@article {pmid42725564,
year = {2026},
author = {Peng, L and Ma, S and Liu, Y and Liu, S and Tang, L},
title = {Artificial liver support therapy alters TNFα and CD4+ T cell counts in liver failure: A pilot self-controlled study.},
journal = {The International journal of artificial organs},
volume = {},
number = {},
pages = {3913988261479971},
doi = {10.1177/03913988261479971},
pmid = {42725564},
issn = {1724-6040},
abstract = {BACKGROUND: Artificial liver support therapy (ALS) is increasingly used in liver failure, but its immunomodulatory effects remain incompletely understood. This pilot study aimed to investigate changes in plasma cytokines and T lymphocyte subsets following ALS.

METHODS: Twenty-seven patients with liver failure who received ALS were enrolled. Plasma levels of TNFα, IL-4, IL-6, IL-10, IL-17, IL-2, and IFN-γ, as well as T lymphocyte subsets (CD4+ T cell absolute count, CD4+/CD8+ ratio), were measured before and after treatment. Paired t‑tests were used for comparisons. Patients were dichotomized by median pre-treatment TNFα level to compare clinical outcomes.

RESULTS: After ALS, TNFα levels decreased significantly (2.537 ± 1.519 vs 1.522 ± 0.749 pg/mL, p = 0.004). IL-4 also showed a significant reduction (1.463 ± 1.165 vs 0.893 ± 0.648 pg/mL, p = 0.031). CD4+ T cell absolute count increased significantly (430.85 ± 220.15 vs 636.63 ± 429.27 cells/μL, p = 0.034). Total T cell count showed an increasing trend (788.70 vs 1093.63 cells/μL, p = 0.064). Patients with low pre-treatment TNFα levels (below median) had a significantly higher improvement rate compared to those with high TNFα levels (100% vs 71.4%, p = 0.036).

CONCLUSION: ALS therapy is associated with a significant reduction in TNFα and a significant increase in CD4+ T cell absolute count, suggesting potential anti‑inflammatory and immune‑restorative effects. Lower baseline TNFα levels may predict favorable short‑term outcomes.},
}

@article {pmid42722112,
year = {2026},
author = {Butt, TH and Strait, M and Marcinczyk, L and Katz, G and Kalia, V and Jaafar, C and Saxena, R and Divjan, A and Saglimbeni, B and Munoz Umanes, ME and Tipps, E and Han, M and Mehta, P and Lee, I and Mitsumoto, H and Factor-Litvak, P and Shneider, NA and Kioumourtzoglou, MA and Re, DB},
title = {Astrocyte-derived extracellular vesicle phosphorylated TDP-43 as a blood-based biomarker for amyotrophic lateral sclerosis.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107601},
doi = {10.1016/j.nbd.2026.107601},
pmid = {42722112},
issn = {1095-953X},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by central nervous system (CNS) neuroglial TAR DNA-binding protein 43 (TDP-43) pathology in ~90-95% of cases. Non-invasive biomarkers are critically needed to reduce diagnostic delay, enable patient stratification, and assess treatment efficacy in clinical trials. Astrocyte-derived extracellular vesicles (ADEVs) represent promising CNS liquid biopsy biomarkers, given astrocyte involvement in ALS pathogenesis and the ability of ADEVs to cross the blood-brain barrier and carry TDP-43. Here, we assessed the diagnostic performance of TDP-43 and its hyperphosphorylated pathological form, phospho-Ser409 (pTDP-43), quantified in ADEVs, for distinguishing ALS cases from matched healthy controls. ADEVs were immunoisolated from whole blood (n = 76) and plasma (n = 86) across three ALS biorepositories/cohorts. ADEV quality and enrichment were validated in accordance with minimal information for studies of extracellular vesicles guidelines, and protein levels were normalized by ratio to tetraspanin cluster of differentiation 81 (CD81). Diagnostic accuracy was evaluated by logistic regression and random forest models with cross-validation, adjusting for age and sex across 100 random seeds. Plasma ADEV pTDP-43/CD81 ratio best predicted ALS case status, with a mean AUC of 0.89 (95% CI: 0.75-0.99) from logistic models, corresponding to a mean sensitivity and specificity of 87% and 89%, respectively, and a mean AUC of 0.86 (95% CI: 0.82-0.90) from random forest models. Although the specificity of ADEV pTDP-43 relative to disease mimics and associations with disease progression require further investigation, these findings support its potential as a biomarker candidate for ALS and for patient stratification in TDP-43-targeted clinical trials.},
}

@article {pmid42725432,
year = {2026},
author = {Wieland, CM and Wright, SE and Willey, S and Purwar, I and Grudzien, SJ and Krans, A and Laimon, EL and Asher, MJ and Isaacs, AM and Garner, AL and Todd, PK},
title = {Altered neuronal start codon stringency favors cap-independent repeat-associated non-AUG translation.},
journal = {Nucleic acids research},
volume = {54},
number = {17},
pages = {},
doi = {10.1093/nar/gkag880},
pmid = {42725432},
issn = {1362-4962},
support = {R01NS086810/NH/NIH HHS/United States ; R01NS099280/NH/NIH HHS/United States ; P50HD104463/NH/NIH HHS/United States ; R35 GM153185/NH/NIH HHS/United States ; F31NS113513/NH/NIH HHS/United States ; T32 GM141840/NH/NIH HHS/United States ; I01BX004842-04/BX/BLRD VA/United States ; //UM MSTP/ ; //NGP/ ; },
mesh = {*Neurons/metabolism ; *Codon, Initiator ; Animals ; Humans ; RNA Caps/metabolism/genetics ; C9orf72 Protein/genetics ; *Peptide Chain Initiation, Translational ; *Protein Biosynthesis ; DNA Repeat Expansion ; Eukaryotic Initiation Factor-4E/antagonists & inhibitors ; RNA, Messenger/metabolism/genetics ; Guanosine/analogs & derivatives/metabolism ; },
abstract = {Intronic GGGGCC repeat expansions in C9orf72 cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This expansion supports a non-canonical form of translational initiation known as repeat-associated non-AUG (RAN) translation to produce toxic dipeptide repeat proteins that contribute to neurodegeneration. Here, we find that the efficiency of RAN translation and its dependency on the 5' 7-methylguanosine mRNA cap are variable across cell types, with both rodent neurons and human iNeurons favoring cap-independent RAN translation from two distinct repeats (CGG and GGGGCC) across multiple reading frames. Treatment with an eIF4E inhibitor that blocks cap-dependent translation enhances RAN translation specifically in neurons. Intriguingly, cap-independent RAN translation exhibits less reliance on near-cognate codons for initiation than cap-dependent RAN translation. This finding led us to identify a surprising global alteration in neuronal start codon stringency as a contributor to the relatively higher cap-independent RAN translation in this cell type. This effect correlates with cytoplasmic redistribution of eIF1 in neurons and is reversed with overexpression of the eukaryotic initiation factor eIF5, which relaxes start codon stringency and preferentially enhances cap-dependent RAN translation. Together, these findings reveal several neuron-specific features of translational regulation that favor cap-independent RAN translation with implications for nucleotide repeat expansion disorder pathogenesis.},
}

*Neurons/metabolism
*Codon, Initiator
Animals
Humans
RNA Caps/metabolism/genetics
C9orf72 Protein/genetics
*Peptide Chain Initiation, Translational
*Protein Biosynthesis
DNA Repeat Expansion
Eukaryotic Initiation Factor-4E/antagonists & inhibitors
RNA, Messenger/metabolism/genetics
Guanosine/analogs & derivatives/metabolism

@article {pmid42716045,
year = {2026},
author = {Teunissen, CE and Vermunt, L and Barthélemy, NR and Benzinger, TLS and Graff-Radford, J and Verberk, IMW and Zetterberg, H and Schindler, SE and Jack, CR},
title = {Fluid biomarkers in the evolving care landscape of Alzheimer's disease and related disorders.},
journal = {The Lancet. Neurology},
volume = {25},
number = {10},
pages = {926-938},
doi = {10.1016/S1474-4422(26)00246-2},
pmid = {42716045},
issn = {1474-4465},
mesh = {Humans ; *Biomarkers/cerebrospinal fluid/blood ; *Alzheimer Disease/cerebrospinal fluid/diagnosis/blood ; tau Proteins/cerebrospinal fluid ; Animals ; },
abstract = {Fluid biomarkers for Alzheimer's disease have advanced rapidly during the past several years driven by breakthroughs including development of ultrasensitive and multiplexing technologies and high specificity antibodies. Blood-based biomarkers, such as neurofilament light for frontotemporal dementia and amyotrophic lateral sclerosis, and phosphorylated tau 217 for the diagnosis of Alzheimer's disease, are now being implemented in clinical practice, which is particularly timely because of the increasing clinical availability of amyloid-targeting treatments in Alzheimer's disease. Multiple fluid biomarkers are needed to capture the complexity of disease mechanisms for precise diagnosis and to measure the diverse pathologies that lead to dementia, such as vascular, α-synuclein, and TDP-43 pathologies. Moreover, fluid biomarkers can aid in capturing heterogeneity in treatment course between patients, probably due to copathologies or key intermediates, including microglia and astrocyte dysregulation. Increased focus on biomarker-pathology relationships in experimental models will likely accelerate biomarker development and further the understanding of their precise substrates. Future clinical implementation of biomarkers to capture the full complexity of pathologies will likely be facilitated by the expansion of diagnostic methods, development of point of care technologies, and remote sampling approaches.},
}

Humans
*Biomarkers/cerebrospinal fluid/blood
*Alzheimer Disease/cerebrospinal fluid/diagnosis/blood
tau Proteins/cerebrospinal fluid
Animals

@article {pmid42719214,
year = {2026},
author = {Mittal, D and Solanki, P and Jain, GK and Jhawat, V and Kesharwani, P and Dutt, R and Arora, S and Singh, RP},
title = {Herbal nanoparticles in the treatment of neurodegeneration: from molecular mechanisms to therapeutic translation.},
journal = {3 Biotech},
volume = {16},
number = {10},
pages = {420},
pmid = {42719214},
issn = {2190-572X},
abstract = {UNLABELLED: Neurodegenerative diseases (NDDs), including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss involving multiple pathological mechanisms, including protein aggregation, oxidative stress, neuroinflammation, and mitochondrial dysfunction. Although conventional therapies provide symptomatic relief, they fail to halt disease progression and are limited by poor blood-brain barrier (BBB) penetration, off-target effects, and systemic toxicity. Likewise, several herbal bioactives, such as curcumin, resveratrol, quercetin, and epigallocatechin gallate, exhibit promising neuroprotective properties but suffer from poor aqueous solubility, low oral bioavailability, rapid metabolism, and inadequate brain delivery. Nanotechnology-based delivery systems have emerged as a promising approach to overcome these pharmacokinetic limitations by enhancing stability, controlled release, BBB transport, and brain accumulation of herbal therapeutics. This review critically summarizes recent advances in herbal nanoformulations, emphasizing disease-specific molecular targets, BBB-targeting strategies, comparative nanocarrier systems, pharmacokinetic optimization, intracellular trafficking, and translational challenges. Unlike previous reviews, it integrates recent evidence on nanotoxicology, manufacturing scalability, quality control, regulatory considerations, and emerging technologies, including biomimetic nanoparticles and extracellular vesicles. Despite encouraging preclinical outcomes, clinical evidence remains limited, and no herbal nanoformulation has yet demonstrated definitive efficacy or received regulatory approval for neurodegenerative diseases. Future clinical translation will require standardized formulations, rigorous safety evaluation, and well-designed clinical trials. Unlike previous reviews that primarily summarize individual nanocarrier systems or herbal therapeutics, the present review provides a comprehensive and critical synthesis of the current evidence by integrating disease-specific molecular mechanisms, herbal bioactives, nanocarrier design strategies, blood-brain barrier transport mechanisms, intracellular trafficking, pharmacokinetic considerations, translational barriers, regulatory challenges, clinical evidence, and emerging technologies. Furthermore, the review identifies major knowledge gaps and future research priorities to facilitate the successful clinical translation of herbal nanoformulations for neurodegenerative disorders.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s13205-026-05048-8.},
}

@article {pmid42720979,
year = {2026},
author = {Huang, CS and Sanchez-Santos, C and Martinez-Gonzalez, L and Gil, C and Martinez, A},
title = {Innovative therapies under clinical development for ALS treatment. Part 2: biologics and natural products.},
journal = {Expert opinion on investigational drugs},
volume = {},
number = {},
pages = {},
doi = {10.1080/13543784.2026.2729512},
pmid = {42720979},
issn = {1744-7658},
abstract = {INTRODUCTION: The clinical trial landscape for Amyotrophic Lateral Sclerosis (ALS) is rapidly expanding despite ongoing translational challenges. Following our 2022 analysis and as a continuation of Part 1, which focused on small molecules, this review provides a structured overview of biologics and natural products in the ALS clinical pipeline. Particular emphasis is placed on candidates that entered, advanced through, or completed clinical evaluation between 2022 and the end of 2025.

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

EXPERT OPINION: Modern biotechnology, ethnopharmacology, and classical pharmacology are increasingly converging in ALS therapeutic development, making this one of the most active areas of neurodegenerative disease research. Nevertheless, major challenges remain, including central nervous system (CNS) penetration, long-term safety, interpatient variability, limited clinical evidence, and the need for reliable biomarkers. Emerging technologies, such as big data analytics and artificial intelligence, may help accelerate and optimize therapeutic development, as well as improve patient recruitment and stratification.},
}

@article {pmid42721706,
year = {2026},
author = {Viljoen, S and Chaves, JCS and Peall, I and White, AR and Oikari, LE},
title = {Dysfunction of the blood-brain barrier and neurovascular unit in amyotrophic lateral sclerosis - From advanced human models to treatments.},
journal = {Journal of the neurological sciences},
volume = {490},
number = {},
pages = {126168},
doi = {10.1016/j.jns.2026.126168},
pmid = {42721706},
issn = {1878-5883},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, characterized by the degeneration of motor neurons, resulting in progressive and eventually complete loss of motor function. The phenotypical heterogeneity of ALS poses a challenge to early diagnosis and treatment, with currently available therapeutics only capable of relieving symptoms and slowing progression. While ALS is classified as a motor neuron disease (MND), research has identified significant impairment to the blood-brain barrier (BBB) and neurovascular unit (NVU) of ALS patients. The BBB along with supporting cells of the NVU selectively control the entry of substances into the central nervous system (CNS) and maintain brain homeostasis, with its many cellular components demonstrating impaired function, specifically relating to inflammation, oxidative stress and TDP-43 proteinopathy. The advent of more advanced in vitro techniques as well as use of patient-derived BBB cells has presented a promising alternative to recreate the in vivo structure of the BBB/NVU in a highly controlled platform. Such approaches have ranged from simple 2-dimensional (2D) cell culture to intricate 3-dimensional (3D) co-culture systems, as well as microfluidic systems and organoids, with a potential to investigate ALS associated BBB/NVU dysfunction and drug discovery. This review provides a comprehensive assessment of known BBB/NVU dysfunction in ALS and methods of investigating this using in vitro and in vivo platforms with a focus on inflammation, oxidative stress and pathological TDP-43 expression. This review also presents a future perspective to overcoming barriers to treatment of ALS using new patient-derived BBB/NVU model systems.},
}

@article {pmid42722039,
year = {2026},
author = {Morisaki, Y and Nomura, N and Matsuda, M and Ohshima, M and Fukuda, R and Komine, O and Okuda, T and Yamanaka, K and Misawa, H},
title = {Anti-LAG-3 antibody treatment initiated after symptom onset extends survival in ALS model mice.},
journal = {Neuroscience research},
volume = {},
number = {},
pages = {105119},
doi = {10.1016/j.neures.2026.105119},
pmid = {42722039},
issn = {1872-8111},
abstract = {Immune checkpoint molecules have emerged as regulators of microglial function in neurodegenerative diseases. We previously demonstrated that LAG-3 shapes disease-associated microglial phenotypes in ALS and that germline LAG-3 deletion in SOD1[G93A] mice accelerated disease onset but extended duration, leaving survival unchanged. Here, we investigated the therapeutic efficacy of anti-LAG-3 antibody treatment starting after symptom onset. Anti-LAG-3 treatment extended survival, slowed neurological and motor decline, preserved body weight and motor neurons, and reduced microgliosis. Within microglia, the Axl[+] phagocytic-module fraction increased while the Dectin-1[+] inflammatory-module fraction decreased. These findings indicate that post-onset LAG-3 inhibition is a promising therapeutic strategy for ALS.},
}

@article {pmid42710553,
year = {2026},
author = {Babu, D and Le, TH and Liu, H and Raji, D and Tran, NH and Lockhart, S and Tran, P and Eldalal, O and Tonoyan, L and Siraki, AG},
title = {Edaravone as an antioxidant adjuvant to attenuate clozapine toxicity in vitro.},
journal = {Toxicology letters},
volume = {},
number = {},
pages = {113188},
doi = {10.1016/j.toxlet.2026.113188},
pmid = {42710553},
issn = {1879-3169},
abstract = {Despite being the gold-standard therapy for treatment-resistant schizophrenia, clozapine use remains constrained by the risk of rare but serious adverse drug reactions, including severe neutropenia and agranulocytosis. Neutrophil myeloperoxidase (MPO)-mediated bioactivation of clozapine to reactive metabolites has long been implicated in agranulocytosis. Although clozapine is metabolized by MPO, there are numerous other compounds that can also be metabolized by this enzyme. Edaravone is a drug used to treat amyotrophic lateral sclerosis and has potent antioxidant activity; we have previously shown that edaravone is metabolized by MPO. Therefore, we hypothesized that edaravone can attenuate early toxicological events associated with clozapine through MPO modulation. Using purified human MPO, MPO-rich human promyelocytic leukemia (HL-60) cells, and isolated human neutrophils, we evaluated clozapine oxidation, competitive intracellular uptake, protein adduct formation, and cytotoxicity. UV-visible spectroscopy demonstrated concentration-dependent inhibition of MPO-catalyzed clozapine oxidation by edaravone, with 100µM edaravone producing suppression comparable to 100µM 4-aminobenzoic acid hydrazide. LC-MS analysis showed that MPO/H2O2 reduced clozapine levels to 26.7 ± 2.9% of control, whereas co-incubation with edaravone preserved clozapine to 67.9 ± 16.2%. Under the same conditions, edaravone was almost completely consumed (0.03 ± 0.02% remaining), consistent with its sacrificial antioxidant activity. In HL-60 cells, edaravone attenuated MPO activity and did not significantly alter clozapine uptake after 30minutes (97.2 ± 7.6% of clozapine alone). Immunoblotting revealed that edaravone reduced clozapine-protein adduct formation in purified MPO, HL-60 cells, and neutrophils. Clozapine (75µM) induced marked HL-60 cytotoxicity after 24hours, whereas edaravone concentration-dependently restored viability, with 200µM fully preventing toxicity. These findings provide proof-of-concept that edaravone mitigates multiple mechanistic events linked to clozapine-induced hematological toxicity and may represent a potential strategy to improve clozapine safety.},
}

@article {pmid42712181,
year = {2026},
author = {Mohajerin, B and Howard, R and Pincus, AL},
title = {A Response to Dimaggio et al.'s Commentary on Mohajerin et al. (2026).},
journal = {Clinical psychology & psychotherapy},
volume = {33},
number = {5},
pages = {e70332},
doi = {10.1002/cpp.70332},
pmid = {42712181},
issn = {1099-0879},
mesh = {Humans ; *Psychotherapy/methods ; Randomized Controlled Trials as Topic ; },
abstract = {Our randomized controlled trial comparing Unified Protocol (UP) and Schema-Focused Therapy (SFT) for grandiose and vulnerable presentations of narcissism has recently been critiqued in a commentary by Dimaggio et al. (2026). These authors raised concerns regarding the study's recruitment and subgroup classification, gender distribution, treatment response patterns, absence of dropouts, randomization, screening and recruitment procedures, trial registration, outcome assessment, supervision and treatment fidelity, treatment dose and duration, and disclosure of the NPD diagnosis. In this response, we clarify these methodological and procedural issues and provide additional information that was not fully described in the original article. We maintain that while both treatments were effective in ameliorating symptoms of narcissism, SFT was more effective in treating grandiose features, while UP was more effective in treating vulnerable features. Trial Registration: Iranian Registry of Clinical Trials identifier: IRCT20231106059970N3.},
}

Humans
*Psychotherapy/methods
Randomized Controlled Trials as Topic

@article {pmid42713950,
year = {2026},
author = {Bernard, ME and Harrison, I},
title = {Dynamically biased microcanonical treatment of HCl dissociative chemisorption on Au(111) yields thermal associative desorption dynamics by detailed balance.},
journal = {The Journal of chemical physics},
volume = {165},
number = {10},
pages = {},
doi = {10.1063/5.0345352},
pmid = {42713950},
issn = {1089-7690},
abstract = {A dynamically biased microcanonical transition state theory model of HCl dissociative chemisorption on Au(111) was recently developed for Shirhatti et al.'s [J. Phys. Chem. Lett. 7, 1346 (2016)] non-equilibrium supersonic molecular beam experiments where normal translational energies varied over a 50-250 kJ/mol range. Model parameters include a relatively low threshold energy for reaction, E0 = 30.88 kJ/mol; an efficiency, εn = 0.26, for molecular normal translational energy to contribute to the active exchangeable energy capable of promoting reaction; and one surface oscillator, s = 1, involved in the local gas-surface collision complex wherein energy was taken as microcanonically exchangeable, although potentially subject to dynamical bias through efficiencies. To validate the model, detailed balance was used to predict the desorbing HCl product state distributions from thermal associative desorption of H(c) + Cl(c) on Au(111) that have been measured by Rettner and Auerbach [Science 263, 365 (1994)] while impinging a H atom beam onto a chlorinated Au(111) surface. Modeling of Rettner's [J. Chem. Phys. 101, 1529 (1994)] rovibrationally resolved HCl product state distributions allowed for the additional establishment of a rotational efficiency of εr = 0.23 that led to consistent prediction of both the thermal associative desorption and the supersonic molecular beam experimental results. The HCl(g) ⇄ H(c) + Cl(c) reactivity on Au(111) is thereby identified as a new benchmark system for gas-surface reactivity where highly detailed experimental data are available coming from both sides of the reaction barrier. The activation energy for thermal associative desorption was estimated as Ea,assoc = 5.6 ± 1.3 kJ/mol based on four independent kinds of measurement. The effect of dynamics on the thermal dissociative sticking coefficient, S(T), of interest in practical catalysis, was quantitatively assessed. As compared to a statistically behaving HCl/Au(111) system with Ea = 31 kJ/mol, dynamics reduced S(T) by a factor of 10 at 800 K, equivalent to an increase in activation energy of ΔEa = 15 kJ/mol.},
}

@article {pmid42716044,
year = {2026},
author = {Cudkowicz, ME and Shefner, J and van den Berg, LH and Chio, A and Fan, D and Großkreutz, J and Lunetta, C and Tsai, RM and Li, Y and Wallstroem, E and Xiong, L and Chen, Y and Atassi, N and , },
title = {Safety, tolerability, and efficacy of RIPK1 inhibitor, SAR443820, in amyotrophic lateral sclerosis (HIMALAYA): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.},
journal = {The Lancet. Neurology},
volume = {25},
number = {10},
pages = {900-910},
doi = {10.1016/S1474-4422(26)00277-2},
pmid = {42716044},
issn = {1474-4465},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Double-Blind Method ; Middle Aged ; Male ; Female ; Aged ; Adult ; Aged, 80 and over ; Young Adult ; Treatment Outcome ; Adolescent ; },
abstract = {BACKGROUND: RIPK1, a protein regulating inflammatory signalling and cell death, is implicated in amyotrophic lateral sclerosis (ALS) pathophysiology. SAR443820 is a selective, oral, CNS-penetrant, reversible RIPK1 inhibitor. We aimed to evaluate the safety, tolerability, and efficacy of SAR443820 in participants with ALS.

METHODS: This multicentre, randomised, double-blind, placebo-controlled, phase 2 trial was conducted at 63 clinical sites in 13 countries (Belgium, Canada, China, France, Germany, Italy, Japan, the Netherlands, Poland, Spain, Sweden, the UK, and the USA). Adults (aged 18-80 years) with a diagnosis of possible ALS, clinically probable ALS, clinically probable laboratory-supported ALS, or clinically definite ALS, in accordance with the revised El Escorial World Federation of Neurology criteria, were randomly assigned (2:1) by use of a stratified block design (blocks of three) to receive either 20 mg SAR443820 orally twice per day or matching placebo in the 24-week double-blind period. Randomisation was done centrally using interactive response technology and stratified by geographical region of trial site, region of ALS onset, use of riluzole, use of edaravone, and use of the combination of sodium phenylbutyrate and taurursodiol. Participants, care providers, investigators, and outcomes assessors were masked to trial intervention. The primary outcome was a change in ALS Functional Rating Scale Revised (ALSFRS-R) total score from baseline to week 24 and was calculated for all participants who had an ALSFRS-R total score available at baseline and at week 24. Safety analyses included all randomly assigned participants receiving one dose or more of trial intervention. This trial is registered with ClinicalTrials.gov (NCT05237284) and was terminated early.

FINDINGS: Between April 13, 2022, and July 17, 2023, 397 participants were screened and 305 randomly assigned to SAR443820 (n=203) or placebo (n=102); six were excluded from the primary analysis due to missing baseline ALSFRS-R values. Mean age was 56·9 years (SD 11·5); 183 (60%) participants were male and 122 (40%) were female. Least squares mean change in ALSFRS-R from baseline to week 24 was -6·73 (95% CI -7·48 to -5·98) for SAR443820 group (n=169) and -6·32 (-7·36 to -5·27) for placebo group (n=87). There was no statistically significant difference between the study groups (least squares mean difference -0·41 [95% CI -1·71 to 0·88]). Participants in the SAR443820 group had higher incidence of adverse events (171 [85%] of 202 vs placebo 80 [78%] of 102) and treatment discontinuations (28 [14%] of 202 vs placebo five [5%] of 102), with elevated hepatic enzymes being the most common cause. Nine deaths occurred in the double-blind period (seven [3%] of 202 in the SAR443820 group and two [2%] of 102 in the placebo group); none was attributed to SAR443820.

INTERPRETATION: SAR443820 did not show clinical benefit and was associated with higher hepatic enzyme increase, indicating that further clinical development of SAR443820 in ALS is not warranted.

