422-0067},
mesh = {Humans ; *Antibodies, Monoclonal/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy/immunology ; Animals ; *Central Nervous System Diseases/drug therapy/immunology ; Neuromyelitis Optica/drug therapy ; Central Nervous System/drug effects/immunology ; Multiple Sclerosis/drug therapy ; },
abstract = {Monoclonal antibodies (mAbs) have revolutionized the treatment landscape for neurological diseases, providing targeted, mechanism-based therapies for conditions ranging from autoimmune demyelinating disorders to neurodegenerative diseases. In multiple sclerosis (MS), mAbs against CD20, CD52, and α4-integrins offer disease-modifying efficacy by altering immune responses, depleting B cells, or blocking leukocyte migration into the central nervous system (CNS). Similarly, novel agents under investigation, such as frexalimab and foralumab, modulate T and B cell interactions and regulatory immunity. In neuromyelitis optica spectrum disorder (NMOSD), mAbs targeting IL-6, the complement cascade, and B cell lineage have demonstrated significant clinical benefit in preventing relapses and disability. In Alzheimer's disease (AD), several anti-amyloid mAbs have gained regulatory approval. Anti-tau and anti-α-synuclein antibodies, though promising, have shown limited efficacy to date in AD and parkinson's disease (PD), respectively. The evolving armamentarium of mAbs reflects a paradigm shift toward personalized neuroimmunology and neurodegeneration-targeted treatments, based on ongoing clarification of molecular and neuroinflammatory mechanisms. In this context, the present review summarizes current evidence on mAbs used in CNS disorders, with an emphasis on their pathophysiological targets, molecular mechanisms, clinical efficacy, and safety.},
}

Humans
*Antibodies, Monoclonal/therapeutic use/pharmacology
*Neurodegenerative Diseases/drug therapy/immunology
Animals
*Central Nervous System Diseases/drug therapy/immunology
Neuromyelitis Optica/drug therapy
Central Nervous System/drug effects/immunology
Multiple Sclerosis/drug therapy

@article {pmid41096646,
year = {2025},
author = {García-Criado, F and Hurtado-García, L and Rojano, E and Esteban-Martos, Á and Pérez-García, J and Seoane, P and Ranea, JAG},
title = {Integrative Transcriptomic and Network-Based Analysis of Neuromuscular Diseases.},
journal = {International journal of molecular sciences},
volume = {26},
number = {19},
pages = {},
doi = {10.3390/ijms26199376},
pmid = {41096646},
issn = {1422-0067},
support = {PID2019-108096RB-C21, PID2022-140047OB-C21, CPP2022-010108//Ministerio de Ciencia, Innovación y Universidades/ ; IMP/00019, ACCI-05-703, ACCI-02-770//Instituto de Salud Carlos III/ ; HORIZON-HLTH-2022-DISEASE-06, 101080580//European Union/ ; RH-0079-2021//Fundación Progreso y Salud/ ; PI RARE 24-03//Instituto de Investigación Biomédica de Málaga/ ; FPU21/01449, PRE2022/000510//Ministerio de Ciencia, Innovación y Universidades/ ; },
mesh = {Humans ; *Transcriptome ; *Neuromuscular Diseases/genetics/metabolism ; *Gene Regulatory Networks ; Protein Interaction Maps/genetics ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Gene Expression Profiling ; Muscular Dystrophy, Duchenne/genetics/metabolism ; Muscular Dystrophies, Limb-Girdle/genetics/metabolism ; Computational Biology/methods ; },
abstract = {Neuromuscular diseases (NMDs) like Duchenne muscular dystrophy (DMD), limb-girdle muscular dystrophy (LGMD), and amyotrophic lateral sclerosis (ALS) are rare, progressive disorders with complex molecular mechanisms. Traditional transcriptomic analyses often struggle to capture systems-level dysregulation, especially given the small sample sizes typical of rare disease studies. Our differential expression analysis of eight public RNA-seq datasets from various cell types in DMD, LGMD, and ALS revealed not only disease-relevant pathways but also unexpected enrichments, such as renal development, suggesting systemic impacts beyond muscle tissue. To address limitations in capturing broader molecular mechanisms, we applied an integrative systems biology approach combining differential expression data, protein-protein interaction (PPI) networks, and network embedding techniques. Comparative functional enrichment revealed shared pathways, including glycosaminoglycan binding in both DMD and FUS-related ALS, implicating extracellular matrix-protein interactions in FUS mutation effects. Mapping DEGs onto the human PPI network and assessing their proximity to causal genes uncovered dysregulated non-coding RNAs, such as PAX8-AS1, SBF2-AS1, and NEAT1, potentially indicating common regulatory roles. We also found candidate genes within disease-proximal clusters, like HS3ST3A1, which may contribute to pathogenesis. Overall, this integrative approach reveals shared transcriptional programs and novel targets, advancing our understanding and potential treatment strategies for NMDs.},
}

Humans
*Transcriptome
*Neuromuscular Diseases/genetics/metabolism
*Gene Regulatory Networks
Protein Interaction Maps/genetics
*Amyotrophic Lateral Sclerosis/genetics/metabolism
Gene Expression Profiling
Muscular Dystrophy, Duchenne/genetics/metabolism
Muscular Dystrophies, Limb-Girdle/genetics/metabolism
Computational Biology/methods

@article {pmid41095781,
year = {2025},
author = {Ferreira Laurentino, EK and Maldaner da Silva, VZ and Costa Meneses, WR and da Costa, LM and Otto-Yañez, M and Vera-Uribe, R and Torres-Castro, R and Carneiro de Sousa, BR and de Abreu Freitas, RP and Menezes Mateus, SR and Vasconcellos, IF and Fernandes Franco, HC and Pinto Nagem, DA and Medeiros Valentim, RA and Dourado Júnior, ME and Rodrigues Lindquist, AR and Santos Andrade, SMMD and Medeiros Fonseca, JD and Resqueti, VR and Freitas Fregonezi, G},
title = {High-Definition Transcranial Direct Current Stimulation (HD-tDCS) Therapy in Amyotrophic Lateral Sclerosis: Study Protocol for a Multicenter Randomized Controlled Clinical Trial.},
journal = {Journal of clinical medicine},
volume = {14},
number = {19},
pages = {},
doi = {10.3390/jcm14196701},
pmid = {41095781},
issn = {2077-0383},
support = {1748/22//Financiadora de Estudos e Projetos/ ; 88887.692599/2022-00 (JDMF)//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; 305960/2021-0 (VRR)//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; 316937/2021-5 (GF)//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; 001 (EKFL)//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; 001 (WRCM)//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; 001 (LMC)//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; 001 (BRCS)//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; },
abstract = {Background/Objectives: Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disease characterized by motor neuron loss, muscle weakness, and respiratory dysfunction, often culminating in ventilatory failure. Evidence suggests that High-Definition Transcranial Direct Current Stimulation (HD-tDCS) may modulate motor cortical excitability and potentially influence motor and respiratory function in ALS. This study aims to evaluate the effects of home-based HD-tDCS applied over the primary diaphragmatic motor cortex on respiratory parameters and disease progression in individuals with ALS. Methods: This is a multicenter, randomized, controlled clinical trial. Eligible participants (aged 18-80, both sexes, diagnosed with ALS) will be randomized into an active HD-tDCS group (gTDCS) or a sham group (gSham). The intervention consists of 30 min daily HD-tDCS sessions (3 mA) applied for two weeks (5 days/week), using a 4 × 1 ring configuration targeting the diaphragmatic motor cortex. Sham stimulation includes an identical setup but only delivers ramp currents (30 s) with a minimal ongoing current (0.1 mA). Results: Pre-, intra-, and post-intervention evaluations will include measures of cortical excitability, cerebral and tissue perfusion, surface electromyography, respiratory and pulmonary function, fatigue, sleep quality, pain, motor performance, dyspnea, quality of life, and adverse effects. All procedures will be conducted at participants' homes with appropriate safety monitoring. Conclusions: This study will investigate the effects of HD-tDCS on respiratory and motor function in ALS and explore the feasibility of a home-based neuromodulation intervention. The outcomes may provide insight into non-pharmacological strategies for respiratory management in ALS.},
}

@article {pmid41095520,
year = {2025},
author = {Whelan, BM and Aldridge, D and Ruhle, J and Whitelock, P and Taubert, S and Collins, A and Kearney, E and Charania, S and Henderson, RD and Wallace, SJ and Mitchell, C and Stipancic, KL and Kuruvilla-Dugdale, M and Vogel, AP},
title = {To Treat or Not to Treat: A Scoping Review of Speech Treatment for Dysarthria in Amyotrophic Lateral Sclerosis (ALS).},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {19},
pages = {},
doi = {10.3390/healthcare13192434},
pmid = {41095520},
issn = {2227-9032},
support = {N/A//University of Queensland, School of Health and Rehabilitation Sciences, New Staff Research Start-Up Fund/ ; },
abstract = {BACKGROUND: Speech loss is recognised as one of the most devastating outcomes for individuals with ALS, yet active speech intervention is rarely targeted in this population. Clinicians face significant challenges in managing dysarthria associated with ALS due to the rapidly progressive nature of the disease, historical concerns around intensive exercise accelerating decline, and an absence of direction on restorative and compensatory intervention strategies in current clinical care guidelines. This review evaluates the scope and quality of evidence for speech treatments in ALS to identify knowledge gaps and establish research priorities to guide clinical care.

METHODS: Studies were retrieved from six electronic databases (PubMed, CINAHL, Embase, Cochrane library, Web of Science, and PsycINFO).

RESULTS: Four studies met inclusion criteria. Treatment approaches included: music-based speech therapy; multisubsystem speech rehabilitation program, tongue strengthening and articulation training; and Lee Silverman Voice Treatment-LOUD[®] combined with additional voice and articulation therapy. Sample sizes were small, with all studies demonstrating notable methodological weaknesses. The limited evidence base, marked by conflicting results and methodological flaws, prevents any reliable conclusions about treatment effectiveness.

CONCLUSIONS: Despite the prevalence and impact of dysarthria in this population, evidence for speech treatment remains sparse, of generally low quality, and provides limited guidance for clinical practice. The changing perspective on exercise in ALS warrants rigorous investigation of tailored dysarthria interventions for this population that are minimally fatiguing and enhance speech by making use of residual physiologic support.},
}

@article {pmid41094045,
year = {2025},
author = {Li, A and Huang, S and Cao, SQ and Lin, J and Zhao, L and Yu, F and Huang, M and Yang, L and Xin, J and Wen, J and Yan, L and Zhang, K and Jiang, M and Le, W and Li, P and Liu, YU and Qin, D and Lu, J and Lu, G and Shen, H and Yao, X and Fang, EF and Su, H},
title = {Isoginkgetin antagonizes ALS pathologies in its animal and patient iPSC models via PINK1-Parkin-dependent mitophagy.},
journal = {EMBO molecular medicine},
volume = {},
number = {},
pages = {},
pmid = {41094045},
issn = {1757-4684},
support = {0093/2024/AFJ//Macau University of Science and Technology (MUST)/ ; #81971327//MOST | National Natural Science Foundation of China (NSFC)/ ; #82271448//MOST | National Natural Science Foundation of China (NSFC)/ ; MYRGGRG2023-00152-ICMS-UMDF//MOST | National Natural Science Foundation of China (NSFC)/ ; #282952; #284930//Cure Alzheimer's Fund (CAF)/ ; #262175,#334361//research council of Norway/ ; 2020001,#2021021,#2023093//HELSE SOR-OST/ ; #282942//Molecule AG/VITADAO/ ; #119986//NordForsk/ ; 269901,#261973,#262960//Høgskolen i Oslo og Akershus (HiOA)/ ; #281931//civitan norges forskningsfond for Alzheimer skydom/ ; TO01000215//Ministerstvo Práce a Sociálních Věcí České Republiky (Ministry of Labour and Social Affairs of the Czech Republic)/ ; #101073251//horizon-TMA-MSCA-DN/ ; #104617//Burroughs Wellcome Fund (BWF)/ ; SKL-QRCM(UM)-2023-2025//Science and Technology Development Fund, MAR/ ; 001/2023/ALC//Science and Technology Development Fund, MAR/ ; },
abstract = {Damaged mitochondria initiate mitochondrial dysfunction-associated senescence, which is considered to be a critical cause for amyotrophic lateral sclerosis (ALS). Thus, mitophagic elimination of damaged mitochondria provides a promising strategy in ALS treatment. Here, through screening of a large natural compound library (n = 9555), we have identified isoginkgetin (ISO), a bioflavonoid from Ginkgo biloba, as a robust and specific mitophagy inducer. ISO enhances PINK1-Parkin-dependent mitophagy via stabilization of the PINK1/TOM complex. In a translational perspective, ISO antagonizes ALS pathology in C. elegans and mouse models; intriguingly, ISO improves mitochondrial function and antagonizes motor neuron pathologies in three ALS patient-derived induced pluripotent stem cell systems (C9, SOD1, and TDP-43), highlighting a potential broad application to ALS patients of different genetic background. At the molecular level, ISO inhibits ALS pathologies in a PINK1-Parkin-dependent manner, as depletion or inhibition of PINK1 or Parkin blunts its benefits. These results support the hypothesis that mitochondrial dysfunction is a driver of ALS pathology and that defective mitophagy is a druggable therapeutic target for ALS.},
}

@article {pmid41093062,
year = {2025},
author = {Bunick, CG and Yang, K and Jafarian, F and Barbieri, JS},
title = {Response to Veenstra et al's "Benzoyl Peroxide Acne Treatment Shows No Significant Association with Benzene-Related Cancers: A Multicenter Retrospective Analysis" on Statistical Design.},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.10.042},
pmid = {41093062},
issn = {1097-6787},
}

@article {pmid41090678,
year = {2025},
author = {Jing, W and Shan, Y and Wu, H and Li, T and Tang, H and Sun, Y and Napattharin, V and Loong, S and Qin, B and Pan, W},
title = {Integrative treatment of the motor neuron disease amyotrophic lateral sclerosis, efficacy of pharmacotherapy, traditional Chinese medicine and importance of respiratory support, life-style, and gastrostomy-assisted nutrition: A review.},
journal = {International journal of clinical pharmacology and therapeutics},
volume = {63 (Suppl. 1)},
number = {},
pages = {S14-S25},
pmid = {41090678},
issn = {0946-1965},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/etiology/physiopathology ; *Gastrostomy ; *Medicine, Chinese Traditional ; *Life Style ; *Integrative Medicine/methods ; Treatment Outcome ; },
abstract = {Currently, there are no effective treatments for amyotrophic lateral sclerosis (ALS), a chronic progressive neurodegenerative disease. Although the etiology of ALS is unknown, it is thought that factors such as diet, the environment, and lifestyle habits play a role. The pathogenesis of ALS includes alterations in glutamate neurotransmission, oxidative stress, mitochondrial dysfunction. Drugs such as riluzole, edaravone, dextromethorphan/quinidine combinations, and the administration of tofersen by injection are approved treatment options for ALS although a number of other agents are being examined in clinical trials. Despite these developments, the availability of effective treatment options is limited. This review summarizes the etiology and pathogenesis of ALS and describes treatments in detail as an integrative medicine approach and including traditional Chinese medicine together with the importance of the timing for interventions, precautions necessary for noninvasive ventilator and gastrostomy surgery, and precautions for dealing with respiratory issues with the overall aim of providing state-of-the-art clinical recommendations for the care and therapy of ALS patients.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/etiology/physiopathology
*Gastrostomy
*Medicine, Chinese Traditional
*Life Style
*Integrative Medicine/methods
Treatment Outcome

@article {pmid41088992,
year = {2025},
author = {Essa, SM and Khosa, NA and Kakar, A and Öztürk, B and Ibrahim, IA and Haq, N},
title = {Unraveling the Potential of Stem Cell Therapy in Motor Neuron Disease: A Narrative Review.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273382519250918103218},
pmid = {41088992},
issn = {1996-3181},
abstract = {Motor neuron disorders (MNDs), including ALS, are deadly neurodegenerative conditions that cause progressive motor neuron degeneration. With neuroprotection and the potential for neuron regeneration employing MSCs, ESCs, iPSCs, and NSCs, stem cell treatment presents a viable alternative to current medicines, which only control a limited number of symptoms. Following PRISMA criteria, this narrative review methodically screened 1248 records from the Cochrane, Web of Science, PubMed, and Scopus databases. Following a thorough screening process, 22 studies, including preclinical models and 19 clinical trials, were analysed to assess the therapeutic mechanisms, safety, and efficacy of stem cell therapies for MNDs. Mesenchymal stem cell (MSC) therapy has shown a promising safety profile and possible therapeutic efficacy in ALS, with no substantial transplant-related toxicity noted. ALS functional rating scale-revised (ALSFRS-R) scores and forced vital capacity (FVC) assessments from clinical trials, such as those evaluating autologous bone marrow-derived MSCs, demonstrated stabilisation in ALS development. Studies have also emphasised as to how immunomodulation and neurotrophic factors play a part in MSC-based therapies. Recent data indicate that repeated intrathecal MSC injection could extend the duration of therapeutic advantages. Clinical trials have shown safety and early efficacy signals for motor neurons produced from embryonic stem cells (ESCs), especially using AstroRx®. This suggests that ESCs could be a viable option for regenerative medicine. Nonetheless, issues, like host integration and differentiation optimisation, still exist. Although clinical translation is still in its early stages, induced pluripotent stem cells (iPSCs) and their derivatives provide disease modelling and patient-specific therapeutic applications. Stem cell therapy holds promise for treating MND, with MSCs leading the way in current trials. It is necessary to enhance ESC- and iPSC-based techniques to tackle integration issues. To ensure long-term safety and efficacy, therapies must be developed using standardised protocols, patient stratification, optimised delivery, and large-scale studies.},
}

@article {pmid41086149,
year = {2025},
author = {Clackson, O and Hamid, MR and Wijesekera, A and Kulick, D and O'Neil, AL},
title = {Exposure to the organochlorine pesticide cis-chlordane induces ALS-like mitochondrial perturbations in stem cell-derived motor neurons.},
journal = {PloS one},
volume = {20},
number = {10},
pages = {e0332422},
pmid = {41086149},
issn = {1932-6203},
mesh = {*Motor Neurons/drug effects/metabolism/pathology ; *Amyotrophic Lateral Sclerosis/pathology/metabolism/chemically induced ; *Mitochondria/drug effects/metabolism/pathology ; Humans ; Reactive Oxygen Species/metabolism ; *Pesticides/toxicity ; *Chlordan/toxicity ; Membrane Potential, Mitochondrial/drug effects ; Animals ; Adenosine Triphosphate/metabolism ; Oxygen Consumption/drug effects ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a debilitating and incurable neurodegenerative disease with unsolved etiology. Due to the large proportion of patients lacking direct disease inheritance, understanding the environmental factors that contribute to ALS development is of high priority. Epidemiological studies have implicated pesticides and other environmental exposures as possible contributors to ALS pathogenesis. Recently, our group determined that the organochlorine pesticide cis-chlordane is toxic to human motor neurons in a dose-dependent manner, causing an ALS-like phenotype in culture and animals with a mode of action independent of its known GABAA antagonism. Here, we aimed to characterize downstream motor neuron phenotypes associated with cis-chlordane treatment. We performed bulk RNA sequencing, live imaging, immunofluorescent labeling, and real-time metabolic assays on stem cell-derived motor neurons to assess chlordane-associated phenotypes in vitro. We demonstrate that cis-chlordane treatment causes a highly altered mitochondrial phenotype in motor neurons, including increased production of reactive oxygen species, decreased oxygen consumption rate and ATP production, and loss of mitochondrial membrane potential. We further implicate cis-chlordane as a possible mediator of potent motor neuron damage, with exposure to the pesticide inducing mitochondrial phenotypes akin to those seen in ALS. Our findings contribute to the growing body of evidence that future studies of investigating the role of pesticides in ALS development should focus on organochlorine molecules.},
}

*Motor Neurons/drug effects/metabolism/pathology
*Amyotrophic Lateral Sclerosis/pathology/metabolism/chemically induced
*Mitochondria/drug effects/metabolism/pathology
Humans
Reactive Oxygen Species/metabolism
*Pesticides/toxicity
*Chlordan/toxicity
Membrane Potential, Mitochondrial/drug effects
Animals
Adenosine Triphosphate/metabolism
Oxygen Consumption/drug effects

