@article {pmid40908789,
year = {2025},
author = {Carletta, O and Perfetto, C and Rifai, OM and Manganelli, F and Waldron, FM and Maniatis, T and Gregory, JM and Gerbino, V},
title = {Genotype-specific interferon signatures in amyotrophic lateral sclerosis relate to disease severity.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awaf324},
pmid = {40908789},
issn = {1460-2156},
abstract = {Innate immune signaling pathways are hyperactivated in the central nervous system (CNS) of patients with Amyotrophic Lateral Sclerosis (ALS), as well as in preclinical models with diverse causative backgrounds including TDP-43, SOD1, and C9orf72 mutations. This raises an important question of whether these pathways are key pathogenic features of the disease, and whether therapeutic amelioration could be beneficial. Here, we systematically profile Type-I interferon (IFN)-stimulated gene (ISG) expression signatures using a non-biased approach in CNS tissue from a cohort of 36 individuals with ALS, including sporadic ALS (sALS; n=18), genetic ALS caused by (i) a C9orf72 hexanucleotide repeat expansion (C9-ALS; n=11), and (ii) a SOD1 mutation (SOD1-ALS; n=5), alongside age- and sex-matched individuals who died of a non-neurological cause (n=12). Using this deeply phenotyped cohort we have implemented targeted transcriptomic analysis and immunohistochemistry to interrogate the nature and extent of the activation of the Type-I IFN response in patients. We determined disease and genotype specific IFN signatures that correlate with clinical phenotype. Correlation analysis linked six ISGs with aggressive disease progression, as indicated by negative correlation with age at death in ALS patients. Notably, significant upregulation of ISGs was observed in C9-ALS patients, with higher ISG expression correlating with shorter disease duration. Noting that our genotype and disease specific signatures correlated with metrics of disease progression, we explored the therapeutic potential of targeting this pathway in a mouse model of ALS. Treatment with an IFN pathway inhibitor reduced IFN response markers, delayed disease progression, including motor decline, and extended survival in ALS mice. We conclude that upregulation of gene expression in the Type-I IFN pathway represents a key pathological feature of ALS and that inhibiting this pathway may provide a promising therapeutic approach for treating ALS.},
}

@article {pmid40908710,
year = {2025},
author = {Giove, E and Ferraro, PM and Lungu, M and Pasquinelli, L and Truffelli, R and Trinchero, C and Rebagliati, B and Caponnetto, C and Vignolo, M and Rao, F},
title = {Effects of Dog-Assisted Occupational Therapy on Upper Limb Functions in ALS and Other Neuromuscular Disorders: A Randomized Controlled Pilot Study.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70012},
pmid = {40908710},
issn = {1097-4598},
abstract = {INTRODUCTION/AIMS: The beneficial effects of animal-assisted therapy (AAT) on balance, walking endurance, and mood symptoms in amyotrophic lateral sclerosis (ALS) have been previously demonstrated. In this study, we aimed at expanding upon these findings by further evaluating its effects on upper limb (UL) functions and mood symptoms both in ALS and other neuromuscular disorders (NMDs).

METHODS: Sixty-eight patients participated in a regular 2-week occupational therapy program once a day. For three days a week, in place of the traditional treatment, the AAT group (N = 34) performed a session in interaction with the therapy dog. Outcome measures included hand grip strength, manual dexterity, and mood symptoms. Differences between baseline and post-treatment values were assessed using the Wilcoxon Signed-Rank Test, and one-way analysis of covariance was used to examine between-group differences in post-treatment values, adjusting for baseline measurements.

RESULTS: Both groups improved in hand grip strength (p = 0.004-0.03), whereas mood symptoms improved exclusively in the AAT group (p = 0.0003-0.03). Post-treatment values were significantly better in the AAT group (p = 0.01-0.03). When ALS patients were analyzed separately, the improvement of hand grip strength and mood symptoms was observed only in the AAT group (p = 0.001-0.04), which accordingly showed better post-treatment values (p = 0.0007-0.05).

DISCUSSION: Our findings indicate that AAT has greater beneficial effects than traditional treatments on UL strength and mood symptoms. These findings have the potential to facilitate more effective rehabilitation strategies both in ALS and other NMDs.},
}

@article {pmid40908696,
year = {2025},
author = {Paul, S and Tiwari, P and Dubey, S},
title = {Precision Enzyme: Targeted Drug Discovery in Neurodegenerative Disorders.},
journal = {Protein and peptide letters},
volume = {},
number = {},
pages = {},
doi = {10.2174/0109298665391103250825102319},
pmid = {40908696},
issn = {1875-5305},
abstract = {INTRODUCTION: Neurodegenerative disorders such as Alzheimer's, Parkinson's, and ALS are characterized by progressive neuronal dysfunction with limited therapeutic options. Recent advances in molecular biology and drug development have highlighted the therapeutic promise of precision enzyme targeting, offering novel strategies for disease modulation and symptom management.

METHODS: A comprehensive literature review spanning recent/current was conducted using PubMed, Scopus, and ScienceDirect. Studies focusing on enzyme-based targets, high-throughput screening, and molecular docking in neurodegeneration were included. Thematic synthesis was employed to categorize findings based on enzyme class, disease relevance, and therapeutic outcomes.

RESULTS: Key enzyme families such as kinases, proteases, and oxidoreductases were identified as pivotal modulators in disease progression. Emerging enzyme-targeted compounds demonstrated enhanced bioavailability, blood-brain barrier permeability, and disease-specific efficacy. Novel screening platforms and computational modeling enabled the precise selection of inhibitors, significantly improving the therapeutic index and reducing off-target effects.

DISCUSSION: Targeting enzymes implicated in neuroinflammation, oxidative stress, and protein misfolding has shown disease-modifying potential. Integrating precision drug discovery tools, such as AI-assisted modeling and enzyme kinetics, supports rational drug design. However, translational challenges persist due to variability in enzyme expression and disease heterogeneity.

CONCLUSION: Future research should focus on refining enzyme inhibitors and integrating biomarkers to facilitate personalized treatment strategies for neurodegenerative disorders. As the understanding of enzymatic roles in neurodegeneration deepens, precision enzyme-targeted drug discovery holds significant promise in transforming neurotherapeutic approaches.},
}

@article {pmid40908144,
year = {2025},
author = {Kim, SK and Gelfand, VI},
title = {PolyQ-expansion of Ataxin-2 disrupts microtubule stability and impairs axon outgrowth.},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1523/JNEUROSCI.0682-25.2025},
pmid = {40908144},
issn = {1529-2401},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by mislocalization and aggregation of proteins in motor neurons. Ataxin-2 (ATXN2), an RNA-binding protein harboring 22-polyglutamine (polyQ) repeats, is a risk factor for ALS, when its polyQ repeats are expanded to 27-33 repeats. However, the physiological function of ATXN2 beyond its role in RNA regulation, and how polyQ expansion in ATXN2 increases risk for ALS, remain unclear. We previously demonstrated that Drosophila Atx2 functions as a regulator of microtubule (MT) dynamics in motor neurons. Here, we uncover the molecular mechanism underlying Atx2-mediated MT regulation and how polyQ expansion disrupts its function, using a mixed-sex population of Drosophila as a model system. Specifically, we show that Atx2 requires its RNA-binding Lsm domain to regulate MTs. Notably, the LSM domains of human ATXN2 rescue MT phenotype in Drosophila, demonstrating an evolutionarily conserved role of ATXN2 in MT regulation. Importantly, we find that polyQ-expanded ATXN2 forms cytoplasmic aggregates and leads to excessive MT destabilization. Additionally, polyQ expansion severely impairs axon outgrowth. Finally, we identify Uncoordinated-76 (UNC-76/FEZ1) as a downstream effector of Atx2 in MT regulation and neuronal development.Significance Statement ALS is a progressive neurodegenerative disease with no effective treatment. Although polyglutamine (polyQ) expansion in the RNA-binding protein ATXN2 is a known risk factor for ALS, its mechanistic role in ALS pathogenesis has remained unclear. We demonstrate that ATXN2 regulates MT dynamics via its RNA-binding domain, and this role is evolutionarily conserved between Drosophila and humans. We further identify UNC-76/FEZ1 as a downstream effector of ATXN2 in regulating MT dynamics and neuronal development. Importantly, this study reveals how polyQ expansion in ATXN2 disrupts MT stability and axon growth, proposing a mechanism that may contribute to increased ALS risk.},
}

@article {pmid40906916,
year = {2025},
author = {Kakoty, V and Kang, JH and Lee, OH and Oh, DH and Ko, YT},
title = {Grueneberg Ganglion: An Unexplored Site for Intranasal Drug Delivery in Alzheimer's Disease.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.5c00376},
pmid = {40906916},
issn = {1948-7193},
abstract = {Neurological disorders such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Multiple Sclerosis, and Amyotrophic Lateral Sclerosis pose significant challenges for treatment. Reasons for the difficulty in finding cures for these conditions include complications in early diagnosis, progressive and irreversible neuronal damage, and the presence of the blood-brain barrier (BBB), which hinders the delivery of drugs to the affected areas of the brain. Intranasal (INL) drug administration has increasingly gained popularity among researchers for targeting neurological conditions, because of its ability to bypass the BBB. However, chronic INL administration leads to nasal mucosa irritation. Additionally, rapid mucociliary clearance, a lack of targeted drug delivery, increased enzymatic degradation, and tight junctions that obstruct drug transport limit the clinical applicability of the INL route. To overcome these challenges, a unique region in the rodent nose, known as the Grueneberg Ganglion (GG), can be considered to be a novel site for INL drug administration. GG is a small structure housed under the snout cartilage of the nasal septum, approximately 1.5 mm from the nasal opening in mice. It is directly connected to the main olfactory bulb through axons. This Perspective aims to expand knowledge on why GG may be a viable option for INL delivery to combat neurological conditions. For better understanding, we have explained the INL administration in GG, using Alzheimer's Disease and INL insulin therapy as a role model for the current review.},
}

@article {pmid40905501,
year = {2025},
author = {Huang, Y and Wan, Y and Chen, J and Qin, M and Wang, J and Liang, H},
title = {Knowledge mapping of biomarkers in amyotrophic lateral sclerosis: a comprehensive bibliometric and visual analysis.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/17582024.2025.2554525},
pmid = {40905501},
issn = {1758-2032},
abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a severe neurodegenerative disease, and there is currently an urgent need to identify valuable biomarkers to accelerate diagnosis, optimize treatment and prognosis.

METHODS: To conduct a bibliometric analysis of publications related to "ALS biomarker" over the past 20 years, utilizing the subject search feature of the Web of Science Core Collection along with CiteSpace, VOSviewer, and Bibliometrix.

RESULTS: This review presents a 20-year bibliometric analysis of ALS biomarker research (2004-2024), analyzing 2535 publications showing rising trends. The United States led contributions, with Turner, Martin R as the most productive/cited author. Key research hotspots included cerebrospinal fluid, tdp-43, clinical trial, and neuroinflammation. Topics such as neurofilament light chain, machine learning, and exosomes could potentially represent the cutting edge of future research.

CONCLUSION: In summary, this study uses bibliometric analysis of ALS biomarker research to provide a forward-looking perspective on its future limitations and potential.},
}

@article {pmid40904817,
year = {2025},
author = {Kuo, T and Reynolds, T and Chen, L and Park, C and Rascati, K and Godley, P},
title = {Racial and ethnic disparities in ALS: a longitudinal electronic health records study.},
journal = {Therapeutic advances in neurological disorders},
volume = {18},
number = {},
pages = {17562864251365001},
pmid = {40904817},
issn = {1756-2856},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with limited treatment options and significant variability in care. Racial and ethnic disparities in ALS management and outcomes have been reported, but findings remain inconsistent.

OBJECTIVES: This study aimed to evaluate racial and ethnic disparities in ALS care, specifically differences in healthcare utilization, treatment patterns, and survival, within a large healthcare system.

DESIGN: This retrospective cohort study analyzed electronic health records from a large healthcare system in Texas for patients diagnosed with ALS between 2013 and 2023, examining racial and ethnic differences in treatment and outcomes.

METHODS: Patients were identified using International Classification of Diseases (ICD) codes. Baseline characteristics, including race/ethnicity and socioeconomic factors, were collected. Primary outcomes included the use of noninvasive ventilation (NIV), tracheostomy, gastrostomy, mobility aids, and ALS medications; secondary outcomes included time to diagnosis and survival. Racial and ethnic disparities were assessed using generalized linear regression and Cox proportional hazards models, adjusting for demographic and socioeconomic factors.

RESULTS: A total of 636 patients were included (74.5% Non-Hispanic White, 5.3% Non-Hispanic Black, 7.4% Hispanic, and 12.7% Other). Non-Hispanic Black patients had significantly higher tracheostomy rates than Non-Hispanic White patients (35.3% vs 8.7%; adjusted odds ratio (OR), 6.20; 95% confidence interval (CI), 2.43-15.84). Hispanic patients had lower odds of receiving riluzole (42.6% vs 61.8%; adjusted OR, 0.36; 95% CI, 0.18-0.71) and higher rates of emergency department visits (adjusted OR, 2.00; 95% CI, 1.09-3.65) and hospitalizations (adjusted OR, 2.57; 95% CI, 1.37-4.81). No significant racial or ethnic differences were observed in time to diagnosis or survival after adjustment.

CONCLUSION: Significant racial and ethnic disparities exist in ALS care, particularly in tracheostomy utilization, medication prescribing, and healthcare access. These findings underscore the need for targeted interventions to promote equitable ALS management, including provider education and improved healthcare accessibility.},
}

@article {pmid40904199,
year = {2025},
author = {Isik, S and Osman, S and Yeman-Kiyak, B and Shamshir, SRM and Sanchez, NME},
title = {Advances in Neurodegenerative Disease Therapy: Stem Cell Clinical Trials and Promise of Engineered Exosomes.},
journal = {CNS neuroscience & therapeutics},
volume = {31},
number = {9},
pages = {e70577},
doi = {10.1111/cns.70577},
pmid = {40904199},
issn = {1755-5949},
mesh = {Humans ; *Exosomes/transplantation/metabolism ; *Neurodegenerative Diseases/therapy ; Animals ; *Stem Cell Transplantation/methods/trends ; *Clinical Trials as Topic/methods ; },
abstract = {AIM: This review provides a systematic evaluation of 94 stem cell clinical trials to treat neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease.

METHODS: Data were collected from using relevant search terms, focusing exclusively on stem cell therapy. Of the 8000+ participants in these trials, nearly 70% were enrolled in AD-related studies. Only three Phase 3 studies were conducted, and most trials were in the early phases (Phases 1 and 2). Mesenchymal stem cells, neural stem cells, induced pluripotent stem cells, and embryonic stem cells are used the most to treat neurodegenerative diseases. This review also explores the emerging fields of preclinical and clinical investigations of stem cell-derived exosome-based therapies for neurodegenerative diseases.

RESULTS: Exosomes can cross the blood-brain barrier to deliver therapeutic molecules directly to the brain, offering a less invasive alternative to stem cell transplantation. Mesenchymal stem cell-derived exosomes, in particular, have demonstrated significant potential in preclinical models by reducing neuroinflammation, oxidative stress, and promoting neuronal regeneration. Additionally, recent advances in exosome engineering, including surface modifications, therapeutic agent loading, and transgenic modifications, have improved targeting, stability, blood-brain barrier delivery, and neural cell interactions, enabling targeted and effective treatment. Exosome-based therapies are in the preliminary phases of clinical investigation, with only three clinical trials.

CONCLUSION: Given the increasing interest in exosome therapy, clinical investigations are expected to increase. This growth will be driven by ongoing advancements in exosome technology, a deeper understanding of their therapeutic potential, and escalating demand for innovative treatment strategies for neurodegenerative diseases.},
}

Humans
*Exosomes/transplantation/metabolism
*Neurodegenerative Diseases/therapy
Animals
*Stem Cell Transplantation/methods/trends
*Clinical Trials as Topic/methods

@article {pmid40903965,
year = {2025},
author = {Parikh, A and Cholavaram, A and Chitti Babu, AK and Deepankumar, K and Vijayan, M},
title = {Role of voltage-dependent anion channel 1 in neurodegeneration: Mechanisms, implications, and therapeutic potential.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00368},
pmid = {40903965},
issn = {1673-5374},
abstract = {Voltage-dependent anion channel 1 is an integral outer membrane protein of the mitochondria that governs apoptosis, enables metabolite exchange, and influences mitochondrial activity. In neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, and Alzheimer's disease, oxidative stress, neuroinflammation, and mitochondrial dysfunction are frequent features. Voltage-dependent anion channel 1 is a key regulator of these processes. This review described the structure, membrane topology, and physiological function of voltage-dependent anion channel 1 in neurons and glial cells. We emphasize how it affects mitophagy, oxidative damage, and changes in mitochondrial permeability. Special attention is focused on how voltage-dependent anion channel 1 interacts with pathogenic proteins that damage mitochondrial integrity and cause neurotoxicity, including mutant huntingtin, phosphorylated tau, α-synuclein, amyloid-beta, and TAR DNA-binding protein 43. Furthermore, the paper examines the function of voltage-dependent anion channel 1 in astrocytic dysfunction and microglial activation, highlighting its impact on neuroinflammation. In a nutshell, we assess treatment strategies that target voltage-dependent anion channel 1, such as VBIT-4, a selective inhibitor of voltage-dependent anion channel 1 oligomerization, and newer methods, including structure-based drug design and CRISPR/Cas9 regulation. Improved knowledge of the hinter voltage-dependent anion channel 1 of the molecular mechanism may allow for new therapeutic approaches in neurodegenerative diseases.},
}

@article {pmid40903956,
year = {2025},
author = {Chen, Y and Yin, P and Chen, Q and Zhang, Y and Tang, Y and Jin, W and Yu, L},
title = {Neurodegenerative diseases and immune system: From pathogenic mechanism to therapy.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00274},
pmid = {40903956},
issn = {1673-5374},
abstract = {Neurodegenerative diseases are a class of disorders with the gradual loss of the central nervous system and peripheral nervous system. Neurodegenerative diseases manifest primarily as cognitive and behavioral disorders that adversely affect the lives of millions of people worldwide. Therefore, it is necessary to elucidate the mechanism of neurodegenerative diseases further and find effective new therapies. In recent years, increasing evidence has shown that the immune system plays a significant role in the pathophysiology of neurodegenerative diseases and regulates this process. The central and peripheral immune systems exert different roles in the disease progression. The development of neurodegenerative diseases is influenced by interactions between them. This review focuses on how the immune system, including microglia mediated nucleotide-binding oligomerization domainlike receptor protein 3 inflammation activation and T cell-mediated neuroinflammation, interactions with neurodegenerative diseases by modulating protein aggregation and blood-brain barrier permeability. Besides, we gave particular attention to glial cell-centered multicellular interactions and the inflammatory signaling pathway. Insight into the immune system's functions and cellular interactions is essential for progressing disease research. In addition, the functions and mechanisms of these immune cells also suggest new ideas and targets for treatment. Therefore, this review summarizes some of the existing treatment strategies for amyloid-beta, tau, neuroinflammation, α-synuclein, associated microbiota, immune modulation, and neural injury repair. In addition, this review summarizes and compares animal models of different common neurodegenerative diseases and clinical research progress. In view of the current research status, new research directions and suggestions are proposed.},
}

@article {pmid40903950,
year = {2025},
author = {Liu, Y and Tang, T and Cai, H and Liu, Z},
title = {Bidirectional communication between the gut microbiota and the central nervous system.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00434},
pmid = {40903950},
issn = {1673-5374},
abstract = {In recent years, an increasing number of researchers have become interested in the bidirectional communication between the gut microbiota and the central nervous system. This communication occurs through the microbiota-gut-brain axis. As people age, the composition of the gut microbiota undergoes considerable changes, which are now known to play an important role in the development of many neurodegenerative diseases. This review aims to investigate the complex bidirectional signaling pathways between the gut and the brain. It summarizes the latest research findings on how the gut microbiota and its metabolites play critical roles in regulating inflammation, maintaining gut health, and influencing the development of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The review also analyzes the current clinical applications of gut microbiota-based treatments for neurological disorders, including fecal microbiota transplantation, probiotics, and prebiotics. Many studies show that the gut microbiota affects the brain in several ways. For example, it can produce substances such as short-chain fatty acids and activate inflammatory pathways. Studies involving animals and laboratory models have demonstrated that adjusting the gut microbiota can help improve behavior and reduce neurological problems. Recent metagenomic and metabolomics studies have shown that the microbiota plays a crucial role in maintaining the organism's health. Microorganisms primarily colonize the gut and are involved in host nutrient metabolism, maintaining the structural integrity of the intestine, preserving the intestinal mucosal barrier, and modulating the immune system. The gut microbiota communicates with the brain through a bidirectional microbiota-gut-brain axis. The composition of the gut flora changes considerably with age, and ecological dysregulation has been recognized as one of the twelve most recent hallmarks of aging. Recent studies have linked these changes to a variety of age-related neurological disorders, including Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, multiple sclerosis, and Huntington's disease. Specifically, the gut microbiota influences the brain through the production of key metabolites such as short-chain fatty acids and the activation of inflammatory and other relevant signaling pathways. In preclinical studies, targeted modulation of the gut microbiota, through methods such as fecal microbiota transplantation, probiotics, and prebiotics, has demonstrated potential in improving host behavioral outcomes. Therefore, gut microbiotabased treatments offer new hope for the treatment of nervous system diseases. However, due to the complexity of the gut microbiota and the potential adverse reactions associated with these therapies, researchers need to carefully assess their safety and efficacy before widespread clinical application.},
}

@article {pmid40901333,
year = {2025},
author = {Agrawal, H and Gupta, N},
title = {Deep learning models for pathological classification and staging of oesophageal cancer.},
journal = {World journal of clinical oncology},
volume = {16},
number = {8},
pages = {109893},
pmid = {40901333},
issn = {2218-4333},
abstract = {This letter comments on Wei et al's study applying the Wave-Vision Transformer for oesophageal cancer classification. Highlighting its superior accuracy and efficiency, we discuss its potential clinical impact, limitations in dataset diversity, and the need for explainable artificial intelligence to enhance adoption in pathology and personalized treatment.},
}

@article {pmid40901171,
year = {2025},
author = {Budha, B and Chapagain, A and Adhikari, D and Bajracharya, S and Poudel, D and Budha, R and Adhikari, S and Gurmaita, RK},
title = {Acquired hemophilia a in a female with minimal change disease and hypothyroidism: a rare case report.},
journal = {Annals of medicine and surgery (2012)},
volume = {87},
number = {9},
pages = {6168-6172},
pmid = {40901171},
issn = {2049-0801},
abstract = {INTRODUCTION: Juvenile amyotrophic lateral sclerosis (J-ALS) is extremely rare neurodegenerative motor neuron disorder that begins in early childhood or adolescence, before the age of 25 years old. It is characterized by gradual disease progression with comparison to adult-onset ALS and is often linked to genetic mutations.

CASE PRESENTATION: A 16-years-old female presented with long history of generalized weakness since age of 10 years, followed by bilateral sensorineural hearing loss, bulbar symptoms, and limb spasticity. Neurological examination revealed upper motor neuron signs in upper limbs, lower motor neuron signs in lower limbs, and bulbar involvement. Nerve conduction test was normal however, MRI showed early degenerative changes, and diagnosed with J-ALS after careful evaluation. She was started on Riluzole. Despite ICU care and supportive interventions including PEG and tracheostomy, she succumbed to respiratory failure.

DISCUSSION: Rarity, atypical presentation, and finical constraints can delay diagnosis of J-ALS. However, early diagnosis after careful evaluation of clinical symptoms, medical history, electrophysiological and imaging studies followed by prompt treatment with Riluzole and supportive interventions can help prolong survival and improve quality of life.

CONCLUSION: J-ALS is a rare motor neuron disease which possess immense diagnostic challenges, can exhibit relentless progression over short period of time with time.},
}

@article {pmid40898684,
year = {2025},
author = {Zhu, Y and Bai, J and Wang, H and Li, M and Yang, F and Pang, X and Du, R and Zhao, J and Huang, X and Cui, F},
title = {The difference between cystatin C- and creatinine-based estimated glomerular filtration rate and survival in amyotrophic lateral sclerosis: a population-based cohort study.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/17582024.2025.2554224},
pmid = {40898684},
issn = {1758-2032},
abstract = {OBJECTIVES: We investigated the relationship between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFRdiff) and amyotrophic lateral sclerosis (ALS) outcomes.