FUNDING: Sanofi.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy
Double-Blind Method
Middle Aged
Male
Female
Aged
Adult
Aged, 80 and over
Young Adult
Treatment Outcome
Adolescent

@article {pmid42701881,
year = {2026},
author = {Zhu, Y and Zhang, Y and Yan, T and Li, Y and Du, H and Zhang, S and Zhang, T and Zhou, W},
title = {The Role of overdose Folic Acid in Promoting Neuroinflammation, Oxidative Stress, and Apoptosis in SOD1-G93A Mice.},
journal = {Free radical research},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/10715762.2026.2729677},
pmid = {42701881},
issn = {1029-2470},
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition that involves the targeted degeneration of motor neurons. The precise pathogenetic mechanisms are still largely unclear. In this study, we utilized the SOD1-G93A mouse model of ALS to investigate the effects of folic acid (FA), an important factor involved in homocysteine metabolism. Our results indicated that a little FA prolong the lifespan of the SOD1-G93A mice and medium and high dose FA significantly shortened the lifespan of the SOD1-G93A mice. Furthermore, we observed that overdose FA significantly elevated inflammation levels in the cerebellum, as evidenced by increased concentrations of tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Cluster of Differentiation 68 (CD68), Cluster of Differentiation 86 (CD86), and Monocyte Chemoattractant Protein-1 (MCP-1), facilitating microglial activation. The low dose FA were the opposite of the overdose FA. Additionally, high dose FA increased the levels of phosphorylated p65 (p-p65)/p65, thereby promoting the NF-κB signaling pathway. Conversely, high dose FA inhibited the expression of total superoxide dismutase (T-SOD) while increasing the level of malondialdehyde (MDA) in the cerebellum; these effects were not observed in muscle tissue. Moreover, high dose FA elevated the levels of Bax2/Bcl-2. Concurrently, high dose FA induced increased apoptosis in SOD1-G93A mice, as demonstrated by TUNEL staining. Notably, the brain iron content of SOD1-G93A mice remained unchanged following FA treatment. These findings provide evidence that overdose FA supplementation may exert pro-inflammatory effects by promoting the NF-κB pathway, oxidative stress, and apoptosis in the context of ALS.},
}

@article {pmid42706741,
year = {2026},
author = {Grouls, A and Ubel, PA and Nguyen, M and Pathapati, N and Doerstling, S and Sloan, CE},
title = {Online Crowdfunding Campaigns for People Living With ALS Demonstrate Financial Burden and Unmet Needs.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70395},
pmid = {42706741},
issn = {1097-4598},
abstract = {INTRODUCTION/AIMS: People living with amyotrophic lateral sclerosis (ALS; pALS) have extensive care needs, from wheelchairs to feeding tubes to caregiving support. The financial impact of these needs on pALS and their caregivers (cALS) has not been fully explored. We aimed to explore the types of expenses for which pALS and cALS crowdfund, and the financial circumstances that lead them to resort to crowdfunding.

METHODS: We randomly selected 320 ALS-related crowdfunding campaigns posted on the GoFundMe platform from 2010-2020. We conducted a summative content analysis to categorize the expenses for which campaigns requested money and descriptions of financial burden.

RESULTS: We included 266 campaigns. Most campaigns were written by people who were not the pALS or cALS, such as children or coworkers (85.3%). Most campaigns fundraised for medication and treatment costs (21.4%), equipment (25.2%), accessibility needs for home (24.0%), and transportation (19.5%), and in-home caregiving services (18%). Multiple campaigns (22.9%) requested assistance with nonmedical expenses ranging from rent and utilities to personal travel and hobby goals. Many campaign writers (47.7%) described financial burden related to the pALS' diagnosis, including medical debt (4.5%) and job loss of the pALS (30.5%) and/or cALS (6.8%).

DISCUSSION: Our analysis of ALS-related crowdfunding campaigns highlights the breadth of medical and nonmedical care needs and quality of life goals for which people request additional financial support throughout the disease course. These findings provide important insights for ALS care teams into the expenses of pALS.},
}

@article {pmid42709165,
year = {2026},
author = {Hamzeh, LH and Seyed, E and Elgendy, MA and Heib, D and Sadek, BI and Mohammed, COS and El Refaei, K and Soliman, YF and Eldmrdash, N and Abdelgalil, MS and Elsayed, MM},
title = {Efficacy and safety of memantine in adults with amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {Journal of neural transmission (Vienna, Austria : 1996)},
volume = {},
number = {},
pages = {},
pmid = {42709165},
issn = {1435-1463},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with limited disease-modifying treatment options. Memantine, an N-methyl-D-aspartate receptor antagonist, has been investigated in ALS, but its safety remains unclear. This study systematically assessed the safety of memantine in adults with ALS. A systematic review and meta-analysis was conducted following PRISMA 2020 guidelines, searching PubMed, Cochrane Library, Scopus, and Web of Science for randomized controlled trials of memantine in adults with ALS. Outcomes included ALSFRS-R and FVC decline, adverse neurological events, total and serious adverse events, treatment discontinuation, and all-cause mortality. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Because of heterogeneous reporting and missing variance estimates, ALSFRS-R and FVC outcomes were synthesized narratively; only safety outcomes were pooled quantitatively. Three randomized controlled trials (706 participants) met the inclusion criteria. Functional and respiratory outcomes could not be pooled because of heterogeneous reporting, and no consistent benefit was observed. Memantine showed lower headache incidence than placebo (RR 0.43; 95% CI 0.19-0.96), with no significant differences in constipation, falls, dizziness, treatment discontinuation, or all-cause mortality. Memantine showed a borderline increase in serious adverse events (RR 1.52; 95% CI 1.00-2.31) and a higher risk of total adverse events (RR 1.19; 95% CI 1.09-1.30). Memantine was associated with a small but significant increase in total adverse events and a trend toward more serious adverse events, without improving functional decline, respiratory function, or survival in ALS. Current evidence does not support its use as a disease-modifying or adjunctive therapy. Trial registration: PROSPERO CRD420261277874.},
}

@article {pmid42709336,
year = {2026},
author = {Colosimo, C},
title = {The Great Transatlantic Divide: The Case of Experimental Neuropharmacology.},
journal = {Clinical drug investigation},
volume = {},
number = {},
pages = {},
pmid = {42709336},
issn = {1179-1918},
abstract = {Despite substantial agreement between the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) on new drug approval in the past decades, a few new drugs for the treatment of some of the most prevalent and severe neurological disorders, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, as well as much rarer neurogenetic disorders, were handled differently by the two regulatory agencies. The possible reasons for the differing behaviors of the FDA and EMA are several and wide-ranging, and they will be examined in this opinion-based analysis. How patients' perceptions of the complex approaches to drug approval and commercialization may create disappointment and confusion will also be reappraised.},
}

@article {pmid42697379,
year = {2026},
author = {Mohammad, SI and Vasudevan, A and Oriquat, G and Gajjar, TB and Hanumanthayya, M and Shukla, SK and Tailor, NK and Baig, MR and Fadaam, O and Abdul, AS},
title = {Extracellular Vesicles in Neurodegenerative Diseases: A New Frontier in Diagnosis and Therapy.},
journal = {Behavioural brain research},
volume = {},
number = {},
pages = {116455},
doi = {10.1016/j.bbr.2026.116455},
pmid = {42697379},
issn = {1872-7549},
abstract = {Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease are among the progressive disorders of the nervous system that are characterized by the gradual destruction of neurons, the accumulation of misfolded proteins, and the limited effective therapeutic options. In recent years, numerous lines of evidence have emphasized the important role of extracellular vesicles (EVs) in the formation and progression of these diseases. These vesicles are membrane-bound nanoscale structures that are secreted by almost all cell types and play a role in cell-cell communication through the transfer of molecules such as proteins, lipids, and nucleic acids. In neurodegenerative disorders, EVs can facilitate the transport and dissemination of disease-related proteins, including amyloid-β, tau, α-synuclein, mutant huntingtin, SOD1, and TDP-43, thus contributing to the spread of pathological processes in different parts of the nervous system. On the other hand, the ability of these vesicles to cross the blood-brain barrier and reflect molecular changes occurring in the central nervous system makes them valuable candidates for the development of minimally invasive biomarkers. This review reviews the biogenesis, classification, isolation methods, and molecular content of EVs, and analyzes their role in the pathogenesis, diagnosis, and treatment of the most important neurodegenerative diseases. Also, the importance of EV-associated proteins, RNAs, and lipids as emerging diagnostic biomarkers, as well as the therapeutic potential of natural and engineered vesicles as drug delivery systems and regulators of neuroinflammation and neurodegenerative processes, is discussed.},
}

@article {pmid42701411,
year = {2026},
author = {Gonzo, P and Dunkl, S and Gatterbauer, M and Heider, S and Girsa, M and Krammel, M and Schnaubelt, S},
title = {Structured Evaluation and Treatment of cardiac arrest via the ABCDE approach (SETA) - Rethinking high-performance CPR and cause-finding during Advanced Life Support.},
journal = {Resuscitation plus},
volume = {31},
number = {},
pages = {101458},
pmid = {42701411},
issn = {2666-5204},
abstract = {The European Resuscitation Council (ERC) Guidelines 2025 continue to summarize the causes of cardiac arrest that should be sought during advanced life support (ALS) as "4Hs and 4Ts". While well established, this list-based mnemonic does not map onto the airway-breathing-circulation-disability-exposure (ABCDE) sequence that emergency teams use for every other patient assessment, and it excludes causes that are clinically treatable but not classically "reversible" in the prehospital phase. We present SETA (Structured Evaluation and Treatment of cardiac arrest via the ABCDE approach), a concept developed within the Emergency Medical Service Vienna that restructures both cause-finding during cardiopulmonary resuscitation (CPR) and evaluation of high-performance CPR around the ABCDE sequence, embeds protocol-linked actions at each step, and is designed to run within ongoing chest compressions without interrupting them. We outline its rationale, its relationship to existing pit-crew and ABCDE-based resuscitation models, and the prospective evaluation now needed before considered for wider use.},
}

@article {pmid42686219,
year = {2026},
author = {Liu, J and Lin, J and Liu, H and Soh, K and Ju, Q and Soh, K and Dong, X},
title = {Efficacy of Antimicrobial Lock Solutions on Central Line-Associated Bloodstream Infection and Catheter Survival in Hemodialysis Patients: A Systematic Review and Meta-Analysis.},
journal = {Seminars in dialysis},
volume = {},
number = {},
pages = {},
doi = {10.1111/sdi.70046},
pmid = {42686219},
issn = {1525-139X},
support = {202301A014//Chengde Science and Technology Program/ ; GJXH2021-126//Hebei Higher Education Association "14th Five-Year Plan" Research Project/ ; H2026406068//Hebei Natural Science Foundation/ ; 202307//Chengde Medical university Project/ ; 202404//Chengde Medical university Project/ ; },
abstract = {Hemodialysis (HD) catheters carry a high risk of life-threatening bloodstream infections and failure. Antimicrobial lock solutions (ALS) are used to reduce this risk, but their overall efficacy on key outcomes like infection rates and catheter survival requires comprehensive evaluation. This systematic review and meta-analysis assess the impact of ALS on preventing catheter-related bloodstream infections (including incidence and density) and on improving catheter survival. A systematic search was conducted across the databases of PubMed, Embase, Scopus, Cochrane Library, and Google Scholar. A meta-analysis was conducted using STATA software. A total of 1183 studies were screened based on title and abstract, and further 282 studies were evaluated in full text. Eventually, 14 studies with 15 treatment arms were included. Key outcomes including central line-associated bloodstream infection (CLABSI), exit infection, and catheter-free survival were conducted separately. ALS demonstrated statistically significant benefits on CLABSI infection and catheter-free survival compared to nonantimicrobial solutions, showing a reduction in CLABSI density with a pooled log odd ratio (logOR) of -1.29 (95% CI: -1.59 to -0.99), lower CLABSI rates (pooled logOR = -1.50, 95% CI: -1.85 to -1.15), and improved catheter-free survival with log hazard ratio (logHR) of -1.11 (95% CI: -1.41 to -0.8). Consistent treatment effects were observed across all lock types with no significant heterogeneity detected. ALS demonstrate statistically significant and clinically important efficacy in reducing CLABSI incidence and density while improving catheter survival in HD patients, establishing them as an essential preventive strategy in clinical practice.},
}

@article {pmid42693185,
year = {2026},
author = {Dalakas, MC and Lünemann, JD},
title = {Role of complement and complement-targeted therapeutics in neurological diseases.},
journal = {Nature reviews. Neurology},
volume = {},
number = {},
pages = {},
pmid = {42693185},
issn = {1759-4766},
abstract = {Complement comprises a group of plasma and membrane proteins that provide an effective bridging function for innate and adaptive humoral immunity. Understanding complement pathophysiology is fundamental given that inappropriate complement function in host defence can lead to infectious diseases and inefficient disposal of altered, damaged or senescent cells can lead to or enhance autoimmune neurological processes. Although the rising number of approved drugs targeting complement pathways remains primarily focused on diseases with complement-fixing pathogenic antibodies (such as myasthenia gravis and neuromyelitis optica spectrum disorder), a robust pipeline of emerging treatments holds promise for expanding complement-targeted therapies to a broader spectrum of autoimmune neurological diseases, such as multiple sclerosis and even neurodegenerative diseases such as Alzheimer disease or amyotrophic lateral sclerosis. This Review presents insights into complement biology as it relates to the development or initiation of autoimmune and possibly degenerative diseases affecting the central and peripheral nervous systems or muscle. The effects, merits, risks and challenges of marketed drugs or biologic agents in ongoing phase I-III clinical trials engineered to inhibit proximal or distal components of the complement cascade are also discussed. Anti-complement therapeutics are destined to change the treatment of autoimmune neurologic conditions in which the therapeutic landscape is now becoming crowded with biologic agents targeting other key autoimmunity factors.},
}

@article {pmid42697152,
year = {2026},
author = {Fernández-Beltrán, LC and García-Toledo, I and Javaloyes García, K and Jiménez-Coca, I and Jiménez-Rodríguez, J and Fernández-Bernal, A and Godoy-Corchuelo, JM and Portero-Otín, M and Corrochano, S},
title = {Pharmacological modulation with the LXR agonist T0901317 attenuates motor pathology in the SOD1[G93A] mouse model of ALS.},
journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics},
volume = {23},
number = {5},
pages = {e01062},
doi = {10.1016/j.neurot.2026.e01062},
pmid = {42697152},
issn = {1878-7479},
abstract = {Dysregulation of cholesterol metabolism and neuroinflammation are critical drivers of Amyotrophic Lateral Sclerosis (ALS) pathology. Liver X receptors (LXRs) are master regulators of cholesterol homeostasis and immune responses. Here, we evaluated the therapeutic potential of chronic pharmacological modulation using the potent synthetic agonist T0901317 (T0) in the hSOD1[G93A] mouse model. To assess both long-term functional outcomes and the underlying molecular mechanisms, T0 was administered via two distinct experimental designs. In a longitudinal cohort treated from postnatal day 60 (P60) until the humane endpoint, T0-treated SOD1G93A mice exhibited delayed body weight loss and sustained improvements in neuromuscular strength and motor coordination. Critically, this continuous treatment preserved functional motor unit connectivity, delayed overall clinical progression, and significantly extended median lifespan. While protective in both sexes, the survival benefit was slightly more pronounced in females. Molecular characterization revealed that the early systemic T0 administration successfully engaged canonical LXR targets in the spinal cord, driving a significant transcriptional upregulation of cholesterol efflux pathways and suppressing pro-inflammatory signaling cascades. This response induced a lipid partitioning, evidenced by a significant accumulation of cholesterol esters within the central nervous system, potentially mitigating lipotoxicity. Taken together, these findings demonstrate that T0901317 treatment exerts a significant beneficial effect, highlighting the pharmacological modulation of these lipid and inflammatory networks as a promising therapeutic strategy for ALS.},
}

@article {pmid42674126,
year = {2026},
author = {Raffaele, S and Bonifacino, T and Mannella, FC and Nguyen, N and Torazza, C and Marangon, D and Chinosi, EM and Schrøder, HD and Hejbøl, EK and Madsen, K and Marchetti, L and Trincavelli, ML and Milanese, M and Lecca, D and Lambertsen, KL and Bonanno, G and Abbracchio, MP and Fumagalli, M},
title = {Selective targeting of the oligodendroglial GPR17 receptor improves myelin integrity and motor function in female SOD1[G93A] mice.},
journal = {Pharmacological research},
volume = {232},
number = {},
pages = {108424},
doi = {10.1016/j.phrs.2026.108424},
pmid = {42674126},
issn = {1096-1186},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no definitive disease-modifying therapies available, underscoring the urgent need to identify novel druggable targets. The G protein-coupled receptor GPR17 is a critical regulator of oligodendrocyte maturation and has emerged as a candidate target in ALS, yet its relevance to human disease and its therapeutic potential remain unclear. Here, we demonstrate that pathological GPR17 upregulation defines a conserved, pathologically immature oligodendroglial state in human ALS that can be pharmacologically leveraged to restore myelin integrity and improve functional outcome in vivo. Publicly available transcriptomics datasets and histological analyses revealed an increased abundance of GPR17-expressing immature oligodendrocytes in post-mortem human spinal cord tissue from ALS cases. Moreover, sustained activation of GPR17 with a selective agonist induced GPR17 internalization in heterologous expression systems and promoted the differentiation of primary oligodendrocyte precursors derived from SOD1[G93A] mice. Translating these findings in vivo, chronic treatment with a brain-penetrant GPR17 agonist derived from the same pharmacological class significantly extended survival, delayed body weight loss, and improved motor performance in female SOD1[G93A] mice, whereas male mice showed no therapeutic benefit. These effects were associated with restored oligodendrocyte maturation, preserved myelin integrity, motor neuron survival, and attenuated reactive gliosis in the spinal cord of female SOD1[G93A] mice, while milder effects were observed in males. Together, these findings establish oligodendroglial GPR17 as a conserved and pharmacologically actionable target in ALS and show that sustained in vivo GPR17 agonism can reprogram altered oligodendroglial states and slow disease progression in a sex-dependent manner.},
}

@article {pmid42685382,
year = {2026},
author = {Ni, CC and Yu, CS and Wei, SY and Dai, JZ and Chang, CL and Ting, HC and Chang, CY and Chen, YC},
title = {UV-programmed gelatin methacryloyl hydrogel microenvironments reveal a bell-shaped vascularization window and enable compartmentalized neuromuscular disease modeling.},
journal = {Biomaterials},
volume = {338},
number = {Pt A},
pages = {124588},
doi = {10.1016/j.biomaterials.2026.124588},
pmid = {42685382},
issn = {1878-5905},
abstract = {Matrix mechanics and microarchitecture jointly regulate tissue morphogenesis and functional maturation; however, defining their combined effects remains challenging when microenvironmental tuning requires changes in material composition. Here, we establish a UV-programmable gelatin methacryloyl (GelMA) hydrogel system in which ultraviolet exposure coordinates changes in construct architecture, pore morphology, and apparent mechanical properties within a constant material formulation. This framework enables systematic mapping of biological responses to UV-programmed architectural-mechanical microenvironments without compositional confounders. In vivo subcutaneous implantation reveals a nonlinear, bell-shaped vascularization response to UV-programmed GelMA hydrogel properties, identifying a narrow microenvironmental window that supports blood-containing vessel formation, human-derived vascular structures, and host-perfused vascular integration. For neuromuscular modeling, a structurally stable UV-defined regime was selected to support long-term compartmentalized co-culture of human induced pluripotent stem cell-derived myoblasts and motor neuron spheroids. Within this same UV-defined compartmentalized neuromuscular microenvironment, amyotrophic lateral sclerosis (ALS)-derived constructs exhibit impaired myogenic maturation, reduced neuromuscular junction (NMJ)-like structural organization, and altered contractile responsiveness compared with gene-corrected Healthy controls. Pharmacological treatment with the FDA-approved drug Riluzole partially restores these disease-associated phenotypes. Together, these findings establish UV-programmed GelMA hydrogels as an adaptable architectural-mechanical platform for identifying vascularization-permissive microenvironments and supporting compartmentalized neuromuscular disease modeling.},
}

@article {pmid42666355,
year = {2026},
author = {Wei, Y and Wang, J and Ji, Y and Shang, T and Shen, Y and Sun, H and Cai, Y},
title = {Therapeutic Challenges and Future Breakthroughs in Amyotrophic Lateral Sclerosis: From Precision Medicine to Innovative Trial Design.},
journal = {Drug design, development and therapy},
volume = {20},
number = {},
pages = {626069},
pmid = {42666355},
issn = {1177-8881},
mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/therapy ; Humans ; *Precision Medicine ; Animals ; *Clinical Trials as Topic ; *Neuroprotective Agents/therapeutic use ; *Research Design ; Genetic Therapy ; Drug Development ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a highly heterogeneous and fatal neurodegenerative disorder, for which clinical management and drug development have long faced formidable challenges. Since the approval of riluzole and edaravone, dozens of promising drug candidates that showed efficacy in preclinical models have failed in Phase III trials, highlighting an urgent need for systematic re-evaluation of the field. This review provides a comprehensive summary of the major limitations of current clinical therapies for ALS. These include the modest survival benefit of riluzole, the narrow eligible population for edaravone, and the complex trajectory of sodium phenylbutyrate-taurursodiol, which received accelerated approval but was subsequently voluntarily withdrawn after its confirmatory Phase III trial failed to meet its primary endpoints. On this basis, we discuss four major challenges that contribute to clinical trial failures: disease heterogeneity, paucity of reliable biomarkers, insufficient translational validity of preclinical models, and inherent flaws in conventional trial designs. Subsequently, we discuss emerging therapeutic strategies, encompassing precision medicine and gene therapy (exemplified by the development of the antisense oligonucleotide tofersen for SOD1-ALS), targeting protein homeostasis, modulation of neuroinflammation, metabolic and energetic support, neuroprotection and regeneration, as well as multi-target combination approaches. Innovative trial designs, including adaptive platform trials (exemplified by the HEALEY ALS Platform Trial), enrichment designs, sequential designs, N-of-1 trials, and virtual clinical trials are fundamentally reshaping the drug development paradigm in ALS. In conclusion, ALS treatment is at a historic turning point from a "one-size-fits-all" approach toward "precisely stratified" medicine. Future success depends on establishing multimodal biomarker panels, implementing genetic testing-guided individualized therapy, developing combination regimens, and integrating patient-reported outcomes with palliative care. Although substantial challenges remain, the clinical success of Tofersen provides evidence that precision therapeutic strategies may gradually transform ALS management toward a more individualized and disease-modifying approach.},
}

*Amyotrophic Lateral Sclerosis/drug therapy/therapy
Humans
*Precision Medicine
Animals
*Clinical Trials as Topic
*Neuroprotective Agents/therapeutic use
*Research Design
Genetic Therapy
Drug Development

@article {pmid42670527,
year = {2026},
author = {Pan, L and Liu, B and Xu, J and Mu, X and Fan, L},
title = {Mesenchymal Stem Cells and Extracellular Vesicles for Neurodegenerative Diseases: Therapeutic Advances and Challenges.},
journal = {International journal of nanomedicine},
volume = {21},
number = {},
pages = {628071},
doi = {10.2147/IJN.S628071},
pmid = {42670527},
issn = {1178-2013},
mesh = {Humans ; *Neurodegenerative Diseases/therapy ; *Extracellular Vesicles/transplantation ; *Mesenchymal Stem Cells/cytology ; *Mesenchymal Stem Cell Transplantation/methods ; Animals ; },
abstract = {Mesenchymal stem cells (MSCs), as a type of adult stem cells, exhibit robust self-renewal, multi-lineage differentiation, paracrine and immunomodulatory capacities, demonstrating broad application prospects in the treatment of neurodegenerative diseases. This review systematically summarizes the mechanisms of action, therapeutic advances and comparative analyses of various MSCs and their derived extracellular vesicles (EVs) in Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), and discusses the optimization effects of gene modification and pretreatment on therapeutic efficacy. This article not only highlights the advantages of various MSCs and their corresponding EVs, but also provides unique insights into their differentiated therapeutic potential and mechanism of action, which have not been fully elucidated in previous studies. Meanwhile, although current research results are encouraging, this paper also critically points out that existing studies suffer from insufficient elucidation of mechanisms and lack of large-scale clinical trials. Finally, the article prospects future directions of MSC-based therapeutic strategies, including mechanism deepening, treatment optimization and standardization system construction, to promote their translation into clinical application. However, most of the current evidence is still preclinical, and the recognized clinical efficacy in humans is still limited. This is a narrative review. Literature was screened from Web of Science and PubMed by thematic relevance and research quality, without systematic review protocol or meta-analysis.},
}

Humans
*Neurodegenerative Diseases/therapy
*Extracellular Vesicles/transplantation
*Mesenchymal Stem Cells/cytology
*Mesenchymal Stem Cell Transplantation/methods
Animals

@article {pmid42664377,
year = {2026},
author = {Escobar-Villegas, PA and Realpe-Camelo, AI and Arana-Salas, DA and Velásquez, JG and Paulo, M and Martínez-Cajas, CH and Amaya-Sanchez, S and Gómez-Mesa, JE},
title = {Endodontic status of patients with coronary atherosclerosis: A cross-sectional study.},
journal = {Dental and medical problems},
volume = {63},
number = {4},
pages = {885-891},
doi = {10.17219/dmp/205472},
pmid = {42664377},
issn = {2300-9020},
mesh = {Humans ; Cross-Sectional Studies ; Female ; Male ; *Coronary Artery Disease/epidemiology/complications/diagnostic imaging ; Middle Aged ; Colombia/epidemiology ; Aged ; *Root Canal Therapy ; Adult ; Prevalence ; Coronary Angiography ; },
abstract = {BACKGROUND: There are no studies in the Colombian population assessing the prevalence and severity of apical lesions (ALs), or the relationship between the frequency and quality of endodontic treatment (ET) obturation and the presence of ALs in patients with coronary atherosclerosis (CA).

OBJECTIVES: The present study aimed to estimate the frequency of ALs and ET in Colombian patients with CA, and to identify a possible association between the frequency and severity of ALs and CA.

MATERIAL AND METHODS: The study had a cross-sectional design. We included patients with the evidence of CA diagnosed by coronary angiography. The main outcome variables were the number of compromised coronary arteries and their degree of obstruction, as well as ET, including ALs and previously treated teeth (PTT). The periapical index (PAI) was assessed using periapical radiographs.

RESULTS: A total of 1,394 teeth from 69 patients were evaluated (δ = 20.2 teeth/patient). The frequency of ALs and ET was 5.7% and 10.1%, respectively, considering all teeth evaluated, with a greater presence in the maxilla (50.6% and 51.4%, respectively). Apical lesions were most frequently observed in premolars and molars (35.4%), whereas ET was more frequent in molars (38.6%). Among teeth with ALs, PAI 3 was the most frequent score. Apical lesions were present in 40.0% of endodontically treated teeth; 79.2% of these teeth had inadequate obturation, of which 40 (39.2%) had ALs (p = 0.021).

