@article {pmid42177450,
year = {2026},
author = {Ghasemi, F and Khoshnam Rad, N and Rashidinejad, B and Nasrollahzadeh, M},
title = {Pulmonary toxocariasis presenting as migratory pulmonary infiltrates and mediastinal lymphadenopathy: a case report and literature review.},
journal = {BMC pulmonary medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12890-026-04362-4},
pmid = {42177450},
issn = {1471-2466},
abstract = {BACKGROUND: Pulmonary toxocariasis, caused by the nematode Toxocara canis or T. cati, is an underdiagnosed cause of eosinophilic lung disease with highly variable radiological presentation that often mimics malignancy or other eosinophilic conditions.

CASE PRESENTATION: A 53-year-old female smoker presented with progressive dyspnea and cough. Initial chest CT revealed right lower lobe consolidation with mediastinal lymphadenopathy (station 4R with short-axis diameters 12 mm), raising concern for lung cancer. Bronchoscopy with EBUS-TBNA was non-diagnostic. The patient was empirically started on dexamethasone (8 mg daily, tapered over 3 months) for suspected organizing pneumonia. During steroid taper, her symptoms recurred with delayed emergence of peripheral eosinophilia (670/µL; initial absolute eosinophil count on presentation was 90/µL), elevated IgE (456 IU/mL), and serial CT scans demonstrating migratory pulmonary infiltrates involving the right lower, right middle, and left lower lobes. A history of raw beef liver consumption prompted serological testing, which confirmed Toxocara canis infection. Treatment with albendazole alone (400 mg twice daily for 14 days, without corticosteroids) resulted in complete clinical and radiological resolution.

LITERATURE REVIEW: We searched PubMed and Scopus (January 2014 - February 2026) for English- and French-language case reports of pulmonary toxocariasis. Fourteen new cases were identified and analyzed alongside the 12 cases from Ranasuriya et al.'s [1] review. These 26 cases demonstrate marked radiologic heterogeneity: multiple bilateral nodules (50%), consolidations (23%), pleural effusion (27%), and migratory infiltrates (8%). Pleural effusion has emerged as a distinct manifestation in seven recent cases. Delayed eosinophilia occurred in 12% of cases. Immunocompromised states (including primary ciliary dyskinesia, hematologic malignancies, and immunosuppressive therapy) were present in 23% of cases and may predispose to atypical presentations.

CONCLUSION: Pulmonary toxocariasis should be considered in patients with migratory infiltrates, unexplained eosinophilic pleural effusion, or lung nodules with eosinophilia. A meticulous dietary and exposure history is essential. Diagnosis is confirmed by serology, and patients respond well to albendazole therapy.},
}

@article {pmid42180530,
year = {2026},
author = {Zhao, W and Lai, Y and Li, Z and Yuan, Z and Wen, Z and Zhang, L},
title = {Targeting non-apoptotic regulated cell death (RCD) to treat neurodegenerative diseases.},
journal = {Acta pharmaceutica Sinica. B},
volume = {16},
number = {5},
pages = {2601-2644},
pmid = {42180530},
issn = {2211-3835},
abstract = {Regulated cell death (RCD) is well-known as a controlled form of cell death regulated by one or more cascading signaling pathways. Over the past few decades, increasing evidence has implicated various non-apoptotic forms of RCD in neurons-including ferroptosis, parthanatos, necroptosis, pyroptosis, autophagic cell death, paraptosis, and cuproptosis-in the pathogenesis of neurodegenerative diseases (NDs) and their associated clinical manifestations. We provide an in-depth analysis of the associations between these RCDs and NDs, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), and highlight the potential of modulating non-apoptotic RCD subtypes as neuroprotective targets. Besides, we highlight the crosstalk mechanisms among different non-apoptotic RCDs in NDs and the key targets regulating the crosstalk, which hold significant promise for developing dual-functional inhibitors that precisely modulate the pathological microenvironment and overcome drug resistance. As our understanding of death signaling networks deepens, such strategies may lead to breakthrough therapies for multiple NDs. Moreover, we further discuss the emerging small molecule compounds targeting non-apoptotic RCDs and their current research progress in clinical trials for the treatment of NDs, which may provide novel directions for related drugs. This comprehensive analysis paves the way for future research and therapeutic strategies aimed at harnessing non-apoptotic RCD pathways to mitigate neurodegeneration and improve patient outcomes.},
}

@article {pmid42181829,
year = {2026},
author = {Kuru Çolak, T and Akçay, B and Weiss, HR and Nan, X and Elliott, L and Akkoyunlu, SZ and Borysov, M},
title = {Treatment outcomes across curve patterns and severities in adolescent idiopathic scoliosis treated with a pattern-specific CAD-CAM brace.},
journal = {Frontiers in rehabilitation sciences},
volume = {7},
number = {},
pages = {1826976},
pmid = {42181829},
issn = {2673-6861},
abstract = {BACKGROUND: Whether treatment outcomes differ according to curve pattern or baseline severity in adolescents with idiopathic scoliosis (AIS) remains a subject of debate. In particular, it is unclear whether pattern-specific, CAD-CAM-designed brace systems provide comparable effectiveness across different curvature types. This study aimed to evaluate the influence of curve pattern and initial curve magnitude on treatment outcomes in AIS patients treated with a pattern-specific CAD-CAM-designed brace.

METHODS: A retrospective analysis was conducted on female AIS patients aged 10-14 years (Risser 0-2) treated between 2015 and 2024. Cobb angle and angle of trunk rotation (ATR) were used as primary outcome measures. Data from four international clinics were analyzed for changes in spinal curvature and curve pattern.

RESULTS: A total of 145 patients were included (mean age 12.2 years; mean Cobb angle 38.4° ± 11.4°). Post-treatment, mean Cobb angle and ATR values decreased significantly (p < 0.001). The overall treatment success rate was 91%, with no significant differences based on apex vertebra location (p = 0.459), ALS patterns (p = 0.705), or baseline curve severity (p = 0.274).

CONCLUSION: In this multicenter cohort of skeletally immature adolescents with idiopathic scoliosis, pattern-specific brace treatment was associated with significant reductions in both radiographic curvature and trunk rotation. Improvements were observed across different curve patterns and baseline severities. However, given the retrospective design and absence of a comparison group, these findings should be interpreted with caution. Prospective controlled studies are warranted to further validate these observations.},
}

@article {pmid42173382,
year = {2026},
author = {Braza, AJ and Viñas-Bastart, M and Sureda-Rosich, M and García-Parra, B and Guiu-Segura, JM and Modamio, P},
title = {Tofersen in SOD1-associated amyotrophic lateral sclerosis: From molecular mechanisms to regulatory milestones.},
journal = {European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences},
volume = {223},
number = {},
pages = {107563},
doi = {10.1016/j.ejps.2026.107563},
pmid = {42173382},
issn = {1879-0720},
abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a progressive and ultimately fatal neurodegenerative disorder characterized by degeneration of upper and lower motor neurons. Mutations in the superoxide dismutase 1 (SOD1) gene account for approximately 2% of ALS cases and are associated with toxic protein misfolding and aggregation. Tofersen is an antisense oligonucleotide therapy designed to reduce the synthesis of mutant SOD1 protein through targeted mRNA degradation. While this strategy represents a gene-specific therapeutic approach for a subset of ALS patients, evidence regarding its efficacy, effectiveness and long-term outcomes continues to be evaluated in clinical trials and post-marketing studies.

OBJECTIVE: First, to describe the molecular mechanisms underlying SOD1-associated ALS and second, to analyze the therapeutic development, clinical outcomes, and regulatory evolution of tofersen.

METHODS: A narrative review was conducted in PubMed on preclinical and clinical studies published from 2016 through late 2025, complemented by an analysis of public registries and regulatory documentation. Clinical trials were identified through ClinicalTrials.gov and the Clinical Trials Information System (CTIS), and official reports from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) were reviewed to contextualize their development and regulatory evaluation.

RESULTS: Fifty-three publications were identified, of which 20 met predefined inclusion criteria after screening and full-text review. Preclinical studies showed reduced mutant SOD1 expression and prolonged survival in transgenic models. Phase I-II trials demonstrated safety, favorable pharmacokinetics, and dose-dependent reductions in SOD1 in the cerebrospinal fluid and plasma neurofilament light chain (NfL) levels. Although the phase III VALOR trial did not meet the primary ALSFRS-R endpoint (a validated questionnaire-based functional rating scale-revised for determining ALS disease progression) at 28 weeks, significant reductions in the surrogate biomarker NfL indicated target engagement and supported accelerated regulatory approval. Extension data suggested potential clinical benefit with early treatment. Ongoing studies, including ATLAS in presymptomatic carriers, and real-world European data support continued evaluation, alongside accelerated regulatory approvals by FDA and EMA.

CONCLUSION: Tofersen marks a paradigm shift in ALS management, establishing the foundation for precision medicine in neurodegenerative diseases. Its ongoing evaluation in the ATLAS trial will determine whether early intervention can prevent or delay disease onset in presymptomatic SOD1 mutation carriers.},
}

@article {pmid42174910,
year = {2026},
author = {Strube, T and Weltermann, L and Weber, J and Defosse, J},
title = {Guideline-Aligned Machine Learning for Predicting Ondansetron Administration at the End of Anaesthesia: Explainable Decision Support for PONV Prophylaxis.},
journal = {Studies in health technology and informatics},
volume = {336},
number = {},
pages = {570-574},
doi = {10.3233/SHTI260235},
pmid = {42174910},
issn = {1879-8365},
mesh = {*Ondansetron/administration & dosage ; *Machine Learning ; Humans ; *Postoperative Nausea and Vomiting/prevention & control ; *Decision Support Systems, Clinical/standards ; *Practice Guidelines as Topic ; *Antiemetics/administration & dosage ; },
abstract = {Artificial Intelligence (AI) and Clinical Practice Guidelines (CPGs) both aim to support clinical decision-making but may provide conflicting suggestions. This manuscript presents a Guideline-Aligned Machine Learning (GAML) model to predict ondansetron administration at the end of anaesthesia, based on Gan et al.'s Fourth Consensus Guidelines for the Management of Postoperative Nausea and Vomiting (PONV). n= 16,240 anaesthesia protocols were analysed for risk factors and administered PONV prophylaxes. Logistic regression, multinomial naïve Bayes, and CatBoost classifiers were trained on 80% of protocols with 12-fold cross-validation; optimal thresholds were set by the mean F1-maximising cut-off across folds. Models were evaluated on the remaining 20%, achieving high accuracy (90 ± 1%) and moderate precision and recall (60 ± 5%, 75 ± 4%) across all models. A SHAP decision plot was further computed on the test set to visualise predictor contributions and illustrate a potential interactive preoperative planning interface. Overall, GAML is a promising basis for explainable decision support in clinical care.},
}

*Ondansetron/administration & dosage
*Machine Learning
Humans
*Postoperative Nausea and Vomiting/prevention & control
*Decision Support Systems, Clinical/standards
*Practice Guidelines as Topic
*Antiemetics/administration & dosage

@article {pmid42171861,
year = {2026},
author = {Condorelli, GA and Iozzia, A and Bonifacio, D and Pelin, A},
title = {TDP-43 Acetylation at the Neuroimmune Interface: A Hypothesis-Driven Framework for Peripheral Inflammatory Stratotypes in ALS.},
journal = {Neurochemical research},
volume = {51},
number = {3},
pages = {},
pmid = {42171861},
issn = {1573-6903},
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/immunology ; Humans ; Acetylation ; *DNA-Binding Proteins/metabolism ; Animals ; *Inflammation/metabolism/immunology ; Blood-Brain Barrier/metabolism ; *Neuroimmunomodulation/physiology ; },
abstract = {Transactive Response Deoxyribonucleic Acid-Binding Protein-43 (TDP-43) acetylation may couple motor-neuron degeneration to systemic immune orchestration in Amyotrophic Lateral Sclerosis (ALS). Upon nuclear clearance and mislocalisation, TDP-43 enters the periphery; acetylation shapes its conformation, trafficking and immunogenicity. This narrative review synthesises single-cell transcriptomics, proteomic immunoprofiling and clinical inflammatory phenotyping to examine whether site-specific acetylated TDP-43 species may be associated with peripheral inflammatory signatures relevant to ALS immunopathology. By integrating separate datasets on acetylated TDP-43, monocyte phenotypes and cytokine modules, we propose two provisional endotypes characterised by monocyte reprogramming, cytokine modules and Blood-Brain Barrier (BBB) dysfunction-each representing clinically actionable pathways. Framed as a provisional neuroimmune interface, the acetylation state is considered here as a plausible molecular correlate and potential therapeutic entry point: a measurable clue to inform pharmacological targeting and, potentially, a modifiable target via p300CREB-Binding Protein (CBP)-Histone Deacetylase (HDAC) axes or sirtuin activity. Recasting TDP-43 from neuropathological hallmark to immunoactive sentinel supports a shift from descriptive nosology to stratified immunotherapy, in which treatment allocation is informed by acetylation-defined peripheral signatures.},
}

*Amyotrophic Lateral Sclerosis/metabolism/immunology
Humans
Acetylation
*DNA-Binding Proteins/metabolism
Animals
*Inflammation/metabolism/immunology
Blood-Brain Barrier/metabolism
*Neuroimmunomodulation/physiology

@article {pmid42170807,
year = {2026},
author = {Renou, Q and Néant, N and Destere, A and Lagoutte-Renosi, J and Grégoire, M and Parant, F and Lalanne, S and Lemaitre, F and Gandia, P and Venisse, N and Bouchet, S and Lê, MP and Muret, P and Peytavin, G and Solas, C and Benaboud, S and , },
title = {External Evaluation of Population Pharmacokinetic Models of Cabotegravir, During Its Oral and Intramuscular Administration in HIV-Infected Patients.},
journal = {CPT: pharmacometrics & systems pharmacology},
volume = {15},
number = {6},
pages = {e70180},
doi = {10.1002/psp4.70180},
pmid = {42170807},
issn = {2163-8306},
support = {ANRS 0255//Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS)/Maladies Infectieuses Emergentes/ ; ANRS 0691b//Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS)/Maladies Infectieuses Emergentes/ ; },
mesh = {Humans ; *HIV Infections/drug therapy ; Injections, Intramuscular ; *Models, Biological ; Female ; Male ; *Anti-HIV Agents/pharmacokinetics/administration & dosage ; Administration, Oral ; Middle Aged ; Adult ; *Pyridones/pharmacokinetics/administration & dosage ; Prospective Studies ; Diketopiperazines ; },
abstract = {Cabotegravir (CAB), combined with rilpivirine, is the first long-acting injectable therapy approved for HIV-1 maintenance treatment. While adherence and patient satisfaction have been improved, pharmacokinetic (PK) variability remains a concern. Two population PK models have been developed: one based on data from phase I-III trials and the other on routine clinical data. However, neither model has undergone thorough external evaluation. The aim of this study was to evaluate the predictive performance of these models using an independent prospective dataset to evaluate their suitability to support model-informed precision dosing (MIPD). External validation was performed using data from the French observational and multicenter (n = 14) ANRS0255 CARLAPOP study (736 HIV-infected patients, representing 2192 concentrations). Models were implemented using MONOLIX software and evaluated using goodness-of-fit, prediction-based, and simulation-based diagnostics. For Han's model, regarding plasma concentrations following intramuscular administration, Median Prediction Error (MDPE) was -1.2% (PRED) and -4.4% (IPRED); Median Absolute Prediction Error (MDAPE) was 36.6% (PRED) and 17.9% (IPRED). For Thoueille's model, MDPE was -24.2% (PRED) and -9.2% (IPRED); MDAPE was 39.0% (PRED) and 15.3% (IPRED). However, < 70% of predictions were within a 20% error margin with both models. Graphical analyses of Thoueille's model showed systemic bias, particularly in women, nonsmokers, and patients with higher body mass index. Therefore, neither model was considered reliable enough for MIPD application in our population. Although Han et al.'s model demonstrated higher predictive performances, further improvements are required before it can be reliably applied for MIPD in daily routine.},
}

Humans
*HIV Infections/drug therapy
Injections, Intramuscular
*Models, Biological
Female
Male
*Anti-HIV Agents/pharmacokinetics/administration & dosage
Administration, Oral
Middle Aged
Adult
*Pyridones/pharmacokinetics/administration & dosage
Prospective Studies
Diketopiperazines

@article {pmid42171198,
year = {2026},
author = {Tian, J and Jin, Z and Chi, Y and Wang, P and Sun, H},
title = {Targeting lipid nanoparticle mediated co-delivery of edaravone and kaempferol for amyotrophic lateral sclerosis therapy.},
journal = {Nanoscale},
volume = {},
number = {},
pages = {},
doi = {10.1039/d6nr00300a},
pmid = {42171198},
issn = {2040-3372},
abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by a progressive and selective loss of motor neurons in the central nervous system, particularly in the brain and spinal cord. However, the main cellular mechanisms and cell death pathways leading to motor neuron degeneration have not yet been clarified. Research indicates evidence of ferroptosis in ALS, and the natural compound kaempferol has been demonstrated to inhibit neuronal ferroptosis. However, damage to the blood-brain barrier (BBB) prevents the drug from penetrating the central nervous system, which significantly reduces its therapeutic efficacy. Here, we developed a targeted delivery system named Eda/Kae@Lip-RGD (EKLR), which consisted of liposome-grafted RGD peptides for the co-delivery of the drugs kaempferol and edaravone, capable of crossing the BBB to provide co-delivery of kaempferol and edaravone for combined treatment of ALS. As expected, treatment with EKLR for one month significantly slowed down weight loss and improved athletic performance in SOD1[G93A] transgenic mice. Mechanistically, this nanomedicine suppressed ferroptosis by upregulating the antioxidant proteins GPX4 and SLC7A11, alongside the downregulation of Nrf2 and ACSL4 levels, thus collectively preserving neuronal integrity. Meanwhile, EKLR restored the normal morphology and the survival rate of neurons and maintained the mitochondrial structure and morphological integrity. Accordingly, this nanoplatform may represent a distinctive and potentially effective strategy for achieving neuroprotection in ALS as well as in other disorders of the central nervous system.},
}

@article {pmid42164185,
year = {2026},
author = {Albesher, AA and Muflehi, NA and Hakami, YA and Barnawi, JA and Softah, RE and Al Ghalib, LH and Bukhari, MA and Almotiri, RA and Algethami, MS and Mahboob, SW and Hakami, RK and Alsaad, A},
title = {Top 50 Cited Articles on the Treatment of Major Depressive Disorder.},
journal = {Cureus},
volume = {18},
number = {4},
pages = {e107337},
pmid = {42164185},
issn = {2168-8184},
abstract = {Major depressive disorder (MDD) is a common mental health disorder and is one of the leading causes of disability. Numerous treatment modalities have been studied for MDD, from interventions to psychotherapies. However, no exhaustive investigation has yet provided an overview of influential research on MDD treatments. Studies do not cover influential efforts occurring in the form of a comprehensive bibliometric review. This bibliometric study aims to fill this gap by thoroughly examining the characteristics of the 50 most cited articles on MDD treatment and providing an essential understanding of the intellectual structure and historical development over time. To guarantee a comprehensive research collection of trends in the treatment of MDD, we reviewed 50 pertinent papers without limiting the search by publication year, and the data collection was performed in a neutral manner. The search focuses on extensive citations from other publications and categorizes them according to their frequencies. Between 1989 and 2018, the top 50 MDD treatment publications received 96-1,837 citations (median 210, IQR 121-299). The 2000s and 2010s had a high level of publication activity (21 articles each, 42% per decade). Geographically, the United States (24, 48%), Canada (12, 24%), and the United Kingdom (5, 10%) dominated the journals. The majority of study types were randomized controlled trials (RCTs) (32, 64%), followed by systematic reviews/meta-analyses (16, 32%) and prospective cohorts (2, 4%). The publications covered a range of treatment modalities, including pharmacological, psychotherapeutic, neurostimulation, and lifestyle/complementary approaches. Elkin et al.'s NIMH Treatment of Depression Collaborative Research Program report (1,738 citations) and Unützer et al.'s IMPACT collaborative care RCT (1,837 citations) were the most referenced publications. Our results shed light on the conceptual framework of MDD treatment research, as current guidelines are shaped by significant randomized trials and systematic reviews. Precision-based and new treatments are growing the field, while traditional therapies continue to play a major role. Global applicability is limited by the geographic concentration of research, underscoring the need for diverse populations, assessment of new treatments, and incorporation of individual patient data to bolster the body of evidence.},
}

@article {pmid42165374,
year = {2026},
author = {Fernández-Gómez, P and Tosat-Bitrián, C and Marugán, T and Fernández-Hernández, L and Cano, A and Martinez-Mulero, JA and López-Carbonero, JI and Pignatelli, J and Corrochano, S and Palomo, V},
title = {Lighting Up Mislocalized Proteins: Quantum Dot Probes for Multiplexed Cytoplasm-Selective Cell Profiling in Neurodegeneration.},
journal = {ACS sensors},
volume = {},
number = {},
pages = {},
doi = {10.1021/acssensors.5c01941},
pmid = {42165374},
issn = {2379-3694},
abstract = {Semiconductor quantum dots (QDs) provide unique stability, brightness, and multiplexed capacity for biomarker detection in complex diseases; however, their distinctive intracellular distribution has rarely been leveraged for spatially resolved diagnostics. Here, we show how QD-based sensors enable selective detection of cytoplasmic proteins and can quantify nucleo-cytoplasm protein mislocalization in patient-derived samples. We validated this approach labeling TAR DNA-binding protein 43 (TDP-43), a key mislocalized protein in amyotrophic lateral sclerosis (ALS). Spatial resolution is achieved in several patient-derived models and mouse brain tissue, underscoring the nanosensor's versatility across biological systems. Multiplexed QD-based immunolabeling, combined with confocal imaging and high-throughput flow cytometry, enables the detection of distinct cytoplasmic biomarker signatures that discriminate ALS patients from healthy controls. These signatures include variations in TDP-43 mislocalization and protein coexpression patterns, which were further modulated by pharmacological treatment. This work establishes QDs as spatially selective, multiplexable nanosensors capable of resolving subtle yet disease-relevant intracellular phenotypes in patient-derived samples. Compared to organic fluorophores, QDs enhance sensitivity, improve signal stability, and enable simultaneous spatially resolved biomarker quantification, broadening their potential for clinical diagnostics and personalized medicine. These findings establish QDs as powerful tools for neurodegeneration research, disease monitoring, and early biomarker discovery, with potential applications in translational neuroscience and precision medicine.},
}