METHODS: We enrolled ALS patients diagnosed between January 2014 and December 2019. Experienced neurologists followed up the participants until January 2022. Absolute difference between eGFR (eGFRabdiff) and relative difference between eGFR (eGFRrediff) were obtained. Cox proportional hazard models were used to evaluate the relationship between eGFRdiff and ALS survival.

RESULTS: Negative eGFRabdiff were common in the patients (74.7%). For each SD increase of eGFRabdiff, the risk of poor prognosis for ALS patients decreased by 1.9% (HR, 0.981; 95% CI, 0.973-0.989). For each 10% increment in eGFRrediff, the risk of poor prognosis for ALS patients decreased by 17.7% (HR, 0.823; 95% CI, 754-0.898).

CONCLUSIONS: We found that large eGFRdiff was associated with poor prognosis in ALS. Monitoring eGFRdiff in ALS population facilitates prognostic stratification assessment and precise management.},
}

@article {pmid40897992,
year = {2025},
author = {Quigley, SE and Quigg, KH and Goutman, SA},
title = {Genetic and Mechanistic Insights Inform Amyotrophic Lateral Sclerosis Treatment and Symptomatic Management: Current and Emerging Therapeutics and Clinical Trial Design Considerations.},
journal = {CNS drugs},
volume = {},
number = {},
pages = {},
pmid = {40897992},
issn = {1179-1934},
support = {R01NS120926/NH/NIH HHS/United States ; R01NS127188/NH/NIH HHS/United States ; R01TS000344/ACL/ACL HHS/United States ; R01TS000327//Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting both upper and lower motor neurons. ALS is classically characterized by painless progressive weakness, causing impaired function of limbs, speech, swallowing, and respiratory function. The disease is fatal within 2-4 years, often the result of respiratory failure. The pathologic hallmark for a majority of ALS cases is aberrant cytoplasmic accumulations of the nuclear protein TAR-DNA binding protein (TDP-43). A total of 10-15% of ALS can be attributed to a single gene mutation, known as genetic or "familial" ALS, while the remainder of cases are termed nongenetic or "sporadic" although heritability has been measured in up to 37% in this population. Complex interactions between genetics, environment, and physiologic susceptibility are thought to contribute to disease. Management is primarily supportive in nature, though there are several approved treatments worldwide. This review details the mechanisms and evidence of approved disease-modifying treatments, relevant measures to track disease burden and progression used in clinical trials, and approaches to pharmacologic management of common symptoms in ALS. As there is not currently a cure for ALS, research into the complex pathophysiologic and genetic alterations contributing to disease is of great interest. This review further discusses the current understanding of genetic etiologies and altered physiology leading to disease, such as neuroinflammation, integrated stress response, aberrant proteostasis and mitochondrial dysfunction, among others. The translation of preclinical discoveries into current investigational therapeutics, novel therapeutic categories such as antisense oligonucleotides and stem cell transplantation, as well as future horizons harnessing the power of artificial intelligence in drug development and clinical trials are discussed.},
}

@article {pmid40897843,
year = {2025},
author = {Lai, Q and Zhang, X and Jiang, S and Krzyaniak, MD and Alayoglu, S and Agarwal, A and Liu, Y and Edenfield, WC and Kobayashi, T and Wang, Y and Dravid, V and Wasielewski, MR and Miller, JT and Kratish, Y and Marks, TJ},
title = {Stable single-site organonickel catalyst preferentially hydrogenolyses branched polyolefin C-C bonds.},
journal = {Nature chemistry},
volume = {},
number = {},
pages = {},
pmid = {40897843},
issn = {1755-4349},
support = {DOE DE-SC0024448//U.S. Department of Energy (DOE)/ ; DE-FG02-99ER14999//U.S. Department of Energy (DOE)/ ; DE-SC0001329//U.S. Department of Energy (DOE)/ ; DE-FG02-99ER14999//U.S. Department of Energy (DOE)/ ; DE-SC0012704//U.S. Department of Energy (DOE)/ ; NSF ECCS-2025633//National Science Foundation (NSF)/ ; NNA04CC36G//NASA | Ames Research Center/ ; },
abstract = {Current methods of processing accumulated polyolefin waste typically require harsh conditions, precious metals or high metal loadings to achieve appreciable activities. Here we examined supported, single-site organonickel catalysts for polyolefin upcycling. Chemisorption of Ni(COD)2 (COD, 1,5-cyclooctadiene) onto Brønsted acidic sulfated alumina (AlS) yields a highly electrophilic Ni(I) precatalyst, AlS/Ni(COD)2, which is converted under H2 to the active AlS/Ni[II]H catalyst. This single-site system exhibits unique hydrogenolysis selectivity that favours cleaving branched polyolefin C-C linkages, enabling the hydrogenolytic separation of polyethylene and isotactic polypropylene (iPP) mixtures. Moreover, AlS/Ni[II]H remains highly selective and active for hydrogenolysis of iPP admixed with polyvinyl chloride, and the spent catalyst can be repeatedly regenerated by AlEt3 treatment. Experimental mechanistic analysis and density functional theory modelling reveal a turnover-limiting C-C scission pathway featuring β-alkyl transfer and strong olefin binding. These results highlight the potential of nickel-based systems for the selective upcycling of complex plastic waste streams.},
}

@article {pmid40894255,
year = {2025},
author = {Hu, N and Chen, L and Hu, G and Ma, R},
title = {Advancements in extracellular vesicle therapy for neurodegenerative diseases.},
journal = {Exploration of neuroprotective therapy},
volume = {5},
number = {},
pages = {},
doi = {10.37349/ent.2025.1004104},
pmid = {40894255},
issn = {2769-6510},
abstract = {Neurodegenerative diseases represent a significant and growing challenge to public health worldwide. Current therapeutic strategies often fall short in halting or reversing disease progression, highlighting the urgent need for novel approaches. Extracellular vesicles (EVs) have garnered attention as potential therapeutic agents due to their role in intercellular communication and their ability to transport bioactive cargo, including proteins, nucleic acids, and lipids. This review provides a comprehensive overview of the biology of EVs, their involvement in neurodegenerative diseases, and the potential for EV-based therapies. We discuss the different types of EVs, their biogenesis, and their cargo composition, emphasizing their relevance to neurological processes such as protein misfolding, neuroinflammation, and oxidative stress. Preclinical studies investigating EVs as carriers of therapeutic cargo and their ability to promote neuronal survival and regeneration are examined, with a focus on evidence from animal models of neurodegenerative disorders. We explore the use of EVs in the treatment of neurodegenerative diseases, including ongoing clinical trials, methods for EV isolation and modification, and future perspectives on personalized EV-based therapies designed to meet the unique needs of individual patients. Overall, this review highlights the potential of EVs as a promising avenue for neurodegenerative disease therapy, while also addressing key research gaps and translational hurdles that need to be overcome for their successful clinical implementation.},
}

@article {pmid40885478,
year = {2025},
author = {Hafiz, B and Aldahlawi, A and Ashqar, A and Hamzah, A and Alotaibi, Y and Bajunaid, K and Baeesa, S},
title = {Outcomes of Surgical Versus Endovascular Treatment of Spinal Dural Arteriovenous Fistula: A Systematic Review and Meta-Analysis.},
journal = {World neurosurgery},
volume = {},
number = {},
pages = {124420},
doi = {10.1016/j.wneu.2025.124420},
pmid = {40885478},
issn = {1878-8769},
abstract = {BACKGROUND: Spinal dural arteriovenous fistulas (SDAVFs) are the most prevalent type of spinal vascular malformation and can lead to progressive neurological impairments if left untreated. Endovascular embolization and microsurgical resection are treatment options, although the optimal treatment method remains a subject of debate.

OBJECTIVE: A comprehensive systematic review and meta-analysis to compare the endovascular and microsurgical treatment outcomes of SDAVFs.

METHODS: An exhaustive literature search was conducted in the PubMed, Embase, Scopus, and Web of Science databases, encompassing publications from 2014 to 2024. A total of 522 patients from seven studies (417 surgical and 105 endovascular) met the inclusion criteria. Information on post-treatment complications, recurrence/failure rates, and functional improvement as assessed by the Aminoff-Logue Scale (ALS) or modified ALS (mALS) was extracted. I[2] statistics were used to evaluate heterogeneity, and random-effects models were used to compute risk ratios (RRs) and odds ratios (ORs).

RESULTS: Compared to endovascular intervention, surgical treatment was linked to significantly lower rates of recurrence or treatment failure (RR: 0.19; 95% CI: 0.09-0.39; p < 0.001), especially in long-term follow-up and thoracic-level studies. With greater ALS/mALS gains and a higher percentage of patients achieving full or partial recovery, functional improvement favored surgery. Although complication types varied, complication rates were similar across modalities (OR: 0.84; 95% CI: 0.48-1.49). Asymmetry in funnel plots indicated possible publication bias in favor of successful surgical outcomes.

CONCLUSION: For SDAVFs, surgical ligation provides better long-term results than endovascular embolization in terms of neurological recovery and recurrence prevention. Even though both procedures are usually safe, surgery is the recommended first-line course of action due to the higher failure and recurrence rates linked to embolization, especially in patients with operable anatomy and progressive symptoms.},
}

@article {pmid40884436,
year = {2025},
author = {Berry, JD and Bowser, R},
title = {Cardiac Troponin T in Tofersen-Treated SOD1 ALS Patients: Beginning to Resolve the Catch-22 of Identifying Treatment Responsive Biomarkers in ALS Drug Development.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70017},
pmid = {40884436},
issn = {1097-4598},
}

@article {pmid40883656,
year = {2025},
author = {García-Parra, B and Guiu, JM and Povedano, M and Modamio, P},
title = {Geographic distribution of amyotrophic lateral sclerosis-related genes: a systematic review.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/17582024.2025.2554382},
pmid = {40883656},
issn = {1758-2032},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rare motor neuron disease. There is no effective treatment, but disease-modifying therapies do exist. Objective. To identify the geographical distribution of ALS-related genes.

METHODS: A systematic review was conducted according to the PRISMA 2020 guidelines in PubMed and Web of Science. Inclusion criteria: patients with ALS, no age or gender restriction, English and Spanish languages, studies published until 31 July 2025.

RESULTS: Thirty-eight results were obtained, 32 were selected, 19 articles were assessed for eligibility, and 8 articles were included from databases. Three articles recommended by clinical experts were added, so 11 results were reviewed. This research showed that published articles on the geographic distribution of ALS-related genes are limited, particularly for underrepresented regions such as Africa.

CONCLUSION: The findings demonstrate the need for intensified international research to improve knowledge of the genetic epidemiology of ALS.},
}

@article {pmid40883810,
year = {2025},
author = {Downs, J},
title = {A shift or a substitution? On naming, exclusion, and co-production in longstanding eating disorders: matters arising from Lubieniecki et al. (2025).},
journal = {Journal of eating disorders},
volume = {13},
number = {1},
pages = {196},
pmid = {40883810},
issn = {2050-2974},
abstract = {This Matters Arising piece responds to the article by Lubieniecki et al. (2025), which explores lived experience perspectives on the 'SEED' (Severe and Enduring Eating Disorder) classification. Written from the standpoint of someone with lived experience of a longstanding eating disorder and professional involvement in research, policy, and service development, the piece supports Lubieniecki et al.'s analysis of 'SEED' as both validating and restrictive. It extends their work by situating the classification within a broader landscape of psychiatric labelling associated with treatment exclusion. The limitations of replacing 'SEED' with alternative terminology alone are considered, with emphasis on the need for corresponding reforms to care pathways and their provision. The author highlights how diagnostic language can serve not only descriptive but also administrative and prognostic functions, often reflecting institutional constraints rather than individual need. The importance of co-produced approaches to diagnostic frameworks is also discussed, with emphasis on embedding lived experience throughout classificationand service design.},
}

@article {pmid40881744,
year = {2025},
author = {Zeppieri, M},
title = {Advantages and future outlooks in the use of telemedicine in liver transplantation.},
journal = {World journal of transplantation},
volume = {15},
number = {3},
pages = {104825},
doi = {10.5500/wjt.v15.i3.104825},
pmid = {40881744},
issn = {2220-3230},
abstract = {To maintain care during the coronavirus disease 2019 outbreak, telemedicine was implemented quickly. Jowell et al's pandemic study on telehealth integration and liver transplant evaluation is examined in this editorial. The study showed that telehealth did not affect clinical outcomes including time to evaluation, listing rates, or pre-transplant death. The study found that telehealth did not increase sociodemographic inequalities, suggesting a fair care framework. The editorial discusses how telemedicine in hepatology might help patients receive expert treatment while reducing logistical and financial burdens. Telehealth can democratize liver transplantation by delivering equivalent clinical results as in-person examinations. However, the editorial highlights technological barriers, difficulties in remotely assessing mental and physical health, and the need for specialized outreach to underserved communities. After the pandemic, telemedicine is essential to a more flexible, patient-centered healthcare system. The editorial encourages creativity and research to overcome challenges, improve hybrid care models, and ensure telehealth's egalitarian and successful potential. Pandemic insights can improve liver transplantation treatment and outcomes for diverse patient populations.},
}

@article {pmid40879603,
year = {2025},
author = {Karimi, S and Ghaheri, A and Madani, H and Beheshti Maal, A and Sadri, B and Khodadoust, E and Sharafi, F and Vosough, M and Nabavi, SM},
title = {Intravenous vs intrathecal transplantation of allogeneic GMP/GCP compliant Wharton's jelly mesenchymal stromal cells in ALS patients: a phase I study.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/17582024.2025.2553499},
pmid = {40879603},
issn = {1758-2032},
abstract = {INTRODUCTION: There are a few therapeutic approaches for Amyotrophic Lateral Sclerosis (ALS) which can only slow down or stop the disease progression for a limited period of time. Since it has been proven that Mesenchymal Stromal Cells (MSCs) produce neurotrophic factors and have some neuroprotective effects, stem cell therapy has been proposed as an alternative or add-on treatment for ALS patients.

METHOD & MATERIAL: In this open-label clinical trial, two-repeated dose of 60 million GMP compliant Wharton's Jelly-derived Mesenchymal Stromal Cells (WJ-MSCs) were transplanted intrathecally (#6 patients) or intravenously (#6 patients) twice with a 3-month interval.

RESULTS: No adverse events related to the intervention or injected cells were reported. While no significant improvement in the total revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) score or overall clinical efficacy was achieved, patients reported improvements in specific sub-items such as salivation, swallowing, and their speech. Additionally, reductions in muscle tremors and fasciculations, as well as increased muscle strength were observed.

CONCLUSION: In conclusion, using WJ-MSCs is safe and feasible in ALS patients, but the efficacy of these cells should be assessed in future studies with more patients, different routes of cell administration, and maybe with higher doses of the injected cells.},
}

@article {pmid40878665,
year = {2025},
author = {Abrahao, A and Da Silva, P and Ciepielewska, M and Zinman, L},
title = {Real-world safety and tolerability of intravenous edaravone in patients with amyotrophic lateral sclerosis.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/17582024.2025.2552610},
pmid = {40878665},
issn = {1758-2032},
abstract = {AIMS: This retrospective cohort study describes real-world safety and tolerability outcomes in United States-based edaravone-treated patients with ALS.

PATIENTS & METHODS: Amerita Specialty Infusion Services provided IV edaravone to patients with ALS treated with their first dose between 25 September 2017-30 September 2022. Mean ALS Functional Rating Scale-Revised (ALSFRS-R) scores and forced vital capacity (FVC) %-predicted measures were recorded within ± 100 days from care initiation to approximate baseline values.

RESULTS: Included patients (n = 243) received/were still receiving IV edaravone/edaravone oral suspension as of 30 September 2022. At initiation, 66.7% were male, mean age ± SD was 61.2 ± 11.2 years, and 61.3% were covered by government insurance. In patients with provider-recorded ALSFRS-R (n = 115) and FVC (n = 84) %-predicted measures within ± 100 days from care initiation, mean ± SD values were 35.1 ± 8.9 and 72.3% ± 21.7%, respectively. Mean ± SD therapy duration was 13.5 ± 11.4 months. Discontinuation reasons included death/hospice (n = 82), patient's choice (n = 38), doctor's choice (n = 31), insurance (n = 18), and other (n = 12). Reasons for IV edaravone discontinuation and IV edaravone administration access device were not associated.

CONCLUSIONS: Treatment discontinuation was primarily related to ALS disease progression/death, rather than safety or tolerability. This study representative of real-world patients with ALS suggests that edaravone showed consistent safety and tolerability profiles with previous studies.},
}

@article {pmid40878249,
year = {2025},
author = {Silva, MM and Cunha, EM and Briois, V and Rochet, A},
title = {Unraveling hydride dynamics on cubic palladium nanoparticles.},
journal = {Physical chemistry chemical physics : PCCP},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5cp02672e},
pmid = {40878249},
issn = {1463-9084},
abstract = {Palladium-based materials exhibit a high affinity for hydrogen molecules, enabling the effortless formation of a hydride phase. This property is widely exploited in several catalytic reactions and hydrogen storage materials. However, the effects of morphological parameters, support interactions, and formation kinetics remain incompletely understood. In this work, we applied in situ time-resolved X-ray absorption spectroscopy (XAS) to investigate the impact of nanoparticle sizes and support materials on the dynamic formation of palladium hydrides during thermal treatment under H2. A detailed analysis using multivariate curve resolution with alternating least squares (MCR-ALS) enabled the extraction of concentration profiles and the identification of pure species involved in the process, thereby revealing distinct kinetic behaviours across the samples. This study provides valuable insights into how particle size and support influence the kinetics of hydrogen absorption in palladium systems, which can significantly impact catalytic performance.},
}

@article {pmid40876427,
year = {2025},
author = {Ibrahim, SI and Zaher, DM and Hersi, FA and Hamouda, AO and Al Hindawi, MA and Omar, HA},
title = {Repurposing edaravone in oncology: Bridging antioxidant defense and immune modulation.},
journal = {International immunopharmacology},
volume = {164},
number = {},
pages = {115413},
doi = {10.1016/j.intimp.2025.115413},
pmid = {40876427},
issn = {1878-1705},
abstract = {Edaravone, a synthetic free radical scavenger originally approved for neurological disorders such as stroke and amyotrophic lateral sclerosis (ALS), is gaining attention for its emerging potential role in cancer. Beyond its well-established antioxidant properties, edaravone demonstrates significant anti-inflammatory and immunomodulatory activities, including the inhibition of key pathways such as NF-κB, JAK2/STAT3, and TLR4/IL-6, suggesting potential to modulate immune responses within the tumor microenvironment. This review discusses how edaravone disrupts oncogenic signaling, induces cell cycle arrest, and enhances apoptosis, particularly in cancer stem cells and therapy-resistant models. It also examines edaravone's dual role in combination therapies, where it may improve the cytotoxicity of chemotherapeutic and radiotherapeutic agents while simultaneously protecting normal tissues from treatment-induced toxicities. By linking mechanistic insights with therapeutic outcomes, this review highlights the rationale for repurposing edaravone as a potential adjuvant in cancer therapy. Although clinical data are currently limited, preliminary findings are encouraging and warrant further investigation into edaravone's potential use in cancer treatment regimens.},
}

@article {pmid40865585,
year = {2025},
author = {Xu, C and Naudet, F and Kim, TT and Hengartner, MP and Horowitz, MA and Kirsch, I and Moncrieff, J and Pigott, E and Plöderl, M},
title = {Large responses to antidepressants or methodological artifacts? A secondary analysis of STAR*D, a single-arm, open-label, non-industry antidepressant trial.},
journal = {Journal of clinical epidemiology},
volume = {},
number = {},
pages = {111943},
doi = {10.1016/j.jclinepi.2025.111943},
pmid = {40865585},
issn = {1878-5921},
abstract = {OBJECTIVES: To replicate Stone et al.'s (2022) [1] finding that the distribution of response in clinical antidepressant trials is trimodal with large, medium-effect, and small subgroups.

METHODS: To apply finite mixture modeling to pre-post Hamilton Depression Rating Scale (HDRS) differences (n = 2184) of STAR*D study's level 1, a single-arm, open-label study. For a successful replication, the best fitting model had to be trimodal, with comparable components as in Stone et al. Secondary/sensitivity analyses repeated the analysis for different baseline levels of depression severity, imputed values, and patient-reported depression symptoms.

RESULTS: The best fitting models were either bimodal or trimodal but the trimodal solution did not meet criteria for replication. The bimodal model had one component with HDRS mean change of M = -13.0, SD = 6.7 and included 65.3% of patients, and another component with M = -1.8, SD = 5.1, 34.7%, respectively. For the trimodal model, the component with the largest change (M = -14.3, SD = 6.4) applied to 52% of patients, which differed substantially from the large effect component in Stone et al. (M = -18.8, SD = 5.1) which applied to 7.2%. Secondary/sensitivity analyses arrived at similar conclusions and for patient-reported depression symptoms the best fitting models were unimodal or bimodal.