CONCLUSIONS: In patients with CA, a high incidence of ALs and ET was observed, with no evidence of an association between the frequency of ALs, the severity of coronary vessel occlusion, and the number of coronary arteries affected. More ALs were observed in teeth with inadequate ET. However, as we did not have a control group for comparison, these findings should be interpreted with caution.},
}

Humans
Cross-Sectional Studies
Female
Male
*Coronary Artery Disease/epidemiology/complications/diagnostic imaging
Middle Aged
Colombia/epidemiology
Aged
*Root Canal Therapy
Adult
Prevalence
Coronary Angiography

@article {pmid42652767,
year = {2026},
author = {Friebel, J and Manni, M and Gozdowsky, SC and Brettschneider, P and Grün, D and Baumann, AM and Spielmann, E},
title = {Reorganisation of the Basic Life Support Segment in a Physician-Led Emergency Medical Service: A Retrospective Evaluation of Operational and Clinical Characteristics.},
journal = {Journal of clinical medicine},
volume = {15},
number = {16},
pages = {},
pmid = {42652767},
issn = {2077-0383},
abstract = {Background: Increasing demand for emergency medical services (EMS) challenges prehospital resource availability, particularly for time-critical emergencies requiring advanced life support (ALS). Although tiered BLS and ALS response models are established in many non-physician-led EMS systems, evidence regarding qualification-based dispatch stratification within physician-led EMS systems remains limited. This study evaluated the clinical and operational characteristics of an expanded BLS dispatch segment in Berlin EMS. Methods: A retrospective observational study analysed 2,132,246 EMS missions in Berlin, Germany, between 2020 and 2024. Missions were retrospectively classified according to dispatch codes included in the expanded BLS segment, designed to allocate incidents with lower expected requirements for ALS-level interventions to appropriately qualified EMS personnel. Analyses included dispatch characteristics, clinical findings from electronic patient care records, observed safety-related indicators, and ALS response intervals. Results: Overall, 28.7% of EMS missions were classified within the expanded BLS segment. Traumatic and psychiatric presentations represented the most frequent diagnostic groups. Based on predefined clinical indicators, no immediately life-threatening condition was documented in more than 95% of missions. Cardiopulmonary resuscitation occurred in 0.03% of cases, and emergency physician involvement was documented in approximately 3% of cases. Conclusions: A substantial proportion of EMS missions represented a population with predominantly lower expected prehospital treatment complexity within a qualification-based dispatch framework. Structured emergency call interrogation combined with dispatch classification and linked clinical data enabled retrospective evaluation of this approach. Further validation against independent clinical reference standards and linkage with downstream outcomes are required to determine broader applicability.},
}

@article {pmid42662266,
year = {2026},
author = {Dresel, FC and Michaelis, M and Gourlay, CW},
title = {The HDAC Inhibitor Butyrate Reduces SOD1 Aggregation and Improves Motor Function in C. elegans and Cellular Models of ALS.},
journal = {International journal of cell biology},
volume = {2026},
number = {},
pages = {3022967},
pmid = {42662266},
issn = {1687-8876},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterised by motor neuron loss and protein aggregation, commonly driven by mutations in superoxide dismutase 1 (Sod1). Recent evidence implicates gut microbiota-derived metabolites, such as butyrate, in modulating neurodegeneration, but the underlying mechanisms remain unclear. Here, we demonstrate that sodium butyrate (NaB), a histone deacetylase inhibitor and microbial metabolite, ameliorates ALS-related phenotypes in C. elegans and mammalian cell models expressing mutant isoforms of Sod1 linked to ALS. NaB treatment prevented Sod1 aggregation and restored motor function and axonal integrity in transgenic worms overexpressing Sod1[G85R]. Mechanistically, NaB recapitulated the effects of the pan-HDAC inhibitor trichostatin A, suggesting HDAC inhibition as key to reducing Sod1 aggregation and its downstream effects. Application of NaB or the HDAC inhibitor valproic acid also prevented aggregation of Sod1[A4V], Sod1[G85R] or Sod1[G37R] in transfected human neuroblastoma cells. These findings support a conserved neuroprotective role for NaB and HDAC inhibitors via their antiaggregation activity. Our findings also verify C. elegans and neuroblastoma cell lines as excellent research tools to explore the mechanisms underlying the antiaggregation action of NaB and HDAC inhibitors, as well as their potential for future therapeutic development.},
}

@article {pmid42646579,
year = {2026},
author = {Calabrò, RS and Calderone, A and Ravi, D and Galipò, C and Crupi, MF and Quartarone, A},
title = {Hospital-to-Home Neurological Transition Care: A Scoping Review Across Selected Chronic Neurological Disorders.},
journal = {Medical sciences (Basel, Switzerland)},
volume = {14},
number = {4},
pages = {},
pmid = {42646579},
issn = {2076-3271},
mesh = {Humans ; *Nervous System Diseases/therapy ; *Transitional Care ; Multiple Sclerosis ; Hospitalization ; Chronic Disease ; Amyotrophic Lateral Sclerosis ; },
abstract = {BACKGROUND: Returning home after neurological hospitalization, rehabilitation, or specialist care transfers responsibility to patients, caregivers, and community services. We mapped mechanisms and gaps across dementia/Alzheimer's disease and related dementias (ADRD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS).

METHODS: Following JBI guidance and PRISMA-ScR, eligibility was derived using population-concept-context. We included empirical reports involving adults with a target condition, a post-discharge, return-home, rehabilitation, telehealth, caregiver, treatment, respiratory, or palliative continuity component, and post-transition patient, caregiver, service, safety, rehabilitation, equity, or implementation outcomes. Five databases were searched through to 11 May 2026. Two reviewers independently screened records; charting and classification were verified by R.S.C., A.C., and A.Q.

RESULTS: Of 24,417 records, 69 reports were included: Dementia/ADRD, 28; PD, 10; MS, 9; and ALS, 22. Eighteen were core transition reports (26.1%), 14 return-home/community re-entry reports (20.3%), 16 adjacent continuity reports (23.2%), and 21 companion/secondary reports (30.4%). Dementia/ADRD provided discharge-anchored evidence; PD and MS mapped functional carry-over; ALS mapped adjacent respiratory, telehealth, and palliative continuity.

CONCLUSIONS: The main contribution is an operational cross-disease framework separating direct discharge, return-home, adjacent-continuity, and companion evidence while linking mechanisms to disease-specific pathways. This framework maps disease-specific functions, not comparative effectiveness. The proposed frameworks are author-derived and hypothesis-generating. Future studies should use explicit anchors, standardized outcomes, longer follow-up, and equity-sensitive implementation measures addressing caregiver workload, digital access, feasibility, and sustainability. They inform testable, context-sensitive intervention designs for future neurological transition-care research and practice.},
}

Humans
*Nervous System Diseases/therapy
*Transitional Care
Multiple Sclerosis
Hospitalization
Chronic Disease
Amyotrophic Lateral Sclerosis

@article {pmid42651639,
year = {2026},
author = {Ciuro, M and Rovetto, C and Sirna, AA and Giunta, S and Leanza, G and Gulino, R},
title = {Targeting Mitochondrial Fission Produces Both Neuroprotective and Detrimental Effects in the SOD1 Mouse Model of Amyotrophic Lateral Sclerosis.},
journal = {Biology},
volume = {15},
number = {16},
pages = {},
doi = {10.3390/biology15161334},
pmid = {42651639},
issn = {2079-7737},
support = {PG_6/2022//Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease characterized by progressive motor neuron (MN) degeneration and severe skeletal muscle atrophy. Despite extensive research, the mechanisms driving disease onset and progression remain incompletely understood. While MN loss is a defining feature of ALS, increasing evidence indicates that mitochondrial dysfunction contributes to disease pathogenesis. Here, we investigated the hypothesis that Mdivi-1, a pharmacological inhibitor of mitochondrial fission protein Drp-1, may exert neuroprotective properties in the SOD1[G93A] mouse model of ALS. Treatment was initiated prior to symptomatic onset to assess its potential disease-modifying effects. Mdivi-1 administration resulted in partial preservation of spinal MNs, however, this benefit did not translate into functional improvement. Moreover, treated animals exhibited exacerbated muscle atrophy, increased cytoplasmic localization of TDP-43 in MNs and compromised synaptic plasticity. Drp-1 expression was reduced in SOD1 mice and further decreased following Mdivi-1 treatment, suggesting that mitochondrial dynamics may already be compromised in this model. Overall, our results also highlight possible off-target effects of Mdivi-1 and point to a context-dependent role of mitochondrial dynamics in ALS.},
}

@article {pmid42638122,
year = {2026},
author = {Zhang, Y and Liu, Y and Shi, S and Li, Q and Huo, Y and You, P and Shu, M and Cheng, X and Zhang, J and Liang, D and Zhang, A and Lu, C and Shen, B and Zhou, J and Niu, Q},
title = {JP1 peptide modulates oxidative stress and autophagy via Keap1-Nrf2-ARE in ALS model mice.},
journal = {BMC medicine},
volume = {24},
number = {1},
pages = {},
pmid = {42638122},
issn = {1741-7015},
support = {82071434//the National Natural Science Foundation of China/ ; DL202410//the clinical Research Disease Project of Jiangsu Provincial People's Hospital/ ; LC202404//Jiangsu Provincial People's Hospital-Zero magnetic Medicine Special Project/ ; JSPH-MA-2023-5//Jiangsu Province Hospital Clinical Capacity Enhancement Project/ ; },
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism ; *Oxidative Stress/drug effects ; *NF-E2-Related Factor 2/metabolism ; *Autophagy/drug effects ; *Kelch-Like ECH-Associated Protein 1/metabolism ; Disease Models, Animal ; Mice ; Mice, Transgenic ; Antioxidant Response Elements ; Signal Transduction/drug effects ; *Oligopeptides/pharmacology ; Male ; Humans ; Spinal Cord/metabolism ; },
abstract = {BACKGROUND: The simultaneous modulation of oxidative stress and autophagy represents a potential therapeutic strategy for amyotrophic lateral sclerosis (ALS), yet agents capable of coordinately regulating both processes remain scarce. The Keap1‑Nrf2‑ARE pathway serves as a critical hub linking redox homeostasis and autophagic regulation, making it an attractive target for ALS intervention. JWA is a stress‑responsive protein involved in cellular protection against oxidative injury, and its neuroprotective effects have been shown to depend on activation of the MEK/ERK‑Nrf2 axis. JP1 is a functional oligopeptide derived from the JWA protein that has been engineered to cross the blood-brain barrier and specifically target integrin αVβ3. Based on the link between JWA and Nrf2 signaling, we hypothesized that JP1 activates the Keap1‑Nrf2‑ARE pathway to coordinate antioxidant defense and autophagic clearance. Here, we evaluated this hypothesis in the SOD1‑G93A mouse model, a well‑established transgenic model of familial ALS, and elucidated the underlying mechanisms.

METHODS: We evaluated the efficacy of JP1 in the SOD1-G93A mice model using behavioral phenotyping and survival analysis. The coordinated mechanism was investigated in spinal cord tissues by profiling the Keap1-Nrf2-ARE pathway and oxidative stress, quantifying autophagic flux (by Western blotting and transmission electron microscopy) and neuronal apoptosis, and evaluating histology (by Nissl staining and immunofluorescence). Integrated transcriptomic and proteomic analyses further elucidated the global molecular landscape underlying the therapeutic effects of JP1.

RESULTS: JP1 treatment ameliorated motor deficits and extended survival in SOD1-G93A mice without adversely affecting liver or kidney function. JP1 crossed the blood-brain barrier, targeted motor neurons expressing integrin αVβ3, and activated the ERK pathway. This promoted Keap1/Cul3 degradation and Nrf2 nuclear translocation, thereby activating the Keap1-Nrf2-ARE pathway to alleviate oxidative stress. Concurrently, JP1 restored autophagic flux, increased autophagic activity, attenuated motor neuron injury, suppressed neuronal apoptosis, and preserved neuronal structural integrity. The Nrf2 inhibitor ML385 reversed the protective effects of JP1 on survival, motor function, autophagy, oxidative stress, and neuronal apoptosis, which confirms that JP1 acts via the Nrf2 pathway.

CONCLUSIONS: JP1 acts as a promising coordinator of antioxidant and autophagic processes by targeting the Keap1-Nrf2-ARE pathway, thus highlighting its therapeutic potential for ALS.},
}

Animals
*Amyotrophic Lateral Sclerosis/drug therapy/metabolism
*Oxidative Stress/drug effects
*NF-E2-Related Factor 2/metabolism
*Autophagy/drug effects
*Kelch-Like ECH-Associated Protein 1/metabolism
Disease Models, Animal
Mice
Mice, Transgenic
Antioxidant Response Elements
Signal Transduction/drug effects
*Oligopeptides/pharmacology
Male
Humans
Spinal Cord/metabolism

@article {pmid42642938,
year = {2026},
author = {Zou, L and Song, L and Yin, P and Cui, H and Lian, L and Peng, X and Jin, T and Wang, H and Liu, W},
title = {Glutathione S-transferase genes PfGSTU6 and PfGSTL1 involved in mesosulfuron-methyl resistance in Polypogon fugax.},
journal = {Pest management science},
volume = {},
number = {},
pages = {},
doi = {10.1002/ps.71227},
pmid = {42642938},
issn = {1526-4998},
support = {//National Natural Science Foundation of China (32372570, 32572857)/ ; //Shandong Provincial Natural Science Foundation (ZR2025MS289)/ ; },
abstract = {BACKGROUND: Polypogon fugax is a major weed in wheat and winter canola fields in China. Two populations, SD-4 and JS-13, showing resistance to the ALS inhibitor mesosulfuron-methyl, were collected from winter wheat fields. This study aimed to characterize their resistance level and cross-resistance profile, investigate the resistance mechanism and identify its functional genes.

RESULTS: Dose-response assays showed that SD-4 and JS-13 have high-level resistance to mesosulfuron-methyl (15.9-and 16.4-fold, respectively) and cross-resistance to the ACCase inhibitors clodinafop-propargyl, fenoxaprop-P-ethyl, quizalofop-p-ethyl, and the PDS inhibitor diflufenican. Sequencing of the ALS gene revealed no known target-site mutations within the eight conserved resistance-associated regions. Pre-treatment with the cytochrome P450 monooxygenase (P450) inhibitor malathion or the glutathione S-transferase (GST) inhibitor NBD-Cl increased herbicide sensitivity in resistant plants. The resistant plants showed higher inducible GST activity. Herbicide residues analysis observed that resistant plants exhibiting increased mesosulfuron-methyl metabolism, and the enhanced metabolism could be reduced by both inhibitors. Integrated transcriptomic and qRT-PCR analysis identified 17 stably upregulated genes, including PfGSTU6 and PfGSTL1. Escherichia coli and rice callus overexpressing PfGSTU6 and PfGSTL1 exhibit significantly enhanced herbicide tolerance to mesosulfuron-methyl, and molecular docking analysis confirmed the strong binding affinity of GST proteins to the target herbicide.

CONCLUSIONS: The P450s and GSTs mediated herbicide metabolism confer mesosulfuron-methyl resistance in P. fugax. This study elucidates the resistance mechanism and provides genetic resources for resistance monitoring and crop breeding. In addition, we characterized the cross-resistance profile of the resistant P. fugax population, which provides guidance for developing targeted field weed resistance management strategies. © 2026 Society of Chemical Industry.},
}

@article {pmid42637106,
year = {2026},
author = {Heinsinger, N and Wang, Y and Grauer, S and Zhang, Z and Wong, J and Simov, V and Bukhtiyarova, M and Ai, X and Parish, C and Klein, RM and Uslaner, J and Smith, S and Tian, Y},
title = {Splicing modulation of ATXN2 as a therapeutic strategy to regulate Ataxin-2 protein levels in ALS.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107582},
doi = {10.1016/j.nbd.2026.107582},
pmid = {42637106},
issn = {1095-953X},
abstract = {ATXN2 is associated with an increased risk of Amyotrophic Lateral Sclerosis (ALS), while down-regulation of ATXN2 has been shown to mitigate TDP-43 proteinopathy in ALS models. In this study, we demonstrated that Ataxin-2 protein levels were upregulated in rNLS8 mice following doxycycline withdrawal, which coincided with TDP-43 overexpression, phosphorylation, and aggregation. To reduce Ataxin-2 protein levels, we explored the approach of splicing modulation at the RNA level. Through bioinformatical analysis, we identified an alternative 5' splicing site of ATXN2 in intron 8. This alternative splicing results in an additional 47 base pairs at the 3' end after Exon 8. The insertion of the extra nucleotides causes a frameshift that leads to reduced mRNA production and, consequently, protein levels. Following the discovery of this alternative splicing site, we conducted an antisense oligonucleotide (ASO) micro-walk to screen ASOs targeting this region. We identified ASOs that specifically modulate this splicing, including those that either enhance or inhibit alternative splicing. We validated that the ASOs that promote alternative splicing and reduce constitutive splicing can lower Ataxin-2 protein levels, which in turn decreases TDP-43 aggregation and stress granule formation in a cell-based model of TDP-43 toxicity. Furthermore, we confirmed that reducing Ataxin-2 levels via previously validated ASO delivery ameliorated TDP-43 pathology in rNLS8 mice. The discovery of ATXN2 alternative splicing, along with the confirmation of splicing modulation using ASOs in human cell-based assays, provides evidence for a proof-of-principle strategy to modulate Ataxin-2 protein levels for the treatment of ALS.},
}

@article {pmid42637886,
year = {2026},
author = {Rashed, AM and El-Sayed, IET and Lu, X and Abdel-Bary, HM and Fouad, MK and Tony, MA},
title = {Re-engineering alum sludge using choline-glycine ionic liquid for enhanced dewatering and dye adsorption in wastewater treatment.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {42637886},
issn = {2045-2322},
abstract = {Large quantities of by-product alum sludge (Al-S) generated from drinking water treatment plants pose significant environmental and disposal challenges due to their high water content and large volume. This study aims to develop a sustainable conditioning and valorization strategy for Al-S using a choline-glycine ionic liquid ([Ch]-[AA]). The ionic liquid was synthesized and applied as a sludge conditioner to enhance dewatering performance. Under optimized conditions, the dewatering efficiency reached 47%, accompanied by a notable zeta potential shift, indicating partial charge neutralization and improved floc structure. To enable sludge valorization, the conditioned sludge was reused as an adsorbent, either directly or after thermal treatment. The modified materials exhibited high adsorption capacities toward Synozol KHL dyes, reaching 43.6 and 90.1 mg g[-][1] for Red and Blue dyes, respectively. Adsorption behavior was well described by the Langmuir isotherm and pseudo-second-order kinetic model. Thermodynamic analysis indicated an exothermic adsorption process, with spontaneity dependent on operating conditions. Overall, the results demonstrate an effective waste-to-resource approach in which enhanced dewatering facilitates the conversion of alum sludge into a functional adsorbent for wastewater treatment, supporting sustainable sludge management.},
}

@article {pmid42632702,
year = {2026},
author = {Wu, L and Zhu, X and Wang, X and Wu, Y and Bu, Q and Dai, T and Wen, X and Zhong, K and Guo, H and Gao, H},
title = {Fermentation with aspergillus costiformis enhances the anti-migratory activity of Aquilaria sinensis leaves with possible involvement of MAPK-related pathways.},
journal = {Food research international (Ottawa, Ont.)},
volume = {242},
number = {Pt 2},
pages = {119955},
doi = {10.1016/j.foodres.2026.119955},
pmid = {42632702},
issn = {1873-7145},
mesh = {Humans ; *Aspergillus/metabolism ; *Plant Leaves/chemistry ; *Fermentation ; *Thymelaeaceae/chemistry/metabolism ; HeLa Cells ; *Plant Extracts/pharmacology ; *Cell Movement/drug effects ; *MAP Kinase Signaling System/drug effects ; Flavonoids ; Cell Proliferation/drug effects ; },
abstract = {Aquilaria sinensis leaves (ALs) are an underutilized plant resource rich in polyphenols and flavonoids. Microbial fermentation has been proposed as an effective strategy to enhance the functional value of plant materials. However, its impact on the bioactivity and mechanisms of ALs remains unclear. This study aimed to evaluate the effects of fermentation with Aspergillus costiformis AHHC on the chemical composition and biological activities of ALs, and to elucidate the molecular mechanisms underlying the fermentation-induced functional changes. Non-targeted metabolomic analysis was performed to assess fermentation-induced metabolic alterations. The biological activities of fermented ALs (ALDT) and non-fermented ALs (ALT) extracts were evaluated using HeLa S3 cell-based assays. Network pharmacology and transcriptomic analyses were integrated to identify potential pathways and molecular targets, which were further validated by molecular analyses. The results revealed that fermentation significantly reshaped the metabolite profile of ALDT, particularly in flavonoid-related pathways. Compared with ALT, ALDT showed a stronger inhibitory effect on HeLa S3 cell migration while maintaining comparable anti-proliferative activities at higher concentrations. The integrated analyses indicated that fermentation-enriched metabolites were mainly associated with pathways related to cell migration and stress response, with prominent involvement of MAPK signaling. Molecular assays confirmed enhanced phosphorylation of MAPK components and increased expression of regulatory genes such as GADD45B and NR4A1 in response to ALDT treatment. Overall, fermentation with A. costiformis enhanced the anti-migratory activity of ALDT in HeLa S3 cells, with possible involvement of MAPK-related signaling pathways. These findings provide molecular-level evidence supporting microbial fermentation as a strategy to improve the functional value of this plant resource.},
}

Humans
*Aspergillus/metabolism
*Plant Leaves/chemistry
*Fermentation
*Thymelaeaceae/chemistry/metabolism
HeLa Cells
*Plant Extracts/pharmacology
*Cell Movement/drug effects
*MAP Kinase Signaling System/drug effects
Flavonoids
Cell Proliferation/drug effects

@article {pmid42626598,
year = {2026},
author = {Pinky, PP and Wang, ZM and Khare, P and Jhaveri, JR and Sullivan, A and Basudkar, V and Rao, KS and Lawrence, A and Pingali, A and Dave, KM and Stolz, DB and Sun, M and Zheng, SY and Shiva, SS and Milligan, C and Delbono, O and Manickam, DS},
title = {Mitochondria-containing large extracellular vesicles target mouse motor neurons upon intramuscular injection.},
journal = {Extracellular vesicle},
volume = {7},
number = {},
pages = {},
pmid = {42626598},
issn = {2773-0417},
support = {R25 NS100118/NS/NINDS NIH HHS/United States ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a neurological disorder that causes progressive degeneration of motor neurons. Mitochondrial dysfunction accelerates neurodegeneration, aggravating the severity of ALS. We hypothesized that increasing the mitochondrial function of motor neurons may promote neuronal survival. Therefore, we investigated the potential of neuron-derived mitochondria containing extracellular vehicles (EVs) as a novel therapeutic approach for ALS using differentiated NSC-34 cells as a surrogate for neurons. Neuron derived-large EVs (lEVs) but not small EVs (sEVs) contained mitochondria. However, we observed increased cell viability and oxygen consumption rates in heat-stressed neurons treated with both sEVs and lEVs suggesting improved mitochondrial function in recipient neurons. The increased oxygen consumption rates in sEV-treated heat-stressed neurons was accompanied by a greater proton leak compared to lEV treatment. The greater proton leak observed with sEVs likely suggests a lower efficiency of oxidative phosphorylation compared to that achieved by cells treated with mitochondria-containing lEVs. These findings suggest that mitochondrial components present in sEVs, such as proteins and mitochondrial DNA, may too contribute to improving cellular respiration. Furthermore, we have demonstrated that lEV mitochondria are transported into the lumbar spinal cord motor neurons following intramuscular injection in C57BL/6 mice in an EV dose-dependent manner. Collectively, for the first time, we have demonstrated the therapeutic effects of neuronal EVs in recipient heat-stressed neurons and the delivery of lEV mitochondria to spinal cord motor neurons in vivo without any EV surface modifications for neuronal targeting. Further studies will determine the therapeutic efficacy of mitochondria-containing EVs in the SOD1[G93A] transgenic mouse model of ALS.},
}

@article {pmid42622454,
year = {2026},
author = {Boccanegra, B and Tulimiero, L and Quarta, R and Conte, E and Licandro, SA and Decio, A and Lenti, R and Ladisa, A and Dinoi, G and Carbone, G and Claudione, L and Camerino, GM and Pierno, S and Mantuano, P and Cappellari, O and Fossati, G and Steinkühler, C and De Luca, A},
title = {LKB1 Dysregulation in Duchenne Muscular Dystrophy Models: Disease Specificity and Epigenetic Control by HDAC Inhibitors.},
journal = {Annals of the New York Academy of Sciences},
volume = {1562},
number = {1},
pages = {e70364},
pmid = {42622454},
issn = {1749-6632},
support = {22.004//Duchenne Parent Project/ ; GJC25P084//Fondazione Telethon/ ; PRIN MUR 2020ELYA32//Ministero dell'Università e della Ricerca/ ; 2023-UNBACLE-0245439//Università degli Studi di Bari "Aldo Moro"/ ; },
mesh = {Animals ; *Histone Deacetylase Inhibitors/pharmacology ; *Muscular Dystrophy, Duchenne/genetics/metabolism/drug therapy ; Mice ; *Protein Serine-Threonine Kinases/genetics/metabolism ; Humans ; *Epigenesis, Genetic/drug effects ; Disease Models, Animal ; AMP-Activated Protein Kinase Kinases ; MicroRNAs/genetics/metabolism ; Mice, Inbred mdx ; Vorinostat ; AMP-Activated Protein Kinases/metabolism ; Muscle, Skeletal/metabolism/drug effects ; },
abstract = {Efficient skeletal muscle contraction requires tight mechano-metabolic coupling, a process regulated by AMP-activated protein kinase (AMPK). Duchenne muscular dystrophy (DMD) is characterized by aberrant AMPK activation and disrupted metabolic signaling. This study investigates the expression and regulation of the LKB1-STRADα-MO25 heterotrimeric complex, the primary upstream activator of AMPK, in DMD models. We analyzed muscles from dystrophic mice (BL10 mdx and D2 mdx) and patient-derived cells and found significant downregulation of the LKB1 complex across all disease stages in the DMD models, a defect not observed in an amyotrophic lateral sclerosis model. Treatment with the broad-spectrum HDAC inhibitor vorinostat effectively restored LKB1 expression at both transcript and protein levels in D2 mdx mice. This restoration was mechanistically linked to downregulation of miR-451, miR-195, and miR-17, which function as post-transcriptional repressors of LKB1. Conversely, the selective HDAC1/2 inhibitor Rodin-A increased Lkb1 mRNA but failed to rescue protein levels or alter miRNA expression. Our data identify the axis LKB1-STRADα-MO25 as a critical regulatory node that is disrupted in DMD, but remains responsive to epigenetic modulation. These findings suggest that restoring LKB1 activity via HDAC inhibition or miRNA targeting may represent a therapeutic avenue to address dystrophic muscle dysfunction.},
}

Animals
*Histone Deacetylase Inhibitors/pharmacology
*Muscular Dystrophy, Duchenne/genetics/metabolism/drug therapy
Mice
*Protein Serine-Threonine Kinases/genetics/metabolism
Humans
*Epigenesis, Genetic/drug effects
Disease Models, Animal
AMP-Activated Protein Kinase Kinases
MicroRNAs/genetics/metabolism
Mice, Inbred mdx
Vorinostat
AMP-Activated Protein Kinases/metabolism
Muscle, Skeletal/metabolism/drug effects

@article {pmid42624937,
year = {2026},
author = {Aboukhalil, FM and Khamis, EF and El-Sayed, MA and Youssef, RM and El-Yazbi, AF},
title = {Green analytical methods for quantification of a new combination therapy for amyotrophic lateral sclerosis: assessment by EPPI framework.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {42624937},
issn = {2045-2322},
mesh = {*Celecoxib/therapeutic use/analysis ; *Ciprofloxacin/therapeutic use/analysis ; *Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; Chromatography, High Pressure Liquid/methods ; *Green Chemistry Technology/methods ; Spectrophotometry, Ultraviolet/methods ; Tablets ; Drug Therapy, Combination ; Reproducibility of Results ; },
abstract = {Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder characterized by the degeneration of upper and lower motor neurons, leading to progressive muscle weakness, paralysis, and respiratory failure. The recently proposed combination therapy consisting of celecoxib and ciprofloxacin hydrochloride has emerged as a potential treatment for amyotrophic lateral sclerosis and other neurodegenerative disorders. The present study aimed to develop and validate simple, sensitive, environmentally friendly, and cost-effective analytical methods for the simultaneous determination of celecoxib and ciprofloxacin hydrochloride in bulk powders, laboratory-prepared tablets and plasma. Two ultraviolet spectrophotometric methods were established. The first method relies on direct absorbance measurements of ciprofloxacin hydrochloride at 318 nm and celecoxib at the isosbestic point at 266 nm, while the second one employs first-derivative ratio spectrophotometry for the selective determination of ciprofloxacin hydrochloride and celecoxib at 280 nm and 254 nm, respectively. Moreover, a reversed-phase high-performance liquid chromatographic method was developed using a C18 stationary phase, an optimized mobile phase composition and both diode array and fluorescence detectors, achieving efficient separation and accurate quantification of both analytes. The developed procedures were successfully applied to laboratory-prepared tablets and plasma following optimization of the sample preparation protocol to minimize matrix interference and to improve analytes recovery. Validation results showed excellent linearity over the investigated concentration ranges together with satisfactory accuracy, precision, selectivity, and sensitivity, confirming the reliability of the proposed methods for routine quality control and bioanalytical applications. The overall analytical performance and environmental sustainability of the developed methods were further assessed using the environmental performance and practicality Index framework, demonstrating their suitability as reliable and sustainable analytical approaches for the determination of celecoxib and ciprofloxacin hydrochloride.},
}

*Celecoxib/therapeutic use/analysis
*Ciprofloxacin/therapeutic use/analysis
*Amyotrophic Lateral Sclerosis/drug therapy
Humans
Chromatography, High Pressure Liquid/methods
*Green Chemistry Technology/methods
Spectrophotometry, Ultraviolet/methods
Tablets
Drug Therapy, Combination
Reproducibility of Results

@article {pmid42625845,
year = {2026},
author = {Wu, IH and Schwarze, JE and Helwig, C and D'Hooghe, T and Schellschmidt, I},
title = {Clinical Appraisal of "Micronized Vaginal Progesterone Dose and Serum Progesterone Thresholds Determine Reproductive Outcomes in Frozen-Thawed Embryo Transfer With Hormone Replacement Therapy".},
journal = {Reproductive medicine and biology},
volume = {25},
number = {1},
pages = {e70088},
pmid = {42625845},
issn = {1445-5781},
abstract = {This paper critically evaluates Sekiguchi et al.'s study of vaginal progesterone dose, serum progesterone thresholds, and reproductive outcomes in hormone replacement therapy frozen embryo transfer (HRT-FET) cycles. The study conflates descriptive, predictive, and causal aims without a clearly prespecified primary question, limiting interpretability. Major concerns include non-random treatment allocation, potential residual confounding, absence of a causal framework for covariate selection, unaddressed temporal confounding related to Japan's 2022 insurance reform, and exclusion of an available progesterone formulation. Additionally, formulation specific pharmacokinetics, single-time-point progesterone measurement, and internally derived thresholding limit comparability, predictive validity, and clinical applicability.},
}

@article {pmid42613694,
year = {2026},
author = {Shukla, S and Srivastava, V and Gaur, H and Rai, A},
title = {Myelin and Oligodendrocyte Dysfunction in Demyelinating and Neurodegenerative Disorders: Signaling Pathways and Therapeutic Targets.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273437393260729093129},
pmid = {42613694},
issn = {1996-3181},
abstract = {INTRODUCTION: Oligodendrocytes (OLs) synthesize myelin, a substance that plays a significant role in ensuring proper functioning of the Central Nervous System (CNS). Myelin abnormalities are involved in disease pathogenesis in AD, MS, and ALS. In contrast, MS involves autoimmune reactions directed against myelin. On the other hand, AD and ALS are characterized by neurodegeneration. This article seeks to give a critical discussion on myelin and OL dysfunction in these diseases, among others.