@article {pmid41083392,
year = {2025},
author = {Guo, Y and Li, CJ and Wei, H and Ding, Y and Guo, LJ and Gao, YN},
title = {[Clinical analysis of a motor neuron disease-like phenotype associated with anti-IgLON5 disease].},
journal = {Zhonghua nei ke za zhi},
volume = {64},
number = {10},
pages = {977-983},
doi = {10.3760/cma.j.cn112138-20241018-00695},
pmid = {41083392},
issn = {0578-1426},
mesh = {Humans ; Aged ; Female ; *Autoantibodies/blood ; *Motor Neuron Disease/immunology/diagnosis ; Male ; Phenotype ; *Cell Adhesion Molecules, Neuronal/immunology ; Amyotrophic Lateral Sclerosis/immunology/diagnosis ; Electromyography ; },
abstract = {We report a case of anti-IgLON5 disease with a motor neuron disease-like presentation admitted to the Department of Neurology, Xuanwu Hospital, Capital Medical University in July 2021. The patient was a 71-year-old female who presented with the chief complaint of limb weakness persisting for 4 months. She showed progressive limb weakness accompanied by muscle atrophy. Electromyography (EMG) revealed extensive neurogenic damage. Initial serum evaluation for neural-specific autoantibodies was positive for IgLON5-Ab (1∶100). Repeat testing confirmed IgLON5-Ab positivity with a titer of 1∶1 000. The patient was diagnosed with anti-IgLON5 disease and treated with methylprednisolone and immunoglobulin, leading to clinical improvement. We found four relevant articles reporting a total of 11 similar cases. Thus, in this study, we analyzed a total of 12 cases, including our patient. Based on their clinical manifestations, these cases can be categorized into two types: amyotrophic lateral sclerosis(ALS)type and isolated bulbar type. Six cases-three males and three females-presented with the ALS type. Of these, three cases had diffuse limb weakness accompanied by muscle atrophy(two cases had diffuse hyperreflexia and one had a normal tendon reflex); one case presented with neck extensor weakness and bilateral asymmetric upper extremity weakness and was hyperreflexic at the bilateral patellar tendons; one case displayed asymmetric weakness in both lower limbs with normal deep reflexes, and one case exhibited neck weakness with hyperreflexia. EMG revealed diffuse lower motor neuron disease involving two or three regions. All patients tested positive for serum anti-IgLON5 antibodies. Four were also positive for anti-IgLON5 antibodies in cerebrospinal fluid, two were negative, and six were not tested. Among the 11 patients who received immunotherapy, 4 showed partial improvement in clinical symptoms, 2 exhibited transient improvement, 2 remained stable, and 3 showed no improvement. Testing for IgLON5-Ab should be considered among patients presenting with bulbar symptoms or ALS-like features, especially those with acute or subacute onset, rapid progression, autonomic dysfunction, vocal cord paralysis requiring tracheotomy, cognitive impairment, or involuntary movements. Early diagnosis and treatment may improve clinical symptoms and reduce adverse outcomes.},
}

Humans
Aged
Female
*Autoantibodies/blood
*Motor Neuron Disease/immunology/diagnosis
Male
Phenotype
*Cell Adhesion Molecules, Neuronal/immunology
Amyotrophic Lateral Sclerosis/immunology/diagnosis
Electromyography

@article {pmid41082679,
year = {2025},
author = {Tabor Gray, L and Sullivan, S and O'Brien, M and Costello, J and Plowman, E and Garand, KLF},
title = {International Survey of Practice Patterns of Speech-Language Pathologists Working With Patients With Amyotrophic Lateral Sclerosis.},
journal = {American journal of speech-language pathology},
volume = {},
number = {},
pages = {1-12},
doi = {10.1044/2025_AJSLP-25-00064},
pmid = {41082679},
issn = {1558-9110},
abstract = {BACKGROUND: Speech-language pathologists (SLPs) evaluate and treat swallowing and communication impairments in individuals with amyotrophic lateral sclerosis (ALS). Standardized clinical practice guidelines for the evaluation and management of bulbar dysfunction in ALS have not yet been established. This study aimed to describe current international practice patterns of SLPs evaluating and treating bulbar dysfunction in ALS.

HYPOTHESIS: Significant variability in practice patterns will exist across SLPs working in different clinical settings with varied resources.

METHOD: A 26-item Qualtrics survey was electronically distributed to SLPs via e-mail, social media, and professional discussion boards.

RESULTS: Data from 245 respondents across 20 countries and 32 states within the United States were collected, with the final analysis including 214 respondents. Most respondents practiced in metropolitan areas (69%) and worked in multidisciplinary ALS clinics (41%), outpatient clinics (16%), and home health settings (17%). Cranial nerve examination (91%), swallow trials (79%), speech intelligibility tasks (85%), and diadochokinetic speech rates (65%) were frequently included in evaluations. Although 81% of clinics had access to instrumental swallowing evaluations, 32% reported performing them in fewer than 25% of patients. Communication evaluations were offered directly by 58% of clinicians, while 26% referred to an outside SLP and 16% collaborated with device representatives. Most clinicians provided patient education on swallowing (87%) and oral health (83%). However, managed practice varied widely, revealing no standardized treatment that is routinely offered. Barriers to optimal ALS care included time constraints, relevant clinical training, timing of treatment, addressing psychosocial components of care, access to resources, interdisciplinary communication, and insurance coverage (United States only).

DISCUSSION: Findings reveal little consensus on symptomatic bulbar management and intervention timing. Results emphasize the urgent need for the development of a standardized minimal data set to best guide the evaluation and management of bulbar dysfunction in ALS.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.30249997.},
}

@article {pmid41076128,
year = {2025},
author = {Chen, CC and Chen, SC},
title = {Comments on Hong et al.'s "Radiotherapy Versus Imiquimod for Complex Lentigo Maligna: a Phase 3 Randomized Clinical Trial".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.08.128},
pmid = {41076128},
issn = {1097-6787},
}

@article {pmid41075758,
year = {2025},
author = {Gery, KL and Ramos, S and Lee, JC},
title = {Correlative Raman and immunofluorescence imaging reveals different protein abundance between stress granules induced by oxidative damage.},
journal = {Journal of inorganic biochemistry},
volume = {274},
number = {},
pages = {113091},
doi = {10.1016/j.jinorgbio.2025.113091},
pmid = {41075758},
issn = {1873-3344},
abstract = {Heavy metal toxicity generates reactive oxygen species (ROS) that can contribute to neurodegeneration. Oxidative damage from exposure to metals such as sodium arsenite will activate the integrated stress response and may result in the cytosolic formation of stress granules (SGs), which have been implicated in neurodegenerative disorders such as amyotrophic lateral sclerosis. Here, two different ROS sources, sodium arsenite and hydrogen peroxide, under acute (1 h) and chronic (24 h) conditions, were used to induce SG formation in human osteosarcoma (U-2 OS) cells and investigate if characteristics of SGs could depend on the induction. Specifically, correlative Raman and immunofluorescence imaging (CRIFI) was developed to evaluate the relative protein abundance found in SGs to ascertain their potential as loci for protein accumulation. Interestingly, while there are differences in the punctate-staining phenotypes for different stressors, two types of puncta visualized by CRIFI were common to all treatment conditions, where notably a subset exhibited protein concentration above cytosolic background, indicating that only some SGs are composed of protein-rich, dense phases. Differences in protein abundance between SGs were also observed within a single cell, suggesting that individual SGs can develop differently. These results demonstrate the versatility and the strength of pairing Raman spectroscopy, which allows for probe-free detection of different chemical functional groups, with specific protein localization granted by immunofluorescence, providing new cellular insights unattainable by either modality alone.},
}

@article {pmid41074071,
year = {2025},
author = {Cole, A and Chege, T and Aman, R and Githuka, G and Muga, R and Aspinall, A and Kokwaro, G},
title = {Health system challenges and facilitators associated with adaptive cycling deployment of multiple first-line treatment for uncomplicated malaria: a pilot study in a malaria-endemic region of Kenya.},
journal = {Malaria journal},
volume = {24},
number = {1},
pages = {328},
pmid = {41074071},
issn = {1475-2875},
support = {PO20/00538//Medicines for Malaria Venture/ ; },
mesh = {Kenya ; Pilot Projects ; *Antimalarials/therapeutic use/administration & dosage ; Humans ; Artemisinins/therapeutic use ; *Malaria/drug therapy ; Female ; Adult ; Male ; Drug Combinations ; Young Adult ; Drug Therapy, Combination ; Adolescent ; Middle Aged ; Artemether, Lumefantrine Drug Combination/therapeutic use ; Amodiaquine/therapeutic use ; },
abstract = {BACKGROUND: Artemisinin-based combination therapy (ACT) has been first-line treatment for uncomplicated malaria in sub-Saharan Africa for over two decades. However, emerging artemisinin partial resistance threatens efficacy. Multiple first-line treatments (MFTs) represent a proposed mitigation strategy, though associated health systems challenges remain unknown. This study evaluated health systems challenges and facilitators for MFT implementation in western Kenya.

METHODS: A 2 year pilot study (June 2020-June 2022) implemented adaptive cycling of four artemisinin-based combinations: Artemether-Lumefantrine (AL), Dihydroartemisin-Piperaquine (DHA-PIP), Amodiaquine-Artesunate (ASAQ), and Pyronaridine-Artesunate (PYR-ART) in western Kenya. Homa Bay (implementation) and Migori (control) counties were compared. Implementation involved 8 month drug cycling on mainland and 12 month cycling on Mfangano Island, while control county continued AL throughout. Adult patients diagnosed with uncomplicated malaria were included (pregnant women and children < 5 years excluded). Health systems assessment used semi-structured questionnaires, key informant interviews, and exit interviews. Outcome measures included diagnostic kit availability, procurement logistics, information system alignment, human resources, stakeholder acceptance, and side effects. Costs were tracked using ingredient approach, and malaria cases compared between counties.

RESULTS: MFT was accepted by key stakeholders. One minor adverse effect (vomiting) was reported. Patients preferred simple once-daily dosing of new drugs over AL's complicated regimen. Major challenges included logistics inefficiencies in drug quantification and stock management, human resource constraints, information system reconfiguration needs, and frequent diagnostic kit stock-outs. Start-up and implementation costs were roughly equal. Economic cost per patient treated was USD 3, lower than reported elsewhere in sub-Saharan Africa. Digital health tools (SMS/WhatsApp) facilitated implementation through improved communication and follow-up. Migori (control) showed 12.5 percentage points higher malaria positivity rates (23.3% vs 10.8%) with better directional consistency. Testing efficiency differed markedly (4.3 vs 9.2 tests per positive case) between counties.

CONCLUSION: Adaptive cycling MFT implementation is feasible in Kenya with adequate planning and addressing health systems challenges. Stakeholder engagement and continuous training were critical for success. Policy implications and regional cooperation potential warrant exploration in other sub-Saharan African countries with different deployment contexts.},
}

Kenya
Pilot Projects
*Antimalarials/therapeutic use/administration & dosage
Humans
Artemisinins/therapeutic use
*Malaria/drug therapy
Female
Adult
Male
Drug Combinations
Young Adult
Drug Therapy, Combination
Adolescent
Middle Aged
Artemether, Lumefantrine Drug Combination/therapeutic use
Amodiaquine/therapeutic use

@article {pmid41073493,
year = {2025},
author = {Montazeri, S and Bijani, S and Rashidzadeh, H and Ramazani, A and Andalib, S and Kalantari-Hesari, A and Cheraghi, G and Hosseini, MJ},
title = {Application of edaravone-loaded nanogel in alleviating behavioral deficits and oxidative stress in schizophrenia rat model.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {35468},
pmid = {41073493},
issn = {2045-2322},
support = {4000397//National Institute for Medical Research Development/ ; },
mesh = {Animals ; *Oxidative Stress/drug effects ; *Schizophrenia/drug therapy/metabolism ; *Edaravone/administration & dosage/pharmacology ; Rats ; Disease Models, Animal ; *Nanogels/chemistry ; Male ; Glutathione/chemistry ; *Behavior, Animal/drug effects ; Rats, Sprague-Dawley ; Prefrontal Cortex/drug effects/metabolism ; },
abstract = {Schizophrenia is considered as a main one of the public health issues, and imposes numerous burdens on patients and society. We previously reported, the pathophysiology of schizophrenia is influenced by inflammation and mitochondrial dysfunction. Edaravone (EDV) as a potent antioxidant with neuroprotective traits, has been approved for the treatment of amyotrophic lateral sclerosis (ALS), effecting through neutralizing soluble/insoluble peroxyl radicals. However, the main disadvantages of EDV are its low stability in aqueous media, poor water solubility, and un-optimized bioavailability. To effectively address these obstacles, nanogel was utilized as the drug vehicle. The decoration of nanogel surface with glutathione (GSH) was carried out to elevate edaravone's brain delivery. The probable improvement in drug delivery of edaravone loaded GSH-nanogel is the main hypothesis of this study. In order to mimic schizophrenia-like behaviors, we applied two month of post-weaning social isolation stress (PWSI) to rodent model. The choice of PWSI model was made due to the maturation and development of prefrontal cortex and hippocampus during adolescence. In addition to causing oxidative stress and upregulating genes linked to innate immunity in the prefrontal cortex (PFC), the data showed that PWSI triggered schizophrenia-like behaviors in rats. This study demonstrated that treatment with edaravone loaded GSH-nanogel decreased the impact of PWSI on behavioral dysfunctions and oxidative stress in the PFC of rats. Edaravone loaded GSH-nanogel (GSH-PMAA-EDV) down-regulated Toll-like receptor 4 (Tlr-4) and AMP-activated protein kinase (Ampk) gene expression which are involved in inflammation and cellular energy homeostasis, respectively. Increase immunoreactivity feedback and Brain-derived neurotrophic factor (Bdnf) as direct impact in neurogenesis and neural cell plasticity was observed in EDV loaded GSH-nanogel treated groups. edaravone loaded GSH-nanogel (100 µg/kg) in comparison to free form of edaravone (5 mg/kg) revealed more beneficial effects, which might be useful for future clinical use especially for the treatment of schizophrenia.},
}

Animals
*Oxidative Stress/drug effects
*Schizophrenia/drug therapy/metabolism
*Edaravone/administration & dosage/pharmacology
Rats
Disease Models, Animal
*Nanogels/chemistry
Male
Glutathione/chemistry
*Behavior, Animal/drug effects
Rats, Sprague-Dawley
Prefrontal Cortex/drug effects/metabolism

@article {pmid41072581,
year = {2025},
author = {Schundler, SF and Amber, KT},
title = {Response to Cao et al.'s "Efficacy, safety, and B-cell depletion capacity of three rituximab dosing regimens in the treatment of moderate-to-severe pemphigus vulgaris and pemphigus foliaceus: a 52-week clinical trial".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.08.126},
pmid = {41072581},
issn = {1097-6787},
}

@article {pmid41066153,
year = {2025},
author = {Su, W and Zhang, C and Sun, L and Xu, H and Zhang, G and Xue, F and Leng, Q and Niu, Y and Wu, R},
title = {Multifaceted Mechanisms of Cyprosulfamide in Mitigating Mesosulfuron-Methyl Phytotoxicity in Maize Seedlings: GST Activation, Oxidative Stress Alleviation, and Target-Site Competition.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c07590},
pmid = {41066153},
issn = {1520-5118},
abstract = {Mesosulfuron-methyl (MS), a sulfonylurea herbicide used in wheat, poses significant residual phytotoxicity risks to subsequent maize (Zea mays L.) crops. This study evaluated the protective role of the safener cyprosulfamide (CSA) through physiological, biochemical, and molecular analyses. MS treatment drastically reduced maize shoot length and fresh weight by 80.74% and 74.24%, respectively, while CSA pretreatment significantly relieved these inhibitory effects, with the mitigation rates of shoot length and fresh weight reaching 66.3% and 63.57%, respectively. Physiologically, CSA alleviated MS-induced chlorophyll and carotenoid losses and reduced oxidative stress by lowering malondialdehyde (MDA) levels (23.39% at 6 days after sowing) while enhancing superoxide dismutase (SOD) and glutathione S-transferase (GST) activity. Molecularly, CSA upregulated nine GST genes, competitively bound to ZmALS1/2, increasing acetolactate synthase (ALS) activity by 70-146%, and reduced MS residues in shoots (4.02%) and roots (33.78%). These findings demonstrate CSA's multifunctional detoxification mechanism, combining gene activation, antioxidant regulation, and target-site competition, offering a viable strategy to mitigate herbicide carryover in crop rotations. CSA application could significantly reduce MS phytotoxicity, advancing sustainable herbicide management.},
}

@article {pmid41065069,
year = {2025},
author = {Shan, Y and Jing, W and Zhang, H and Liu, Y and Wei, S and Wu, F and Pan, W},
title = {Amyotrophic lateral sclerosis rehabilitation management and non-pharmacological symptomatic treatment: A review.},
journal = {International journal of clinical pharmacology and therapeutics},
volume = {},
number = {},
pages = {},
doi = {10.5414/CP204744},
pmid = {41065069},
issn = {0946-1965},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that lacks effective treatment options for the prevention of progression. Relieving swallowing difficulties, reducing breathing difficulties, and alleviating muscle spasms are essential to improving the quality of life in patients with ALS. Many symptoms can be treated clinically with medication; however, the evidence level of related research is relatively low. Rehabilitation management can aid in improving various functional impairments and enhancing quality of life. This review introduces and describes the relevant evaluations of rehabilitation and nonpharmacological symptomatic treatment methods for functional disorders from the perspectives of motor and nonmotor symptoms. This review may promote the popularization of ALS rehabilitation management and provide an additional reference for ALS treatment.},
}

@article {pmid41061670,
year = {2025},
author = {James, RE and Bekier, M and Lee, PJ and Schroeder, FA and Evans, LT and Wagner, FF and Hickman, D and Richardson, T and Hatzipetros, T and Vieira, F and Callizot, N and Modi, S and Hooker, JM and Kranz, JE and Brown, RH and Barmada, SJ and Gilbert, TM},
title = {A next-generation HDAC6 inhibitor for amyotrophic lateral sclerosis and frontotemporal dementia.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awaf380},
pmid = {41061670},
issn = {1460-2156},
abstract = {Dysregulated proteostasis and intracellular transport contribute to neurodegeneration. HDAC6, a therapeutic target of interest for neurodegenerative diseases, acts at a nexus modulating both proteostasis and intracellular transport. Inhibition of HDAC6 deacetylase activity promotes autophagic clearance of protein aggregates and increases ⍺-tubulin acetylation, thereby enhancing microtubule resiliency and motor protein-microtubule binding, which facilitates intracellular transport and, subsequently, proteostasis. Despite these benefits, advancement of HDAC6 inhibitor therapeutics for neurodegenerative disease has been hindered by inadequate selectivity and CNS-penetrance of first-generation compounds. Here we characterize a next-generation small molecule HDAC6 inhibitor, EKZ-438, in preclinical models of amyotrophic lateral sclerosis and frontotemporal dementia. We present the pharmacological properties of EKZ-438, which demonstrate high selectivity for HDAC6 (>8,500-fold selectivity for HDAC6 versus all other HDAC6 paralogs), low nanomolar potency (12 nM) for HDAC6, and, importantly, CNS-penetrance (Kp,uu,brain) ≥ 0.55 and high oral bioavailability (F% = 70). In complementary preclinical in vitro and in vivo immunolabeling and live imaging studies we tested the hypothesis that selective inhibition of HDAC6 deacetylase activity is sufficient to improve pathophysiological proteostasis and intracellular transport deficits in animal models of familial and sporadic amyotrophic lateral sclerosis and frontotemporal dementia. Notably, we extended these findings to human induced pluripotent stem cell-derived neuronal cellular models, supporting the relevance of our findings to human disease. EKZ-438 treatment fully rescued SOD1 (q < 0.0001) and TDP-43 (q < 0.001) proteostasis defects following an excitotoxic glutamate challenge, and increased survival of SOD1G93A and wildtype motor neurons by 59% (q < 0.0001) and 37% (q < 0.01), respectively, demonstrating in vitro neuroprotection. In SOD1G93A mice, EKZ-438 improved axonal transport by 16% (q < 0.05), motor performance by ∼40% (q < 0.05), and decreased plasma neurofilament light chain levels by 35% (q < 0.05), demonstrating in vivo neuroprotection. In a TDP-43 mouse model, EKZ-438 reduced TDP-43 pathology by ∼30% (q < 0.05) and neuroinflammation by ∼26% (q < 0.05) in the brain, supporting HDAC6 inhibition for sporadic amyotrophic lateral sclerosis and frontotemporal dementia. Furthermore, EKZ-438 treatment improved intracellular transport by 39% (q < 0.001), rescued cytoplasmic TDP-43 accumulation by 87% (q < 0.0001), and restored nuclear TDP-43 splicing activity (P < 0.05) in human TARDBP neurons. These mechanistic improvements aligned with nearly complete rescue of human TARDBP and C9orf72 mutant neuron survival (P < 0.0001). We conclude that selective HDAC6 inhibition represents a promising therapeutic approach for potential disease modification in amyotrophic lateral sclerosis and frontotemporal dementia.},
}

@article {pmid41058966,
year = {2024},
author = {Donohue, C and Perry, B and Focht Garand, KL},
title = {A Clinical Focus on Shared Decision Making in Clinical Practice When Providing Dysarthria and Dysphagia Services to Individuals With Amyotrophic Lateral Sclerosis.},
journal = {Perspectives of the ASHA special interest groups},
volume = {9},
number = {4},
pages = {1003-1015},
pmid = {41058966},
issn = {2381-4764},
support = {K23 NS123369/NS/NINDS NIH HHS/United States ; L30 NS123988/NS/NINDS NIH HHS/United States ; },
abstract = {PURPOSE: Traditional health care decision-making models center on clinicians making decisions for patients/caregivers based on the best available research evidence. However, this diminishes patient/caregiver involvement in their care and hinders the ability to align care plans with patient values and preferences. Shared decision making is a potentially beneficial process to implement with individuals with amyotrophic lateral sclerosis (ALS) to provide more holistic, patient-centered dysarthria and dysphagia treatment. Shared decision making promotes active involvement by patients/caregivers by informing them of potential treatment options, understanding their values and preferences, and aligning their desires with treatment options to determine the most optimal individualized care plan.