CONCLUSIONS: This analysis failed to identify the trimodal distribution of response reported in Stone et al. In addition to being difficult to operationalize for regulatory purposes, results from mixture modeling are not sufficiently reliable to replace the more robust approach of comparing mean differences in depression rating scale scores between treatment arms.},
}

@article {pmid40865525,
year = {2025},
author = {McEachin, ZT and Chung, M and Stratton, SA and Han, C and Kim, WJ and Sheth, U and Thomas, EV and Issenberg, E and Kamra, T and Merino, P and Levites, Y and Raj, N and Dammer, EB and Duong, DM and Ping, L and Shantaraman, A and Trautwig, AN and Gadhavi, J and Assefa, E and Gearing, M and Kelly, KM and Roemer, SF and DeTure, M and Asress, S and Kukar, T and Fournier, C and Dickson, DW and Petrucelli, L and Golde, TE and Oskarsson, B and Gendron, TF and Seyfried, NT and Glass, JD},
title = {Molecular impact of antisense oligonucleotide therapy in C9orf72-associated ALS.},
journal = {Cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cell.2025.07.045},
pmid = {40865525},
issn = {1097-4172},
abstract = {C9orf72-associated amyotrophic lateral sclerosis (c9ALS) is caused by an intronic G4C2 repeat expansion that leads to toxic RNA transcripts and dipeptide repeat proteins (DPRs). A clinical trial using the antisense oligonucleotide (ASO) BIIB078 to target these transcripts was discontinued after failing to provide clinical benefit. Here, we determine the extent of target engagement in the central nervous system (CNS) and elucidate pharmacodynamic cerebrospinal fluid (CSF) biomarkers following treatment. CSF from BIIB078-treated cases showed reduced DPRs and sustained increases in inflammatory biomarkers, including C-C motif chemokine ligand 26 (CCL26). BIIB078 was widely distributed in postmortem CNS tissue; however, DPRs and phosphorylated TDP-43 remained abundant. Proteomic signatures in c9ALS spinal cord were not altered with treatment, although a distinct increase in RNase T2 abundance that correlated with BIIB078 concentration was observed. Thus, despite widespread distribution, BIIB078 did not significantly impact key CNS pathologies, emphasizing the need to identify pharmacodynamic biomarkers that reflect disease-relevant neuropathological changes in response to ASO therapies.},
}

@article {pmid40860154,
year = {2025},
author = {Li, D and Wei, Y and Yang, R and Luo, X and Liu, Y and Zhao, W and Yang, H and Wu, Y and Wang, Y and Huang, Z},
title = {An unrecognized mechanism of self-protection in degenerating neurons mediated by astrocytic YAP through Wnts/β-catenin/EAAT2 signaling in C9orf72-poly-GA mice.},
journal = {Theranostics},
volume = {15},
number = {16},
pages = {8176-8201},
pmid = {40860154},
issn = {1838-7640},
mesh = {Animals ; *Astrocytes/metabolism/pathology ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; YAP-Signaling Proteins ; Mice ; Disease Models, Animal ; *C9orf72 Protein/genetics/metabolism ; Mice, Knockout ; *Excitatory Amino Acid Transporter 2/metabolism ; *Cell Cycle Proteins/metabolism ; *Adaptor Proteins, Signal Transducing/metabolism/genetics ; beta Catenin/metabolism ; Motor Neurons/metabolism/pathology ; *Wnt Signaling Pathway ; Neurons/metabolism ; Humans ; Signal Transduction ; },
abstract = {Rationale: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive loss of motor neurons in the central nervous system (CNS). Non-neuronal cells, particularly astrocytes, have been recognized as pivotal contributors to ALS onset and progression. However, the underlying mechanisms of interactions between astrocytes and motor neurons during ALS remain unclear. Recent studies have identified the neuronal Hippo kinase mammalian sterile 20-like kinase 1 (MST1) as a key regulator of neurodegeneration in ALS. Yes-associated protein (YAP), a major downstream effector of the Hippo pathway, is predominantly expressed in astrocytes. However, the role of astrocytic YAP in ALS and its underlying mechanisms remain unexplored. Methods: To evaluate the function of YAP in ALS, we established a C9orf72-poly-GA mouse model (ALS mice) via intracerebroventricular injection of AAV viruses. Furthermore, mice with conditional knockout (CKO) of YAP in astrocytes (YAP[GFAP]-CKO mice) were generated and then YAP[GFAP]-CKO ALS mice and their littermate controls (YAP[f/f] ALS mice) were used as experimental subjects. Behavioral tests, immunostaining, Nissl staining, quantitative real-time PCR (qPCR), and Western blotting were used to assess the effects of astrocytic YAP deletion in ALS progression. In addition, we investigated the role and mechanism of astrocytic YAP in the pathogenesis of ALS by integrating RNA sequencing (RNA-seq) from primary cultured astrocytes with single-nucleus transcriptomic (snRNA-seq) from C9orf72-ALS/FTD patients. Then, in vitro experiments including primary cultured astrocytes and neurons were used to further elucidate the potential molecular mechanism of astrocytic YAP in ALS. Finally, we evaluated the therapeutic effects of the excitatory amino acid transporter-2 (EAAT2) activator LDN-212320 and the Hippo kinase MST1/2 inhibitor XMU-MP-1 as candidate treatments for ALS. Results: We found that YAP was upregulated and activated specifically in astrocytes, but not in neurons or microglia, within the motor cortex of ALS mice. Conditional knockout of YAP in astrocytes exacerbated motor deficits, neuronal loss, pathological translocation of TDP-43, inflammatory infiltration, and reduced astrocytic proliferation in ALS mice. Mechanistically, Wnts secreted by degenerating neurons and astrocytes activated YAP/β-catenin signaling and further promoted the expression of EAAT2 in astrocytes, which prevented neuronal glutamate excitotoxicity, neuronal loss, and motor dysfunction in ALS mice. Interestingly, treatment with LDN-212320 promoted EAAT2 expression and partially restored motor deficits and neuronal loss in YAP[GFAP]-CKO ALS mice. Finally, activation of YAP by XMU-MP-1 upregulated β-catenin and EAAT2 expression, and partially alleviated motor deficits and neurodegeneration in ALS mice. Conclusions: These results identify an unrecognized mechanism of self-protection in degenerating neurons mediated by astrocytic YAP through Wnts/β-catenin/EAAT2 signaling to prevent glutamate excitotoxicity of neurons in ALS mice, and provide a novel drug target for ALS.},
}

Animals
*Astrocytes/metabolism/pathology
*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics
YAP-Signaling Proteins
Mice
Disease Models, Animal
*C9orf72 Protein/genetics/metabolism
Mice, Knockout
*Excitatory Amino Acid Transporter 2/metabolism
*Cell Cycle Proteins/metabolism
*Adaptor Proteins, Signal Transducing/metabolism/genetics
beta Catenin/metabolism
Motor Neurons/metabolism/pathology
*Wnt Signaling Pathway
Neurons/metabolism
Humans
Signal Transduction

@article {pmid40859959,
year = {2025},
author = {Mao, S and Qiao, R and Wang, Q and Shen, L and Li, D and Huo, X and Wang, J and Liu, K and Chen, W and Zhu, T and Zhang, B and Leng, S and Bai, Y},
title = {Activity and Heterogeneity of Astrocytes in Neurological Diseases: Molecular Mechanisms and Therapeutic Targets.},
journal = {MedComm},
volume = {6},
number = {9},
pages = {e70329},
pmid = {40859959},
issn = {2688-2663},
abstract = {Astrocytes, the most prevalent glial cells in the central nervous system (CNS), play crucial roles in maintaining CNS homeostasis and responding to various pathological stimuli. They play key roles in neural development, neurotransmission, neuroinflammation, metabolic support, and tissue repair. Recent advancements in single-cell sequencing have revealed the remarkable heterogeneity of astrocytes, with distinct subpopulations differentially contributing to disease progression in neurological disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, ischemic stroke, intracerebral hemorrhage, and multiple sclerosis. In addition, they play an important role in various behavioral neuropsychiatric disorders. This review highlights the dual roles of astrocytes in disease progression, driven by their diverse molecular profiles and functions. It outlines the key molecular mechanisms underlying astrocyte heterogeneity and their impact on neuroinflammation, neuronal support, and ionic balance regulation. Additionally, the review discusses potential therapeutic strategies targeting astrocytes to modulate these processes, aiming to improve treatment outcomes in neurological diseases. By elucidating the specific roles of astrocyte subsets in disease, this review seeks to advance the development of precision medicine for astrocyte-related neurological disorders.},
}

@article {pmid40857020,
year = {2025},
author = {Krivickas, B and Scirocco, E and Giacomelli, E and Sharma, S and Benson, M and Keegan, M and Kulesa-Kelley, J and Chibnik, LB and Casagrande, G and Heyd, L and Chase, M and Drake, K and Mohapatra, S and Hagar, JL and Hasenoehrl, MG and Dagostino, D and Sherman, AV and Leite, A and Yu, H and Rosenthal, J and Miller, T and McCaffrey, A and Gwathmey, K and Locatelli, E and Bayat, E and Heitzman, D and Young, E and Goyal, NA and Whitesell, J and Felice, K and Ilieva, H and Swenson, A and Walk, D and Alameda, G and Foster, L and McIlduff, CE and Walsh, A and Zilliox, L and Ajroud-Driss, S and Bodkin, C and Katz, J and Ladha, S and Rivner, M and Rosow, L and Twydell, P and Wasiewski, W and Babu, S and Berry, JD and Paganoni, S},
title = {Multicenter Expanded Access Protocol for Research Through Access to Trehalose in People With Amyotrophic Lateral Sclerosis.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70011},
pmid = {40857020},
issn = {1097-4598},
support = {UF1NS131791//Office of the Director of the National Institutes of Health/ ; },
abstract = {INTRODUCTION/AIMS: Expanded access protocols (EAPs) allow individuals ineligible for clinical trials to receive investigational products. EAP data can be collected in parallel to randomized clinical trials (RCTs) and serve as a source of evidence in clinical practice. Here, we present the results of a National Institutes of Health (NIH)-funded EAP for amyotrophic lateral sclerosis (ALS).

METHODS: Participants received trehalose, a drug studied in a parallel RCT, for up to 24 weeks; clinical and biomarker data were collected throughout the study.

RESULTS: Seventy participants were enrolled at 20 study centers across the United States. Treatment with trehalose did not affect the levels of neurofilament light chain [estimated flat slope per month was -0.005, SE = 0.0078; 95% CI (-0.021, 0.011)] or disease progression [estimated least square mean change of the ALS Functional Rating Scale-Revised total score and slow vital capacity (percent predicted) from baseline to Week 24 were -5.6 (0.67); 95% CI (-7.0, -4.3) and -4.53 (4.308); 95% CI (-13.55, 4.48)], respectively. No unexpected treatment-related risks were identified. Serious adverse events were deemed not related to trehalose (20 occurrences in 13 [18.6%] participants with eight deaths).

DISCUSSION: This EAP establishes a framework for implementing multi-center EAPs that complement data collected from RCTs. Additional NIH-funded EAPs are currently underway. Data and additional serum samples collected in this study are available to the research community for further study.

TRIAL REGISTRATION: ClinicalTrials.gov: NCT05597436.},
}

@article {pmid40854024,
year = {2025},
author = {Stiles, K and LaBarbera, V},
title = {Recognition and Treatment of Concurrent Amyotrophic Lateral Sclerosis and Myasthenia Gravis.},
journal = {Rhode Island medical journal (2013)},
volume = {108},
number = {9},
pages = {16-18},
pmid = {40854024},
issn = {2327-2228},
}

@article {pmid40851280,
year = {2025},
author = {Tröger, J and Rouvalis, A and Dörr, F and Schwed, L and Linz, N and König, A and Machts, J and Vielhaber, S and Thies, T and Prudlo, J and Hermann, A and Kasper, E},
title = {Automatically measured speech intelligibility models bulbar-specific disease severity and progression in Amyotrophic Lateral Sclerosis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/21678421.2025.2549317},
pmid = {40851280},
issn = {2167-9223},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to widespread motor deterioration, including significant motor speech impairments. Speech intelligibility is a crucial component of communication affected in ALS, requiring objective, scalable assessment methods as an indicator of disease progression and treatment efficacy. Objective: This study investigates whether speech and bulbar function in ALS could be evaluated and monitored utilizing an automated digital measure of speech intelligibility derived from naturalistic picture descriptions. Methods: Speech recordings from 44 patients living with ALS (plwALS) and 49 matched healthy controls (HC) were analyzed and processed utilizing an automated speech analysis pipeline to extract an intelligibility score. These were part of a cross-sectional and longitudinal study involving two assessments. Results: The findings confirmed that speech intelligibility is significantly reduced in plwALS compared to HC. Those with bulbar-onset ALS have lower intelligibility than those with spinal-onset ALS, and the intelligibility of individuals with bulbar symptoms-regardless of the onset type-is lower than in plwALS without bulbar symptoms. Declining ALS-related speech scores correspond with worsening intelligibility in longitudinal assessments. Intelligibility correlates strongly with bulbar-specific clinical measures but not with global scores, highlighting its role in tracking bulbar progression. In some plwALS, we were able to demonstrate that automated speech analyses are more effective in detecting worsening in intelligibility earlier than standard clinical scoring. Conclusion: Our findings highlight that automated speech intelligibility assessments can be a valuable marker to improve clinical monitoring and facilitate earlier intervention in ALS as a supplement to standard assessments.},
}

@article {pmid40849781,
year = {2025},
author = {Kurochkina, N and Rudrabhatla, P},
title = {Role of Calmodulin in Neurodegeneration and Neuroprotection.},
journal = {Mini reviews in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0113895575403663250812115441},
pmid = {40849781},
issn = {1875-5607},
abstract = {Intracellular calcium (Ca2+) levels are critical in maintaining cellular activities and are tightly regulated. Neuronal degeneration and regeneration rely on calcium-binding proteins. Calmodulin (CaM) is a calcium sensor and the primary regulator of receptors and ion channels that maintain calcium homeostasis. The calmodulin binding domains are present in proteins that serve as risk factors and biomarkers associated with Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, and other neurodegenerative diseases, suggesting calmodulin ligands as emerging therapeutic targets for treatment. Inhibiting CaM to develop new therapies has drawbacks, as CaM is a ubiquitous molecule involved in many regulatory pathways. Recently, new strategies for disrupting CaM interactions with its targets have shown promising approaches to treatment. The structures of human CaM, its binding proteins, and inhibitors are well studied, with particular emphasis on the conservation of CaM amino acid sequences and the ability to bind protein fragments of high sequence variability, which exhibit common characteristics of amphipathic helices carrying basic amino acids. In this review, we discuss structural characteristics of CaM and its ligands in the context of transcriptional regulation. Specific binding of CaM to (1) basic region/helix-loop-helix/leucine zipper and (2) helix-turn-helix high mobility group box containing Sox families of transcription factors highlights common features of CaM binding sequences, which suggest their regulatory functions. We describe key proteins involved in neurodegeneration and transcription factors subject to calmodulin regulation that are candidates for the development of new approaches to treating neuronal diseases.},
}

@article {pmid40849485,
year = {2025},
author = {Helal, MM and AbouShawareb, H and Abbas, OH and Haddad, R and Zain, Y and Osman, ASA and Hassan, AK},
title = {GLP-1 receptor agonists in Parkinson's disease: an updated comprehensive systematic review with meta-analysis.},
journal = {Diabetology & metabolic syndrome},
volume = {17},
number = {1},
pages = {352},
pmid = {40849485},
issn = {1758-5996},
abstract = {Previous studies have demonstrated an increased risk of developing Parkinson's disease (PD) in patients with type 2 diabetes mellitus (T2DM), as well as more severe and rapid motor and non-motor deterioration in diabetic PD patients compared to their non-diabetic counterparts. Additional research has suggested that diabetic subjects treated with glucagon-like peptide-1 (GLP-1) receptor agonists exhibit a reduced incidence of PD compared to those receiving other anti-diabetic medications. GLP-1 receptor agonists are FDA-approved therapies for T2DM, and recent studies have explored their potential as repurposed treatments for neurodegenerative diseases, including PD, AD, and ALS, as well as cerebrovascular disorders. This systematic review aims to assess the available literature on the efficacy and safety profiles of GLP-1 receptor agonists in PD management. A comprehensive search of PubMed, Scopus, CENTRAL, Web of Science, Embase, and ClinicalTrials.gov was conducted to identify relevant studies. The primary outcomes of this review include motor impairment in PD, as assessed by MDS-UPDRS Part III, as well as motor complications (Part IV) and motor experiences of daily living (Part II), and the incidence of gastrointestinal and systemic side effects. Meta-analysis showed that GLP-1 receptor agonists significantly improved motor function, as reflected by MDS-UPDRS Part III scores in the ON state (mean difference = - 2.88; p = 0.01; I[2] = 30%), although they were associated with a higher incidence of adverse events across all safety outcomes. Findings and conclusions of this review will contribute to a clearer understanding of the therapeutic potential of GLP-1 receptor agonists in PD, guiding future clinical research and treatment strategies.},
}

@article {pmid40849231,
year = {2025},
author = {Fu, X and Gable, K and Gupta, SD and Zhang, K and Jia, B and Wang, W and Yang, X and Wang, L and Ge, L and Bönnemann, CG and Dunn, TM and Xiong, H},
title = {Characterization of novel and recurrent SPTLC2 variants in childhood-onset amyotrophic lateral sclerosis: Insights into sphingolipid dysregulation.},
journal = {Journal of neuromuscular diseases},
volume = {},
number = {},
pages = {22143602251370586},
doi = {10.1177/22143602251370586},
pmid = {40849231},
issn = {2214-3602},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disorder that progressively affects motor neurons. Gain-of-function mutations in serine palmitoyltransferase (SPT) genes, notably SPTLC1 and SPTLC2, have been linked to juvenile ALS. Here, we describe two childhood-onset ALS cases with distinct SPTLC2 mutations, providing new insights into sphingolipid dysregulation and its role in ALS pathogenesis.

MATERIAL AND METHODS: Two Chinese patients with early-onset ALS, both carrying SPTLC2 mutations, were recruited from Beijing Children's Hospital. We conducted whole-exome sequencing (WES) to identify genetic variants, followed by Sanger sequencing for validation. Sphingolipid profiles were analyzed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Clinical evaluations included neurological assessments, brain MRI and electromyography. Additionally, mutant cell lines were established to assess the functional effects of the specific mutations.

RESULTS: Patient 1, a 6-year-old male, exhibited a novel heterozygous de-novo SPTLC2 variant (c.197T > G, p.T66R). Patient 2, a 7-year-old female, had a recurrent heterozygous de-novo SPTLC2 variant (c.778G > A, p.E260K). Both patients showed elevated levels of specific sphingolipids compared to controls, with distinct profiles between the SPTLC2-ALS and SPTLC1-hereditary sensory and autonomic neuropathy type 1 (HSAN1) cases. The novel p.T66R mutation was predicted to alter protein interactions within the SPT complex, potentially impairing sphingolipid homeostasis. Functional studies further revealed that the p.T66R variant reduces the inhibitory regulation of SPT by ORMDL proteins, leading to unrestrained SPT activity and excess sphingolipid production.

CONCLUSIONS: Our findings identify a novel SPTLC2 variant linked to childhood-onset ALS and reveal altered sphingolipid profiles associated with different genetic mutations. These results underscore the importance of sphingolipid metabolism in ALS and suggest potential avenues for targeted therapeutic interventions. Further research is needed to explore treatment options aimed at modulating sphingolipid levels and correcting genetic defects, as well as investigating potential biomarkers for early diagnosis.},
}

@article {pmid40848858,
year = {2025},
author = {Chen, X and Ma, Y and Liu, H and Wang, Y},
title = {Multifunctional regulation and treatment of ubiquitin specific protease 10.},
journal = {Biochemical pharmacology},
volume = {},
number = {},
pages = {117251},
doi = {10.1016/j.bcp.2025.117251},
pmid = {40848858},
issn = {1873-2968},
abstract = {USP10 is a critical deubiquitinating enzyme within the ubiquitin-specific protease family, playing multifaceted roles in cellular physiology and disease pathogenesis. Structurally composed of a G3BP1-interacting motif, a N-terminal domain (mediating most protein interactions), and a catalytic USP domain (residues 415-795, catalytic triad C424-H736-D751), USP10 regulates diverse cellular pathways by stabilizing key proteins through deubiquitination. It exhibits context-dependent functional duality, particularly in cancer: USP10 promotes tumorigenesis in various cancers (e.g., glioblastoma, esophageal, pancreatic, breast cancers) by stabilizing oncoproteins like CCND1, YAP1, HDAC7, and RUNX1, enhancing proliferation, metastasis, and immune evasion. Conversely, it suppresses tumors (e.g., NSCLC, CRC, thyroid cancer) by stabilizing tumor suppressors like p53, PTEN, and Axin1, inhibiting pathways such as Wnt/β-catenin. Beyond oncology, USP10 contributes to neurodegenerative diseases (neuroprotective in PD/ALS, neurotoxic in AD via Tau stabilization), viral immunity (inhibits SARS-CoV-2 infection), inflammatory responses, male reproduction, and metabolic/cardiovascular disorders. Its regulatory mechanisms include phosphorylation (e.g., by AMPK, AKT, ATM) controlling subcellular localization and activity, and ubiquitination via USP13. USP10's therapeutic significance drives inhibitor development (Spautin-1, D1, Wu-5, P22077, Parthenolide), though cross-reactivity within the USP family due to conserved catalytic domains remains a challenge. Novel strategies like PROTACs and engineered ubiquitin variants (UbVs) offer promise for future selective targeting of USP10 dysregulation in diverse diseases. A comprehensive understanding of its structure and context-specific functions is essential for exploiting its full therapeutic potential.},
}

@article {pmid40848625,
year = {2025},
author = {Gauden, AJ and Gu, B and Han, S and Telischak, NJ and Dodd, R and Do, HM and Marks, MP and Steinberg, GK},
title = {Multimodality treatment maximizing outcome in spinal dural arteriovenous fistulae.},
journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia},
volume = {141},
number = {},
pages = {111571},
doi = {10.1016/j.jocn.2025.111571},
pmid = {40848625},
issn = {1532-2653},
abstract = {BACKGROUND: Spinal dural arteriovenous fistula (sDAVF) is a rare cause of myelopathy and progressive paraplegia. sDAVFs are the most frequent type of spinal vascular malformation and comprise 70 % of all vascular spinal malformations. Despite the availability and published efficacy of both microsurgical resection and endovascular embolization, the optimal treatment for sDAVFs remains to be determined. We aimed to assess the efficacy of a multimodal treatment approach to sDAVFs at our institution.

METHODS: A retrospective review of all sDAVFs treated between 1998 and 2021 at Stanford Hospital and Clinics was conducted. The medical records were inspected and data, including presenting symptoms, duration, angiographic features, and treatment modality, were extracted. Cure was defined as the absence of an arteriovenous fistulous connection on digital subtraction angiography and radiologic improvement on follow-up MRI. Functional outcomes were assessed at presentation and at last follow-up using the Aminoff-Logue Scale (ALS).

RESULTS: 47 patients underwent treatment of sDAVFs between August 1998 to May 2021. As an initial treatment, 32 patients underwent microsurgical excision, and 15 had endovascular embolization. Radiological cure was achieved in 84.4 % of patients during the first treatment and in 97.9 % of patients at the final treatment time point. At initial treatment, surgery cured the sDAVF in 84.4 % of patients, with endovascular embolization curing in 86.7 % of patients. When assessed as an additional treatment for failed prior treatment, surgery achieved cure in 80 % of patients and endovascular embolization in 100 % of patients. At all time points, high cure rates were observed, with success rates achieving 96.9 % and 100 % for surgery and endovascular embolization, respectively. A significant improvement in ALS Gait score was noted after treatment, with a mean reduction of 0.6 from baseline (p = 0.0003). A similar improvement trend was observed in the ALS Micturition score with a mean decrease of 0.3 points (p = 0.057).

CONCLUSIONS: Our study demonstrates high efficacy for cure and improved functional outcomes in both surgical and endovascular treatments, assuming good patient selection. This series also highlights the importance of a multimodality treatment approach in managing spinal dural arteriovenous fistulae. Further delineation is required to determine the radiological and patient factors that might recommend specific initial treatment modalities.},
}

@article {pmid40837865,
year = {2025},
author = {Khan, H and Riaz, H and Ahmed, A and Kiyani, MM and Jawad, SM and Ud Din Shah, SS and Abualait, T and Al-Hussain, F and Li, HT and Bashir, S},
title = {CRISPR/Cas9 a genomic engineering technology for treatment in ALS mouse models.},
journal = {Regenerative therapy},
volume = {30},
number = {},
pages = {575-583},
pmid = {40837865},
issn = {2352-3204},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by the death of motor neurons in the spinal cord and brain regions, leading to a reduced survival rate in patients. Nearly 20 gene mutations are associated with ALS, with SOD1, FUS, TARDBP, and C9orf72 mutations being more common. Ninety percent of ALS cases are related to sporadic ALS, while the remaining 10 % are associated with familial ALS. CRISPR/Cas9, a genome engineering technology known as clustered regularly interspaced short palindromic repeats/CRISPR-associated system 9, has the potential for gene editing and for studying the underlying mechanisms of ALS in mouse models. This technique enables neuroscientists to reverse mutations found in ALS mouse models, providing new hope for understanding the complexities of ALS. Additionally, this tool can create mutations to probe the functional changes of genetic diseases. Using CRISPR/Cas9 with an in vivo delivery method involving adeno-associated vectors, it is possible to silence mutations in the SOD1-linked ALS mouse model. Some limitations related to CRISPR/Cas9 have been discussed in previous studies and need to be addressed before clinical trials can proceed. In this review-based study, we summarise the latest research on CRISPR/Cas9 genome editing for ALS in mouse models and discuss its limitations and future prospects as well.},
}

@article {pmid40834467,
year = {2025},
author = {Bocquier, A and Simon, M and Michel, M and Bonnay, S and Adam, I and Gilberg, S and Bruel, S and Gauchet, A and LeDuc-Banaszuk, AS and Gagneux-Brunon, A and Mueller, JE and Giraudeau, B and Thilly, N and , },
title = {Implementation evaluation of a school- and primary care-based multicomponent intervention to improve HPV vaccine coverage: Results from the PrevHPV randomized controlled trial.},
journal = {Journal of infection and public health},
volume = {18},
number = {11},
pages = {102931},
doi = {10.1016/j.jiph.2025.102931},
pmid = {40834467},
issn = {1876-035X},
abstract = {BACKGROUND: Human papillomavirus (HPV) vaccine coverage (VC) remains lower than expected in France. The PrevHPV national research program aimed to codevelop and evaluate an intervention including three components: 'education and motivation' of adolescents in schools, 'at-school vaccination', 'general practitioners (GPs)' training'. This study aimed to evaluate the implementation outcomes of each component, whether they affected effectiveness, and identify factors influencing implementation in schools.