@article {pmid42168009,
year = {2026},
author = {Corcia, P and Bernard, E and de la Cruz, E and Danel, V and Soriani, MH and Guy, N and Esselin, F and Bruneteau, G and Pradat, PF and Goutines, V and Catherine, J and Eyraud, N and Cheve, P and Fernandez, A and Erazo, D and Couratier, P},
title = {Primary Lateral Sclerosis French National Diagnostic and Care Protocol.},
journal = {Revue neurologique},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neurol.2026.04.006},
pmid = {42168009},
issn = {0035-3787},
abstract = {Primary lateral sclerosis (PLS) is a rare neurodegenerative motor neuron disease characterized by progressive and selective involvement of the central motor neuron within the bulbar and spinal regions. It is estimated to account for 1-5% of motor neuron diseases and typically presents in the fifth or sixth decade of life, with a slight male predominance. According to current consensus criteria, the diagnosis relies on the demonstration of progressive upper motor neuron dysfunction in the absence of lower motor neuron involvement, with persistence of isolated upper motor neuron signs for at least four years in order to exclude a slowly progressive upper motor neuron-predominant form of amyotrophic lateral sclerosis (ALS). The French Motor Neuron Disease Network (FILSLAN) developed a National Diagnostic and Care Protocol (PNDS) with the aim of standardizing diagnostic criteria, optimizing differential diagnosis, and providing evidence-based recommendations for therapeutic management and follow-up across the national territory. These recommendations were elaborated in accordance with the methodological framework of the French National Authority for Health for rare diseases. The protocol provides practical guidance for establishing PLS as a diagnosis of exclusion, distinguishing it from ALS and hereditary spastic paraplegias, and organizing appropriate clinical and paraclinical investigations. It also outlines indications for genetic testing in selected cases and defines a multidisciplinary management strategy centered on symptomatic treatment, early rehabilitation, respiratory and nutritional surveillance, and psychosocial support. Given the slower progression of PLS compared with ALS, biannual multidisciplinary follow-up is generally appropriate. This protocol aims to harmonize clinical practice and improve patient care while acknowledging the current absence of disease-modifying therapies.},
}

@article {pmid42170793,
year = {2026},
author = {Michelon, H and Lefèvre-Dognin, C and Paquereau, J and Guidoni, R and Boudy, V and Ruiz, F and Vallet, T},
title = {Acceptability of Atropine Eyedrops Administered Sublingually for Sialorrhea Treatment Related to Neurological Conditions.},
journal = {Pharmacology research & perspectives},
volume = {14},
number = {3},
pages = {e70250},
doi = {10.1002/prp2.70250},
pmid = {42170793},
issn = {2052-1707},
mesh = {Humans ; *Sialorrhea/drug therapy/etiology ; *Atropine/administration & dosage ; Male ; Middle Aged ; Cross-Sectional Studies ; Female ; Adult ; Ophthalmic Solutions/administration & dosage ; Aged ; Administration, Sublingual ; *Nervous System Diseases/complications ; France ; *Patient Acceptance of Health Care ; *Cholinergic Antagonists/administration & dosage ; },
abstract = {Off-label use of anticholinergic agents (atropine eye drops) administered sublingually are a first-line treatment in standard clinical practice in France to treat sialorrhea in patients with neurological conditions. The ability and willingness to using and administering such medication have become key factors to ensure safe and effective therapy. Given that the critical aspects for ophthalmic product development differ from those for oral medicine, the objectives of this study were to investigate patient acceptability of atropine eye drops for treating sialorrhea. A multi-centric, cross-sectional study using the CAST-ClinSearch Acceptability Score Test methodology was conducted in France between February 2021 and April 2023. In total, 31 evaluations were collected. Most patients were males (74.2%) and the mean age was 51.6 ± 20 years. Poor acceptability was reported in real-life settings. A lack of a suitable administration device combined with excessive saliva flow and patient disabilities made it difficult to ensure the required dose intake. Due to the bitter taste of the drug, poor palatability of the product appeared to be a key concern for oral administration. Designing a suitable form of atropine in accordance with the specificities of patients with neurological disabilities is needed to ensure the effective treatment of sialorrhea.},
}

Humans
*Sialorrhea/drug therapy/etiology
*Atropine/administration & dosage
Male
Middle Aged
Cross-Sectional Studies
Female
Adult
Ophthalmic Solutions/administration & dosage
Aged
Administration, Sublingual
*Nervous System Diseases/complications
France
*Patient Acceptance of Health Care
*Cholinergic Antagonists/administration & dosage

@article {pmid42152867,
year = {2026},
author = {Cho, Y and Won, SY and Kim, H and Lee, HK and Cho, SR},
title = {The effects of a mobile healthcare application on speech and swallowing in amyotrophic lateral sclerosis.},
journal = {Digital health},
volume = {12},
number = {},
pages = {20552076261452405},
pmid = {42152867},
issn = {2055-2076},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) impairs oral motor function, negatively affecting patients' speech and swallowing abilities, as well as quality of life.

OBJECTIVE: This study aims to evaluate the effectiveness of A Successful Swallowing with Effortful Training (ASSET) program, included in the 'The 365 Healthy Swallow Health Coach application' in preserving speech and swallowing abilities in ALS patients through self-training.

METHODS: In this 8-week quasi-experimental study, 13 participants were allocated to either the app-guided ASSET training group (n=7; three sessions per day, five days per week) or a usual-care control group (n=6) based on their clinical visit schedules. To evaluate changes over time and compare the two groups, linear mixed models were employed. Changes in ALS severity scale (ALSSS), Diadochokinetic (DDK) task, speech intensity, Speech Handicap Index-15, Dysphagia Handicap Index, Swallowing Quality of Life (SWAL-QOL), and Brief Inventory of Swallowing Assessment-15 were assessed.

RESULTS: ALSSS speech scores was relatively preserved from 5.43 (95% CI 3.01-7.84) to 5.29 (95% CI 2.87-7.70) in the ASSET treatment group, but declined from 6.33 (95% CI 3.73-8.94) to 4.83 (95% CI 2.23-7.44) in the control group, with a significant group-by-time interaction (p=.017). DDK/tuh/and/kuh/were relatively preserved from 11.86 to 11.71 and from 12.29 to 11.57 respectively in ASSET group, but declined from 11.67 to 7.50 and from 11.83 to 7.17 in the control group, with significant interactions in/tuh/(p=.032) and/kuh/(p=.044). SWAL-QOL total score was relatively preserved from 155.86 to 149.71 in ASSET group, but declined from 154.67 to 125.17 in the control group, with a significant interaction (p=.011).

CONCLUSIONS: The findings suggest that ASSET program may help preserve speech and swallowing function in patients with ALS. Future research should validate the ASSET program with a larger, adequately powered sample size.},
}

@article {pmid42155417,
year = {2026},
author = {Simpson, J and Zarotti, N},
title = {Distress, not symptoms: Reframing psychological difficulties in neurodegenerative diseases of the motor system.},
journal = {Cortex; a journal devoted to the study of the nervous system and behavior},
volume = {200},
number = {},
pages = {262-271},
doi = {10.1016/j.cortex.2026.05.004},
pmid = {42155417},
issn = {1973-8102},
abstract = {Psychological distress is common among people living with neurodegenerative diseases of the motor system (NDMS) such as Parkinson's disease, motor neurone disease/amyotrophic lateral sclerosis, and Huntington's disease. Yet the way psychological difficulties are conceptualised in these populations is heavily shaped by medicalised language. Terms such as 'non-motor symptoms' and 'neuropsychiatric manifestations' were originally introduced to draw attention to difficulties beyond movement changes but they now risk positioning mood, anxiety, apathy, and related experiences solely as direct manifestations of neurological degeneration. This framing can obscure the rich psychosocial contexts in which distress arises, blur distinctions between emotional responses and disease processes, and reinforce deficit-based and disease-focused understandings that privilege biological explanations over person-centred ones. It may also influence clinical communication, treatment decisions, help-seeking behaviour, and access to psychological therapy and psychosocial interventions, contributing to inequities in care. This article argues that linguistic choices are not neutral: they construct the boundaries of what counts as legitimate knowledge, shape expectations about causality, and delimit the interventions considered appropriate. Without critical attention to these assumptions, individuals may experience distress as biologically inevitable and clinicians may overlook psychosocial contributors that are amenable to change. We propose that greater awareness of the power of language, coupled with empirical investigation into its effects, is essential for developing a linguistic reformulation of psychological distress in NDMS and more holistic, contextually grounded approaches to supporting psychological wellbeing.},
}

@article {pmid42156174,
year = {2026},
author = {Su, X and Tan, X and Wang, Y and Liang, W and Wang, D and Huo, D and Wang, H and Qi, Y and Zhang, W and Han, L and Zhang, D and Wang, M and Xu, J and Wang, S and Wang, J and Feng, H},
title = {COMMD1 Induces Copper Deficiency of SOD1 by Inhibiting the Palmitoylation of CCS in ALS.},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1523/JNEUROSCI.1803-25.2026},
pmid = {42156174},
issn = {1529-2401},
abstract = {Mutations in superoxide dismutase 1 (SOD1) compromise its metal-binding capacity, resulting in protein misfolding and aggregation, which ultimately induces cellular apoptosis in amyotrophic lateral sclerosis (ALS). Copper metabolism domain containing 1 (COMMD1), a gene implicated in copper homeostasis, has not been thoroughly characterized in the context of ALS pathogenesis. In this study, we identified elevated COMMD1 expression in ALS, potentially contributing to diminished copper incorporation into SOD1. Knockdown of COMMD1 enhanced palmitoylation of the copper chaperone for SOD1 (CCS), facilitating its membrane translocation and promoting copper loading into SOD1, thereby conferring neuroprotection in ALS. Mechanistically, we established that COMMD1 knockdown augments CCS palmitoylation via activation of the hypoxia inducible factor 1 subunit alpha (HIF-1α)/fatty acid synthase (FASN) signaling axis. In vivo investigations utilizing male hSOD1[G93A] transgenic mice demonstrated that COMMD1 deficiency markedly ameliorated the deterioration of motor function and prolonged survival duration. These findings collectively suggest that COMMD1 represents a potential therapeutic target for ALS intervention.Significance Statement Superoxide dismutase 1 (SOD1) was the first identified mutant gene associated with amyotrophic lateral sclerosis (ALS). Mutations in SOD1 compromise its metal-binding function, resulting in neuronal apoptosis, a hallmark of ALS pathogenesis. Utilizing the SOD1[G93A] models of ALS, our findings revealed that COMMD1 deficiency significantly elevates copper incorporation into SOD1, consequently attenuating cellular apoptosis. These results suggest that targeted inhibition of COMMD1 could represent a potential therapeutic strategy for ALS treatment.},
}

@article {pmid42161327,
year = {2026},
author = {Vallikivi, JK and Kooyman, M and , and Kirby, J and Nigel Leigh, P and Iacoangeli, A and Al-Chalabi, A and Al Khleifat, A},
title = {CYP2D6 variants in amyotrophic lateral sclerosis: an association study of risk and survival.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag178},
pmid = {42161327},
issn = {1460-2156},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with limited therapeutic options. Riluzole remains the only widely available disease-modifying treatment for ALS, yet its survival benefit is modest and likely to vary substantially between patients. Cytochrome P450 2D6 (CYP2D6), is a highly polymorphic enzyme that contributes to interindividual variability in the metabolism of many drugs. CYP2D6 is also expressed in the brain, and experimental and translational studies indicate that brain CYP2D activity can influence local metabolism of neuroactive compounds. Accordingly, CYP2D6 poor function variants have been examined as susceptibility modifiers in the development of other neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease, with heterogenous evidence; however, the role of CYP2D6 in ALS has not been established.},
}

@article {pmid42163674,
year = {2026},
author = {Qi, M and Fei, L and Cui, W and Ho, PW and Lee, SM and Li, J and Zhang, Z},
title = {Unraveling the Pathological Mechanisms and Biomarkers of Amyotrophic Lateral Sclerosis: A Comprehensive Review.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X431460260227095109},
pmid = {42163674},
issn = {1875-6190},
abstract = {Amyotrophic lateral sclerosis (ALS) is an devastating neurodegenerative disorder with a very fast course and a very high fatality rate. The review discusses the intricate pathophysiology of ALS, such as the alterations caused by the genetic mutations of the C9orf72 and SOD1 genes, the misfolding and aggregation of proteins, oxidative stress, the excitotoxicity of glutamate, neuroinflammation, malfunctions in mitochondria, and axonal transport. Heterogeneity of the disease makes the development of biomarkers in ALS challenging; however, some promising candidates have been identified. Protein aggregation markers, including TDP-43 and SOD1, oxidative stress markers, such as 8-oxodG, neuroinflammatory markers, such as CRP and MCP-1, and neurological injury markers, such as NfL and pNfH, have potential in diagnosis, monitoring, and prediction. The miRNAs and particular metabolites can also provide clues to the molecular basis of ALS. The creation of biomarkers is challenged by the presence of a significant amount of disease heterogeneity and the lack of animal model reliability. The review highlights the importance of further research on biomarkers aimed at improving the diagnosis, treatment, and development of drugs for ALS. It supports the concept of a systematic biomarker development process, including genetic testing and molecular subgroup analysis, to enhance diagnostic accuracy and prognostic prediction capabilities. Exploring the interrelationship between the pathological process of ALS and the treatment based on multi-biomarker strategies is crucial for achieving effective management of this disease. As our understanding of ALS deepens, we expect to discover more new biomarkers in the future. This will significantly improve the diagnosis, treatment, and overall management of this devastating diseas.},
}

@article {pmid42164014,
year = {2026},
author = {Cheung, N},
title = {Symptom-Level Precision Neurology in Amyotrophic Lateral Sclerosis (ALS): Linking Microglial Pruning, Mitochondrial Nicotinamide Adenine Dinucleotide (NAD+) Compensation, and Autophagy Failure Across the Aging Spectrum.},
journal = {Cureus},
volume = {18},
number = {5},
pages = {e109147},
pmid = {42164014},
issn = {2168-8184},
abstract = {Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurological disease with limited disease-modifying treatment options and, for many patients, a short survival window. The clinical course varies widely. Limb weakness, bulbar impairment, respiratory decline, fine-motor dysfunction, cognitive change, mood symptoms, and fatigue may each appear at different times and progress at different rates. This variability suggests that motor neuron loss alone may not fully explain the patient-level pattern of symptoms. This article is a narrative hypothesis framework, not a clinical guideline or a validated stratification tool. Established ALS biology, associative genomic findings, preclinical observations, computational predictions, and author-derived hypotheses are therefore separated throughout the article. This review brings together four interlinked studies by the current author as a primary hypothesis-generating corpus, which proposes that synaptic plasticity fragility may initiate a microglial pruning continuum shared by major depressive disorder and ALS, while ALS-specific progression may depend on mitochondrial stress, oxidized nicotinamide adenine dinucleotide (NAD+) compensation failure, and collapse of autophagy under aging-related limits. The model presented here maps symptom domains to vulnerable circuit compartments and separates three broad biological states: compensated plasticity, fragile plasticity, and network collapse. A compact mechanistic formulation is used to describe the balance between pruning pressure, glutamatergic burden, and aging stress on one side, and oxidative phosphorylation capacity, NAD+ reserve, and autophagic clearance on the other. The framework also incorporates opposing phosphoinositide 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α) pathway patterns that may distinguish ALS from frontotemporal dementia (FTD) within an aging context. The result is a falsifiable, biomarker-oriented hypothesis model for future studies, not an evidence-based diagnostic or therapeutic algorithm.},
}

@article {pmid42136278,
year = {2026},
author = {Sharma, A and Mittal, V and Sharma, D and Deswal, G and Das, A and Guarve, K and Grewal, AS},
title = {Therapeutic Insights into Natural Products for Modulating Neurodegenerative Disease Pathways.},
journal = {Central nervous system agents in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715249405308251210104405},
pmid = {42136278},
issn = {1875-6166},
abstract = {INTRODUCTION: Neurodegenerative Disorders (NDs), such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis (ALS), are chronic and progressive conditions marked by the gradual loss of neuronal structure and function. These disorders lead to cognitive, motor, and sensory decline, significantly reducing quality of life and posing a major global health burden due to rising healthcare costs and the absence of curative therapies. This review aims to comprehensively explore the therapeutic potential of natural products in targeting cellular and molecular mechanisms underlying NDs, highlighting their neuroprotective roles and potential for disease modification.

METHODS: A comprehensive literature review was conducted using databases including PubMed, Scopus, Web of Science, and Google Scholar. Peer-reviewed articles, clinical trials, and experimental studies were analyzed to evaluate the therapeutic potential of natural products and their bioactive compounds in the management of NDs.

RESULTS: ND pathogenesis involves oxidative stress, neuroinflammation, mitochondrial dysfunction, and abnormal protein aggregation, ultimately leading to neuronal death. Current therapies largely provide symptomatic relief without altering disease progression. Natural products from plants, fungi, and marine sources demonstrate strong neuroprotective potential through multitargeted mechanisms. Bioactive compounds such as flavonoids, alkaloids, terpenoids, and polyphenols exhibit antioxidant, anti-inflammatory, anti-apoptotic, and neuroprotective activities. Key molecules, including curcumin, resveratrol, luteolin, quercetin, and catechins, modulate signaling pathways such as NF-κB, MAPK, PI3K/AKT, Nrf2, apoptosis, and autophagy, thereby reducing amyloid-beta aggregation, protecting dopaminergic neurons, improving mitochondrial function, and enhancing cognition in preclinical and clinical studies.

DISCUSSION: Natural products represent promising candidates for disease modification in NDs due to their multi-pathway actions and relatively low toxicity. However, major limitations, such as poor bioavailability, pharmacokinetic variability, and the lack of standardized formulations, hinder clinical translation. Innovative strategies, including advanced drug-delivery systems, structural modifications, and synergistic formulations, are needed to overcome these barriers.

CONCLUSION: Natural products hold significant therapeutic potential in managing neurodegenerative diseases by targeting multiple pathological mechanisms. Their integration into ND treatment could provide safer and more effective alternatives, but further well-designed clinical trials are essential to establish their efficacy and facilitate clinical application.},
}

@article {pmid42136293,
year = {2026},
author = {Ramesh, J and Jayanthi, B and Mohan, VK and Srinivasan, S and Vijayalakshmi, MK and Mohan, M},
title = {Targeted Nanotechnology Approaches to Bypass the Blood-brain Barrier in Neurodegenerative Disorders.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273444679260416064255},
pmid = {42136293},
issn = {1996-3181},
abstract = {Neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Huntington's disease (HD) are a growing health burden across the world because of the progressive loss of brain cells and the ineffective nature of the available treatment. One significant challenge in the treatment of these conditions is the Blood- -Brain Barrier (BBB), a highly selective interface that limits the access of most therapeutic molecules to the central nervous system. Nanotechnology has become an attractive approach to addressing this difficulty, as it enables the delivery of drugs with high accuracy and actively engages in the repair of the BBB. This review provides an overall synthesis of focused nanotechnology solutions aimed at both circumventing and restoring BBB function in neurodegenerative illnesses. It discusses various nanoparticle (NP) platforms such as polymeric, lipid-based, micellar, metallic, and carbon-derived systems in the light of their physicochemical aspects, transport across the BBB, and therapeutic efficacy. Particular emphasis is put on the receptor-mediated transcytosis, neurovascular unit modulations, and the regulation of Wnt, Shh, and Tie-2 signalling pathways, which are BBB integrity pathways. The review incorporates mechanisms of BBB repair in combination with neuroprotective nanotherapies, rather than focusing solely on end repair. This review covers the role of targeted nanotechnology in the future of therapeutic approaches for neurodegenerative diseases. By connecting materials science, molecular neuroscience, and clinical innovation, it demonstrates how next-generation brain-targeted therapies can be developed using targeted nanotechnology.},
}

@article {pmid42143042,
year = {2026},
author = {Ferrari, V and Tedesco, B and Cozzi, M and Pramaggiore, P and Gagliani, MC and Magdalena, R and Cornaggia, L and Casarotto, E and Chierichetti, M and Mohamed, A and Brodnanovà, M and Milioto, C and Piccolella, M and Galbiati, M and Crippa, V and Provenzani, A and Cortese, K and Rusmini, P and Cristofani, R and Poletti, A},
title = {VCP modulation ameliorates pathological features in C9orf72 models.},
journal = {Cell death & disease},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41419-026-08856-1},
pmid = {42143042},
issn = {2041-4889},
support = {23236//AFM-Téléthon (French Muscular Dystrophy Association)/ ; 29514//AFM-Téléthon (French Muscular Dystrophy Association)/ ; 29514//AFM-Téléthon (French Muscular Dystrophy Association)/ ; GGP19128//Fondazione Telethon (Telethon Foundation)/ ; GMR25T1103//Fondazione Telethon (Telethon Foundation)/ ; PRIN-Progetti di ricerca di interesse nazionale n. 2022EFLFL8//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; National Center for Gene Therapy and Drugs Based on RNA Technology (CN3) CN00000041//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; PRIN-Progetti di ricerca di interesse nazionale n. 2020PBS5MJ//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; PRIN-Progetti di ricerca di interesse nazionale n.//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; PRIN-Progetti di ricerca di interesse nazionale n. 2022KSJZF5//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; PRIN-Progetti di ricerca di interesse nazionale n. P2022B5J32//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; piano di sviluppo della ricerca (PSR) UNIMI -linea B//Università degli Studi di Milano (Universitas Studiorum Mediolanensis)/ ; piano di sviluppo della ricerca (PSR) UNIMI -linea B//Università degli Studi di Milano (Universitas Studiorum Mediolanensis)/ ; piano di sviluppo della ricerca (PSR) UNIMI -linea B//Università degli Studi di Milano (Universitas Studiorum Mediolanensis)/ ; 2025-0708//Fondazione Cariplo (Cariplo Foundation)/ ; 2025-0708//Fondazione Cariplo (Cariplo Foundation)/ ; 2021-1544//Fondazione Cariplo (Cariplo Foundation)/ ; Grant 2020//Kennedy's Disease Association (KDA)/ ; Grant 2018//Kennedy's Disease Association (KDA)/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurodegenerative diseases linked by similar pathological mechanisms, which, in some familial forms, may be associated with the same genetic alterations. Among them, the most common is the C9ORF72 (C9) mutation. The C9 mutation consists in an aberrant expansion of the hexanucleotide repeat (G4C2)n that leads to the production and accumulation of toxic dipeptide repeat proteins (DPRs). Some of these C9-DPRs contribute to neuronal dysfunction and degeneration through different mechanisms. One of these involves alterations in the protein quality control (PQC) system, specifically in the autophagy-lysosomal pathway. Valosin-containing protein (VCP) is a critical component of the PQC system, assisting the degradation of misfolded proteins and damaged organelles and the maintenance of cellular homeostasis. In this study, we investigated the role of VCP in modulating pathological features associated with C9 mutation. Using neuronal cell models, we demonstrated that VCP overexpression significantly reduced C9-DPRs levels. This reduction is mediated by mechanisms involving both the ubiquitin-proteasome system (UPS) and autophagy. Additionally, we also observed that C9-DPRs induce lysosomal damage, which is counteracted by VCP overexpression, as indicated by decreased galectin-3 puncta and restored lysosomal pH. We then pharmacologically activated VCP-mediated clearance through SMER28, increasing the clearance of the most toxic DPR, the polyPR. We also determined that in this model, SMER28 activity is mediated by the UPS and is associated with the mitigation of DPR-induced lysosome damage. Additionally, using motor neurons derived from induced pluripotent stem cells (iPSC-MNs) from C9-ALS mutation carriers, we demonstrated that SMER28 treatment significantly decreased polyGA levels, a marker for C9-DPR accumulation. Moreover, SMER28 rescued C9-MNs commitment to differentiation and the alteration in the expression of autophagy-related genes. Taken together, our findings strongly support VCP as a modulator of C9 pathology and highlight its potential as a therapeutic target.},
}