CONCLUSIONS: The benefits and barriers to incorporating shared decision making within ALS multidisciplinary clinics are discussed in this clinical focus article. Furthermore, a fictional case study example of how to apply shared decision making to dysarthria and dysphagia management of individuals with ALS is provided.},
}

@article {pmid41057909,
year = {2025},
author = {Hunter, E and Alshaker, H and Bundock, O and Weston, C and Bautista, S and Gebregzabhar, A and Virdi, A and Croxford, J and Dring, A and Powell, R and Vugrinec, D and Kingdon, C and Wilson, C and Dowrick, S and Green, J and Akoulitchev, A and Pchejetski, D},
title = {Development and validation of blood-based diagnostic biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) using EpiSwitch[®] 3-dimensional genomic regulatory immuno-genetic profiling.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {1048},
pmid = {41057909},
issn = {1479-5876},
support = {6514//Oxford BioDynamics plc, Oxford UK/ ; },
abstract = {UNLABELLED: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating, multifactorial disorder characterised by profound fatigue, post-exertional malaise, cognitive impairments, and autonomic dysfunction. Despite its significant impact on quality of life, ME/CFS lacks definitive diagnostic biomarkers, complicating diagnosis and management. Recent evidence highlights potential blood tests for ME/CFS biomarkers in immunological, genetic, metabolic, and bioenergetic domains. Chromosome conformations (CCs) are potent epigenetic regulators of gene expression and cross-tissue exosome signalling. We have previously developed an epigenetic assay, EpiSwitch[®], that employs an algorithm-based CCs analysis. Using EpiSwitch[®] technology, we have shown the presence of disease-specific CCs in peripheral blood mononuclear cells (PBMCs) of patients with amyotrophic lateral sclerosis (ALS), rheumatoid arthritis (RA), prostate and colorectal cancers, diffuse Large B-cell lymphoma and severe COVID-19. In a recent paper, we have identified a profile of systemic chromosome conformations in cancer patients reflective of the predisposition to respond to immune checkpoint inhibitors, PD-1/PD-L1 antagonists, with 85% accuracy. In this Retrospective case/control study (EPI-ME, Epigenetic Profiling Investigation in Myalgic Encephalomyelitis), we used whole blood samples retrospectively collected from n = 47 patients with severe ME/CFS and n = 61 age-matched healthy control patients to perform whole-genome 3D DNA screening for CCs correlating to ME/CFS diagnosis. We identified a 200-marker model for ME/CFS diagnosis (Episwitch[®]CFS test). First testing on the retrospective independent validation cohort demonstrated a strong systemic ME/CFS signal with a sensitivity of 92% and a specificity of 98%.Pathways analysis revealed several likely contributors to the pathology of ME/CFS, including interleukins, TNFα, neuroinflammatory pathways, toll-like receptor signalling and JAK/STAT. Comparison with pathways involved in the action of Rituximab and glatiramer acetate (Copaxone) (therapies with potential in ME/CFS treatment) identified IL2 as a shared pathway with clear patient clustering, indicating a possibility of a potential responder group for targeted treatment.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-025-07203-w.},
}

@article {pmid41055678,
year = {2025},
author = {Byrne, SM and McClelland, J and Fursland, A},
title = {The Overlooked Burden of Atypical Anorexia Nervosa: Commentary on Melville et al. (2025).},
journal = {The International journal of eating disorders},
volume = {58},
number = {10},
pages = {1907-1910},
pmid = {41055678},
issn = {1098-108X},
mesh = {Humans ; *Anorexia Nervosa/diagnosis/epidemiology ; Body Mass Index ; *Obesity/epidemiology ; Adult ; },
abstract = {Obesity and eating disorders (EDs) have historically been viewed as distinct conditions; however, emerging evidence suggests a significant overlap, particularly among individuals seeking obesity treatment. While binge-eating disorder (BED) is commonly identified in this population, restrictive EDs such as atypical anorexia nervosa (atypical AN) can go largely undetected. This paper comments on findings from Melville et al.'s systematic review of 85 studies assessing ED prevalence in adults with high Body Mass Index (BMI) seeking obesity treatment. We highlight the striking absence of atypical AN diagnoses despite substantial evidence supporting its prevalence in broader populations. We explore several reasons for this under-recognition, including the definitional ambiguities of atypical AN in the DSM-5, limitations of assessment tools that emphasize binge eating, and weight stigma that tends to mask restrictive eating as "normal" dieting. The implications are significant: failure to identify atypical AN may lead to delayed or inappropriate care and reinforce harmful stereotypes that restrictive EDs only affect underweight individuals. We argue for greater clinical vigilance, the refinement and clarification of diagnostic criteria and the development of validated tools for detecting atypical AN, particularly in higher-weight individuals. Clinicians, particularly those providing weight loss interventions, should be trained to identify restrictive eating irrespective of BMI and prioritize behaviors and psychological impairment over weight status. Recognizing atypical AN as a serious, underdiagnosed condition is critical to ensuring ethical, equitable and effective care across the weight spectrum, in both ED and weight-loss treatment settings.},
}

Humans
*Anorexia Nervosa/diagnosis/epidemiology
Body Mass Index
*Obesity/epidemiology
Adult

@article {pmid41053519,
year = {2025},
author = {Amiri, M and Afshary, H and Bezaatpour, A and Hatamikia, S and Wei, J and Boukherroub, R and Szunerits, S},
title = {A critical review on neurodegenerative biomarker diagnostics: where is the field heading to?.},
journal = {Analytical and bioanalytical chemistry},
volume = {},
number = {},
pages = {},
pmid = {41053519},
issn = {1618-2650},
abstract = {Neurodegenerative diseases (NDD), a collection of disorders with different underlying causes and clinical presentations, are recognized as a major area of concern of our society today. The most common NDD are Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Huntington's disease, each one of them being characterized by the progressive degradation of nerve cells and accumulation of misfolded and aggregated proteins in the affected brain region. Diagnosing NDD is challenging, due to the heterogeneity of the disease and the overlap of symptoms. Yet, early detection and accurate diagnosis are crucial for effective NDD management. With the emergence of disease-modifying therapies for AD, monitoring disease progression and treatment success is becoming essential. The future of NND diagnostics is focusing on developing less invasive, cost-effective strategies that enable early NDD identification and detection with improved patient outcomes. The integration of biotechnology and nanotechnology is seen as crucial for advancing the analytical science aspect of NDD. The creation of these innovative tools and methodologies is on the verge of enabling new possibilities for clinical diagnostics, but is also faced with several hurdles that will be critically evaluated.},
}

@article {pmid41051689,
year = {2025},
author = {Azam, HMH and Mumtaz, M and Rödiger, S and Schierack, P and Hussain, N and Aisha, A},
title = {MicroRNAs in neurodegenerative diseases: from molecular mechanisms to clinical biomarkers, detection methods and therapeutic strategies-advances and challenges.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {},
number = {},
pages = {},
pmid = {41051689},
issn = {1590-3478},
abstract = {Neurodegenerative diseases (NDDs) pose significant challenges in early detection and treatment due to their complex pathophysiology and heterogeneous clinical presentations. MicroRNAs (miRNAs), small noncoding RNAs that regulate gene expression, have emerged as promising diagnostic biomarkers and therapeutic targets in NDDs. Pathological examination of affected tissues reveals early synaptic dysfunction, protein misfolding, and neuroinflammation occur prior to overt clinical symptoms, highlighting the importance of sensitive diagnostics approaches in prodromal stages. This review summarizes for researchers on the role of miRNAs in NDDs by examining their diagnostic potential in biofluids such as blood and cerebrospinal fluid, and their therapeutic applicability through inhibition or replacement strategies. Literature from peer-reviewed databases was assessed with a focus on recent advances in molecular detection platforms, computational modeling of miRNA-mRNA interactions, and preclinical/clinical investigations.More than 2600 human miRNAs have been identified, collectively regulating over half of mammalian protein-coding genes. Quantitative methodologies, particularly reverse transcription quantitative PCR (RT-qPCR), enable reliable miRNA profiling, facilitating early diagnosis and prognosis of NDDs. Therapeutic strategies, including antagomirs, mimics, sponges and viral or non-viral delivery systems, show promise in modulating disease pathways. However, significant challenges remain, including variability in miRNA extraction and quantification protocols, off-target effects, delivery barriers across the blood brain barrier and limited reproducibility across studies. MiRNAs represent a class of molecular tools with potential to transform diagnostics and therapeutics in NDDs. Future research should prioritize methodological standardization, validation in large multicenter cohorts, and improved computational approaches to elucidate miRNA-mediated regulatory networks in NDDs. Replication studies and translational research are essential harnessing the the full clinical utility of miRNAs in the management of Alzheimer disease, Parkinson disease and other NDDs. Graphical Abstract.},
}

@article {pmid41042311,
year = {2025},
author = {Ouyang, C and Jin, X and Zhao, H and Chen, S and Zhao, G and Li, D and Liu, W and He, X and Wu, Y and Yang, J and An, B},
title = {Generating Broad-Spectrum Resistance to ALS-Inhibiting Herbicides in Rice by CRISPR/Cas9-Mediated NHEJ.},
journal = {Rice (New York, N.Y.)},
volume = {18},
number = {1},
pages = {86},
pmid = {41042311},
issn = {1939-8425},
support = {2020B1212060047//The Program of Guangdong Provincial Key Laboratory of New Technology in Rice Breeding/ ; 2020B1212060047//The Program of Guangdong Provincial Key Laboratory of New Technology in Rice Breeding/ ; 2020B1212060047//The Program of Guangdong Provincial Key Laboratory of New Technology in Rice Breeding/ ; 2020B1212060047//The Program of Guangdong Provincial Key Laboratory of New Technology in Rice Breeding/ ; 2020B1212060047//The Program of Guangdong Provincial Key Laboratory of New Technology in Rice Breeding/ ; 2020B1212060047//The Program of Guangdong Provincial Key Laboratory of New Technology in Rice Breeding/ ; 2020B1212060047//The Program of Guangdong Provincial Key Laboratory of New Technology in Rice Breeding/ ; 2020B1212060047//The Program of Guangdong Provincial Key Laboratory of New Technology in Rice Breeding/ ; 2020B1212060047//The Program of Guangdong Provincial Key Laboratory of New Technology in Rice Breeding/ ; NO.ZDYF2024XDNY179//Hainan Province Science and Technology Special Fund/ ; NO.ZDYF2024XDNY179//Hainan Province Science and Technology Special Fund/ ; NO.ZDYF2024XDNY179//Hainan Province Science and Technology Special Fund/ ; NO.ZDYF2024XDNY179//Hainan Province Science and Technology Special Fund/ ; },
abstract = {Herbicides are pivotal for modern agriculture, but challenges like weed resistance and crop rotation issues necessitate the development of herbicide-resistant genetic resources. This study focused on acetolactate synthase (ALS), a key enzyme targeted by numerous herbicides. Using CRISPR/Cas9-mediated non-homologous end joining (NHEJ) and combining with whole-stage selection, we induced mutations in the OsALS gene of indica rice and identified novel in-frame mutations at the P171 and S627 sites, respectively. Among them, one mutation at the P171 site, the triple mutation P171T/R172G/M174L (ALS-TM) conferred broad-spectrum resistance to Imidazolinones Pyrimidinylthiobenzoates Sulfonylaminocarbonyltriazolinones and Sulfonylureas herbicides. Compared to wild-type (WT) rice, ALS-TM showed 1153-fold higher resistance to imazethapyr (IMT) than WT based on GR50 values (The herbicide dose causing a 50% reduction in growth), with minimal growth inhibition at 10-fold IMT treatment. Enzymatic assays revealed that ALS-TM maintained catalytic efficiency while reducing herbicide binding, which validated the resistance at the protein level. Field trials showed that ALS-TM mutant retained normal agronomic traits even after IMT spraying, indicating no yield penalty. Additionally, ALS mutations were validated as effective transgenic selection markers, enabling efficient rice transformation under different selection systems. These results demonstrated that ALS-TM could also serve as a reliable tool in basic research, facilitating the selection and identification of transgenic materials in laboratory studies. This study provided a robust method for generating herbicide-resistant rice germplasm and highlighted the potential of CRISPR-mediated NHEJ for creating novel resistant mutations.},
}

@article {pmid39605372,
year = {2025},
author = {Kumaresan, V and Hung, CY and Hermann, BP and Seshu, J},
title = {Role of Dual Specificity Phosphatase 1 (DUSP1) in influencing inflammatory pathways in macrophages modulated by Borrelia burgdorferi lipoproteins.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.11.20.624562},
pmid = {39605372},
issn = {2692-8205},
support = {G12 MD007591/MD/NIMHD NIH HHS/United States ; R01 AI135005/AI/NIAID NIH HHS/United States ; R21 AI149263/AI/NIAID NIH HHS/United States ; U19 AI166761/AI/NIAID NIH HHS/United States ; },
abstract = {UNLABELLED: Borrelia burgdorferi (Bb) , the spirochetal agent of Lyme disease, has a large array of lipoproteins that play a significant role in mediating host-pathogen interactions within ticks and vertebrates. Although there is substantial information on the effects of B. burgdorferi lipoproteins (Bb LP) on immune modulatory pathways, the application of multi-omics methodologies to decode the transcriptional and proteomic patterns associated with host cell responses induced by lipoproteins in murine bone marrow-derived macrophages (BMDMs) has identified additional effectors and pathways. S ingle- c ell RNA-Seq (scRNA-Seq) performed on BMDMs treated with various concentrations of borrelial lipoproteins revealed macrophage subsets within the BMDMs. Differential expression analysis showed that genes encoding various receptors, type I IFN-stimulated genes, signaling chemokines, and mitochondrial genes are altered in BMDMs in response to lipoproteins. Unbiased proteomics analysis of lysates of BMDMs treated with lipoproteins corroborated several of these findings. Notably, du al s pecificity p hosphatase 1 (Dusp1) gene was upregulated during the early stages of BMDM exposure to Bb LP. Pre-treatment with benzylidene-3-cyclohexylamino-1-indanone hydrochloride (BCI), an inhibitor of both DUSP1 and 6 prior to exposure to Bb LP, demonstrated that DUSP1 negatively regulates NLRP3-mediated pro-inflammatory signaling and positively regulates the expression of interferon-stimulated genes and those encoding Ccl5 , Il1b , and Cd274 . Moreover, DUSP1, IkB kinase complex and MyD88 also modulate mitochondrial changes in BMDMs treated with borrelial lipoproteins. These findings advance the potential for exploiting DUSP1 as a therapeutic target to regulate host responses in reservoir hosts to limit survival of B. burgdorferi during its infectious cycle between ticks and mammalian hosts.

IMPORTANCE: Borrelia burgdorferi , the agent of Lyme disease, encodes numerous lipoproteins that play a crucial role as a pathogen associated molecular pattern affecting interactions with tick- and vertebrate-host cells. Single cell transcriptomics validated using unbiased proteomics and conventional molecular biology approaches have demonstrated significant differences in gene expression patterns in a dose- and time-dependent manner following treatment of murine bone marrow derived macrophages with borrelial lipoproteins. Distinct populations of macrophages, alterations in immune signaling pathways, cellular energy production and mitochondrial responses were identified and validated using primary murine macrophages and human reporter cell lines. Notably, the role of Dual Specificity Phosphatase 1 (DUSP1) in influencing several inflammatory, metabolic and mitochondrial responses of macrophages were observed in these studies using known pharmacological inhibitors. Significant outcomes include novel strategies to interfere with immunomodulatory and survival capabilities of B. burgdorferi in reservoir hosts affecting its natural infectious life cycle between ticks and vertebrate hosts.},
}

@article {pmid41041029,
year = {2024},
author = {Zareei, A and Razeghinejad, R and Talebnejad, MR and Khalili, MR and Masoumpour, MS and Shayan, Z and Mahdaviazad, H and Keshtkar, M and Mohammadi, E and Tajbakhsh, Z and Shahmohammadi, M and Nowroozzadeh, MH},
title = {Macular Sublayer Thickness in Healthy Iranian Children: An Optical Coherence Tomography Study from the Population-Based Shiraz Pediatric Eye Study.},
journal = {Journal of current ophthalmology},
volume = {36},
number = {4},
pages = {393-399},
pmid = {41041029},
issn = {2452-2325},
abstract = {PURPOSE: To establish normative values for macular sublayer thickness in healthy Iranian children using optical coherence tomography (OCT) and to assess the effects of age and gender.

METHODS: This study was part of the population-based Shiraz pediatric eye study. Of 2400 children aged 6-12 years invited, 480 were randomly selected for optical biometry and macular spectral-domain OCT (SD-OCT) imaging. Finally, 431 OCT scans from children with medium axial length (AL; 21.5-26.5 mm) were analyzed. The OCT device automatically segmented seven retinal sublayers, and their thickness was measured across Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. Thickness in the central 1-mm subfield was assessed by gender and age groups (6-9 vs. 10-12 years), adjusted for AL. Regression analysis examined the impact of age, sex, and AL on retinal sublayer thickness. Only data from the right eye were used.

RESULTS: The mean age of participants was 9.12 ± 1.59 years (range, 6-12), with 254 (58.9%) being girls. The mean AL was 22.91 ± 0.71 mm, and the mean foveal thickness was 258 ± 8 µm. A normative database was created for the total retinal thickness and the seven retinal sublayers across the nine ETDRS subfields. Boys had longer globes (by approximately 0.4 mm; P < 0.001) and thicker foveae (by about 5 µm; P = 0.001) compared to girls. Among the seven sublayers studied, boys had a thicker ganglion cell complex layer (P = 0.014) and outer nuclear layer (ONL; P = 0.012), while girls had a thicker retinal pigment epithelium (RPE; P = 0.029). The inner nuclear layer and outer plexiform layer showed no significant differences (P = 0.075 and P = 0.810, respectively). The mean AL was 22.78 ± 0.68 mm in the 6-9 age group and 23.10 ± 0.72 mm in the 10-12 age group (P < 0.001). The older age group (10-12 years) exhibited thicker ONL (P = 0.009) and RPE (P = 0.002) layers compared to the younger group.