METHODS: A mixed-method study embedded in a cluster randomized controlled trial in 91 French municipalities (July 2021-June 2022). Quantitative data were collected through activity reports and questionnaires, and qualitative data through focus groups with school staff. The implementation outcomes were fidelity, dose, reach, acceptability and sustainability, as defined in the Medical Research Council guidance for process evaluation of complex interventions and Proctor et al.'s Implementation Outcomes Framework; the effectiveness outcome was HPV VC (≥ 1 dose) two months after the end of the intervention. Qualitative data were analyzed using the Consolidated Framework for Implementation Research.

RESULTS: The fidelity, acceptability, and sustainability of all three components among participants who completed the intervention were high. However, the withdrawal of one-third of schools before the trial started and difficulties in mobilizing GPs negatively impacted the dose and reach outcomes. Estimates for the on-treatment analyses of the effectiveness were greater than those for which the dose of intervention received was not considered; 'at-school vaccination' (11.25 percentage points, p < 0.001) and 'GPs' training' (3.56 percentage points, p = 0.049) increased VC, while 'education and motivation' remained nonsignificant.

CONCLUSIONS: Increasing HPV VC among adolescents could be achieved by combining interventions in both schools and primary care settings. This study provides practical implications for implementing such interventions in real life.

TRIAL REGISTRATION: Clinicaltrials.gov, NCT04945655. Registered 30 June 2021, https://clinicaltrials.gov/study/NCT04945655.},
}

@article {pmid40832750,
year = {2025},
author = {Erdi-Krausz, G and Shaw, PJ},
title = {Antisense oligonucleotide therapy in amyotrophic lateral sclerosis.},
journal = {Current opinion in neurology},
volume = {},
number = {},
pages = {},
doi = {10.1097/WCO.0000000000001413},
pmid = {40832750},
issn = {1473-6551},
abstract = {PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with few treatment options available. The approval of tofersen, an antisense oligonucleotide, for SOD1-ALS by the FDA and EMA may herald a new era of treatment in these patients.

RECENT FINDINGS: So far, trials against the most common genetic form of ALS, C9orf72, have been unsuccessful, but new preclinical data may show a promising new direction to take. Clinical trials targeting other, more rare genetic mutations associated with familial ALS are currently underway. Other research assessing the use of ASOs to target aberrant splicing associated with sporadic forms of ALS has also produced promising results in preclinical models, using patient-derived induced cellular models and animal models. These therapies are focussed largely on alleviating and reversing TDP-43 pathology, opening up the possibility of not only arresting disease progression, but reversing neurodegeneration.

SUMMARY: ASO therapies have made some promising steps towards treating familial ALS, particularly SOD1. Ongoing early clinical/preclinical phase research is underway to utilise this technology in other genetic mutations linked with ALS, as well as in sporadic cases.},
}

@article {pmid40832743,
year = {2025},
author = {Verde, F},
title = {Neurochemical biomarkers of amyotrophic lateral sclerosis: recent developments.},
journal = {Current opinion in neurology},
volume = {},
number = {},
pages = {},
doi = {10.1097/WCO.0000000000001411},
pmid = {40832743},
issn = {1473-6551},
abstract = {REVIEW PURPOSE: To provide an overview of the recent developments in the field of neurochemical biomarkers of amyotrophic lateral sclerosis (ALS).

RECENT FINDINGS: Neurofilaments, especially NFL, have been confirmed to be good biomarkers for ALS. NFL may be diagnostically useful but its main role is as prognostic and pharmacodynamic biomarker. Inflammatory biomarkers, especially the chitinases, might also serve as pharmacodynamic biomarkers in treatment trials targeting neuroinflammation. GFAP could reflect cognitive-behavioural impairment. CSF dipeptides are diagnostic biomarkers for ALS caused by the C9ORF72 exanucleotide repeat expansion and may be used to confirm target engagement by experimental drugs. Levels of TDP-43 (virtually the ideal biomarker for ALS) in CSF and plasma have not been demonstrated to be consistently altered in ALS. However, promising advancements have been achieved in seed amplification assays for the protein, in its quantification in plasma extracellular vesicles, and in the measurement of CSF levels of a protein reflecting splicing dysfunction of TDP-43. Finally, blood phosphorylated tau has emerged as an ALS biomarker linked to lower motor neuron (or muscle) pathology.

SUMMARY: NFL is still the best neurochemical biomarker for ALS. However, substantial advances have been recently made, especially regarding detection of TDP-43 and blood phosphorylated tau.},
}

@article {pmid40828270,
year = {2025},
author = {Harerimana, A and Pillay, JD and Mchunu, G},
title = {The pitfalls of "toughing it out": mapping stoic attitudes in cancer patients. A scoping review.},
journal = {Medicine, health care, and philosophy},
volume = {},
number = {},
pages = {},
pmid = {40828270},
issn = {1572-8633},
abstract = {Stoicism (with an upper-case 'S') as a life philosophy promotes resilience, self-control and rational acceptance of adversity. In contrast, lower-case stoicism, including pseudo-stoicism or stoic attitudes-characterised by emotional suppression and the silent endurance of pain or hardship-has been linked to adverse health outcomes among cancer patients. Thus, further research is needed to understand the drawbacks of stoic attitudes in cancer patients. This scoping review aims to map stoic attitudes in cancer patients, particularly in relation to potential health consequences. The review adhered to Levac et al.'s framework for scoping reviews. A systematic search was conducted from five electronic databases: CINAHL, Emcare, Medline Ovid, Scopus, and Web of Science. Manual searches were conducted using Google and Google Scholar. A total of 955 records were identified, 526 were screened (title and abstracts), and 450 were excluded. After reviewing 76 full-text articles, 12 studies satisfied the inclusion criteria for data extraction and thematic analysis, consisting of five qualitative and seven quantitative studies. A time frame of 10 years was considered, ranging from 2014 to 2024. This scoping review revealed that pseudo-stoic attitudes in cancer patients often lead to emotional suppression, reduced social support, delayed help-seeking and poor management of symptoms such as pain. These attitudes were linked to poorer psychological outcomes and underreporting of symptoms, especially among older males and rural cancer patients. Studies found that stoic traits were sometimes associated with persistence and treatment adherence among cancer patients. Pseudo-stoicism hinders emotional expression and delays help-seeking, leading to adverse health outcomes; however, stoic attitudes are also associated with adaptive qualities, such as psychological endurance and a commitment to care. Therefore, it is vital to promote balanced coping strategies that honour resilience while encouraging open emotional engagement among cancer patients.},
}

@article {pmid40826812,
year = {2025},
author = {Asano, H and Kawaguchi, T and Kato, C and Morimoto, S and Yano, M and Minaguchi, M and Yasuda, D and Fukushima, K and Okano, H},
title = {Ropinirole Functions Through a Dopamine Receptor D2-Independent Mechanism to Ameliorate Amyotrophic Lateral Sclerosis Phenotypes in TARDBP-Mutant iPSC-Derived Motor Neurons.},
journal = {Journal of neurochemistry},
volume = {169},
number = {8},
pages = {e70183},
doi = {10.1111/jnc.70183},
pmid = {40826812},
issn = {1471-4159},
support = {JP21H05278//Japan Society for the Promotion of Science/ ; JP22K15736//Japan Society for the Promotion of Science/ ; JP20H00485//Japan Agency for Medical Research and Development/ ; JP21wm0425009//Japan Agency for Medical Research and Development/ ; JP22bm0804003//Japan Agency for Medical Research and Development/ ; JP22ek0109616//Japan Agency for Medical Research and Development/ ; JP23bm1123046//Japan Agency for Medical Research and Development/ ; JP23bm1423002//Japan Agency for Medical Research and Development/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron (MN) degeneration. Ropinirole hydrochloride (ROPI), a dopamine receptor D2 (DRD2) agonist, was identified through phenotypic screening of MNs derived from patient-derived induced pluripotent stem cells (iPSCs) as a disease model and has emerged as a promising candidate drug for ALS treatment. The ROPALS trial, a phase I/IIa trial in patients with ALS, suggested the safety and efficacy of ROPI, albeit in a small sample size. Interestingly, a DRD2 antagonist and modulator only partially mitigated the suppressive effect of ROPI on the ALS phenotype, and the detailed mechanism of ROPI activity remains unclear. Therefore, in this study, we investigated whether the therapeutic effects of ROPI in ALS are dependent on DRD2. For this purpose, we generated DRD2-deficient iPSCs and showed that ROPI effectively reduced neuronal cell death, reactive oxygen species (ROS) production, and neuronal hyperexcitation, independently of DRD2. Further analyses revealed that ROPI corrected aberrant RNA splicing and restored the mRNA expression of mitochondrial proteins in a DRD2-independent manner. Our findings suggest that ROPI not only functions as a canonical DRD2 agonist but also has pleiotropic DRD2-independent effects, offering a novel avenue for treatment strategies that target multiple pathways involved in ALS pathology.},
}

@article {pmid40822241,
year = {2025},
author = {Tan, X and Gao, N},
title = {The emerging role of cellular senescence in amyotrophic lateral sclerosis.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1599492},
pmid = {40822241},
issn = {1662-4548},
abstract = {Cellular senescence is a state of permanent cell cycle arrest and is considered a key contributor to aging and age-related diseases, including amyotrophic lateral sclerosis (ALS). The physiological processes of aging lead to a variety of molecular and cellular phenotypes, and evidence of overlap between ALS and aging-related biomarkers suggests that cell type-specific senescence may be a critical factor in ALS. Senescent microglial cells, astrocytes, and neurons have been detected in ALS patients and animal models. However, while accumulating evidence suggests a potential link between cellular senescence and ALS, this connection remains not yet conclusively established. Importantly, how senescent cells may contribute to the neuropathophysiology of ALS remains largely unknown. Additionally, the growing popularity of anti-aging therapies has highlighted the potential of senescent cell clearance as a promising strategy for treating age-related diseases, including ALS. This review provides an overview of cellular senescence, discusses recent advances in understanding how senescence in different cell types influences ALS pathogenesis, and explores the potential role of anti-senescence therapies in ALS treatment.},
}

@article {pmid40810164,
year = {2025},
author = {Alo, B and Lamers, C},
title = {Crossing Barriers: Advancements in Macromolecular Therapeutics for Neurodegenerative Diseases and Strategies to Overcome the Blood-Brain Barrier.},
journal = {ACS pharmacology & translational science},
volume = {8},
number = {8},
pages = {2353-2383},
pmid = {40810164},
issn = {2575-9108},
abstract = {Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, present considerable challenges for our societies and health systems due to their progressive nature, the demographic shift toward older populations, and limited treatment options. Recent advances in macromolecular therapeutics, including antibodies, peptides, and proteins, offer novel therapeutic modalities for a broad range of diseases. Their high potency and specificity hold promise for disease-modifying therapies to combat neurodegenerative diseases. However, the blood-brain barrier poses a significant challenge for the effective delivery of these large molecules to the central nervous system. This review discusses the physiological role of the blood-brain barrier and its influence on restricting the exposure of macromolecules in the brain. Furthermore, emerging strategies for enhancing blood-brain barrier permeability to macromolecules are highlighted. This review summarizes modifications designed to utilize receptor-mediated uptake, adsorptive-mediated transcytosis, carrier-mediated transport, and nanoparticle-based delivery systems to overcome the blood-brain barrier. Additionally, we emphasize the importance of testing macromolecular therapeutics for their blood-brain barrier permeability and review the methods for such in vitro and in vivo testing. Finally, we shed light on therapeutics in preclinical and clinical development for neurodegenerative diseases and their challenges.},
}

@article {pmid40807333,
year = {2025},
author = {Godela, A and Rogacz, D and Pawłowska, B and Biczak, R},
title = {Natural Neuroinflammatory Modulators: Therapeutic Potential of Fungi-Derived Compounds in Selected Neurodegenerative Diseases.},
journal = {Molecules (Basel, Switzerland)},
volume = {30},
number = {15},
pages = {},
pmid = {40807333},
issn = {1420-3049},
abstract = {Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis remain incurable. Current therapeutic strategies primarily focus on slowing disease progression, alleviating symptoms, and improving patients' quality of life, including the management of comorbid conditions. Over the past few decades, the incidence of diagnosed neurodegenerative disorders has risen significantly. As the number of affected individuals continues to grow, so does the urgent need for effective treatments that can halt or mitigate the progression of these diseases. Among the most promising therapeutic resources are bioactive compounds derived from fungi. The high quality of proteins, polysaccharides, unsaturated fatty acids, triterpenoids, sterols, and secondary metabolites found in fungi have attracted growing interest from researchers across multiple disciplines. One intensively studied direction involves the use of naturally occurring fungi-derived nutraceuticals in the treatment of various diseases, including neurodegenerative conditions. This article provides an overview of recent findings on fungal compounds-such as phenolic compounds, carbohydrates, peptides and proteins, and lipids-that may have potential applications in the treatment of neurodegenerative diseases and the alleviation of their symptoms.},
}

@article {pmid40800723,
year = {2025},
author = {Jansen, J and Geijtenbeek, TBH and Kootstra, NA},
title = {Inducible HIV-1 Reservoir Reduction Assay (HIVRRA), a Fast and Sensitive Assay to Test Cytotoxicity and Potency of Cure Strategies to Reduce the Replication-Competent HIV-1 Reservoir in Ex Vivo PBMCs.},
journal = {Bio-protocol},
volume = {15},
number = {14},
pages = {e5384},
pmid = {40800723},
issn = {2331-8325},
abstract = {The HIV-1 reservoir, consisting of transcriptionally silent integrated HIV-1 proviruses, is a major barrier to a cure, as it persists during effective antiretroviral therapy (ART) and is the source of viral rebound upon treatment interruption. Some of the strategies explored for HIV cure focus on the identification of compounds to either reactivate and eliminate the HIV reservoir ("shock and kill") or to prevent HIV reservoir reactivation and induce deep proviral latency ("block and lock"). Paramount in developing these HIV-1 cure strategies is determining the effect of the compounds on the size of the inducible HIV-1 reservoir in blood from people living with HIV-1 (PWH). Traditionally, viral outgrowth assays have been the primary method to determine the inducible HIV-1 reservoir in CD4+ T cells from PWH. However, these assays are labor-intensive, time-consuming, and often have low sensitivity. We have recently developed the inducible HIV-1 reservoir reduction assay (HIVRRA), a rapid, cost-effective, and sensitive method to measure the impact of compounds on the inducible replication-competent HIV-1 reservoir in total peripheral blood mononuclear cells (PBMCs) from PWH ex vivo. The HIVRRA simultaneously evaluates the effect of test conditions on the size of the inducible replication-competent HIV-1 reservoir as well as the specificity and toxicity of the test strategy. Using total PBMCs instead of purified CD4+ T cells reduces processing time and resource requirements. This makes the HIVRRA a more practical, scalable tool for evaluating potential HIV-1 cure strategies. Key features • The HIVRRA builds on the TZM-BL cell-based assay to quantify the HIV-1 reservoir by Sanyal et al.'s [1] method. • The HIVRRA uses total PBMCs from PWH to determine infectious units per million cells. • The HIVRRA requires low PBMC input compared to other reservoir analysis methods. • The HIVRRA determines the toxicity of the compounds on HIV-1-infected and uninfected cells in the same assay.},
}

@article {pmid40794238,
year = {2025},
author = {Jellinger, KA},
title = {Comorbid pathologies and their impact on progressive supranuclear palsy: current view.},
journal = {Journal of neural transmission (Vienna, Austria : 1996)},
volume = {},
number = {},
pages = {},
pmid = {40794238},
issn = {1435-1463},
support = {Society for the Promotion of Research in Experimental Neurology, Vienna, Austria//Society for the Promotion of Research in Experimental Neurology, Vienna, Austria/ ; },
abstract = {Progressive supranuclear palsy, a four-repeat tauopathy, is clinically characterized by early postural instability and falls, vertical supranuclear palsy, levodopa poorly-responsive parkinsonism, pseudobulbar palsy, and cognitive impairment. It is morphologically featured by accumulation of hyperphosphorylated tau protein in neurons and glia predominantly in the basal ganglia, brainstem tegmentum and frontal cortex, associated with degeneration of the extrapyramidal system and cortical atrophy. Isolated PSP neuropathology is uncommon, with nearly 70% showing co-neuropathologies including Alzheimer-type, Lewy body, TDP-43 pathologies, argyrophilic grains, and other tauopathies and neurodegenerative disorders (Parkinson disease, amyotrophic lateral sclerosis). The most common comorbid conditions are hypertension, cardiovascular and cerebrovascular diseases, diabetes mellitus, polyneuropathies, muscular and urological disorders. Due the increased prevalence of comorbidities and their eminent impact on the progress and outcome of the disease, clinical trials should account for them in their design and selection. However, currently little is known about co-pathologies in these patients. In view of the eminent burden of comorbidities and resulting therapeutic consequences, the frequency of the different co-pathologies in PSP and their clinical impact will be discussed. It should provide insight into their pathogenic backgrounds as a basis for adequate treatment procedures to improve the quality of life of patients with this fatal disease.},
}

@article {pmid40787733,
year = {2025},
author = {Raaphorst, J and Gullick, NJ and Shokraneh, F and Brassington, R and Min, M and Ali, SS and Gordon, PA},
title = {Non-targeted immunosuppressive and immunomodulatory therapies for idiopathic inflammatory myopathies.},
journal = {The Cochrane database of systematic reviews},
volume = {8},
number = {8},
pages = {CD015855},
pmid = {40787733},
issn = {1469-493X},
mesh = {Humans ; *Myositis/drug therapy ; *Immunosuppressive Agents/therapeutic use/adverse effects ; Randomized Controlled Trials as Topic ; Dermatomyositis/drug therapy ; *Immunomodulating Agents/therapeutic use/adverse effects ; Bias ; Child ; Adult ; Polymyositis/drug therapy ; },
abstract = {BACKGROUND: Idiopathic inflammatory myopathies (IIM) are autoimmune-mediated inflammatory disorders of skeletal muscles with non-muscle involvement in some people, which carry significant morbidity and mortality. Treatment of IIM represents an area of unmet need. This review is an update of a review previously published in 2012, as new and promising data on non-targeted treatments have emerged.

OBJECTIVES: To assess the effects (benefits and harms) of non-targeted immunosuppressant and immunomodulatory treatments for IIM: dermatomyositis (DM, including juvenile dermatomyositis, jDM), immune-mediated necrotising myopathy (IMNM), anti-synthetase syndrome (ASS), overlap-myositis (OM) and polymyositis (PM). We also included cancer-related myositis and amyopathic dermatomyositis.

SEARCH METHODS: On 3 February 2023, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, Embase, MEDLINE, ClinicalTrials.gov and WHO ICTRP. We intended to check references and citations, and contact experts to identify additional studies, but lacked the resources.

SELECTION CRITERIA: We included all randomised controlled trials (RCTs) or quasi-RCTs involving participants (adults and children) with IIM according to defined criteria. We included non-targeted immunosuppressants and immunomodulatory treatments alone or in combination, compared with a placebo, no treatment or another non-targeted immunosuppressant or immunomodulatory treatment. Our two primary outcomes were improvement of function or disability and improvement of muscle strength compared with baseline. By preference, we used the Health Assessment Questionnaire Disability Index (HAQ-DI) for disability and the Manual Muscle Test-8 (MMT8) score (adults or children) for muscle strength. Other outcomes were achievement of definitions of improvement (DOI) (the International Myositis Assessment and Clinical Studies (IMACS) Group or the more recent total improvement scores (TIS); for children, we reported achievement of improvement defined by the Paediatric Rheumatology International Trials Organisation (PRINTO)), cumulative corticosteroid dose, change in skin disease activity, serious adverse event and withdrawals for lack of benefit or adverse events.

DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess the risk of bias, we used the domain-based Cochrane risk of bias tool (RoB 1). We used fixed-effect models and, when needed, random-effects models for meta-analysis. We created summary of findings tables for any comparison for which data were available but prioritised comparisons of the following with placebo, no treatment or standard care: immunoglobulin, azathioprine and methotrexate. We included other comparisons as additional tables. We assessed the certainty of evidence using the GRADE approach.

MAIN RESULTS: We identified 16 studies (789 participants). The risk of bias in all but one study was high or unclear. Intravenous immunoglobulin (IVIg), compared to placebo, probably improves disability and muscle strength in participants with refractory IIM (standardised mean difference (SMD) 0.86, 95% confidence interval (CI) 0.51 to 1.21 (disability) and 0.78, 95% CI 0.43 to 1.13 (muscle strength); 3 RCTs, 136 participants; both moderate-certainty evidence). IVIg has a higher response rate based on American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria than placebo (risk ratio (RR) 1.80, 95% CI 1.26 to 2.56; 1 RCT, 95 participants; moderate-certainty evidence). IVIg, compared to placebo, improves skin symptoms (Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) total activity score 0 to 100; higher worse) in people with refractory DM (mean difference (MD) -8.20, 95% CI -11.91 to -4.49; 1 RCT, 95 participants; moderate-certainty evidence). There may be more serious adverse events with IVIg than with placebo (RR 1.91, 95% CI 0.50 to 7.30; 2 RCTs, 144 participants; very low-certainty evidence), but little or no difference between IVIg and placebo in withdrawals for either lack of benefit or adverse events (RR 1.02, 95% CI 0.24 to 4.33; 3 RCTs, 154 participants; very low-certainty evidence). For azathioprine versus placebo, one study showed little or no effect of azathioprine on improvement in muscle strength, but the evidence was very uncertain (RR 1.33, 95% CI 0.43 to 4.13; 1 RCT; 16 participants; very low-certainty evidence). The evidence was also very uncertain for cumulative steroid dose (MD 12.06 mg/kg, 95% CI -6.09 to 30.21; 1 RCT, 16 participants; very low-certainty evidence). This early study did not assess IMACS DOI or CDASI or measure function or disability. Serious adverse events and withdrawals for either lack of benefit or adverse events were not systematically reported. For methotrexate, there may be little or no improvement in adults with DM or PM in function (Amyotrophic Lateral Sclerosis Functional Rating Scale 0 to 40, higher better) (MD 1.24, 95% CI -1.60 to 4.08; 1 RCT, 27 participants; very low-certainty evidence), muscle strength (MMT scale 0 to 80, higher better) (MD -5.68, 95% CI -12.94 to 1.58; 1 RCT, 27 participants; very low-certainty evidence), achievement of IMACS DOI (RR 1.01, 95% CI 0.74 to 1.39; 1 RCT, 27 participants; very low-certainty evidence). Cumulative steroid dose was measured, but the data could not be analysed, and change in CDASI was not measured. In children with new-onset jDM on a background therapy of prednisone, a higher proportion may achieve minimal improvement according to the PRINTO criteria with methotrexate than with placebo (RR 1.40, 95% CI 1.01 to 1.96; 1 RCT, 93 participants; low-certainty evidence). Serious adverse events may occur slightly more frequently with methotrexate (RR 1.48, 95% CI 0.54 to 4.07; 2 RCTs, 124 participants; low-certainty evidence). There may be fewer withdrawals for lack of benefit or adverse events with methotrexate (RR 0.62, 95% CI 0.37 to 1.05; 3 RCTs, 151 participants; low-certainty evidence).