METHODS: A narrative literature search was carried out in various databases including Scopus, Google Scholar, Web of Science, and PubMed, focusing on papers relating to myelination, remyelination, and OLs, particularly those addressing signaling pathways and treatment strategies.

RESULTS: MS is an autoimmune disease characterized by inflammation that causes demyelination and OL dysfunction. Oxidative stress and mitochondrial dysfunction play roles in the pathogenesis of ALS, whereas AD is a result of disrupted neuronal supportive functions and myelin damage. Important signaling pathways involved in OL formation and myelin repair include the Wnt/β-catenin, AKT/mTOR, and ERK/MAPK pathways. Drugs like edaravone, ocrelizumab, and siponimod have been identified for promoting myelin repair.

DISCUSSION: The relationship between abnormal oligodendrocyte function, demyelination, and specific disease-related pathological processes demonstrates that although there is a similarity among MS, AD, and ALS, each condition possesses its own unique molecular foundation. One potential treatment approach would be targeting shared signaling pathways relevant to myelination and remyelination. Nonetheless, disease variability and specific pathogenic characteristics demand a targeted therapy approach.

CONCLUSION: Myelin integrity and oligodendrocyte function are central to the progression of demyelinating and neurodegenerative diseases. Targeting molecular pathways involved in myelination offers significant potential for improving disease outcomes and developing advanced therapeutic strategies.},
}

@article {pmid42620667,
year = {2026},
author = {Hawley, ZCE and Guise, AJ and Pardo, ID and Chowdhury, T and Hana, S and Zavodszky, MI and Engle, L and Wiltberger, K and Bartlett, D and Raitcheva, D and Bommegowda, S and Lee, WH and Chen, SK and Sheehy, A and Driscoll, R and Peterson, M and Sebalusky, J and Hamann, S and Marsh, G and Doherty, J and Chicoine, KE and Cundiff, P and Dwyer, S and Clarner, P and Zeng, W and Ferretti, D and Tuczkewycz, T and Isaza, I and Patrovanie, M and Mcgladrigan, C and Chu, J and Morrison, JP and Arnold, HM and Shen, S and Hurt, JA and Trapa, P and Graham, DL and Plowey, ED and Lo, SC},
title = {Antisense oligonucleotide treatment following viral delivery of artificial SOD1-targeting miRNA shows improved efficacy in SOD1-G93A mice.},
journal = {Molecular therapy. Advances},
volume = {34},
number = {3},
pages = {201818},
pmid = {42620667},
issn = {3117-387X},
abstract = {Adeno-associated virus (AAV) artificial microRNAs (amiRNAs) targeting superoxide dismutase 1 (SOD1) have been proposed as a therapeutic strategy for people living with amyotrophic lateral sclerosis (ALS) who harbor toxic gain-of-function variants in the SOD1 gene. Clinical efforts have primarily focused on AAV delivery via the cerebrospinal fluid (CSF), as blood-brain-barrier-crossing capsids are still being developed preclinically. However, intra-CSF delivery has been shown to be highly variable and increases the risk for AAV-related adverse events such as dorsal root ganglion (DRG) toxicity. Here, we show that immunosuppressants (IMS) following intra-CSF delivery of AAV9-amiR-SOD1 in non-human primates (NHPs) prevented AAV-related DRG toxicity, and this benefit was maintained for over 300 days even after immunotherapy stopped at 90 days post-AAV treatment. In line with prior literature, we found intra-CSF delivery of AAV9-amiR-SOD1 to be highly variable in adult mice and NHPs, requiring higher doses of virus to achieve efficacious endpoints. To address this concern, we developed a proof-of-principle study showing that AAV9-amiR-SOD1, in combination with a SOD1-targeting antisense oligonucleotide, provided an additive therapeutic benefit in SOD1-G93A mice compared with AAV9-amiR-SOD1 alone. This combinatorial approach lowered the viral load needed to reach efficacious endpoints, which could mitigate AAV-related adverse events alongside IMS.},
}

@article {pmid42613144,
year = {2026},
author = {Valverde, A and Blasco, H and Corcia, P and Herault, O and Magistretti, P and Herault, L and Cali, C and Bartesaghi, L and Stone, J and Mitrofanis, J},
title = {Exploring the effect of red and near-infrared light on neurodegenerative disease: A focus on amyotrophic lateral sclerosis, Charcot's devastating disease of the motor system.},
journal = {International review of neurobiology},
volume = {189},
number = {},
pages = {205-236},
doi = {10.1016/bs.irn.2026.01.013},
pmid = {42613144},
issn = {2162-5514},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/radiotherapy ; Animals ; *Infrared Rays/therapeutic use ; Red Light ; *Neurodegenerative Diseases/therapy ; },
abstract = {All neurodegenerative diseases, from Alzheimer's disease to amyotrophic lateral sclerosis (ALS), are characterised by a relentless and progressive degeneration of neurones. The degenerating neurones suffer from mitochondrial dysfunction, glutamate excitotoxicity, metabolic disorder and atypical protein aggregations; there is also widespread neuroinflammation and damage to the neurovascular unit across the nervous system. Unfortunately, there is no current treatment option that addresses all, if not many, of these striking abnormalities, one that stops or even slows the progression of the disease (ie neuroprotective). In this chapter, we explore the potential effectiveness of red and near infrared light (R-NIr) on ALS, one of the most devastating of all the neurodegenerative diseases. This condition impacts the motor system, from the cerebral cortex and brainstem to the spinal cord, as well as many skeletal muscles. Individuals suffer greatly and the survival period after onset of the first signs is often very short, averaging just over 2 years, as against 4-8 years in dementia. We outline two main reasons why R-NIr may have positive outcomes in ALS; (1) R-NIr has been shown to be neuroprotective in many other neurodegenerative diseases, improving cell function and survival, and; (2) unlike many other treatments attempted previously, R-NIr addresses many, if not all features of pathology associated with ALS. In summary, we suggest that R-NIr, with its multi-modal effect, could be a valuable treatment option for patients with ALS, particularly if the treatment is started early, before the development of excessive cellular damage.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/radiotherapy
Animals
*Infrared Rays/therapeutic use
Red Light
*Neurodegenerative Diseases/therapy

@article {pmid42613627,
year = {2026},
author = {Jamali, MC and Shafie, A and Alqahtani, AJ and Al-Samawi, RI and Alyami, HM and Ashour, AA and Felemban, MF and Mansuri, N and Tayeb, FJ and Ahmad, I and Mudhafar, M and Sheweita, SA},
title = {Advances in the clinical application of mesenchymal stem cells for neurological disorders.},
journal = {Stem cell research & therapy},
volume = {17},
number = {1},
pages = {},
pmid = {42613627},
issn = {1757-6512},
mesh = {Humans ; *Mesenchymal Stem Cell Transplantation/methods ; *Mesenchymal Stem Cells/cytology/metabolism ; *Nervous System Diseases/therapy/pathology ; Animals ; Amyotrophic Lateral Sclerosis/therapy/pathology ; Alzheimer Disease/therapy/pathology ; },
abstract = {Therapeutic approaches employing mesenchymal stem cells (MSCs) have emerged as a promising avenue for investigating treatments for neurological disorders. This strategy aims to capitalize on the biological properties of MSCs to support the repair of damaged neural tissue and modulate pathological processes. This review provides a comprehensive overview of the current clinical evidence regarding MSC applications in major neurological disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, spinal cord injury (SCI), and other pertinent disorders. Across clinical studies, MSC administration has generally demonstrated a favorable safety profile and procedural feasibility. However, therapeutic efficacy remains variable and inconsistent across trials. Importantly, differences in MSC sources, manufacturing procedures, delivery routes, dosing strategies, and patient selection contribute substantially to the heterogeneity of reported outcomes. Therefore, the current body of evidence supports the safety of MSC-based interventions, but their clinical effectiveness has not yet been consistently demonstrated. Future progress will depend largely on the standardization of cell preparation and treatment protocols, improved biomarker-driven patient stratification, and rigorously designed large-scale randomized trials.},
}

Humans
*Mesenchymal Stem Cell Transplantation/methods
*Mesenchymal Stem Cells/cytology/metabolism
*Nervous System Diseases/therapy/pathology
Animals
Amyotrophic Lateral Sclerosis/therapy/pathology
Alzheimer Disease/therapy/pathology

@article {pmid42606797,
year = {2026},
author = {Raghunathan, T and Parthasarathy, B and Prabhu, P and Mahesh, P and Dhanushkodi, A},
title = {Regenerative strategies for ALS: stem cells and extracellular vesicles.},
journal = {Discover nano},
volume = {21},
number = {1},
pages = {},
pmid = {42606797},
issn = {2731-9229},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is caused by progressive degeneration of upper and lower motor neurons. The disease is late onset, and to date, no early diagnosis is possible. Patients with ALS have a 5-year survival rate since diagnosis. Though recent studies highlighted the possible mechanisms of motor neuron degeneration in ALS, the treatment options are extremely limited. This underscores the urgent need to develop effective therapeutic strategies that can prolong patient survival and ultimately slow/halt ALS progression. Extracellular vesicles released from the degenerative milieu contribute to ALS propagation and progression by shuttling misfolded proteins, proinflammatory cytokines, and neurotoxins; thus, they could serve as a biomarker for diagnosis and prognosis. The advancement of stem cell-based therapies for neurodegenerative diseases and the evolving understanding of extracellular vesicles as potential biotherapeutics provide a ray of hope for millions of patients suffering from neurological disorders/neurodegenerative diseases like ALS.},
}

@article {pmid42597576,
year = {2026},
author = {Maeta, T and Kobayashi, K and Asano, K and Sato, T and Ito, S},
title = {Ruxolitinib-Associated Improvement in Post-transplant Air-Leak Syndrome Complicating Steroid-Dependent Organizing Pneumonia: A Case Report.},
journal = {Cureus},
volume = {18},
number = {7},
pages = {e112618},
pmid = {42597576},
issn = {2168-8184},
abstract = {Air-leak syndrome (ALS), including pneumothorax, pneumomediastinum, and subcutaneous emphysema, is a rare but life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). However, no standard treatment has yet been established. Here, we report the case of a 60-year-old man with acute myeloid leukemia who underwent allogeneic HSCT. He developed chronic graft-versus-host disease (GVHD) and cryptogenic organizing pneumonia (COP) on day 126 after transplantation. Although initial corticosteroid therapy improved the COP, the relapse occurred during tapering, and repeated steroid treatment failed to achieve sustained disease control. The patient subsequently developed pneumomediastinum, consistent with ALS. Ruxolitinib treatment was initiated on day 265 for steroid-dependent chronic GVHD and organizing pneumonia. Following treatment, oxygenation improved, pneumomediastinum improved, and corticosteroids were successfully tapered and discontinued without COP recurrence. Serum Krebs von den Lungen-6 (KL-6) levels decreased in parallel with clinical and radiological improvement. The introduction of ruxolitinib is associated with improvements in ALS and enabled the discontinuation of steroids. Adverse events included cytopenia and mild liver dysfunction, consistent with known safety profiles. The patient died of acute respiratory failure after transfusion, which was not considered a direct complication of the ruxolitinib treatment. This case suggests that ruxolitinib may facilitate corticosteroid tapering and radiographic improvement of organizing pneumonia-associated ALS after allogeneic transplantation.},
}

@article {pmid42594365,
year = {2026},
author = {Berry-Kilgour, N and Wiseman, R and Grundy, K},
title = {Prescribing and monitoring of riluzole in amyotrophic lateral sclerosis: a retrospective cohort study from Health New Zealand - Te Whatu Ora Waitaha Canterbury.},
journal = {The New Zealand medical journal},
volume = {139},
number = {1640},
pages = {23-30},
doi = {10.26635/6965.7367},
pmid = {42594365},
issn = {1175-8716},
mesh = {Humans ; Retrospective Studies ; *Riluzole/therapeutic use/adverse effects ; New Zealand ; *Amyotrophic Lateral Sclerosis/drug therapy ; Female ; Male ; Middle Aged ; Aged ; *Guideline Adherence/statistics & numerical data ; *Drug Monitoring ; *Neuroprotective Agents/therapeutic use/adverse effects ; Practice Guidelines as Topic ; *Practice Patterns, Physicians'/statistics & numerical data ; Spirometry ; Adult ; },
abstract = {AIM: This retrospective cohort study assessed adherence to the Motor Neurone Disease New Zealand best practice guidelines and Pharmac Special Authority criteria for riluzole in a Canterbury-based amyotrophic lateral sclerosis (ALS) cohort. Secondary objectives included reasons for not prescribing, side effects and treatment initiation relative to diagnosis.

METHOD: A retrospective cohort study was conducted using the Christchurch Hospital respiratory department's ALS database. Patients diagnosed between January 2020 and November 2024 were included. Electronic health records and Special Authority records were reviewed. Patients with incomplete data or non-motor neurone disease (MND) diagnoses were excluded.

RESULTS: Of 115 patients, 69 (60%) were prescribed riluzole. Less than 45% of patients had baseline blood tests, and pre-treatment spirometry was completed in 70% of patients. Delays in prescribing improved rates of baseline spirometry, but not blood test completion. Ongoing monitoring was poor, with less than 60% of patients completing recommended tests across all time points. Eight patients (11.6%) reported side effects, and three discontinued treatment following alanine aminotransferase derangement.

CONCLUSION: Adherence to recommended monitoring and Special Authority criteria for riluzole was inconsistent in this cohort. In the context of emerging evidence supporting broader survival benefit and reduced drug cost, further evaluation of current Special Authority prescribing criteria may be warranted.},
}

Humans
Retrospective Studies
*Riluzole/therapeutic use/adverse effects
New Zealand
*Amyotrophic Lateral Sclerosis/drug therapy
Female
Male
Middle Aged
Aged
*Guideline Adherence/statistics & numerical data
*Drug Monitoring
*Neuroprotective Agents/therapeutic use/adverse effects
Practice Guidelines as Topic
*Practice Patterns, Physicians'/statistics & numerical data
Spirometry
Adult

@article {pmid42583074,
year = {2026},
author = {Glynne-Jones, R and Mawdsley, S},
title = {The historical perspective on anal cancer therapy: what have we learnt, where did we fail?.},
journal = {ESMO gastrointestinal oncology},
volume = {13},
number = {Pt A},
pages = {100151},
pmid = {42583074},
issn = {2949-8198},
abstract = {Squamous-cell cancer of the anus is a rare entity. Fifty years ago, understanding the natural history was limited by the lack of an agreed staging system and a largely irrelevant but complex histological categorisation. Retrospective reports described a small number of patients, generally with small tumours, treated by diverse methods with limited follow-up. The use of therapeutic radiation was limited by observed acute toxicity. Some centres gained substantial experience with interstitial radiation, but knowledge and expertise regarding the natural history and optimal methods of treatment were difficult to accumulate and hand on. Radiotherapy (RT) with or without interstitial radiation as the primary treatment, chemoradiotherapy (CRT) both definitive and preoperative, local excision for residual after CRT and small margin carcinomas and 'prophylactic' groin dissections after radical surgery all had advocates in different centres. The dogma in Europe at the time favoured split-course treatments. Early experiments combining fluoropyrimidines and RT were refined with Nigro et al.'s landmark study in 1974. Subsequent regimens are variations and today CRT with concurrent fluoropyrimidines and mitomycin C is accepted as the standard primary treatment. Early randomised phase III trials proved CRT to be more effective than external beam RT alone, but uncertainty remained over the optimal integration of chemotherapy, the type of chemotherapy, the ideal RT doses and potential late effects. These questions were imperfectly addressed and led to subsequent pragmatic phase III trials testing the impact of induction and consolidation chemotherapy and dose escalation. We describe the historical perspective and examine the opportunities we failed to grasp.},
}

@article {pmid42594043,
year = {2026},
author = {Nair, T and Larson, T and Raymond, J and Horton, DK and Mehta, P},
title = {Motor Neuron Disease Mortality in the United States, 2010-2023: A demographic, geographic, and temporal analysis.},
journal = {Neuroepidemiology},
volume = {},
number = {},
pages = {1-24},
doi = {10.1159/000551599},
pmid = {42594043},
issn = {1423-0208},
abstract = {INTRODUCTION: Our objective was to calculate age-adjusted motor-neuron disease (MND) mortality rates in the United States, 2010-2023, by year, age, sex, race, origin, period, and state. Amyotrophic lateral sclerosis makes up almost 80% of all MNDs.

METHODS: Multiple cause mortality data was obtained from the National Center for Health Statistics (NCHS) for years 2010-2023. Cases were included if code G12.2, the code for MND listed in the International Classification of Disease, 10th Revision (ICD-10), was listed as a cause of death. Using the direct method, cases were age-adjusted to the 2000 U.S. Standard population and mortality rates were calculated.

RESULTS: The overall national MND associated mortality rate was 2.07 per 100,000 population (95% CI 2.06, 2.09). Rates were highest in those aged 80+ years (13.69, 95% CI 13.49, 13.89) at death, non-Hispanic (2.17, 95% CI 2.15, 2.18), and male (2.50, 95% CI 2.48, 2.52). Northern states had higher rates (2.26, 95% CI 2.23, 2.29) with a rate ratio of (1.05, (95% CI 1.04, 1.07) when compared to the middle state tier (2.14, 95% CI 2.12, 2.17, p<0.01). State rates ranged from 3.07 (95% CI 2.75, 3.42) in Vermont to 1.41 (95% CI 1.27, 1.57) in Hawaii. The average annual percentage change was -1.62, corresponding to a statistically significant negative trend.

CONCLUSION: MND associated mortality rates were higher among northern states, decedents who were male, White, or non-Hispanic, which is consistent with previous studies of U.S. MND mortality. Decreasing mortality rates may indicate longer patient life spans due to increased treatment options and care access, but further research is needed.},
}

@article {pmid42580829,
year = {2026},
author = {Gaube, LM and Sparks, ED and Iten, M and Knapp, J and Fürholz, M and Schefold, JC and Hunziker Munsch, L and Hänggi, M and Krummrey, G and Müller, M and Hautz, WE},
title = {In-hospital cardiopulmonary resuscitation with balloon occlusion of the descending aorta: protocol of the randomised controlled CPReboa study.},
journal = {BMJ open},
volume = {16},
number = {8},
pages = {e119691},
doi = {10.1136/bmjopen-2026-119691},
pmid = {42580829},
issn = {2044-6055},
mesh = {Humans ; *Balloon Occlusion/methods ; *Cardiopulmonary Resuscitation/methods ; Prospective Studies ; *Heart Arrest/therapy/mortality ; *Aorta, Thoracic ; Randomized Controlled Trials as Topic ; Return of Spontaneous Circulation ; Female ; Adult ; },
abstract = {INTRODUCTION: Cardiac arrest (CA) remains a major health burden with poor survival and poor neurological outcomes despite decades of advances in resuscitation science. Although high-quality cardiopulmonary resuscitation is essential, it provides only limited cerebral and coronary perfusion, and current strategies relying on high-dose epinephrine may adversely affect cerebral microcirculation. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has emerged as a potential adjunct to improve coronary and cerebral perfusion without compromising microvascular blood flow. Although animal studies and small human case series suggest physiological and clinical benefits of REBOA in CA, randomised clinical trials are lacking.

METHODS AND ANALYSIS: This prospective, randomised controlled, single-centre clinical trial investigates the effect of REBOA during the treatment of CA. The planned study duration is 36 months, with a total of 98 patients to be randomised to either standard advanced life support (ALS) or ALS plus REBOA. Adult patients with an in-hospital CA, successful placement of a femoral artery introducer sheath and any electrical cardiac activity in the initial rhythm analysis are eligible for inclusion. Exclusion criteria comprise traumatic CA, asystole as the initial rhythm, pregnancy and CA occurring on intensive care units, in the operating room or in cardiac catheter laboratory. The primary outcome is sustained return of spontaneous circulation lasting for at least 20 min. Secondary and exploratory outcomes include survival, neurological outcome, changes in aortic blood pressure, end-tidal CO₂ and near-infrared spectroscopy values as well as causes of death and vascular complications related to the intervention. Statistical analyses will be performed on a modified intention-to-treat basis.

ETHICS AND DISSEMINATION: The study protocol (Version 2.1, 11.02.2026) was approved by the Cantonal Ethics Committee of Cantone Bern (2025-D0108). Study results will be disseminated through peer-reviewed journals.

TRIAL REGISTRATION NUMBER: NCT07434726.},
}

Humans
*Balloon Occlusion/methods
*Cardiopulmonary Resuscitation/methods
Prospective Studies
*Heart Arrest/therapy/mortality
*Aorta, Thoracic
Randomized Controlled Trials as Topic
Return of Spontaneous Circulation
Female
Adult

@article {pmid42581415,
year = {2026},
author = {Goehring, K and Abler, E and Vavra, J and Mayer, K and Dorst, J and Elmas, Z and Wiesenfarth, M and Richter, L and Petri, S and Regensburger, M and Reilich, P and Bjelica, B and Lumi, R and Süß, P and Tumani, H and Otto, M and Weishaupt, JH and Ludolph, AC and Oeckl, P},
title = {Blood SOD1 Activity in ALS Patients Receiving Tofersen Treatment.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78328},
pmid = {42581415},
issn = {1531-8249},
abstract = {OBJECTIVE: The antisense oligonucleotide tofersen is the first disease-modifying drug for SOD1-related amyotrophic lateral sclerosis (ALS) and was approved because of its ability to reduce SOD1 protein and neurofilament levels. The effect of tofersen on SOD1 activity is unclear but of clinical relevance because homozygous SOD1 mutations, linked to reduced SOD1 activity, cause severe motor neuron impairment and tofersen-induced reduction could be deleterious. Therefore, monitoring of SOD1 activity is urgently needed.

METHODS: SOD1 activity was analyzed in blood samples from a discovery (n = 120) and a validation cohort (n = 208), including controls, patients with sporadic ALS (sALS), C9orf72 mutation carriers (c9ALS), asymptomatic (SOD1-asym), and symptomatic SOD1 mutation carriers (SOD1-ALS). SOD1 activity was characterized in 18 patients receiving tofersen treatment.

RESULTS: SOD1 activity was significantly lower in both SOD1-asym (median = 7.5 U/mg, interquartile range [IQR] = 7.0-9.0 U/mg) and SOD1-ALS (median = 7.9 U/mg, IQR = 7.1-9.1 U/mg) relative to controls (median = 9.2 U/mg, IQR = 8.9-10.0 U/mg, p < 0.0001), c9ALS (median = 9.4 U/mg, IQR = 8.9-10.2 U/mg, p < 0.0001) and sALS (median 9.5 U/mg, IQR 8.8-9.9 U/mg, p < 0.0001). SOD1 activity was significantly lower in individuals with deleterious SOD1 variants than in individuals with neutral variants. During tofersen treatment, neurofilament and SOD1 protein levels decreased, whereas SOD1 activity remained stable.