CONCLUSIONS: This study provides normative data for macular sublayer thickness in Iranian children aged 6-12 years using Heidelberg SD-OCT. Boys had longer ALs and thicker maculae, while girls had a thicker RPE layer. Older children had longer globes and thicker retinas, mainly due to increased ONL and RPE thickness.},
}

@article {pmid41040684,
year = {2025},
author = {Kwan, JY and Lantz, CI and Korobeynikov, VA and Snyder, A and Huang, X and Haselhuhn, T and Dore, KN and Madruga, A and Danielian, LE and Schindler, AB and Chia, R and Rasheed, M and Crook, J and Szabo, M and Portley, M and Sherer, CM and King, MC and Huang, TH and Kosa, P and Bielekova, B and Ward, ME and Grunseich, C and Shneider, NA and Traynor, BJ and Narendra, DP},
title = {Clinical, neuropathological, and biochemical characterization of ALS in a large CHCHD10 R15L family.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.09.22.25335938},
pmid = {41040684},
abstract = {Familial forms of ALS are potential candidates for gene-directed therapies, but many recently identified genes remain poorly characterized. Here, we provide a comprehensive clinical, neuropathological, and biochemical description of fALS caused by the heterozygous p.R15L missense mutation in the gene CHCHD10. Using a cross-sectional study design, we evaluate five affected and nine unaffected individuals from a large seven-generation pedigree with at least 68 affected members. The pedigree suggests a high (68 - 81%) but incomplete disease penetrance. Through cloning of the disease-allele from distant members of the family, we establish the disease haplotype in the family. Notably, the haplotype was distinct from that of a previously reported p.R15L mutation carrier with ALS, demonstrating that the variant is in a mutational hotspot. The clinical presentation was notable for being highly stereotyped; all affected individuals presented with the rare ALS variant Flail Arm Syndrome (FAS; also known as, brachial amyotrophic diplegia or Vulpian-Bernhardt Syndrome), suggesting greater involvement of the cervical spinal cord. Consistently, neuropathology from one family member demonstrated substantially increased CHCHD10 protein aggregation and neuronal loss (though absent TDP-43 pathology) in the cervical vs. lumbar spinal cord. This FAS phenotype could be captured by a simple timed finger tapping task, suggesting potential utility for this task as a clinical biomarker. Additionally, through analysis of fibroblast lines from 12 mutation carriers, isogenic iPSC cells, and a knockin mouse model, we determined that CHCHD10 with the R15L variant is stably expressed and retains substantial function both in cultured cells and in vivo , in contrast to prior reports. Conversely, we find loss of function (LoF) variants are more common in the population but are not associated with a highly penetrant form of ALS in the UK Biobank (31 in controls; 0 in cases). Together, this argues against LoF and in favor of toxic gain-of-function as the mechanism of disease pathogenesis, similar to the myopathy-causing variants in CHCHD10 (p.G58R and p.S59L). Finally, through proteomic analysis of CSF of variant carriers, we identify that CHCHD10 protein levels are elevated approximately 2-fold in mutation carriers, and that affected and unaffected individuals are differentiated by elevation of two neurofilaments: neurofilament light chain (NfL) and Peripherin (PRPH). Collectively, our findings help set the stage for gene-directed therapy for a devasting form of fALS, by establishing the likely disease mechanism and identifying clinical and fluid biomarkers for target engagement and treatment response.},
}

@article {pmid41036176,
year = {2025},
author = {Toro, CA and Zhao, W and Garcia Silva, P and Retamal-Santibáñez, D and Rojas, F and Pan, J and Johnson, N and Duarte, Y and Cardozo, CP and Sáez, JC and van Zundert, B},
title = {Boldine as a neuroprotective agent against motor neuron degeneration in models of amyotrophic lateral sclerosis.},
journal = {Frontiers in cellular neuroscience},
volume = {19},
number = {},
pages = {1640590},
pmid = {41036176},
issn = {1662-5102},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron loss. Current FDA-approved treatments offer only modest benefits. Connexins (Cx), proteins that mediate intercellular communication have emerged as potential therapeutic targets, with increased Cx hemichannel (HC) activity observed in ALS models, and blocking Cx HC activity prevents motor neuron loss in vitro. Boldine, a natural compound with both Cx HC-blocking and antioxidant properties, has shown neuroprotective potential. This study investigated boldine's effects in ALS models. In vitro, spinal cord cell cultures exposed to conditioned media from mutant SOD1[G93A] astrocytes showed a 50% reduction in motor neuron survival, elevated Cx HC activity, and increased reactive oxygen species (ROS). Boldine treatment significantly reduced Cx HC activity and ROS, and increased motor neuron viability. In vivo, oral boldine was well-tolerated in male mutant SOD1[G93A] mice starting at 7 weeks of age. Mice receiving 50 mg/kg/day showed a median survival increase of 9 days (132 vs. 123 days), though not statistically significant. Functional assessments revealed delayed disease progression: in the horizontal ladder rung walk test, boldine-treated mice exhibited a 36.8% reduction in crossing time and 21.2% fewer stepping errors. Improved scores were also observed on the Basso Mouse Scale at later stages, indicating preserved locomotor function. However, boldine had no significant effect in the rotarod test. These results support boldine's neuroprotective effects in ALS, particularly in fine motor coordination and locomotor performance. Its reduction of Cx HC activity and oxidative stress highlights boldine's promise as a potential therapeutic candidate for ALS.},
}

@article {pmid41035727,
year = {2025},
author = {Wanner, GK and Dworkin, M and Rosenbaum, RA},
title = {Statewide Prehospital Buprenorphine in Delaware: Two-Years of Paramedic-Initiated Medication for Opioid Use Disorder After Overdose.},
journal = {Delaware journal of public health},
volume = {11},
number = {3},
pages = {24-28},
pmid = {41035727},
issn = {2639-6378},
abstract = {The Delaware Division of Public Health, Office of Emergency Medical Services (EMS) implemented the first statewide program enabling paramedics throughout the state to initiate buprenorphine treatment for opioid use disorder (OUD) in the prehospital setting. Building on a model from Camden, New Jersey, this protocol was approved in 2022 in response to rising overdose deaths and was fully implemented across Delaware's advanced life support (ALS) EMS agencies in April 2023. Eligible patients-those 18 years or older, resuscitated with naloxone, and able to consent-received up to 24 mg of sublingual buprenorphine along with ondansetron for nausea. Between April 2023 and May 2025, paramedics administered 118 buprenorphine doses to 105 patients, with improvement in withdrawal symptoms reported after 63.6% of doses. Despite a rise in patient ineligibility due to altered mental status-likely linked to sedating adulterants,such as xylazine and medetomidine,in regional street drugs-paramedics increased the percentage of eligible patients accepting offered buprenorphine from 19.0% to 22.8% between the first and second year of the program. This protocol not only addresses acute overdose management in the field but also connects patients to ongoing care, aiming to reduce mortality and expand access to medications for opioid use disorder.},
}

@article {pmid41032491,
year = {2025},
author = {Burkhill, L and Davies, TM},
title = {A case study exploring the management of dyspnoea in motor neurone disease.},
journal = {British journal of community nursing},
volume = {30},
number = {10},
pages = {488-492},
doi = {10.12968/bjcn.2025.0023},
pmid = {41032491},
issn = {1462-4753},
mesh = {Humans ; *Dyspnea/etiology/therapy/nursing ; Male ; *Amyotrophic Lateral Sclerosis/complications/nursing ; *Motor Neuron Disease/complications ; United Kingdom ; Quality of Life ; Analgesics, Opioid/therapeutic use ; Middle Aged ; Aged ; },
abstract = {Motor neurone disease affects around 5000 people in the UK at any given time. It is a progressive disease with a poor prognosis and carries a high symptom burden. Dyspnoea (breathlessness) is one of its most challenging yet common symptoms and occurs because of a weakening of the muscles that control breathing. This case study explores the management of a man diagnosed with amyotrophic lateral sclerosis in the community. His advance decision to refuse treatment directive to avoid non-invasive ventilation during the day was managed through a combination of opioid medication, breath stacking, positioning and other strategies recommended by the National Institute for Health and Care Excellence. Individualised care planning and maintaining quality of life was key in his management.},
}

Humans
*Dyspnea/etiology/therapy/nursing
Male
*Amyotrophic Lateral Sclerosis/complications/nursing
*Motor Neuron Disease/complications
United Kingdom
Quality of Life
Analgesics, Opioid/therapeutic use
Middle Aged
Aged

@article {pmid41030970,
year = {2025},
author = {Peethambaran Mallika, A and Yu, JG and Sitzman, O and Baghel, MS and Renganathan, S and Sinha, IR and Melnikova, T and Ling, JP and Wong, PC},
title = {Symptomatic treatment by a BBB-permeable AAV engineered to restore TDP-43 function slows motor neuron disease and prevents paralysis.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.08.14.670400},
pmid = {41030970},
issn = {2692-8205},
abstract = {TAR DNA-binding protein 43kDa (TDP-43) dysfunction is an early pathogenic mechanism that underlies amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disorder that lacks disease modifying therapies. We previously developed a mouse model in which TDP-43 is selectively deleted from motor neurons (ChAT-Cre;Tardbp [f/f]) that mimics the early stages of ALS. Here, we demonstrate that intravenous delivery of a blood-brain-barrier (BBB) permeable AAV capsid expressing our rationally designed splicing repressor CTR (AAV-PHP.eB-CTR) in symptomatic ChAT-Cre;Tardbp [f/f] mice markedly slowed disease progression and prevented paralysis. Systemic delivery of AAV-PHP.eB-CTR led to transduction of ∼80% of spinal motor neurons, repression of TDP-43-associated cryptic exons within motor neurons expressing CTR, and attenuation of motor neuron loss. Notably, the addition of the TARDBP 3'UTR autoregulatory element to CTR maintained its expression within a physiological range. In control littermates that received AAV-PHP.eB-CTR and were monitored for >20 months, grip strength and body weight remained normal, and no histopathological abnormalities were observed, underscoring a favorable safety profile for this gene therapy. These results provide preclinical proof-of-concept that BBB-crossing AAV delivery of CTR can rescue motor neuron disease through the restoration of TDP-43 function, offering a promising mechanism-based therapeutic strategy for ALS.},
}

@article {pmid41028829,
year = {2025},
author = {Jiang, Q and Yang, D and Jiang, R and Wan, S and Wu, M and Xu, D and Zhou, J},
title = {Analysis of factors influencing sleep disorders in patients with amyotrophic lateral sclerosis.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {34104},
pmid = {41028829},
issn = {2045-2322},
support = {2025AFD532//Hubei Provincial Natural Science Foundation (Joint Fund)/ ; 2024AFD279//Hubei Provincial Natural Science Foundation (Joint Fund)/ ; 2023AFD128//Hubei Provincial Natural Science Foundation (Joint Fund)/ ; GZY-KJS-2025-008//Science and Technology Special Project of State Administration of Traditional Chinese Medicine/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/physiopathology ; Male ; Female ; Middle Aged ; *Sleep Wake Disorders/etiology/epidemiology/complications ; Cross-Sectional Studies ; Aged ; Fatigue/complications ; Adult ; Sleep Quality ; Anxiety/complications ; Disease Progression ; Pain ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease frequently accompanied by sleep disorders. Conventional insomnia interventions are often unsuitable for ALS patients due to cognitive and respiratory impairments. There is a lack of targeted studies addressing sleep-related issues using multifactorial analyses specific to this group. This cross-sectional study included 266 ALS patients at the Motor Neuron Disease Rehabilitation and Treatment Center of Hubei Provincial Hospital of Traditional Chinese Medicine. Participants were evaluated using tools like the Pittsburgh Sleep Quality Index (PSQI) and ALS Functional Rating Scale-Revised (ALSFRS-R). Regression models identified factors affecting sleep disorders and quality. Patients with sleep disorders were more likely to have non-motor symptoms like anxiety, depression, pain, and excessive daytime sleepiness compared to those without. Fatigue severity and anxiety levels were identified as independent influencing factors of sleep disorders. Additionally, fatigue, anxiety, pain intensity, and disease progression rate were significantly linked to sleep quality. This study is the first comprehensive analysis of sleep-related factors in Chinese ALS patients, highlighting the crucial roles of fatigue, anxiety, pain, and disease progression rate. It provides a basis for future personalized, non-pharmacological interventions tailored to the specific needs of ALS patients.},
}

Humans
*Amyotrophic Lateral Sclerosis/complications/physiopathology
Male
Female
Middle Aged
*Sleep Wake Disorders/etiology/epidemiology/complications
Cross-Sectional Studies
Aged
Fatigue/complications
Adult
Sleep Quality
Anxiety/complications
Disease Progression
Pain

@article {pmid41028049,
year = {2025},
author = {Spiteri, AG and Steele, JR and Lee, HC and Zhang, H and Sun, J and Schittenhelm, RB and Yu, CH and McLean, C and Masters, CL and Goudey, B and Jin, L and Pan, Y},
title = {Proteomic analysis of brain and spinal cord tissue reveals distinct immune and mitochondrial processes between human and mouse ALS models.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {33959},
pmid = {41028049},
issn = {2045-2322},
support = {GNT2007912//National Health and Medical Research Council/ ; GNT2022203//NHMRC-AMED 2022 Dementia Collaborative Research/ ; AARF1020292//Alzheimer's Association grant/ ; },
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/immunology/pathology/genetics ; *Spinal Cord/metabolism/pathology/immunology ; Humans ; Disease Models, Animal ; Mice ; *Proteomics/methods ; *Mitochondria/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Mice, Transgenic ; *Brain/metabolism/pathology/immunology ; *Proteome ; Motor Neurons/metabolism ; Male ; Female ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease resulting in the progressive loss of motor neurons in the brain and spine. More than 95% of cases are pathologically characterized by the cytoplasmic accumulation of hyperphosphorylated and ubiquitinated transactive response DNA-binding protein 43 (TDP-43). Multiple mouse models with TDP-43 accumulation have been developed, however, whether they recapitulate molecular features of ALS pathology is unclear. Given the lack of curative treatment for ALS, there is an urgent need to identify the precise biological processes contributing to disease pathogenesis for the development of effective therapeutic treatments. Thus, in this study we employed label-based untargeted proteomics to characterize the ALS proteome and related biological processes in the spinal cord and brain of TDP-43[Q331K] mice, a transgenic mouse model of ALS and the motor cortex and the cervical, thoracic, and lumbar spinal cord regions from humans. In humans, we observed highly overlapping responses across the four tissues examined, primarily related to the upregulation of immune processes and the downregulation of mitochondrial function. In contrast, TDP-43[Q331K] mice demonstrate a lack of enrichment for immune activation and the opposite regulation of mitochondrial processes. A meta-analysis of previously published mouse datasets identified the Ubqln2 knock-out mouse model as showing stronger parallels with our late-stage human ALS. Overall, this study provides in-depth analysis of the site-specific dysregulated proteomes and their associated functional processes across species. Thereby, identifying potential therapeutic targets while emphasizing the limitations of specific mouse models at certain timepoints in recapitulating ALS-related processes for future model development.},
}

Animals
*Amyotrophic Lateral Sclerosis/metabolism/immunology/pathology/genetics
*Spinal Cord/metabolism/pathology/immunology
Humans
Disease Models, Animal
Mice
*Proteomics/methods
*Mitochondria/metabolism
DNA-Binding Proteins/genetics/metabolism
Mice, Transgenic
*Brain/metabolism/pathology/immunology
*Proteome
Motor Neurons/metabolism
Male
Female

@article {pmid41026411,
year = {2025},
author = {Eraslan, A and Kose, O},
title = {Prevalence and patterns of adductor lesions on MRI in athletes with osteitis pubis.},
journal = {Journal of orthopaedics and traumatology : official journal of the Italian Society of Orthopaedics and Traumatology},
volume = {26},
number = {1},
pages = {65},
pmid = {41026411},
issn = {1590-9999},
mesh = {Humans ; Male ; Adult ; *Osteitis/diagnostic imaging/epidemiology ; Retrospective Studies ; Cross-Sectional Studies ; *Magnetic Resonance Imaging ; Adolescent ; Prevalence ; Young Adult ; Middle Aged ; *Athletic Injuries/diagnostic imaging/epidemiology ; Athletes ; Tendinopathy/diagnostic imaging/epidemiology ; *Tendon Injuries/diagnostic imaging/epidemiology ; },
abstract = {PURPOSE: Adductor lesions (ALs) frequently coexist with osteitis pubis (OP) in athletes, yet the prevalence and clinical impact of different AL types have not been comprehensively evaluated. This study aimed to determine the frequency of various AL types using magnetic resonance imaging (MRI) and to investigate their association with clinical outcomes in athletes with OP.

MATERIALS AND METHODS: This retrospective cross-sectional study included male athletes aged 18-45 years with MRI-confirmed OP. ALs were classified into four types on the basis of MRI: type 1 (strain), type 2 (tendon avulsion), type 3 (tendinopathy), and type 4 (secondary cleft sign). Types 1-2 were considered acute, and types 3-4 chronic lesions. The relationships between AL types, age, symptom side, return to sport (RTS), and hip outcome score (HOS) were analyzed.

RESULTS: Among 132 athletes with OP, 90% had concurrent AL, while 10% had isolated OP. Type 3 AL was the most frequent type (77.3%), followed by type 4 (23.5%), type 1 (15.9%), and type 2 (2.3%). Logistic regression revealed that type 3 was more likely to be found in younger athletes, while types 1 and 4 were found in older athletes. Although 95% of athletes had bilateral OP, 72% reported unilateral symptoms. The symptom side showed better consistency with the AL side than the OP side (Cohen's kappa = 0.489 versus 0.057). All athletes were treated conservatively, 50 chronic AL cases were applied also injection (31 corticosteroid-CS, 19 platelet reach plasma-PRP). Athletes with isolated OP achieved a higher RTS rate than those with AL (100% versus 75%, p = 0.033). RTS rates were higher in acute AL cases than in chronic cases (91% versus 72%) and in CS injections than in PRP injections (80% versus 63%), but without statistical significance. HOS scores were comparable across groups.

CONCLUSIONS: Adductor lesions, particularly chronic types, are highly prevalent in athletes with OP. While age influences the type of AL, the symptom side is compatible with the AL side, regardless of the type. RTS rates are more satisfactory in isolated OP and acute AL cases, but chronic AL cases were less successful in RTS outcomes despite injection treatments. These findings underscore the importance of identifying and classifying ALs for prognosis and treatment strategy in athletic groin pain.

LEVEL OF EVIDENCE: level IV, retrospective cohort study.},
}

Humans
Male
Adult
*Osteitis/diagnostic imaging/epidemiology
Retrospective Studies
Cross-Sectional Studies
*Magnetic Resonance Imaging
Adolescent
Prevalence
Young Adult
Middle Aged
*Athletic Injuries/diagnostic imaging/epidemiology
Athletes
Tendinopathy/diagnostic imaging/epidemiology
*Tendon Injuries/diagnostic imaging/epidemiology

@article {pmid41023992,
year = {2025},
author = {Nehring, C and Kaifie, A and Reddy, A and Willis, M and Schlumberger, F and Chaudhuri, N and Fastenau, A},
title = {Barriers to seeking healthcare services and contributing factors to grade 2 disability among women affected by leprosy in Telangana, India - a qualitative study.},
journal = {International journal for equity in health},
volume = {24},
number = {1},
pages = {240},
pmid = {41023992},
issn = {1475-9276},
abstract = {BACKGROUND: Leprosy, a neglected tropical disease, remains a significant global health issue, with India accounting for nearly 60% of cases in 2022. Untreated Leprosy can result in irreversible disabilities and lead to social stigma, significantly affecting the lives of patients and their families. This study explores the barriers faced by women with leprosy in accessing healthcare and other factors that contributed to the development of Grade 2 disability in India.

METHODS: Qualitative data were gathered through 20 interviews with women affected by leprosy at the Sivananda Rehabilitation Home, a leprosy clinic in Hyderabad, India. An interview guide was developed to conduct semi-structured interviews, specifically regarding the time between the onset of symptoms, diagnosis, and treatment start. An inductive analysis followed by the application of Levesque et al.’s framework was undertaken to identify themes and patterns in the participants’ experiences with the disease and treatment.

RESULTS: Six key themes were identified. The social environment plays a pivotal role in disease progression, with participants often prioritising societal expectations over their own health, such as being good wives and mothers. Stigmatisation led to social isolation, as many women avoided contact outside their families to hide deformities. Most participants visited several healthcare facilities before receiving a diagnosis, facing financial and emotional burdens. Communication gaps were evident both within healthcare facilities - where companions were sometimes informed before the patient – and in their social environments. Finally, individual factors such as lack of knowledge, awareness, and trust in medical advice also contributed to care-seeking delays.