AUTHORS' CONCLUSIONS: Our review shows improvement in disability, muscle strength and skin symptoms following IVIg in people with refractory DM (for PM, these data are not reliable; other subtypes have not been investigated in RCTs). The improvements related to IVIg in DM may be clinically meaningful, but the absence of established minimal clinically important differences (MCIDs) for both disability and muscle strength in IIM does not facilitate interpretation. For the other agents, the small number of trials of immunosuppressive and immunomodulatory therapies is inadequate to decide whether these agents are beneficial in IIM (excluding IBM). Our review shows room for improvement in the conduct and reporting of clinical trials in IIM, as well as the need to further investigate MCIDs for important outcome measures in IIM.},
}

Humans
*Myositis/drug therapy
*Immunosuppressive Agents/therapeutic use/adverse effects
Randomized Controlled Trials as Topic
Dermatomyositis/drug therapy
*Immunomodulating Agents/therapeutic use/adverse effects
Bias
Child
Adult
Polymyositis/drug therapy

@article {pmid40779080,
year = {2025},
author = {Huo, X and Wang, L and Ma, J and Wu, Z and Wang, K},
title = {Bibliometric analysis of publication trends in meningioma research (1992 - 2023).},
journal = {Neurosurgical review},
volume = {48},
number = {1},
pages = {595},
pmid = {40779080},
issn = {1437-2320},
support = {2024-4-2048//Capital's Funds for Health Improvement and Research/ ; 2022YFE0112500//National Natural Science Foundation of China/ ; 62027813//National Natural Science Foundation of China,China/ ; YGLX202518//Beijing Hospitals Authority Clinical medicine Development of special funding support/ ; },
mesh = {*Meningioma ; *Bibliometrics ; Humans ; *Meningeal Neoplasms ; *Biomedical Research ; },
abstract = {The purpose of this study was providing an overview of meningioma research and its current situation. We conducted a bibliometric study of 14,027 articles and reviews on meningioma between January, 1992 to June, 2023 with the bibliometrix tool and VOSviewer. The distribution of authorship and collaboration patterns among countries, institutions, publications, and authors were analyzed. Core sources was analyzed with Bradford's law and author productivity was analyzed with Lotka's Law. The current situation and key areas were assessed through co-occurrence analysis. The number of publications has steadily increased over the years. The United States and University California San Francisco made the most contribution country and institution, respectively. Among the cited authors, Zhang J. emerged as the leading contributor while Perry A. was the most productive. Black P.M. had the highest h-index and Nassiri F. ranked first among the m-index. The most frequently cited study was Louis D.N. et al.'s 2016 publication in Acta Neuropathologica, titled "The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary." The journals with the most published articles and most cited publications were World Neurosurgery and Journal of Neurosurgery, respectively. According to keyword analysis, treatment option, chemotherapy, NF2 gene and estrogen receptor, and progesterone receptor are becoming more popular. This study provided a comprehensive overview of meningioma research, as well as potential future research fields, such as the chemotherapy and NF2 gene.},
}

*Meningioma
*Bibliometrics
Humans
*Meningeal Neoplasms
*Biomedical Research

@article {pmid40778462,
year = {2025},
author = {Schvey, NA and Tanofsky-Kraff, M},
title = {Commentary on: The Prevalence of Eating Disorders and Disordered Eating in Adults Seeking Obesity Treatment: A Systematic Review With Meta-Analyses by Melville et al.},
journal = {The International journal of eating disorders},
volume = {},
number = {},
pages = {},
doi = {10.1002/eat.24522},
pmid = {40778462},
issn = {1098-108X},
abstract = {Melville et al.'s 2025 systematic review and meta-analysis highlight the prevalence of eating disorders and disordered eating among adults seeking obesity treatment. Findings showed that the prevalence of binge-eating disorder in obesity treatment-seeking samples exceeds community norms. Results corroborate prior research suggesting that high body weight and eating pathology frequently co-occur and that individuals seeking weight management may be a high-risk population for both sub- and full-threshold eating disorders. Although concerns persist that weight loss efforts may promote or worsen eating disorder symptoms, research indicates that structured, evidence-based interventions typically have neutral or positive effects on disordered eating outcomes. However, rigorous and consistent screening for eating disorders among individuals with high weight is lacking. Importantly, obesity and eating disorders share many common etiological factors, suggesting that integrated intervention is both feasible and highly beneficial. Despite this, the fields of obesity and eating disorders remain siloed. This bifurcation disproportionately impacts youth and adolescents who are at high risk for the onset of both conditions. Currently, standards of care fail to include screening for eating disorders, particularly in youth with high weight, who may be overlooked or misdiagnosed due, in part, to weight-based stigma. Universal, developmentally sensitive screening tools and comprehensive assessment of eating disorder risk factors are urgently needed in pediatric primary care settings. As evidence mounts for concurrent treatment models of high weight and eating disorders, integration across science and clinical care is vital to improve outcomes for youth affected by both conditions.},
}

@article {pmid40712303,
year = {2025},
author = {Arulmoorthy, MP},
title = {Navigating the diagnostic delay: optimizing timely biopsy and integrating NIR-based technologies for head and neck cancer.},
journal = {Oral oncology},
volume = {168},
number = {},
pages = {107518},
doi = {10.1016/j.oraloncology.2025.107518},
pmid = {40712303},
issn = {1879-0593},
abstract = {Lee et al.'s study critically explores the detrimental effects of diagnostic delays in head and neck cancer (HNC), focusing on patients who initially present through emergency departments (ED). The findings reveal that delayed biopsies, especially those performed more than 34 days after initial imaging, are associated with worse survival outcomes, highlighting the need for timely tissue diagnosis. Notably, the study identifies a 34-day threshold for biopsy completion that should guide clinical practice to improve patient prognosis. This commentary expands on the study's findings, emphasizing the importance of optimizing care coordination to minimize time from imaging to biopsy. Moreover, the integration of innovative diagnostic and theranostic technologies, particularly near-infrared (NIR) organic small molecules, presents a promising solution to expedite cancer diagnosis and treatment. NIR fluorophores, with their ability to penetrate deep tissues and provide real-time imaging, could significantly enhance the early detection and management of HNC, thereby reducing diagnostic delays and improving patient survival rates.},
}

@article {pmid40711733,
year = {2025},
author = {Granito, A and Muratori, P and Czaja, AJ},
title = {Autoimmune Hepatitis Treatment: Can Low-Dose Steroids Be Generalized?.},
journal = {Digestive diseases and sciences},
volume = {},
number = {},
pages = {},
pmid = {40711733},
issn = {1573-2568},
abstract = {We critically examine the implications of Aggarwal et al.'s study on low- versus high-dose prednisolone induction in autoimmune hepatitis (AIH). While acknowledging the study's contribution, this letter argues that the predominantly cirrhotic and often decompensated patient cohort limits the generalizability of its findings to the broader AIH population. We emphasize the potential influence of advanced liver disease on treatment response and side effect profiles, suggesting that similar efficacy between low- and high-dose prednisolone may not extend to all AIH patients. We contend that future research should prioritize more representative AIH cohorts across the spectrum of disease severity to establish universally applicable corticosteroid dosing strategies.},
}

@article {pmid40690850,
year = {2025},
author = {Sharma, A and Raj, R},
title = {Treatment comparisons for MS fatigue: A network meta-analysis in light of Toljan et al.'s findings.},
journal = {Multiple sclerosis and related disorders},
volume = {102},
number = {},
pages = {106618},
doi = {10.1016/j.msard.2025.106618},
pmid = {40690850},
issn = {2211-0356},
}

@article {pmid40648551,
year = {2025},
author = {Al-Ajlouni, YA and Al Ta'ani, O and Zweig, SA and Bak, M and Tanashat, M and Gabr, A and Khamis, Z and Al-Bitar, F and Islam, M},
title = {Assessing the Therapeutic Role of Rehabilitation Programs in Chemotherapy-Induced Peripheral Neuropathy (CIPN)-A Scoping Review.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {13},
pages = {},
pmid = {40648551},
issn = {2227-9032},
abstract = {Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating side effect of cancer treatment. Characterized by symptoms like pain, numbness, and muscle weakness, CIPN significantly impacts patients' quality of life. Current management strategies vary, with limited consensus on effective treatments. This scoping review aims to explore comprehensive rehabilitation interventions for CIPN, focusing on enhancing patient well-being and functional abilities. Methods: A scoping review, guided by Arksey and O'Malley's framework and Levac et al.'s refinements, was conducted to assess rehabilitation programs for CIPN. Searches across six databases were performed, with inclusion and exclusion criteria focusing on studies with physical rehabilitation interventions. Data were charted, detailing interventions, demographics, and outcomes. Results were synthesized descriptively and presented narratively with tables. Results: The review included 24 studies covering diverse cancer types and treatments, involving a total of 1167 participants. Various interventions for CIPN were assessed, and results were thematically categorized according to exercise category. Physical modalities like ultrasound and exercise showed promise in symptom relief for colorectal and breast cancer patients. No distinct advantage was found in the timing of exercise interventions. Complementary therapies such as acupuncture and yoga demonstrated effectiveness in managing CIPN symptoms. Conclusions: This review highlights the effectiveness of diverse physical and complementary interventions in managing CIPN, advocating for their integration into standard protocols. It emphasizes the need for holistic, patient-centered approaches that combine exercises, physical therapy, and complementary therapies to improve patient outcomes. These findings set a direction for future research and clinical practices focused on comprehensive and personalized CIPN management strategies.},
}

@article {pmid40640475,
year = {2025},
author = {Heydari, K and Enichen, EJ and Li, B and Kvedar, JC},
title = {Leveraging retinal vascular features in non-invasive, early diagnosis of preeclampsia.},
journal = {NPJ digital medicine},
volume = {8},
number = {1},
pages = {422},
pmid = {40640475},
issn = {2398-6352},
abstract = {Wu et al.’s recent article, “Noninvasive early prediction of preeclampsia in pregnancy using retinal vascular features,” documents significant differences in retinal vascular features among women who develop preeclampsia and those with normotensive pregnancies. These findings provide evidence that retinal screening has the potential to be used as a low-cost, non-invasive screening strategy to support the earlier detection, prevention, and treatment of preeclampsia.},
}

@article {pmid40614949,
year = {2025},
author = {Sarkar, SK and Gubert, C and Hannan, AJ},
title = {The microbiota-inflammasome-brain axis as a pathogenic mediator of neurodegenerative disorders.},
journal = {Neuroscience and biobehavioral reviews},
volume = {176},
number = {},
pages = {106276},
doi = {10.1016/j.neubiorev.2025.106276},
pmid = {40614949},
issn = {1873-7528},
abstract = {In various neurodegenerative disorders, inflammation and associated inflammasome activation play an important role. The most prevalent and extensively researched inflammasomes are NLRP3 inflammasomes, which are triggered by pathogens or danger signals mediating inflammatory reaction. Extracellular ATP also activates NLRP3 by stimulating the purinergic receptor P2X7 (P2X7R). Central and peripheral cells, including those in the gut, have been shown to have activated inflammasomes during pathological changes co-occurring with inflammation in various neurodegenerative disorders. Gut injury or dysfunction is increasingly recognised as one of the peripheral pathogenic characteristics of many neurodegenerative disorders, and has been found to associate with changes in gut microbes. In this article, we review data from preclinical and clinical studies regarding the involvement of the NLRP3 inflammasome and the purinergic receptor P2X7R in the pathophysiology of major CNS disorders involving neurodegeneration, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), and the most common form of motor neuron disease, amyotrophic lateral sclerosis (ALS). We also scrutinise the relationship of the NLRP3 inflammasome to intestinal microbiota alterations in these diseases. Both the NLRP3 inflammasome and P2X7R have been shown to play important roles in the pathogenesis and progression of these neurodegenerative diseases. However, most studies have focused on central nervous system (CNS) pathology, particularly within the brain, with comparatively less attention given to their contribution to gut pathology. Additionally, changes in the microbial ecosystems of the intestine have also been implicated in these disorders. However, the association between gut microbiota alterations and inflammasome activity in the pathology of these neurodegenerative disorders remains poorly understood. Therefore, further investigation is urgently needed to explore the microbiota-inflammasome-brain axis in these neurodegenerative conditions, in order to better understand their contribution to disease pathogenesis and progression, and identify novel therapeutic targets and new approaches to prevention and treatment.},
}

@article {pmid40602557,
year = {2025},
author = {Rodriguez-Romano, A and Gonzalez-Valdivieso, J and Moreno-Martinez, L and Vázquez Costa, JF and Osta, R and Rico, P},
title = {Injectable borax-loaded alginate hydrogels reduce muscle atrophy, modulate inflammation, and promote neuroprotection in the SOD1[G93A] mouse model of ALS through mechanisms involving IGF-Akt-mTOR signaling.},
journal = {International journal of biological macromolecules},
volume = {319},
number = {Pt 4},
pages = {145645},
doi = {10.1016/j.ijbiomac.2025.145645},
pmid = {40602557},
issn = {1879-0003},
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology/genetics ; *Hydrogels/chemistry ; Mice ; *Muscular Atrophy/drug therapy/pathology/metabolism ; Disease Models, Animal ; *Alginates/chemistry ; Signal Transduction/drug effects ; Proto-Oncogene Proteins c-akt/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Superoxide Dismutase-1/genetics ; Inflammation/drug therapy/pathology ; Motor Neurons/drug effects/metabolism ; *Neuroprotection/drug effects ; Neuroprotective Agents/pharmacology ; Mice, Transgenic ; Muscle, Skeletal/drug effects/pathology/metabolism ; Borates ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a prevalent condition characterized by motor neuron loss and skeletal muscle paralysis. Despite being associated to mutations in over 40 genes, its etiology remains elusive without a cure or effective treatment. ALS, historically considered a motor neuron disease, is defined today as a multisystem disorder involving non-neuronal cell types, including early muscle pathology independent of motor neuron degeneration (dying back hypothesis), thus skeletal muscle actively contributes to disease pathology, making it a viable therapeutic target for ALS. Our previous research has shown that boron transporter NaBC1 (encoded by the SLC4A11 gene), after activation co-localizes with integrins and growth factor receptors synergistically enhancing muscle repair. Here we investigate the effects of injectable alginate-based hydrogels for controlled local borax release in Amyotrophic Lateral Sclerosis muscle. Treated mice showed improved motor function, prolonged survival, and activation of essential muscle metabolic pathways, leading to enhanced muscle repair and reduced atrophy and inflammation. Interestingly, local muscle repair activation provided retrograde neuroprotection by preserving motor neurons and reducing neuro-inflammation. This study highlights the role of muscle tissue in ALS pathology, supporting its targeting with NaBC1-based therapies for muscle regeneration.},
}

Animals
*Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology/genetics
*Hydrogels/chemistry
Mice
*Muscular Atrophy/drug therapy/pathology/metabolism
Disease Models, Animal
*Alginates/chemistry
Signal Transduction/drug effects
Proto-Oncogene Proteins c-akt/metabolism
TOR Serine-Threonine Kinases/metabolism
Superoxide Dismutase-1/genetics
Inflammation/drug therapy/pathology
Motor Neurons/drug effects/metabolism
*Neuroprotection/drug effects
Neuroprotective Agents/pharmacology
Mice, Transgenic
Muscle, Skeletal/drug effects/pathology/metabolism
Borates

@article {pmid40569742,
year = {2025},
author = {Kimonis, ER and Gooi, CH},
title = {Treating populations with antagonistic traits-Reflections on Hyatt, Phillips, et al. (2025) and considerations for clinical psychology training programs.},
journal = {Personality disorders},
volume = {16},
number = {4},
pages = {310-314},
doi = {10.1037/per0000719},
pmid = {40569742},
issn = {1949-2723},
support = {//The University of New South Wales/ ; },
mesh = {Humans ; *Psychology, Clinical/education ; *Antisocial Personality Disorder/therapy ; *Clinical Competence ; *Conduct Disorder/therapy ; },
abstract = {The treatment of populations with antagonistic traits and disorders, particularly psychopathic personalities, poses a significant challenge for mental health practitioners and trainees. This commentary reviews Hyatt, Phillips, et al. (2025), highlighting the critical clinical training gaps related to working with individuals exhibiting externalizing and antagonistic behaviors. Hyatt, Phillips, et al.'s (2025) findings reveal that graduate students receive less training and experience working with these populations compared to clients with internalizing disorders, contributing to lower self-efficacy and greater emotional strain in therapeutic encounters. This commentary discusses the urgent need for enhanced training, including exposure to structured evidence-based interventions for child conduct disorders, such as Parent-Child Interaction Therapy and its adaptation for children with callous-unemotional traits. It also discusses possible reasons for Hyatt, Phillips, et al.'s (2025) findings, including the pervasive underfunding of research on conduct disorders and psychopathy, which contributes to the scarcity of effective treatments. Finally, future training initiatives are considered, including the potential of novel training techniques such as deliberate practice and simulation-based education to improve psychology trainee's clinical competence in working with clients with antagonism. This commentary emphasizes the importance of equipping future clinicians with the skills needed to address the complex needs of these challenging populations to help reduce their societal burden. (PsycInfo Database Record (c) 2025 APA, all rights reserved).},
}

Humans
*Psychology, Clinical/education
*Antisocial Personality Disorder/therapy
*Clinical Competence
*Conduct Disorder/therapy

@article {pmid40543562,
year = {2025},
author = {Pope, E and Ameral, V and Falcón, A and Smith, J and Shoemaker-Hunt, SJ and Bounthavong, M and McCullough, M and Kim, B},
title = {Knowledge and attitudes regarding substance use disorder treatment and harm reduction practices among US pharmacists: a scoping review.},
journal = {Journal of the American Pharmacists Association : JAPhA},
volume = {},
number = {},
pages = {102462},
doi = {10.1016/j.japh.2025.102462},
pmid = {40543562},
issn = {1544-3450},
abstract = {BACKGROUND: Pharmacists are uniquely positioned to address substance use disorders (SUDs) and expand harm reduction services due to their accessibility and expertise in medication management. However, attitudinal and structural barriers may limit their full potential in this role.

OBJECTIVE: This scoping review examines pharmacists' knowledge, attitudes, and engagement in SUD treatment and harm reduction.

METHODS: A scoping review was conducted using Levac et al.'s enhancement of Arksey and O'Malley's framework. A systematic search of MEDLINE (PubMed), PsycInfo, Embase, ProQuest Health & Medical, and ProQuest Psychology was performed on August 3, 2024, yielding 87 articles addressing pharmacists' knowledge, attitudes, and practices related to SUD and harm reduction.

RESULTS: Pharmacists generally acknowledge the efficacy of medications for opioid use disorder (MOUDs) in reducing opioid-related mortality but often hold stigmatizing beliefs about individuals with SUDs. While supportive of harm reduction strategies, such as naloxone distribution and needle and syringe programs, engagement varies widely. Significant gaps in education and training persist, leaving pharmacists with limited confidence and practical experience in SUD care, despite their reported familiarity with MOUDs and naloxone pharmacology.

CONCLUSION: This review highlights a complex interplay of support, barriers, and knowledge gaps shaping pharmacists' roles in SUD treatment and harm reduction. Targeted education, supportive policies, and interprofessional collaboration are crucial to enabling pharmacists to provide stigma-free, comprehensive care for individuals with SUDs.},
}

@article {pmid40534156,
year = {2025},
author = {Persson, S and Liljegren, AE and Olsson, C and Rydén, P},
title = {Use and Perception of Video Consultations Among Swedish Dietitians Before and After COVID-19 Onset.},
journal = {Journal of human nutrition and dietetics : the official journal of the British Dietetic Association},
volume = {38},
number = {3},
pages = {e70080},
pmid = {40534156},
issn = {1365-277X},
support = {//This study was supported by Företagsforskarskolan för Samverkan och Innovation, Umeå Universitet and The Swedish Centre for Rural Health, Region Västerbotten./ ; },
mesh = {Humans ; *COVID-19/epidemiology ; Sweden/epidemiology ; *Nutritionists/psychology/statistics & numerical data ; Male ; Female ; *Telemedicine/statistics & numerical data ; Adult ; Middle Aged ; Surveys and Questionnaires ; SARS-CoV-2 ; *Remote Consultation/statistics & numerical data ; *Dietetics ; Pandemics ; Health Services Accessibility ; *Videoconferencing ; Perception ; },
abstract = {INTRODUCTION: The implementation of telehealth began globally before the onset of COVID-19 but the use of telehealth, particularly video consultations (VCs), is expected to have increased with pandemic restrictions on face-to-face consultations (FTFCs). However, little is known about its actual usage. In Sweden, VCs have the potential to bridge long distances between Registered Dietitians (RDs) and their patients. This study investigates the use and perceptions of VCs among Swedish RDs before and after the onset of COVID-19.

METHODS: Swedish RDs were invited to participate in web-based surveys in 2016 (n = 61) and 2021 (n = 112). Data are analysed and later discussed through the lens of Levesque et al.'s framework for patient-centred access to healthcare.

RESULTS: More RDs reported having VC-experience in 2021 compared to the 2016 survey, 67% and 16% respectively. A majority of the RDs (85%-88%) believed that access to dietetic care would increase with the use of VCs compared to FTFCs. In 2021, about half of RDs (55% and 46%) perceived treatment quality and relational quality to be unaffected by VCs, while approximately one-third (31% and 43%) saw it as being reduced. With their additional experience, there was the caution by 69% of RDs in 2021 that consultations requiring language interpretation services were less suitable for VCs.

CONCLUSIONS: The findings suggest broader VC usage among Swedish RDs participating in the study. Implications for clinical practice include maintained access to healthcare and further practice development to meet quality needs and increased equity.},
}

Humans
*COVID-19/epidemiology
Sweden/epidemiology
*Nutritionists/psychology/statistics & numerical data
Male
Female
*Telemedicine/statistics & numerical data
Adult
Middle Aged
Surveys and Questionnaires
SARS-CoV-2
*Remote Consultation/statistics & numerical data
*Dietetics
Pandemics
Health Services Accessibility
*Videoconferencing
Perception

@article {pmid40529608,
year = {2025},
author = {Hailu, DT and Melaku, MS and Abebe, SA and Walle, AD and Tilahun, KN and Gashu, KD},
title = {A modified UTAUT model for acceptance to use telemedicine services and its predictors among healthcare professionals at public hospitals in North Shewa Zone of Oromia Regional State, Ethiopia.},
journal = {Frontiers in digital health},
volume = {7},
number = {},
pages = {1469365},
pmid = {40529608},
issn = {2673-253X},
abstract = {INTRODUCTION: The shortage of healthcare professionals, long waiting time for treatment, inadequate transportation, and hard-to-reach geographical locations remained challenging in the healthcare service delivery in resource-limited settings. To overcome these challenges, healthcare providers are looking to use telemedicine technologies as an alternative solution. However, user resistance has consistently been identified as a major obstacle to the successful implementation of telemedicine. Thus, this study aimed to assess acceptance to use telemedicine services and its predictors among healthcare professionals at public hospitals in the North Shewa Zone of Oromia Regional State, Ethiopia.

METHOD: A cross-sectional study design was employed among a total of 627 healthcare professionals working at public hospitals in the North Shewa Zone from 3 April to 1 May 2023. The study participants were selected using simple random sampling techniques. A questionnaire, which is adapted from the original instrument developed by Venkatesh et al.'s study and several studies regarding the UTAUT model was used. Data were collected using a self-administered structured questionnaire in English version. The descriptive statistics were estimated using the SPSS version 25, and structural equation modeling analysis was employed using AMOS V.21 software.

RESULTS: In this study, 601 (95.85% response rate) study subjects participated. The study has shown that 315 (52.4%) (95% CI: 48.3-56.5) of the participants accepted to use telemedicine in their routine healthcare services. Performance expectancy (β = 0.184, p = 0.001), effort expectancy (β = 0.183, p < 0.001), facilitating conditions (β = 0.249, p < 0.001), and digital literacy (β = 0.403, p < 0.001) had a significant positive effect on the acceptance to use telemedicine services. Age was used to moderate facilitating conditions (β = 0.400, p < 0.001) and digital literacy (β = 0.598, p < 0.001) in relation to acceptance to use telemedicine services.

CONCLUSION: The healthcare professionals' acceptance to use the offered telemedicine services was promising for the future. Additionally, our research found significant effects between healthcare professionals' acceptance to use telemedicine services with the predictors except social influence. Facilitating conditions and digital literacy with acceptance to use were moderated by age. Thus, the health facility should strengthen its telemedicine technology by raising awareness of its usefulness and ease of use.},
}

@article {pmid40498248,
year = {2025},
author = {Pahwa, R and Molho, E and Lew, M and Dashtipour, K and Gil, RA and Revilla, FJ and Clinch, T and Qin, P and Isaacson, SH and , },
title = {Long-Term Safety and Efficacy of Repeated Cycles of RimabotulinumtoxinB in the Treatment of Chronic Sialorrhea: Results of the OPTIMYST Trial.},
journal = {Neurology and therapy},
volume = {14},
number = {4},
pages = {1553-1567},
pmid = {40498248},
issn = {2193-8253},
abstract = {INTRODUCTION: Botulinum toxin injections into the salivary glands inhibit saliva production by reducing the release of acetylcholine at the parasympathetic nerve terminals within the salivary gland. The phase 3 study reported here assessed the safety, tolerability, and effectiveness of repeated cycles of rimabotulinumtoxinB (RIMA) injections in adults with troublesome sialorrhea.