@article {pmid42134658,
year = {2026},
author = {Purushotham, SS and Chesworth, R and Keembiyage, N and Münch, G and Gyengesi, E and Buskila, Y},
title = {The impact of long-term feeding with curcuminoids phospholipids enriched diet on disease progression of fALS.},
journal = {Neurochemistry international},
volume = {197},
number = {},
pages = {106183},
doi = {10.1016/j.neuint.2026.106183},
pmid = {42134658},
issn = {1872-9754},
abstract = {Amyotrophic lateral sclerosis (ALS) is a debilitating and fatal neurodegenerative disease characterised by the progressive loss of motor functions affecting both upper and lower motor neurons. Although considered multifactorial with an unclear aetiology, it is believed that the interplay between genetic and environmental factors, with neuroinflammation playing a key role in disease progression, contributes to its development. There is currently no effective treatment for ALS. Curcumin has been recently highlighted for its potential therapeutic role in treating neurodegenerative diseases. Curcumin phospholipids, a highly bioavailable form of curcumin that allow the curcumin to be absorbed into the bloodstream more effectively than standard curcumin extracts, is considered as a natural cytokine-suppressive anti-inflammatory compound (CSAID) that is well-known for its therapeutic properties and is considered safe for humans and rodents at low to moderate concentrations. In this study, we investigated whether a long-term feeding regimen incorporating curcuminoids phospholipids-enriched diet early in disease progression could mitigate motor deficits and affect the lifespan of the SOD1 mouse model of familial ALS (fALS). Our results indicate sex-differences regarding the effect of curcumin supplementation on motor deficits and anxiety-like behaviour. While long-term feeding with curcuminoids phospholipids enriched diet had a complex effect on SOD1 female mice expressed as reduced anxiety like behaviour and motor deficits at the walking beam test, it had no effect on SOD1 male mice. Moreover, curcuminoids supplementation had a limited effect on disease onset and progression in SOD1 mice model for fALS.},
}

@article {pmid42117777,
year = {2026},
author = {Dong, J and Yan, M and Farmer, A and Jiang, L and Zhen, J and Tong, Y and Dong, Y and Zhang, G and Wu, L and Guo, Y and Yin, X and Fang, L and Xu, Z},
title = {The Impact of Social Isolation on Treatment Burden Among Community-Dwelling Adults With Disability and Multimorbidity: A Longitudinal Qualitative Study in Urban China.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {29},
number = {3},
pages = {e70693},
pmid = {42117777},
issn = {1369-7625},
support = {2024KY1026//Medical Science and Technology Project of Zhejiang Province/ ; //National Institute of Health and Care Research Oxford Biomedical Research Centre/ ; },
mesh = {Humans ; *Social Isolation/psychology ; Female ; Male ; Longitudinal Studies ; Qualitative Research ; China ; *Persons with Disabilities/psychology/statistics & numerical data ; Aged ; *Multimorbidity ; Middle Aged ; *Independent Living/psychology ; Interviews as Topic ; Urban Population ; *Cost of Illness ; Adult ; Chronic Disease ; },
abstract = {BACKGROUND: Social isolation is a critical social determinant of health that amplifies the significant treatment burden faced by community-dwelling adults with disabilities and multimorbidity. While an association between these factors is established, longitudinal evidence capturing their dynamic interplay is scarce, limiting the development of effective, equitable interventions. This study aimed to longitudinally explore how treatment burden evolves among this population and to elucidate the mechanisms through which social isolation appears to operate through these changes.

METHODS: We conducted a longitudinal qualitative study using interpretive description in Hangzhou, China. Participants were adults with physician-diagnosed disabilities and ≥ 2 chronic conditions, recruited via purposive sampling from community health centres. Each participant completed three in-depth, semi-structured interviews over 12 months. We conceptualized treatment burden using Demain et al.'s adaptation of the Cumulative Complexity Model. Data analysis was an iterative process involving constant comparison to identify key themes regarding the interplay of social isolation and treatment burden over time.

RESULTS: A total of 24 participants (13 were women; median age 67.5 years) completed the study. Our analysis revealed that social isolation was described by participants as dynamically contributing to increased treatment burden through four interconnected mechanisms: (1) Eroding autonomy, leading to passive healthcare decision-making; (2) Compromising emotional well-being, which depleted self-management capacity; (3) Straining relational networks, resulting in the loss of crucial informal support; and (4) Creating navigational barriers, which led to difficulties managing complex treatments. A key cross-cutting theme was the apparent role of depressive symptoms, which participants described as being exacerbated by isolation and, in turn, appearing to contribute to more negative illness perceptions and functional decline. This pattern was consistent with a progressive intensification of treatment burden as emotional and physical challenges fed into each other over time.

CONCLUSION: Social isolation appeared to function not merely as a passive correlate but as a factor that longitudinally contributed to greater treatment burden, thereby exacerbating health inequities for adults with disabilities and multimorbidity. This pattern appeared to be further shaped by the intersection with depressive symptoms. To mitigate this, multi-level interventions are essential. Priorities should include addressing structural barriers through policies that foster community integration, strengthening mental health support within primary care, and redesigning services to be more relationally-centred and less burdensome.

Patients, care-givers, people with lived experience or members of the public were not involved in the study design, conduct, data analysis or preparation of the manuscript. However, preliminary findings were shared and discussed with two patient advisors who had lived experience of disability and multimorbidity but were not participants in the interviews. Their feedback helped refine the presentation and contextual relevance of the themes.},
}

Humans
*Social Isolation/psychology
Female
Male
Longitudinal Studies
Qualitative Research
China
*Persons with Disabilities/psychology/statistics & numerical data
Aged
*Multimorbidity
Middle Aged
*Independent Living/psychology
Interviews as Topic
Urban Population
*Cost of Illness
Adult
Chronic Disease

@article {pmid42131110,
year = {2026},
author = {Zhang, M and Su, L and Han, W and Song, F and Fu, Y and Chi, MB and Chen, X and Wu, YH and Gao, SJ},
title = {Single cell Raman spectroscopic profiles predict treatment responses in patients with de novo acute myeloid leukemia.},
journal = {Frontiers in cell and developmental biology},
volume = {14},
number = {},
pages = {1767226},
pmid = {42131110},
issn = {2296-634X},
abstract = {INTRODUCTION: Leukemia is a clonal malignant proliferative disease originating from hematopoietic stem cells. Although its treatment strategy has gradually developed from traditional chemotherapy to a multimodal treatment system including novel targeted therapy and immunotherapy, primary drug resistance in particular remains the core clinical problem leading to poor patient prognosis. This clinical dilemma indicates that the traditional genotyping system based on genomics has not been able to fully resolve the molecular heterogeneity of acute myeloid leukemia (AML), and it is urgent to establish a precise stratified model that can dynamically reflect the functional status of tumor cells in the initial stage of treatment.

METHODS: In this study, Raman spectroscopy (RS) combined with machine learning algorithm was used to construct a metabolic prognosis prediction model for AML chemotherapy response. Bone marrow single cell Raman spectroscopy data of newly diagnosed AML patients were collected, and the molecular fingerprint was analyzed by principal component analysis linear discriminant analysis (PCA-LDA) and multivariate curve resolute alternating least square method (MCR-ALS).

RESULTS: The results showed that the PCALDA model achieved complete remission or non-remission (CR/NR) classification through 24 principal components (cumulative variance contribution of 90.1%), the accuracy of external validation was 94.8% (sensitivity 97.9%, specificity 92.0%), and the AUC reached 96.27%. Protein, lipid, nucleic acid and mixed components were decomposed by MCR-ALS, and lipid and nucleic acid metabolic pathways were enriched in NR group (P < 0.001).

DISCUSSION: Studies have shown that RS single-cell metabolic fingerprint can decode the metabolic reprogramming features associated with chemotherapy resistance in AML, providing a new marker-free and highly sensitive tool for real-time prognostic stratification and targeted intervention.},
}

@article {pmid41922953,
year = {2026},
author = {Xing, Z and Cheng, Z and Yang, X and Hu, L and Wang, K and Wang, Y and Hu, D and Wang, YH and Du, J and Wang, L and Li, J},
title = {Integrated genomic and transcriptomic analysis reveals candidate genes underlying herbicide resistance in Sorghum.},
journal = {BMC plant biology},
volume = {26},
number = {1},
pages = {},
pmid = {41922953},
issn = {1471-2229},
support = {32372134//The National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Herbicide-resistant germplasms provide critical genetic resources for improving weed control and understanding resistance mechanisms in crops.

OBJECTIVE: To screen sorghum accessions for tolerance to ACCase and ALS inhibitor herbicides at the seedling stage, identify the major locus and strong candidate gene associated with feproxydim resistance, and verify the gene expression pattern and genetic variation by quantitative real‑time PCR (qRT‑PCR) and KASP genotyping.

METHOD: A total of 316 sorghum accessions were screened for seedling-stage herbicide tolerance using gradient herbicide treatments. Bulked segregant analysis sequencing (BSA-Seq) was performed on resistant and susceptible gene pools constructed from the F₂ population derived from IS1219 × RTx430. Transcriptome sequencing (RNA-Seq) was conducted on leaf tissues after feproxydim treatment to identify candidate genes within the mapped interval. KASP markers were developed for the functional variation site of the key candidate gene for genotyping validation. Quantitative real‑time PCR (qRT-PCR) was used to measure the relative expression level of the target gene and compare it with the susceptible control line. Protein sequence comparison was used to detect variations in the key candidate gene between resistant and susceptible lines.

RESULT: In the screening with the ACCase inhibitor 10% feproxydim, IS1219 exhibited high-level resistance. Preliminary screening under the ALS inhibitor mesosulfuron-methyl treatment identified only SJ304 with visible tolerance, which was not subjected to further mapping or validation. BSA-Seq identified a major feproxydim resistance QTL on chromosome 1. RNA-Seq revealed five co-expressed candidate genes in the target interval, among which Sobic.001G431500 (encoding carboxylesterase 17, an α/β‑hydrolase) was markedly upregulated in the resistant line IS1219 but not in the susceptible line RTx430. Quantitative real‑time PCR (qRT-PCR) analysis confirmed that Sobic.001G431500 was significantly upregulated in the resistant line IS1219 compared with the susceptible control. KASP genotyping demonstrated that the IS1219 allele cosegregated with feproxydim resistance. Protein sequence comparison showed that the IS1219 allele carried a missense mutation V300A and a deletion P301_P303 at and after position 300.

CONCLUSION: These findings identify a major QTL and a strong candidate gene Sobic.001G431500 associated with feproxydim resistance in the sorghum line IS1219, based on differential expression, genetic variation, and genotype–phenotype cosegregation. This study provides valuable genetic resources and functional markers for marker-assisted selection and breeding of feproxydim-tolerant sorghum varieties.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12870-026-08624-5.},
}

@article {pmid42116584,
year = {2026},
author = {Bala, VC and Singh, MK and Kumar, A and Tiwari, SK and Gupta, AK and Chawla, R and Kumar, S},
title = {Targeting α-Synuclein: Current Strategies and Emerging Therapies for Synucleinopathies.},
journal = {Protein and peptide letters},
volume = {33},
number = {1},
pages = {258-274},
doi = {10.2174/0109298665429866260217115717},
pmid = {42116584},
issn = {1875-5305},
mesh = {Humans ; *alpha-Synuclein/metabolism/genetics/antagonists & inhibitors ; *Synucleinopathies/metabolism/therapy/drug therapy/pathology ; *Parkinson Disease/metabolism/therapy/drug therapy/pathology ; Autophagy/drug effects ; Animals ; Oxidative Stress ; },
abstract = {Alpha-synuclein (α-syn) is a crucial protein involved in the pathogenesis of Parkinson's Disease (PD) and other synucleinopathies. It is important with respect to neuron health, regulation of α-syn protein synthesis, and its degradation. Numerous cellular pathways implicated in the process of autophagy, chaperone, and proteolysis play a vital role in the maintenance of α-syn protein homeostasis. Autophagy dysfunction defeats α-syn protein accumulation and neuroinflammation, as present in dementia with Lewy bodies and sporadic PD. Oxidative stress is another key factor that intensifies α-syn protein misfolding and aggregation, thereby leading to neurodegeneration. Involvement in the treatment of α-syn related disorders includes passive and active immunization, inhibitors of protein aggregation, gene silencing technology, modulators of synaptic function, and target drug delivery systems. Other α-syn related therapy approaches include the development of a novel herbal formulation focusing on the gut-brain axis and interventions designed to enhance protein quality control. As clinical trials move forward, minimizing challenges related to the target involved, biomarkers, and patient stratification is crucial to decoding these therapies into effective management. These insights not only advance our understanding of α-syn biology but also highlight the urgency of early and multi-targeted therapeutic interventions.},
}

Humans
*alpha-Synuclein/metabolism/genetics/antagonists & inhibitors
*Synucleinopathies/metabolism/therapy/drug therapy/pathology
*Parkinson Disease/metabolism/therapy/drug therapy/pathology
Autophagy/drug effects
Animals
Oxidative Stress

@article {pmid42116599,
year = {2026},
author = {Saha, T and Vats, T and Mehan, S},
title = {Rituximab Beyond Oncology: Targeting B-Cell-Mediated Immunomodulatory Therapy in Neurodegenerative and Neuropsychiatric Disorders.},
journal = {Immunopharmacology and immunotoxicology},
volume = {},
number = {},
pages = {1-77},
doi = {10.1080/08923973.2026.2671714},
pmid = {42116599},
issn = {1532-2513},
abstract = {Neurological and neuropsychiatric disorders, including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), and autoimmune encephalitis (AE), represent a growing global health burden due to their multifaceted pathophysiology and limited treatment options. These disorders are characterized by neuroinflammation, oxidative stress, protein aggregation, and blood-brain barrier (BBB) disruption, which contribute to neuronal damage and progressive functional decline. Emerging evidence underscores the pivotal role of B cells in driving disease progression through antibody production, antigen presentation, and cytokine release. Rituximab, a chimeric monoclonal antibody targeting CD20 on B cells, has shown promise as a potential immunomodulatory therapy for these conditions. Rituximab mediates its therapeutic effects via mechanisms including complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and induction of apoptosis. In MS, rituximab reduces pro-inflammatory cytokines, demyelination, and immune cell activity, thereby delaying disease progression. Preclinical studies suggest its neuroprotective potential in AD and PD by mitigating B-cell-mediated neuroinflammation and oxidative stress. Furthermore, rituximab demonstrates efficacy in AE, NMOSD, and MOGAD by depleting pathogenic B cells and reducing relapse rates. Despite its proven efficacy, rituximab poses risks such as hypogammaglobulinemia, infection, and infusion-related reactions, necessitating careful patient selection, continued monitoring, and optimization of dosing regimens. This review highlights rituximab's immunomodulatory mechanisms and its expanding role in neurodegenerative and neuropsychiatric disorders. While ongoing clinical trials explore its efficacy in ALS, depression, and schizophrenia, future research should focus on identifying biomarkers of treatment response, improving CNS penetration, and combining rituximab with other therapies to enhance safety and therapeutic outcomes. Rituximab's ability to target B-cell-driven pathology positions it as a promising agent in the evolving landscape of neuroimmunology.},
}

@article {pmid42095090,
year = {2026},
author = {Tremblay, E and Arbour, D and Vallée, J and Piovesana, R and Vallières, G and Mechichi, E and Robitaille, R},
title = {Neuromuscular junction innervation and motor function are preserved by restoring muscarinic signaling in perisynaptic glia in ALS.},
journal = {iScience},
volume = {29},
number = {5},
pages = {115565},
pmid = {42095090},
issn = {2589-0042},
abstract = {Neuromuscular junction (NMJ) denervation is an early pathological event in amyotrophic lateral sclerosis (ALS) causing motor dysfunction and paralysis. Glial cells at the NMJ, perisynaptic Schwann cells (PSCs), ensure a balance between maintenance and repair via muscarinic receptor signaling. However, in ALS mouse models, PSCs show an aberrant muscarinic hyperactivation. We posited that this excessive activation impairs the PSC capacity to support NMJ repair in ALS. Beginning at symptoms onset, SOD1 [G37R] mice received daily oral administration of darifenacin, a clinically approved type 3 muscarinic receptor antagonist, to reduce PSC hyperactivation. The treatment improved locomotion and preserved NMJ innervation in male mice, with comparable effects observed in females, and extended survival in males. Functional benefits were supported by signs of glial repair and enhanced survival of lumbar motor neurons. These preclinical data indicate that pathological PSC hyperactivity contributes to NMJ denervation in ALS and support therapeutic strategies targeting NMJs in ALS.},
}

@article {pmid42107892,
year = {2026},
author = {Chen, G and Zhao, C and Wang, C and Chen, G and Shi, J and Chen, H},
title = {Microglia crosstalk with T cells in neurodegenerative diseases: pathogenesis and treatment targets.},
journal = {International immunopharmacology},
volume = {182},
number = {},
pages = {116781},
doi = {10.1016/j.intimp.2026.116781},
pmid = {42107892},
issn = {1878-1705},
abstract = {Immune cells play a central role in driving inflammation and neurodegeneration across various neurological disorders. Central nervous system (CNS)-resident microglia and infiltrating T cells represent the innate and adaptive immune systems, respectively, and have been reported to contribute to the pathogenesis of neurodegenerative diseases individually. Growing evidence suggests that the encounter between activated microglia and infiltrating T cells amplifies their neurotoxic potential. In this review, we discussed alterations in microglial phenotype and function, and the contributions of different T cell subsets in neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Multiple sclerosis (MS), Amyotrophic lateral sclerosis (ALS) and glaucoma. We emphasized the crosstalk between microglia and T cells via antigen presentation, chemotactic signals, and pro-inflammatory mediators. We also explored emerging therapeutic strategies aimed at modulating T cell and microglial responses, as well as their interactions, for the treatment of neurodegenerative diseases.},
}

@article {pmid42111077,
year = {2026},
author = {Zhou, S and Li, X and Jiao, Y and Wu, J},
title = {Efficacy and safety of pharmacological and biological therapies for amyotrophic lateral sclerosis: a network meta-analysis.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1754716},
pmid = {42111077},
issn = {1664-2295},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder for which disease-modifying treatment options remain limited. This study aimed to systematically assess the efficacy and safety of pharmacological and biological therapies for ALS via a network meta-analysis (NMA).

METHODS: PubMed, EMBASE, Cochrane, and Web of Science were searched until February 25, 2025. Randomized controlled trials (RCTs) evaluating any pharmacological or biological intervention in ALS were eligible. Risk of bias was assessed using the Cochrane RoB 2 tool. A Bayesian NMA was performed in R (gemtc package). Effect estimates were expressed as mean differences (MDs) or risk ratios (RRs) with 95% credible intervals (CrIs). Interventions were ranked using the surface under the cumulative ranking curve (SUCRA). Publication bias was explored with funnel plots (Stata 18.0). Subgroup analyses were conducted for drug classes demonstrating significant efficacy and including at least three RCTs.

RESULTS: 109 trials involving 16,353 participants were included. The primary outcome was the ALS Functional Rating Scale-Revised (ALSFRS-R); secondary outcomes included forced vital capacity (FVC), mortality, and serious adverse events (SAEs). Compared with placebo, the combination of cell therapy and neuroprotective agents produced the greatest attenuation of ALSFRS-R decline (MD: 3.65, 95% CrI: 1.27-6.05) and was associated with the lowest SAE risk. Receptor agonists ranked highest for preservation of FVC, whereas alkaloids ranked first for mortality reduction; however, no intervention demonstrated a statistically significant survival benefit versus placebo. Within-class subgroup analyses further identified several specific agents, such as masitinib, talampanel, and EH301, as demonstrating relatively consistent efficacy, although substantial heterogeneity remained among enzyme inhibitors.