INTERPRETATION: The data indicate that the positive tofersen treatment effect is independent of SOD1 activity. Lower SOD1 activity is specific to SOD1-ALS, already present in the asymptomatic phase and depends on the mutation type. Future studies should determine whether tofersen treatment affects cerebrospinal fluid (CSF) SOD1 activity. ANN NEUROL 2026.},
}

@article {pmid42576069,
year = {2026},
author = {Saleem, M and Khan, MS and Syed Khaja, AS and Alraey, Y and Ahmad, I and Almuzaini, Y and AlShammari, A and Alshamamri, YM and Alharbi, T},
title = {Prevalence, antifungal susceptibility, and virulence determinants of Candida species causing vulvovaginal candidiasis in pregnant women in Saudi Arabia.},
journal = {Antonie van Leeuwenhoek},
volume = {119},
number = {9},
pages = {},
pmid = {42576069},
issn = {1572-9699},
support = {RGP.01/146/46//the Deanship of Research and Graduate Studies at King Khalid University/ ; },
mesh = {Humans ; Female ; *Candidiasis, Vulvovaginal/epidemiology/microbiology/drug therapy ; Saudi Arabia/epidemiology ; *Antifungal Agents/pharmacology ; Pregnancy ; Prevalence ; *Virulence Factors/genetics ; Microbial Sensitivity Tests ; *Candida/drug effects/pathogenicity/genetics/classification/isolation & purification ; Adult ; Young Adult ; Adolescent ; *Pregnancy Complications, Infectious/microbiology/epidemiology ; Drug Resistance, Fungal ; Virulence ; },
abstract = {Vulvovaginal candidiasis (VVC) is a common opportunistic fungal infection of the female genital tract, primarily associated with Candida overgrowth influenced by host factors, hormonal changes, microbial imbalance, and environmental conditions. This study examined the prevalence, antifungal susceptibility, and virulence factors of Candida species in 440 pregnant women (ages 18-55) with vulvovaginitis and vaginal discharge at a Saudi Arabian hospital. The study was conducted from March 2022 to February 2023 at a tertiary hospital in Hail, Saudi Arabia, including 440 pregnant women with vaginitis. Vaginal swabs were cultured for Candida, with species identification and antifungal susceptibility testing performed using the Vitek-2 Compact system against five antifungals. Multiplex PCR was used to detect virulence genes (Hwp, Als, Sap, Hlp). Among them, 114 (25.9%) tested positive for Candida species, with Candida albicans being most prevalent (42.1%), followed by C. glabrata (19.3%) and C. tropicalis (12.3%). Most cases occurred during the second trimester (67%), with an average age of 27 years. Antifungal susceptibility testing showed that nystatin exhibited 49.1% susceptibility, 19.3% susceptible-dose dependence (SDD), and 31.6% resistance. Clotrimazole demonstrated 40.4% susceptibility, 26.3% SDD, and 33.3% resistance. Itraconazole showed 50.9% susceptibility, 28% SDD, and 21.1% resistance. Fluconazole exhibited 43.8% susceptibility, 8.8% SDD, and the highest resistance rate (47.4%). Voriconazole was the most effective antifungal agent, with 93% susceptibility, 3.5% SDD, and 3.5% resistance. Virulence analysis showed C. albicans had high Hwp (91.7%) and Sap (54.2%) gene detection, while C. glabrata and C. tropicalis exhibited elevated Hlp and Als levels, respectively. This study highlights the high prevalence of VVC in the second trimester and emphasizes the importance of virulence factors in pathogenicity. Voriconazole emerges as the most effective treatment, emphasizing the need for targeted diagnostics and therapies.},
}

Humans
Female
*Candidiasis, Vulvovaginal/epidemiology/microbiology/drug therapy
Saudi Arabia/epidemiology
*Antifungal Agents/pharmacology
Pregnancy
Prevalence
*Virulence Factors/genetics
Microbial Sensitivity Tests
*Candida/drug effects/pathogenicity/genetics/classification/isolation & purification
Adult
Young Adult
Adolescent
*Pregnancy Complications, Infectious/microbiology/epidemiology
Drug Resistance, Fungal
Virulence

@article {pmid42576199,
year = {2026},
author = {Zheng, F and Guan, R and Yu, X and Yang, J and Zhao, H and Yang, F},
title = {ADAR-mediated RNA editing in CNS disorders: from pathogenic mechanisms to therapeutic opportunities.},
journal = {Cellular & molecular biology letters},
volume = {31},
number = {1},
pages = {},
pmid = {42576199},
issn = {1689-1392},
mesh = {Humans ; *RNA Editing/genetics ; *Adenosine Deaminase/metabolism/genetics ; *Central Nervous System Diseases/genetics/therapy/pathology/metabolism ; Animals ; *RNA-Binding Proteins/metabolism/genetics ; },
abstract = {The adenosine deaminases acting on RNA (ADAR) family of enzymes (ADAR1 and ADAR2) catalyze adenosine-to-inosine (A-to-I) RNA editing. This post-transcriptional change is remarkably prevalent in the central nervous system (CNS). ADAR-mediated editing is critical for proper brain development, synaptic plasticity, and immunological homeostasis in the central nervous system (CNS) via recoding neurotransmitter receptors and ion channels. Conversely, a wide range of CNS disorders, such as neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis), neuropsychiatric conditions (schizophrenia, bipolar disorder, and major depression), cerebrovascular diseases, and gliomas, are now linked to dysregulation of ADAR activity, whether through loss-of-function mutations, altered expression, or mislocalization. To address the main question of whether altered RNA editing is a fundamental driver of pathogenesis, a compensatory response, or a context-dependent modulator, this review critically synthesizes existing evidence. The basic processes of ADAR enzymes and their regulation throughout neurodevelopment are first described. Next, we thoroughly assess the unique molecular fingerprints of ADAR dysregulation across several CNS disorders, emphasizing recurring themes such as Alu RNA hypo-editing, induction of innate immunity, and GRIA2 editing, which can cause excitotoxicity. Lastly, we examine new treatment approaches that use or reinstate ADAR activity, such as small-molecule modulators and site-directed RNA editing tools (leveraging endogenous ADAR for programmable editing of RNA [LEAPER], clustered ADAR-recruiting guide RNAs (gRNAs) for effective RNA editing [CLUSTER], and mimicking inverted repeats to recruit ADARs using engineered oligoribonucleotides [MIRROR]). We summarize by reviewing key obstacles to clinical translation, including crossing the blood-brain barrier, the risks of off-target editing, and the challenges of achieving spatiotemporal accuracy. We also list important open topics for further investigation.},
}

Humans
*RNA Editing/genetics
*Adenosine Deaminase/metabolism/genetics
*Central Nervous System Diseases/genetics/therapy/pathology/metabolism
Animals
*RNA-Binding Proteins/metabolism/genetics

@article {pmid42580389,
year = {2026},
author = {Bu, J and Nie, X and Luo, H and Wang, J and Jiang, D and Xu, N and Zhuang, P and Zhang, Y and Yin, Q},
title = {Neuron-Derived Neuroinflammation in Neurodegenerative Diseases: Mechanisms and Intervention Prospects.},
journal = {Pharmacological research},
volume = {},
number = {},
pages = {108383},
doi = {10.1016/j.phrs.2026.108383},
pmid = {42580389},
issn = {1096-1186},
abstract = {Neurodegenerative diseases represent a major global public health challenge, imposing substantial societal and economic burdens. Their complex pathogenesis and limited therapeutic options underscore an urgent need for new paradigms. Emerging evidence indicates that dysregulation of the brain's immune microenvironment is a critical driver of disease progression. Conventional wisdom posits that peripheral immune cells and central glial cells serve as the primary initiators of neuroimmune responses, whereas neurons are regarded merely as passive recipients of inflammatory damage. Emerging evidence suggests that upon receiving pathological signals in the central nervous system, neurons may become more vulnerable and participate in the onset of neuroimmune processes, positioning them as potential targets for early intervention in neurodegenerative diseases. This article systematically reviews the contribution of neuron-derived immune-inflammatory responses in neurodegenerative diseases and potential intervention strategies. We first outline the capacity of neurons to regulate neuroimmune responses and detail the underlying molecular mechanisms. Then we compare the specific mechanisms by which neurons with different susceptibility drive and amplify neuroinflammation in various neurodegenerative diseases such as alzheimer's disease, parkinson's disease, amyotrophic lateral sclerosis, vascular cognitive impairment, and transformed these mechanisms into intervention strategies targeting neurons,. This article aims to break through the traditional concept of passive neuronal damage, systematically integrate intervention strategies that shift from targeting peripheral immune and glial cells to regulating neuron-derived immunity, thereby providing a new theoretical framework for overcoming current clinical limitations and identifying effective therapeutic targets for the prevention and treatment of neurodegenerative diseases.},
}

@article {pmid42568823,
year = {2026},
author = {Ding, M and Lu, J},
title = {The Influence of Applied Voltage on Drying Kinetics, Quality, and Mathematical Modeling of Ginger During Electrohydrodynamic (EHD) Drying.},
journal = {Food science & nutrition},
volume = {14},
number = {8},
pages = {e72218},
pmid = {42568823},
issn = {2048-7177},
abstract = {This paper systematically evaluated the effects of electrohydrodynamic (EHD) on the drying characteristics, color, texture, moisture state, volatile components, and drying kinetics model of ginger. The results showed that EHD significantly increased the drying rate, rehydration rate, and effective moisture diffusion coefficient (D eff) of ginger. Among all the evaluated parameters, a voltage of 17 kV can produce the highest quality ginger. The drying rate of the 21 kV treatment group was 4.48 times higher than that of the control group (CG). ln[MR] showed a highly linear relationship with time (R [2] > 0.9). Among the ten thin-layer drying kinetics models, Midilli et al.'s model performed the best. Under 17 kV conditions, the best color retention was achieved for dried ginger. EHD drying significantly improved the texture of ginger. LF-NMR results showed a significant decrease in free water and an increase in bound water. Compared with the CG group, EHD showed good retention of most terpenoid compounds in dry ginger. SwissADME predicted six volatile compounds with good drug-like properties. Based on this study, it has been confirmed that the EHD technology has a good application in the ginger industry, providing theoretical support and experimental basis for the further expansion of EHD technology in the field of food drying.},
}

@article {pmid42575772,
year = {2026},
author = {Russo, AG and Hawkshaw, MJ and Sataloff, RT},
title = {Voice Disorders as Early Biomarkers of Cognitive Decline.},
journal = {Journal of voice : official journal of the Voice Foundation},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jvoice.2026.07.037},
pmid = {42575772},
issn = {1873-4588},
abstract = {BACKGROUND: Dementia affects greater than 57 million people worldwide. With an aging population and limited disease-curing treatments available, early identification of biomarkers is crucial. The 2020 Lancet Commission identified hearing loss as the largest modifiable risk factor for dementia globally, and a randomized controlled trial found that hearing intervention reduced 3-year cognitive change in older adults who were at increased risk for cognitive decline. Similarly, studies have found that abnormalities in acoustic measures of voice are correlated with cognitive status and can potentially predict decline. The association between hearing loss and cognitive decline might have both social and neurological mechanisms. Dysphonia might pose similar problems. Socially, voice disorders may reduce engagement in social and cognitively stimulating activities. Neurologically, one example is in Parkinson's disease in which the vagus nerve is one of the earliest sites of Lewy body pathology in Braak staging, and dysphonia and dysarthria can precede motor symptoms by years. Voice changes have been associated with different neurological conditions such as amyotrophic lateral sclerosis, multiple system atrophy, and Alzheimer's disease. Despite this, no prior large-scale study has examined whether diagnosed voice disorders are associated independently with incident cognitive decline. Our study is the first to examine this potential association, using the TriNetX US Collaborative Health Network platform to compare patients with diagnosed voice disorders and matched controls, with a hearing loss cohort as a standard of comparison given that it is the largest established modifiable risk factor for dementia, as dysphonia is also a modifiable condition.

RESULTS: This study included 833,417 total patients in the voice disorders and control cohorts. Voice disorders were associated with a significantly elevated risk of incident cognitive decline compared to controls (HR=1.291, 95% CI 1.155-1.443, P<0.0001). Hearing loss alone was associated with a slightly lower risk of cognitive decline (HR=1.267, 95% CI 1.203-1.334, P<0.0001). Voice disorders without concurrent hearing loss were associated with an elevated risk of incident cognitive decline compared to hearing loss alone (HR=1.261, 95% CI 1.121-1.419, P=0.0001), while voice disorders with hearing loss were associated with the highest risk among all cohorts (HR=2.038 vs controls; HR=1.545 vs hearing loss). Both voice disorder subgroups did not differ when compared with each other (HR=1.088, P=0.376).

CONCLUSION: The results from our study indicate that voice disorders are associated with an elevated risk of incident cognitive decline and may represent a stronger early biomarker than hearing loss alone. These findings highlight otolaryngology and family medicine/internal medicine encounters as potential entry points for cognitive assessment, and early voice treatment needs to be investigated for possible beneficial cognitive effect.},
}

@article {pmid42562776,
year = {2026},
author = {Wan, Y and Gao, C and Li, J and Luan, M and Lu, Y and Wang, J and Yang, B and Zheng, J and Yuan, Y and Wei, J and Wang, Z and Deng, J},
title = {Neural stem cell-derived small extracellular vesicles ameliorate disease progression in the SOD1 G93A murine model of amyotrophic lateral sclerosis.},
journal = {Journal of neuropathology and experimental neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnen/nlag013},
pmid = {42562776},
issn = {1554-6578},
support = {2025ZD0217600//Brain Science and Brain-like Intelligence Technology-National Science and Technology Major Project/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that primarily affects motor neurons leading to muscle weakness, paralysis, and ultimately, respiratory failure. Extracellular vesicles (EVs) facilitate intercellular communication by mimicking the functions of their parent cells. In this study, we found that repeated administration of neural stem cell-derived extracellular vesicles (NSC-derived EVs) improved motor performance and provided protection to lumbar motor neurons, the neuromuscular junctions, and muscle morphology in the SOD1 G93A transgenic mouse model of ALS. Furthermore, by analyzing the RNA-sequencing of muscle specimens from ALS-SOD1 patients, we demonstrated that the rescue effects of NSC-derived EVs might be linked to the p53 pathway. Compared to the PBS control treatment group, both TP53 and the p53 upregulated modulator of apoptosis (PUMA) were downregulated in the spinal cord of mice treated with NSC-derived EVs. These data provide additional knowledge for the promising use of NSC-derived EVs as a potential therapy for ALS.},
}

@article {pmid42554695,
year = {2026},
author = {Krajewski, TJ and Koch, GG},
title = {Randomization-based covariance analysis for hypothesis testing of treatment comparisons based on restricted mean survival time with categorized time-to-event data.},
journal = {Journal of biopharmaceutical statistics},
volume = {},
number = {},
pages = {1-20},
doi = {10.1080/10543406.2026.2699854},
pmid = {42554695},
issn = {1520-5711},
abstract = {This paper introduces randomization-based analysis of covariance (RB-ANCOVA) for hypothesis testing of restricted mean survival time (RMST) differences between two randomized treatments in trials with categorized time-to-event data. RMST treatment differences over a prespecified time period are clinically meaningful and avoid assumptions like proportional hazards. The proposed method tests the strong null hypothesis that each participant's time-to-event would remain unchanged regardless of treatment assignment. Covariate adjustment is achieved by constraining baseline covariate means to be equal across arms, which reduces variance. The follow-up period is partitioned into mutually exclusive intervals, and RMST is approximated as the area under the survival curve. Under the strong null hypothesis, the joint asymptotic covariance structure of RMST and covariate means is known and used to construct a chi-squared test statistic for the covariate-adjusted RMST difference. The method accommodates stratified trial designs and supports hypothesis testing over single or several time intervals, enabling testing within internal intervals. The difference in RMSTs over an interval can be divided by its length to yield an average survival rate difference. Additionally, the approach allows the computation of essentially exact p-values via re-randomization. We illustrate the method with data from a randomized, placebo-controlled trial evaluating a test treatment for amyotrophic lateral sclerosis. This method provides a hypothesis testing approach for RMST treatment differences that leverages RB-ANCOVA to adjust for their correlations with baseline covariate differences. Under the strong null hypothesis, it enables hypothesis testing with clear control of Type I error and reduced variance without relying on model-based assumptions.},
}

@article {pmid42556956,
year = {2026},
author = {Rahman, U and Yang, SC},
title = {Management of Anastomotic Leaks: Endoscopic, Interventional, and Surgical Strategies.},
journal = {Advances in surgery},
volume = {60},
number = {1},
pages = {259-270},
doi = {10.1016/j.yasu.2026.03.017},
pmid = {42556956},
issn = {1878-0555},
mesh = {Humans ; *Anastomotic Leak/therapy/surgery/etiology ; },
abstract = {Anastomotic leaks (ALs) are a significant source of morbidity and mortality. Every step should be implemented to prevent AL, including careful patient selection, optimizing patient's clinical and nutritional status, and ensuring proper technique. The appropriate management of an AL depends on several factors, such as patient's clinical status, the type of surgery, location of the AL, induction therapies, and the resources available. Surgeons should be familiar with the armamentarium of treatment modalities available to manage AL and use a patient-tailored approach when selecting the most appropriate treatment.},
}

Humans
*Anastomotic Leak/therapy/surgery/etiology

@article {pmid42558984,
year = {2026},
author = {Pourasghari, M and Babaie, S and Markazi-Movaghar, R and Salehpour, S and Eftekharsadat, B and Farshbaf-Khalili, A},
title = {The Effectiveness Based on Optimal Dose and Administration Route, and Safety Profiles of Stem Cells and Derived Products in the Treatment of Patients With Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.},
journal = {Stem cells international},
volume = {2026},
number = {},
pages = {4122493},
pmid = {42558984},
issn = {1687-966X},
abstract = {BACKGROUND: This systematic review and meta-analysis aimed to evaluate the effectiveness of stem cell therapies for patients with amyotrophic lateral sclerosis (ALS) based on optimal dosing and administration routes, as well as the safety profiles of stem cells and their derived products.

METHODS: The review followed PRISMA guidelines and involved a comprehensive literature search up to October 2025, receiving ethical approval from Tabriz University of Medical Sciences and registration in PROSPERO. It utilized international databases, including PubMed/MEDLINE, Embase, Cochrane Library, Scopus, Web of Science, ProQuest, ClinicalTrials.gov, and Science Direct. The included studies comprised randomized controlled trials (RCTs), quasi-experimental studies, and other interventional designs involving ALS patients treated with stem cell therapies. In total, 31 studies were analyzed, featuring 7 controlled trials with 370 participants and 24 non-controlled pre-post studies with 460 participants. Heterogeneity was evaluated using I [2] statistics, and subgroup analyses were conducted based on treatment duration and dosing.

RESULTS: A pooled analysis (treatment group: n = 93; control group: n = 90) demonstrated a significant attenuation in the progression of disease severity, as measured by the ALS Functional Rating Scale (ALSFRS), in stem cell groups versus controls (weighted mean difference [WMD]: 8.89 95% CI: 4.12-13.67; p = 0.0003), which was beneficial for both the ≥10 × 10[6] and <10 × 10[6] dose sub-groups. However, a meta-analysis of single-arm studies in two control (pre-intervention) and intervention phases (n = 88) demonstrated no significant difference in progression of ALSFRS between study phases by time: month 3 (WMD: -1.27 (-3.01 to 0.47); p = 0.15), month 6 (WMD: -2.69 (-5.62 to 0.25); p = 0.07), month 9 (WMD: -1.55 (-3.49 to 0.39); p = 0.12), and month 12 (WMD: -7.59 (-13.95 to -1.26); p = 0.02). An accelerated decline in forced vital capacity (FVC) was observed during the intervention phase, with statistically significant reductions at month 3 (WMD: -10.91; 95% CI: -16.39 to -5.43; p < 0.0001) and month 6 (WMD: -15.97; 95% CI: -28.60 to -3.33; p = 0.01) compared with the pre-intervention control phase. Nevertheless, sensitivity analyses excluding studies involving high-dose mesenchymal stem cell (MSC) therapies demonstrated that these differences were no longer statistically significant. Moreover, no significant change in progression rate was observed at month 9 (WMD: -8.10 (-18.25 to 2.06); p = 0.12). The route of MSCs administration (intrathecal [IT], intramuscular [IM], and intravenous [IV]) had no effect on the results of ALSFRS and FVC, reinforced by sensitivity analyses. Adverse events were mostly mild, with headaches most frequent in high-dose groups.

CONCLUSION: Stem cell therapy for ALS appears to be safe, with preliminary evidence suggesting potential therapeutic benefit in slowing disease progression in selected patients. Nevertheless, the existing evidence base remains exploratory, and definitive conclusions regarding clinical effectiveness cannot yet be drawn. Future research should prioritize large-scale and multicenter RCTs with standardized cell manufacturing protocols and longer follow-up periods.},
}

@article {pmid42561511,
year = {2026},
author = {Al Ojaimi, Y and Dupuis, A and Palla, M and Lanznaster, D and Hergesheimer, R and Galineau, L and Serriere, S and Chami, AA and Martineau, P and Alouane, T and Marouillat, S and Dupuy, C and Schneider, BL and Veyrat-Durebex, C and Masse, F and Trovero, F and Andres, CR and Corcia, P and Vourcʼh, P and Blasco, H},
title = {Intrabody B1 targeting TDP-43 modulates neuroinflammatory and metabolic pathways in a preclinical ALS model.},
journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics},
volume = {23},
number = {5},
pages = {e01032},
doi = {10.1016/j.neurot.2026.e01032},
pmid = {42561511},
issn = {1878-7479},
abstract = {TDP-43 pathology is a hallmark of Amyotrophic Lateral Sclerosis (ALS), yet no therapeutic strategy effectively targets its upstream molecular consequences. Here, we investigated whether the anti-TDP-43 intrabody scFv B1 modulates neuroinflammatory and metabolic pathways in a preclinical ALS model, and whether these effects translate into functional benefit after symptom onset. Using phage display, we previously identified single-chain variable fragments (scFvs) binding TDP-43, including the candidate therapeutic scFv B1. In NSC-34 motor neuron-like cells overexpressing human wildtype TDP-43, B1 reduced NF-κB activation, consistent with disruption of TDP-43-driven inflammatory signaling. For in vivo assessment, B1 was delivered via AAV-CAP.B10 after symptom onset in the hTDP-43(WTxA315T) transgenic mouse model, enabling neuro-specific expression. Two cohorts were analyzed - longitudinal (nine months) and terminal (six months post-treatment) - through behavioral testing, PET imaging, metabolomics, transcriptomics, and plasma biomarker analyses. B1 achieved robust CNS expression and modulated several disease-relevant molecular pathways. RNA-sequencing revealed attenuation of NF-κB-related inflammatory signatures and partial normalization of metabolic and trophic gene expression. Metabolomic profiling identified shifts toward wild-type-like levels in oxidative stress, mitochondrial, and membrane phospholipid metabolites. Despite these molecular effects, symptomatic B1 administration did not improve motor behavior or reduce plasma neurofilament light chain (NfL) concentrations. Notably, plasma TDP-43 levels were stabilized, indicating systemic target engagement. Collectively, scFv B1 modulates upstream pathogenic processes associated with TDP-43 proteinopathy but is insufficient to reverse established neurodegeneration after symptom onset, underscoring the need for earlier and likely combinatorial intervention strategies in ALS.},
}

@article {pmid42561943,
year = {2026},
author = {Rostalski, H and Hietanen, T and Hoffmann, D and Heikkinen, S and Huber, N and Dhingra, A and Rodriguez-Nieto, S and Kuulasmaa, T and Ohtonen, S and Jäntti, H and Pekkala, V and Leskelä, S and Mäkinen, P and Katisko, K and Hartikainen, P and Lehtonen, Š and Solje, E and Koistinaho, J and Malm, T and Portaankorva, AM and Natunen, T and Martiskainen, H and Takalo, M and Hiltunen, M and Haapasalo, A},
title = {C9orf72-associated and sporadic FTD patient iPSC-microglia show differences in phagocytosis and gene expression.},
journal = {Stem cell reports},
volume = {},
number = {},
pages = {103026},
doi = {10.1016/j.stemcr.2026.103026},
pmid = {42561943},
issn = {2213-6711},
abstract = {C9orf72 hexanucleotide repeat expansion (C9-HRE) is a major genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (FTD). However, approximately half of the FTD patients are sporadic without a clear genetic background. To compare characteristics of microglia from different FTD subtypes, we generated induced pluripotent stem cell-derived microglia (iMG) from sporadic and C9-HRE-carrying behavioral variant FTD (bvFTD) patients and healthy controls. C9-HRE iMG displayed C9-HRE-associated RNA foci and dipeptide repeat proteins. All bvFTD iMG had fewer LAMP2-A-positive vesicles compared to control iMG. Additionally, C9-HRE iMG showed significantly increased LC3BII/I conversion after bafilomycin A1 treatment and altered phagocytic activity. The gene expression profile of C9-HRE iMG only modestly differed from the control iMG, but was greatly different from the sporadic bvFTD patient iMG. Our data show alterations in phagocytic and autophagosomal/lysosomal pathways and gene expression profiles between C9-HRE and sporadic bvFTD iMG for the first time.},
}

@article {pmid42561977,
year = {2026},
author = {Helmold, B and Armon, C and Benatar, M and Bertorini, T and Bromberg, M and Brown, A and Cadavid, JM and Carbunar, O and Carter, GT and Crayle, J and Feldman, E and Foucher, J and Glass, J and Greenstein, E and Jhooty, S and Jiang, N and Kochen, NN and McDermott, C and Olby, N and Pattee, G and Porter, D and Premasari, A and Rao, A and Ratner, D and Staats, K and Tito, E and Vieira, F and Wicks, P and Bedlack, R},
title = {ALSUntangled #84 - ivermectin.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-6},
doi = {10.1080/21678421.2026.2714724},
pmid = {42561977},
issn = {2167-9223},
abstract = {ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). In this review, we explore the possibility of using ivermectin to slow ALS progression. Ivermectin's ability to modulate neuroinflammation and excitotoxicity give it plausible mechanisms for treating ALS, though it does not get into the brain very well. One preclinical study demonstrated that ivermectin lengthened lifespan within a mouse model of mSOD1 genetic ALS. This finding has not been replicated. The 2 PALS we found who had data comparing ALSFRS-R progression on and off ivermectin appeared to have no benefit from it. We found no trials of ivermectin in PALS. Ivermectin is low cost and generally well tolerated with most adverse effects being mild and transient, but serious side effects can rarely occur, and it has not been carefully studied in PALS. We cannot at present endorse ivermectin as an ALS treatment.},
}

@article {pmid42552039,
year = {2026},
author = {Venu, G and A, VP and Justin, A},
title = {Molecular insights of peroxisome proliferator-activated receptor-γ signalling in amyotrophic lateral sclerosis and Huntington's disease.},
journal = {International review of neurobiology},
volume = {188},
number = {},
pages = {113-143},
doi = {10.1016/bs.irn.2026.05.014},
pmid = {42552039},
issn = {2162-5514},
mesh = {Humans ; *PPAR gamma/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism ; *Signal Transduction/physiology ; Animals ; *Huntington Disease/metabolism ; },
abstract = {Progressive neuronal loss is a hallmark of neurodegenerative diseases like Huntingtons disease (HD) and Amyotrophic lateral sclerosis (ALS) which are caused by convergent mechanisms such as oxidative stress, mitochondrial dysfunction, neuroinflammation, impaired autophagy and dysregulated cell death pathways. Both conditions share significant disruptions in metabolic and inflammatory signalling despite having different genetic origins and clinical manifestations; underscoring the necessity of pathway-oriented treatment approaches. In the central nervous system, peroxisome proliferator-activated receptor-γ (PPAR-γ), a ligand-activated nuclear receptor has become an important regulator of inflammation, redox homeostasis, mitochondrial biogenesis and cellular stress responses. After giving a thorough overview of PPAR-γ structure activation and transcriptional regulation and the PGC-1α-mediated mitochondrial biogenesis axis, this chapter delves deeply into its interactions with major signalling pathways such as NF-κB, Wnt/β-catenin Nrf2/ARE and the autophagy-apoptosis networks. With a focus on experimental data showing PPAR-γ signaling's neuroprotective, anti-inflammatory, antioxidant and metabolic regulatory roles the pathophysiology of ALS and HD is critically investigated. Lastly the need for improved biomarkers, tailored multi-target strategies and selective modulators is highlighted in the discussion of current therapeutic limitations and translational difficulties.},
}

Humans
*PPAR gamma/metabolism
*Amyotrophic Lateral Sclerosis/metabolism
*Signal Transduction/physiology
Animals
*Huntington Disease/metabolism

@article {pmid42553297,
year = {2026},
author = {Li, Q and You, M},
title = {Targeting mitochondria for the treatment of neurodegenerative diseases.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1835506},
pmid = {42553297},
issn = {1662-4548},
abstract = {Mitochondria are central regulators of cellular metabolism, redox balance, calcium signaling, and cell survival, making them essential for neuronal function. Because neurons rely heavily on mitochondrial oxidative phosphorylation to meet their high energetic demands, mitochondrial dysfunction has emerged as a key pathogenic driver in major neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Defects in mitochondrial bioenergetics, excessive reactive oxygen species production, impaired mitochondrial dynamics, disrupted mitophagy, and dysregulated calcium handling collectively contribute to neuronal damage, synaptic dysfunction, and neuroinflammation. These insights have prompted growing interest in therapeutic strategies that directly target mitochondria to restore organelle homeostasis. Recent advances in chemical biology and nanomedicine have enabled the development of mitochondria-targeted ligands, peptide-based targeting systems, and carrier or nanotechnology-enabled delivery platforms designed to overcome biological barriers and selectively deliver therapeutic cargos to mitochondria within the central nervous system. In this Review, we summarize mitochondrial pathological mechanisms in neurodegenerative diseases and discuss emerging mitochondria-targeted therapeutic strategies, highlighting delivery technologies, therapeutic modalities, and translational challenges. Although most strategies remain at the preclinical or proof-of-principle stage, these advances are beginning to shape a conceptual framework for precision mitochondrial medicine, with the longer-term goal of developing disease-modifying interventions for neurodegenerative disorders.},
}

@article {pmid42546549,
year = {2026},
author = {Silvagi, R and Rodriguez-Fohn, E and Reece, RJ and Cranford, JA and Alangaden, K and Byrd, M and Klausner, H and Pravin, R and Li, J and Conn, C and Dunne, R and O'Neil, BJ},
title = {Advanced vs basic life support outcomes in treatment of out-of-hospital-cardiac-arrest: A registry-based cohort study.},
journal = {The American journal of emergency medicine},
volume = {109},
number = {},
pages = {263-267},
doi = {10.1016/j.ajem.2026.07.021},
pmid = {42546549},
issn = {1532-8171},
abstract = {IMPORTANCE: The absolute effect on outcomes with Advanced, (ALS) as compared to Basic Life Support, (BLS) care in Out of Hospital Cardiac Arrest, (OHCA) remains unclear.