METHODS: In this phase 3, open-label multicenter study, 187 adult participants with troublesome sialorrhea due to Parkinson disease (65.8%), amyotrophic lateral sclerosis (13.9%), and other etiologies (20.3%) received up to 4 cycles of RIMA treatment (3500 U every 11-15 weeks).

RESULTS: Participants (69% male, 31% female; mean age 64.1 years) had sialorrhea for a mean of 3.2 years at baseline with a mean Unstimulated Salivary Flow Rate (USFR) of 0.63 ± 0.49 g/min. During the first treatment cycle, RIMA significantly reduced the mean±standard deviation (SD) USFR from baseline to week 4 by - 0.34 ± 0.37 g/min (p < 0.0001), and efficacy was maintained through week 13 (- 0.14 ± 0.29 g/min; p < 0.0001). Reductions were maintained at subsequent injection cycles 2-4, with mean absolute USFRs at weeks 4 and 13 of each cycle similar to those of cycle 1. Most adverse events (AEs) were mild, and the most commonly reported AEs in each cycle that were considered to be treatment-related were dry mouth (≤ 15.5% participants/cycle) and dental caries (≤ 6.0% participants/cycle).

CONCLUSION: This study demonstrates that RIMA 3500 U safely reduces saliva production over repeated treatment cycles through 1 year, thereby supporting its utility in the management of troublesome sialorrhea in adults.

GOV IDENTIFIER: NCT02610868.},
}

@article {pmid40464500,
year = {2025},
author = {Dedoni, S and Avdoshina, V and Olianas, MC and Onali, P},
title = {Role of Lysophosphatidic Acid in Neurological Diseases: From Pathophysiology to Therapeutic Implications.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {30},
number = {5},
pages = {28245},
doi = {10.31083/FBL28245},
pmid = {40464500},
issn = {2768-6698},
mesh = {Humans ; *Lysophospholipids/metabolism ; *Nervous System Diseases/physiopathology/metabolism/drug therapy ; Animals ; Receptors, Lysophosphatidic Acid/metabolism ; Signal Transduction ; },
abstract = {Lysophosphatidic acid (LPA), a bioactive lipid molecule, has been identified as a critical regulator of several cellular processes in the central nervous system, with significant impacts on neuronal function, synaptic plasticity, and neuroinflammatory responses. While Alzheimer's disease, Multiple Sclerosis, and Parkinson's disease have garnered considerable attention due to their incidence and socioeconomic significance, many additional neurological illnesses remain unclear in terms of underlying pathophysiology and prospective treatment targets. This review synthesizes evidence linking LPA's function in neurological diseases such as traumatic brain injury, spinal cord injury, cerebellar ataxia, cerebral ischemia, seizures, Huntington's disease, amyotrophic lateral sclerosis, Hutchinson-Gilford progeria syndrome, autism, migraine, and human immunodeficiency virus (HIV)-associated complications Despite recent advances, the specific mechanisms underlying LPA's actions in various neurological disorders remain unknown, and further research is needed to understand the distinct roles of LPA across multiple disease conditions, as well as to investigate the therapeutic potential of targeting LPA receptors in these pathologies. The purpose of this review is to highlight the multiple functions of LPA in the aforementioned neurological diseases, which frequently share the same poor prognosis due to a scarcity of truly effective therapies, while also evaluating the role of LPA, its receptors, and signaling as promising actors for the development of alternative therapeutic strategies to those proposed today.},
}

Humans
*Lysophospholipids/metabolism
*Nervous System Diseases/physiopathology/metabolism/drug therapy
Animals
Receptors, Lysophosphatidic Acid/metabolism
Signal Transduction

@article {pmid40457369,
year = {2025},
author = {Zangouei, Z and Amouzeshi, Z and Mohsenizadeh, SM and Ayati, R},
title = {The impact of self-care training using the teach-back method with telephone follow-up on adherence to treatment in patients with hypothyroidism: a randomized controlled clinical trial.},
journal = {BMC health services research},
volume = {25},
number = {1},
pages = {781},
pmid = {40457369},
issn = {1472-6963},
abstract = {BACKGROUND: Thyroid disorders represent a prevalent chronic disease category in the general population and become more prevalent with age. Adherence to treatment and regular follow-up are critical issues determining the recovery of these patients. The present study aimed to determine the impact of self-care training using the teach-back method combined with telephone follow-up on adherence to treatment in patients with hypothyroidism.

METHODS: A randomized controlled clinical trial was conducted in 2024. A total of 62 eligible patients with hypothyroidism visiting Vali-e-Asr Hospital, affiliated with Birjand University of Medical Sciences, were selected and randomly assigned to two groups. The intervention group members received self-care training using the teach-back method over two sessions, each lasting 45 to 60 min. The control group only received the routine care provided by the center. Data were collected using Fatemi et al.’s Adherence to Treatment Questionnaire and a demographic characteristics form. Data were analyzed using SPSS software version 23 and independent t-test, Mann-Whitney, Repeated measures ANOVA, Friedman non-parametric test, Fisher’s Exact test and chi-square test.

RESULTS: According to findings, 80.6% (n = 25) of the participants were women. The mean age of the intervention and the control group was 45.42 ± 15.74 and 43.97 ± 15.77 years, respectively, with no statistically significant difference (P = 0.72). The results showed a statistically significant difference in the mean overall adherence score (P < 0.001) and its components (P < 0.001) between the two groups. The effect size for all variables immediately and 2 months after the intervention, based on Cohen’s d formula, is greater than 0.80.

CONCLUSION: It seems that self-care training using the teach-back method has a significant impact on adherence to treatment in patients with hypothyroidism. Therefore, it is recommended to use teach-back method alongside other educational methods to enhance adherence to treatment in patients with hypothyroidism.

TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT20241125063855N1, Registration Date:22/12/2024).},
}

@article {pmid40456872,
year = {2025},
author = {Pertek Hatipoğlu, F and Magat, G and Karobari, MI and Madarati, AA and Tulegenova, I and Hatipoğlu, Ö and Taha, N and Makahleh, N and Fernández-Grisales, R and Bekjanova, O and Rahimi, M and Donnermeyer, D and Madfa, AA and Petridis, X and Intriago, MG and Shah, T and Allawi, S and Ivica, A and Lim, WY and Hamouda, A and Jagtap, R and Martín-Biedma, B and Lehmann, AP and Alfirjani, S and Palma, PJ and Buchanan, GD},
title = {Root and canal configurations of maxillary first premolars in 22 countries using two classification systems: a multinational cross-sectional study.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {19290},
pmid = {40456872},
issn = {2045-2322},
mesh = {Humans ; Female ; Male ; Cross-Sectional Studies ; *Bicuspid/diagnostic imaging/anatomy & histology ; Adult ; *Tooth Root/diagnostic imaging/anatomy & histology ; Cone-Beam Computed Tomography ; *Maxilla/diagnostic imaging/anatomy & histology ; Adolescent ; Young Adult ; *Dental Pulp Cavity/diagnostic imaging/anatomy & histology ; Middle Aged ; },
abstract = {This study aimed to evaluate the root and root canal morphology of maxillary first premolars (M1Ps) globally using cone-beam computed tomography (CBCT), comparing results with Vertucci's and Ahmed et al.'s classification systems. CBCT images were obtained for various purposes such as orthodontic treatment planning, tooth impaction, implant surgery, and trauma cases. M1Ps were evaluated in three planes to determine root and root canal morphology, and root bifurcation levels were assessed using integrated software. Prevalence variations between countries and overall prevalence were analyzed using meta-analysis software. A total of 6,600 patients (13,200 bilateral M1Ps) were examined. According to Vertucci's classification, Type IV (59%), Type II (12%), Type I (9%), and Type III (8%) were the most common configurations. Based on Ahmed's classification,[2]MP B[1] P[1] was the most prevalent configuration (53%), followed by [1]MP[1] (9%),[1]MP[1-2-1] (8%), and [1]MP[2-1-1] (7%). The prevalence of [2]MP B[1] P[1] by gender revealed a pooled prevalence of 58% in males and 50% in females. No significant difference was found across age ranges (p > 0.05). Ahmed's classification system provided a more comprehensive analysis by successfully classifying all cases, whereas Vertucci's system failed to categorize 1.8-2.7% of the cases. Significant bilateral symmetry in root morphology was noted. There are regional and gender-specific differences in the root canal morphology of M1Ps. Ahmed et al.'s classification system was more comprehensive, effectively categorizing all observed morphologies compared to Vertucci's system, which had limitations and left some morphologies unclassified.},
}

Humans
Female
Male
Cross-Sectional Studies
*Bicuspid/diagnostic imaging/anatomy & histology
Adult
*Tooth Root/diagnostic imaging/anatomy & histology
Cone-Beam Computed Tomography
*Maxilla/diagnostic imaging/anatomy & histology
Adolescent
Young Adult
*Dental Pulp Cavity/diagnostic imaging/anatomy & histology
Middle Aged

@article {pmid40444312,
year = {2025},
author = {Noble, FJ and Lahane, ST and Lahane, TP and Parekh, RH and Lahane, ST and Dhaytadak, PP and Jain, AK},
title = {Validation of ocular trauma score (OTS) in open- and closed-globe injuries in Indian patients.},
journal = {Indian journal of ophthalmology},
volume = {73},
number = {Suppl 3},
pages = {S498-S501},
pmid = {40444312},
issn = {1998-3689},
mesh = {Humans ; Male ; Female ; India/epidemiology ; Prospective Studies ; Adult ; *Visual Acuity ; Middle Aged ; Young Adult ; Adolescent ; *Eye Injuries, Penetrating/diagnosis/epidemiology ; *Wounds, Nonpenetrating/diagnosis/epidemiology ; Child ; *Eye Injuries/epidemiology/diagnosis ; Follow-Up Studies ; Predictive Value of Tests ; Child, Preschool ; Reproducibility of Results ; },
abstract = {PURPOSE: To validate the predictive value of the ocular trauma score (OTS) in open- and closed-globe eye injuries in the Indian context.

DESIGN: Prospective interventional case series.

METHODS: This study, conducted at a tertiary healthcare institute from January 2018 to June 2019, included 150 eyes of 150 patients with open- and closed-globe injuries. Inclusion criteria were patients with globe injuries who provided informed consent and had complete OTS data. Exclusion criteria included electric, chemical, and thermal injuries, prior surgery, pre-existing poor visual acuity (VA), and severe systemic injuries. There was no randomization. Demographic details, initial and final VA, injury type, and OTS variables were recorded. Patients were classified into OTS categories preoperatively based on Kuhn et al.'s system, and VA distribution was compared with the original study. The main outcome was to assess the correlation between the final BCVA at 6 months post-intervention and the predicted VA based on the OTS category.

RESULTS: A total of 150 patients (72% open globe, 28% closed globe) were included, with a male-to-female ratio of 4.5:1. The mean age ± SD was 29.34 ± 17.49 years. OTS classification showed 6% in OTS 1, 17% in OTS 2, 67% in OTS 3, 4% in OTS 4, and 6% in OTS 5. Final VA was ≤20/40 (41%), 20/50-20/200 (20%), 20/200-1/200 (15%), HM/PL (15%), and NLP (9%). Final VA post-treatment correlated with predicted VA as per the OTS category (Spearman's r = 0.53, P < 0.001).

CONCLUSION: OTS provides reliable prognostic information and has fair predictive value for final VA in open- and closed-globe injuries.},
}

Humans
Male
Female
India/epidemiology
Prospective Studies
Adult
*Visual Acuity
Middle Aged
Young Adult
Adolescent
*Eye Injuries, Penetrating/diagnosis/epidemiology
*Wounds, Nonpenetrating/diagnosis/epidemiology
Child
*Eye Injuries/epidemiology/diagnosis
Follow-Up Studies
Predictive Value of Tests
Child, Preschool
Reproducibility of Results

@article {pmid40426065,
year = {2025},
author = {Schantz, C and Gnangnon, FHR and Aboubakar, M and Agbodande, AK and Puig, P and Denakpo, JL and Tonato Bagnan, A and Bottin, M and Agbodjavou, KM and Sacca, HR and Teixeira, L and Ridde, V and , },
title = {Barriers and opportunities related to access to oncology care in Benin: a qualitative study on breast cancer.},
journal = {BMC cancer},
volume = {25},
number = {1},
pages = {947},
pmid = {40426065},
issn = {1471-2407},
support = {DA N°2022-135 SCHANTZ//Institut National Du Cancer/ ; ANR-17- CONV-0001//French Collaborative Institute on Migration/ ; IdEx University of Paris, ANR-18-IDEX-0001//Cité du Genre/ ; },
mesh = {Humans ; Female ; Benin/epidemiology ; *Breast Neoplasms/therapy/diagnosis/epidemiology ; *Health Services Accessibility ; Qualitative Research ; Middle Aged ; Adult ; Aged ; Palliative Care ; *Medical Oncology ; },
abstract = {BACKGROUND: Breast cancer is the most prevalent cancer among women globally, including in Africa. Oncology is a relatively new discipline in many West African countries, particularly in Benin. There is currently a lack of data concerning the current state of cancer care infrastructure and oncology practices within these countries. The aim of the article is to describe the barriers and opportunities related to access to oncology care in Benin.

METHODS: We employed a qualitative research design. Fifty-six semi-structured interviews were conducted with caregivers treating cancer (n=26), women with breast cancer (n=23), and representatives of associations (n=2). Additionally, 18 days of participant observation were conducted in a chemotherapy and palliative care departments in Cotonou, Benin. The data was analysed using Levesque et al.'s theoretical framework on access to healthcare.

RESULTS: Women encounter obstacles such as delayed diagnosis and unequal access to information, as well as socio-cultural beliefs that favour traditional medicine and discourage surgical interventions like mastectomy. The treatment pathway is often chaotic due to insufficient specialised caregivers and limited infrastructure, with services centralised in Cotonou forcing patients to travel long distances around the country. The current lack of radiotherapy requires patients in need to travel abroad for treatment. High costs of biomedical tests and treatments often lead to care abandonment, worsening health inequalities. However, positive changes should be highlighted, such as the establishment of the Inter-University Diploma in Gynaecological and Breast Oncology in 2013, the expansion of palliative care services in the country, and the planned opening of the Calavi International Hospital Centre in 2025. Challenges include continuing to train health professionals in oncology, further developing health financing and supporting civil society to raise awareness of breast cancer.

CONCLUSIONS: Benin is facing several challenges in relation to the provision of timely and high-quality care for women with breast cancer. However, there is a growing commitment to enhancing breast cancer care in Benin.},
}

Humans
Female
Benin/epidemiology
*Breast Neoplasms/therapy/diagnosis/epidemiology
*Health Services Accessibility
Qualitative Research
Middle Aged
Adult
Aged
Palliative Care
*Medical Oncology

@article {pmid40417702,
year = {2025},
author = {Hoang, K and Prayotamornkul, S and Kuo, CY and Jang, H and Shi, L},
title = {Optical imaging of metabolic dynamics in ALS under methionine regulation.},
journal = {Journal of biomedical optics},
volume = {30},
number = {Suppl 2},
pages = {S23906},
pmid = {40417702},
issn = {1560-2281},
support = {R01 GM149976/GM/NIGMS NIH HHS/United States ; R21 NS125395/NS/NINDS NIH HHS/United States ; U01 AI167892/AI/NIAID NIH HHS/United States ; R01 NS111039/NS/NINDS NIH HHS/United States ; },
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/diagnostic imaging ; *Methionine/metabolism/pharmacology ; Humans ; *Optical Imaging/methods ; Mitochondria/metabolism ; Reactive Oxygen Species/metabolism ; Oxidative Stress ; Spectrum Analysis, Raman/methods ; Cytochromes c/metabolism ; Imaging, Three-Dimensional ; Oxidation-Reduction ; },
abstract = {SIGNIFICANCE: Excessive reactive oxygen species (ROS) in dysfunctional mitochondria, combined with inefficient antioxidant defenses, can drive amyotrophic lateral sclerosis (ALS) progression. L-methionine (Met) can neutralize ROS by modulating metabolism and activating antioxidants; however, its impact on ALS remains unknown.

AIM: We aim to investigate the influence of excess Met on cellular metabolism and ROS accumulation and its role in ALS using multimodal optical imaging techniques.

APPROACH: We applied deuterium oxide-probed stimulated Raman scattering imaging to study metabolic changes of lipids, proteins, and cytochrome c and two-photon excitation fluorescence imaging to assess mitochondrial redox state (nicotinamide adenine dinucleotide and flavin adenine dinucleotide ratio) in ALS cellular models under excess Met treatment. With three-dimensional (3D) image reconstruction, we investigated morphological changes of lipid droplets (LDs) and stress granules (SGs) in ALS models.

RESULTS: Excess Met not only promoted syntheses of lipids and unsaturated lipid membranes but also reduced protein synthesis, cytochrome c oxidation, and oxidative stress. Moreover, 3D image reconstruction showed that LDs increased in volume and number to promote cellular repair, whereas SGs decreased in volume but increased in number in response to reduced cellular stress.

CONCLUSIONS: Excess Met offers a protective mechanism against oxidative stress and promotes cellular repair in ALS.},
}

*Amyotrophic Lateral Sclerosis/metabolism/diagnostic imaging
*Methionine/metabolism/pharmacology
Humans
*Optical Imaging/methods
Mitochondria/metabolism
Reactive Oxygen Species/metabolism
Oxidative Stress
Spectrum Analysis, Raman/methods
Cytochromes c/metabolism
Imaging, Three-Dimensional
Oxidation-Reduction

@article {pmid40413932,
year = {2025},
author = {Nuryana, Z and Herdian, },
title = {Addressing the policy gap between adolescent mental health and school systems in indonesia.},
journal = {Asian journal of psychiatry},
volume = {109},
number = {},
pages = {104543},
doi = {10.1016/j.ajp.2025.104543},
pmid = {40413932},
issn = {1876-2026},
mesh = {Humans ; Indonesia ; Adolescent ; *Health Policy/legislation & jurisprudence ; *Mental Health ; *Adolescent Health ; *Adolescent Health Services/legislation & jurisprudence ; *School Health Services ; *Mental Disorders/therapy ; *School Mental Health Services ; *Mental Health Services ; },
abstract = {Adolescent mental health remains an under-addressed priority in national policies across Southeast Asia, including Indonesia. Although mental health legislation and adolescent health programs exist, integration within the school system is limited and inconsistent with international standards. This commentary builds on Mudunna et al.'s regional policy review by highlighting the critical gap in Indonesia's cross-sectoral coordination between health and education. Drawing on recent national data, we underscore the urgency of school-based mental health interventions in Indonesia, where prevalence rates of anxiety, depression, and suicidal ideation among adolescents are high, yet treatment access remains alarmingly low. We argue that adolescence must be understood not only as a period of psychological vulnerability but also as a transformative stage shaped by biological, social, and legal factors. In the context of LMICs like Indonesia, policy development must consider rights-based, participatory, and culturally appropriate approaches. We call for context-specific frameworks to embed mental health within the national education system as an essential investment in Indonesia's youth and national development.},
}

Humans
Indonesia
Adolescent
*Health Policy/legislation & jurisprudence
*Mental Health
*Adolescent Health
*Adolescent Health Services/legislation & jurisprudence
*School Health Services
*Mental Disorders/therapy
*School Mental Health Services
*Mental Health Services

@article {pmid40398684,
year = {2025},
author = {Naufal, E and Shadbolt, C and Wouthuyzen-Bakker, M and Rele, S and Sahebjada, S and Thuraisingam, S and Babazadeh, S and Choong, PF and Dowsey, MM},
title = {Clinical prediction models to guide treatment of periprosthetic joint infections: a systematic review and meta-analysis.},
journal = {The Journal of hospital infection},
volume = {162},
number = {},
pages = {53-61},
doi = {10.1016/j.jhin.2025.04.035},
pmid = {40398684},
issn = {1532-2939},
mesh = {Humans ; *Prosthesis-Related Infections/therapy ; },
abstract = {BACKGROUND: Several clinical prediction models that aim to guide decisions about the management of periprosthetic joint infections (PJIs) have been developed. While some models have been recommended for use in clinical settings, their suitability remains uncertain.

METHODS: We systematically reviewed and critically appraised all multi-variable prediction models for the treatment of PJI. We searched MEDLINE, EMBASE, Web of Science, and Google Scholar from inception until 1[st] March 2024 and included studies that developed or validated models that predict the outcome of PJI. We used PROBAST (Prediction model Risk Of Bias ASsessment Tool) to assess the risk of bias and applicability. Model performance estimates were pooled via random effect meta-analysis.

RESULTS: Thirteen predictive models and seven external validations were identified. Methodological issues were identified in all studies. Pooled estimates indicated that the KLIC (Kidney, Liver, Index surgery, Cemented prosthesis, C-reactive protein) score had fair discriminative performance (pooled c-statistic 0.62, 95% CI 0.55-0.69). Both the τ[2] (0.02) and I[2] (33.4) estimates indicated that between-study heterogeneity was minimal. Meta-analysis indicated Shohat et al.'s model had good discriminative performance (pooled c-statistic 0.74, 95% CI 0.57-0.85). Both the τ[2] (0.0) and I[2] (0.0) indicated that between study heterogeneity was minimal.

CONCLUSIONS: Clinicians should be aware of limitations in the methods used to develop available models to predict outcomes of PJI. As no models have consistently demonstrated adequate performance across external validation studies, it remains unclear whether any available models would provide reliable information if used to guide clinical decision making.},
}

Humans
*Prosthesis-Related Infections/therapy

@article {pmid40393206,
year = {2025},
author = {Fatima, A and Adnan, M and Hussain Bakhtiari, MI},
title = {Anti-NMDAR encephalitis and MOGAD - Clinical and treatment insights.},
journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia},
volume = {137},
number = {},
pages = {111333},
doi = {10.1016/j.jocn.2025.111333},
pmid = {40393206},
issn = {1532-2653},
mesh = {Humans ; *Anti-N-Methyl-D-Aspartate Receptor Encephalitis/therapy/complications/drug therapy ; Autoantibodies/immunology ; *Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease ; Rituximab/therapeutic use ; },
abstract = {This letter responds to Yan et al.'s study on anti-NMDAR encephalitis combined with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), highlighting its valuable findings on clinical features, MRI lesion diversity, high relapse rates, and rituximab's efficacy in reducing recurrence. We emphasize limitations including reliance on the modified Rankin Scale, which overlooks cognitive and psychosocial impairments, advocating for comprehensive neuropsychological and quality-of-life assessments in future research. The absence of control groups limits comparison to isolated NMDARE or MOGAD cases. Additionally, we propose that the observed high cortical encephalitis rate may reflect additive rather than synergistic effects of both antibodies, given that cortical involvement is known in each condition independently. Further studies should clarify these mechanisms to improve understanding and management of this complex overlap syndrome.},
}

Humans
*Anti-N-Methyl-D-Aspartate Receptor Encephalitis/therapy/complications/drug therapy
Autoantibodies/immunology
*Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease
Rituximab/therapeutic use

@article {pmid40383754,
year = {2025},
author = {Heidari, N and Ghannadzadeh Kermani Pour, R and Farshbafnadi, M and Heidari, A and Ghane, Y},
title = {A systematic review of tumor necrosis factor-α blockers, anti-interleukins, and small molecule inhibitors for dissecting cellulitis of the scalp treatment.},
journal = {Orphanet journal of rare diseases},
volume = {20},
number = {1},
pages = {236},
pmid = {40383754},
issn = {1750-1172},
mesh = {Humans ; *Cellulitis/drug therapy ; *Scalp/pathology/drug effects ; *Scalp Dermatoses/drug therapy ; *Skin Diseases, Genetic/drug therapy ; *Tumor Necrosis Factor-alpha/antagonists & inhibitors ; },
abstract = {BACKGROUND: Dissecting cellulitis of the scalp (DCS) is a type of neutrophilic scarring alopecia identified by the development of folliculitis with clusters of perifollicular pustules and then progresses to abscesses and intercommunicating sinus formation. In the absence of evidence-based guidelines, the treatment of DCS remains a therapeutic challenge. Our study aimed to assess the safety and efficacy of biologics, including tumor necrosis factor-α (TNF-α) blockers, anti-interleukins (ILs), and small molecule inhibitors, including Janus kinase (JAK) inhibitors and phosphodiesterase inhibitors in treating DCS.