CONCLUSIONS: This study highlights significant gaps in healthcare access for women with leprosy in India. Family dynamics, societal roles, and stigma delay care, while physical and emotional burdens add to challenges. Communication gaps and limited awareness further reinforce neglect and mistrust. Addressing these barriers is crucial for effective policy and program implementation to reduce the burden of leprosy among women.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12939-025-02642-9.},
}

@article {pmid41021147,
year = {2025},
author = {Xie, X and Wu, P and Wen, T and Jia, R and Zhang, R and Hu, F and Jin, J and Qin, X and Chen, QY},
title = {Iron and Ferritin Dyshomeostasis Intersect with Sex, Age, and Disease Severity in Amyotrophic Lateral Sclerosis.},
journal = {Journal of molecular neuroscience : MN},
volume = {75},
number = {4},
pages = {127},
pmid = {41021147},
issn = {1559-1166},
support = {82302973//National Natural Science Foundation of China/ ; YX6J010//Xi'an Jiaotong University "Young Talent Support Plan"/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood ; Male ; Female ; Middle Aged ; *Iron/blood ; *Ferritins/blood ; Aged ; Adult ; Homeostasis ; Sex Factors ; Age Factors ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, characterized by progressive loss of motor neurons. Due to heterogeneity in both cause and clinical phenotype, accuracy of diagnosis and efficacy of treatment remain challenging. An evolving body of evidence point to the importance of the "gene-time-environment" hypothesis in ALS onset and progression. Despite extensive research, understanding of the complex environmental risk factors remains fragmented. In this study, we comprehensively analyzed the associations between trace elements, biochemical signatures, and modifiable risk factors among ALS patients stratified by age, sex, type of onset, disease severity, and progression. Specifically, we investigated blood concentrations of cadmium (Cd), lead (Pb), copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), and iron (Fe) levels in 121 participants. Moreover, we examined the associations between trace metals, biochemical indicators including serum ferritin (SF), blood glucose, cholesterol (CHOL), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), cerebrospinal fluid (CSF) cell count, CSF total protein, as well as history of hypertension, hazardous chemical exposure, drinking, and smoking in ALS patients. Specifically, we report that high Fe levels were found in male and spinal-onset patients. Moreover, high serum ferritin was positively associated with age of onset, blood iron and glucose, as well as high disease severity. Results from this study highlight the complex characteristics of ALS and provide new insight for understanding the intricate relationship between disease phenotype, metal homeostasis, and modifiable risk factors.},
}

Humans
*Amyotrophic Lateral Sclerosis/blood
Male
Female
Middle Aged
*Iron/blood
*Ferritins/blood
Aged
Adult
Homeostasis
Sex Factors
Age Factors

@article {pmid41018945,
year = {2025},
author = {Vucic, S and Shahrizaila, N and Kano, O and Menon, P and Agustini, S and Kulkantrakorn, K and Atchayaram, N and Lee, YC and Prado, MB and Ng, KWP and Chai, J and Son, B and Talman, P and Nghia, HTT and Tuan, LTQ and Shibuya, K and Izumi, Y and Atsuta, N and Henderson, RD and Cui, L and Liu, M and Ohnmar, O and Rabani, R and Hong, YH and Sung, JJ and Fan, D and Raykar, V and Kuwabara, S and Kim, SH and Sobue, G and Kiernan, MC},
title = {Pan-Asian consortium for treatment and research in ALS (PACTALS) guidelines for management of amyotrophic lateral sclerosis.},
journal = {The Lancet regional health. Western Pacific},
volume = {62},
number = {},
pages = {101684},
pmid = {41018945},
issn = {2666-6065},
abstract = {The Pan-Asian Consortium for Treatment and Research in ALS (PACTALS) guidelines were developed for the management of amyotrophic lateral sclerosis (ALS) patients living in the Asia-Pacific countries, taking into consideration the ethnic, racial and economic diversity of the region. The majority of patients reside in low-income (limited-resource setting) and middle-income countries. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was utilised for development of the PACTALS management guidelines. Nine broad research questions, divided into sections, were addressed. Evidence was derived from existing Cochrane reviews, systematic reviews, meta-analysis, and randomized controlled trials (RCT) along with consensus when evidence was limited. Recommendations were provided for diagnostic pathways, use of disease modifying therapies, appropriateness of multidisciplinary care models, management of respiratory dysfunction, communication and nutrition, addressing symptoms that affect the quality of life, managing cognitive, behavioural and emotional symptoms as well as appropriate implementation of palliative care services and addressing end-of-life issues. The PACTALS guidelines provide a much-needed framework for the management of ALS patients living in the Asia-Pacific region. The management guidelines will be updated as the treatment landscape evolves and evidence of novel management approaches becomes available.},
}

@article {pmid41017705,
year = {2025},
author = {Wang, H and Wei, Y and Wang, J and Liu, J and Ou, S and Wang, J},
title = {Structure and function of voltage-gated sodium channel Nav1.6: Involvement in the pathological process of neural injury.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00354},
pmid = {41017705},
issn = {1673-5374},
abstract = {The voltage-gated sodium channel Nav1.6, encoded by the sodium voltage-gated channel alpha subunit 8 gene, is a crucial regulator of neuronal excitability, with widespread expression throughout the central and peripheral nervous systems. Recent breakthroughs in structural biology, particularly the elucidation of the cryo-EM architecture of Nav1.6 at a resolution of 0.31 nm, have provided unprecedented insights into its molecular organization and functional modulation. As a key mediator of action potential initiation and propagation, Nav1.6 possesses unique biophysical properties, including persistent and resurgent sodium currents that critically influence neuronal firing patterns. This comprehensive review synthesizes current knowledge on the physiological functions and pathological roles of Nav1.6 in multiple neurological conditions. Key findings include the following: (1) Epilepsy studies reveal more than 250 sodium voltage-gated channel alpha subunit 8 mutations with distinct genotype-phenotype correlations, where gain-of-function variants lead to severe epileptic encephalopathies, while loss-of-function variants are associated with generalized epilepsy, highlighting the potential of Nav1.6-selective blockers such as XEN901 and GS967. (2) In Alzheimer's disease, Nav1.6 mediates amyloid-β oligomer-induced neuronal hyperexcitability through amyloid precursor protein-dependent membrane trafficking and regulates beta-secretase 1 expression via nuclear factor of activated T cells 1 signaling, suggesting novel disease-modifying strategies. (3) Parkinson's disease research has demonstrated that Nav1.6 upregulation in reactive astrocytes in the globus pallidus contributes to motor deficits through calcium-mediated abnormalities in neuronal synchronization. (4) Amyotrophic lateral sclerosis involves Nav1.6-dependent cortical hyperexcitability preceding motor neuron degeneration, with riluzole showing partial efficacy through sodium current modulation. (5) Multiple sclerosis pathophysiology features Nav1.6 redistribution in demyelinated axons, which drives calcium-dependent axonal injury via reverse Na+/Ca2+ exchange. (6) Chronic pain mechanisms involve Nav1.6 overexpression in dorsal root ganglia neurons, regulated by the p38 mitogen-activated protein kinase and tumor necrosis factor-α signaling pathways. (7) Traumatic brain injury models show that exercise-induced cognitive improvement is correlated with the normalization of Nav1.6-mediated excitability. Therapeutic development has progressed from nonselective sodium channel blockers to precision approaches, including state-dependent pore blockers designed using structural insights; allosteric modulators targeting specific conformations; gene therapy strategies using clustered regularly interspaced short palindromic repeats and antisense oligonucleotides; and miRNA-based regulation of channel expression. Current challenges include achieving sufficient subtype selectivity, optimizing blood-brain barrier penetration, and developing clinically relevant biomarkers for patient stratification. Future directions emphasize the integration of advanced technologies-such as singlecell multiomics to map neuronal subtype-specific expression patterns, patient-derived organoids for personalized drug testing, and machine learning-assisted drug design-to accelerate translation. Large-scale collaborative efforts will be essential to validate therapeutic candidates and establish genotype-guided treatment protocols for Nav1.6-related disorders.},
}

@article {pmid41011076,
year = {2025},
author = {Della Toffola, J and Ricci, E and Quagliotto, M and Manganotti, P and Benussi, A},
title = {Non-Invasive Brain Stimulation for Amyotrophic Lateral Sclerosis: Current Evidence and Future Perspectives.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {61},
number = {9},
pages = {},
pmid = {41011076},
issn = {1648-9144},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/physiopathology ; *Transcranial Magnetic Stimulation/methods/trends/standards ; *Transcranial Direct Current Stimulation/methods/trends/standards ; Brain/physiopathology ; },
abstract = {Background and Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting the upper and lower motor neurons, with a bleak prognosis and few treatment options. Non-invasive brain stimulation (NIBS) techniques, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), represent emerging approaches aimed at modulating cortical hyperexcitability, a relevant pathogenetic mechanism in ALS. Materials and Methods: A systematic review of the literature was conducted following the PRISMA guidelines, exploring the Scopus and PubMed databases from April to June 2025 with terms related to ALS and NIBS. A total of 18 relevant studies were selected from the initial 708 articles, analysing stimulation protocols, clinical and neurophysiological outcomes, and associated biomarkers; their validity was assessed using the revised Cochrane risk-of-bias (RoB2) tool. Results: The selected studies were extremely heterogeneous, with NIBS techniques, including magnetic (rTMS, cTBS, tSMS) and electrical (tDCS) stimulation, showing variable effects. Low-frequency protocols (1 Hz rTMS) and cTBS showed a slight slowing of clinical progression, while prolonged home stimulation with tDCS and tSMS showed more significant improvements in terms of efficacy, tolerability, and adherence. The main limitations concern the heterogeneity of patients and protocols and the lack of standardised biomarkers, which is why the analysis remained at a descriptive level. The use of telemonitoring and caregiver training are essential to ensure safety and accessibility. Conclusions: NIBS represents a promising therapeutic approach for ALS, but further multicentre, standardised studies with prolonged follow-up are needed. Future strategies should include customisation of stimulation, combination with other therapies, and extension of application to pre-symptomatic phases.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/physiopathology
*Transcranial Magnetic Stimulation/methods/trends/standards
*Transcranial Direct Current Stimulation/methods/trends/standards
Brain/physiopathology

@article {pmid41008332,
year = {2025},
author = {Bernetti, C and Cea, L and Buoso, A and Greco, F and Rossi, M and Pilato, F and Calandrelli, R and Di Gennaro, G and Di Lazzaro, V and Zobel, BB and Mallio, CA},
title = {A Comprehensive Overview of Subacute Combined Degeneration: MRI Diagnostic Challenges and Treatment Pathways.},
journal = {Brain sciences},
volume = {15},
number = {9},
pages = {},
pmid = {41008332},
issn = {2076-3425},
abstract = {Subacute combined degeneration (SCD) is a neurological disorder primarily caused by vitamin B12 deficiency. This condition leads to progressive demyelination and axonal damage, predominantly affecting the dorsal and lateral columns of the spinal cord. This review provides a comprehensive overview of SCD, detailing its complex etiology, pathophysiology, and clinical presentation. We highlight the critical role of magnetic resonance imaging (MRI) in the diagnostic process, discussing both the characteristic spinal cord findings and the more subtle intracranial abnormalities. Furthermore, we address the diagnostic challenges presented by conditions that mimic SCD in MRI, such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). We conclude by outlining current treatment pathways and identifying key areas for future research, including the use of advanced neuroimaging techniques and the potential for new therapeutic approaches. This updated synthesis aims to provide a clear framework for clinicians and researchers to better understand and manage SCD.},
}

@article {pmid41005925,
year = {2026},
author = {Marín-García, M and Gonzalez-Olmos, R and Gómez-Canela, C},
title = {Direct UV photolysis of cloperastine in aqueous solution: Kinetic model and degradation pathway.},
journal = {Journal of environmental sciences (China)},
volume = {159},
number = {},
pages = {670-682},
doi = {10.1016/j.jes.2025.03.025},
pmid = {41005925},
issn = {1001-0742},
mesh = {*Photolysis ; *Water Pollutants, Chemical/chemistry/radiation effects ; *Ultraviolet Rays ; Kinetics ; *Piperidines/chemistry/radiation effects ; Models, Chemical ; },
abstract = {The increasing production and release of synthetic organic chemicals, including pharmaceuticals, into our environment has allowed these substances to accumulate in our surface water systems. Current purification technologies have been unable to eliminate these pollutants, resulting in their ongoing release into aquatic ecosystems. This study focuses on cloperastine (CPS), a cough suppressant and antihistamine medication. The environmental impact of CPS usage has become a concern, mainly due to its increased detection during the COVID-19 pandemic. CPS has been found in wastewater treatment facilities, effluents from senior living residences, river waters, and sewage sludge. However, the photosensitivity of CPS and its photodegradation profile remain largely unknown. This study investigates the photodegradation process of CPS under simulated tertiary treatment conditions using UV photolysis, a method commonly applied in some wastewater treatment plants. Several transformation products were identified, evaluating their kinetic profiles using chemometric approaches (i.e., curve fitting and the hard-soft multivariate curve resolution-alternating least squares (HS-MCR-ALS) algorithm) and calculating the reaction quantum yield. As a result, three different transformation products have been detected and correctly identified. In addition, a comprehensive description of the kinetic pathway involved in the photodegradation process of the CPS drug has been provided, including observed kinetic rate constants.},
}

*Photolysis
*Water Pollutants, Chemical/chemistry/radiation effects
*Ultraviolet Rays
Kinetics
*Piperidines/chemistry/radiation effects
Models, Chemical

@article {pmid41005713,
year = {2025},
author = {Didier, J and Landtsheer, S and Pacheco, MP and Kishk, A and Schneider, JG and Goldeck, D and Pawelec, G and Spira, D and Demuth, I and Sauter, T},
title = {Clinical Data-Driven Classification of Pre-Frailty Reveals Sex-Specific Patterns - Data from the Berlin Aging Study II (BASE-II).},
journal = {Mechanisms of ageing and development},
volume = {},
number = {},
pages = {112114},
doi = {10.1016/j.mad.2025.112114},
pmid = {41005713},
issn = {1872-6216},
abstract = {Frailty is a geriatric condition with multidimensional consequences that strongly affect older adults' quality of life. The lack of a universal standard to describe, diagnose, and treat frailty further complicates this situation. Nowadays, multitudinous frailty assessment tools are applied depending on the regional and clinical context, adding complexity by increasing heterogeneity in the definition and characterization of frailty. Better insights into the causes and pathophysiology of frailty and its early stages are required to establish strong and accurately tailored treatment rationales for frail patients. We analysed participants aged 60 and above using cross-sectional biochemical and survey data from the Berlin Aging Study II (BASE-II, N=1512, pre-frail=470, frail=14), applying machine-learning techniques to investigate determinants of physical frailty measured by Fried et al.'s 5-item frailty phenotype. Our findings highlight new prognostic sex-specific biomarkers of pre-frailty (the early stage of frailty) with possible clinical applications, enriching the current sex-agnostic diagnostic scores with easy monitorable physical and physiological characteristics. Low appendicular lean mass and high fat composition in men, or vitamin D deficiency and high white blood cell counts in women, emerged as strong indicators of the respective pre-frailty profiles. Because the number of fully frail individuals was extremely small (n = 14, <1%), our findings should be interpreted as reflecting predictors of pre-frailty, not of frailty itself. We conclude that understanding the development of frailty remains a complex challenge, and that sex-specific differences must be considered by clinical geriatricians and researchers.},
}

@article {pmid41005474,
year = {2025},
author = {Li, Y and Liu, D and Li, S},
title = {IRE1/Xbp1 promotes the clearance of poly(GR) dipeptide repeats in Amyotrophic Lateral Sclerosis.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {110764},
doi = {10.1016/j.jbc.2025.110764},
pmid = {41005474},
issn = {1083-351X},
abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders characterized by the expansion of GGGGCC (G4C2) repeats in the C9orf72 gene and progressive motor neuron degeneration. A key pathological hallmark of these diseases is the accumulation and cytoplasmic mislocalization of dipeptide repeat (DPR) proteins, particularly poly(GR), which are neurotoxic. Enhancing the clearance of poly(GR) represents a promising therapeutic strategy; however, the molecular mechanisms regulating poly(GR) turnover are not fully understood. Our previous work demonstrated that translationally stalled poly(GR) is targeted by the ribosome-associated quality control (RQC) pathway. In the present study, we identify the IRE1/Xbp1s signaling axis as an essential regulator of poly(GR) degradation. Ectopic expression of IRE1 or its downstream effector Xbp1s, as well as pharmacological activation of IRE1 using IXA4, significantly reduces poly(GR) protein levels in a Drosophila disease model, mammalian cell lines, fibroblasts derived from C9orf72-ALS patients, and a C9orf72 transgenic mouse model. Mechanistically, RNA-sequencing analysis reveals that IRE1/Xbp1s signaling upregulates heat shock protein Hsp70Ba, which plays a critical role in maintaining poly(GR) proteostasis. Additionally, we show that the Rictor/AKT/VCP pathway contributes to the translational regulation and turnover of poly(GR). Importantly, activation of IRE1, either through ectopic expression or IXA4 treatment, mitigates motor neuron loss in the C9orf72 mouse model. Collectively, our findings highlight the IRE1/Xbp1s axis as a key modulator of poly(GR) clearance and suggest its therapeutic potential in ALS/FTD.},
}

@article {pmid41003732,
year = {2025},
author = {Yang, X and Jia, Z and Lian, X and Zhang, R and Li, B and Tian, D and Gao, X and Guo, S and Wang, B and Liu, H and Long, Y and Wang, L and Zhang, J and Xue, Q and Liang, Z and Han, Y and Feng, H and Huang, L and Wang, P and Shao, N and Shi, FD and Zhang, C},
title = {Ofatumumab treatment in patients with neuromyelitis optica spectrum disorder: a retrospective multicenter cohort study.},
journal = {Journal of neurology},
volume = {272},
number = {10},
pages = {655},
pmid = {41003732},
issn = {1432-1459},
support = {82301469//National Natural Science Foundation of China/ ; 82171777//National Natural Science Foundation of China/ ; 20JCJQJC00280//Natural Science Foundation of Tianjin Municipal Science and Technology Commission/ ; 24ZXGZSY00030//Tianjin Public Health Science and Technology Major Project/ ; TJSQNYXXR-D2-120//Tianjin Health Research Project/ ; TJWJ2024RC001//Tianjin Health Research Project/ ; 2024CZLJ003//Leading Talent of Changzhou "The 14th Five-Year Plan" High-Level Health Talents Training Project/ ; },
mesh = {Humans ; Female ; Male ; *Neuromyelitis Optica/drug therapy ; Retrospective Studies ; Adult ; Middle Aged ; *Antibodies, Monoclonal, Humanized ; Aquaporin 4/immunology ; Treatment Outcome ; Cohort Studies ; *Antibodies, Monoclonal/therapeutic use/adverse effects ; Disability Evaluation ; },
abstract = {BACKGROUND: Ofatumumab is a fully human anti-CD20 monoclonal antibody that selectively and highly depletes B cells. However, limited data on ofatumumab treatment are available in patients with neuromyelitis optica spectrum disorders (NMOSD). In this study, we aimed to evaluate the efficacy and safety of subcutaneous ofatumumab in patients with NMOSD.

METHODS: We conducted a retrospective multicenter cohort study of patients with NMOSD who received ofatumumab treatment at 15 tertiary hospitals in China. The primary outcome was the annualized relapse rate (ARR). The secondary outcomes included disability measures (Expanded Disability Status Scale score, EDSS; the Aminoff-Logue Disability Scale, ALS), changes in aquaporin-4 IgG (AQP4-IgG) titers, and safety profiles during ofatumumab treatment.

