@article {pmid41613186,
year = {2025},
author = {An, W and Jin, Z and Li, Y},
title = {Dual role of exosomes in neurodegenerative diseases: a molecular bridge between neuroinflammation and transmission of pathological proteins.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1708655},
pmid = {41613186},
issn = {1664-2295},
abstract = {Neurodegenerative diseases (NDDs) are complex disorders characterized by the progressive loss of neuronal function. Their pathological mechanisms involve multiple levels, including neuroinflammation, abnormal protein aggregation, and disrupted cell signaling. Diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), multiple sclerosis (MS), and prion diseases not only severely impact patients' quality of life but also pose significant challenges for medical research due to their complex pathogenesis and the lack of effective treatments. In recent years, extracellular vesicles (EVs), particularly exosomes, have garnered increasing attention for their critical role in cell-to-cell communication. Exosomes are membrane-enclosed nanovesicles approximately 30-150 nm in diameter that can carry proteins, lipids, nucleic acids, and other bioactive molecules, influencing recipient cells through paracrine or distant signaling. This review aims to summarize the roles of exosomes as mediators of neuroinflammation and as vehicles for intercellular transmission of pathogenic proteins in neurodegenerative diseases.},
}

@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 = {32},
number = {8},
pages = {539-556},
pmid = {40908696},
issn = {1875-5305},
mesh = {Humans ; *Drug Discovery/methods ; *Neurodegenerative Diseases/drug therapy/enzymology ; Molecular Docking Simulation ; *Enzyme Inhibitors/chemistry/therapeutic use/pharmacology ; Animals ; },
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.},
}

Humans
*Drug Discovery/methods
*Neurodegenerative Diseases/drug therapy/enzymology
Molecular Docking Simulation
*Enzyme Inhibitors/chemistry/therapeutic use/pharmacology
Animals

@article {pmid41612406,
year = {2026},
author = {Bigi, A and Chiti, F},
title = {Understanding liquid-liquid phase separation through TDP-43: fundamental principles, subcellular compartmentalisation, and role of solid inclusion formation.},
journal = {Genome biology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13059-026-03956-9},
pmid = {41612406},
issn = {1474-760X},
support = {#NEXTGENERATIONEU (NGEU) - National Recovery and Resilience Plan (NRRP), Investment PE8─Project Age-It: "Ageing Well in an Ageing Society" (D.R. 1557 11.10.2022).//Ministero dell'Università e della Ricerca/ ; Fondi di Ateneo RICATEN 2024 and RICATEN 2025//Università degli Studi di Firenze/ ; Fondi di Ateneo RICATEN 2023, RICATEN 2024 and RICATEN 2025//Università degli Studi di Firenze/ ; },
abstract = {Phase separation is an important process in biology associated with formation of membraneless organelles but possibly related to the emergence of solid inclusions. TDP-43 is a largely studied paradigmatic case, as it forms neuronal cytoplasmic inclusions in neurodegenerative diseases and is an essential component of many membraneless organelles. Here, we review the physicochemical fundamentals of liquid-liquid phase separation (LLPS) of TDP-43 and its fragments in vitro, showing that full-length TDP-43 requires RNA or chaperones to form stable liquid droplets. We describe TDP-43-containing membraneless organelles and the debate on whether these assemblies represent reservoirs for pathological solid inclusion formation.},
}

@article {pmid41605610,
year = {2026},
author = {Oreskovic, E and Petzold, A and Petropoulos, IN and Hau, S},
title = {Corneal confocal microscopy as a paraclinical test in neurodegenerative disease: a scoping review.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-328181},
pmid = {41605610},
issn = {1468-2079},
abstract = {Corneal confocal microscopy (CCM) is a non-invasive imaging technique that enables quantification of the corneal sub-basal nerve plexus and has emerged as a potential surrogate biomarker for peripheral neurodegeneration. This scoping review evaluated current evidence on the use of CCM in assessing corneal nerve fibre changes across neurodegenerative diseases (NDDs) and explored its potential as a paraclinical diagnostic and monitoring tool. A comprehensive search of PubMed and Scopus was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines to identify studies reporting quantitative CCM metrics, including corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fibre length (CNFL). Both cross-sectional and longitudinal studies of patients with NDDs were included, and findings were narratively synthesised. 50 studies were included: Parkinson's disease (n=13), multiple sclerosis (n=11), cerebrovascular accidents (n=7), post-COVID-19 neuropathy (n=5), amyotrophic lateral sclerosis (n=4), chronic inflammatory demyelinating polyneuropathy (n=4), Alzheimer's disease (n=3), Fabry disease (n=2) and neurofibromatosis type 1 (n=1). CNFL and CNFD were consistently reduced in Parkinson's disease, multiple sclerosis, cerebrovascular accidents, amyotrophic lateral sclerosis, chronic inflammatory demyelinating polyneuropathy and post-COVID-19 neuropathy, whereas CNBD results were inconsistent. The strongest evidence supported the role of CCM in Parkinson's disease and multiple sclerosis. CNFL and CNFD emerged as the most reliable CCM-derived metrics across NDDs, supporting their potential as objective biomarkers for neurodegeneration. While findings support the potential of CCM as a paraclinical diagnostic tool, methodological heterogeneity in image acquisition, analysis software and study design limited comparability. Standardised imaging and analysis protocols are needed to enable broader clinical application and validation across NDDs.},
}