METHODS: PubMed/Medline, Scopus, and Ovid Embase databases were systematically searched until February 4th, 2024. Study selection was restricted to case reports, case series, cohort studies, and clinical trials published in English-language. NIH and Murad et al.'s quality assessment tools were utilized for critical appraisal.

RESULTS: A total of 34 articles involving 81 patients met the inclusion criteria. The immunomodulators studied for the treatment of DCS include adalimumab, infliximab, certolizumab pegol, ustekinumab, secukinumab, guselkumab, risankizumab, tildrakizumab, apremilast, upadacitinib, and baricitinib. Our findings implied that TNF-α blockers and IL inhibitors were associated with clinical improvement in most individuals with moderate-to-severe DCS, especially in those who had failed earlier treatments. Moreover, certolizumab pegol could be a safe option for DCS in pregnancy. In addition, the prescription of small molecule inhibitors, including JAK inhibitors and apremilast in DCS patients, demonstrated a significant amelioration in DCS symptoms with a desirable safety profile. Nevertheless, the available data was limited, warranting further investigation. Besides, all aforementioned immunomodulators are still debated for their effectiveness on hair regrowth and reversing the scarring process.

CONCLUSIONS: The application of immunomodulators in treating DCS was associated with satisfactory outcomes, although there is still a need to assess the long-term safety and effectiveness of these therapeutic agents in preventing disease progression and new flare-ups.},
}

Humans
*Cellulitis/drug therapy
*Scalp/pathology/drug effects
*Scalp Dermatoses/drug therapy
*Skin Diseases, Genetic/drug therapy
*Tumor Necrosis Factor-alpha/antagonists & inhibitors

@article {pmid40371978,
year = {2025},
author = {Shafran, R and Egan, SJ},
title = {Widening the Reach: The Broad Impact of Unguided Self-Help for Eating Disorders.},
journal = {The International journal of eating disorders},
volume = {58},
number = {8},
pages = {1432-1435},
pmid = {40371978},
issn = {1098-108X},
mesh = {Humans ; *Feeding and Eating Disorders/therapy/psychology/prevention & control ; *Cognitive Behavioral Therapy/methods ; *Self Care ; Self Concept ; },
abstract = {A systematic review and meta-analysis conducted by Linardon and colleagues on 27 controlled trials using pure self-help for the prevention and treatment of eating disorders, reported small benefits for co-occurring difficulties such as anxiety, depression, distress and self-esteem. The findings were strongest for pre-selected samples considered at risk or who were symptomatic, and are consistent with literature from other areas indicating that focused interventions have a positive impact on comorbid difficulties. The meta-analysis raises questions about the optimal approach to address comorbidity both within and beyond pure self-help. Understanding the wider impact of disorder-specific approaches compared to transdiagnostic approaches is critical to helping clinicians determine what interventions to use and when. It is notable that CBT interventions across disorders often share treatment techniques and methods to optimize the generalization of learning across difficulties, but such common elements are rarely made explicit. The value of session-by-session measurement as an essential tool to guide clinical decision-making in the context of comorbid difficulties is emphasized. Whilst further work is needed, particularly in clinical samples, the message from Linardon et al.'s meta-analysis is straightforward-pure self-help for the prevention and treatment of eating disorders can have a broad impact in improving mental health.},
}

Humans
*Feeding and Eating Disorders/therapy/psychology/prevention & control
*Cognitive Behavioral Therapy/methods
*Self Care
Self Concept

@article {pmid40369790,
year = {2025},
author = {Suga, T and Toyofuku, A},
title = {Challenging the 'Central vs. Peripheral' Classification in Burning Mouth Syndrome: A Critical Analysis of Yang et al.'s Studies.},
journal = {Journal of oral rehabilitation},
volume = {52},
number = {7},
pages = {1160-1163},
doi = {10.1111/joor.14031},
pmid = {40369790},
issn = {1365-2842},
support = {//Japan Society for the Promotion of Science/ ; },
mesh = {Humans ; *Burning Mouth Syndrome/classification/physiopathology/diagnosis ; Nerve Block/methods ; Pain Measurement ; },
abstract = {OBJECTIVE: To critically evaluate the classification of Burning Mouth Syndrome (BMS) into 'peripheral' or 'central' subtypes based on short-term pain relief (≥ 1 cm on the Visual Analogue Scale, VAS) following lingual nerve block, and to explore how quantitative sensory testing (QST) might refine BMS diagnosis.

MATERIALS AND METHODS: We reviewed two recent publications by Yang et al. investigating conditioned pain modulation (CPM) and lingual nerve block efficacy in BMS. We examined their reliance on immediate VAS reductions, sample size, QST findings, and adherence to International Classification of Headache Disorders (ICHD-3) criteria.

RESULTS: Yang et al. reported diminished CPM responses, particularly in the wind-up ratio, among patients classified as central BMS, and highlighted short-term pain relief exclusively in the peripheral subtype. However, categorising patients solely by a ≥ 1 cm VAS reduction may oversimplify the multifactorial nature of BMS, especially when QST findings did not consistently distinguish between groups. Additionally, a small sample size (n = 20) could limit generalisability and obscure subtle pathophysiological differences.

CONCLUSION: Although Yang et al. appropriately applied standard diagnostic guidelines, we recommend integrating subjective (e.g., McGill Pain Questionnaire, Pain Catastrophizing Scale) and objective (e.g., QST, CPM) assessments to capture the complex interplay of peripheral and central mechanisms in BMS. These findings underscore the difficulty of reducing BMS to a strict dichotomy and highlight the need for nuanced, multidimensional approaches. Larger, more diverse cohorts and multidimensional evaluations may improve patient stratification and treatment targeting, ultimately enhancing clinical outcomes for individuals with BMS.},
}

Humans
*Burning Mouth Syndrome/classification/physiopathology/diagnosis
Nerve Block/methods
Pain Measurement

@article {pmid40337818,
year = {2025},
author = {Shaw, L and Masood, M and Neufeld, K and Connelly, DM and Stanley, M and Guitar, NA and Garnett, A and Nikkhou, A},
title = {A conceptual framework for defining work disparities: A case of nurses in long term care.},
journal = {Work (Reading, Mass.)},
volume = {80},
number = {4},
pages = {1927-1937},
doi = {10.1177/10519815241295931},
pmid = {40337818},
issn = {1875-9270},
mesh = {Humans ; *Long-Term Care/methods ; *Nurses/psychology ; Workplace/psychology/standards ; Surveys and Questionnaires ; },
abstract = {BackgroundIncreasing the recruitment and retention of nurses within long-term care (LTC) is a growing challenge faced by the healthcare community. Addressing this problem will require a greater understanding of the day-to-day experiences of nurses, including the disparities and unequal treatment experienced by this group of workers (e.g., pay parity, discrimination, and unfair job demands). However, while there is a need to better understand work disparities faced by nurses, a formalized definition and framework for examining work disparities do not exist within the literature.ObjectiveTo create a conceptual framework to define and analyze work disparities experienced by nurses in LTC.MethodsThis analysis was conducted in adherence to Podsakoff et al.'s four-stage series of recommendations. A partial survey of the literature and operationalizations of work disparities were analyzed to create a core list of attributes of work disparities among nurses in LTC. A definition and framework for classifying work disparities were then posited through a dialogic process and refined by testing on two studies.ResultsA definition of work disparities was posited and four categories of work disparities were identified: job security, work compensation, work opportunities, and workplace treatment. A matrix for classifying the variables of work disparities and comparator groups was refined.ConclusionWith the increasing recognition of unequal treatment of nurses in LTC, this framework can enable further research within this area to support and enhance opportunities for the retention and health of the LTC workforce.},
}

Humans
*Long-Term Care/methods
*Nurses/psychology
Workplace/psychology/standards
Surveys and Questionnaires

@article {pmid40335852,
year = {2025},
author = {Chea, MS and Keller, EX and Uvin, P and De Coninck, V},
title = {RE: transurethral resection of the prostate across continents: a meta-analysis evaluating quality of gold standard in the twenty-first century.},
journal = {World journal of urology},
volume = {43},
number = {1},
pages = {281},
pmid = {40335852},
issn = {1433-8726},
mesh = {Humans ; Male ; Meta-Analysis as Topic ; *Prostatic Hyperplasia/surgery ; Systematic Reviews as Topic ; *Transurethral Resection of Prostate/standards ; },
abstract = {Porto et al.'s systematic review and meta-analysis of transurethral resection of the prostate (TURP) outcomes across different regions reveals significant improvements in IPSS, Qmax, and postvoid residual (PVR) volume. However, the study is limited by high heterogeneity in PVR outcomes, with substantial variability in clot evacuation, irritative symptoms, and incontinence, suggesting inconsistencies in patient populations, methodologies, and surgical techniques. The study fails to address key confounders such as prostate size, age at surgery, and the use of antiplatelet or anticoagulant therapy, which could significantly influence TURP's outcomes. Additionally, the analysis overlooks the rise of newer treatment alternatives like endoscopic enucleation of the prostate (EEP), which offers better outcomes for high-risk patients. Despite presenting valuable data, the lack of standardization, the omission of emerging treatment options, and failure to consider clinical guidelines limit the generalizability and applicability of Porto et al.'s conclusions on TURP as the gold standard for benign prostatic obstruction.},
}

Humans
Male
Meta-Analysis as Topic
*Prostatic Hyperplasia/surgery
Systematic Reviews as Topic
*Transurethral Resection of Prostate/standards

@article {pmid40316871,
year = {2025},
author = {Veit, W and Browning, H and Garcia-Pelegrin, E and Davies, JR and DuBois, JG and Clayton, NS},
title = {Dimensions of corvid consciousness.},
journal = {Animal cognition},
volume = {28},
number = {1},
pages = {35},
pmid = {40316871},
issn = {1435-9456},
mesh = {*Consciousness ; Animals ; Animal Welfare ; *Crows ; },
abstract = {Corvids have long been a target of public fascination and of scientific attention, particularly in the study of animal minds. Using Birch et al.'s (2020) 5-dimensional framework for animal consciousness we ask what it is like to be a corvid and propose a speculative but empirically informed answer. We go on to suggest future directions for research on corvid consciousness and how it can inform ethical treatment and animal welfare legislation.},
}

*Consciousness
Animals
Animal Welfare
*Crows

@article {pmid40314217,
year = {2025},
author = {Ju, T and Zhang, Y and Liu, L and Zhao, X and Li, X and Liu, C and Sun, S and Wu, LA},
title = {The role of gut microbiota-mitochondria crosstalk in neurodegeneration: Underlying mechanisms and potential therapies.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-24-01419},
pmid = {40314217},
issn = {1673-5374},
abstract = {Emerging evidence suggests that the gut microbiota is closely associated with the pathological manifestations of multiple neurodegenerative diseases via the gut-brain axis, which refers to the crosstalk between the gut and the central nervous system. More importantly, mitochondria have been considered prominent mediators of the interplay between the gut microbiota and the brain. Intestinal microbes may modulate mitochondrial function in the central nervous system to affect the progression of neurodegenerative diseases. Mitochondria are essential for meeting the host's substantial neuronal metabolic demands, maintaining excitability, and facilitating synaptic transmission. Dysfunctional mitochondria are considered critical hallmarks of various neurodegenerative diseases. Therefore, this review provides novel insights into the intricate roles of gut microbiota-mitochondrial crosstalk in the underlying mechanisms during the progression of neurodegeneration, as well as the existing potential therapeutic strategies for neurodegenerative disorders. These suggest intestinal microbiota-mitochondrial interaction play a crucial role in the occurrence and development of neurodegenerative diseases, and targeting this interaction may be a promising therapeutic approach to neurodegenerative diseases. However, this review found that there was relatively little research on the effect of this crosstalk on other neurodegenerative diseases, such as Huntington's disease and Multiple sclerosis, and the potential therapeutic strategies were translated into clinical trials, which face many challenges in developing personalized treatment plans based on the unique gut microbiota of different individuals.},
}

@article {pmid40313114,
year = {2026},
author = {Zhou, M and Zheng, M and Liang, S and Li, M and Ma, J and Zhang, S and Song, X and Hu, Y and Lyu, Y and Ou, X and Yue, C},
title = {Inherent potential of mitochondria-targeted interventions for chronic neurodegenerative diseases.},
journal = {Neural regeneration research},
volume = {21},
number = {4},
pages = {1409-1427},
doi = {10.4103/NRR.NRR-D-24-01507},
pmid = {40313114},
issn = {1673-5374},
abstract = {The cure rate for chronic neurodegenerative diseases remains low, creating an urgent need for improved intervention methods. Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases. This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases, aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options. We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy, inhibiting mitochondrial fission, enhancing mitochondrial biogenesis, applying mitochondria-targeting antioxidants, and transplanting mitochondria. Each method has unique advantages and potential limitations, making them suitable for various therapeutic situations. Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression, especially in the early stages. In contrast, those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism. Mitochondrial transplantation, while still experimental, holds great promise for restoring the function of damaged cells. Future research should focus on exploring the mechanisms and effects of these intervention strategies, particularly regarding their safety and efficacy in clinical settings. Additionally, the development of innovative mitochondria-targeting approaches, such as gene editing and nanotechnology, may provide new solutions for treating chronic neurodegenerative diseases. Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.},
}

@article {pmid40287687,
year = {2025},
author = {Seo, M and Ryu, J and Park, J},
title = {Effectiveness of a competency-based coordinator of advance care planning competency enhancement program: a mixed method.},
journal = {BMC palliative care},
volume = {24},
number = {1},
pages = {116},
pmid = {40287687},
issn = {1472-684X},
support = {2018R1C1B5086052//National Research Foundation of Korea/ ; 2018R1C1B5086052//National Research Foundation of Korea/ ; 2018R1C1B5086052//National Research Foundation of Korea/ ; },
mesh = {Humans ; *Advance Care Planning/standards/trends ; Female ; Male ; Adult ; Qualitative Research ; Middle Aged ; *Clinical Competence/standards ; },
abstract = {BACKGROUND: Clinical Ethics Support Services (CESS) improve health-care quality by systematically identifying and resolving ethical issues. CESS providers should be trained to understand patients' difficulties with existential issues and advocate on their behalf. This study evaluates the effectiveness of educational programs to enhance the competencies to solve ethical issues in clinical practice for CESS providers related to life-sustaining-treatment, based on Jonsen et al.'s "the four topics approach."

METHODS: This is an explanatory sequential mixed-method study conducted in quantitative and qualitative phases. Participants included 52 life-sustaining medical workers at general hospitals. The participants were categorized into 24 experimental and 28 control groups, including nurses, social workers, and legal administrations. The program encompassed bioethics, end-of-life care, critical thinking, decision-making training through clinical ethics cases, role-playing, communication skills, and discussions. In the quantitative phase, a quasi-experimental study design with pre-test, intervention, and post-test was used. The program for experimental group was provided through 8 sessions spread across 4 weeks. The participants' experiences were explored through semi-structured interviews in the qualitative phase.

RESULTS: After the education, the experimental and control groups differed significantly in critical thinking disposition, and hospice and palliative care knowledge. Participants acknowledged that critical thinking education improved their ability to analyze and evaluate clinical ethical dilemmas.

DISCUSSION: The case-based, role-playing intervention effectively enhanced participants' communication and critical thinking skills concerning life-sustaining treatments. Participants highlighted the importance of ongoing education and professional development to maintain core knowledge and skills, aiming to enhance the quality of care for patients, families, and colleagues.

TRIAL REGISTRATION: This study was retrospectively registered as a code (No: KCT0009687) in the Korean Clinical Trial Service on August 9, 2024.URL: https://cris.nih.go.kr/cris/search/detailSearch.do?seq=27805&status=5&seq_group=27805&search_page=M .},
}

Humans
*Advance Care Planning/standards/trends
Female
Male
Adult
Qualitative Research
Middle Aged
*Clinical Competence/standards

@article {pmid40280282,
year = {2025},
author = {Matsuda, KM and Kotani, H and Sato, S and Yoshizaki, A},
title = {Unveiling the hidden syndrome: The enigma of anti-transcobalamin receptor autoantibodies.},
journal = {Immunology letters},
volume = {275},
number = {},
pages = {107028},
doi = {10.1016/j.imlet.2025.107028},
pmid = {40280282},
issn = {1879-0542},
mesh = {Humans ; *Autoantibodies/immunology ; *Autoimmune Diseases/immunology ; Vitamin B 12/therapeutic use ; Animals ; *Vitamin B 12 Deficiency/immunology ; Syndrome ; *Antigens, CD/immunology ; *Receptors, Cell Surface/immunology ; },
abstract = {The transcobalamin receptor (CD320) functions as a critical mediator for vitamin B12 uptake in cells, with emerging evidence linking autoantibodies against CD320 to various autoimmune conditions. Pluvinage et al.'s recent study identified anti-CD320 autoantibodies as a cause of autoimmune vitamin B12 central deficiency, specifically affecting the central nervous system while sparing peripheral nerves. Their findings align with our previous work showing anti-CD320's role in cutaneous arteritis. Both studies identified overlapping CD320 epitopes targeted by autoantibodies and demonstrated the therapeutic efficacy of high-dose vitamin B12 supplementation in mitigating symptoms. Expanding on these findings, we observed anti-CD320 autoantibodies in other inflammatory disorders such as systemic sclerosis, suggesting a broader clinical relevance. The work by Pluvinage et al. and our group supports the concept of an "anti-CD320-associated syndrome," with high-dose B12 supplementation as a promising treatment strategy. Further research is needed to fully elucidate the tissue-specific mechanisms and pathophysiology underlying these autoimmune conditions.},
}

Humans
*Autoantibodies/immunology
*Autoimmune Diseases/immunology
Vitamin B 12/therapeutic use
Animals
*Vitamin B 12 Deficiency/immunology
Syndrome
*Antigens, CD/immunology
*Receptors, Cell Surface/immunology

@article {pmid40271071,
year = {2025},
author = {Luo, H and Wei, S and Fu, S and Han, L},
title = {Role of Achyranthes aspera in neurodegenerative diseases: current evidence and future directions.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1511011},
pmid = {40271071},
issn = {1663-9812},
abstract = {Neurodegenerative diseases are caused by the progressive degeneration of neurons and/or their myelin sheaths, ultimately leading to cognitive and motor dysfunction. Due to their complex pathogenesis and the limited efficacy of therapeutic drugs, these diseases have attracted significant attention. Achyranthes aspera, belongs to family Amaranthaceae, has been extensively used in the traditional and folk medicines for the treatment of various ailments. Modern research has revealed that Achyranthes aspera possesses various pharmacological effects, including cardiocerebrovascular protection, immune regulation, antioxidation, and anti-aging. Furthermore, the neuroprotective effects of Achyranthes aspera have been confirmed by numerous scientific studies. This review focuses on the primary pharmacological effects and mechanisms of Achyranthes aspera in the prevention and treatment of neurodegenerative diseases, as well as their potential application prospects. This review aims to provide insights into the potential clinical applications and research directions of Achyranthes aspera in neurodegenerative diseases.},
}

@article {pmid40178423,
year = {2025},
author = {Cheong, WSC and Au, XYJ and Lim, MY and Fu, EW and Li, H and Pua, U and Soon, YQA and Gan, YJ},
title = {The efficacy and safety of radiofrequency ablation in papillary thyroid carcinoma: A systematic review and meta-analysis.},
journal = {Annals of the Academy of Medicine, Singapore},
volume = {54},
number = {3},
pages = {170-177},
doi = {10.47102/annals-acadmedsg.2024241},
pmid = {40178423},
issn = {2972-4066},
mesh = {Humans ; *Radiofrequency Ablation/adverse effects/methods ; *Thyroid Cancer, Papillary/surgery ; *Thyroid Neoplasms/surgery ; Treatment Outcome ; Postoperative Complications/epidemiology/etiology ; },
abstract = {INTRODUCTION: Radiofrequency ablation (RFA) avoids the complications of general anaesthesia, reduces length of hospitalisation and reduces morbidity from surgery. As such, it is a strong alternative treatment for patients with comorbidities who are not surgical candidates. However, to our knowledge, there have only been 1 systematic review and 3 combined systematic review and meta-analyses on this topic to date. This systematic review and meta-analysis seeks to evaluate the efficacy and safety of RFA in the treatment of papillary thyroid carcinoma (PTC) with longer follow-up durations.

METHOD: PubMed, Embase and Cochrane databases were searched for relevant studies published from 1990 to 2021; 13 studies with a total of 1366 patients were included. The Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and Sandelowski et al.'s approach1 to "negotiated consensual validation" were used to achieve consensus on the final list of articles to be included. All authors then assessed each study using a rating scheme modified from the Oxford Centre for Evidence-Based Medicine.

RESULTS: Pooled volume reduction rates (VRRs) from 1 to 48 months after RFA, complete disappearance rates (CDR) and complications were assessed. Pooled mean VRRs were 96.59 (95% confidence interval [CI] 91.05-102.13, I2=0%) at 12 months2-6 and 99.31 (95% CI 93.74-104.88, I2=not applicable) at 48 months.2,5 Five studies showed an eventual CDR of 100%.2,4,7-9 No life-threatening complications were recorded. The most common complications included pain, transient voice hoarseness, fever and less commonly, first-degree burn.

CONCLUSION: RFA may be an effective and safe alternative to treating PTC. Larger clinical trials with longer follow-up are needed to further evaluate the effectiveness of RFA in treating PTC.},
}

Humans
*Radiofrequency Ablation/adverse effects/methods
*Thyroid Cancer, Papillary/surgery
*Thyroid Neoplasms/surgery
Treatment Outcome
Postoperative Complications/epidemiology/etiology

@article {pmid40164635,
year = {2025},
author = {Roithmeier, M and Geck, S and Bühner, M and Wehr, S and Weigel, L and Priller, J and Davis, JM and Leucht, S},
title = {COSMIN review of the PANSS Marder factor solution and other factor models in people with schizophrenia.},
journal = {Schizophrenia (Heidelberg, Germany)},
volume = {11},
number = {1},
pages = {51},
pmid = {40164635},
issn = {2754-6993},
abstract = {The Positive and Negative Syndrome Scale (PANSS) is widely used to assess schizophrenia symptoms. Initially designed with three subscales, Marder et al.´s 5-factor-Model (M5M) first proposed in 1997 has been frequently used in treatment trials, but it has never been systematically reviewed for its measurement properties. We utilized the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guideline for systematic reviews and meta-analytical procedures to assess the psychometric properties of the M5M-PANSS. COSMIN comprises several steps: literature search, risk-of-bias assessments, assessing the updated criteria for good measurement properties, feasibility aspects and grading the quality of the evidence. We further assessed the goodness of fit of other PANSS factor models. We included 95 publications. The M5M-PANSS showed good construct validity, but "insufficient" structural validity. Evidence of other COSMIN domains is largely lacking. Among the multiple (73) factor solutions examined with confirmatory methods, several other 5-factor solutions had better model fit. According to COSMIN rules the M5M should not be recommended for use. Other five-factor models such as the one proposed by Wallwork et al.[1] warrant further evaluation. Nevertheless, the factor composition of the M5M and these other models was relatively similar, so previously published results should not be disregarded.},
}

@article {pmid40132732,
year = {2025},
author = {He, Y and Zheng, Q and Zhifang, Z and Xiaofeng, N and Shenggen, W and Xue, M and Zheng, C and Liu, Z},
title = {When COVID-19 meets diabetes: A bibliometric analysis.},
journal = {Diabetes research and clinical practice},
volume = {223},
number = {},
pages = {112118},
doi = {10.1016/j.diabres.2025.112118},
pmid = {40132732},
issn = {1872-8227},
mesh = {*COVID-19/epidemiology/complications ; Humans ; *Bibliometrics ; *Diabetes Mellitus/epidemiology ; SARS-CoV-2 ; },
abstract = {Coronavirus disease 2019 (COVID-19) survivors are concerned about the likelihood of developing further diseases. This study examines the global trends in scientific research on diabetes associated with COVID-19 from several perspectives. Bibliometric analyses are used to undertake a scientific review of the literature. The Web of Science Core Collection (WoSCC) database was used to acquire bibliographic information on diabetes related to COVID-19 from Jan 2020 to Dec. 2023. The visual map was built via advanced CiteSpace 6.2.R6. 7,348 papers were found. Khunti Kamlesh and Rizzo-Manfredi are the most well-known high-yield authors in this area, and the top ten authors collaborate extensively. Most of these papers came from universities. Harvard Medical School has the most publications, followed by Wuhan University and Huazhong University of Science and Technology. China and the United States are the countries with the most publications. Angiotensin-converting enzymes, chronic disease, intensive care unit, viral infection, and gestational diabetes mellitus were scored 0-11, 2, 3, and 4, respectively. Zhou et al.'s work on this topic, which appeared in the prominent medical journal The Lancet, was cited 1,366 times, highlighting its importance. "clinical characteristics," "diabetes mellitus," "metabolic syndrome," and "angiotensin-converting enzyme" were used as keywords for reference co-citation and clustering data identify. Over the last four years, related investigations have focused primarily on observing clinical aspects. This report is important for developing treatment strategies, directing future research, and guiding clinical practice.},
}

*COVID-19/epidemiology/complications
Humans
*Bibliometrics
*Diabetes Mellitus/epidemiology
SARS-CoV-2

@article {pmid40114332,
year = {2025},
author = {Yildirim, JG and Lawn, S},
title = {Psychometric Properties of the Turkish Version of the Partners in Health Scale: Chronic Disease Self-Management in Primary Healthcare.},
journal = {International journal of nursing practice},
volume = {31},
number = {2},
pages = {e70007},
pmid = {40114332},
issn = {1440-172X},
mesh = {Humans ; Turkey ; *Psychometrics ; *Primary Health Care ; Female ; Middle Aged ; Male ; Aged ; Cross-Sectional Studies ; Adult ; Chronic Disease/therapy ; Aged, 80 and over ; *Self-Management ; Reproducibility of Results ; Surveys and Questionnaires ; *Self Care ; },
abstract = {BACKGROUND: This study aimed to assess the psychometric properties of the Turkish version of the Partners in Health Scale (PIH-TR), which was developed to assess the perceptions of patients with chronic conditions in primary care. Accurate assessment of facilitators and barriers to self-management of chronic conditions, from the patients' perspective, is important for working effectively with them to promote better health outcomes.