OBJECTIVE: To assess the association of ALS compared to BLS alone prehospital care on return of spontaneous circulation, (ROSC), survival to hospital discharge, and neurological outcome in OHCA in Detroit, MI.

METHODS: Retrospective analysis of 6746 patients from the Cardiac Arrest Registry to Enhance Survival database from January 2016 to December 2021 who had non-traumatic OHCA and received cardiopulmonary resuscitation. Cohorts were grouped by ALS v BLS care then initial rhythm and then compared by chi-squared, multivariable logistic, and multinomial regression analysis for outcomes of sustained ROSC, survival to hospital discharge and favorable neurological outcome at hospital discharge. The BLS cohort is defined by units that provided manual CPR, automated rhythm and defibrillation, airway management, but no endotracheal intubation or parenteral medications. ALS care was defined as manual rhythm interpretation, manual defibrillation, intravenous or intraosseous drug administration or endotracheal intubation.

RESULTS: Mean age was 62.6 years (SD-16.7), with 56.3% male and 84.6% Black. Cohort breakdown: shockable ALS (S-ALS; n = 330, 4.9%); shockable BLS (S-BLS; n = 466, 6.9%); non-shockable ALS (NS-ALS; n = 2793, 41.4%); non-shockable BLS (NS-BLS; n = 3157, 46.8%). ROSC rates by cohort: S-ALS (37.9%); S-BLS (19.5%); NS-ALS (18.6%); NS-BLS (9.3%). ALS was associated with increased sustained ROSC for all initial rhythms (p < .001). S-ALS was associated with increased survival (p = .03), and neurologic outcome (p = .01) when compared to S-BLS.

CONCLUSION & RELEVANCE: Advanced Life Support, relative to Basic Life Support alone, was associated with improved sustained return of spontaneous circulation across all initial rhythms, and improved survival to discharge and favorable neurologic outcome in shockable initial rhythms.},
}

@article {pmid42548517,
year = {2024},
author = {Palm, A and Grote, L and Einarsson, J and Hansson, D and Ljunggren, M and Sundh, J and Ekström, M},
title = {Evolution of Home Mechanical Ventilation in Sweden Over 27 Years: Changing Trends in Incidence, Prevalence, and Patient Characteristics - The Population-Based the Course of Disease in Patients Reported to the Swedish CPAP Oxygen and Ventilator Registry (DISCOVERY) Study.},
journal = {CHEST pulmonary},
volume = {2},
number = {4},
pages = {100108},
pmid = {42548517},
issn = {2949-7892},
abstract = {BACKGROUND: Home mechanical ventilation (HMV), noninvasive ventilation and invasive ventilation outside a hospital setting, is a key treatment to improve outcomes in chronic hypoventilation.

RESEARCH QUESTION: What are the temporal trends observed over 27 years in Sweden regarding the incidence, prevalence, diagnostic spectrum, and patient characteristics associated with HMV?

STUDY DESIGN AND METHODS: This was a national population-based longitudinal analysis of the Course of Disease in Patients Reported to the Swedish CPAP Oxygen and Ventilator Registry (DISCOVERY) study of patients initiating HMV between 1996 and 2022. Time trends stratified by the underlying diagnosis group (lung disease, predominantly COPD, restrictive thoracal diseases, obesity hypoventilation syndrome [OHS], neuromuscular diseases, amyotrophic lateral sclerosis, and other neurologic disorders) were analyzed using linear regression models.

RESULTS: We included 10,555 patients aged ≥ 16 years (mean age 63 [SD, 15] years; 50% women). Between 1996 and 1998 and 2020 and 2022, the HMV incidence increased threefold to 7 per 100,000 people, and the prevalence increased sixfold to 33 per 100,000 people. The most common indication for incident HMV shifted from restrictive thoracal diseases (35% in 1996-1998 to 3% in 2020-2022) to lung disease (14% to 31%), OHS (23% to 33%), and amyotrophic lateral sclerosis (4% to 14%) by 2020 to 2022 (P < .001). The proportion of women increased from 47% to 54% (P < .013) and the age at initiation of HMV increased from 58 [SD, 15] to 66 [SD, 14] years (P < .001). Lung function measured as vital capacity at treatment start increased significantly in all diagnosis groups except for OHS, where both vital capacity and FEV1 decreased. In the registry's first and last 3-year periods, the proportion of patients ventilated invasively decreased from 10% to 2% (P < .001).

INTERPRETATION: In the 27 years until 2022, the incidence and prevalence of HMV in Sweden have increased markedly, patient demographics have changed, and use of invasive ventilation has decreased. The average age of patients initiated on HMV has increased, but treatment is started earlier in the disease trajectory.},
}

@article {pmid42548788,
year = {2026},
author = {Erazo, D and Hesters, A and Bruneteau, G and De La Cruz, E and Bernard, E and Grapperon, AM and Le Masson, G and Cintas, P and Soriani, MH and Guy, N and Cassereau, J and Camdessanché, JP and Genestet, S and Corcia, P and Pittion, S and Danel, V and Filliatre, M and Choumert, A and Jacquin-Piques, A and Salachas, F and Esselin, F and Bohic, A and Lautrette, G and Attarian, S and Catteau, J and Guissart, C and Vincent, MC and Mouzat, K and Temple, M and Vourc'h, P and Couratier, P},
title = {Tofersen Treatment in SOD1-ALS: Real-World Evidence from a Retrospective Multicenter Study in France (FORSLA Study).},
journal = {Mayo Clinic proceedings. Innovations, quality & outcomes},
volume = {10},
number = {5},
pages = {100739},
pmid = {42548788},
issn = {2542-4548},
abstract = {OBJECTIVE: To evaluate the effectiveness of Tofersen in patients with superoxide dismutase 1 gene (SOD1-ALS) patients in France in a real-world setting, using disease progression within patient comparisons and with a historical cohort.

PATIENTS AND METHODS: Patients with SOD1-ALS were included from across 19 French FILSLAN network centers. Baseline was defined as the treatment initiation date. Main endpoints were the ALSFRS-R progression rate and plasmatic neurofilament light chain (NfL) levels at baseline and 12 months after baseline.

RESULTS: In the Tofersen Cohort (N=46), within-group comparisons showed that the mean ALS functional rating scale revised (ALSFRS-R) progression rate slowed from 0.53 ± 0.5 at baseline to 0.22 ± 0.3 point/month at 12 months (P=.006). NfL levels significantly decreased from 89.0 ± 9.0 pg/ml at baseline to 29.2 ± 19.5.5 at 12 months (P=.004). Exploratory comparisons with a propensity score (PS) matched historical cohort (39 matched pairs) using a mixed-effects model, ALSFRS-R progression rate at baseline, 6 months, and 12 months after baseline, showed no statistically significant differences between groups P=.30, whereas longitudinal ALSFRS-R scores differed significantly between groups (time-treatment interaction P=.006). The mean survival of the PS matched population was longer in the Tofersen Cohort (42.6 months) than the Historical Cohort (31.8 months) P=.004. Time-dependent adjusted cox analysis showed that Tofersen was associated with a reduction in mortality risk (adjusted HR=0.34; 95% CI, 0.12-0.91; P=.03).

CONCLUSION: Tofersen seems to be associated with slower functional decline and reduced NfL levels. While limitations of retrospective design and ALSFRS-R sensitivity must be acknowledged, these findings provide real-world evidence suggesting a clinical benefit of Tofersen.},
}

@article {pmid42541567,
year = {2026},
author = {Estevez-Fraga, C and Alvarez-Velasco, R and Afroz, T and Costa, MR and Jovičić, A and Yeh, FL and McColgan, P and Malaspina, A and McCampbell, A},
title = {Targeting TDP-43 in sporadic amyotrophic lateral sclerosis.},
journal = {Journal of neurology},
volume = {273},
number = {8},
pages = {},
pmid = {42541567},
issn = {1432-1459},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/therapy/pathology ; *DNA-Binding Proteins/metabolism/genetics ; Animals ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder characterized by motor neuron degeneration leading to early mortality. Despite advances in understanding genetic and molecular contributors, effective disease-modifying therapies for sporadic ALS are of limited utility. The identification of the accumulation of TAR DNA-binding protein 43 (TDP-43) in 97% of total ALS cases represents a critical pathogenic hallmark. This review examines key biological mechanisms underlying TDP-43 pathology, emerging therapeutic strategies, and evolving approaches to clinical trial design and biomarker development. TDP-43 loss of nuclear function, leading to widespread RNA missplicing, and inclusion of cryptic exons, represents an early and critical event in ALS pathogenesis causing downstream dysregulation of key neuronal genes such as STMN2 and UNC13A contributing to axonal degeneration and synaptic dysfunction. Therapeutic strategies targeting these pathways are currently under investigation. Additional approaches aim to ameliorate TDP-43 gain-of-function through cytoplasmic TDP-43 aggregation or modulating processes such as stress responses and RNA metabolism, although clinical translation has been challenging. Advances in biomarkers, including neurofilament light chain and cryptic exon-derived peptides, provide tools for developing efficient clinical trials. However, heterogeneity in disease progression and limitations of available clinical endpoints complicate trial design. Integration of biological insights with biomarker-driven patient stratification and optimized trial methodologies is essential to improve clinical trial outcomes. Emerging biomarkers may enable earlier diagnosis, monitoring of therapeutic response, and personalized treatment approaches. Continued alignment of biological discovery with innovative clinical trial design holds promise for advancing effective therapies and transforming the future of ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/metabolism/genetics/therapy/pathology
*DNA-Binding Proteins/metabolism/genetics
Animals

@article {pmid42533344,
year = {2026},
author = {Bublitz, SK and Becker, B and Demleitner, AF and Dietz-Laukemann, P and Lingor, P and Littger, B and Lorenzl, S and Feddersen, B},
title = {Ethical challenges in treatment-goal transitions in invasively ventilated ALS: a case-based topical review.},
journal = {Neurological research and practice},
volume = {8},
number = {1},
pages = {},
pmid = {42533344},
issn = {2524-3489},
abstract = {INTRODUCTION: In advanced amyotrophic lateral sclerosis (ALS), eye movements often represent the last channel for intentional communication. While oculomotor function has traditionally been considered relatively preserved, emerging evidence indicates progressive impairment in long-term survivors on tracheostomy-invasive ventilation (TIV). As a result, eye-based communication may become increasingly unreliable before complete loss, challenging clinical decision-making and advance care planning (ACP).

METHODS: We conducted a case-based topical review integrating clinical observation and literature to examine the trajectory of oculomotor decline, its impact on communication, and implications for treatment decisions. Three patients with ALS receiving TIV in a home-care setting illustrate key clinical and ethical challenges.

RESULTS: Across cases and literature, oculomotor decline followed a gradual trajectory from effective eye-tracking communication to a complete locked-in syndrome. We identify a transitional phase of communicative ambiguity, in which residual ocular signals persist but can no longer be reliably attributed to intentional, patient-controlled communication. This phase is characterized by increasing inconsistency of signals and a divergence between observable responses and their interpretive certainty, creating uncertainty in assessing patient preferences.

IMPLICATIONS: Communicative ambiguity represents a clinically underrecognized but critical threshold in advanced ALS, marking the transition from direct patient autonomy to interpretative and surrogate-based decision-making. Failure to recognize this phase risks misinterpretation of patient intent and may undermine goal-concordant care. Timely and iterative ACP, initiated before communication becomes unreliable, is essential. We further propose four clinical pathways for treatment goal conversations, highlighting their differing implications for timing, symptom burden, and ethical decision-making.},
}

@article {pmid42539252,
year = {2026},
author = {Wieland, CM and Wright, SE and Willey, S and Purwar, I and Grudzien, SJ and Krans, A and Laimon, E and Asher, MJ and Isaacs, A and Garner, AL and Todd, PK},
title = {Altered neuronal start codon stringency favors cap-independent repeat-associated non-AUG translation.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.07.16.739042},
pmid = {42539252},
issn = {2692-8205},
abstract = {Intronic GGGGCC repeat expansions in C9orf72 cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This expansion supports a non-canonical form of translational initiation known as repeat-associated non-AUG (RAN) translation to produce toxic dipeptide repeat proteins that contribute to neurodegeneration. Here, we find that the efficiency of RAN translation and its dependency on the 5' 7-methylguanosine mRNA cap are variable across cell types, with both rodent neurons and human iNeurons favoring cap-independent RAN translation from two distinct repeats (CGG and GGGGCC) across multiple reading frames. Treatment with an eIF4E inhibitor that blocks global cap-dependent translation enhances RAN translation specifically in neurons. Intriguingly, cap-independent RAN translation exhibits less reliance on near-cognate codons for initiation than cap-dependent RAN translation. This finding led us to identify a surprising global increase in start codon stringency in neurons as a contributor to the relatively higher cap-independent RAN translation in this cell type. This effect correlates with a cytoplasmic redistribution of eIF1 in neurons and is reversed with neuronal overexpression of the eukaryotic initiation factor eIF5, which relaxes start codon stringency and selectively enhances cap-dependent RAN translation. Taken together, these findings reveal several neuron-specific features of translational regulation that favor cap-independent RAN translation with implications for nucleotide repeat expansion disorder pathogenesis and neuronal translational regulation.},
}

@article {pmid42529685,
year = {2026},
author = {Cheung, N},
title = {Cellular Logistics and Synaptic Vesicle Vulnerability in Major Depressive Disorder and Amyotrophic Lateral Sclerosis Comorbidity: Insights From Nicotinamide Mononucleotide Rescue and Transcriptome-Wide Association Study Integration.},
journal = {Cureus},
volume = {18},
number = {7},
pages = {e113549},
pmid = {42529685},
issn = {2168-8184},
abstract = {BACKGROUND: Major depressive disorder (MDD) and amyotrophic lateral sclerosis (ALS) are usually treated as unrelated, yet depressive symptoms occur in a substantial minority of people with ALS and may appear early. These symptoms are heterogeneous and may reflect syndromal MDD, psychological and functional burden, fatigue, apathy, pseudobulbar affect, frontotemporal involvement, sleep or respiratory disturbance, medication effects, or shared affective vulnerability. A proposed pruning-continuum model suggests both disorders may share vulnerability in microglia-mediated synaptic pruning, with ALS amplified by autophagy and protein-quality-control failure and MDD by RNA-processing, stress, and immune dysregulation. We performed an exploratory secondary transcriptome-wide association study (TWAS)/pathway-integration analysis to test whether predefined nicotinamide mononucleotide (NMN)-nominated pathways map onto this vulnerability.

METHODS: We integrated precomputed S-PrediXcan outputs for MDD and ALS across available brain-relevant tissues. Ten Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were predefined from a prior re-analysis of NMN-associated transcriptional programs in aged mouse metabolic tissues. Mouse-derived candidates were represented by human ortholog symbols before the human TWAS screen. The analysis tested nominated pathways rather than the 35-gene NMN-robust list as a standalone set. Cross-tissue screening used Stouffer Z aggregation, tissue-level Wilcoxon testing, competitive permutation testing, percentile bootstrap intervals, pairwise disease statistics, Levene variance tests, concordance measures, and leave-one-out sensitivity analysis. No analysis was treated as confirmatory or evidence of causal mediation.

RESULTS: MDD showed the strongest Stouffer-based exploratory signal in the synaptic vesicle cycle pathway, with a meta-across-tissue Stouffer Z of 3.41 and a wide bootstrap 95% confidence interval of -0.46 to 7.40. This signal did not survive competitive permutation testing (p = 0.1222) or Wilcoxon testing (p = 0.1926). The strongest tissue-level result occurred in the amygdala (Z = 4.057; nominal Wilcoxon p = 0.0093), although tissue-level permutation testing was not performed in the multi-gene-set run. ALS showed no significant meta-across-tissue enrichment among the 10 nominated pathways but displayed candidate gene-level signals in autophagy, endosomal, and vesicle-related genes, including TBK1 and C9orf72. Exploratory Levene tests indicated variance heterogeneity in the regulation of the actin cytoskeleton, endocytosis, and neuroactive ligand-receptor interaction; the actin cytoskeleton and endocytosis remained significant in pooled global false discovery rate (FDR) analysis. Fourteen genes were influential in at least two focus pathways, including EGF, KNG1, FGF8, RAC1, PAK1, PAK2, RAF1, MAPK1, and FGFR1.

CONCLUSIONS: These findings are hypothesis-generating. MDD and ALS may stress overlapping cellular logistics processes while engaging largely different genes. MDD showed the strongest exploratory pathway-level signal in synaptic vesicle biology, whereas ALS showed candidate gene-level coherence in autophagy and endosomal processes without significant meta-pathway enrichment. NMN/NAD+ repletion is not established as a treatment for MDD, ALS, or their comorbidity. These findings generate hypotheses about NAD+-linked cellular stress pathways for future preclinical and clinical studies.},
}

@article {pmid42523591,
year = {2026},
author = {Balanis, T and Doulberis, M and Tutuian, R},
title = {EUS-guided transmural treatment of afferent loop syndrome: a systematic review and meta-analysis.},
journal = {Frontiers in gastroenterology (Lausanne, Switzerland)},
volume = {5},
number = {},
pages = {1853386},
pmid = {42523591},
issn = {2813-1169},
abstract = {BACKGROUND: Afferent loop syndrome (ALS) is an uncommon but clinically relevant complication after pancreaticobiliary or upper gastrointestinal reconstruction, most often in patients with recurrent malignant disease. Endoscopic ultrasound-guided creation of a transmural bypass, either as gastroenterostomy or enteroenterostomy, has emerged as a minimally invasive alternative to surgery or percutaneous drainage. We aimed to systematically review the available evidence and provide a pooled descriptive analysis of the efficacy and safety of EUS-guided treatment for ALS.

METHODS: A systematic review was performed in accordance with PRISMA principles. PubMed/MEDLINE, Embase and the Cochrane Library were searched up to 15 May 2025 for studies reporting EUS-guided gastroenterostomy or enteroenterostomy for ALS. Case reports, case series and observational studies with extractable outcome data were eligible. Data on study design, indication, stent type, technical success, clinical success, adverse events and follow-up were extracted and synthesized.

RESULTS: Twelve studies involving 134 patients were included. On crude analysis, technical success was achieved in 132/134 patients (98.5%), clinical success in 127/134 (94.8%), and adverse events were reported in 13/134 (9.7%). In the pooled random-effects analysis, the technical success rate was 93.5% (95% CI 87.1-96.8; I²=0%), the clinical success rate was 91.0% (95% CI 84.5-94.9; I²=0%), and the overall adverse-event rate was 14.6% (95% CI 9.1-22.5; I²=0%). Adverse events were mainly procedure-related pain, fever, stent misdeployment, peritonitis or intra-abdominal infection. Electrocautery-enhanced lumen-apposing metal stents were used in most studies, whereas fully covered self-expandable metal stents were used in a smaller subset. Reported follow-up ranged from 1 to 15 months.

CONCLUSIONS: EUS-guided transmural bypass represents a promising, minimally invasive, and technically feasible alternative for the management of ALS. However, given the retrospective nature and small sample sizes of the available evidence, larger comparative trials are warranted to define its definitive role.},
}

@article {pmid42521811,
year = {2026},
author = {Willemse, SW and Demaegd, KC and Koole, W and van Eijk, RPA and van Rheenen, W and Veldink, JH and van den Berg, LH and van Es, MA},
title = {Tofersen treatment in respiratory onset amyotrophic lateral sclerosis and a variant of uncertain significance in SOD1; a case report.},
journal = {European journal of human genetics : EJHG},
volume = {},
number = {},
pages = {},
pmid = {42521811},
issn = {1476-5438},
support = {09150161810018//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)/ ; V0000319//ZonMw (Netherlands Organisation for Health Research and Development)/ ; },
abstract = {The antisense oligonucleotide tofersen is available for treating amyotrophic lateral sclerosis (ALS) caused by pathogenic SOD1 variants. However, it is unknown whether Variants of Uncertain Significance (VUS) are a viable treatment target. We assessed clinical and biomarker trajectories prior to and after initiation of tofersen in a patient with respiratory onset ALS and a novel c.234_236del p.(Glu79del) VUS in SOD1. After six months of treatment, cerebrospinal fluid (CSF) SOD1 protein decreased by 47%, CSF NfL by 55% and serum NfL by 50%, with trajectories comparable to known pathogenic variants. Functional decline on the ALSFRS-R slowed from 1.52 points per month pre-treatment to 0.52 points per month post-treatment, muscle strength remained stable, and EQ-VAS quality of life scores remained between 60 and 70. The ability to evaluate treatment response on an individual level will help to determine the clinical relevance of VUS as new gene-targeted treatments for ALS become available.},
}

@article {pmid42508294,
year = {2026},
author = {Liu, X and Fu, W and Cui, X and Feng, Y and Wen, B and Shan, L and Xu, X and Yang, J and Zhang, J and He, L and Zang, Y and Zhao, S and Yao, X and Liu, Y and Ma, M and Du, B and Dang, J and Zou, Z and Feng, H and Lu, Z and Zhang, Y and Wu, Z and Shang, H and Yin, P and Fan, D},
title = {Huoling Shengji granule in amyotrophic lateral sclerosis: A multicenter, randomized, double-blind, riluzole-controlled trial.},
journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics},
volume = {23},
number = {5},
pages = {e00953},
doi = {10.1016/j.neurot.2026.e00953},
pmid = {42508294},
issn = {1878-7479},
abstract = {Currently, no curative therapies exist for Amyotrophic Lateral Sclerosis (ALS). This study aimed to evaluate the efficacy and safety of Huoling Shengji granules (HLSJ), a traditional Chinese medicine (TCM), compared to the standard treatment riluzole. A multicenter, randomized, double-blind, double-dummy, active-controlled Phase II clinical trial was conducted across 11 centers in China. A total of 140 ALS patients were randomly assigned (1:1) to receive either HLSJ or riluzole for 48 weeks. The primary endpoint, analyzed in the full analysis set (FAS), was the change in the ALS Functional Rating Scale-Revised (ALSFRS-R) score from baseline to Week 48. Safety profiles were comparable between groups, with no significant difference in adverse events (80.28% vs. 80.56%, P = 0.9671). Analysis using the pre-specified Last Observation Carried Forward (LOCF) method showed a numerical advantage for HLSJ (1.07 points) but lacked statistical superiority. However, a more scientific analysis using the Mixed Model for Repeated Measures (MMRM), recommended for progressive diseases, indicated that HLSJ was significantly superior to riluzole in slowing ALSFRS-R score decline (Least Squares Mean Difference [LSMD]: 2.29 points; 95% confidence interval [CI]: 0.52 to 4.06; P = 0.0114). While the LOCF model showed no statistical difference, the MMRM analysis confirmed that HLSJ demonstrated significant efficacy superior to riluzole with a favorable safety profile. These findings provide a critical basis for conducting pivotal Phase III confirmatory trials of HLSJ for ALS treatment.},
}

@article {pmid42510722,
year = {2026},
author = {Avitabile, A and Rusciano, D and Amato, R and Cannizzaro, L and Gagliano, C},
title = {Sex-Dependent Brain Plasticity in Neurological Disease: From Biological Variability to Adaptive, Compensatory, and Maladaptive Trajectories.},
journal = {Biology},
volume = {15},
number = {14},
pages = {},
doi = {10.3390/biology15141176},
pmid = {42510722},
issn = {2079-7737},
abstract = {Brain plasticity is often described as the capacity of the nervous system to change in response to development, experience, injury, disease, or treatment. That definition is useful, but it can obscure two clinically important points: plasticity is biologically constrained, and change is not always beneficial. This narrative review examines sex-dependent brain plasticity as a context-sensitive process rather than as a simple male-female contrast. We distinguish four operational outcomes of plasticity: (i) reparative plasticity, which restores structure or function; (ii) compensatory plasticity, which preserves performance through alternative or more costly strategies; (iii) insufficient plasticity, in which reorganization is too weak or unstable to sustain function; and (iv) maladaptive plasticity, in which plastic change reinforces dysfunction, pain, excitability, rigidity, or decline. We also define adaptive reserve as the integrated capacity of neural, glial, vascular, immune, metabolic, endocrine, and gene-regulatory systems to support useful reorganization under stress. The review evaluates endocrine, synaptic, neuroimmune, mitochondrial, vascular, stress-related, and epigenetic mechanisms, indicating where evidence for sex-dependent effects is relatively strong and where it remains indirect, inconsistent, or context-dependent. Disease examples include autism spectrum disorder, attention-deficit/hyperactivity disorder, epilepsy, intellectual disability, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, traumatic and ischemic injury, multiple sclerosis, chronic pain, aging, and systemic metabolic or inflammatory disorders. Throughout, biological sex is separated from gender-related social, diagnostic, and health-care determinants. We conclude that therapeutic strategies should not aim simply to enhance plasticity, but to guide it by matching intervention, timing, dose, biological readiness, and monitoring to the patient's adaptive state.},
}

@article {pmid42512450,
year = {2026},
author = {Yogi, S and Singh, A},
title = {Molecular Mechanisms of Neurodegenerative Diseases: Emerging Biomarkers and Therapeutic Targets.},
journal = {Brain sciences},
volume = {16},
number = {7},
pages = {},
doi = {10.3390/brainsci16070675},
pmid = {42512450},
issn = {2076-3425},
abstract = {Neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), involve the gradual loss of structure or function of neurons in the nervous system and are an increasing threat to the aging population worldwide. Although these disorders have different clinical features which affect cognition, movement and other vital body functions, they share key underlying molecular and cellular processes. This starts with protein misfolding and aggregation, mitochondrial dysfunction, oxidative stress, dysregulated protein homeostasis, neuroinflammation, and disrupted cell death pathways. Recent findings have added disease-specific processes, like amyloid-β and tau aggregates in AD, α-synuclein aggregation and mitophagy failure in PD's, TDP-43-related impaired RNA metabolism in ALS, and mutant huntingtin causing transcription aberrations in HD. Protein interactome network analysis showed mechanistic crosstalk between pathogenic proteins of AD and PD. New evidence highlights how lysosomal dysfunction, endoplasmic reticulum stress, and microglial activation, act as a common axis in neurodegeneration. Advancements in genomics and epigenomics have found shared genetic risk loci and regulatory processes that affect how diseases develop and progress. Simultaneously, new biomarkers like circulating microRNAs, exosome-related pathological proteins, neurofilament light chain, inflammatory cytokines, and microglial activation markers are powering early diagnosis tools and disease variations. New imaging techniques also allow for the identification of protein aggregations before symptoms appear. Overall, these findings are accelerating targeted treatments and personalized medicine aimed at disease progression. This review highlights current insights into the molecular mechanisms of NDs and discusses new biomarkers and treatment targets that help future diagnostic and treatment strategies.},
}