CONCLUSION: Cell therapy combined with neuroprotective agents may slow functional decline in ALS. Receptor agonists may help preserve respiratory function. Survival benefits remain inconclusive, underscoring the continued importance of comprehensive supportive care.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251000672, identifier CRD420251000672.},
}

@article {pmid42088060,
year = {2026},
author = {Hou, DL and Ho, J and Guan, T and Dong, XX and Zeng, L and Sanders, LH and Wu, YC and Tan, EK and Zhou, ZD},
title = {E3 ubiquitin ligases in neurodegenerative diseases.},
journal = {Military Medical Research},
volume = {13},
number = {1},
pages = {100032},
pmid = {42088060},
issn = {2054-9369},
mesh = {Humans ; *Ubiquitin-Protein Ligases/therapeutic use ; *Neurodegenerative Diseases/physiopathology ; },
abstract = {Neurodegenerative diseases (NDs) are characterized by progressive neuronal loss and proteostatic failure, driven by impaired clearance of misfolded proteins via the ubiquitin-proteasome system (UPS) and autophagy. In UPS, E3 ubiquitin ligases are crucial for regulating protein ubiquitination and degradation. Mutations in E3 ligases, along with dysfunctions of specific ligases such as Parkin, the C-terminus of HSC70-interacting protein (CHIP), and tripartite motif-containing proteins, have been identified as key factors in the buildup of amyloid-β, α-synuclein, tau, trans-active response DNA-binding protein 43, and mutant huntingtin. These accumulations are associated with NDs like Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Therapeutic strategies targeting E3 ligases, particularly proteolysis-targeting chimeras (PROTACs), are being developed for ND treatment and are currently in clinical trials. These approaches aim to enhance E3 ligase activity and promote selective protein degradation. Here, we examine how individual E3 ligases influence cell-fate decisions in NDs, showing that their substrate selection determines whether neurons survive or die. Building on this knowledge, we present an innovative therapeutic pipeline that includes ligase activators, PROTAC degraders, and miRNA switches, which are molecules designed to transition from research to clinical application.},
}

Humans
*Ubiquitin-Protein Ligases/therapeutic use
*Neurodegenerative Diseases/physiopathology

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

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

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

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

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

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

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

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

@article {pmid42055109,
year = {2026},
author = {Zhu, Y and Zhang, H and Zhang, Z and Song, G and Fu, J and Wang, H},
title = {The role of ultrasound in addressing neurodegenerative diseases: A review of mechanisms, applications, and challenges.},
journal = {Neuroscience},
volume = {606},
number = {},
pages = {126-137},
doi = {10.1016/j.neuroscience.2026.04.024},
pmid = {42055109},
issn = {1873-7544},
abstract = {With the aging of the global population, neurodegenerative diseases have become a major public health challenge. Currently, there are many limitations in the traditional treatment of neurodegenerative diseases, such as medicine, deep brain stimulation, transcranial magnetic stimulation, and transcranial direct current stimulation, including the inability to penetrate the blood-brain barrier (BBB) accurately and challenges in achieving precise and quantitative control during the treatment process. Ultrasound is an emerging neural modulation technology that stands out for its non-invasive nature, precise targeting, and unique ability to penetrate the BBB, demonstrating tremendous application potential. In this review, we summarized the common types of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS), and the limitations of traditional treatments. It delves into the physical principles, classification, mechanisms, and unique advantages of ultrasound therapy in neuromodulation. It provides a detailed account of the current status of application of ultrasound in neurodegenerative diseases, and represents the advantages and challenges currently faced by ultrasound therapy, which offers insights into future research directions and technological improvements.},
}

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

@article {pmid42036024,
year = {2026},
author = {Xiao, Y and Li, S and Cao, X},
title = {Comments on Chiu et al.'s " Comparative risk of reactivation of hepatitis B and C after treatment with biologics and targeted synthetic DMARDs in psoriasis and psoriatic arthritis: A 15-year multicenter cohort study".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.03.113},
pmid = {42036024},
issn = {1097-6787},
}

@article {pmid42031611,
year = {2026},
author = {Etik, DÖ and Dişibeyaz, S and Özmert, EH},
title = {Pancreatitis due to afferent loop syndrome: A case report and a brief review of the literature.},
journal = {Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajg.2026.02.003},
pmid = {42031611},
issn = {2090-2387},
abstract = {Afferent loop syndrome (ALS) should be a part of the differential diagnosis in a patient with acute pancreatitis with a history of gastric surgery. Although it is a rare clinical entity, association of ALS with acute pancreatitis can lead to poor clinical outcomes. Herein, we report the case of a 41-year-old man with a history of subtotal gastrectomy and Roux-en-Y gastric bypass who presented with abdominal pain and tenderness. Treatment of choice in this case was purely medical. A brief review of similar cases in the literature highlights the wide array of etiologies of acute pancreatitis due to ALS and reveals a broad spectrum of treatment options from medical to surgical.},
}

@article {pmid42033202,
year = {2026},
author = {Yusuf, S and Allen, MD and Kang, H and Phillips, DE and Genge, A},
title = {Opportunities and challenges related to participant stratification and cohort enrichment in ALS clinical trials.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/21678421.2026.2659128},
pmid = {42033202},
issn = {2167-9223},
abstract = {Amyotrophic lateral sclerosis (ALS) is marked by substantial clinical heterogeneity. This heterogeneity has impacted clinical trials by obscuring treatment effects and causing inefficiency. In this review, we summarize potential approaches for addressing heterogeneity in ALS via patient stratification and cohort enrichment methods and highlight potential challenges and limitations. These categories include stratification based on genetics, clinical characteristics (e.g. pattern of weakness, ALS Functional Rating Scale rates of progression), wet biomarkers (e.g. neurofilament light chain), neuroimaging, and novel methods employing statistical modeling or machine learning. These stratification methods have yet to be fully leveraged in clinical trial design. But these strategies must be employed thoughtfully and judiciously due to potential issues stratification can introduce. Future clinical trials should explore how participant stratification and cohort enrichment strategies may improve our ability to identify treatment effects, which may ultimately aid in the quest to establish more personalized medicine for persons with ALS.},
}

@article {pmid42031371,
year = {2026},
author = {Kamate, DP and Neumayr, A and Blum, J},
title = {Konzo: a nutrition-related tropical spastic paraparesis.},
journal = {BMJ case reports},
volume = {19},
number = {4},
pages = {},
doi = {10.1136/bcr-2025-270728},
pmid = {42031371},
issn = {1757-790X},
mesh = {Humans ; *Manihot/poisoning/adverse effects ; *Paraparesis, Tropical Spastic/etiology/diagnosis ; Male ; Adult ; },
abstract = {Konzo, derived from the Yaka term for 'tired legs' (Democratic Republic of the Congo, DRC) and also known as Buka-buka in the Bandundu region of DRC, is a nutrition-related neurotoxic disorder confined to sub-Saharan Africa. It predominantly affects impoverished and underserved rural populations who depend on bitter cassava as a dietary staple. Cases of konzo most often arise during the dry season or prolonged droughts, when limited water availability hinders adequate soaking or processing of cassava roots, preventing the effective removal of their toxic cyanide content prior to consumption. Clinically, konzo presents as an acute-onset, symmetrical, isolated motor disorder characterised by non-progressive yet permanent spastic paraparesis. In the absence of a curative treatment, the lifelong consequences of konzo impose a substantial burden on affected individuals and their communities.},
}

Humans
*Manihot/poisoning/adverse effects
*Paraparesis, Tropical Spastic/etiology/diagnosis
Male
Adult

@article {pmid42027094,
year = {2026},
author = {McElvaney, R and Starrs, B},
title = {Adolescents' Positive Experiences of Psychotherapy Following Sexual Abuse: A Systematic Review.},
journal = {Trauma, violence & abuse},
volume = {},
number = {},
pages = {15248380261437090},
doi = {10.1177/15248380261437090},
pmid = {42027094},
issn = {1552-8324},
abstract = {While a small body of work focuses directly on young people's experiences of psychotherapy following sexual abuse, to our knowledge, there are no existing reviews of this literature. This systematic review was conducted using Siddaway et al.'s guidelines. Inclusion criteria were: published between 2000 and 2022; used qualitative methodologies; and captured adolescents' perspectives. Eleven studies were identified, representing an aggregated sample size of 72 young people aged 12 to 18. Methodologies used included thematic analysis, content analysis, conversation analysis, and narrative analysis. A total of 9 of the 11 studies addressed experiences of individual therapy using semi-structured interviews; 2 studies explored experiences of group therapy through focus groups. The review identified three key processes that reflect adolescents' experiences: engagement, ambivalence to trust; painful processing: exercising agency; and integrating: taking responsibility. Young people struggled to engage in therapy, and it took time to build trust; they experienced improvements in mood and general well-being, facilitated by psychoeducation, talking about the abuse, experiencing difficult emotions, and learning coping skills. They described integrating their abuse experience into their life story, discovering their inner strength and resilience. The therapeutic experience was underpinned by two key support processes: the therapeutic relationship and a supportive environment outside of therapy. This review supports the components of trauma-focused therapy alongside personalizing psychotherapy to the needs of adolescents for agency and autonomy.},
}

@article {pmid42008764,
year = {2026},
author = {Stone, AK and Veinot, TC},
title = {Access to Technology-Mediated Community Mental Health Care Among Low-Socioeconomic Status Consumers With Serious Mental Illness: Qualitative Study.},
journal = {JMIR formative research},
volume = {10},
number = {},
pages = {e79608},
pmid = {42008764},
issn = {2561-326X},
mesh = {Humans ; *Mental Disorders/therapy/psychology ; *Health Services Accessibility/statistics & numerical data ; Qualitative Research ; Female ; Male ; Adult ; Middle Aged ; *Community Mental Health Services/statistics & numerical data/methods ; Telemedicine ; Social Class ; Poverty ; },
abstract = {BACKGROUND: Access to mental health care is critical for the effective management of serious mental illness (SMI), but consumers with low socioeconomic status (SES) have lower rates of service usage and worse retention in care. Digital technologies are often lauded as a way to bridge access gaps; however, little is known about how technology-mediated care may influence care access among low-SES consumers and how consumers use technology in care access.

OBJECTIVE: This study aimed to examine the applicability of Levesque et al's access framework to technology-mediated care for SMI and analyze how low-SES consumers use technology to facilitate care access. Furthermore, the study assesses whether and how technologies are involved in care access at multiple points within the process of accessing care.

METHODS: This study used 2 qualitative methods: ethnographic observations at a mental health treatment court and interviews with low-SES consumers with SMI using community mental health care (n=14) and key informant interviews with health and service providers working with this population (n=14). Observations occurred from July 2022 through September 2023, and interviews occurred between January 2022 and May 2024. Data analysis involved both inductive and deductive coding approaches. Data from both the interviews and observations were analyzed in NVivo and further triangulated through analytic memos.

RESULTS: Levesque et al's framework required several extensions to accommodate technology-mediated care related to SMI for low-SES consumers: (1) a cyclical rather than linear trajectory; (2) simultaneous care acquisition from multiple health and service providers; (3) staying in care long-term; (4) identification of both one-time and ongoing health needs; and (5) an emergency pathway for entering care. Consumers often faced challenges related to the varied digital requirements of each provider and a dearth of integrative, patient-facing tools like portals. Within this context, some consumers use mobile apps, communication, and telehealth technologies across various care access stages. Consumers used technology by figuring out how to navigate technology-mediated care, especially by leaning on others, such as case managers, for support. These others provided consumers with temporary technologies, showed them how to use technologies, and accompanied them through the process of using technology for accessing care.

CONCLUSIONS: This study highlights that accessing care is iterative and ongoing, involving multiple forms of co-occurring service provision. A theoretical contribution of this work is its extension of Levesque et al's care access framework to better reflect technology-mediated care for SMI among low-SES consumers. This work also underscores ongoing challenges for accessing technology-mediated care and the importance of human support in addressing access difficulties. Clinical implications include incorporating digital readiness assessments and providing comprehensive guidance on how consumers can effectively use technologies for care. Future work should investigate how technology-mediated care can make care access easier rather than harder.},
}

Humans
*Mental Disorders/therapy/psychology
*Health Services Accessibility/statistics & numerical data
Qualitative Research
Female
Male
Adult
Middle Aged
*Community Mental Health Services/statistics & numerical data/methods
Telemedicine
Social Class
Poverty

@article {pmid42013353,
year = {2026},
author = {Szabo, A},
title = {When treatment becomes the problem: A qualitative analysis of addiction components in rhinitis medicamentosa.},
journal = {Journal of behavioral addictions},
volume = {},
number = {},
pages = {},
doi = {10.1556/2006.2025.00461},
pmid = {42013353},
issn = {2063-5303},
abstract = {Prolonged use of topical nasal decongestants such as xylometazoline or oxymetazoline can lead to rhinitis medicamentosa (RM). This medication-induced condition is characterized by rebound congestion and compulsive reuse. A debated question is whether RM signifies physiological dependence, addiction, or simply a habit. This commentary aimed to evaluate Lakatos et al.'s (2025) work, which investigated this issue through qualitative interviews with 20 affected individuals. Using directed content analysis based on Griffiths' (2005) components model of addiction, Lakatos et al., identified all six elements (salience, mood modification, tolerance, withdrawal, conflict, and relapse) in patient histories. Lakatos et al. (2025) performed a timely and conceptually sophisticated study that connects addiction theory to a common otorhinolaryngological condition. Their qualitative approach captures the everyday lived experience of patients with RM with robust ecological validity and clinical relevance. However, the theory-driven analysis risks confirmation bias by fitting data to Griffiths' addiction model, and the small, convenience-based sample limits generalizability. Despite these constraints, the paper offers valuable insight into how negative reinforcement and conditioned anxiety sustain compulsive nasal spray use. Overall, it successfully bridges clinical observation and theoretical debate, advancing understanding of iatrogenic dependence within everyday medical practice.},
}

@article {pmid42013406,
year = {2026},
author = {Weemering, DN and van Unnik, JWJ and Genge, A and van den Berg, LH and van Eijk, RPA},
title = {Heterogeneity in the Analysis of the ALSFRS-R in ALS Clinical Trials and its Effect on the Validity and Precision of Trial Conclusions.},
journal = {Neurology},
volume = {106},
number = {9},
pages = {e214937},
doi = {10.1212/WNL.0000000000214937},
pmid = {42013406},
issn = {1526-632X},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/drug therapy/therapy ; *Randomized Controlled Trials as Topic/standards ; Reproducibility of Results ; *Disability Evaluation ; Severity of Illness Index ; },
abstract = {BACKGROUND AND OBJECTIVES: Disability rating scales play a pivotal role in clinical trials, but there is a notable lack of guidance on how to analyze these scales. Using amyotrophic lateral sclerosis as a case study, our aim was to explore how disability rating scales have been analyzed in completed clinical trials and to assess how these different approaches influence both the risk of false-positive findings and the statistical power to detect true treatment effects.

METHODS: We searched PubMed and Embase to systematically identify randomized, placebo-controlled clinical trials using the revised ALS functional rating scale (ALSFRS-R) as primary end point, with ≥20 randomly assigned patients and ≥12-weeks of follow-up. Data were extracted on the statistical analysis approaches and strategies for handling missing data. Variability in statistical methods was mapped to the various research questions that the trials aimed to address. A simulation study assessed how each statistical method influenced validity (false-positive rate) and precision (statistical power), using the Ceftriaxone trial data set to model a realistic trial scenario.

RESULTS: Our analysis included 45 randomized clinical trials, comprising a total sample size of 7,338 patients, and identified 39 distinct statistical methods using a mixture of longitudinal and cross-sectional techniques. Most trials (55.6%) did not use all available (longitudinal) ALSFRS-R measurements, resulting in suboptimal utilization of patient data and reduced statistical precision. Applying the different statistical methods to the same trial data set resulted in large differences in the estimated treatment effect size, ranging from a negative 1.33 to a positive 2.33 SD difference. Among the methods used, 38.9% (95% CI 24.8%-55.1%) were at risk of increasing false-positive rates, potentially contributing to the erroneous advancement of ineffective treatments. Statistical power of valid strategies varied widely, ranging from 17.9% to 78.2%.

DISCUSSION: Our results demonstrate considerable variability in statistical methods, with the choice of method able to influence the estimated treatment effects, potentially resulting in misleading conclusions and uncertainty about treatment effects. This limits the interpretability and comparability of clinical trials and influences clinical decision-making and drug development. Establishing statistical consensus recommendations could improve the utility of disability scales in clinical trials and accelerate progress toward effective therapies for neurodegenerative diseases.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/drug therapy/therapy
*Randomized Controlled Trials as Topic/standards
Reproducibility of Results
*Disability Evaluation
Severity of Illness Index

@article {pmid41821014,
year = {2026},
author = {Sligar, C and Sluyter, R and Ooi, L},
title = {Immune imbalance between T helper 1, T helper 17 and regulatory T cells fuels amyotrophic lateral sclerosis pathogenesis: disease trajectory, diagnosis and therapeutic implications.},
journal = {Journal of neuroinflammation},
volume = {23},
number = {1},
pages = {},
pmid = {41821014},
issn = {1742-2094},
support = {AL210095//U.S. Department of Defense/ ; CE230100021//Australian Research Council Centre of Excellence in Quantum Biotechnology/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal, rapidly progressive neurodegenerative disease, causing motor neuron loss and with limited treatment options. Although traditionally considered non-immune in origin, accumulating evidence implicates the adaptive immune system, particularly CD4[+] T cell subsets, as key modulators of disease progression. Among these, T helper (Th)1 and Th17 cells are elevated in ALS blood, cerebrospinal fluid and central nervous system tissues, and drive pro-inflammatory cascades. By contrast, regulatory T cells (Tregs) suppress pathogenic inflammation and maintain immune homeostasis; however, in ALS, both Treg number and suppressive function decline, with remaining Tregs showing reduced FOXP3 (the master transcription factor governing Treg function) expression and impaired regulatory capacity. Integrating human and preclinical evidence, we describe how ALS-associated proteins can act as autoantigens that trigger adaptive immune responses, and how Th1/Th17 amplification and Treg insufficiency couple to microglial activation, blood–brain barrier disruption, and motor neuron degeneration, to impact disease trajectory. Convergent signalling pathways and their intersection with metabolic stress provide a mechanistic link between the adaptive immune response and neurodegeneration. We outline biomarker frameworks, spanning immune cell phenotypes, cytokine signatures and transcriptional readouts that define alterations in Th1, Th17 and Treg responses in ALS. Finally, we address the emerging immunomodulatory therapeutic approaches, including the targeted blockade of specific cytokines and signalling pathways, augmentation of Treg number and function, and attenuation of Th1/Th17 activity, while preserving protective Tregs using selective small-molecule approaches. Collectively, the evidence we provide establishes adaptive T cell imbalance as a central, targetable driver of ALS neuroinflammation and provides a rationale for biomarker-guided therapeutics designed to rebalance adaptive immunity and slow disease progression.},
}

@article {pmid42000269,
year = {2026},
author = {Desnuelle, C and Couratier, P and Corcia, P and Duburcq, A and Torreton, E and Baffert, S and Nevoret, C and Turgeman, S},
title = {Treatment pathway, healthcare resource utilization and direct cost of ALS in France: A nationwide claims database study.},
journal = {Revue neurologique},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neurol.2026.02.159},
pmid = {42000269},
issn = {0035-3787},
abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a severe, progressive disease, associated with high clinical burden. The aim of this study was to estimate ALS-related healthcare resource utilization (HCRU), associated direct costs and their determinants in France.

METHODS: A retrospective cohort study was conducted among newly diagnosed patients with ALS identified between 2012 and 2022 (11 years) in the French National Health Data System (SNDS) through a validated algorithm. This incident population was compared with non-ALS controls (1:2) matched on age, sex, and region. Direct all-cause healthcare reimbursable costs were estimated. Survival, HCRU and direct costs were analyzed over the first five years after diagnostic.

RESULTS: A total of 16,814 newly diagnosed ALS patients were identified who could be matched with 33,628 non-ALS controls. The median age was 68.0 year and 55.3% were males. Over the first year after diagnosis, the direct all-cause medical cost per patient was €19,497 of which 47.2% was related to inpatient care, compared to €4,921 for controls which led to an ALS-attributable cost of €14,474 per patient per year. ALS patients had significantly (P<0.0001) higher HCRU than controls in all items of inpatient and outpatient care but especially for utilization of medical devices, frequencies of nurse and physiotherapist visits and acute care hospitalizations. The annual direct cost per patient who survived the successive annual period after diagnosis increased during the second, third and fourth year to €22,358, €22,276 and €21,372 respectively and then declined in year 5 to €19,720. These results largely underestimated the real cost of the management of ALS by not considering the out-of-pocket expenses associated with informal care and home renovation as well as productivity loss.

CONCLUSIONS: Patients with ALS had higher HCRU and direct medical cost, compared with controls. The economic burden of ALS was substantial even when restricted to the medical costs covered by the public health insurance system. There is an important need for novel therapies that might lower disease progression in early disease stages.},
}

@article {pmid42006515,
year = {2026},
author = {Cheung, N},
title = {Synaptic Plasticity Fragility Underlies a Microglial Pruning Continuum in Major Depressive Disorder and Amyotrophic Lateral Sclerosis.},
journal = {Cureus},
volume = {18},
number = {4},
pages = {e107259},
pmid = {42006515},
issn = {2168-8184},
abstract = {Background Major depressive disorder (MDD) and amyotrophic lateral sclerosis (ALS) are clinically distinct yet show intriguing comorbidity, often early in the disease course. We hypothesized a shared microglia-mediated synaptic pruning vulnerability, amplified differently by disorder-specific pathways, autophagy collapse in ALS versus RNA processing and immune dysregulation in MDD, thereby creating a biological continuum. Methods Using large-scale genome-wide association study (GWAS) from the Psychiatric Genomics Consortium (PGC) (MDD, N=829,249) and Project MinE (ALS, effective N=87,381), we applied Multi-marker Analysis of GenoMic Annotation (MAGMA) for gene- and set-level associations, Gene Set Enrichment Analysis (GSEA)/Differential Gene Set Enrichment Analysis (DGSEA) for pathway enrichment and differential enrichment, S-PrediXcan transcriptome-wide association study (TWAS) across 14 GTEx tissues, and linkage disequilibrium score regression (LDSC) for partitioned heritability and cross-trait genetic correlation. Eight gene sets (housekeeping controls, monoaminergic, neurosteroid, glutamatergic, synaptic pruning, autophagy/protein quality, RNA processing, and immune/neuroinflammation) were tested for convergence and divergence. Results Synaptic pruning emerged as the sole consistent cross-disorder signal, with robust enrichment in MDD (LDSC 1.32×, GSEA NES=1.415, p=0.0001) and nominal but consistent signals in ALS (GSEA NES=1.40, p=0.011; TWAS HLA-B). Autophagy dominated ALS (LDSC 2.20×, TWAS C9orf72 Z=13.43, GSEA NES=1.94) but was depleted in MDD. RNA processing and immune pathways were prominent in MDD (LDSC 1.48× and 1.89×, respectively), with only nominal signals in ALS. Overall genetic correlation was near zero (rg=-0.044, p=0.196). Conclusions These findings support a microglial pruning continuum model: shared pruning liability as the foundation, with autophagy failure driving ALS neurodegeneration and RNA/immune dysregulation shaping MDD stress sensitivity. The low rg explains the modest overlap, while pathway specificity accounts for comorbidity and divergent progression. This framework offers testable predictions for polygenic risk score (PRS) stratification, complement modulators in ALS mood subsets, and microglial therapies in treatment-resistant MDD.},
}

@article {pmid42006781,
year = {2026},
author = {Raikes, AC and Garza, M and Murrell, AN and Brinton, RD},
title = {Meta analysis of glucose metabolism across Alzheimer's, Parkinson's and ALS Reveals emergence of adaptive brain glucometabolic responses and associated neurological functional profiles.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.04.07.26350339},
pmid = {42006781},
abstract = {IMPORTANCE: Glucose metabolic dysregulation in brain is a common feature of late-onset age-associated neurodegenerative disease (A [2] ND). Prior meta-analyses have identified disease-specific effects compared to healthy, unimpaired individuals. Yet, a unifying A [2] ND glucose dysregulation spatial signature remains undescribed.