METHODS: A cross-sectional validation study was conducted and designed according to the STROBE guidelines. One hundred thirty-six patients, aged 30-90 years (86.7% aged > 60), were recruited from family care centres. Data were collected using the revised PIH, an adapted version of Model-2 (PIH-TR), which is a 12-item self-rated measure of self-management of chronic conditions. The PIH was translated into Turkish using Beaton et al.'s method. Content, construct validity and internal consistency analyses were undertaken to evaluate the data.

RESULTS: The PIH-TR had satisfactory reliability and validity and revealed a four-factor structure appropriate to the original scale: knowledge, partnership in treatment, recognition and management of symptoms and coping. Omega coefficient (0.860), test-retest reliability (0.841) and comparative fit indices (CFI) (0.99) were high.

CONCLUSION: The PIH-TR has good specifics and is reliable and valid as an objective self-rated tool to assess self-management of Turkish patients' chronic conditions.},
}

Humans
Turkey
*Psychometrics
*Primary Health Care
Female
Middle Aged
Male
Aged
Cross-Sectional Studies
Adult
Chronic Disease/therapy
Aged, 80 and over
*Self-Management
Reproducibility of Results
Surveys and Questionnaires
*Self Care

@article {pmid40110864,
year = {2025},
author = {Kornhaber, R and Mc Kittrick, A and Rossiter, R and Cleary, M},
title = {Pain experiences in adult burn survivors during rehabilitation and recovery: A qualitative systematic review.},
journal = {Journal of burn care & research : official publication of the American Burn Association},
volume = {},
number = {},
pages = {},
doi = {10.1093/jbcr/iraf031},
pmid = {40110864},
issn = {1559-0488},
abstract = {Despite advancements in burn care, pain persists despite multidisciplinary management efforts. This review aimed to synthesise the qualitative research that explored the impact of pain on burn survivors' rehabilitation and recovery. In September 2023, PubMed, CINAHL, and Scopus were searched for peer-reviewed published research in English. Nineteen articles from 17 studies met the inclusion criteria. The review used Thomas and Harden's thematic synthesis framework for qualitative research evidence. Two descriptors of pain were described, physical and psychological pain. Pain in burn survivors, both physical and psychological, was complex, intertwined, and dynamic across three stages: before, during, and after interventions. This was found to closely align with Cleary et al.'s trauma-informed model of care in burn settings, which emphasises a three-stage process, underlining that pain is not static but evolves and fluctuates, necessitating adaptive and patient-centred burn care and post-treatment mental health support. Adopting a Trauma-Informed Care (TIC) approach in burn injury settings is crucial. Individuals post-burn encounter varying degrees of physical and psychological pain, which for some remains persistent. Using patient-reported measures throughout recovery deepens the understanding of burn survivors' pain, respecting their personal experiences and insights. It is essential to conduct future longitudinal research and push for a burn-specific qualitative pain assessment to address these complex needs effectively.},
}

@article {pmid40038221,
year = {2025},
author = {Mustafa, F and Mittal, S and Garg, D and Agarwal, A and Garg, A and Gupta, BK and Soneja, M and Srivastava, AK},
title = {HIV associated motor neuron disease (MND): A case series with systematic review of literature.},
journal = {Journal of neurovirology},
volume = {31},
number = {1},
pages = {1-15},
pmid = {40038221},
issn = {1538-2443},
mesh = {Humans ; *HIV Infections/drug therapy/complications/virology ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/virology/drug therapy/diagnostic imaging/pathology ; Female ; Adult ; *Motor Neuron Disease/virology/drug therapy ; Viral Load ; CD4 Lymphocyte Count ; Anti-HIV Agents/therapeutic use ; },
abstract = {Human immunodeficiency virus (HIV) associated motor neuron disease (MND) is very rare. HIV infection can cause an MND-like syndrome due to central nervous system (CNS) involvement de novo or during antiretroviral therapy (ART) due to CNS escape. We present two cases: one with a classic amyotrophic lateral sclerosis (ALS) phenotype, which was the manifestation of symptomatic CNS escape from ART, and the second with a primary lateral sclerosis (PLS) phenotype associated with underlying HIV infection. A systematic review of published literature of people living with HIV (PLHIV) who developed ALS/ MND was conducted using the PubMed, Embase, and Lilacs databases. A total of 91 cases were found, 89 of which were obtained from 37 articles, and two were included from our own case series. In patients with HIV-associated MND, 63 patients reviewed had a classic ALS phenotype followed by progressive muscular atrophy variant (12), progressive bulbar palsy (8), PLS (7) and bulbar onset ALS (1). Neuroimaging, electrophysiology, cerebrospinal fluid (CSF) analysis, CSF and serum HIV viral load, and CD4 count investigations were used for diagnosis. Following the initiation or modification of antiretroviral therapy (ART), approximately 70% exhibited an improvement or a stable disease course. HIV-associated MND is a rare condition that can occur in both ART-naive individuals and those on treatment. A proportion of cases (~ 70%) show improvement with ART. Accurate diagnosis requires the exclusion of opportunistic infections, which remains a critical yet challenging aspect of managing this condition.},
}

Humans
*HIV Infections/drug therapy/complications/virology
Male
Middle Aged
*Amyotrophic Lateral Sclerosis/virology/drug therapy/diagnostic imaging/pathology
Female
Adult
*Motor Neuron Disease/virology/drug therapy
Viral Load
CD4 Lymphocyte Count
Anti-HIV Agents/therapeutic use

@article {pmid40035928,
year = {2025},
author = {Amos, J and Moase, J and Sladeczek, IE},
title = {A scoping review of school-based expressive writing implementation reporting practices: missed opportunities and new research directions.},
journal = {Discover mental health},
volume = {5},
number = {1},
pages = {27},
pmid = {40035928},
issn = {2731-4383},
abstract = {BACKGROUND: Expressive writing (EW) interventions are an effective, flexible, and cost-efficient option for mental health promotion, making them ideally suited for resource-limited school settings. However, the effectiveness of EW interventions varies greatly across studies, which may be partly explained by how EW interventions are implemented. As school-based EW interventions become increasingly popular and more widely used, rigorous reporting of implementation can help advance this emerging field by informing how variation in implementation across studies influences intervention outcomes.

PURPOSE: The purpose of this scoping review was to evaluate the implementation reporting practices of EW interventions in school settings as they can profoundly impact EW effectiveness.

METHODS: The present scoping review assessed the current state of fidelity of implementation (implementation) reporting in the school-based EW literature and identified areas where more rigorous reporting is needed. Out of an initial sample of 367 studies, 19 were eligible for inclusion in the review. Data were analyzed for critical issues and themes derived from Cargo et al.'s (2015) Checklist for Implementation (Ch-IMP).

RESULTS: Overall, the results of this scoping review indicate that researchers who implement EW in school settings have not consistently assessed key implementation domains such as dose received and fidelity.

CONCLUSIONS: To address this problem, the present review adds a unique contribution to the literature by identifying how rigorous reporting of implementation can strengthen the evidence base for school-based EW interventions. Specifically, researchers can support the use of EW interventions in schools through increased implementation reporting to better understand how variability in fidelity of implementation affects treatment outcomes.},
}

@article {pmid40032170,
year = {2025},
author = {Placidi, E and Fionda, B and Rosa, E and Tagliaferri, L and De Spirito, M},
title = {Commentary on feliciani Giacomo et al.'s study of comparison of HDR-brachytherapy and tomotherapy for the treatment of non-melanoma skin cancers of the head and neck.},
journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology},
volume = {206},
number = {},
pages = {110826},
doi = {10.1016/j.radonc.2025.110826},
pmid = {40032170},
issn = {1879-0887},
}

@article {pmid39998031,
year = {2025},
author = {Burke, KM and Shea, C and Arulanandam, V and Sullivan, S and Ellrodt, AS and MacAdam, C and Carney, K and Casagrande, G and Christiansen, E and Paganoni, S},
title = {Cervical Collar Satisfaction and Functional Impact in Amyotrophic Lateral Sclerosis: A Survey Study.},
journal = {American journal of physical medicine & rehabilitation},
volume = {104},
number = {9},
pages = {809-813},
doi = {10.1097/PHM.0000000000002716},
pmid = {39998031},
issn = {1537-7385},
abstract = {OBJECTIVES: Many people with amyotrophic lateral sclerosis develop cervical muscle weakness, often managed with cervical collars. Finding supportive and comfortable collars can be challenging. This study aimed to evaluate satisfaction with various collars and their impact on activities of daily living.

DESIGN: This electronic survey study collected demographic information, clinical status, and participant experiences with commonly used cervical collars.

RESULTS: Thirty-four participants (33 with amyotrophic lateral sclerosis, 1 with primary lateral sclerosis) completed the survey, with 79% reporting neck weakness and 38% experiencing neck pain. Among those who tried cervical collars (65%), many had tried multiple options. The mean satisfaction across all collar types was 5.03 (SD = 2.92) out of 10.

CONCLUSIONS: These findings suggest current collars do not fully meet the needs of people living with amyotrophic lateral sclerosis, emphasizing the importance of improved treatment options. Future research should explore innovative technologies to improve cervical support, function, and quality of life.},
}

@article {pmid39980064,
year = {2025},
author = {Downs, J},
title = {Furthering the benefits of DBT for eating disorders: a lived experience correspondence on McColl et al.},
journal = {Journal of eating disorders},
volume = {13},
number = {1},
pages = {37},
pmid = {39980064},
issn = {2050-2974},
abstract = {This Correspondence article provides a lived experience perspective on McColl et al.'s study, which examines the use of Dialectical Behaviour Therapy for individuals with eating disorders. Drawing on experiences of DBT treatment for longstanding and severe anorexia, the author critically engages with the study's findings, highlighting both the strengths and limitations of the treatment approach McColl et al. describe. While DBT has shown promise in addressing the emotional dysregulation and distress tolerance that underlie many eating disorder behaviours, the author emphasises the need for further adaptation to cater to the complexities of co-occurring physical, psychological, and neurodivergent conditions. The benefits of DBT for eating disorders are explored through personal reflections which emphasise the value and importance of skill-development, therapeutic validation, and motivation to build a "life worth living". Additional, co-produced research is required to further develop the evidence for DBT-based approaches, with particular attention needed in addressing language, stigma, cultural biases, and exclusionary research and clinical practices. Writing from a UK context, the author ends by advocating for the reinstatement of DBT within national guidelines for eating disorder treatment, highlighting its transdiagnostic relevance and potential to provide comprehensive, holistic support for those with more complex presentations.},
}

@article {pmid39968231,
year = {2025},
author = {Nagadi, E and Muryani, A and Adang, RAF},
title = {Integrated Endodontic and Restorative Management of C-Shaped Canals with Severe Coronal Loss in Mandibular Second Molar: A Case Report.},
journal = {Clinical, cosmetic and investigational dentistry},
volume = {17},
number = {},
pages = {121-134},
pmid = {39968231},
issn = {1179-1357},
abstract = {This case report describes the endodontic treatment of a lower right second molar with a C-shaped root canal in a 49-year-old woman exhibiting severe loss of coronal structure. Clinical examination revealed a cavity with temporary filling on tooth 47, which tested negative to cold stimuli but was positive to percussion and bite tests. Cone beam computed tomography (CBCT) scan revealed a C-shaped canal morphology with associated periapical radiolucency, graded as CBCT-PAI score 4. The canal was classified as C3 subdivision III (Melton et al), C3 type II (Fan et al), and [2]47 M[2-2]D[2-1] (Ahmed et al's). A non-surgical endodontic procedure was performed using metallurgically gold heat-treated files, passive ultrasonic irrigation, and warm hydraulic condensation obturation. Post-endodontic restoration included a post and core build-up with the wallpapering technique and a zirconia overlay. This case highlights the importance of CBCT imaging for diagnosis and treatment planning, careful selection of endodontic instruments and technique, and the use of advanced restoration methods to improve the outcome of challenging C-shaped canal treatments with extensive cavity involvement.},
}

@article {pmid39966966,
year = {2025},
author = {Downs, J},
title = {Eating disorders, dentistry, and the need for shared learning: a lived experience commentary on Gidlund et al.},
journal = {Journal of eating disorders},
volume = {13},
number = {1},
pages = {35},
pmid = {39966966},
issn = {2050-2974},
abstract = {This Commentary builds upon the findings of Gidlund et al.'s study on the oral health experiences of women in remission from eating disorders. By exploring the nuanced and deeply embodied dimensions of oral health in eating disorders, their findings also highlight the intersectional challenges faced by individuals when accessing dental care, including stigma, shame, and ambivalence about treatment. Drawing on lived experience examples and published research, this Commentary aims to add to existing evidence demonstrating the need for a more integrated, patient-centred approach to both dental and eating disorders treatment, advocating for harm-reduction strategies to prevent and minimise damage during active illness alongside more inclusive and nuanced conceptualisations of illness, treatment, and recovery. Recommendations are made to adopt non-stigmatising language, expand demographic diversity in research, and to co-produce research and treatment provision alongside people with lived experience. The bidirectional relationship between oral health and eating disorder symptoms requires the creation of greater collaboration between dentistry and ED treatment providers, where shared learning and co-produced training can improve care pathways and address systemic gaps in knowledge and treatment.},
}

@article {pmid39957320,
year = {2025},
author = {Lubbers-Wolterink, R and van Os-Medendorp, H and Jansen Klomp, W and Kamphorst, K},
title = {Exploring patient, informal caregiver, and nurse experiences with home-based hospital-level care for decompensated heart failure: a mixed-methods study.},
journal = {European journal of cardiovascular nursing},
volume = {24},
number = {4},
pages = {569-577},
doi = {10.1093/eurjcn/zvaf025},
pmid = {39957320},
issn = {1873-1953},
mesh = {Humans ; *Heart Failure/nursing/therapy ; *Caregivers/psychology ; Female ; Male ; Middle Aged ; Aged ; *Home Care Services, Hospital-Based ; *Patient Satisfaction ; Adult ; Surveys and Questionnaires ; Aged, 80 and over ; *Attitude of Health Personnel ; Qualitative Research ; Quality of Health Care ; },
abstract = {AIMS: Hospitals are encouraged to provide care closer to patients' homes. This study investigates how patients, informal caregivers, and nurses experience home-based hospital-level care for decompensated heart failure.

METHODS AND RESULTS: This mixed-methods study employed semi-structured interviews with 11 patients and 4 informal caregivers, a questionnaire administrated to 16 nurses from the intensive care, cardiac care, and general cardiology ward, and interviews with 4 nurses, supplemented by two group discussions.A convenience sample was utilized, member checks were performed, and two researchers analysed the patient interviews using thematic analysis based on the normalization process theory. Five overarching themes emerged: (i) Appreciation of personal environment, routines, and autonomy. (ii) Quality of care. (iii) Commitment to the treatment. (iv) Influence of personal characteristics. (v) Changing role of informal caregivers.Regarding nurse satisfaction, findings were mapped according to Proctor et al.'s implementation outcomes: acceptability: hospital-at-home care increases job satisfaction, through increased autonomy, personalized care, and patient satisfaction; appropriateness: hospital-at-home was perceived positively, although safety and adherence needed attention; adoption: hospital-at-home was not particularly challenging but offered a refreshing change; feasibility: on-call duty impacted personal commitments for some nurses; fidelity: information folders with clear protocols were deemed helpful.

CONCLUSION: Patients, caregivers, and nurses generally favour home-based heart failure treatment over hospital-based treatment. Key conditions include comprehensive education on home treatment, adherence support like dietary restriction maintenance, prioritizing patient autonomy, recognizing caregiver burden, and exploring cost-effective strategies such as collaboration with home care organizations.},
}

Humans
*Heart Failure/nursing/therapy
*Caregivers/psychology
Female
Male
Middle Aged
Aged
*Home Care Services, Hospital-Based
*Patient Satisfaction
Adult
Surveys and Questionnaires
Aged, 80 and over
*Attitude of Health Personnel
Qualitative Research
Quality of Health Care

@article {pmid39954940,
year = {2025},
author = {Satao, KS and Doshi, GM},
title = {Intercellular communication via exosomes: A new paradigm in the pathophysiology of neurodegenerative disorders.},
journal = {Life sciences},
volume = {365},
number = {},
pages = {123468},
doi = {10.1016/j.lfs.2025.123468},
pmid = {39954940},
issn = {1879-0631},
mesh = {Humans ; *Exosomes/metabolism/physiology ; *Neurodegenerative Diseases/physiopathology/metabolism/pathology ; *Cell Communication/physiology ; Animals ; },
abstract = {Neurodegenerative disorders are one of the leading causes of death and disability and pose a great economic burden on healthcare systems. Generally, these neurodegenerative disorders have a progressive deterioration in neural function and structure, and deposition of misfolded proteins commonly occurs, such as amyloid-β in AD and α-synuclein in PD. However, there exists a special class of exosomes, which acts like a transmitter and enhances communication between cells. The present review discusses the significant role of exosomes in neurodegenerative diseases, with a focus on Amyotrophic lateral Sclerosis (ALS), AD, PD, and Huntington's disease (HD). In this review, the biogenesis of exosomes is discussed from multivesicular bodies and onwards to their release into the extracellular environment. The present review focuses on recent data concerning the possible use of modified exosomes as ND therapy. Indeed, future work is needed to explain the processes driving exosome biogenesis and cargo selection, while opening new routes by the use of exosome-based therapeutics in neurodegenerative disease diagnosis and treatment.},
}

Humans
*Exosomes/metabolism/physiology
*Neurodegenerative Diseases/physiopathology/metabolism/pathology
*Cell Communication/physiology
Animals

@article {pmid39945200,
year = {2025},
author = {Rovito, MJ and Martinez, S and Thomas, K and Chauhan, K and Gibson, S},
title = {Women, Men, and Cancer Survivorship: A Commentary on Current Data and Possible Underlying Issues.},
journal = {American journal of men's health},
volume = {19},
number = {1},
pages = {15579883241309039},
pmid = {39945200},
issn = {1557-9891},
mesh = {Humans ; Male ; Female ; *Cancer Survivors/statistics & numerical data ; *Neoplasms/mortality/epidemiology/diagnosis ; *Survivorship ; United States/epidemiology ; Survival Rate ; Sex Factors ; },
abstract = {Tonorezos et al.'s recent analysis of U.S. cancer survivorship prevalence provides insightful commentary on the dramatic increase of those surviving the disease over the last 50 years. This growth is reflective of improvements in cancer detection, treatment, and the effects of an aging population. While survival rates have seen a significant increase, more focus is needed on the long term and postsurvivorship health care. What Tonorezos et al.'s piece also indicates is that survivorship trends reveal disparities based on several variables, such as age, sex, and cancer type. Women tend to be diagnosed earlier and have higher survival rates when compared to men, arguably due to more frequent screenings vis-a-vis a sequela of increased utilization of care. Men have higher cancer incidence rates among the aging population, accompanied by lower survival rates, frequently linked to late diagnosis and less utilization of preventive care. Addressing sex-specific disparities is pivotal to developing future treatment plans among cancer survivors. Health care providers must adjust to the multifaceted demands of the population. Public health movements should focus on increasing awareness and promotion of early detection in the male population, taking note of the successful initiatives seen in women's health. It is imperative that these disparities and long-term needs are assimilated into the comprehensive conversation about cancer care to improve outcomes for all survivors.},
}

Humans
Male
Female
*Cancer Survivors/statistics & numerical data
*Neoplasms/mortality/epidemiology/diagnosis
*Survivorship
United States/epidemiology
Survival Rate
Sex Factors

@article {pmid39924695,
year = {2025},
author = {Liu, S and Geng, D},
title = {White-Matter Structural Connectivity and Alzheimer's Disease: A Mendelian Randomization Study.},
journal = {Brain and behavior},
volume = {15},
number = {2},
pages = {e70286},
pmid = {39924695},
issn = {2162-3279},
support = {82372048//National Natural Science Foundation of China/ ; 22TS1400900//Science and Technology Commission of Shanghai Municipality/ ; 22ZR1409500//Science and Technology Commission of Shanghai Municipality/ ; 23S31904100//Science and Technology Commission of Shanghai Municipality/ ; 24SF1904200//Science and Technology Commission of Shanghai Municipality/ ; 24SF1904201//Science and Technology Commission of Shanghai Municipality/ ; },
mesh = {Humans ; *Alzheimer Disease/genetics/pathology/diagnostic imaging ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Magnetic Resonance Imaging ; Mendelian Randomization Analysis/methods ; Neural Pathways/pathology ; *White Matter/diagnostic imaging/pathology ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) and white-matter structural connectivity have been linked in some observational studies, although it is unknown if this is a causal relationship. The purpose of this study was to examine the impact of various white-matter structural connectivity on AD via a two-sample multivariate Mendelian randomization (MR) approach.

METHODS: The genome-wide association study (GWAS) of Wainberg et al. provided the summary data on white-matter structural connectivity, and Bellenguez et al.'s study provided the GWAS aggregated data for AD. MR methods included inverse variance weighted, Mendelian randomization Egger, simple mode, weighted median, and weighted mode. Heterogeneity, horizontal pleiotropy, and "leave-one-out" analysis guaranteed the robustness of causation. Finally, reverse MR analysis was conducted on the white-matter structural connectivity that showed positive results in the forward MR analysis.

RESULTS: Among 206 white-matter structural connections, we identified 10 connections were strongly correlated with genetic susceptibility to AD. Right-hemisphere limbic network to thalamus white-matter structural connectivity and Right-hemisphere salience_ventral attention network to accumbens white-matter structural connectivity were positively correlated with the likelihood of AD, while the remaining 8 white-matter structural connections were negatively related with AD. None of the above 10 white-matter structural connections have a reverse causal relationship with AD.

CONCLUSION: Our MR study reveals a certain degree of association between white-matter structural connectivity and AD, which may provide support for future diagnosis and treatment of AD.},
}

Humans
*Alzheimer Disease/genetics/pathology/diagnostic imaging
Genetic Predisposition to Disease
Genome-Wide Association Study
Magnetic Resonance Imaging
Mendelian Randomization Analysis/methods
Neural Pathways/pathology
*White Matter/diagnostic imaging/pathology