@article {pmid42514481,
year = {2026},
author = {Xie, P and Wang, J and Tong, B and Di, C and Zhou, F and Wang, W},
title = {Genome-Wide Characterization of the HaALS Gene Family Reveals Its Potential Roles in Imazethapyr Tolerance in Sunflower (Helianthus annuus L.).},
journal = {Plants (Basel, Switzerland)},
volume = {15},
number = {14},
pages = {},
doi = {10.3390/plants15142113},
pmid = {42514481},
issn = {2223-7747},
support = {CARS-14-1-06//Project of China Agriculture Research System/ ; CX25JC27//Heilongjiang Agricultural Science and Technology Innovation Leap Project/ ; },
abstract = {Acetolactate synthase (ALS; EC 2.2.1.6) catalyzes the first committed step in branched-chain amino acid (BCAA) biosynthesis and is the molecular target of multiple herbicide classes, including the imidazolinones. Here, we performed a genome-wide characterization of the HaALS gene family in sunflower (Helianthus annuus L.) and investigated genotype-dependent transcriptional responses to imazethapyr. A total of 11 HaALS genes were identified and classified into three phylogenetic clades (Groups A-C). All HaALS proteins contained the conserved TPP_enzyme domains (TPP_enzyme_N, TPP_enzyme_M, and TPP_enzyme_C), and purifying selection (Ka/Ks < 1) indicated strong evolutionary constraint on their core enzymatic function. Promoter analyses revealed abundant cis-regulatory elements associated with diverse stress and signaling inputs, supporting regulatory potential for herbicide-triggered transcriptional modulation. qRT-PCR analysis following imazethapyr application (0, 24, and 48 h) showed pronounced genotype-dependent expression reprogramming between the susceptible (S) and resistant (R) cultivars. In the R genotype, multiple HaALS members were strongly induced after treatment; specifically, HaALS4 reached a ~6-fold increase at 24 h and a >10-fold increase at 48 h, and HaALS11 increased to ~6-7-fold at 24 h while remaining above the baseline at 48 h; several additional paralogs exhibited intermediate induction (~3-8-fold by 48 h). In contrast, the S genotype showed limited changes (typically ~0.8-2-fold). Collectively, these findings define the evolutionary features of the sunflower HaALS family and identify herbicide-responsive paralogs that may contribute to imidazolinone tolerance, providing candidates for functional validation and molecular breeding.},
}

@article {pmid42514807,
year = {2026},
author = {Cazacu, G and Pamfil, D and Chirilă, O and Totolin, M and Ciolacu, D and Ghilan, A and Niţă, L and Niţă, T and Vasile, C},
title = {Chemical Treatment of Some Lignosulfonates Under DBD Plasma Conditions-II: Characterization of the Modified Lignosulfonates Microparticles.},
journal = {Polymers},
volume = {18},
number = {14},
pages = {},
doi = {10.3390/polym18141756},
pmid = {42514807},
issn = {2073-4360},
abstract = {The chemically modified ammonium lignosulfonate (ALS) powders with carboxylic acids such as, oleic (OA) and lactic acid (LA) and γ-butyrolactone (BL) under dielectric barrier plasma discharge (DBD) have been characterized by average molecular weight and particle size determinations, morphology examination by optical and electronic microscopy (SEM), the study of the thermal properties by thermogravimetry (TG/DTG), differential scanning calorimetry (DSC), differential thermal analysis (DTA) and antioxidant activity tests by DPPH method. The thermal characterization of the modified lignosulfonates reveals their improved thermal stability comparatively with ALS. It has been established that the obtained microparticles are aggregates of particles, covered by modified polymer and exhibit a particular behavior depending on the chemical structure of the used modifier, leading to multifunctional active lignin-based products with better homogeneity. By surface modification, the antioxidant capacity of modified lignosulfonate powders has been maintained.},
}

@article {pmid42503607,
year = {2026},
author = {Sanghai, N and Kelley, R and Lao, Y and Madlangsakay, MIR and Paul, P and Llanes-Cuesta, MA and Wang, JF and Zahedi, RP and Kong, J and Tranmer, GK},
title = {Introducing Borsantrazole: A Trifunctional Boron-Based Pyrazole That Extends the Lifespan of Amyotrophic Lateral Sclerosis Mice.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e76432},
doi = {10.1002/advs.76432},
pmid = {42503607},
issn = {2198-3844},
support = {//Research Manitoba 2017 Health Research New Investigator Operating Grant/ ; //Natural Sciences and Engineering Research Council of Canada/ ; /CAPMC/CIHR/Canada ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is considered a highly complex, heterogeneous, fatal disease with a high unmet medical need that affects multiple pathophysiological pathways and has no known singular cause. Oxidative stress, however, is implicated as a central player in the progression of ALS and other neurodegenerative diseases. To date, only two FDA-approved drugs, Edaravone, an antioxidant, and Riluzole, an antiglutamatergic, have been widely used clinically, albeit with modest effects on the clinical course of ALS disease progression. Additionally, preclinical studies of both drugs in ALS mouse models have not shown any significant survival benefit, although some abatement in disease progression is observed and translated from preclinical animal models to clinical human studies.

METHODS: Using a trifunctional boron-based drug design strategy, we have synthesized a pyrazole small molecule called Borsantrazole (BSZ) and evaluated BSZ in cell-based experiments, acute and chronic toxicity models, and the SOD1-G37R ALS mouse model. We have also evaluated untargeted global proteomic and phosphoproteomic changes induced by BSZ.

RESULTS: Borsantrazole (a small molecule that can selectively target oxidative stress) with favorable CNS drug like properties (low ER values of 0.9 and 1.0 at 1 and 10 µm, respectively, suggesting lower Pgp efflux liability and the LogD at pH 7.4 was within the range of 1.2 to 3.1, suggesting BSZ is lipophilic at pH 7.4.) shows no signs of treatment associated toxicity (acute or chronic (120 days)), significantly increases survival (whole animals, 15.1 days (p = 0.0326); males, 16.5 days; females, 13.7 days), rescued weight loss (27.1% control, 18.3% BSZ, p < 0.0001), delays symptom onset (whole animals, 24.9 days (p = 0.0011); males, 23.3 days; females, 26.4 days), delays disease onset (whole animals, 25.5 days (p = 0.0001); males, 21.1 days; females, 29.8 days) and affects global proteomic changes in the SOD1-G37R mouse model of ALS. In total, 51 proteins were found to be significantly differentially expressed (p < 0.05), including Ca3, Gan, Cplx2, Lrp4, Sqstm1, and 29 phosphorylation sites were differentially expressed and considered statistically significant, including T317 and T72 for neurofilaments light and heavy chain, respectively.

CONCLUSIONS: Herein, we report that BSZ has demonstrated a favorable safety profile and compelling proof-of-concept efficacy in a ALS mouse model and has the potential to become a disease-modifying ALS therapeutic following further clinical development. Within a broader perspective of treatments for neurodegenerative diseases, BSZ offers a new paradigm for trifunctional small molecule targeting of oxidative stress that can mitigate neuronal deterioration and serve as a potential treatment.},
}

@article {pmid42505224,
year = {2026},
author = {Collaço, N and Kennington, A and Greenberg, N and Imber, T and Warne, D and Sodergren, S},
title = {Mapping Support-Seeking After Cancer Treatment: A Co-Designed Model of Triggers, Timing and Support Pathways in Young People with Lived Experience of Cancer.},
journal = {Current oncology (Toronto, Ont.)},
volume = {33},
number = {7},
pages = {},
doi = {10.3390/curroncol33070422},
pmid = {42505224},
issn = {1718-7729},
mesh = {Humans ; *Neoplasms/psychology/therapy ; *Social Support ; Female ; Male ; Young Adult ; Adolescent ; *Help-Seeking Behavior ; Adult ; },
abstract = {Post cancer treatment, many young people often live with ongoing emotional, social, and physical difficulties, but support is not always accessed when it is needed. This study aimed to co-produce a conceptual model of support-seeking after cancer treatment with young people with lived experience of cancer, to better understand the triggers, timing, and pathways influencing engagement with support. This co-design work, informed by Bird et al.'s generative framework for co-production, built upon a prior study involving interviews and co-design workshops with young people and healthcare/allied health professionals, and informed a preliminary model of support-seeking. The current work involved two further co-production stages through an online survey and workshop to refine this model. Data were analysed using a thematic approach to support conceptual model development. Four interconnected themes shaped support-seeking: (1) readiness to engage: recognition, emotional readiness, and relational safety; (2) access and appraisal of support: visibility, fit, feasibility, and burden; (3) pathways to support: multi-modal, layered, and non-linear engagement; and (4) support trajectory: changing needs and recurrent engagement. Engagement in support-seeking depended on the alignment of readiness, recognition of need, and relational safety. This model offers a framework to improve how post-treatment support is designed and delivered in practice.},
}

Humans
*Neoplasms/psychology/therapy
*Social Support
Female
Male
Young Adult
Adolescent
*Help-Seeking Behavior
Adult

@article {pmid42501325,
year = {2026},
author = {Jia, Y and Cui, B and Liang, Y and Zhang, M and Wang, S and Wang, Y and Chen, H},
title = {Focal epilepsy expands the phenotype of FUS-associated amyotrophic lateral sclerosis.},
journal = {Epilepsia},
volume = {},
number = {},
pages = {},
doi = {10.1002/epi.70409},
pmid = {42501325},
issn = {1528-1167},
support = {82401705//National Natural Science Foundation of China/ ; 82371461//National Natural Science Foundation of China/ ; 2022YFC2503802//National Key Research and Development Program of China/ ; },
abstract = {Epileptic seizures are an exceedingly rare manifestation in classic amyotrophic lateral sclerosis (ALS). Emerging case reports suggest a potential link between ALS associated with FUS gene mutations (FUS-ALS) and seizures, expanding the disease's phenotypic spectrum. A 25-year-old man presented with a 5-month history of rapidly progressive limb weakness, atrophy, and both upper and lower motor neuron signs, consistent with ALS. Notably, he developed two types of epileptic seizures during the disease course, including focal motor seizures and focal seizures evolving to bilateral tonic-clonic seizures. Electroencephalography revealed epileptiform discharges over the right frontotemporal region. Brain [18]F-fluorodeoxyglucose positron emission tomography-computed tomography showed focal hypometabolism in the right frontal cortex. Genetic testing identified a de novo pathogenic FUS variant (c.1574C>T, p.Pro525Leu). The patient was diagnosed with FUS-ALS with comorbid focal epilepsy. Treatment with levetiracetam partially controlled the seizures, but motor function continued to deteriorate. This case highlights focal epilepsy as a comorbid feature in FUS-ALS, broadening the recognized phenotypic spectrum. Genetic testing for FUS mutations should be considered in young-onset ALS patients presenting with seizures.},
}

@article {pmid42498658,
year = {2026},
author = {Palm, A and Ekström, M and Einarsson, J and Ersson, K and Ingre, C and Kläppe, U and Lindberg, E and Ljunggren, M and Nygren, I and Sundh, J and Grote, L},
title = {Home mechanical ventilation for amyotrophic lateral sclerosis-a national study of survival and treatment trends across 27 years.},
journal = {Annals of the American Thoracic Society},
volume = {},
number = {},
pages = {},
doi = {10.1093/annalsats/aaoag219},
pmid = {42498658},
issn = {2325-6621},
abstract = {RATIONALE: Home mechanical ventilation (HMV) improves survival in Amyotrophic lateral sclerosis (ALS) and may be provided non-invasively (NIV) or invasively (IV). While NIV is guideline-recommended, the role of IV remains controversial, and data on long-term outcomes and NIV-to-IV transitions are limited.

OBJECTIVES: To examine survival across HMV strategies in people with ALS (pwALS) in Sweden over 27 years, factors associated with IV initiation, temporal trends in IV use and survival, and regional variation in IV utilisation.

METHODS: A longitudinal cohort study of pwALS in the Swedish National Registry of Ventilatory Failure (Swedevox) 1996-2022, cross-linked with national registries. Factors associated with mortality and treatment patterns were assessed using multivariable regression models.

RESULTS: Among 1,360 pwALS, initial NIV was most common (92%), followed by IV (5%) and NIV-to-IV transitions (3%). Most IV initiations were non-elective (77% vs. 18% NIV, p < 0.001). NIV-to-IV transitions occurred mainly in metropolitan areas (OR 5.11; 95% CI 2.30-11.4). Median survival differed across observed treatment pathways (p < 0.001): 1.7 years with NIV, 4.9 years with IV, and 6.5 years with NIV-to-IV. Mortality was associated with higher age (aHR 1.33 per decade; 95% CI 1.26-1.41), female sex (aHR 1.15; 95% CI 1.02-1.29), and acute initiation (aHR 1.26; 95% CI 1.08-1.47). Longer time from diagnosis to NIV initiation was associated with reduced mortality risk (aHR 0.58 per year; 95% CI 0.55-0.62). Over time, patients initiated HMV at older age with better lung function and lower PaCO2 values among those with available measurements, whereas overall survival remained unchanged.

CONCLUSION: Patients receiving IV had longer observed survival, likely reflecting the benefits of a secured airway as well as patient selection and underlying disease trajectory. Most IV initiations were unplanned. Over three decades, HMV was initiated in older patients at an earlier stage of respiratory decline, but overall survival remained unchanged. IV use increased with marked regional variation.},
}

@article {pmid42492371,
year = {2026},
author = {Majumder, M and Borucki, DM and Chowdhury, N and Mallah, K and Tomlinson, S},
title = {Site-targeted proximal complement C3 inhibition, but not C5 blockade, attenuates neurodegeneration in a mouse model of amyotrophic lateral sclerosis: Implications for failed clinical trials.},
journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics},
volume = {23},
number = {5},
pages = {e00969},
doi = {10.1016/j.neurot.2026.e00969},
pmid = {42492371},
issn = {1878-7479},
abstract = {Complement activation contributes to amyotrophic lateral sclerosis (ALS) neuropathology, but whether motor neuron degeneration is driven by proximal or terminal activation products remains unresolved. Failed trials of C5 inhibition - ravulizumab (CHAMPION-ALS) and zilucoplan (ATHLEET/HEALEY ALS Trial), and of systemic C3 inhibition (pegcetacoplan, MERIDIAN) underscore this mechanistic gap. We compared two pharmacologically distinct inhibitors in hSOD1[G93A] mice. CR2Crry blocks complement at C3 and localizes to sites of active deposition. BB5.1, functionally equivalent to ravulizumab, selectively blocks C5a generation and membrane attack complex (MAC) assembly. Treatment began at symptom onset and continued to humane endpoint. Both agents achieved robust target engagement across spinal cord, sciatic nerve, and neuromuscular junction (NMJ). Only CR2Crry extended survival, preserved motor function, and attenuated weight loss. CR2Crry reduced microglial activation and C3 opsonization in the ventral horn, diminished macrophage infiltration, preserved sciatic nerve axonal integrity, and maintained NMJ innervation. BB5.1 failed to modify any functional or neurodegenerative pathology despite confirmed MAC suppression. Proximal C3 activation products, not C5a or MAC, are the dominant drivers of complement-mediated neurodegeneration in the hSOD1[G93A] model of ALS. Site-targeted C3 inhibition may address the mechanistic limitation underlying recent clinical trial failures and represents a translationally justified therapeutic strategy.},
}

@article {pmid42484074,
year = {2026},
author = {Carberry, N and Wuu, J and Benatar, M},
title = {SOD1-lowering therapy for patients with wildtype SOD1-ALS: a case report.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/21678421.2026.2705142},
pmid = {42484074},
issn = {2167-9223},
abstract = {Background and Objectives: To describe clinical and biomarker experience using an SOD1 antisense oligonucleotide (ASO) in a patient with non-SOD1 amyotrophic lateral sclerosis (ALS). Methods: Case report. Results: In a 72-year-old male with non-SOD1 ALS, rapid decline on the ALS functional rating scale revised (ALSFRS-R) and a rise in serum neurofilament light chain (NfL) concentration were observed following 3 loading doses of an SOD1 ASO before the patient succumbed to disease. The time from symptom onset to death was 9 months. Discussion: While treatment was initiated relatively late (∼7 months) after symptom onset and follow-up duration was short, the observed increase (as opposed to a reduction) in serum NfL and accompanying rapid functional decline, suggest the lack of a therapeutic effect in someone with fast progressing non-SOD1 ALS.},
}

@article {pmid42474734,
year = {2026},
author = {Zheng, Y and Bhalala, OG and Chin, KS and Watson, R and Yassi, N},
title = {Use of blood-based neurofilament light chain as an endpoint in clinical trials of neurodegenerative conditions: a scoping review.},
journal = {Journal of neurology},
volume = {273},
number = {8},
pages = {},
pmid = {42474734},
issn = {1432-1459},
mesh = {Humans ; *Neurofilament Proteins/blood ; *Neurodegenerative Diseases/blood/diagnosis ; Biomarkers/blood ; *Clinical Trials as Topic ; },
abstract = {INTRODUCTION: Neurofilament light chain (NfL) is a structural axonal protein measurable in CSF and blood, increasingly investigated as a biomarker of neuroaxonal injury in clinical and research contexts. This review aims to explore the use of blood-based NfL as an endpoint in clinical trials of neurodegenerative conditions.

METHOD: A database search of MEDLINE and EMBASE was conducted to identify interventional clinical trials and/or related post hoc analyses for neurodegenerative diseases, published between 2013 and 2024 that reported the use of serum or plasma NfL as an endpoint. Additional studies from reference lists of included trials were manually considered for inclusion where relevant. Data were charted descriptively by disease type and summarised.

RESULTS: 49 studies were included, 29 in multiple sclerosis (MS), eight in amyotrophic lateral sclerosis (ALS), six in Alzheimer's disease (AD), and six in other diseases. Across studies, reductions in NfL often paralleled improvements in primary efficacy outcomes, supporting its use as a biomarker of disease activity and treatment response. However, several studies demonstrated a lack of concordance between change in NfL and in clinical outcomes, some of which may be related to the non-disease-modifying mechanisms of the interventions studied. This necessitates careful consideration when applying blood-based NfL as a biomarker endpoint for studies involving such interventions.

CONCLUSION: Blood NfL is a promising biomarker with potential utility as a surrogate endpoint in neurological clinical trials, particularly for diseases with active axonal injury. Further validation, particularly around disease- and intervention-specific interpretation, is needed before blood NfL can be incorporated more routinely as a clinical endpoint.},
}

Humans
*Neurofilament Proteins/blood
*Neurodegenerative Diseases/blood/diagnosis
Biomarkers/blood
*Clinical Trials as Topic

@article {pmid42471754,
year = {2026},
author = {Xia, CA and Salarian, M and Gartshore, CJ and Scaglione, A and Hayes, T and Liu, S and Tsai, HM and Echavarren, J and Cid, JM and Matzeu, A and Szardenings, AK},
title = {Development and characterization of a novel TDP-43 positron emission tomography tracer: [[18]F]JNJ-TDP43-1.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {7},
pages = {e71675},
pmid = {42471754},
issn = {1552-5279},
support = {//Johnson & Johnson/ ; },
mesh = {Animals ; *Positron-Emission Tomography/methods ; *DNA-Binding Proteins/metabolism ; *Brain/diagnostic imaging/metabolism ; Rats ; Mice ; Humans ; Male ; Disease Models, Animal ; TDP-43 Proteinopathies/diagnostic imaging ; *Radiopharmaceuticals/pharmacokinetics ; Fluorine Radioisotopes ; },
abstract = {INTRODUCTION: Neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), limbic-predominant age-related TDP-43 encephalopathy (LATE), and Alzheimer's disease (AD) are associated with TAR DNA-binding protein 43 (TDP-43) pathology. A positron emission tomography (PET) tracer targeting TDP-43 aggregates could improve early diagnosis and guide treatment development for TDP-43-related conditions.

METHODS: Specific binding was evaluated using fluorescent labeling of compound, surface plasmon resonance (SPR), and autoradiography (ARG). Brain PET imaging in rats, nonhuman primate (NHP), and a disease mouse model was performed to characterize tracer pharmacokinetics and in vivo target binding.

RESULTS: JNJ-TDP43-1 exhibited high binding affinity for pathological TDP-43 (Kd = 7.1 nM) and remarkable selectivity over other proteinopathies. PET imaging demonstrated robust brain uptake and rapid washout in rodents and NHP. In vivo target engagement was confirmed in an AAV-hTDP43 disease model.

DISCUSSION: [[18]F]JNJ-TDP43-1 is a promising PET ligand for early diagnosis and evaluating therapies in TDP-43-related diseases.},
}

Animals
*Positron-Emission Tomography/methods
*DNA-Binding Proteins/metabolism
*Brain/diagnostic imaging/metabolism
Rats
Mice
Humans
Male
Disease Models, Animal
TDP-43 Proteinopathies/diagnostic imaging
*Radiopharmaceuticals/pharmacokinetics
Fluorine Radioisotopes

@article {pmid42473218,
year = {2026},
author = {Keskin, A and Mogulkoc, R and Baltaci, AK},
title = {Relationship Between miRNA and Neurodegenerative Diseases Such as Alzheimer's disease, Parkinson's, Huntington's disease, Amyotrophic Lateral Sclerosis.},
journal = {Mini reviews in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0113895575484348260702044851},
pmid = {42473218},
issn = {1875-5607},
abstract = {The regulatory roles of miRNAs on CNS homeostasis, neuronal differentiation, and synaptic plasticity make these molecules indispensable for healthy brain functions. miRNA dysregulation, by triggering abnormal neurodevelopment, has a critical impact on the etiology and progression of neurodegenerative diseases. MicroRNAs (miRNAs) are short, single-stranded, non-coding ribonucleic acid (RNA) molecules, 18 to 24 nucleotides long. They play a role in posttranscriptional gene regulation by binding to complementary sequences on messenger RNA (mRNA), thereby promoting mRNA degradation or preventing translation into protein. MiRNAs are essential regulators of the genome because they bind targets and alter gene expression. MiRNA biogenesis and functions are tightly regulated, and their dysregulation is associated with various diseases, including cancer, cardiovascular diseases, and neurodegenerative disorders. In particular, disruption of the Blood-Brain Barrier in neurodegenerative diseases allows molecules to leak into the bloodstream, enabling the detection of miRNAs in other body fluids and making these fluids potential biomarker sources. In this context, miRNAs can be measured in blood, cerebrospinal fluid, and other biological samples. It has significant potential for early diagnosis, disease progression monitoring, and evaluation of treatment efficacy. In this review, the relationship between MiRNAs and neuronal degeneration diseases was evaluated. In this review, prepared in light of the current literature scanned through the PubMed database, we examined data from the last 5 years (2021-2026) on neurodegenerative diseases associated with miRNA dysregulation, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Huntington's Disease (HD).},
}

@article {pmid42473814,
year = {2026},
author = {Shao, D and Wen, X and Xu, X and Liu, X and Guo, B and Li, B and Wang, G and Liu, X and Men, S},
title = {Cyprosulfamide mitigates nicosulfuron phytotoxicity in maize through activation of GST-associated phase II detoxification involving ZmGST24.},
journal = {Pest management science},
volume = {},
number = {},
pages = {},
doi = {10.1002/ps.71142},
pmid = {42473814},
issn = {1526-4998},
support = {32370271//National Natural Science Foundation of China/ ; 2026KJCXZX-LYS-14//HAAFS Agriculture Science and Technology Innovation Project/ ; 254Z6303G//Project of Central Guidance for Local Science and Technology Development Funds/ ; 23JCYBJC01180//Natural Science Foundation of Tianjin/ ; 24YFXTHZ00050//Key Research and Development Program of Tianjin/ ; },
abstract = {BACKGROUND: Nicosulfuron is an acetolactate synthase (ALS)-inhibiting herbicide widely used in maize production. However, under unfavorable environmental conditions, its phytotoxicity to maize remains a practical concern. Cyprosulfamide (CSA) is an effective safener for maize, yet the contribution of glutathione S-transferases (GST)-associated phase II detoxification to CSA-conferred protection against nicosulfuron injury remains poorly understood.

RESULTS: CSA markedly alleviated nicosulfuron-induced growth inhibition in maize seedlings and effectively reduced herbicide injury under field conditions. Inhibitor assays showed that both cytochrome P450-mediated phase I metabolism and GST-associated phase II detoxification contribute to maize tolerance to nicosulfuron. Proteomic analysis further revealed that, relative to nicosulfuron treatment alone, co-application of nicosulfuron and CSA significantly enriched the glutathione metabolism pathway in maize leaves. Among the induced GST candidate genes, ZmGST24 showed the strongest transcriptional response. Phylogenetic and conserved motif analyses supported its functional similarity to previously reported GSTs involved in herbicide detoxification. Molecular docking suggested favorable binding of ZmGST24 to nicosulfuron, and heterologous expression in yeast demonstrated that ZmGST24 not only enhanced tolerance to nicosulfuron, but also increased tolerance to several herbicides commonly used in maize fields.

CONCLUSION: These findings indicate that the protective effect of CSA against nicosulfuron phytotoxicity in maize is associated with activation of GST-associated phase II detoxification. The pronounced response of the glutathione metabolism pathway, together with the functional characterization of ZmGST24, identifies this gene as a promising candidate involved in CSA-induced herbicide tolerance and as a potential target for improving herbicide safety in maize. © 2026 Society of Chemical Industry.},
}

@article {pmid42467750,
year = {2026},
author = {Deressa, JD and Behaksra, SW and Molla, E and Letebo, A and Shumie, G and Adnew, B and Alemayehu, DH and Kassa, FA and Seyoum, T and Tafa, EB and Woldekidan, K and Ejigu, LA and Huwe, T and Keffale, M and Bayissa, GA and Koepfli, C and Chala, B and Asmamaw, Y and Tadesse, FG and Gadisa, E},
title = {Therapeutic efficacy of artemether-lumefantrine plus single low dose primaquine for the treatment of uncomplicated Plasmodium falciparum malaria in a high transmission setting, Western Ethiopia.},
journal = {PloS one},
volume = {21},
number = {7},
pages = {e0335833},
pmid = {42467750},
issn = {1932-6203},
mesh = {Humans ; *Primaquine/therapeutic use/administration & dosage ; *Artemether, Lumefantrine Drug Combination/therapeutic use/administration & dosage ; *Malaria, Falciparum/drug therapy/transmission/epidemiology/parasitology ; *Antimalarials/therapeutic use/administration & dosage ; Female ; Male ; Ethiopia/epidemiology ; Plasmodium falciparum/drug effects/genetics ; Child, Preschool ; Adolescent ; Treatment Outcome ; Child ; Adult ; Drug Therapy, Combination ; Young Adult ; },
abstract = {BACKGROUND: The development and spread of drug-resistant parasites continue to threaten progress toward malaria elimination. Therapeutic efficacy and molecular resistance marker studies are needed to guide national control programs. In African settings, evidence of partial resistance to artemisinin-based combination therapies (ACTs) associated with Pfkelch13 mutations is accumulating, and World Health Organization (WHO) recommends regular monitoring of first line antimalarial drugs for early detection of resistant parasites. In this study, we evaluated the efficacy of artemether-lumefantrine (AL) combined with a single low dose of primaquine (PQ) for treating uncomplicated Plasmodium falciparum malaria in a co-endemic area where P. falciparum predominates.