OBJECTIVE: To determine the common signature of dysregulated glucose metabolism on FDG-PET using activation likelihood estimation (ALE) meta-analyses across A [2] ND.

DATA SOURCES: Searches were conducted using MEDLINE, Embase, PsycINFO, Scopus, and Cochrane from inception through July 2025. The search terms included controlled vocabulary and keywords for four neurodegenerative diseases Parkinson Disease, Amyotrophic Lateral Sclerosis, Alzheimer Disease, and Multiple Sclerosis, Fluorodeoxyglucose F18, glucose, and positron-emission tomography (PET).

STUDY SELECTION: Studies comparing adults with late-onset neurodegenerative diseases to non-diseased controls using FDG-PET to quantify brain glucose uptake and reporting whole-brain coordinate findings in either Talairach or Montreal Neurological Institute space were included.

DATA EXTRACTION AND SYNTHESIS: Three researchers, assisted by an AI screening tool, screened 7275 potential titles and abstracts for inclusion. Full texts were then retrieved for potentially relevant articles and were evaluated by three researchers using prespecified inclusion/exclusion criteria.

MAIN OUTCOMES AND MEASURES: Cluster peak and subpeak coordinates, cluster-wise t-or Z-values, and annotations indicating the disease of interest, whether the outcome was for hyper-(disease group > control) or hypometabolism (disease group < control), were extracted from included texts and analyzed using ALE.

RESULTS: A total of 130 FDG-PET studies were included in the meta-analysis, with a combined sample of 5298 individuals with A [2] ND and 3499 controls. Meta-analyses revealed dysregulated glucose metabolism as a unifying feature across A [2] ND which included both hypo-and hypermetabolic patterns. Neuroanatomical metabolic pattern was unique and disease specific. Each A [2] ND metabolic phenotype was associated with unique and complex patterns of neurological functionalities.

CONCLUSIONS AND RELEVANCE: These data demonstrate dysregulated glucose metabolism as a common A [2] ND feature, suggesting responsive remodeling of neural bioenergetics. While hypometabolism is a common research focus, due to functional relevance, hypermetabolism may reflect a compensatory, maladaptive, or neuroinflammatory signal, that requires focused investigation. A [2] ND prevention and treatment efficacy may depend on addressing bidirectional metabolic dysregulation in addition to disease-specific drivers of pathology.},
}

@article {pmid42008451,
year = {2026},
author = {Pena, C and Sinar, MK and Koza, LA and Boehler, N and Buechler, E and Smith, AC and McGarr, A and Baybayon-Grandgeorge, AN and Herda, MS and Jaques, S and Linseman, DA},
title = {Preclinical study of red dragon fruit (Hylocereus polyrhizus) betacyanins in the G93A mutant hSOD1 mouse model of amyotrophic lateral sclerosis.},
journal = {Nutritional neuroscience},
volume = {},
number = {},
pages = {1-20},
doi = {10.1080/1028415X.2026.2661760},
pmid = {42008451},
issn = {1476-8305},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by loss of cortical and spinal motor neurons, oxidative stress, neuroinflammation, and mitochondrial dysfunction. Betacyanins, betalain pigments found in red dragon fruit and beetroot, display powerful anti-inflammatory and free-radical scavenging properties which may help ameliorate ALS pathology and slow disease progression. The present study characterized the therapeutic effects of a betacyanin-rich red dragon fruit extract (DFE) in the G93A mutant hSOD1 transgenic mouse model of ALS. Mice were treated orally with 5% (v/v) DFE in drinking water ad libitum, from disease onset until end-stage. DFE treatment had a statistically significant effect on survival, with an approximate 13-day extension of median lifespan in the treated G93A mutant hSOD1 group. Treatment with DFE also significantly preserved muscle strength and endurance, as assessed by grip strength and rotarod behavioral testing. This was associated with a modest but statistically significant preservation of gastrocnemius muscle weight in the DFE-treated group. Histopathological analyses demonstrated improvements in NMJ size and complexity, an increase in surviving spinal cord motor neurons, and a reduction in spinal cord astrogliosis in G93A mutant hSOD1 mice treated with DFE, when compared to their untreated mutant littermates. Overall, these findings indicate that DFE, or purified betacyanin compounds, should be investigated further as potential therapeutic agents for patients with SOD1-related ALS. Additional preclinical studies in non-SOD1 models of ALS will need to be completed to determine the potential benefit of betacyanin compounds in sporadic ALS.},
}

@article {pmid41992463,
year = {2026},
author = {Veith, PD and Leeming, MG and Chen, YY and Reynolds, EC},
title = {Cargo Secreted by the Type IX Secretion System of Porphyromonas gingivalis Are Tethered to O-Lipopolysaccharides via a Pentasaccharide Linker.},
journal = {MicrobiologyOpen},
volume = {15},
number = {2},
pages = {e70296},
pmid = {41992463},
issn = {2045-8827},
support = {1123866//Australian National Health and Medical Research Council/ ; DP200100914//Australian Research Council/ ; 20080108//Australian Government Department of Industry, Innovation and Science/ ; },
mesh = {*Porphyromonas gingivalis/metabolism/genetics/chemistry ; *Lipopolysaccharides/chemistry/metabolism ; *Bacterial Secretion Systems/metabolism ; Mass Spectrometry ; *Bacterial Proteins/metabolism ; *O Antigens/metabolism/chemistry ; Virulence Factors/metabolism ; },
abstract = {The Gram-negative oral pathogen, Porphyromonas gingivalis, uses the Type IX Secretion System (T9SS) to secrete major virulence factors (cargo proteins) and anchor them to the cell surface via a novel linking sugar, 2-N-seryl, 3-N-acetylglucuronamide (SAGA), which is a component of a specific type of lipopolysaccharide, A-LPS. The reported structure of the polysaccharide component (A-PS) was a repeating phosphorylated mannan whereas the PS of conventional O-LPS (O-PS) is a repeating Gal-Glu-Rha-GalNAc unit. Here, we have performed extensive mass spectrometric analyses of cargo protein-linked LPS with and without proteinase K treatment to determine the structure of A-LPS. Limited acid hydrolysis of the PS backbone with trifluoromethanesulfonic acid enabled long PS fragments linked to cargo-derived peptides to be identified for the first time. Unexpectedly, rather than finding A-PS units, up to eleven O-PS repeating units were found linked to cargo via a novel pentasaccharide linker designated A-LS, composed of SAGA-Hex-dHex(C4H4O3)(Pent)-Hex. In addition, samples from a wzzP/porT double mutant that produced free truncated O-PS were specifically hydrolyzed to cleave lipid A prior to MS analysis. In these samples A-LS was found attached to a limited number of O-PS repeating units that in turn were associated with a putative core oligosaccharide that included the LPS-specific sugar, 3-deoxy-d-manno-octulosonic acid (Kdo). The proposed structure of A-LPS explains all 11 genes specific to A-LPS biosynthesis, and provides the first structural evidence that cargo proteins such as the gingipains are anchored to the cell surface via a complete LPS molecule.},
}

*Porphyromonas gingivalis/metabolism/genetics/chemistry
*Lipopolysaccharides/chemistry/metabolism
*Bacterial Secretion Systems/metabolism
Mass Spectrometry
*Bacterial Proteins/metabolism
*O Antigens/metabolism/chemistry
Virulence Factors/metabolism

@article {pmid41994661,
year = {2026},
author = {Shah, T and Babcock, J},
title = {Tailored Interventions for Intimate Partner Violence: Examining the Differential Effectiveness of Randomized Communication Skills Exercises with Situationally and Characterologically Violent Couples.},
journal = {Journal of family violence},
volume = {},
number = {},
pages = {},
pmid = {41994661},
issn = {0885-7482},
support = {R03 MH066943/MH/NIMH NIH HHS/United States ; },
abstract = {PURPOSE: This study examines the differential effectiveness of communication skills interventions for situationally and characterologically violent male-perpetrated intimate partner violence (IPV).

METHOD: Using data from Babcock et al.'s (2011) proximal change experiment, latent class analysis was used to categorize IPV perpetrators into situational or characterological groups based on patterns of physical aggression, psychological abuse, and coercive control. Differential effectiveness of two communication-based interventions, "Accepting Influence," and "Editing out the Negative," and a placebo control condition was tested between the two groups.

RESULTS: We found that men in the situationally violent group reported significantly higher levels of increases in positive affect after both interventions compared to men in the characterologically violent group. On psychophysiological outcomes, significant interactions emerged showing that both active interventions led to a greater increase in post-intervention skin conductance for situationally violent men than for characterologically violent men. However, there was no evidence for differential responding based on other physiological variables, observed behaviors, or partners' self-report.

CONCLUSIONS: The current study contributes to scalable and practical solutions for treatment matching in experimental designs for IPV.},
}

@article {pmid41991114,
year = {2026},
author = {Zhang, W and Zhang, D and Han, L and Wang, D and Huo, D and Tan, X and Su, X and Wang, M and Xu, J and Cheng, J and Feng, H},
title = {The neuroprotective effect of guanabenz combined with α-lipoic acid in the hSOD1-G93A amyotrophic lateral sclerosis model.},
journal = {Brain research bulletin},
volume = {239},
number = {},
pages = {111890},
doi = {10.1016/j.brainresbull.2026.111890},
pmid = {41991114},
issn = {1873-2747},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, and although its pathogenesis is not yet clear, the multifactorial mechanisms that affect motor neuron death are intertwined, exacerbating the disease. Here, we explore the effectiveness and mechanism of a combination medication that combines guanabenz with α-lipoic acid in an in vitro as well as in vivo model of ALS. In this research, we initially determined the independent action targets and synergistic action targets of the two drugs through network pharmacology and molecular docking. Subsequently, we further investigated their specific action mechanisms in both in vivo and in vitro studies. In NSC34 cells transfected with hSOD1-G93A, we observed that the combined drugs could more effectively safeguard against cell damage and the production of reactive oxygen species (ROS) generated by mutant hSOD1, superior to monotherapy. This was achieved by upregulating the p-AKT/HO-1 pathway and synergistically suppressing the GRP78/CHOP pathway. Moreover, we found that combination drugs can effectively delay the decline in motor function of hSOD1-G93A transgenic mice by synergistically inhibiting GRP78/CHOP pathway. They can protect the motor neurons in the anterior horn of the spinal cord and suppress gliosis in hSOD1-G93A transgenic mice. In summary, our research indicates that the combination therapy of guanabenz and α-lipoic acid can serve as a viable treatment option for ALS.},
}

@article {pmid41987881,
year = {2026},
author = {Li, R and Wang, L and Bu, W and Zhang, X and Li, X and Li, J and Shen, J and Li, J and Cai, Z},
title = {Autologous SVF therapy modulates neuroinflammation in ALS: phase I trial demonstrating safety and CSF biomarker dynamics.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1784115},
pmid = {41987881},
issn = {1663-4365},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with limited treatments. Stromal vascular fraction (SVF), a cell population derived from autologous adipose tissue, exhibits multimodal immunomodulatory and neuroprotective properties, positioning it as a promising therapeutic candidate.

METHODS: This trial aimed to assess autologous stromal vascular fraction (SVF) safety and efficacy in patients with ALS. 26 patients received combined intravenous (0.5 × 106 cells/kg) and intrathecal (20 × 10[6] cells) autologous SVF (An exploratory second dose of SVF was administered intrathecally to three patients 45 days later). The trial is registered with the Chinese Clinical Trial Registry (ChiCTR2400091754).

RESULTS: SVF administration was well-tolerated. Five mild adverse events (adverse events, AEs) (subcutaneous bleeding, headache, and low-grade fever) occurred, with no serious AEs reported. Although ALSFRS-R scores showed non-significant improvement post-treatment, 15/26 participants (57.7%) self-reported symptomatic improvement after treatment. Critically, cerebrospinal fluid biomarker analysis revealed significant reductions in neurofilament light chain (NfL; Δ530.29 pg/mL, P = 0.039) and glial fibrillary acidic protein (GFAP; Δ622.23 pg/mL, P = 0.038), indicating attenuation of neuroaxonal degeneration and astroglial activation. While ALSFRS-R scores showed no significant change (Δ-0.53, P = 0.384), prognostic modeling identified female sex (OR = 0.011, P = 0.008) and shorter disease duration (OR = 1.35/month, P = 0.005) as predictors of response. Three patients who underwent the second treatment were well tolerated without any adverse events.

CONCLUSION: These findings indicate that Autologous SVF therapy might possess an acceptable safety profile for patients with ALS. The significant reduction in CSF NfL and GFAP levels provides objective evidence of their potential neuroprotective effects that modulates ALS-relevant neuroinflammation pathways. Female participants and those with shorter disease duration may derive greater benefits.},
}

@article {pmid41989758,
year = {2026},
author = {Ahmed, M and Volkening, K and Mclellan, C and Shoesmith, C and Balci, TB and Strong, MJ},
title = {Emerging strategies for interpreting variants of uncertain significance (VUS) in amyotrophic lateral sclerosis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-15},
doi = {10.1080/21678421.2026.2655734},
pmid = {41989758},
issn = {2167-9223},
abstract = {As the use of genetic testing for neurological diseases increases exponentially, interpreting variants of uncertain significance (VUS) has become a challenging problem. Nowhere has this become more evident than in amyotrophic lateral sclerosis (ALS) and the frontotemporal dementias (FTDs), both of which are complex heterogeneous disorders in which an increasing array of disease-causative and modifying genetic variants are observed. Moreover, while traditionally identified as distinct clinical syndromes, ALS and FTD are increasingly recognized to exist along a spectrum of clinical syndromes (termed the frontotemporal spectrum disorders of ALS; ALS-FTSD) with shared genetic risk. While VUS are generally not used in clinic for decision-making or counseling given their obvious limitations in being medically actionable, their correct interpretation is dynamic and rapidly evolving. VUS are increasingly the subject of intensive study as potential determinants of biological outcomes. It is timely therefore to review the current state of VUS interpretation and to critically evaluate how this can be applied to enhance both patient care and treatment decisions in the broader context of neurological disorders and more specifically in the context of ALS and ALS-FTSD. In doing so, we also explore the evolving challenge of defining pathogenicity of oligogenic inheritance in the context of multiple VUS detection in a single individual using an illustrative case example.},
}

@article {pmid41978444,
year = {2026},
author = {Stokholm, JB and Küchen, SHL and Møller, K and Gätke, MR and Svenstrup, K and Staehr-Rye, AK},
title = {Outpatient versus inpatient initiation of home mechanical ventilation in patients with amyotrophic lateral sclerosis - a protocol for a randomised trial.},
journal = {Danish medical journal},
volume = {73},
number = {4},
pages = {},
doi = {10.61409/A09250733},
pmid = {41978444},
issn = {2245-1919},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/complications ; *Noninvasive Ventilation/methods ; Telemedicine ; *Hospitalization ; *Home Care Services ; Quality of Life ; *Ambulatory Care/methods ; Male ; Randomized Controlled Trials as Topic ; Female ; Patient Satisfaction ; Middle Aged ; Patient Compliance ; *Hypoventilation/therapy/etiology ; },
abstract = {INTRODUCTION: In-home non-invasive ventilation (NIV) is associated with prolonged life and improved quality of life in patients with hypoventilation due to amyotrophic lateral sclerosis (ALS). The initiation of NIV is scheduled for a 1-2-night hospital stay. Telemedicine enables remote monitoring and adjustment of respiratory treatment. These possibilities should be examined to improve patients' experiences and adherence to treatment while freeing up resources in the healthcare system. We hypothesise that outpatient initiation of NIV combined with close telemonitoring in patients with ALS is non-inferior to standard initiation of NIV in adherence to treatment.

METHODS: This is a randomised, controlled, non-inferiority study. A total of 46 patients with ALS scheduled for initiation of NIV are randomised to start NIV either as an outpatient combined with close telemonitoring or during hospitalisation for 1-2 nights. The primary outcome is NIV adherence after three months, measured as minutes per day for the past seven days. Secondary outcomes are patient satisfaction with NIV treatment and its initiation after three months, assessed on a 1-5 rating scale.

CONCLUSIONS: The study is the first randomised, controlled study assessing the combination of outpatient initiation of NIV and close telemedical follow-up in patients with a progressive neuromuscular disease. The results may be applicable to other patient populations initiating NIV, e.g., patients with obesity hypoventilation syndrome.

FUNDING: The study was supported by grants from ALS-fonden and Muskelsvindfonden.

TRIAL REGISTRATION: NCT05829330.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/complications
*Noninvasive Ventilation/methods
Telemedicine
*Hospitalization
*Home Care Services
Quality of Life
*Ambulatory Care/methods
Male
Randomized Controlled Trials as Topic
Female
Patient Satisfaction
Middle Aged
Patient Compliance
*Hypoventilation/therapy/etiology

@article {pmid41985161,
year = {2026},
author = {Pervushina, EV and Rushkevich, YN and Turuspekova, ST and Kutlubaev, MA},
title = {Challenges in medical care for amyotrophic lateral sclerosis: a survey of physicians from Republic of Bashkortostan (Russia), Belarus, and Kazakhstan.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/21678421.2026.2652327},
pmid = {41985161},
issn = {2167-9223},
abstract = {OBJECTIVE: To identify and compare the main challenges in diagnosing and managing amyotrophic lateral sclerosis (ALS) from the perspective of neurologists in Republic of Bashkortostan (Russia), Belarus, and Kazakhstan.

METHODS: An anonymous online survey was distributed to neurologists via professional networks from May to October 2025. The questionnaire collected data on demographics, diagnostic and therapeutic approaches, barriers, and suggestions for improvement.

RESULTS: The survey included 294 neurologists. Over half (58.2%) diagnosed ALS less than once a year. Major diagnostic barriers were limited access to key investigations like electromyography (62.6%) and a lack of specialized ALS centers (37.8%). For treatment, 48% prescribed riluzole, while only 12.9% used edaravone. Critically low rates of gastrostomy placement and respiratory support provision (<10% of terminal patients) were noted by over 80% of respondents. Significant cross-country differences were found: neurologists in Kazakhstan utilized genetic testing and edaravone more frequently; neurologists in Belarus employed muscle/tongue ultrasound more often; neurologists in the Republic of Bashkortostan (Russia) reported higher use of speech therapy and gastrostomy. The most frequently proposed solutions were establishing specialized ALS centers (34%), enhancing physician training (20%), and improving palliative care services (16.5%).