RESULTS: A total of 112 patients (88% female, median age 44.0 years with interquartile range [IQR 29.5-57.5]) received ofatumumab treatment for a median of 1.7 years (IQR: 1.1-2.0). The median ARR decreased significantly from 2.0 (IQR 0.7-10.0) before ofatumumab to 0 (IQR 0.0-0.0; p < 0.001) after ofatumumab. Twenty-two patients (20%) experienced 25 relapses, with 20 (80%) occurring within the first year of initiating ofatumumab treatment and 19 (76%) classified as minor. The EDSS score from start to the last follow-up also improved significantly (median: pre-treatment 3.5, IQR 2.0-6.5, post-treatment: 2.0, IQR1.0-3.5, p < 0.001). Among 94 patients, 71 (76%) showed reduced AQP4-IgG titers at last follow-up. Injection-related reactions were reported in 13 (12%) of 112 patients. Twenty-four infections occurred in 20 patients (18%) during the ofatumumab treatment, with 92% (22/24) being grade 1 or 2 (CTCAE version 5.0). Only 2 patients (2%) experienced pneumonia requiring hospitalization and recovered after antibiotic treatment (grade 3). Hypogammaglobulinemia was recorded in 14% (13/95) of patients and was not associated with infection.

CONCLUSIONS: Subcutaneous ofatumumab treatment significantly reduces the relapse risk, limits worsening of disability, and reduces AQP4-IgG titers in NMOSD. Moreover, the safety profiles were generally acceptable. Further research is necessary to explore the sustained clinical response of ofatumumab in NMOSD.},
}

Humans
Female
Male
*Neuromyelitis Optica/drug therapy
Retrospective Studies
Adult
Middle Aged
*Antibodies, Monoclonal, Humanized
Aquaporin 4/immunology
Treatment Outcome
Cohort Studies
*Antibodies, Monoclonal/therapeutic use/adverse effects
Disability Evaluation

@article {pmid41002740,
year = {2025},
author = {Bardhan, M and Anand, A and Javed, A and Chilo, MA and Khan, N and Garg, T and Surana, A and Huang, H and Samim, MM and Suresh, V and Khare, A and Menon, B and Kundu, T},
title = {Polymorphism of Melanocortin Receptor Genes-Association with Inflammatory Traits and Diseases.},
journal = {Diseases (Basel, Switzerland)},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/diseases13090305},
pmid = {41002740},
issn = {2079-9721},
abstract = {Melanocortin receptors (MCRs) are responsible for various functions ranging from skin pigmentation, regulation of appetite, stress response and cognition, steroid synthesis, and energy balance to cellular regeneration and immunomodulation. The genetic polymorphism with tissue distribution ranging from the brain, limbic system, and adrenal cortex to neutrophils, monocytes, and macrophages is evident in MCRs. The mutations in MC1R, MC2R, MC3R, and MC4R genes are associated with risk of melanoma, familial glucocorticoid deficiency, obesity, and type 2 diabetes mellitus, respectively. Meanwhile, MC1R, MC2R, and MC5R genes are involved in the risk of major depressive disorder. Melanocortin receptors are involved in different inflammatory disorders, i.e., atopic dermatitis, autoimmune uveitis, sarcoidosis, respiratory diseases, multiple sclerosis, scleroderma, inflammatory bowel disease, amyotrophic lateral sclerosis, Alzheimer's disease, arthritis, and reperfusion injury. Several newer therapeutic agents related to MCRs have numerous advantages over the current anti-inflammatory drugs, demonstrating therapeutic relevance. Among them, α-MSH analogs play a role in atopic dermatitis and scleroderma, and MC1R agonist Dersimelagon has shown effectiveness in systemic sclerosis. The FDA has recently approved the repository corticotropin injection (RCI) to treat sarcoidosis. The FDA has also approved various melanocortin agonists, i.e., Bremelanotide, Afamelanotide, and Setmelanotide, for the treatment of hypoactive sexual desire disorder, Erythropoietic protoporphyria, and obesity, due to pro-opiomelanocortin and leptin receptor deficiency, respectively. Therefore, this review aims to summarize the function and genetic polymorphism of melanocortin receptors, regulatory pathways involving MCRs, and the existing evidence of the prime effect of MCRs on inflammatory responses via different mechanisms and their potential therapeutic use in inflammatory diseases.},
}

@article {pmid40997459,
year = {2025},
author = {de Oliveira Pires, L and Wasicki, B and Abaei, A and Scekic-Zahirovic, J and Roselli, F and Fernandes, S and Bączyk, M},
title = {A computational model of tsDCS effects in SOD1 mice: from MRI-based design to validation.},
journal = {Computers in biology and medicine},
volume = {197},
number = {Pt B},
pages = {111082},
doi = {10.1016/j.compbiomed.2025.111082},
pmid = {40997459},
issn = {1879-0534},
abstract = {During trans-spinal direct current stimulation (tsDCS) the transmembrane potential of neurons is modified by an electric field (EF) induced due to externally applied direct current (DC). The resultant functional effects are being harnessed in the treatment of various neurological conditions; however, the fundamental mechanisms of action underlying tsDCS remain unclear. This ambiguity is largely attributed to the limited knowledge of the geometrical constraints of the EF in the polarized spinal regions. It is, then, essential to develop tools that enable researchers to plan tsDCS approaches in a controlled and systematic manner, ensuring the reproducibility of stimulation effects at spinal targets. With this paper, we aim to provide a comprehensive computational model of tsDCS intervention in mice to support further fundamental research in this area. Our model was constructed using high-resolution MRI scans of C57/B6 mice, which were segmented and reconstructed into a realistic mouse computational model. In vivo electrophysiological measurements of voltage gradients in SOD1 G93A mice were used to validate our model predictions in real-life scenarios. In both the modeling and in vivo studies, we employed a rostrocaudal arrangement of DC electrodes to replicate stimulation parameters that have proven effective for modulating murine spinal circuits. Both the computational and in vivo approaches yielded highly consistent results, with EF parameters primarily influenced by the distance between the target site and the tsDCS electrodes. We conclude that this developed model offers high accuracy in EF distribution and can significantly substantiate basic research in tsDCS.},
}

@article {pmid40992657,
year = {2025},
author = {Almaguer-Mederos, LE and Kandi, AR and Sen, NE and Canet-Pons, J and Berger, LM and Stokes, MP and Abell, K and Key, J and Gispert, S and Auburger, G},
title = {Spinal cord phosphoproteome of SCA2 mouse model reveals alteration of ATXN2-N-term PRM-SH3-actin interactome and of autophagy.},
journal = {Molecular & cellular proteomics : MCP},
volume = {},
number = {},
pages = {101072},
doi = {10.1016/j.mcpro.2025.101072},
pmid = {40992657},
issn = {1535-9484},
abstract = {Toxic polyglutamine (polyQ) expansions in ATXN2 trigger neurodegenerative processes, causing Spinocerebellar Ataxia type 2 (SCA2), and enhancing TDP-43-dependent pathology in Amyotrophic Lateral Sclerosis (ALS) / Fronto-Temporal Dementia (FTD). Primary disease events can be compensated transiently, delaying disease manifestation. To define potential therapy targets, here we studied how cells modify phosphoprotein signals, using preferentially affected nervous tissue from end-stage Atxn2-CAG100-KnockIn mice. The spinal cord phosphoproteome revealed massive hyperphosphorylations flanking the polyQ expansion in ATXN2 and for SQSTM1, and moderate hyperphosphorylations also for ALS proteins OPTN, UBQLN2, TNIP1 and TBK1-targeted TAX1BP1. Conversely, strong hypophosphorylations of WNK1, SPARCL1 and PSMD9 were found. Significant enrichments of SH3-containing proteins, autophagy / endocytosis factors, and actin modulators could be explained by N-terminal, polyQ-adjacent, proline-rich motifs (PRM) in ATXN2, suggesting that SCA2 pathogenesis is highly similar to Huntington's disease where neurotoxicity is mediated by abnormal polyQ-PRM-SH3 interactions. Validation of protein and mRNA levels were done in mouse spinal cord, and embryonic fibroblasts or patient fibroblasts after bafilomycin or arsenite treatment, observing polyQ-dependent OPTN deficiency and SQSTM1 induction impairment. Overall, this phosphoproteome profile identified and quantified the main cellular efforts in adapting autophagy pathways to the aggregation propensity of the ATXN2-N-term.},
}

@article {pmid40988456,
year = {2025},
author = {Tian, J and Bai, D and He, S and Cao, Y and Liao, Y and Wang, J and Bai, L and Pan, L},
title = {Pro-197-his/ser mutation and the metabolic gene DsUGT84A1, synergistically confer resistance to tribenuron-methyl in Descurainia sophia.},
journal = {The Plant journal : for cell and molecular biology},
volume = {123},
number = {6},
pages = {e70487},
doi = {10.1111/tpj.70487},
pmid = {40988456},
issn = {1365-313X},
support = {2023YFD1401100//National Key Research and Development Program of China/ ; CARS-01//China Agriculture Research System/ ; CARS-16-E19//China Agriculture Research System/ ; 2022-31//Modern Agricultural Industrial Technology System of Hunan Province/ ; },
mesh = {*Herbicide Resistance/genetics ; *Herbicides/pharmacology ; *Arylsulfonates/pharmacology/metabolism ; Acetolactate Synthase/genetics/metabolism/antagonists & inhibitors ; *Plant Proteins/genetics/metabolism ; Mutation ; Cytochrome P-450 Enzyme System/genetics/metabolism ; *Plant Weeds/genetics/drug effects ; Plants, Genetically Modified ; Gene Expression Regulation, Plant ; },
abstract = {Descurainia sophia, an invasive weed in wheat fields of China, has developed notable resistance to the acetolactate synthase (ALS)-inhibiting herbicide tribenuron-methyl. In this study, a suspected resistant population (R) of D. sophia was investigated to assess its resistance level and elucidate the underlying mechanisms. Whole-plant bioassays revealed that the R population exhibited a 35.20-fold higher resistance index (RI) to tribenuron-methyl compared with a sensitive (S) population. Treatment with the cytochrome P450 inhibitor malathion partially reversed this resistance, indicating a metabolic component. Target-site resistance (TSR) analysis identified a mutation from proline (Pro) to histidine (His) or serine (Ser) at position 197 of the ALS gene in the R population. Additionally, high-performance liquid chromatography (HPLC) analysis indicated that enhanced tribenuron-methyl metabolism occurred in the R population compared with the S population. Three candidate P450 genes (CYP96A15, CYP81F1, CYP734A1), and one UDP-glycosyltransferase (UGT) gene (UGT84A1) were found to be upregulated in the R population, as verified by RNA sequencing and quantitative reverse transcription PCR (RT-qPCR). Candidate resistance genes were identified and expressed heterologously in Arabidopsis thaliana. Experimental data showed that compared with the green fluorescent protein (GFP) control group, the resistance of three transgenic Arabidopsis lines overexpressing the DsUGT84A1 gene to tribenuron-methyl was significantly increased. When all the plants in the GFP control group died, the fresh weight of these three transgenic lines remained above 20%. The above results fully confirm that the DsUGT84A1 gene demonstrates significant functions pertaining to resistance against tribenuron-methyl. However, the current data suggest that this novel metabolic gene (DsUGT84A1) may not confer cross-resistance among various ALS-inhibiting herbicides. In this respect, the TSR conferred by the Pro197His/Ser mutation may be responsible for cross-resistance. Additionally, antioxidant-related genes were upregulated in A. thaliana overexpressing DsUGT84A1, leading to a reduction in the toxicity level of reactive oxygen species (ROS). Notably, this study identifies and functionally characterizes the UGT gene DsUGT84A1 related to herbicide resistance in broadleaf weeds. This contributes to the understanding of herbicide resistance mechanisms, especially highlighting the role of UGT genes, and enhances the current understanding of resistance evolution in weeds.},
}

*Herbicide Resistance/genetics
*Herbicides/pharmacology
*Arylsulfonates/pharmacology/metabolism
Acetolactate Synthase/genetics/metabolism/antagonists & inhibitors
*Plant Proteins/genetics/metabolism
Mutation
Cytochrome P-450 Enzyme System/genetics/metabolism
*Plant Weeds/genetics/drug effects
Plants, Genetically Modified
Gene Expression Regulation, Plant

@article {pmid40983218,
year = {2025},
author = {Teixeira-Pinheiro, LC and Gonçalves, RGJ and Furtado, M and Decotelli, AB and Vasques, JF and Maturano, M and Quintanilha Barbosa, RA and Marques da Costa, FV and Souza, LRQ and de Lima, MN and Maron-Gutierrez, T and Gomes, HR and Pizzochero, M and Domizi, P and Santiago, MF and Mendez-Otero, R and Gubert, F},
title = {Regional modulation of neurodegeneration and microglial activation by intravenous Wharton's jelly mesenchymal stromal cell therapy in a mouse model of amyotrophic lateral sclerosis.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2025.09.029},
pmid = {40983218},
issn = {1873-7544},
abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative condition characterized by rapid degeneration of motoneurons (MNs), leading to progressive muscle atrophy and, ultimately, mortality within a few years of diagnosis. Although the precise mechanisms initiating MN degeneration are not fully understood, the involvement of non-neuronal cells, including microglia, in ALS pathophysiology is increasingly recognized. Mesenchymal stromal cell (MSC)-based therapies have emerged as a promising avenue for ALS treatment, yet clinical outcomes remain variable, underscoring the necessity for additional pre-clinical investigations. This study evaluated the therapeutic potential of human MSCs derived from Wharton's jelly (WJMSC) in the female SOD1[G93A] mouse model of ALS. Our results indicated that intravenous administration of WJMSC during the presymptomatic phase of the disease notably delayed the onset of motor deficits and extended the lifespan. This functional benefit was associated with the preservation of MNs in the cervical spinal cord. In the lumbar spinal cord, we did not observe MN neuroprotection, but we noted a temporary increase in microgliosis following WJMSC treatment. Our results supported the therapeutic benefits of human MSC in ALS, while also highlighting the differential responses of spinal-cord regions to the treatment during the disease progression. This study underscores the importance of targeting specific disease stages and regions for MSC therapy in ALS, paving the way for refined and potentially more effective therapeutic strategies.},
}

@article {pmid40982298,
year = {2025},
author = {Moojen, TB and Vlug, MS and Visser, E and Reijntjes, MA and Lange, JFM and Bislenghi, G and Carvello, M and Warusavitarne, J and Hompes, R and Stassen, LPS and Faiz, OD and Spinelli, A and D'Hoore, A and Bemelman, WA},
title = {Anastomotic leakage after ileoanal pouch surgery: risk factors and salvage rate.},
journal = {BJS open},
volume = {9},
number = {5},
pages = {},
doi = {10.1093/bjsopen/zraf110},
pmid = {40982298},
issn = {2474-9842},
support = {974823//The Crohn's & Colitis Foundation/ ; },
mesh = {Humans ; *Anastomotic Leak/etiology/epidemiology/therapy/diagnosis ; Male ; Female ; Retrospective Studies ; *Proctocolectomy, Restorative/adverse effects ; Adult ; Risk Factors ; Middle Aged ; *Colonic Pouches/adverse effects ; *Salvage Therapy/statistics & numerical data ; *Colitis, Ulcerative/surgery ; Europe/epidemiology ; Anastomosis, Surgical/adverse effects ; },
abstract = {BACKGROUND: Chronic anastomotic leakage (AL) is the most common cause of pouch failure after restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis. This study investigated factors associated with AL and successful salvage of leaking anastomoses after ileoanal pouch surgery.

METHOD: This multicentre retrospective cohort study included patients aged ≥ 18 years with ulcerative colitis or unclassified inflammatory bowel disease who underwent ileoanal pouch surgery between 2016 and 2021 in six European centres, with a > 12-month follow-up. The primary outcome was AL rate. Secondary outcomes included factors associated with AL occurrence, timing of AL diagnosis (early (< 21 days) versus late), AL management, AL salvage rate, and stoma-free survival.

RESULTS: Overall, 411 patients were included, of whom 13.6% (56) had a diagnosed AL. The rate of AL was significantly higher in low-volume (less than ten procedures annually) centres (28.0% versus 12.7%; P = 0.031). Of the 56 ALs, 44 were diagnosed as early leaks and 12 were diagnosed as late leaks. A three-stage approach was associated with late diagnosis and treatment. AL was managed using various techniques, including diverting ileostomy, antibiotics, and drainage. The overall AL salvage rate was 85.4%, but increased to 92% when diagnosed and treated early (compared with 60% when diagnosed and treated late; P = 0.010). Successful AL salvage was associated with long-term stoma-free status (P = 0.002). The median follow-up was 3.8 years (range 1.0-8.1 years). The long-term stoma-free rate was 95.5% in patients with AL diagnosed and treated early, but only 41.7% when diagnosed and treated late (P < 0.001).

CONCLUSION: Early diagnosis and treatment of AL diminishes the negative effect of AL after ileoanal pouch surgery. Proactive anastomotic assessment enable early diagnosis and management, especially in patients undergoing a three-stage approach.},
}

Humans
*Anastomotic Leak/etiology/epidemiology/therapy/diagnosis
Male
Female
Retrospective Studies
*Proctocolectomy, Restorative/adverse effects
Adult
Risk Factors
Middle Aged
*Colonic Pouches/adverse effects
*Salvage Therapy/statistics & numerical data
*Colitis, Ulcerative/surgery
Europe/epidemiology
Anastomosis, Surgical/adverse effects

@article {pmid40981102,
year = {2025},
author = {Juranek, JK and Kordas, B and Podlasz, P and Bossowska, A and Banach, M},
title = {Current Evidence on the Involvement of RAGE-Diaph1 Signaling in the Pathology and Treatment of Neurodegenerative Diseases-An Overview.},
journal = {Pathophysiology : the official journal of the International Society for Pathophysiology},
volume = {32},
number = {3},
pages = {},
pmid = {40981102},
issn = {1873-149X},
abstract = {Neurodegenerative diseases are a group of disorders characterized by the progressive deterioration of the structure and function of central nervous system neurons and include, among others, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson's (PD), Alzheimer's (AD), and Huntington's (HD) diseases. And while all these diseases seem to have different genetic and environmental components, growing evidence shows that they share common underlying pathological features such as increased neuroinflammation and excessive oxidative stress. RAGE, the receptor for advanced glycation end-products, is a signal transduction receptor, and its activation triggers an increase in proinflammatory molecules, oxidative stressors, and cytokines. Diaph1, protein diaphanous homolog 1, is an actin modulator and an intracellular ligand of RAGE. Studies demonstrated that RAGE and Diaph1 act together, and their downstream signaling pathways play a role in neurodegeneration. Here, based on current evidence and our own research, we provide an overview of the RAGE-Diaph1 signaling and discuss the therapeutic potential of targeted therapy aimed at RAGE-Diaph1 signaling inhibition in the prevention and treatment of neurodegenerative diseases.},
}

@article {pmid40979210,
year = {2025},
author = {Grimm, T and Otto-Sobotka, F and Steinker, D and Summ, O and Timmer, A and Groß, M},
title = {Patients and treatments in a neuropalliative outpatient clinic: an analysis of clinical routine data from five years of care.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1616153},
pmid = {40979210},
issn = {1664-2295},
abstract = {INTRODUCTION: The increasing prevalence of life-threatening neurological diseases raises the need for neuropalliative care. Setting up neurological palliative outpatient clinics is one way of addressing this need. This study aims to describe the patient clientele of a neurological palliative outpatient clinic and the spectrum of necessary treatments and interventions.

METHODS: In this longitudinal analysis, clinical routine data from a single centre were collected retrospectively from adult patients. The patient characteristics related to disease and treatment were evaluated descriptively. Factors influencing the need for ventilation were modelled in a logistic regression. The required treatment effort was modelled with a zero-inflated Beta regression. Results were reported as odds ratios with 95% confidence intervals (CIs).

RESULTS: Two hundred and thirty-two patients were included in the study. Ninety-one patients were women, 141 were men, and the mean age was 55.42 years. Neuropalliative patients represented diagnoses such as amyotrophic lateral sclerosis (ALS) (n = 81), ischemic stroke (n = 15), intracerebral haemorrhage (n = 15), Duchenne muscular dystrophy (n = 12), or craniocerebral trauma (n = 10). Palliative care counselling was the most common intervention for patients (n = 203), their close relatives (n = 177), and their nursing services (n = 75). Respiratory therapy (n = 188), speech and language therapy (n = 145), and physiotherapy (n = 143) were also frequently applied interventions. Sixty patients received botulinum toxin A treatment for hypersalivation, and 32 for spasticity. The odds of needing invasive ventilation increased by 3.7 (CI 1.7-7.8), and the need for mechanical insufflation-exsufflation increased by 2.2 (CI 1.1-4.3) in patients previously discharged from early neurological-neurosurgical rehabilitation. Prior intensive care treatment increased the odds of invasive ventilation by 5.1 (CI 2.2-11.5) and the use of mechanical insufflation-exsufflation by 2.3 (CI 1.1-4.8).