METHODS AND FINDINGS: One hundred twenty-three patients with P. falciparum mono-infection were enrolled between November 2020 to March 2021 and treated with artemether-lumefantrine (AL) plus a single low dose of primaquine (PQ) as per the national malaria treatment guideline and followed up for 28 days. Ethical approval was obtained from the AHRI/ALERT ethics committee (Po/23/19), and the study was registered at Pan-African clinical trials registry (PACTR) with unique identification number of PACTR202509595696440. Pfmsp2 capillary electrophoresis (CE) genotyping was used to differentiate recrudescence from new infections. More than half (56.1%) of the participants had high parasitemia (>10,000 parasites/μL) at enrollment. On day 3, 16.9% (20/118) remained parasitemic, and of the 10 individuals with detectable gametocytes at enrollment, only 3.4% remained gametocytemic on day 3, and 100% parasite clearance was observed on day 7, respectively. Multiplicity of infection was 3.8 at enrollment and 1.7 at the time of recurrence. The adequate clinical and parasitological responses at 28-day (ACPR) of per protocol analysis (PPA) was 73.7% for PCR-uncorrected and 91.3% for PCR-corrected, respectively and while, the intention-to-treat analysis (ITA), the Kaplan-Meier estimated treatment success at day 28 was 93.2% (95% CI: 88.5-98.2) after PCR correction, compared with 78.3% (95% CI: 71.0-86.4) in the PCR-uncorrected analysis. In our study assessment, no cases of severe malaria or serious adverse events occurred.

CONCLUSIONS: The efficacy observed in this study, although remaining above the WHO policy change threshold after PCR correction, may indicate a potential decline in AL's effectiveness in this high transmission setting. However, because antimalarial drug concentrations were not measured and evening doses were not fully directly observed, reduced drug exposure or imperfect adherence cannot be excluded as possible contributors to the observed treatment outcomes Therefore, we suggest regular therapeutic efficacy monitoring and further investigation using advanced molecular techniques, such as next-generation sequencing (NGS), to enable early detection of resistance-associated parasite variants that may compromise treatment efficacy.},
}

Humans
*Primaquine/therapeutic use/administration & dosage
*Artemether, Lumefantrine Drug Combination/therapeutic use/administration & dosage
*Malaria, Falciparum/drug therapy/transmission/epidemiology/parasitology
*Antimalarials/therapeutic use/administration & dosage
Female
Male
Ethiopia/epidemiology
Plasmodium falciparum/drug effects/genetics
Child, Preschool
Adolescent
Treatment Outcome
Child
Adult
Drug Therapy, Combination
Young Adult

@article {pmid42465739,
year = {2026},
author = {You, Y and Zhu, H and Zhang, Q and Wang, J and Dong, C and Yang, Z and Zhang, J and Zhang, Y and Zhang, M and Lu, M and Du, C},
title = {Development and efficacy of ex vivo expanded autologous regulatory T cells for the treatment of amyotrophic lateral sclerosis.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1854252},
pmid = {42465739},
issn = {1664-3224},
mesh = {*Amyotrophic Lateral Sclerosis/therapy/immunology/genetics ; *T-Lymphocytes, Regulatory/immunology/transplantation/metabolism ; Animals ; Humans ; Mice ; Disease Models, Animal ; Female ; Superoxide Dismutase-1/genetics ; Mice, Transgenic ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited therapeutic options, in which neuroinflammation critically drives disease progression. Regulatory T cells (Tregs) exert potent immunosuppressive and neuroprotective effects, offering great potential for ALS treatment. However, clinical application of Treg therapy is hampered by low peripheral cell abundance and unstable expansion quality. Here, we established and optimized a GMP-grade protocol for sorting and expanding peripheral blood-derived Tregs, and validated cryopreserved apheresis products as feasikble starting materials. Although ALS patient-derived Tregs showed reduced expansion capacity compared with healthy donor counterparts, they maintained comparable purity, stable regulatory phenotypes, and robust immunosuppressive function. Transcriptomic analysis confirmed the lineage fidelity and low pro-inflammatory characteristics of expanded Tregs. Therapeutic efficacy was verified in SOD1G93A ALS and GvHD mouse models with delayed disease progression and relieved inflammation. This study provides standardized GMP manufacturing strategies and solid preclinical evidence to support the ongoing clinical trial (NCT06671236) and facilitate Treg immunotherapy translation for ALS.},
}

*Amyotrophic Lateral Sclerosis/therapy/immunology/genetics
*T-Lymphocytes, Regulatory/immunology/transplantation/metabolism
Animals
Humans
Mice
Disease Models, Animal
Female
Superoxide Dismutase-1/genetics
Mice, Transgenic

@article {pmid42467293,
year = {2026},
author = {Hassan, MA and Al Amin, M and Sweilam, SH and Abohassan, M and Krishnan, K and Gupta, JK and Jahnavi, P and Vodeti, R and Radha, R and Gupta, PS and Reddy, KTK},
title = {Resveratrol and neuroprotection: modulation of cellular dynamics and signaling networks in neurodegenerative diseases.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {42467293},
issn = {1568-5608},
abstract = {Progressive loss of neurons, oxidative stress, neuroinflammation, and mitochondrial dysfunction are hallmarks of neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Resveratrol, a polyphenolic phytoalexin mainly found in grapes and red wine, is a promising treatment candidate due to its diverse biological effects and neuroprotective properties. This review demonstrates the regulatory effects of resveratrol on cellular signaling pathways linked to NDs and its neuroprotective mechanisms. Resveratrol enhances neuronal survival, boosts mitochondrial biogenesis, and mitigates oxidative stress by affecting key molecular pathways, including SIRT1/AMPK, PI3K/Akt, MAPK, and Nrf2/ARE. The PI3K/Akt and ERK1/2 pathways promote neuronal regeneration by modulating pro-apoptotic and anti-apoptotic factors. Resveratrol inhibits NF-κB, reducing cytokine release and microglial activation, thereby exhibiting anti-inflammatory properties. It improves cognitive function, synaptic plasticity, and neuronal survival. Despite an increasing pharmacological profile, its practical applicability is limited by inadequate bioavailability, rapid metabolism, and restricted brain penetration. This review demonstrates resveratrol's effect on interconnected signaling networks related to neurodegeneration. We critically compare evidence from preclinical and clinical studies, demonstrating both therapeutic potential and translational limitations. Emerging nanotechnology-based delivery strategies are demonstrated to overcome bioavailability and blood-brain barrier penetration challenges. These insights provide a translational perspective for the future development of resveratrol-based interventions in NDs.},
}

@article {pmid42458512,
year = {2026},
author = {Jo, M and Kim, S and Woo, J and Park, JS and Kim, SH and Nahm, M and Kim, SR and Lee, S and Kim, HJ},
title = {Targeting astrocyte-mediated neurotoxicity induced by ALS/FTD-associated RNA binding proteins.},
journal = {Cell communication and signaling : CCS},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12964-026-03082-w},
pmid = {42458512},
issn = {1478-811X},
support = {RS-2024-00454715//National Research Foundation of Korea/ ; RS-2024-00343239//National Research Foundation of Korea/ ; 26-BR-02-03//Korea Brain Research Institute/ ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders characterized by reactive astrocytes that contribute to neuronal injury through TAR DNA-binding protein 43 (TDP-43)-or fused in sarcoma (FUS)-driven neuroinflammatory signaling. Dehydrocostus lactone (DHE), a blood-brain barrier-permeable sesquiterpene lactone with established anti-inflammatory activity, represents a promising but unexplored therapeutic candidate for ALS/FTD.

METHODS: The therapeutic effects of DHE were evaluated in primary mouse and human astrocytes expressing ALS/FTD-associated RNA-binding protein pathology, ALS patient-derived fibroblasts, and primary cortical neurons exposed to astrocyte-conditioned medium. Drosophila models expressing mutant FUS or TDP-43 in glial cells were used to assess locomotor performance and survival. Molecular analyses examined nuclear factor kappa B (NF-κB) signaling, nuclear factor erythroid 2-related factor 2 (NRF2)-dependent antioxidant responses, protein aggregation, mitochondrial function, and inflammatory mediator production. Plasma concentrations of inflammatory cytokines and chemokines were measured in patients with sporadic ALS.

RESULTS: DHE exerted neuroprotective effects through a dual mechanism involving suppression of NF-κB-dependent inflammatory signaling and activation of NRF2-mediated antioxidant pathways in astrocytes exhibiting FUS or TDP-43 proteinopathy. DHE attenuated astrocyte-mediated neurotoxicity and improved neuronal mitochondrial function in conditioned-medium assays. In addition, DHE reduced pathological FUS accumulation in FUS P525L-expressing astrocytes and in stress-challenged patient-derived fibroblasts. In Drosophila models, DHE significantly improved locomotor function and extended survival. Translationally, the chemokines CXCL10, CCL3, and CCL19 were elevated in plasma from patients with ALS, were induced by FUS or TDP-43 pathology in astrocytes, and were suppressed by DHE treatment, supporting the clinical relevance of the inflammatory pathways targeted by DHE.

CONCLUSION: DHE mitigates astrocyte-driven neurotoxicity associated with ALS/FTD-related RNA-binding protein pathology by suppressing inflammatory signaling and enhancing antioxidant defense mechanisms. The consistent therapeutic effects observed across mouse and human cellular models, patient-derived samples, and in vivo Drosophila models support further investigation of DHE as a potential therapeutic strategy for ALS/FTD and highlight astrocyte-mediated signaling pathways as actionable targets in neurodegenerative disease.},
}

@article {pmid42459857,
year = {2026},
author = {Hu, M and You, L and Zhang, X and Xuan, Z and Ma, S and Wu, X},
title = {Experimental evidence of electroacupuncture in ALS mouse models: a systematic review and meta-analysis.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1780176},
pmid = {42459857},
issn = {1664-2295},
abstract = {OBJECTIVE: This study aimed to systematically evaluate the therapeutic efficacy of electroacupuncture (EA) in amyotrophic lateral sclerosis (ALS) and to elucidate the underlying neurobiological mechanisms by synthesizing preclinical evidence.

METHODS: According to the PICOS principle, relevant studies were searched in the following databases: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and CNKI. Search terms and strategies were determined based on MeSH terms. The methodological quality of the included studies was assessed using the SYRCLE's Risk of Bias tool and the CAMARADES checklist. Meta-analysis was performed using Stata 15.0 and Rstudio software.

RESULTS: Seventeen studies involving 372 animals were included. The quality scores of the included studies ranged from 5 to 8, with an average score of 7. The meta-analysis of the primary outcome, the rotarod test score, showed a significant improvement in the EA group compared to the control group [SMD = 3.31, 95% CI (2.05, 4.57), Z = 5.151, p < 0.001], indicating that EA can enhance motor function in ALS mice. Regarding secondary outcomes, EA intervention alleviated neuroinflammation, promoted neuronal survival, improved axonal regeneration inhibition, and stabilized RNA metabolism homeostasis. Consequently, it slowed disease progression, improved motor performance, prolonged survival time, and effectively protected motor neurons at the histopathological level (p < 0.05). These findings underscore the potential of EA as a promising multimodal therapeutic strategy for ALS. For the heterogeneity observed in the rotarod test, sensitivity analysis, subgroup analysis, and meta-regression did not identify its source. However, potential publication bias was detected, which might contribute to the heterogeneity. The heterogeneity for other outcome measures might originate from differences in stimulation parameters (e.g., waveform), acupoint selection, or treatment duration.

CONCLUSION: This meta-analysis demonstrates that EA confers significant neuroprotective benefits in preclinical ALS models, primarily through multi-target modulation of key pathological processes such as neuroinflammation, aberrant cell death signaling, and RNA metabolism. These preclinical findings underscore the potential of electroacupuncture as a complementary neuroprotective strategy and warrant further investigation in rigorous clinical trials.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251229183.},
}

@article {pmid42461162,
year = {2026},
author = {Zhang, R and Zhang, N and Li, B and Liu, Q and Xu, C and Li, B and Zhang, J},
title = {Nursing a Patient With Amyotrophic Lateral Sclerosis Stage 4B With Epilepsy: A Case Study.},
journal = {Nursing in critical care},
volume = {31},
number = {4},
pages = {e70573},
doi = {10.1111/nicc.70573},
pmid = {42461162},
issn = {1478-5153},
support = {25ZZJJLW-015//Medical Research Council Foundation of the 305 Hospital of the PLA/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/nursing/complications ; *Epilepsy/nursing/complications ; Male ; Intensive Care Units ; *Critical Care Nursing/methods ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a rare motor neuron disease characterised by progressive muscle weakness, which can eventually lead to death. So far there is no effective cure for it. This case report discusses the nursing of a patient with stage 4B amyotrophic lateral sclerosis complicated with epilepsy and sudden disturbance of consciousness during his stay in an intensive care unit (ICU). After 34 days of treatment and care, the patient regained consciousness with stable vital signs before being transferred out of the ICU. This report focusses on nursing interventions adopted in terms of respiratory management, nutritional management, psychological care and exercise during both the epileptic seizure and the awake period of the patient in the hope of providing a reference for the nursing of patients with amyotrophic lateral sclerosis with epilepsy in intensive care units.},
}

Humans
*Amyotrophic Lateral Sclerosis/nursing/complications
*Epilepsy/nursing/complications
Male
Intensive Care Units
*Critical Care Nursing/methods

@article {pmid42461445,
year = {2026},
author = {Mitsumoto, H and Cheung, K and Matsumoto, T and Lanza, I and Oskarsson, B and Johnson, S and Petterson, XT and Jang, GE and Andrews, HF},
title = {Metabolomic analyses of amyotrophic lateral sclerosis, muscle cramps, and TJ-68 treatment.},
journal = {Metabolomics : Official journal of the Metabolomic Society},
volume = {22},
number = {4},
pages = {},
pmid = {42461445},
issn = {1573-3890},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy/blood ; *Muscle Cramp/drug therapy/metabolism/blood ; *Metabolomics/methods ; Female ; Male ; Middle Aged ; Aged ; Cross-Over Studies ; Medicine, Kampo ; *Drugs, Chinese Herbal/therapeutic use ; },
abstract = {INTRODUCTION: Most patients with amyotrophic lateral sclerosis (ALS), a fatal motor neuron disease, experience painful muscle cramps. Our recent pilot trial of the Japanese Kampo medicine TJ-68 suggested its efficacy in improving muscle cramps in patients with ALS.

OBJECTIVES: This study analyzed plasma metabolomic changes to identify the underlying mechanisms of muscle cramps in ALS and the effects of TJ-68.

METHODS: Plasma was obtained from 11 participants with ALS in the repeated crossover trial at five time points (baseline, two placebo phases, and two TJ-68 phases). Metabolites were analyzed using mass spectrometry. Linear mixed-effects models were applied to identify metabolite changes associated with muscle cramps, determine the effects of TJ-68 on metabolites, and predict which participants would respond to TJ-68.

RESULTS: Higher glutamine/glutamate, arginine, and leucine levels were associated with more severe muscle cramps. TJ-68 treatment increased tryptophan and aconitate levels but reduced serotonin and acetylcarnitine levels. Long-chain acylcarnitine levels were correlated with muscle cramp severity, and their levels tended to decrease with treatment. Uric acid, β-aminoisobutyric acid, α-aminoadipic acid, and acetylcholine emerged as predictors of the efficacy of TJ-68.

CONCLUSION: This study identified the metabolite profile of muscle cramps in ALS and the changes in metabolite levels after TJ-68 treatment. Several baseline metabolites were associated with the prediction of the response to muscle cramps following TJ-68 treatment. Uric acid might be particularly useful because of its easy measurement in standard assays. Our study affirms the value of metabolomic technology for future pharmacotherapy and studies in ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/metabolism/drug therapy/blood
*Muscle Cramp/drug therapy/metabolism/blood
*Metabolomics/methods
Female
Male
Middle Aged
Aged
Cross-Over Studies
Medicine, Kampo
*Drugs, Chinese Herbal/therapeutic use

@article {pmid42451691,
year = {2026},
author = {Singh, AA and Arukha, AP and Song, M},
title = {Indole-Derived Compounds as Redox-Modulators: Antioxidant Mechanisms in Neuronal Protection.},
journal = {Molecules (Basel, Switzerland)},
volume = {31},
number = {13},
pages = {},
doi = {10.3390/molecules31132323},
pmid = {42451691},
issn = {1420-3049},
mesh = {Humans ; *Antioxidants/pharmacology/chemistry ; *Indoles/chemistry/pharmacology ; Animals ; *Neuroprotective Agents/pharmacology/chemistry ; Oxidation-Reduction/drug effects ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neurons/drug effects/metabolism ; Oxidative Stress/drug effects ; Signal Transduction/drug effects ; Reactive Oxygen Species/metabolism ; },
abstract = {Neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Amyotrophic lateral sclerosis, are distinguished by progressive neuronal dysfunction caused primarily by oxidative stress, mitochondrial impairment, neuroinflammation, and redox imbalance. Growing evidence suggests that indole-derived compounds have significant neuroprotective potential due to their antioxidant, anti-inflammatory, and redox-modulating properties. This review summarizes the structural and biological significance of indole scaffolds, focusing on the mechanisms by which natural, endogenous, microbiota-derived, and synthetic indole compounds protect neuronal networks. Indole-3-carbinol, 3,3'-diindolylmethane, indole-3-propionic acid, and melatonin are major indole derivatives that control important neuroprotective pathways like Nrf2/ARE signaling, mitochondrial bioenergetics, neurotrophic factor expression, apoptotic regulation, and suppression of proinflammatory mediators. These compounds also maintain synaptic plasticity, reduce reactive oxygen species production, and improve neuronal survival in neurodegenerative disease models. Additionally, updated information from translational and clinical research indicates that indole-based compounds may have promising therapeutic applications; however, obstacles like low bioavailability, metabolic instability, and blood-brain barrier penetration continue to be major obstacles to clinical application. Development in nanoparticle delivery systems, microbiome-targeted interventions, and rational structural optimization may improve therapeutic efficacy and translational potential. Overall, indole-derived compounds are a versatile class of redox modulators with potential applications in the prevention and treatment of neurodegenerative diseases via integrated antioxidant and neuroprotective mechanisms.},
}

Humans
*Antioxidants/pharmacology/chemistry
*Indoles/chemistry/pharmacology
Animals
*Neuroprotective Agents/pharmacology/chemistry
Oxidation-Reduction/drug effects
*Neurodegenerative Diseases/drug therapy/metabolism
*Neurons/drug effects/metabolism
Oxidative Stress/drug effects
Signal Transduction/drug effects
Reactive Oxygen Species/metabolism

@article {pmid42453524,
year = {2026},
author = {Yang, HI and Hsueh, KW and Ding, DC and Harn, HJ and Lin, YC and Chang, CY and Tsai, ST and Lin, SZ},
title = {Therapeutic potential of adipose-derived stem cell transplantation in amyotrophic lateral sclerosis: A combined clinical case and preclinical study.},
journal = {Tzu chi medical journal},
volume = {38},
number = {3},
pages = {332-339},
pmid = {42453524},
issn = {2223-8956},
abstract = {OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is an inevitably fatal neurodegenerative disease with no adequate treatment. Transplantation of adipose-derived stem cells (ADSCs) may be an effective therapeutic strategy for delaying progression or restoring neurological function in ALS.

MATERIALS AND METHODS: We evaluated the safety and therapeutic efficacy of intravenous (i.v.) and intracerebral (i.c.) ADSC injection in a late-stage ALS patient and in a SOD1 transgenic (Tg) mouse model. Magnetic resonance imaging (MRI) and computed tomography (CT) were conducted to examine potential cerebral hemorrhage and tumor generation in the treated patient. In addition, maximal inspiratory pressure, maximal expiratory pressure, tidal volume, and respiratory rate were measured as indices of respiratory function.

RESULTS: ADSC transplantation was safe, with MRI and CT showing no hemorrhage or tumorigenesis up to 12 months. The patient's Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score improved from 7 to 9 at 3 months and remained above baseline for 6 months. Respiratory function was preserved during this period. In SOD1 Tg mice, i.c. and i.v. ADSC infusion significantly prolonged survival (165.0 ± 10.4 and 147.3 ± 4.5 days vs. 129.7 ± 3.9 days) and improved motor scores (P < 0.01).

CONCLUSION: This preliminary finding suggests potential therapeutic feasibility, but further studies with larger cohorts are needed to confirm its safety and efficacy.},
}

@article {pmid42458007,
year = {2026},
author = {Chen, W and Jiang, L and Duan, C and Kang, M and Ye, J and Wang, L and Pan, Y and Qu, H and Liao, X and Zhou, X and Li, Y and Gan, Z and Chen, J and Schacht, I and Place, RF and Li, LC and Wang, Y},
title = {Oligonucleotide-siRNA conjugate for SOD1 amyotrophic lateral sclerosis: a phase 1 trial.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {42458007},
issn = {1546-170X},
support = {No.Z231100004823036//Beijing Municipal Science and Technology Commission/ ; 20230484245//Beijing Nova Program/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease partly caused by gain-of-function mutations in superoxide dismutase 1 (SOD1). Here we developed RAG-17, an siRNA-targeting SOD1, using an accessory oligonucleotide conjugate platform for enhanced central nervous system (CNS) delivery. Preclinically, RAG-17 rescued motor neuron degeneration, delayed disease progression, preserved motor function and extended survival in SOD1[G93A] ALS rodents, even with advanced-stage treatment. In cynomolgus monkeys, intrathecal RAG-17 led to dose-dependent, durable reductions in SOD1 mRNA (CNS) and protein (cerebrospinal fluid (CSF)). In a first-in-human trial in patients with SOD1-ALS (n = 6), participants were assigned to two cohorts-cohort 1 (n = 3) received an initial 60 mg dose (seven doses total) and cohort 2 (n = 3) received an initial 90 mg dose (six doses total). The dose was escalated in 30 mg steps to maintenance doses of 150 mg (n = 5) or 180 mg (n = 1). Thus, the primary safety endpoint was met, showing acceptable safety and tolerability. Treatment-emergent adverse events (TEAEs) occurred in 33% of participants (two of six). All TEAEs were mild to moderate, including muscle tremor (two patients) and elevated alanine aminotransferase (one patient), all of which resolved. No serious adverse events were reported. Furthermore, no other clinically meaningful changes were observed in laboratory parameters, vital signs, the ALS Functional Rating Scale-Revised score, physical or neurological examinations or ECG. The key secondary endpoints showed CSF SOD1 reductions of 69% (cohort 1, day 240) and 56% (cohort 2, day 210), and plasma neurofilament light chain reductions of 62% (cohort 1) and 52% (cohort 2), from baseline; no patient required invasive mechanical ventilation or died by the end of the study. These results demonstrate a favorable safety outcome, supporting the continued clinical evaluation of RAG-17 for SOD1-ALS. ClinicalTrials.gov registration: NCT05903690 .},
}

@article {pmid42447123,
year = {2026},
author = {Wohnrade, C and Thau-Habermann, N and Gschwendtberger, T and Rückoldt, J and Huang, Z and Schreiber, S and Haastert-Talini, K and Petri, S},
title = {Neuromuscular ultrasound as a biomarker in the SOD1 mouse model of amyotrophic lateral sclerosis.},
journal = {PloS one},
volume = {21},
number = {7},
pages = {e0353397},
doi = {10.1371/journal.pone.0353397},
pmid = {42447123},
issn = {1932-6203},
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology/genetics/physiopathology ; Mice ; *Superoxide Dismutase/genetics ; Disease Models, Animal ; Superoxide Dismutase-1 ; Biomarkers/metabolism ; Ultrasonography ; Mice, Transgenic ; Humans ; Sciatic Nerve/diagnostic imaging/pathology ; Muscle, Skeletal/diagnostic imaging/pathology ; Motor Neurons/pathology ; Disease Progression ; },
abstract = {A progression marker that indicates early disease-related changes and treatment responses in the to date incurable neurodegenerative disease amyotrophic lateral sclerosis (ALS) is highly desirable. Translation of therapeutics that have been successful in in vivo models into trials in human patients has proven difficult in recent decades. This failure can be attributed, at least in part, to the lack of specific biomarkers for ALS diagnosis and progression in human ALS patients as well as in in vivo models. Neuromuscular ultrasound is an easily accessible, non-invasive tool to support diagnosis of ALS in humans. Our current study shows for the first time that the disease can be detected in an ALS mouse model with the help of neuromuscular ultrasound. We characterized disease progression regarding changes in the peripheral nerves and muscles of the hind limb in the SOD1G93A mouse model of ALS using different techniques (neuromuscular ultrasound, electroneurography, motor function tests, phenotypic assessments and histology). By neuromuscular ultrasound, we measured the cross-sectional area and diameter of the sciatic nerve and analyzed hind limb muscle texture and thickness. Our results show that motor neuron loss and muscle atrophy - analogous to ALS in humans - can be measured by ultrasound in the SOD1G93A mouse model. Changes in nerve and muscle morphology appear at the same time or even before changes in the established tests (including electroneurographic measurements) performed in vivo in this model. Correlations with histologic features of disease progression make neuromuscular ultrasound a sensitive, non-invasive outcome marker for preclinical studies.},
}

Animals
*Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology/genetics/physiopathology
Mice
*Superoxide Dismutase/genetics
Disease Models, Animal
Superoxide Dismutase-1
Biomarkers/metabolism
Ultrasonography
Mice, Transgenic
Humans
Sciatic Nerve/diagnostic imaging/pathology
Muscle, Skeletal/diagnostic imaging/pathology
Motor Neurons/pathology
Disease Progression

@article {pmid42432671,
year = {2026},
author = {Chen, F and Wang, L and Liu, H and Khan, Q and Tang, B and Bao, N},
title = {The role of AI-assisted drug repurposing in neurological disorders: a systematic review of validation strategies, challenges and opportunities.},
journal = {Journal of nanobiotechnology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12951-026-04551-7},
pmid = {42432671},
issn = {1477-3155},
abstract = {Neurological disorders refer to a diverse group of conditions that affect the brain, peripheral nerves, and spinal cord and impair socioemotional, cognitive, motor, and sensory functions. Alzheimer's disease (AD), Multiple Sclerosis (MS), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS) are some of the well-known neurodegenerative diseases that affect millions of people worldwide. Despite the advanced technologies and nano-drug delivery systems, the success rate of developing drugs for neurological disorders is significantly low. Among several constraints, including gastrointestinal irritation, rapid metabolism, and low stability, the blood-brain barrier (BBB) emerges as one of the key challenges in the development and application of drugs against neurological disorders. These challenges necessitate innovative approaches to develop cost-effective therapeutic strategies. Drug repurposing, the discovery of new therapeutic benefits of existing drugs, is a promising drug discovery approach for discovering potential treatment options for complex neurological disorders. This review aims to explore the advanced and significant progress in drug repurposing for major neurological disorders, including MS, AD, PD, ALS, HD, stroke, and neuropsychiatric conditions. It places an explicit emphasis on discussing the potential role of artificial intelligence (AI)-assisted drug repurposing and understanding of the biological mechanisms in discovering new drugs for these neurological conditions. This also examines current challenges in drug repurposing and provides a critical review of the available opportunities and limitations in AI-assisted drug repurposing.},
}