CONCLUSIONS: This multinational survey provides important insights into ALS care in the studied countries, identifying key areas for further development. The results point to opportunities for enhancing diagnostic resources, therapeutic strategies, and palliative care approaches. Enhancing the quality of ALS care requires the development of specialized clinical pathways, the implementation of consensus-based protocols, and the expansion of professional education in multidisciplinary management.},
}

@article {pmid41985725,
year = {2026},
author = {Wintz, K and Lechtape, PL and Klenzendorf, J and Schemmert, S and Dingley, AJ and Willuweit, A and Kutzsche, J},
title = {Elucidation of the influence of the CaV2.2 calcium channel on ALS disease progression in the SOD1*G93A mouse model.},
journal = {Neurobiology of disease},
volume = {224},
number = {},
pages = {107396},
doi = {10.1016/j.nbd.2026.107396},
pmid = {41985725},
issn = {1095-953X},
abstract = {Amyotrophic lateral sclerosis (ALS) is a late-onset, fatal neurodegenerative disease affecting upper and lower motor neurons in the central nervous system. Drugs like riluzole, edaravone, and tofersen treat disease symptoms or are designed for a specific pathological mutation (e.g., SOD1), but they cannot prevent or halt the disease. For this reason, the search for new therapeutic strategies continues. The voltage-gated calcium channel CaV2.2 might be a novel target in ALS treatment as the channel was shown to be overexpressed in murine SOD1*G93A cortical neurons, resulting in higher mortality. Further, murine SOD1*G93A motor neurons showed increased calcium currents mainly by an increased expression of the CaV2.2 channel. In addition, inhibition of the channel was hypothesized as mode of action for the all-d-enantiomeric peptide RD2RD2, a novel drug candidate for the treatment of ALS, which already demonstrated its efficacy in SOD1*G93A mice. To investigate the influence of the CaV2.2 channel on the progression of disease symptoms in the SOD1*G93A mouse model, a new double-transgenic line was created, combining the ALS phenotype with a knockout of the CaV2.2 channel. The study showed that the CaV2.2 knockout on the SOD1*G93A background led to reduced SHIRPA and splay scores, and a delayed disease onset. Additionally, differences were detected between wildtype and single-transgenic CaV2.2 knockout mice. However, survival was not affected. Post mortem analysis of human tissue found more CaV2.2 in ALS cases in comparison to healthy control subjects confirming involvement of the channel in human ALS. These results indicate that the CaV2.2 calcium channel may play an influential role in early disease progression of ALS.},
}

@article {pmid41973722,
year = {2026},
author = {Ge, D and Wu, L and Yang, J and Sun, J and Wang, J and Wang, J and Song, H and Wei, R and Xu, Z and Zhao, B and Sun, R and Wang, Y},
title = {Adverse events in different administration routes of Edaravone: A pharmacovigilance study based on the FDA adverse event reporting system.},
journal = {PloS one},
volume = {21},
number = {4},
pages = {e0346797},
pmid = {41973722},
issn = {1932-6203},
mesh = {*Edaravone/adverse effects/administration & dosage ; Humans ; United States ; United States Food and Drug Administration ; *Adverse Drug Reaction Reporting Systems ; *Pharmacovigilance ; Female ; Male ; Middle Aged ; Administration, Oral ; Amyotrophic Lateral Sclerosis/drug therapy ; Aged ; Administration, Intravenous ; Adult ; *Drug-Related Side Effects and Adverse Reactions/epidemiology ; },
abstract = {The U.S. Food and Drug Administration (FDA) approved intravenous edaravone for the treatment of amyotrophic lateral sclerosis (ALS) in 2017, followed by the approval of the oral formulation in 2022. This study aims to utilize the FDA#39;s Adverse Event Reporting System (FAERS) to investigate the spectrum and timing of adverse events (AEs) associated with edaravone administration, employing repeatability analysis, the Reporting Odds Ratio (ROR) approach, Weibull distribution, and stratification methods. The investigation focuses on data collected from the first quarter of 2017 through the fourth quarter of 2024, aiming to identify adverse event signals and their temporal patterns related to both intravenous and oral edaravone administration. In total, 3,262 records of edaravone-related adverse reactions were identified; among these, 1,534 incidents were associated with intravenous administration, while 453 incidents pertained to oral administration. The analysis revealed distinct adverse reaction profiles for the two routes of administration. Notably, the spectrum of adverse reactions resulting from oral administration predominantly involved the respiratory system, digestive system, and skin damage. In contrast, intravenous administration was more frequently linked to complications associated with invasive procedures and local tissue damage. Furthermore, the timing of adverse reactions exhibited significant variability between the two routes. Weibull distribution analysis indicated that the median onset time for adverse reactions following intravenous administration was 35 days, whereas for oral administration, it was 27 days. Both analytical approaches identified early failure signals, suggesting that the risk of adverse events diminishes over time.},
}

*Edaravone/adverse effects/administration & dosage
Humans
United States
United States Food and Drug Administration
*Adverse Drug Reaction Reporting Systems
*Pharmacovigilance
Female
Male
Middle Aged
Administration, Oral
Amyotrophic Lateral Sclerosis/drug therapy
Aged
Administration, Intravenous
Adult
*Drug-Related Side Effects and Adverse Reactions/epidemiology

@article {pmid41977439,
year = {2026},
author = {Bougea, A},
title = {Targeting Non-Coding RNAs as a Potential Therapeutic and Delivery Strategy Against Neurodegenerative Diseases.},
journal = {International journal of molecular sciences},
volume = {27},
number = {7},
pages = {},
pmid = {41977439},
issn = {1422-0067},
mesh = {Humans ; *Neurodegenerative Diseases/genetics/therapy ; Animals ; *RNA, Untranslated/genetics ; MicroRNAs/genetics ; RNA, Long Noncoding/genetics ; Genetic Therapy/methods ; },
abstract = {Neurodegenerative diseases (NDs), including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (ALS), represent a growing global health challenge characterized by progressive neuronal loss and a lack of definitive disease-modifying treatments. This review explores the emerging potential of targeting non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and exosomal RNAs, to modulate pathogenic molecular pathways and address the underlying molecular origins of neurodegeneration. We evaluate the integration of advanced computational techniques for RNA structure prediction and gene regulatory network analysis, alongside chemical engineering strategies-such as Locked Nucleic Acids (LNAs) and phosphorothioate modifications-aimed at enhancing the stability and specificity of RNA-based molecules. Furthermore, we analyze cutting-edge delivery and editing technologies, including nanotechnology-driven solutions for precise neuronal targeting and the CRISPR/Cas13 system for direct ncRNA manipulation.The findings indicate that while challenges in delivery efficiency and long-term efficacy persist, the synergy of chemical engineering and computational modeling significantly improves the therapeutic profile of ncRNAs, with exosomal pathways offering a novel route for intercellular signaling modulation and biomarker discovery. Therapeutic interventions directed at specific clinical targets, such as miR-34a and BACE1-AS, demonstrate the capacity to influence protein aggregation and neuroinflammatory cascades. Although ncRNA-based therapies are currently in nascent stages, ongoing technological advancements in RNA editing and nanotechnology offer a transformative framework that could redefine the future of ND treatment and successfully halt disease progression rather than merely managing symptoms.},
}

Humans
*Neurodegenerative Diseases/genetics/therapy
Animals
*RNA, Untranslated/genetics
MicroRNAs/genetics
RNA, Long Noncoding/genetics
Genetic Therapy/methods

@article {pmid41954708,
year = {2026},
author = {Luo, S and Zheng, Q and Wang, M and Wang, X and Ma, B and Liu, D and Li, L and Lu, Y and Sang, D and Yang, L},
title = {Synergistic Neuroprotection of MFSD2A Overexpression and DHA Supplementation in Amyotrophic Lateral Sclerosis.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41954708},
issn = {1559-1182},
support = {202304295107020076//Clinical Medicine Research and Translational Project of Anhui Province/ ; 2022AH051480//University Natural Science Research Project of Anhui Province/ ; 2022//Anhui Province "Jianghuai Famous Doctors" Cultivation Project/ ; 2020byzd169//Natural Science Key Project of Bengbu Medical College/ ; BB21B032//Bengbu Think Tank Construction and Social Science Planning Project/ ; 20230131//Bengbu science and technology innovation guidance project/ ; BBWK2024B204//Bengbu Health and Health Research Project Intestinal Transplantation Technology Clinical Special General Project/ ; AHWJ2024Aa30089//Anhui Province Health and Health Research Project Youth Project/ ; },
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology/genetics ; *Docosahexaenoic Acids/pharmacology/therapeutic use/administration & dosage ; Male ; *Neuroprotection/drug effects ; *Dietary Supplements ; *Neuroprotective Agents/pharmacology/therapeutic use ; Mice ; Mice, Transgenic ; Mice, Inbred C57BL ; Oxidative Stress/drug effects ; Humans ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron loss, with limited effective therapies. Docosahexaenoic acid (DHA) exhibits neuroprotective effects, but its limited transport across the blood-brain barrier (BBB) restricts clinical utility. Major facilitator superfamily domain-containing protein 2A (MFSD2A) is the primary transporter of DHA into the central nervous system, yet its role in ALS remains unclear. This study investigated the therapeutic potential and mechanisms of MFSD2A overexpression combined with DHA supplementation in male SOD1^G93A ALS mice. We found that MFSD2A expression was markedly reduced in ALS mice and correlated with impaired motor function and neuronal damage. DHA supplementation or MFSD2A overexpression partially improved behavioral deficits, while their combination produced synergistic benefits. Histological analyses revealed attenuated neuronal degeneration and reduced muscle fibrosis following combined treatment. Furthermore, MFSD2A physically interacted with the E3 ubiquitin ligase TRIM21, regulating glycolytic metabolism by modulating key enzymes (GLUT1, HK2, LDHA, PDK1) and products (lactate/pyruvate and NADH/NADPH ratio). TRIM21 knockdown reversed MFSD2A-mediated neuroprotection and impaired glycolytic metabolism, indicating its critical role in this pathway. The combined intervention also suppressed systemic inflammation and oxidative stress by decreasing pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and restoring antioxidant enzyme activities (GSH-Px), while reducing lipid peroxidation (MDA). These findings suggest that MFSD2A facilitates DHA's neuroprotective effects by enhancing glycolytic metabolism and mitigating neuroinflammation. This study highlights MFSD2A and DHA as promising therapeutic targets in ALS and provides novel insights into overcoming BBB transport limitations for neurodegenerative disease treatment.},
}

Animals
*Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology/genetics
*Docosahexaenoic Acids/pharmacology/therapeutic use/administration & dosage
Male
*Neuroprotection/drug effects
*Dietary Supplements
*Neuroprotective Agents/pharmacology/therapeutic use
Mice
Mice, Transgenic
Mice, Inbred C57BL
Oxidative Stress/drug effects
Humans

@article {pmid41956140,
year = {2026},
author = {Wang, P},
title = {Response to Tahir et al.'s commentary on our BSRS causal framework for longitudinal well-being data.},
journal = {Journal of biomedical informatics},
volume = {},
number = {},
pages = {105037},
doi = {10.1016/j.jbi.2026.105037},
pmid = {41956140},
issn = {1532-0480},
abstract = {We thank Tahir et al. for their respectful and constructive commentary on our article proposing the Behaviour Self-Regulation Score (BSRS) and a causally-informed workflow for longitudinal self-report well-being data (Wang et al., 2026). We clarify that (i) the completeness threshold was established a priori to support stable estimation, and we reported included-versus-excluded baseline comparisons showing no statistically significant differences on key measured variables; (ii) while treatment- and outcome-related items were collected via an evening daily questionnaire, we defined day-level temporal ordering and stated identification assumptions; and (iii) our causal interpretation is conditional on standard assumptions, which we complemented with exposure-specific backdoor adjustment and three refutation checks (random common cause, placebo permutation, and data-subset stability), while transparently noting remaining limitations including self-report bias and potential time-varying confounding. We welcome the opportunity to clarify these points in response to the Letter to the Editor.},
}

@article {pmid41953903,
year = {2026},
author = {Ansari, MS and Heidari, S and Pourgholi, E and Bahramian, S and Tootoonchi, N and Vahabi, SM},
title = {Janus Kinase Inhibitors for Treatment of Palmoplantar Pustulosis, Generalized Pustular Psoriasis, and Palmoplantar Pustular Psoriasis: A Systematic Review of the Literature.},
journal = {Health science reports},
volume = {9},
number = {4},
pages = {e72301},
pmid = {41953903},
issn = {2398-8835},
abstract = {INTRODUCTION: Palmoplantar pustulosis (PPP) is a chronic, recurrent, inflammatory disease and assumed to be a subtype of psoriasis. Pustular psoriasis (PP) is a chronic inflammatory disease that is further subclassified into various entities with different presentations including generalized pustular psoriasis (GPP) and palmoplantar pustular psoriasis (PPPP). Given the central role of the JAK-STAT pathway in cytokine signaling, this systematic review evaluated the effectiveness and safety of Janus kinase inhibitors (JAK-I) in these PP subtypes.

METHODS: Following PRISMA 2020 guidelines, a systematic search was conducted across PubMed/Medline, Scopus, Web of Science, and Embase up to November 13, 2025. Eligible studies included assessing JAK-I in PPP, GPP, or PPPP. Exclusion criteria were reviews, articles without full-text, SAPHO syndrome, and animal/in vitro studies. Risk of bias was assessed using the NHLBI quality assessment tool for clinical studies and Murad et al.'s checklist for case reports/series.

RESULTS: Thirty-seven studies were included (29 case reports, 4 case series, and 4 clinical studies), encompassing 157 patients (60.5% female; mean age 46.8 years). Treatments involved tofacitinib, upadacitinib, baricitinib, abrocitinib, and topical ruxolitinib. In PPP, pooled meta-analysis demonstrated a PPPASI-50 response rate of 85.5% (95% CI, 71.3-93.3), with upadacitinib achieving 90.9% (95% CI, 81.7-95.7). Case reports and series showed 88.1% clearance or near-clearance within a mean of 2.5 months. GPP patients (n = 5) achieved rapid clearance or marked improvement within 2-12 weeks. Adverse events (18.7%) were generally mild, most commonly acneiform eruptions, headache, and transient liver enzyme elevations, with no severe events reported.

CONCLUSION: JAK-I demonstrate high response rates and rapid improvement with manageable safety profiles. However, the current evidence is limited by small sample sizes, short follow-up durations, and reliance on case-based data. They represent a promising therapeutic option and warrant further evaluation in larger controlled studies to establish long-term efficacy and safety.},
}

@article {pmid41932651,
year = {2026},
author = {Scaricamazza, S and Nesci, V and Fenili, G and Tiberi, M and Percio, A and Rosina, M and Salvatori, I and Riggio, F and Candelise, N and Pieroni, L and Greco, V and Chiurchiù, V and Ferri, A and Valle, C},
title = {The hypothalamus is an early site of mitochondrial failure and neuro-immune circuit disruption in amyotrophic lateral sclerosis.},
journal = {Molecular metabolism},
volume = {},
number = {},
pages = {102360},
doi = {10.1016/j.molmet.2026.102360},
pmid = {41932651},
issn = {2212-8778},
abstract = {BACKGROUND: Metabolic dysfunction is a defining feature of amyotrophic lateral sclerosis (ALS), emerging early and strongly associated with disease progression and prognosis. While systemic hypermetabolism is well documented, the central mechanisms underlying energy imbalance remain poorly understood. The hypothalamus, a key regulator of whole-body energy homeostasis, has recently been implicated in ALS, but its mechanistic contribution to metabolic failure and disease progression remains unclear.

METHODS: We analyzed the hypothalamus SOD1-G93A mouse model using proteomics (ProteomeXchange ID: PXD070931), mitochondrial bioenergetic assays, immunofluorescence, flow cytometry, and gene expression to assess hypothalamic mitochondrial function, glial activation, and melanocortin system integrity. Limited analyses in the hFUS model confirmed the presence of key hypothalamic alterations, supporting a shared vulnerability across ALS models. In SOD1-G93A mice, the metabolic modulator trimetazidine (TMZ) was administered presymptomatically to evaluate effects on hypothalamic pathology, metabolic regulation, disease onset, and survival.

FINDINGS: We provide the first evidence that mitochondrial bioenergetic defects arise specifically in the hypothalamus of ALS models before symptom onset. Proteomic profiling revealed dysregulation of mitochondrial pathways, while functional assays confirmed impaired bioenergetics in the hypothalamus. These deficits were accompanied by local pro-inflammatory activation of astrocytes and microglia, mitochondrial dysfunction in glial cells, and early disruption of the arcuate nucleus melanocortin system. Limited analyses in hFUS mice confirmed selective hypothalamic vulnerability. Early TMZ treatment in SOD1-G93A mice specifically restored hypothalamic bioenergetics, normalized local glial activation and melanocortin signaling, delayed disease onset, and extended survival.

INTERPRETATION: These findings establish the hypothalamus as an early and selectively vulnerable site in ALS, where region-specific mitochondrial dysfunction contributes to metabolic and neuroinflammatory alterations. Targeting hypothalamic bioenergetics represents a promising therapeutic strategy.},
}

@article {pmid41943810,
year = {2026},
author = {Khandelwal, N and Geremakis, C and Riaz, F and Ryan, G and Saundankar, V and Sheer, R and Suehs, B},
title = {Epidemiology, Patient Characteristics, Real-World Treatment Patterns, and Healthcare Utilization and Spending for Patients with Multifocal Motor Neuropathy: A US Claims-Based Analysis.},
journal = {Journal of health economics and outcomes research},
volume = {13},
number = {1},
pages = {111-119},
pmid = {41943810},
issn = {2327-2236},
abstract = {BACKGROUND: Multifocal motor neuropathy (MMN) is a rare, progressive neurological disease characterized by asymmetrical limb weakness. The real-world healthcare burden of MMN is not well established.

OBJECTIVES: To characterize the epidemiology, diagnostic procedures, treatment patterns, healthcare resource utilization (HCRU), and healthcare spending associated with MMN in patients in the US.

METHODS: This retrospective, observational claims study extracted data from the Humana Healthcare Research Database, comprising US Medicare Advantage plan members. Eligible patients were aged 18-89 years, had ≥2 nondiagnostic medical claims (the first being the index date) associated with an MMN diagnosis code (January 1, 2017-June 30, 2022), and continuous enrollment for 12 months pre-index (baseline) and post-index (follow-up). Patients with amyotrophic lateral sclerosis, chronic inflammatory demyelinating neuropathy, or immunosuppressant use were excluded. Outcomes were assessed during the baseline and follow-up periods.

RESULTS: Deidentified data were extracted for 248 patients with MMN. Median (Q1, Q3) age at index was 70.0 (62.0, 77.0) years; most patients were male (53.6%) and White (78.2%). Diagnostic procedures included (baseline/follow-up periods) spinal magnetic resonance imaging (21.4%/18.1%), nerve conduction studies (19.8%/14.5%), and electromyography (17.7%/15.3%). Anticonvulsants, pain medications, corticosteroids, and central muscle relaxants were the most commonly used medications. Overall, 5.2% of patients had intravenous immunoglobulin (IVIG) during follow-up. Mean (standard deviation [SD]) time from index to IVIG initiation was 63.1 (52.2) days, with 6.5 (5.4) administrations, 28.7 (22.9) days between administrations, and 147.5 (133.9) days of total treatment. For all-cause HCRU, 23.8% of patients had ≥1 inpatient stay in the baseline period, with mean (SD) length of stay of 12.7 (14.5) days; during follow-up, 27.8% of patients had ≥1 inpatient stay (length of stay, 13.4 [16.2] days). During the baseline/follow-up periods, 43.1%/46.8% of patients had ≥1 emergency department visit, and 18.5%/28.6% used telehealth services. Median all-cause spending (baseline/follow-up) was 11   299 / 16 074 for total healthcare, 6745 / 10 630 for medical resources, and 1374 / 1701 for pharmacy.

DISCUSSION: Further studies are needed to enhance our understanding of the real-world diagnostic and treatment patterns associated with MMN and to determine long-term clinical outcomes.

CONCLUSION: These real-world data highlighted the considerable burden associated with MMN on the healthcare system and patients.},
}

@article {pmid41945020,
year = {2026},
author = {Qin, K and Xu, Y and Liang, W},
title = {Letter to the editor regarding "Comparison of the therapeutic effects of modified 15-mm incision minimally invasive approach with the conventional approach in the treatment of AO 23-B3 distal radius fractures".},
journal = {Injury},
volume = {},
number = {},
pages = {113224},
doi = {10.1016/j.injury.2026.113224},
pmid = {41945020},
issn = {1879-0267},
abstract = {This letter comments on Liu et al.'s study comparing a modified 15 mm mini-incision volar plating approach to conventional ORIF for AO 23-B3 distal radius fractures. While endorsing the reported cosmetic and recovery benefits of MIPO, we highlight the need for longitudinal functional data during early rehabilitation and detailed classification of postoperative complications. Addressing these gaps would enhance the understanding of the early recovery trajectory and safety profile of this minimally invasive technique.},
}

@article {pmid41953830,
year = {2026},
author = {Baby, P and John, J and Binesha, PB and Keerthipriya, MS and Ramazanu, S and Nashi, S and Menon, D and Vengalil, S and Thomas, PT and Nalini, A},
title = {Amyotrophic Lateral Sclerosis: A Cross-sectional Survey on Sialorrhoea.},
journal = {Indian journal of palliative care},
volume = {32},
number = {1},
pages = {85-90},
pmid = {41953830},
issn = {0973-1075},
abstract = {OBJECTIVES: One of the major distressing symptoms related to Amyotrophic Lateral Sclerosis (ALS) is excessive drooling of saliva, also termed sialorrhoea. Evaluating its prevalence and severity among Indian patients with ALS is essential for understanding the magnitude and impact of the problem. A cross-sectional survey was conducted to estimate the prevalence and severity of sialorrhoea among individuals diagnosed with ALS. We also intended to assess the current pharmacological management practice for sialorrhoea in ALS patients.

MATERIALS AND METHODS: Patients with ALS enrolled in the Neuropalliative Registry of a quaternary care centre for neurological disorders were included in the study. As part of routine follow-up, telephonic interviews were conducted with either the patients or their next of kin. The extent of sialorrhoea was assessed using the sialorrhoea scoring scale.

RESULTS: Seventy patients were included in the study. The mean age at presentation was 51.8 (standard deviation [SD]-12.8) years. The majority were males (74.3%). The mean duration of illness was 21.6 (SD 15.7) months. The majority (80%) had limb onset ALS. Forty per cent of the patients in the study had some degree of sialorrhoea. Mild drooling was present in 15 patients (21.4%), moderate in 9 (12.9%), severe in 2 (2.9%) and profuse drooling in another 2.9% of patients. A total of 9 patients (12.9%) were receiving anticholinergic medication. Patients diagnosed with bulbar onset ALS had a significantly greater degree of sialorrhoea than those with limb onset presentation (P = 0.008). In addition, a longer duration of illness showed a positive correlation with the severity of sialorrhoea (r = 0.30, P = 0.012).