CONCLUSION: Neuropalliative outpatient clinics demand a wide range of diagnostic measures and interventions as well as a multidisciplinary approach. Further research is necessary to investigate the relation between diagnosis and treatment needs.

CLINICAL TRIAL REGISTRATION: https://drks.de/search/en/trial/DRKS00030778, identifier DRKS00030778.},
}

@article {pmid40976462,
year = {2025},
author = {Shi, M and Chu, F and Zhu, J},
title = {Stem cells therapy in neurodegenerative and neuroimmune diseases: current status of treatments and future prospects.},
journal = {Pharmacological research},
volume = {},
number = {},
pages = {107960},
doi = {10.1016/j.phrs.2025.107960},
pmid = {40976462},
issn = {1096-1186},
abstract = {Neurodegenerative and neuroimmune diseases, such as multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) share a common pathologic hallmark i.e. loss of neurons in the central nervous system (CNS), despite diverse pathological manifestations. These diseases present major challenges to global health due to incurable or extremely difficult to treat, imposing a heavy burden on society and families. Stem cell therapy, as a novel promising approach for treating various neurological diseases, harnesses the regenerative potential of stem cells to repair damaged neural tissues and circuits, and has become the only hope for patients to recover their health or delay the deterioration of disease symptoms. In recent years, researchers have successfully generated neurons from multiple types of stem cells, and good curative effects have been achieved in their animal models and in clinical trials. This comprehensive review elaborates on the relevant content of stem cell biology, focuses on conducting an in-depth analysis of the current application status of various stem cells in major neurodegenerative and neuroimmune diseases including MS, AD, PD and ALS, kindling the hope for the development of stem cell-based cell therapies in neurological diseases.},
}

@article {pmid40974909,
year = {2025},
author = {Fazeli, B and Botzenhardt, S and Bachhuber, F and Klassen, P and Klose, V and Dorst, J and Wiesenfarth, M and Uzelac, Z and Jesse, S and Brenner, D and Anderl-Straub, S and Ludolph, AC and Otto, M and Weishaupt, J and Tumani, H and Halbgebauer, S},
title = {Comparative analysis of cerebrospinal fluid neurofilament medium, light and heavy chain in neurodegenerative diseases using an in-house assay for the detection of neurofilament medium chain.},
journal = {EBioMedicine},
volume = {120},
number = {},
pages = {105930},
doi = {10.1016/j.ebiom.2025.105930},
pmid = {40974909},
issn = {2352-3964},
abstract = {BACKGROUND: Neurofilaments are key axonal proteins, with neurofilament light (NfL) and heavy (NfH) chain recognised as promising biomarkers for neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). However, neurofilament medium chain (NfM) remained previously underexplored due to a lack of quantitative assays. In this study, we developed a sensitive immunoassay to measure NfM in cerebrospinal fluid (CSF) and analysed its levels in ALS, Alzheimer's disease (AD), frontotemporal dementia (FTD), and Lewy body dementia (LBD). Correlations among neurofilaments and their diagnostic performance were also evaluated.

METHODS: In this study CSF levels of three neurofilament proteins were measured in 305 participants, including patients with ALS (n = 91), AD (n = 59), FTD (n = 38), LBD (n = 18), non-neurodegenerative controls (CTRL, n = 51), and 48 individuals initially evaluated for ALS but ultimately diagnosed with other conditions (CTRL.DD). NfM levels were quantified using a homemade sandwich ELISA, while NfL and NfH were measured using commercialised Ella cartridges.

FINDINGS: All three neurofilaments were significantly elevated in ALS compared to CTRL and CTRL.DD groups (p < 0.0001 for both), with NfM and NfL also increased in FTD (p < 0.0001 for both) and AD (NfM, p < 0.0001; NfL, p = 0.0001) compared to CTRL. NfH demonstrated the greatest distinction between ALS and FTD (p < 0.0001). Strong correlations were observed among neurofilament subunits, particularly between NfM and NfL (r = 0.93, 95% CI: 0.91-0.94, p < 0.0001). All neurofilaments effectively distinguished ALS from CTRL and CTRL.DD, with AUC values ranging from 0.92 to 0.99. NfM and NfL showed high accuracy in differentiating AD (NfM, AUC: 0.91; NfL, AUC: 0.89) and FTD (NfM, AUC: 0.91; NfL, AUC: 0.92) from CTRL, while NfH best separated ALS from FTD (AUC: 0.96).

INTERPRETATION: This study provides a quantitative comparison of NfM with NfL and NfH in a neurodegenerative cohort, highlighting its potential diagnostic value. Further research with larger cohorts, longitudinal studies, and investigations into neurofilament distribution in different compartments is needed to clarify the distinct roles of NfM, NfL, and NfH in the diagnosis and treatment of neurological diseases.

FUNDING: The present study was supported by the Else Kroener-Fresenius Foundation (2024-EKEA.126) and Chemische Fabrik Karl Bucher GmbH.},
}

@article {pmid40966020,
year = {2025},
author = {Welzel, J and Jacobsen, N and Cockx, H and Jeung, S and Romijnders, R and Hansen, C and Wollesen, B and Maetzler, W},
title = {Beyond protocol standardization: The importance of data curation and software transparency.},
journal = {Journal of Parkinson's disease},
volume = {},
number = {},
pages = {1877718X251377876},
doi = {10.1177/1877718X251377876},
pmid = {40966020},
issn = {1877-718X},
abstract = {Mancini et al.'s framework for gait assessment in Parkinson's disease (PD) is a valuable contribution, enabling a harmonization of study protocols in this research field and, consequently, a substantial improvement of data interpretation across different cohorts. However, we believe that recommendations concerning data curation and software use should be provided in more detail. To ensure data interoperability and facilitate robust data aggregation from such protocols, appropriate and harmonized data formatting and metadata standards are necessary. We further advocate for the open sharing of gait analysis algorithms, to enhance reproducibility and foster collaborative development.},
}

@article {pmid40965373,
year = {2025},
author = {Calcagno, N and Scirocco, E and Clampffer, E and Addy, G and Morgan, S and Parikh, N and Neel, DV and Scalia, J and Young, R and Locatelli, M and Mackie, DS and Berry, JD and Paganoni, S},
title = {Real-World Clinical Experience With Sodium Phenylbutyrate and Taurursodiol at a Single Amyotrophic Lateral Sclerosis Center in the United States.},
journal = {European journal of neurology},
volume = {32},
number = {9},
pages = {e70360},
pmid = {40965373},
issn = {1468-1331},
support = {//Amylyx Pharmaceuticals Inc/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Male ; Female ; *Phenylbutyrates/therapeutic use/adverse effects ; Retrospective Studies ; Middle Aged ; Aged ; United States ; Adult ; },
abstract = {INTRODUCTION/AIMS: Sodium phenylbutyrate (PB) and taurursodiol (TURSO)-PB and TURSO-was approved as a treatment for amyotrophic lateral sclerosis (ALS) in the United States in 2022 based on the results of a phase 2 trial, but was voluntarily withdrawn from the market in 2024 after negative results from its phase 3 trial. The objective of our study was to describe the real-world clinical experience with PB and TURSO at one ALS clinic.

METHODS: This was a retrospective chart review of all ALS patients receiving a PB and TURSO prescription at the Massachusetts General Hospital ALS Clinic between October 1, 2022, and September 30, 2023. Data were extracted from patients' electronical medical records up to December 31, 2023.

RESULTS: A total of 441 ALS patients received a PB and TURSO prescription, with 329 (75%) initiating the medication. The average length of treatment was 285 days, and the rate of drug discontinuation during the study period was 41% (N=135). The most common reason for drug discontinuation was side effects (N=93, 69%), with the most common being gastrointestinal issues (N=69). No hospitalizations, deaths, or serious adverse events were considered related to treatment with PB and TURSO.

DISCUSSION: Experience in real-world clinical settings can help supplement trial data with information on the drug performance at various stages of disease progression. Adverse events impacted treatment persistence in routine clinical practice, underscoring the need for vigilant monitoring and tailored supportive interventions to optimize treatment adherence.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy
Male
Female
*Phenylbutyrates/therapeutic use/adverse effects
Retrospective Studies
Middle Aged
Aged
United States
Adult

@article {pmid40964461,
year = {2025},
author = {Chen, HW},
title = {Sustained Bulbar and Respiratory Function in a Case Most Consistent With Bulbar-Onset Amyotrophic Lateral Sclerosis Following Axial Spinal Traction: A 21-Month Report.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e92341},
pmid = {40964461},
issn = {2168-8184},
abstract = {Bulbar-onset amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease characterized by early decline in speech, swallowing, and respiratory function, and is associated with a poor prognosis. We report the case of a woman whose treating neurologist determined, eight months after symptom onset, that her presentation was most consistent with bulbar-onset ALS. At 16 months, she began receiving intermittent pelvis-stabilized axial spinal traction (PSAST) as a supportive intervention. Remarkably, over the subsequent 21 months, she maintained oral intake and preserved respiratory function, an outcome atypical of the expected trajectory of bulbar-onset ALS. While this single case relies on provider reports for diagnostic confirmation, it raises the hypothesis that axial spinal traction may help sustain bulbar and respiratory function in ALS. Given the lack of effective treatment options, we present this case to raise awareness of a potential supportive approach that warrants further investigation.},
}

@article {pmid40958782,
year = {2025},
author = {Sun, LC and Li, WS and Chen, W and Zhao, DQ and Zhang, X and Li, CX and Ren, Z},
title = {Frontiers and Emerging Trends in Edaravone Research: A Bibliometric Analysis of Molecular Basis and Clinical Studies Using CiteSpace and VOSviewer.},
journal = {Journal of multidisciplinary healthcare},
volume = {18},
number = {},
pages = {5743-5758},
pmid = {40958782},
issn = {1178-2390},
abstract = {PURPOSE: Edaravone is a potent free-radical scavenger and antioxidant that has been widely investigated for its therapeutic potential in neurodegenerative diseases and oxidative stress-related conditions. Although previous studies have explored its molecular structure, pharmacological effects, and clinical applications, a comprehensive bibliometric analysis of its research trends and future directions remains lacking.

METHODS: This study employed bibliometric methods to analyze edaravone-related publications from 2000 to 2024, using the Web of Science Core Collection database. The analysis examined publication trends; contributions by countries, institutions, and authors; and keyword clustering. Data visualization tools, such as CiteSpace and VOSviewer, were utilized to identify research clusters and emerging trends in edaravone research.

RESULTS: The findings revealed a significant increase in edaravone-related publications, with China, Japan, and the United States as the leading contributors. Notable researchers, including Abe K and Yoshino H, have made substantial contributions to this field. Four major research clusters were identified: free radical scavenging, cerebral infarction, amyotrophic lateral sclerosis, and oxidative stress. Emerging trends suggest a growing interest in edaravone dexbornel for acute ischemic stroke treatment, as well as its potential applications in blood-brain barrier interactions and Alzheimer's disease.

CONCLUSION: This bibliometric analysis highlights the growing interest in edaravone and its potential clinical application, particularly in neuroprotection. While this study provides valuable insights into current research trends, future studies should incorporate a broader range of sources and languages to obtain a more comprehensive understanding of the impact and scope of edaravone.},
}

@article {pmid40958367,
year = {2025},
author = {Gao, M and Han, J and Zhu, Y and Wen, X and Feng, L and Zhou, T},
title = {Obesity Impacts Post-Myocardial Infarction Neovascularization by Downregulating AQP1 Expression via the TRPC5-NFATc3 Signaling Pathway.},
journal = {Comprehensive Physiology},
volume = {15},
number = {5},
pages = {e70048},
doi = {10.1002/cph4.70048},
pmid = {40958367},
issn = {2040-4603},
support = {82470455//National Natural Science Foundation of China/ ; 82200463//National Natural Science Foundation of China/ ; },
mesh = {Animals ; *Myocardial Infarction/metabolism ; *TRPC Cation Channels/metabolism/genetics ; Mice ; *Obesity/metabolism/complications ; *Aquaporin 1/metabolism/genetics ; *NFATC Transcription Factors/metabolism/genetics ; Signal Transduction/physiology ; Down-Regulation ; Male ; Mice, Inbred C57BL ; Humans ; Neovascularization, Physiologic ; Endothelial Cells/metabolism ; },
abstract = {Obesity is associated with impaired angiogenesis and poor recovery following myocardial infarction (MI), yet the underlying molecular mechanisms remain poorly defined. The transient receptor potential cation channel subfamily C member 5 (TRPC5) is known to regulate angiogenesis, but its role in the context of obesity-related MI is unclear. Here, we show that TRPC5 expression is downregulated in obese mice hearts following MI, resulting in compromised angiogenic function. Riluzole, an FDA-approved drug for amyotrophic lateral sclerosis, activates TRPC5 and restores the migration, sprouting, and tube formation function of coronary artery endothelial cells isolated from diet-induced obese (DIO) MI mice. In obese mice, riluzole enhances post-MI neovascularization, reduces infarct size, and improves cardiac function. Notably, TRPC5-mediated angiogenesis requires aquaporin-1 (AQP1), whose expression is regulated by TRPC5 via the nuclear factor of activated T cells 3 (NFATc3) transcription factor. Silencing AQP1 abolishes the pro-angiogenic effects of TRPC5 activation, establishing AQP1 as a critical downstream effector. In conclusion, our data provide evidence that the TRPC5-NFATc3-AQP1 pathway is essential for post-MI angiogenesis in obesity and support riluzole as a promising therapeutic approach to enhance angiogenesis in obese individuals following MI.},
}

Animals
*Myocardial Infarction/metabolism
*TRPC Cation Channels/metabolism/genetics
Mice
*Obesity/metabolism/complications
*Aquaporin 1/metabolism/genetics
*NFATC Transcription Factors/metabolism/genetics
Signal Transduction/physiology
Down-Regulation
Male
Mice, Inbred C57BL
Humans
Neovascularization, Physiologic
Endothelial Cells/metabolism

@article {pmid40955309,
year = {2025},
author = {Wang, L and Feng, L and Ning, B and Wang, Z and Dai, C and Li, M},
title = {Natural Products from Chinese Medicine Targeting NF-κB Signaling: Emerging Therapeutic Avenues for Neurodegenerative Diseases.},
journal = {Drug design, development and therapy},
volume = {19},
number = {},
pages = {8135-8159},
pmid = {40955309},
issn = {1177-8881},
mesh = {Humans ; *NF-kappa B/metabolism/antagonists & inhibitors ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Biological Products/pharmacology/chemistry ; *Medicine, Chinese Traditional ; Signal Transduction/drug effects ; Animals ; *Drugs, Chinese Herbal/pharmacology/chemistry ; },
abstract = {This review summarizes recent advances in leveraging natural products from Chinese medicine to modulate the nuclear factor kappa B (NF-κB) signaling pathway for the prevention and treatment of neurodegenerative diseases (NDDs), focusing specifically on Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS). NF-κB proteins regulate cellular biological activity by binding to promoter regions in the nucleus and transcribing various protein-coding genes. Emerging evidence indicates that NF-κB plays a pivotal role in driving key hallmarks of NDD progression, including neuroinflammation, oxidative stress, mitochondrial dysfunction, and dysregulation of the cell cycle. Natural products from Chinese medicine exert modulatory effects on NF-κB signaling through diverse pharmacological mechanisms, ultimately improving cognitive and motor impairments in preclinical NDDs models. The pleiotropic nature of natural products derived from traditional Chinese medicine (TCM)-which operate through subunit-specific modulation of NF-κB-underscores their potential as next-generation therapeutics. Investigating the intricate regulation of NF-κB by natural products from Chinese medicine will not only enrich our understanding of the pathogenesis of NDDs but also establish a theoretical foundation for the development of new therapeutic drugs for NDDs, providing innovative strategies for prevention and treatment.},
}

Humans
*NF-kappa B/metabolism/antagonists & inhibitors
*Neurodegenerative Diseases/drug therapy/metabolism
*Biological Products/pharmacology/chemistry
*Medicine, Chinese Traditional
Signal Transduction/drug effects
Animals
*Drugs, Chinese Herbal/pharmacology/chemistry

@article {pmid40949727,
year = {2025},
author = {Gu, Q and Shen, J and Chu, S and Huang, Q and Chen, A and Li, L and Li, R},
title = {Analysis of the resistance level and target site resistance mechanisms of Echinochloa crus-galli to penoxsulam from Hubei Province, China.},
journal = {PeerJ},
volume = {13},
number = {},
pages = {e19973},
pmid = {40949727},
issn = {2167-8359},
mesh = {*Echinochloa/drug effects/genetics/enzymology ; Acetolactate Synthase/genetics/antagonists & inhibitors/metabolism ; China ; *Herbicide Resistance/genetics ; *Sulfonamides/pharmacology ; *Herbicides/pharmacology ; Mutation ; *Plant Weeds/drug effects/genetics ; Oryza/parasitology ; Plant Proteins/genetics/metabolism/antagonists & inhibitors ; Uridine/analogs & derivatives ; },
abstract = {Echinochloa crus-galli is a grass weed that infests rice fields and causes significant crop yield losses. In this study, we surveyed 15 resistant E. crus-galli populations collected from rice fields in Hubei Province, China, and investigated the resistance levels and target site resistance mechanisms to the acetolactate synthase (ALS) inhibitor penoxsulam. The results of whole-plant bioassay experiments revealed that 15 populations presented different levels of resistance to penoxsulam. The Trp-574-Leu mutation was detected in ten resistant populations, and the Pro-197-Leu mutation was detected in one resistant population. Additionally, the in vitro ALS activity in resistant populations (18-ETF, 18-WJJ, and 18-WMJ) was 51.28-, 5.51-, and 8.46-fold greater than that in the susceptible population. The ALS from these resistant populations requires a much higher penoxsulam concentration for activity inhibition. ALS gene expression in three resistant populations (18-ETF, 18-WJJ, and 18-WMJ) was 1.53-, 1.58-, and 1.41-fold greater than that in the susceptible population 18-NJ before penoxsulam treatment. Our results indicated that target-site mutation in ALS is at least partially responsible for barnyardgrass resistance to penoxsulam in Hubei Province.},
}

*Echinochloa/drug effects/genetics/enzymology
Acetolactate Synthase/genetics/antagonists & inhibitors/metabolism
China
*Herbicide Resistance/genetics
*Sulfonamides/pharmacology
*Herbicides/pharmacology
Mutation
*Plant Weeds/drug effects/genetics
Oryza/parasitology
Plant Proteins/genetics/metabolism/antagonists & inhibitors
Uridine/analogs & derivatives

@article {pmid40949612,
year = {2025},
author = {Gao, L and Wang, J and Bi, Y},
title = {Nanotechnology for Neurodegenerative Diseases: Recent Progress in Brain-Targeted Delivery, Stimuli-Responsive Platforms, and Organelle-Specific Therapeutics.},
journal = {International journal of nanomedicine},
volume = {20},
number = {},
pages = {11015-11044},
pmid = {40949612},
issn = {1178-2013},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; Animals ; Blood-Brain Barrier/metabolism ; Brain/metabolism/drug effects ; *Drug Delivery Systems/methods ; Nanomedicine/methods ; Nanoparticles/chemistry ; Organelles/drug effects/metabolism ; Liposomes/chemistry ; *Nanoparticle Drug Delivery System/chemistry ; Drug Carriers/chemistry ; },
abstract = {Neurodegenerative diseases-including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis-are characterized by progressive neuronal loss and complex pathological mechanisms such as protein aggregation, mitochondrial dysfunction, and neuroinflammation. Conventional therapies offer limited efficacy due to the blood-brain barrier (BBB) and lack of targeted delivery. Nanotechnology has emerged as a transformative strategy for precise brain-targeted treatment. This review summarizes recent advances in nanoparticle-based drug delivery systems, including polymeric nanoparticles, liposomes, inorganic nanomaterials, and biomimetic carriers, highlighting their design features, BBB-penetration mechanisms, and disease-specific applications. Emphasis is placed on stimuli-responsive nanocarriers that react to pH, reactive oxygen species, or enzyme activity, enabling site-specific drug release. Additionally, organelle-targeting strategies-particularly those directed at mitochondria and lysosomes-are explored for their role in subcellular precision therapy. The integration of diagnostic and therapeutic modalities in theranostic nanoplatforms is also discussed. By consolidating preclinical progress and emerging technologies, this review offers insights into the future of nanomedicine in treating neurodegenerative diseases and lays the groundwork for clinical translation.},
}