CONCLUSION: Sialorrhoea is a prevalent and clinically significant symptom in individuals with ALS. The severity of sialorrhoea is greater in patients with bulbar onset ALS and tends to increase with longer illness duration. A substantial proportion of patients may benefit from recommended treatment for excessive salivation and saliva-related issues. This study underscores the need for screening of distressing symptoms as sialorrhoea, in ALS patients. The treating teams need to have a heightened awareness regarding the same so that treatment options can be offered to the patients.},
}

@article {pmid41930586,
year = {2026},
author = {Pavithra, N and Begum, RF and Ashwini, ST and Nirenjen, S and Singh, A and Manisha, M and Sridevi, S and Singh, SA},
title = {AI-Driven Biomarker Discovery in Motor-Related Neurodegenerative Diseases.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273436955260126215111},
pmid = {41930586},
issn = {1996-3181},
abstract = {Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and spinocerebellar ataxias (SCAs) are examples of neurodegenerative disorders (NDDs) that share overlapping neuropathological processes and largely affect motor coordination. For early diagnosis, illness monitoring, and treatment targeting, it is essential to find trustworthy biomarkers that represent motor circuit dysfunction. The purpose of this study is to summarize the state of the art regarding molecular, neurochemical, and imaging biomarkers that are pertinent to motor impairment and to investigate the function of artificial intelligence (AI) in their identification and verification Methods: With an emphasis on biomarker discovery, validation, and AI/ML applications in PD, HD, ALS, and SCAs, a thorough literature search was carried out in the PubMed, Scopus, and Google Scholar databases for research published between 2015 and 2025. The motor-specific correlations of key molecular (α-synuclein, tau, neurofilament light chain, TDP-43, mutant huntingtin), neuroimaging, and digital biomarkers were carefully examined Results: AI-driven methods, such as deep learning and machine learning, have shown great promise in combining multimodal data from digital, fluid, and imaging sources. These techniques enhanced the detection of disease-specific biomarker signatures, especially those associated with deficiencies in motor coordination Discussion: Data heterogeneity, biomarker standardization, model interpretability, and limited cross-disease validation are still issues despite encouraging developments. Improving the clinical reliability of AI-based biomarker models requires filling in these gaps Conclusion: An effective foundation for deciphering intricate motor neurological pathways is provided by AI-assisted biomarker discovery. Transparent algorithms, multicenter data integration, and ethical frameworks should be given top priority in future research to guarantee clinical translation and better patient stratification.},
}

@article {pmid41930760,
year = {2026},
author = {Patel, S and Sood, R and Shrivastava, S and Jeengar, MK},
title = {Neuroprotective Mechanisms of Erucin: Therapeutic Pathways in Neurodegenerative Disorders.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X385491251208144807},
pmid = {41930760},
issn = {1875-6190},
abstract = {Neurodegenerative Disorders (NDDs), including Alzheimer's Disease (AD), Parkinson's Disease (PD), Huntington's Disease (HD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), and other less prevalent conditions, represent a growing challenge in medical science due to their progressive nature and the absence of curative treatments. Cruciferous vegetables, such as those from the Brassicaceae family and other species in the Brassicales order, have been reported to offer potential benefits for treating and preventing NDDs. Their neuroprotective effects have been attributed to secondary metabolites, glucosinolates (GLs), and their hydrolytic products, isothiocyanates (ITCs). One of these ITCs is Erucin (ERU), chemically known as 4-isothiocyanatobutane, which is a specific type of ITC. ERU is the isothiocyanate derivative of erucic acid and is structurally related to sulforaphane (SFN), another well-known ITC. This review aims to synthesize current scientific knowledge on ERU's mechanisms of action in neurodegeneration, highlighting preclinical evidence supporting its neuroprotective effects in diseases such as AD and PD, and suggesting its potential as a treatment strategy for NDDs. Preliminary studies suggest that ERU may confer neuroprotection through antioxidative stress pathways, modulation of neuroinflammatory responses, and upregulation of neurotrophic factors. This article discusses ERU's chemical properties, pharmacokinetics, and observed impacts on neurodegenerative models, suggesting potential therapeutic pathways it may influence, thereby highlighting its promise as a future component of neuroprotective strategies against NDDs.},
}

@article {pmid41917198,
year = {2026},
author = {Yin, H and Ren, Z and Zhang, Y and Wang, Y and Sun, Y and Fu, X and Yan, W and Zhang, F and Zeng, L},
title = {Lisinopril activates BI1 to reprogram lipid metabolism and restore autophagy in ALS.},
journal = {Communications biology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s42003-026-09930-2},
pmid = {41917198},
issn = {2399-3642},
support = {20250206017ZP//Department of Science and Technology of Jilin Province (Jilin Province Science and Technology Department)/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) involves disrupted lipid metabolism. Bax inhibitor 1 (BI1), an endoplasmic reticulum protein downregulated in ALS neuroprotective, represents a therapeutic target, but its metabolic regulatory mechanisms are incompletely understood. Using transcriptomics in skeletal muscle of ALS mice pre- and post-BI1 treatment, we identified BI1-regulated pathways. Structure-based virtual screening of FDA-approved compounds nominated lisinopril as a BI1 activator. Lisinopril upregulated BI1 protein expression, stabilizing mitochondrial membrane potential and protecting against SOD1[G93A]-induced apoptosis in NSC34 cells. Concurrently, it regulated TGF-β1/mTOR-dependent autophagy, maintained NMJ integrity, and reshaped triglyceride/sphingolipid/glycerophospholipid metabolism to attenuate spinal cord pathology in ALS mice, promoting energy metabolism shift toward glucose oxidation. Additionally, lisinopril inhibited the TGF-β1/Smad2/3 pathway to alleviate muscle fibrosis, downregulate Acp5/FN expression, and reduce type I collagen deposition. In conclusion, this study provides evidence that pharmacological activation of BI1 by lisinopril suppresses TGF-β1, modulates lipid metabolism, and ameliorates ALS pathology, demonstrating promising therapeutic repurposing potential.},
}

@article {pmid41921847,
year = {2026},
author = {Dong, YR and Wang, JR and Yang, Y and Chen, QZ and Jiang, YQ and Yang, X and Zhou, MC and Cao, SP and Zeng, SX and Zang, CX and Li, FF and Bao, XQ and Zhang, D},
title = {Unveiling the UFMylation Pathway: Implications in neurodegenerative diseases.},
journal = {Journal of molecular biology},
volume = {},
number = {},
pages = {169772},
doi = {10.1016/j.jmb.2026.169772},
pmid = {41921847},
issn = {1089-8638},
abstract = {UFMylation is a recently characterized post-translational modification (PTM) system that conjugates Ubiquitin-Fold Modifier 1 (UFM1) to target proteins via a dedicated enzymatic cascade. This modification system regulates critical cellular processes by controlling protein subcellular localization, modulating protein-protein interactions, and coordinating with ubiquitination to regulate protein stability. Emerging evidence highlights UFMylation as a critical modifier of pathological proteins, including tau and α-synuclein, while impaired UFMylation pathways are observed in the brains of individuals with neurodegenerative disorders. In this review, we summarize the current role and mechanism of UFMylation in the pathogenesis of neurodegenerative diseases, offering the first comprehensive framework for targeting UFMylation in the treatment of neurodegenerative diseases.},
}

@article {pmid41925076,
year = {2026},
author = {Krajewski, T and Koch, G},
title = {Randomization-Based Covariance Analysis for Confidence Intervals of Treatment Comparisons Based on Restricted Mean Survival Time With Categorized Time-to-Event Data.},
journal = {Statistics in medicine},
volume = {45},
number = {8-9},
pages = {e70422},
doi = {10.1002/sim.70422},
pmid = {41925076},
issn = {1097-0258},
support = {T32 ES007018/ES/NIEHS NIH HHS/United States ; },
mesh = {Humans ; *Randomized Controlled Trials as Topic/methods/statistics & numerical data ; Confidence Intervals ; Survival Analysis ; Analysis of Variance ; Amyotrophic Lateral Sclerosis/drug therapy/mortality ; Models, Statistical ; Double-Blind Method ; Computer Simulation ; Data Interpretation, Statistical ; Random Allocation ; },
abstract = {This paper introduces a randomization-based method for covariate-adjusted comparisons of restricted mean survival time (RMST) between treatment arms in randomized controlled trials. Existing approaches for covariate-adjusted RMST analysis have model-based assumptions that may not be compatible with the complexity of survival data. We estimate the treatment difference in RMST using randomization-based analysis of covariance (RB-ANCOVA) for categorized time-to-event data by constraining the covariate mean differences between treatment groups to zero. Accordingly, we provide corresponding confidence intervals that offer greater precision than those based on unadjusted RMST differences. The methodology is detailed for comparing two treatment groups for a single or multiple time intervals, as well as for multiple treatment groups over a single interval. We demonstrate the application of these methods using data from a randomized, double-blind, placebo-controlled clinical trial evaluating three doses of a test treatment for ALS.},
}

Humans
*Randomized Controlled Trials as Topic/methods/statistics & numerical data
Confidence Intervals
Survival Analysis
Analysis of Variance
Amyotrophic Lateral Sclerosis/drug therapy/mortality
Models, Statistical
Double-Blind Method
Computer Simulation
Data Interpretation, Statistical
Random Allocation

@article {pmid41929167,
year = {2026},
author = {Mahrous, AA and Heit, BS and Heckman, CJ},
title = {Riluzole treatment paradoxically increases motoneuron excitability in ALS due to hyperactive homeostasis.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.03.23.713695},
pmid = {41929167},
issn = {2692-8205},
abstract = {Riluzole is the most commonly prescribed among the limited approved therapies for amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized by progressive motoneuron loss and paralysis. It is thought to act by suppressing motoneuron excitability and glutamate release, but its clinical benefits are modest and often diminish over time. We previously showed that homeostatic mechanisms in the SOD1 [G93A] (mSOD1) mouse model of ALS are hyperactive and prone to overcompensation. Here, we tested whether such dysregulated homeostasis antagonizes the effects of riluzole. Wild-type (WT) and presymptomatic mSOD1 mice received therapeutic doses of riluzole in drinking water for 10 days, with untreated littermates of both genotypes serving as controls. Motoneuron excitability and synaptic inputs were then examined using intracellular recordings from the isolated sacral spinal cord. The data showed that chronic riluzole treatment increased motoneuron excitability and polysynaptic inputs in mSOD1 mice but produced no detectable changes in WT motoneurons. These results suggest that hyperactive homeostatic mechanisms in ALS counteract the suppressive effects of riluzole. Notably, mSOD1 motoneurons exhibited larger membrane capacitance than WT, consistent with their increased cell size at this disease stage. Riluzole treatment reduced motoneuron membrane capacitance in mSOD1 mice to the range observed in WT animals, indicating normalization of cell size and potentially reduction in metabolic demand. Together, these findings help explain the limited clinical efficacy of riluzole while revealing a previously unrecognized neuroprotective mechanism of the drug in ALS.},
}

@article {pmid41929709,
year = {2026},
author = {Gazwi, K and Zaza, T and Mitwally, H and Davda, N and Ganaw, A},
title = {Botulinum toxin injection induced autoimmune thyroiditis and myxedema coma: A case report.},
journal = {SAGE open medical case reports},
volume = {14},
number = {},
pages = {2050313X261430649},
pmid = {41929709},
issn = {2050-313X},
abstract = {This case describes a 28-year-old female with amyotrophic lateral sclerosis and recurrent urinary tract infections who developed myxedema coma following a botulinum toxin type-A (Btx) injection for muscle spasticity. On intensive care unit admission, she presented with hypothermia, bradycardia, and reduced consciousness. Laboratory evaluation revealed markedly elevated thyroid-stimulating hormone levels, confirming myxedema coma. Prompt treatment with intravenous levothyroxine and hydrocortisone resulted in rapid improvement in temperature and mental status. Further investigation showed elevated antithyroid peroxidase antibodies, suggesting drug-induced autoimmune thyroiditis triggered by Btx. This case highlights the potential link between Btx injection and thyroid autoimmunity, emphasizing the importance of early recognition and monitoring of thyroid function to prevent life-threatening complications in at-risk patients.},
}

@article {pmid41916622,
year = {2026},
author = {Addington, C and Davies, N and Howell, P and Cruickshank, S and Hainsworth, E},
title = {Lived experiences of cancer care for people living with HIV who are treated for anal cancer: a scoping review.},
journal = {BMJ open},
volume = {16},
number = {3},
pages = {e114180},
doi = {10.1136/bmjopen-2025-114180},
pmid = {41916622},
issn = {2044-6055},
mesh = {Humans ; *Anus Neoplasms/therapy/psychology/complications ; *HIV Infections/complications/psychology ; *Quality of Life ; },
abstract = {OBJECTIVE: This scoping review aims to identify existing evidence on the lived experiences of people living with HIV and treated for anal cancer, and to identify what aspects of health and well-being are addressed in clinical guidance.

DESIGN: A preregistered protocol (Open Science Framework, 2025) guided the review. We followed the Arksey and O'Malley framework, incorporating Levac et al's refinements around stakeholder consultation. Joanna Briggs Institute (JBI) guidance informed eligibility and data for charting, and reporting adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.

DATA SOURCES: Systematic searches were performed across multiple databases, including CINAHL, MEDLINE, PsycINFO and Embase, using EBSCOhost and Ovid, supplemented handsearching reference lists. Two search strategies were used: one for research studies and one for clinical guidelines.

ELIGIBILITY CRITERIA: Sources included people living with HIV treated for anal cancer, capturing lived experiences directly through qualitative studies or indirectly via quantitative patient-reported outcomes and/or health-related quality of life. Guidelines addressing HIV or anal cancer were also included.

DATA CHARTING AND SUMMARIES: Data were charted to capture patient experiences and outcomes on living with and beyond cancer, and how these are addressed in clinical management and guidance, including biomedical, psychosocial, sexual and functional aspects, and patient-reported outcomes.

RESULTS: Of 945 records, three studies and four guidelines met criteria. No study focused exclusively on people living with HIV; findings reflect broader anal cancer populations with HIV-positive subsets. Studies addressed aspects of health-related quality of life which we mapped into physical, psychosocial and sexual domains. Clinical guidance prioritised treatment dosage and survival, with limited attention to broader effects. Stakeholders highlighted that existing research and guidance miss important nuances of lived experience and care needs.

CONCLUSIONS: No identified research solely explored the lived experiences of people living with HIV treated for anal cancer, leaving guidance non-specific and biomedical. The identified domains offer a starting point for future research; however, to inform patient-centred care, stakeholders emphasised the need to understand how living with HIV and anal cancer shapes health needs.},
}

Humans
*Anus Neoplasms/therapy/psychology/complications
*HIV Infections/complications/psychology
*Quality of Life

@article {pmid41912988,
year = {2026},
author = {Zheng, H and Yu, S and Zhou, T and Fu, S and Zhang, J and Zhang, N and Liu, Y and Huang, Y and He, Z and Zhang, J and Liu, P and Gong, M and Zhou, C},
title = {Distinct amino acid metabolic subtypes predict prognosis and stratify treatment response in acute-on-chronic liver failure: a multicenter prospective study.},
journal = {Hepatology international},
volume = {},
number = {},
pages = {},
pmid = {41912988},
issn = {1936-0541},
support = {82305067//National Natural Science Foundation of China/ ; 2018ZX10725506-002//National Science and Technology Major Project of China during the 13th Five-Year Plan Period/ ; },
abstract = {BACKGROUND: Acute-on-chronic liver failure (ACLF) exhibits high mortality and heterogeneity, demanding precise risk stratification. We aimed to identify metabolic subtypes and explore their association with prognosis and real-world artificial liver support (ALS) responsiveness.

METHODS: This prospective, multicenter, observational cohort study enrolled 142 ACLF patients. Serum was collected at baseline, prior to ALS initiation. Patients were subtyped via metabolomics clustering. ALS exposure was analyzed using inverse probability of treatment weighting (IPTW) and Cox models to test for heterogeneity of treatment effect.

RESULTS: Two subtypes were identified (Cluster 1/2). Cluster 2 showed significantly higher 90 day mortality (p = 0.032) and severe amino acid metabolic reprogramming, particularly in branched-chain amino acid and glutamine pathways. Exploratory analysis suggested a differential association between ALS and survival across subtypes (interaction p = 0.12). ALS showed a weaker survival association in Cluster 2 after IPTW adjustment.

CONCLUSION: ACLF patients possess distinct amino acid-based metabolic subtypes that are potent prognostic indicators. Baseline metabolic profiling can serve as a stratification tool to identify patients who may derive the greatest clinical benefit from ALS therapy, guiding personalized treatment strategies.},
}

@article {pmid41910849,
year = {2026},
author = {Akram, SW and K, C},
title = {Enhancing Parkinson's Disease Staging: An Integrative Deep Learning Framework for Multimodal Feature Selection.},
journal = {Journal of molecular neuroscience : MN},
volume = {76},
number = {2},
pages = {},
pmid = {41910849},
issn = {1559-1166},
mesh = {Humans ; *Parkinson Disease/diagnostic imaging/genetics/pathology/diagnosis ; *Deep Learning ; Neuroimaging/methods ; Magnetic Resonance Imaging ; Male ; Female ; },
abstract = {Parkinson's disease (PD) affects 10 million globally, with accurate staging essential for personalized treatment planning. Current UPDRS assessments achieve < 93% accuracy due to subjective clinical judgment and unimodal data limitations, failing to capture complex genetic-neuroimaging-clinical interactions driving disease heterogeneity. This study introduces MAFNet, a novel deep learning framework pioneering Iterative Adaptive Vold-Kalman Filter (IAVKF) temporal denoising, Accelerated Binary Particle Swarm Optimization (ABPSO) swarm feature selection, Multilayer Perceptron-Lagrangian Support Vector Machine (MLP-LSVM) classification, and Graph-Attention Based Multimodal Fusion Network (GAMF). Applied to PPMI cohort (200 patients) with genetic SNPs (50), neuroimaging voxels (1,024), and UPDRS-III scores, the end-to-end pipeline delivers 97.6% accuracy, 98.2% precision, 96.8% recall, and 97.3% F1-score-outperforming CNN (92.4%), Autoencoder (90.8%), InceptoFormer (96.6%), and HCT (97.0%). IAVKF boosts SNR + 15.2dB (+ 2.9% accuracy vs. PCA/t-SNE); ABPSO reduces 1,276→340 features (73% reduction); regularization cuts overfitting gap to 0.9% (vs. 4.2% baseline). SHAP interpretability validates clinical plausibility (top predictors: LRRK2 SNPs, UPDRS-III tremor, hippocampal volume). Five-fold CV confirms stability with the Indian cohort external validation. Real-time inference (0.2s/patient, RTX 3090) enables clinical deployment. Future scope includes longitudinal temporal modelling, modality-agnostic fusion, edge deployment, federated learning, and extension to Alzheimer's/ALS. MAFNet transforms PD staging from subjective assessments to objective precision medicine, enabling biomarker discovery, progression forecasting, and personalized therapies across diverse global populations.},
}

Humans
*Parkinson Disease/diagnostic imaging/genetics/pathology/diagnosis
*Deep Learning
Neuroimaging/methods
Magnetic Resonance Imaging
Male
Female

@article {pmid41911331,
year = {2026},
author = {Kwan, JY and Lantz, CI and Korobeynikov, VA and Snyder, A and Huang, X and Haselhuhn, T and Dore, KN and Madruga, A and Danielian, LE and Schindler, AB and Chia, R and Rasheed, M and Crook, J and Szabo, M and Portley, M and Sherer, CM and King, MC and Huang, TH and Kosa, P and Bielekova, B and Ward, ME and Grunseich, C and Shneider, NA and Traynor, BJ and Narendra, DP},
title = {Clinical and biochemical characterization of amyotrophic lateral sclerosis in a CHCHD10 R15L family.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag115},
pmid = {41911331},
issn = {1460-2156},
abstract = {Familial forms of ALS are potential candidates for gene-directed therapies, but many recently identified genes remain poorly characterized. Here, we provide a comprehensive clinical, neuropathological, and biochemical description of fALS caused by the heterozygous p.R15L missense mutation in the gene CHCHD10. Using a cross-sectional study design, we evaluated five affected and nine unaffected individuals from a large seven-generation pedigree with at least 68 affected members. The pedigree suggests a high (68 - 81%) but incomplete disease penetrance. Through cloning of the disease-allele from distant members of the family, we establish the disease haplotype in the family. Notably, the haplotype was distinct from that of a previously reported p.R15L mutation carrier with ALS, demonstrating that the variant is in a mutational hotspot. The clinical presentation was notable for being highly stereotyped; all affected individuals presented with the rare ALS variant Flail Arm Syndrome (FAS; also known as, brachial amyotrophic diplegia or Vulpian-Bernhardt Syndrome), suggesting greater involvement of the cervical spinal cord. Consistently, neuropathology from one family member demonstrated substantially increased CHCHD10 protein aggregation and neuronal loss (though absent TDP-43 pathology) in the cervical vs. lumbar spinal cord. This FAS phenotype could be captured by a simple timed finger tapping task, suggesting potential utility for this task as a clinical biomarker. Additionally, through analysis of fibroblast lines from 12 mutation carriers, isogenic iPSC cells, and a knockin mouse model, we determined that CHCHD10 with the R15L variant is stably expressed and retains substantial function both in cultured cells and in vivo, in contrast to prior reports. Conversely, we find loss of function (LoF) variants are more common in the population but are not associated with a highly penetrant form of ALS in the UK Biobank (31 in controls; 0 in cases). Together, this argues against LoF and in favor of toxic gain-of-function as the mechanism of disease pathogenesis, similar to the myopathy-causing variants in CHCHD10 (p.G58R and p.S59L). Finally, through proteomic analysis of CSF of variant carriers, we identify that CHCHD10 protein levels are elevated approximately 4-fold in mutation carriers, and that affected and unaffected individuals are differentiated by elevation of two neurofilaments: neurofilament light chain (NfL) and Peripherin (PRPH). Collectively, our findings help set the stage for gene-directed therapy for a devasting form of fALS, by establishing the likely disease mechanism and identifying clinical and fluid biomarkers for target engagement and treatment response.},
}

@article {pmid41899342,
year = {2026},
author = {Hermann, M and Stoiber, A and Schmid, A and Hamp, T and Santos, AA and Grassmann, D and Krammel, M and Lintschinger, JM and Ulbing, S and Stria, A and Hafner, C},
title = {Relevance of Reversible Causes of Out-of-Hospital Cardiac Arrest: The "REBECCA" Interactive Checklist.},
journal = {Journal of clinical medicine},
volume = {15},
number = {6},
pages = {},
pmid = {41899342},
issn = {2077-0383},
abstract = {Background/Objectives: Adequate cardiopulmonary resuscitation (CPR), defibrillation, and treatment of reversible causes are essential for improving the survival of patients suffering from out-of-hospital cardiac arrests (OHCAs). The Advanced Life Support (ALS) algorithm includes reversible causes for cardiac arrest. This study aimed to develop an interactive mobile checklist to identify reversible causes of OHCA (REBECCA) and evaluate their usability and usefulness among emergency physicians. Methods: This mixed-methods study was conducted at the Emergency Medical Service Vienna, Austria. All participants were emergency physicians from the Medical University of Vienna. An interactive mobile checklist was developed using a participatory design approach involving a focus group of 10 emergency physicians. Usability and applicability were assessed using structured questionnaires. Descriptive statistics were used to summarize participant characteristics and evaluation outcomes. Results: Among the included participants, 70% were specialists with a median prehospital experience of 2.0 (1.0-4.3) years. Although most participants were confident about their level of professional experience with OHCA, 85% still found the checklist to be helpful. The majority of the participants preferred the digital checklist over the paper-based checklist and appreciated its integration with the point-of-care ultrasound (POCUS) application. Although the participants did not communicate a significant need for further details on most causes, a small majority favored more information on intoxication and electrolyte disorders. Conclusions: The majority of the included emergency physicians found the REBECCA checklist helpful regardless of training level, whereas almost no physician needed further detailed information on the reversible causes. Our findings underscore the potential importance of future investigations aiming to reduce the cognitive load of emergency physicians during OHCA scenarios.},
}

@article {pmid41903869,
year = {2026},
author = {Yang, Y and Yang, Y and Zhang, X and Ma, H and Ji, S and Zou, F and Yu, X and Du, G and Zhu, X and Tian, J},
title = {Targeting ME1 rescues redox-metabolic coordination in ALS: A core effector of NRF2-directed therapy.},
journal = {Neuropharmacology},
volume = {},
number = {},
pages = {110940},
doi = {10.1016/j.neuropharm.2026.110940},
pmid = {41903869},
issn = {1873-7064},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss, muscle weakness, and respiratory failure, with dysregulated energy metabolism and oxidative stress representing core pathological features. Epidemiological studies indicate geographical variations in incidence, and recent multi-omics evidence identifies a hypermetabolic state and mitochondrial dysfunction as key drivers of disease progression. The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2), which regulates antioxidant response and metabolism, represents a promising therapeutic target; however, the exploration of specific activators remains insufficient. This study evaluated the efficacy and mechanism of a novel KEAP1-NRF2 activator, MKL01351, in SOD1 G93A transgenic mice and NSC-34 motor neuron-like ALS models. Behavioral analyses demonstrated that MKL01351 significantly delayed disease onset, improved motor coordination in the rotarod and hanging tests, and extended survival. The compound alleviated oxidative stress by reducing malondialdehyde (MDA) levels and restoring the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, while also ameliorating the energy deficit by modulating glycolytic and mitochondrial functions, as confirmed by Seahorse analysis. Mechanistic investigations revealed that MKL01351 activated the NRF2 pathway, upregulating downstream targets such as NQO1 and HO-1, and specifically enhanced the expression of malic enzyme 1 (ME1). Loss-of-function experiments confirmed that ME1 knockdown abolished the protective effects, indicating that the NRF2-ME1 axis is a central hub for the synergistic regulation of metabolic and oxidative homeostasis. In conclusion, MKL01351 concurrently ameliorates oxidative stress and metabolic dysregulation via the NRF2-ME1 signaling pathway, offering a novel neuroprotective strategy for ALS treatment.},
}

@article {pmid41905645,
year = {2026},
author = {Martín-Sánchez, FJ and Marcos Sastre, MC and Muñoz de Maya, E and Sánchez-Pinto Pinto, B and Trueba Vicente, Á and Artero Ortiz, J and Arribas Guerrero, J and Soto Vargas, N and García Sánchez, IM and Marco Martínez, J and , },
title = {Six months of experience at a specialized daytime care center for people with amyotrophic lateral sclerosis (ALS) in the Community of Madrid.},
journal = {Neurologia},
volume = {},
number = {},
pages = {502006},
doi = {10.1016/j.nrleng.2026.502006},
pmid = {41905645},
issn = {2173-5808},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, leading to motor deterioration and a reduced quality of life. In the Community of Madrid, the ALS Network was established to improve patient care. In April 2024, the Specialized Day Care Centre for ALS (CEADELA) was inaugurated, complementing the care provided by the ALS Network. The aim of this study was to describe the experience of CEADELA during its first six months.

MATERIALS AND METHODS: A retrospective descriptive study was conducted on a cohort of CEADELA patients between April and October 2024. Clinical, functional, and therapeutic data were analyzed, along with overall satisfaction levels.

RESULTS: A total of 91 patients were included, with a mean age of 65.2 years (SD 11); of these, 59 (64.8%) were men. Most had spinal-onset ALS and were receiving treatment with riluzole. A significant increase was observed in the use of physiotherapy, speech therapy, and occupational therapy after referral to the centre. Functionality significantly declined over six months. The mortality rate was 12.1% (18.2% opted for assisted dying). Overall, 76 patients (83.5%) responded to the survey, with 100% reporting satisfaction or high satisfaction with the centre (80.2% very satisfied and 18.4% satisfied).

CONCLUSIONS: CEADELA has improved access to specialized therapies with a high level of satisfaction, although disease progression remains a challenge. The need to continue developing integrated, evidence-based care models to optimize ALS management is highlighted.},
}

@article {pmid41895196,
year = {2026},
author = {Schmidlin, D and Thaysen, EM and Platikanov, S and Xu, J and Chesa, MJ and Tauler, R and Vázquez-Suñé, E and Teixidó, M},
title = {Impact of the superblock model on key components of the urban water cycle: Trace metals and dissolved organic matter dynamics across the built environment.},
journal = {Journal of hazardous materials},
volume = {508},
number = {},
pages = {141867},
doi = {10.1016/j.jhazmat.2026.141867},
pmid = {41895196},
issn = {1873-3336},
abstract = {Climate change, growing urban pollution, and increasing water scarcity are forcing cities to adopt strategies that enhance resilience to both climatic and anthropogenic pressures. The Barcelona Superblock model is a novel urban planning strategy that highly restricts vehicle traffic, converts streets into pedestrian-priority corridors, and promotes green spaces. Within this framework, green infrastructures, also called sustainable urban drainage systems (SUDS), are implemented as local, site-specific measures to capture (i.e., flood control), treat, and infiltrate treated stormwater (i.e., aquifer recharge). To evaluate the Superblock model impact on urban water quality, we conducted seven sampling campaigns across three Barcelona districts, targeting rainfall, stormwater "first-flush" from roads and pedestrianized streets, as well as SUDS influent and effluent within and in the vicinity to Superblocks, with a focus on dissolved trace metals and dissolved organic matter (DOM). Results showed that Superblocks reduced pollutant loads and mitigated ecotoxicological risks. Trace metal and DOM concentrations followed the trend: Rain < SUDS effluent < Pedestrian Street runoff < Road runoff, highlighting traffic-related impacts and SUDS treatment capacity (23-70% in best case scenario). Risk assessment indicated episodic ecotoxicological risk in stormwater, especially in road runoff due to elevated concentrations of Cu and Zn, while SUDS consistently remained below risk thresholds. SUDS also transform DOM into more stable, humic-like forms. Trace metals and DOM emerged as biogeochemical proxies for stormwater quality, enabling more effective and sustainable urban water management. These findings support the integration of Superblock-like strategies into urban planning to control and reduce contaminant urban discharges.},
}

@article {pmid41897327,
year = {2026},
author = {Romano, R and Ruotolo, G and Perrone, F and Tomaselli, S and Mazzoni, M and Spataro, R and Conforti, FL and Rosati, J and Bucci, C},
title = {Selective Silencing of TDP-43 P. G376D Mutation Reverses Key Amyotrophic Lateral Sclerosis-Related Cellular Deficits.},
journal = {Biomolecules},
volume = {16},
number = {3},
pages = {},
pmid = {41897327},
issn = {2218-273X},
support = {PRIN2022 N. 2022XTM2S3//Ministero dell'università e della ricerca/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; Humans ; *DNA-Binding Proteins/genetics/metabolism ; Motor Neurons/metabolism/pathology ; RNA, Small Interfering/genetics ; Induced Pluripotent Stem Cells/metabolism ; *Mutation ; Oxidative Stress ; Cell Survival ; Lysosomes/metabolism ; Gene Silencing ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease for which there is currently no cure. Dominant mutations in the TARDBP gene are causative of ALS. In particular, the p. G376D substitution in TDP-43 causes familial ALS and it is associated with TDP-43 mislocalization in the cytosol, increased presence of cytoplasmic aggregates, and lysosomal and mitochondrial dysfunction. We previously designed a small interfering RNA (siRNA) that specifically targets and silences the mutant allele and we demonstrated that, in patient-derived fibroblasts, it can reduce TDP-43 aggregation, decrease oxidative stress, and improve cell viability. Here, we investigated the ability of this siRNA to revert some ALS-associated pathological phenotypes in motor neurons derived from induced pluripotent stem cells (iPSCs), as motor neurons are the primary cells affected in ALS. siRNA treatment reduced TDP-43 mislocalization, enhanced lysosomal function and cell viability, and decreased oxidative stress. These findings indicate that this allele-specific siRNA effectively reverses key ALS-related cellular deficits in motor neurons, representing a promising candidate for targeted therapy in patients carrying the TDP-43 G376D mutation.},
}

*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism
Humans
*DNA-Binding Proteins/genetics/metabolism
Motor Neurons/metabolism/pathology
RNA, Small Interfering/genetics
Induced Pluripotent Stem Cells/metabolism
*Mutation
Oxidative Stress
Cell Survival
Lysosomes/metabolism
Gene Silencing

@article {pmid41876403,
year = {2026},
author = {Yan, K and Jiang, Y and Yong, Y and Zhang, T and Zhang, N and Zeng, Q and Gong, X and Meng, L and Bi, F and Liu, Y},
title = {ALDOA Promotes Glycolysis and NLRP3/GSDMD Pyroptosis to Accelerate ALS Progression.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.70372},
pmid = {41876403},
issn = {2328-9503},
support = {81760238//National Natural Science Foundation of China/ ; 82171433//National Natural Science Foundation of China/ ; 2022JJ30918//Natural Science Foundation of Hunan Province/ ; 2023JJ30927//Natural Science Foundation of Hunan Province/ ; TSYC202401B119//Xinjiang Uygur Autonomous Region Health Commission "Tianshan Talent" High-Level Medical and Health Personnel Project/ ; 2025D01E38//Natural Science Foundation of Xinjiang Uygur Autonomous Region/ ; },
abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron degeneration. Glycolytic dysregulation is implicated in disease progression, yet the underlying mechanisms remain unclear. This study investigates how Aldolase A (ALDOA) drives ALS progression through glycolysis-mediated motor neuron pyroptosis.

METHODS: In vivo, tamoxifen-induced TDP-43 cKO mice were assessed for motor function (rotarod/suspension tests), motor cortex L-lactic acid, and ALDOA/NLRP3/GSDMD expression. The ALDOA inhibitor Aldometanib was administered. In vitro, TDP-43 KO NSC34 cells were used to measure viability, glucose uptake, and L-lactic acid.

RESULTS: ALS model mice exhibited significant motor deficits, progressive weight loss, and reduced survival. Their motor cortex showed elevated ALDOA expression, L-lactic acid accumulation, and NLRP3/GSDMD inflammasome activation. Aldometanib treatment suppressed glycolysis, prolonged survival, and slowed disease progression by inhibiting NLRP3/GSDMD-mediated pyroptosis. In vitro, TDP-43-deficient NSC34 cells displayed increased ALDOA levels, enhanced glycolytic flux, NLRP3/GSDMD pathway activation, and impaired proliferation.

CONCLUSION: We show that ALDOA-mediated glycolytic dysregulation activates the NLRP3/GSDMD inflammasome, leading to pyroptosis in motor neurons. Pharmacological inhibition of ALDOA alleviates glycolytic dysregulation and extends survival, identifying ALDOA as a potential therapeutic target.},
}

@article {pmid41885541,
year = {2026},
author = {Chen, RF and Liu, KF and Lee, CC and Li, YT and Chen, WY and Kuo, YR},
title = {Transcriptomic Analysis of Adipose-Derived Stem Cell Therapy Modulating B Cell Immune Tolerance in Vascularized Composite Allotransplantation.},
journal = {Plastic and reconstructive surgery},
volume = {},
number = {},
pages = {},
doi = {10.1097/PRS.0000000000013074},
pmid = {41885541},
issn = {1529-4242},
abstract = {BACKGROUND: Adipose-derived stem cells (ADSCs) have been shown to prolong vascularized composite allotransplantation (VCA) survival in rodent hindlimb transplantation. However, the mechanisms by which ADSCs modulate B cell responses and induce immune tolerance remain unclear. This study used next-generation sequencing (NGS) to investigate B cell gene expression after ADSC treatment.

METHODS: A rodent orthotopic hind-limb transplantation model was established using Brown-Norway to Lewis rats. The tolerance treatment group received a combination of ADSCs, short-term cyclosporine A (CsA) and anti-lymphocyte serum (ALS), while the control rejection group received no treatment. B cells were isolated from the spleens of rejection control group at 10-14 days post-transplantation when rejection was diagnosed, or tolerance group at least ≥100 days post-transplantation without rejection. RNA sequencing (RNA-Seq) was conducted to assess transcriptomic differences. Differentially expressed genes (DEGs) were analyzed using the EBSeq bioinformatics tool and pathway enrichment analyses, with validation by qPCR.

RESULTS: RNA-Seq identified 94 DEGs (out of 13,284 mRNAs) between the tolerance and rejection groups. Gene ontology and KEGG pathway analyses revealed significant enrichment in pathways associated with cytokine secretion, B cell receptor signaling, and humoral immunity. The tolerance group exhibited upregulation of key chemokines (e.g., Cxcl1, Cxcl2, Ccl4) and downregulation of pro-inflammatory genes (e.g., Tlr3, Siglec5, C3). qPCR validation confirmed the RNA-Seq findings. These results suggest that ADSCs modulate B cell-mediated immune responses and promote a shift toward an anti-inflammatory, tolerogenic profile.

CONCLUSIONS: ADSC-based therapy combined with short-term immunosuppression promotes immune tolerance in VCA by modulating B cell-related gene expression. These findings suggest that targeting B cell-mediated pathways may provide a novel approach may offer a novel therapeutic strategy for clinical application in VCA.},
}

@article {pmid41870813,
year = {2026},
author = {Upadhayay, S},
title = {Role of Pentacyclic Triterpenes in the Management of Neurological Disorders: An Insight into Molecular Mechanisms and Therapeutic Approaches.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41870813},
issn = {1559-1182},
mesh = {Humans ; Animals ; *Nervous System Diseases/drug therapy/metabolism ; *Pentacyclic Triterpenes/therapeutic use/pharmacology ; *Neuroprotective Agents/therapeutic use/pharmacology ; Signal Transduction/drug effects ; Oxidative Stress/drug effects ; },
abstract = {Neurological disorders represent major public health concerns globally, as they profoundly affect motor function, memory, and cognitive abilities, thus compromising patients' independence and quality of life. Despite extensive research, current treatment approaches predominantly offer palliative care, failing to hinder disease progression. The rising incidence of these disorders underscores an urgent necessity for more efficacious and disease-modifying therapies. According to findings, pentacyclic triterpenoids exhibit neuroprotective properties by inhibiting neuronal oxidative stress, neuroinflammation, apoptosis, and degeneration, making them promising candidates for targeting the underlying causes of neurodegeneration. Therefore, in this review, we explore natural and synthetic pentacyclic triterpenoids that exhibit neuroprotective effects by modulating signaling pathways, such as HMGB1, TLR4, NLRP3, NF-κB, Nrf2, PI3K, Akt, and CREB, which play crucial roles in regulating cell proliferation, differentiation, and neuronal plasticity. The present literature survey is performed by searching various keywords with several combinations: "pentacyclic triterpenes", "neurological disorders", Parkinson's Disease", "Huntington's Disease", "Alzheimer's Disease", "Multiple sclerosis", "Amyotrophic Lateral Sclerosis" "Epilepsy", "mitochondria dysfunction", "oxidative stress", "preclinical studies", "molecular mechanisms", and "clinical studies". Studies indicates that pentacyclic triterpenoids have a wide range of therapeutic potentials, current findings summarizes existing knowledge and examines the neuroprotective properties and potential molecular mechanisms of pentacyclic triterpenoids related with health benefits and neurological diseases. Available evidence suggests that pentacyclic triterpenoids possess the capacity to impede disease progression and may be beneficial in the treatment of neurological disorders. This review strengthens the understanding of pentacyclic triterpenoids and their molecular mechanisms, while also facilitating pharmaceutical discovery and development for neurodegenerative disorders.},
}

Humans
Animals
*Nervous System Diseases/drug therapy/metabolism
*Pentacyclic Triterpenes/therapeutic use/pharmacology
*Neuroprotective Agents/therapeutic use/pharmacology
Signal Transduction/drug effects
Oxidative Stress/drug effects

@article {pmid41868729,
year = {2026},
author = {Sethi, N and Levy, OA and Richardson, A and Harari, OA and Sellati, R},
title = {A Qualitive Investigation of Geographic Disparities in Genetic Testing and Care Access for Amyotrophic Lateral Sclerosis: Insights From Patient Journey Mapping.},
journal = {Patient preference and adherence},
volume = {20},
number = {},
pages = {566747},
pmid = {41868729},
issn = {1177-889X},
abstract = {PURPOSE: Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease that is associated with a high patient burden, reduced lifespan, and reduced quality of life. People living with ALS (PLwALS) often experience delays in diagnosis of ~1 year, and while current treatment options can slow disease progression, improve quality of life, and offer modest benefits in functional decline, they do not reverse neuronal damage. Defining and understanding the experiences of PLwALS can help identify gaps and barriers to optimal care.

PATIENTS AND METHODS: This non-interventional study was intended to obtain insights on the patient experience from the perspective of PLwALS. We sought to develop an ALS patient journey map from initial presentation through to end-of-life care for 4 regions (North America, Asia-Pacific, Latin America, and Europe/Middle East/Africa). The map was based on results from a global audit of data sources (including publications, patient narratives, society guidelines, academic reports, industry white papers [n=104]), and one-to-one, 60-minute, semi-structured interviews with PLwALS (n=12) or those caring for PLwALS (n=2). The initial patient journey map was subsequently reviewed during 2 advisory sessions with patient advocates (7 PLwALS and 2 caregivers) in September and November 2023.

RESULTS: We identified several barriers and challenges that most impact PLwALS, caregivers, and clinicians, with many similarities but also some differences across the regions.

CONCLUSION: These insights will enable targeted improvements in education, personalized care, resource allocation, care coordination, policy development, and funding, ultimately improving patient outcomes.},
}

@article {pmid41868461,
year = {2026},
author = {Yu, J},
title = {Postoperative acute ultra-early fish mouthing of a Surpass Evolve flow diverter leading to ischemic complication.},
journal = {Radiology case reports},
volume = {21},
number = {6},
pages = {2346-2354},
pmid = {41868461},
issn = {1930-0433},
abstract = {Currently, the Surpass Evolve flow diverter (SE FD) is widely adopted for endovascular treatment of intracranial aneurysms. Although generally safe, acute ultra-early fish mouthing remains an exceptionally rare complication. Following Torche et al.'s 2023 report of the first case, the present case represents the second documented instance. A 66-year-old woman was diagnosed with a left posterior communicating artery aneurysm and a left ophthalmic artery aneurysm. Physical examination revealed no abnormalities. The endovascular treatment (EVT) procedure was performed. After advancing a microcatheter into the left middle cerebral artery, an SE FD with appropriate size was deployed to cover both aneurysms, achieving confirmed complete expansion and optimal wall apposition. Two hours postoperatively, the patient developed aphasia and hemiparesis. Subsequent angiography at 4 hours revealed thrombosis within the SE FD and fish mouthing at the proximal segment. Successful microguidewire traversal through the affected site restored complete FD expansion and wall apposition. Postoperatively, the patient's hemiparesis improved, and her motor aphasia resolved. Magnetic resonance imaging confirmed multiple acute infarctions, while computed tomography demonstrated proper FD expansion. At 3-month follow-up, near-normal functional recovery was observed. This case indicates that SE FD deployment may be complicated by acute ultra-early fish mouthing attributable to post-deployment tension release. Preventive strategies should emphasize appropriate device sizing, adequate landing zone selection, and post-implant tension assessment.},
}

@article {pmid41863659,
year = {2026},
author = {Mullick, S and Chakraborty, A and Porel, P and Nath, R and Chaudhary, P and Islam, A and Das, J and Pramanik, S and Panigrahy, UP and Sridhar, SB and Mondal, M and Debnath, B and Ashique, S},
title = {Decoding Neuroinflammatory Pathways: The Role of the CXCL12-CXCR4/CXCR7 Axis in ALS-Related Cognitive Impairment.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41863659},
issn = {1559-1182},
mesh = {Humans ; *Chemokine CXCL12/metabolism ; *Receptors, CXCR/metabolism ; *Amyotrophic Lateral Sclerosis/metabolism/complications/pathology ; Animals ; *Receptors, CXCR4/metabolism ; *Cognitive Dysfunction/metabolism ; *Signal Transduction/physiology ; *Neuroinflammatory Diseases/metabolism/pathology ; Inflammation/metabolism/pathology ; },
abstract = {Cognitive impairment (CI) and accelerating neuronal deterioration are hallmarks of amyotrophic lateral sclerosis (ALS). Under these circumstances a crucial molecular mechanism in the pathophysiology of CI has been identified: the CXC chemokine receptor type 7 (CXCR7)/CXC chemokine receptor type 4 (CXCR4)/Cysteine-X-cysteine chemokine ligand 12 (CXCL12) region. Research on ALS shows that the CXCR7/CXCR4/CXCL12 complex plays a role in the degeneration of motor neurons and the resulting cognitive decline. JAK/STAT, PI3K/AKT, MAPK, and other signaling pathways are among the ways the axis controls neuronal inflammation, synaptic remodeling, and neuronal maintenance in each of these scenarios. The CXC motif chemokine ligand 12 (CXCL12) and CXC chemokine receptor type 4 (CXCR4) axis is crucial for the start of the inflammatory mechanism because of their function in mediating the chemotaxis of inflammatory cells. By preventing the migration of inflammatory cells via CXCL12 in the inflammatory area, the response to inflammation can be prevented or reduced. Consequently, the development of CXCR4 antagonists has emerged as a cutting-edge strategy for inflammation treatment. Recent research suggests that managing this relationship could reduce cognitive deficits and offer neuroprotective benefits. According to the current review, the CXCL12/CXCR4/CXCR7 pathway may be a promising target for treating cognitive dysfunction in neurodegenerative disorder. It also emphasizes the need for additional research to completely comprehend its function and identify efficient treatments which may result in improved clinical treatment modalities for these debilitating illnesses.},
}

Humans
*Chemokine CXCL12/metabolism
*Receptors, CXCR/metabolism
*Amyotrophic Lateral Sclerosis/metabolism/complications/pathology
Animals
*Receptors, CXCR4/metabolism
*Cognitive Dysfunction/metabolism
*Signal Transduction/physiology
*Neuroinflammatory Diseases/metabolism/pathology
Inflammation/metabolism/pathology