Humans
*Neurodegenerative Diseases/drug therapy
Animals
Blood-Brain Barrier/metabolism
Brain/metabolism/drug effects
*Drug Delivery Systems/methods
Nanomedicine/methods
Nanoparticles/chemistry
Organelles/drug effects/metabolism
Liposomes/chemistry
*Nanoparticle Drug Delivery System/chemistry
Drug Carriers/chemistry

@article {pmid40949365,
year = {2025},
author = {Dai, JW and Xing, YX and Sun, NZ},
title = {Adjuvant chemotherapy for gallbladder cancer: Current evidence, controversies, and future directions.},
journal = {World journal of gastrointestinal surgery},
volume = {17},
number = {8},
pages = {108160},
pmid = {40949365},
issn = {1948-9366},
abstract = {Gallbladder cancer is an aggressive malignancy notorious for its poor prognosis and treatment challenges, even at early stages. In their recent work, Kim et al utilized data from the National Cancer Database to explore whether adding chemotherapy to surgical intervention could improve survival outcomes for patients diagnosed with stage II gallbladder cancer. The use of adjuvant chemotherapy following curative surgery in this patient population has been a long-standing source of debate. Historically, the lack of clear guidelines for managing stage II gallbladder cancer has resulted in inconsistent, sometimes contradictory findings from various studies regarding the effectiveness of postoperative chemotherapy. Consequently, many clinicians have relied on studies involving other biliary tract cancers to justify the routine use of prophylactic chemotherapy after surgery, aiming to minimize recurrence risk. Given the rarity, high mortality rate, and the small sample sizes typical in gallbladder cancer studies, Kim et al's contribution represents a significant and commendable effort to address these challenges. Kim et al designed a retrospective cohort study with well-defined inclusion criteria and clear treatment classifications. Notably, their findings suggested that in stage II gallbladder cancer, adjuvant chemotherapy did not yield a meaningful survival benefit over surgery alone. These results therefore casted doubt on the routine practice of administering chemotherapy to all patients postoperatively, prompted clinicians to reconsider their approach. Furthermore, this controversy directly influences clinical decisionmaking and guideline recommendations, as uncertainty regarding the benefit of adjuvant chemotherapy may lead to heterogeneous practices across different institutions and regions. This article critically assessed the research design, methodology, and clinical implications of the study by Kim et al. It also provided an in-depth exploration of the broader question regarding the appropriateness of adjuvant chemotherapy following surgery for stage II gallbladder cancer, highlighting the necessity of rigorous study designs to produce reliable evidence.},
}

@article {pmid40947692,
year = {2025},
author = {Manubolu, K and Peeriga, R},
title = {Revolutionizing Neurodegenerative Disease Management: The Synergy of AI and Pharmacy.},
journal = {Current aging science},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118746098375978250820220024},
pmid = {40947692},
issn = {1874-6128},
abstract = {Neurodegenerative diseases, including Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis (ALS), represent major healthcare challenges worldwide. Despite advances in diagnosis and treatment, these conditions remain incurable, and there is a need for more effective management strategies. The integration of artificial intelligence (AI) in healthcare has emerged as a promising solution, offering new approaches to diagnosis, personalized treatment, and patient care. This paper explores the potential of AI to revolutionize the management of neurodegenerative diseases, with a focus on its synergistic role in pharmacy. By leveraging AI in drug discovery, personalized treatment plans, and clinical decision-making, AI can enhance therapeutic outcomes and improve patient quality of life. The study reviews the current landscape of AI applications in neurodegenerative disease management, with a focus on pharmacy-related interventions. The review includes AI-driven approaches in genomics, biomarkers, drug repurposing, and clinical trials. It also examines AI's role in optimizing pharmaceutical care, improving medication adherence, and tailoring treatments based on individual genetic profiles. AI has demonstrated its capability to analyze vast datasets, from genetic information to clinical records, to identify novel drug targets and predict patient responses to specific therapies. The use of AI in precision medicine has enabled more accurate diagnosis and has facilitated the development of personalized treatments for neurodegenerative diseases. Additionally, AI tools are enhancing medication management by providing personalized therapy adjustments and improving adherence. AI offers transformative potential for the future of neurodegenerative disease management. Its integration into pharmacy practice promises more effective, individualized treatments, accelerating drug discovery, and optimizing patient care. As AI technologies continue to advance, their role in managing complex neurological disorders will become increasingly vital.},
}

@article {pmid40943950,
year = {2025},
author = {Pochhammer, J and Kiani, S and Hobbensiefken, H and Hobbensiefken, H and Reichert, B and Taivankhuu, T and Becker, T and Gundlach, JP},
title = {Lactate in Drainage Fluid to Predict Complications in Robotic Esophagectomies-A Pilot Study in a Matched Cohort.},
journal = {Journal of clinical medicine},
volume = {14},
number = {17},
pages = {},
pmid = {40943950},
issn = {2077-0383},
abstract = {Background/Objectives: Despite advances in minimally invasive procedures, anastomotic leakages (ALs) after esophageal resections mark the most feared complication. Its early detection can lead to quick interventional treatment with improved survival. Nonetheless, early detection remains challenging, and scores are imprecise and complex. Methods: In our study we analyzed mediastinal drainage fluid to find parameters suggesting AL even before it became clinically evident and correlated them to routine biomarkers. All patients with AL after robotically assisted esophageal resections were included and matched 1:1 with uneventful controls. Additionally, transhiatal distal esophageal resections operated during this period were included. Drainage fluid was collected on postoperative days (PODs) 1-4 with consecutive blood gas analysis. Test quality was determined by the area under the curve (AUC) of the receiver operating characteristic curve (ROC). Results: In total, 40 patients were included, with 17 developing AL. There were no significant differences in gender, age, BMI or oncological treatment. The 30-day morbidity rate was 65.0%. The study was restricted to events in the first 12 days. While lactate value in drainage fluid differed significantly from POD 3 onwards in the two groups, serum CRP remained without significant differences. We developed the LacCRP score (CRP/30 + lactate/2). The AUC on POD 3 was 0.96, with a sensitivity and specificity of 100% and 75%, respectively. An estimator of 1.08 was found in multivariate analysis: one-point increase in the LacCRP score increases AL probability by 8%. Conclusions: This study demonstrates that postoperative lactate determinations in drainage fluid can predict AL after esophageal resection, and its combination with serum CRP results in a reliable LacCRP score.},
}

@article {pmid40943341,
year = {2025},
author = {Yang, EJ},
title = {The Emerging Role of the Brain-Gut Axis in Amyotrophic Lateral Sclerosis: Pathogenesis, Mechanisms, and Therapeutic Perspectives.},
journal = {International journal of molecular sciences},
volume = {26},
number = {17},
pages = {},
pmid = {40943341},
issn = {1422-0067},
support = {(KIOM) KSN2224011//KIOM/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. Although genetic and environmental factors are established contributors, recent research has highlighted the critical role of the gut-brain axis (GBA) in ALS pathogenesis. The GBA is a bidirectional communication network involving neural, immune, and endocrine pathways that connect the gut microbiota with the central nervous system. Dysbiosis in ALS disrupts this axis, leading to increased intestinal permeability, neuroinflammation, and excitotoxicity. Notably, reductions in butyrate-producing bacteria, alterations in microbial metabolites, and enhanced NLRP3 inflammasome activation have been observed in patients with ALS. These changes may precede motor symptoms, suggesting a potential causative role. Interventions targeting the microbiome, such as dietary modulation, have shown promise in delaying disease onset and reducing inflammation. However, the clinical evidence remains limited. Given that gut dysbiosis may precede neurological symptoms, microbiota-targeted therapies offer a novel and potentially modifiable approach to ALS treatment. Understanding the role of GBA in ALS will open new avenues for early diagnosis and intervention. Further clinical trials are required to clarify the causal links and evaluate the efficacy of microbiome-based interventions. Understanding the brain-gut-microbiota axis in ALS could lead to new diagnostic biomarkers and therapeutic strategies.},
}

@article {pmid40940798,
year = {2025},
author = {Li, L and Zheng, X and Ma, H and Zhu, M and Li, X and Sun, X and Feng, X},
title = {TREM2 in Neurodegenerative Diseases: Mechanisms and Therapeutic Potential.},
journal = {Cells},
volume = {14},
number = {17},
pages = {},
pmid = {40940798},
issn = {2073-4409},
abstract = {Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), represent significant global health challenges, affecting millions and straining healthcare systems. These disorders involve progressive neuronal loss and cognitive decline, with incompletely elucidated underlying mechanisms. Chronic neuroinflammation is increasingly recognized as a critical contributor to disease progression. The brain's resident immune cells, microglia, are central to this inflammatory response. When overactivated, microglia and other immune cells, such as peripheral macrophages, can exacerbate inflammation and accelerate disease development. Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) is a transmembrane receptor of the immunoglobulin superfamily that demonstrates high expression on microglia in the central nervous system. TREM2 serves a vital role in regulating phagocytosis, synaptic pruning, and energy metabolism. This review examines the functions of TREM2 in neurodegenerative diseases and its potential as a therapeutic target, aiming to inform future treatment strategies.},
}

@article {pmid40932199,
year = {2025},
author = {Spittel, S and Grehl, T and Weydt, P and Kettemann, D and Fabian, R and Rödiger, A and Smesny, U and Steinbach, R and Ilse, B and Weyen, U and Petri, S and Lumi, R and Bjelica, B and Lingor, P and Grosskreutz, J and Göricke, BM and Pfeilschifter, W and Schmeja, W and Dorst, J and Mensch, A and Siebert, J and Norden, J and Bernsen, S and Subramanian, SK and Hildebrandt, B and Walter, B and Münch, C and Maier, A and Meyer, T},
title = {Dextromethorphan/quinidine (DMQ) for reducing bulbar symptoms in amyotrophic lateral sclerosis - assessment of treatment experience in a multicenter study.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/21678421.2025.2557932},
pmid = {40932199},
issn = {2167-9223},
abstract = {BACKGROUND: In amyotrophic lateral sclerosis (ALS), dextromethorphan/quinidine (DMQ) has been reported to reduce bulbar symptoms, including dysarthria and dysphagia. However, data on patients' perceptions of DMQ treatment are limited.

METHODS: Data on DMQ treatment were collected from 1065 ALS patients treated at 13 ALS centers between 10-2015 and 06-2025. Patient-reported outcome measures (PROM) of 179 participants were remotely assessed via the "ALS App". PROM included the self-explanatory version of the ALS Functional Rating Scale (ALSFRS-R-SE), the Net Promoter Score (NPS); and Treatment Satisfaction Questionnaire for Medication (TSQM-9).

RESULTS: Mean disease duration was 29.3 months (SD 38.1). ALS progression before treatment was 0.82 points/month (ALSFRS-R). Mean DMQ treatment duration was 8.4 months (SD 10.8), including 35.2% (n = 374) of shorter (<3 months), 35.3% (n = 375) of longer (3-9 months), and 29.5% (n = 313) of very long DMQ treatment (>9 months). Patients' recommendation (n = 178) was positive (NPS: +23) with higher scores after very long DMQ treatment (NPS +37) compared to longer (NPS +15) and shorter treatment (NPS +7.5), respectively. TSQM-9 scores (n = 163) demonstrated high satisfaction for effectiveness 60.0 (SD 25.9), convenience 73.8 (SD 18.2), and global satisfaction 63.4 (SD 29.8).

INTERPRETATION: The positive perception in PROM underscores the value of DMQ as an individualized treatment option for bulbar symptoms in ALS. However, shortage of clinical data, online assessment, and selection biases are among the limitations of this study that need to be addressed in further investigations.},
}

@article {pmid40931498,
year = {2025},
author = {Alemán-Villa, KM and Armienta-Rojas, DA and Camberos-Barraza, J and Rábago-Monzón, ÁR and Camacho-Zamora, A and Osuna-Ramos, JF and Magaña-Gómez, JA and Guadrón-Llanos, AM and Calderón-Zamora, L and Norzagaray-Valenzuela, CD and Valdez-Flores, MA and Picos-Cárdenas, VJ and De la Herrán-Arita, AK},
title = {Neuroinflammation across the spectrum of neurodegenerative diseases: mechanisms and therapeutic frontiers.},
journal = {Neuroimmunomodulation},
volume = {},
number = {},
pages = {1-33},
doi = {10.1159/000548021},
pmid = {40931498},
issn = {1423-0216},
abstract = {Neuroinflammation has emerged as a central and dynamic component of the pathophysiology underlying a wide range of neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Far from being a secondary consequence of neuronal damage, inflammatory processes (mediated by microglia, astrocytes, peripheral immune cells, and associated molecular mediators) actively shape disease onset, progression, and symptomatology. This review synthesizes current knowledge on the cellular and molecular mechanisms that govern neuroinflammatory responses, emphasizing both shared and disease-specific pathways. We examine how innate and adaptive immune interactions contribute to neuronal vulnerability and neurodegenerative cascades, and explore the reciprocal communication between systemic and central immune compartments. Particular attention is given to emerging therapeutic strategies aimed at modulating neuroinflammation, including immunomodulatory drugs, glial-targeted interventions, and novel delivery platforms. By integrating findings across disciplines and disease models, we outline key translational challenges and propose future directions to harness neuroinflammation as a therapeutic target in the era of precision medicine. Ultimately, a deeper understanding of neuroimmune dynamics holds promise for redefining both the diagnosis and treatment of neurodegenerative disorders.},
}

@article {pmid40931339,
year = {2025},
author = {Epplen, ASC and Rothöft, M and Stahlke, S and Theiss, C and Matschke, V},
title = {Caffeine mitigates ROS accumulation and attenuates motor neuron degeneration in the wobbler mouse model of amyotrophic lateral sclerosis.},
journal = {Cell communication and signaling : CCS},
volume = {23},
number = {1},
pages = {394},
pmid = {40931339},
issn = {1478-811X},
mesh = {Animals ; *Caffeine/pharmacology/therapeutic use ; *Amyotrophic Lateral Sclerosis/pathology/drug therapy/metabolism ; *Motor Neurons/drug effects/pathology/metabolism ; Disease Models, Animal ; *Reactive Oxygen Species/metabolism ; Mice ; Oxidative Stress/drug effects ; Male ; *Neuroprotective Agents/pharmacology ; *Nerve Degeneration/pathology/drug therapy ; NAD/metabolism ; Humans ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by oxidative stress and progressive motor neuron degeneration. This study evaluates the potential neuroprotective effects of caffeine in the Wobbler mouse, an established model of ALS.

METHODS: Wobbler mice received caffeine supplementation (60 mg/kg/day) via drinking water, and key parameters, including muscle strength, NAD metabolism, oxidative stress, and motor neuron morphology, were assessed at critical disease stages.

RESULTS: Caffeine delayed motor performance decline, as observed in grip strength tests during the early symptomatic phase. Histological analyses revealed that significantly fewer motor neurons were lost in caffeine-treated mice at p41, despite no changes in soma morphology. Biochemical assays demonstrated that caffeine significantly reduced ROS levels and restored NAD levels to wildtype-like values, although NMNAT2 protein expression remained unaffected. The data suggest that caffeine mitigates oxidative stress through alternative pathways, potentially involving enhanced mitochondrial function and antioxidative defenses.

CONCLUSIONS: These findings highlight the potential of caffeine as a protective agent for delaying motor neuron degeneration in ALS. Future studies should explore optimal dosing strategies, combinatorial treatment approaches, and the underlying molecular mechanisms, to enable translation of these findings to human ALS patients.},
}

Animals
*Caffeine/pharmacology/therapeutic use
*Amyotrophic Lateral Sclerosis/pathology/drug therapy/metabolism
*Motor Neurons/drug effects/pathology/metabolism
Disease Models, Animal
*Reactive Oxygen Species/metabolism
Mice
Oxidative Stress/drug effects
Male
*Neuroprotective Agents/pharmacology
*Nerve Degeneration/pathology/drug therapy
NAD/metabolism
Humans

@article {pmid40930472,
year = {2025},
author = {Roger, AL and Huston, ML and Spaulding, M and Metz, CM and Froeb, R and Wu, R and Kehoe, S and Mitchell, GS and ElMallah, MK},
title = {Therapeutic Acute Intermittent Hypoxia Modestly Improves Breathing in Pompe Disease.},
journal = {Respiratory physiology & neurobiology},
volume = {},
number = {},
pages = {104489},
doi = {10.1016/j.resp.2025.104489},
pmid = {40930472},
issn = {1878-1519},
abstract = {Pompe disease is an autosomal recessive neuromuscular disorder characterized by a deficiency of acid α-glucosidase (GAA), an enzyme responsible for lysosomal glycogen degradation in all cells. Respiratory distress is a common symptom among patients with Pompe disease resulting from weakness of primary respiratory neuromuscular units of the diaphragm and genioglossus and the motor neurons which innervate them. The only FDA approved treatment is enzyme replacement therapy (ERT) of recombinant human GAA (rhGAA) which slows the decline of motor function and extends life expectancy. However, ERT does not cross the blood-brain barrier and thus, is unable to treat the critical pathology present in motor neurons hindering long-term efficacy. In the present study, we sought to explore an alternative treatment for Pompe patients to improve breathing by improving the function of motor neurons. Therapeutic acute intermittent hypoxia (tAIH) is a non-invasive therapeutic modality which has had success in improving respiratory and non-respiratory motor function in patients with spinal cord injury, amyotrophic lateral sclerosis, multiple sclerosis, and stroke. Here, we treated adult Gaa[-/-] mice with a single, week-long tAIH protocol, followed by bi-weekly tAIH for 4 months. We report three critical findings: (1) both short and long-term tAIH therapy modestly improve breathing in Gaa[-/-] mice; (2) long-term tAIH-therapy in WT mice moderately elevates breathing responses; and (3) these trending improvements to respiration in Gaa[-/-] may be related to changes in chemoreflex activation, reduced kyphosis, and improved overlap of acetylcholine receptors and phrenic motor neuron axon terminals in the diaphragm muscle.},
}

@article {pmid40926822,
year = {2025},
author = {Guo, W and Dong, L and Lu, Q and Xie, M and Yang, Y and Zhang, Y and Lu, X and Yu, Q},
title = {Association Between Cannabis Use and Neuropsychiatric Disorders: A Two-sample Mendelian Randomization Study.},
journal = {Alpha psychiatry},
volume = {26},
number = {4},
pages = {46108},
pmid = {40926822},
issn = {2757-8038},
abstract = {BACKGROUND: The progressive legalization and widespread use of cannabis has led to its use as a treatment for certain neuropsychiatric disorders. Traditional epidemiological studies suggest that cannabis use has an effect on some neurocognitive aspects. However, it is unclear whether cannabis use is causally related to common neuropsychiatric disorders. The present study was conducted to illustrate the causal relationships of genetically predicted cannabis use with common neuropsychiatric disorders.

METHODS: We used a two-sample Mendelian randomization method using genome-wide association study (GWAS) summary statistics obtained from publicly available databases on lifetime cannabis use and 10 neuropsychiatric disorders, including multiple sclerosis (MS), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), autism spectrum disorder (ASD), epilepsy, generalized epilepsy, focal epilepsy, migraine, migraine with aura, migraine without aura, schizophrenia (SCZ), anorexia nervosa (AN), attention-deficit/hyperactivity disorder (ADHD), and Parkinson's disease (PD) were studied with a two-sample Mendelian randomization method for GWAS summary statistics. The inverse variance weighted (IVW) method was used as the main analysis model.

RESULTS: Our study suggests that lifetime cannabis use is associated with an increased risk of developing PD (odds ratio (OR) = 1.782; 95% CI 1.032-3.075; p = 0.038) and an increased risk of ADHD in female participants (OR = 1.650; 95% CI 1.051-2.590; p = 0.029).

CONCLUSIONS: Cannabis intake may cause adverse effects relating to certain neuropsychiatric disorders. Therefore, special attention should be paid to the side effects of addictive drugs during clinical treatment to avoid harmful effects on the brain and neurocognition.},
}