@article {pmid41604971,
year = {2026},
author = {Ahamad, S and Akshinthala, P and Fazal, F and Sah, GK and Khan, MH and Upadhyay, A and Bhat, SA and Hussain, MK},
title = {Small-molecule-based activation of Wnt/β-catenin signaling: An underexplored yet promising strategy for neuroprotection.},
journal = {Bioorganic chemistry},
volume = {170},
number = {},
pages = {109540},
doi = {10.1016/j.bioorg.2026.109540},
pmid = {41604971},
issn = {1090-2120},
abstract = {The Wnt/β-catenin pathway regulates key processes such as neurogenesis, synaptic plasticity, and neuroinflammation, each disrupted in neurodegenerative disorders like AD, PD, ALS, and stroke. Small molecules have shown potential to restore this signaling axis and confer neuroprotection. While these molecules modulate Wnt activity, none has achieved FDA approval, primarily due to poor brain permeability, off-target effects, and insufficient biomarker-based validation. Moreover, current strategies remain disproportionately focused on GSK-3β, with other viable targets, such as DKK1, NOTUM, SFRP-1, sclerostin, and Dvl-CXXC5 or Axin-β-catenin interactions, largely underexplored. Natural products, particularly flavonoids and diterpenoids, offer valuable scaffolds; however, their SAR remain poorly characterized, and promising synthetic leads often lack further development. This review highlights recent pharmacological advances, emerging molecular targets, and key translational barriers. Future success will depend on optimizing pharmacokinetics, improving brain-targeted delivery, and integrating biomarker-driven strategies into clinical trial design.},
}

@article {pmid41604235,
year = {2026},
author = {Al-Ameer, HJ and Basheer, NM and H, M and Shankhyan, A and Panigrahi, R and Arora, V and Azizjanov, K and Eshchanov, E and Ataullaev, Z},
title = {Neuroimmune Cross-Talk and Multilevel Cascades in Fentanyl Toxicity: Interplay of Hypoxic Stress, Glial Activation, and Synaptic Dysregulation in Systems-Level Neurodegeneration.},
journal = {Journal of applied toxicology : JAT},
volume = {},
number = {},
pages = {},
doi = {10.1002/jat.70069},
pmid = {41604235},
issn = {1099-1263},
abstract = {Fentanyl, an ultra-potent synthetic opioid, has traditionally been characterized by its acute toxic effects, particularly respiratory depression. However, accumulating research indicates that its neurobiological influence extends far beyond its short pharmacological window, intersecting with several core mechanisms implicated in major neurodegenerative disorders. This review integrates multiscale evidence to propose a unified conceptual framework in which fentanyl may function not only as an acute neurotoxin but also as a putative accelerator of long-term neurodegenerative vulnerability. Drawing from molecular signaling, cellular stress pathways, glial-neuronal cross-talk, neurovascular regulation, synaptic architecture, and large-scale neural networks, we highlight fentanyl's capacity to trigger a convergent cascade encompassing hypoxic-metabolic reprogramming, mitochondrial fragmentation, TLR4-NF-κB-driven inflammation, NLRP3 inflammasome activation, complement-mediated synaptic pruning, astrocytic EAAT2 downregulation, and blood-brain barrier compromise. These alterations propagate through recursive cross-talk loops that progressively diminish neuronal resilience, destabilize oscillatory coherence, and weaken circuit-level adaptability. Importantly, mechanistic overlaps with Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis suggest that fentanyl exposure may be mechanistically associated with processes capable of accelerating disease onset, exacerbating progression, or unmasking latent vulnerabilities, particularly in genetically or metabolically predisposed individuals. By reframing fentanyl as a systems-level destabilizer capable of imprinting persistent neurobiological changes, this model underscores the need for comprehensive biomarker development, longitudinal risk assessment, and targeted neuroprotective interventions. The integrative framework presented herein offers a foundation for predicting the long-term neurological consequences of fentanyl exposure and calls for urgent reconsideration of its role in population-level neurodegenerative risk.},
}

@article {pmid41601803,
year = {2025},
author = {An, X and Hou, D and Miao, MY and Zhou, YM and Qi, S and Zhang, L and Li, H and Zhou, JX},
title = {Noninvasive monitoring of inspiratory effort in mechanical ventilation: a dual-database bibliometric analysis from 1990 to 2025.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1747437},
pmid = {41601803},
issn = {2296-858X},
abstract = {INTRODUCTION: This study conducts a bibliometric analysis to map the intellectual structure, evolution, and emerging trends in research on airway pressure-based indexes for monitoring inspiratory effort.

METHODS: Systematic searches of the Web of Science Core Collection (WOSCC) and Pubmed were performed for publications dated between 1990 and 2025. Bibliometric parameters, including publication trends, country and affiliation contributions, author influence, journal distribution, keyword co-occurrence, and reference co-citation networks, were analyzed using Bibliometrix and CiteSpace.

RESULTS: The analysis included 291 publications from WOSCC. The annual publication output showed a near U-shaped trend, with an initial decline after the 1990s, followed by a strong resurgence after 2011. Italy was the most productive country, followed by the USA and France. The Institut National de la Sante et de la Recherche Medicale emerged as the leading institution. The journal Chest published the most articles, while the American Journal of Respiratory and Critical Care Medicine had the highest total citations. Laurent Brochard was identified as the most prolific and influential author. Keyword analysis highlighted "occlusion pressure" and "mechanical ventilation" as core themes. Reference co-citation clustering revealed major research domains, including "acute respiratory distress syndrome," "self-inflicted lung injury," and "nasal high flow." Burst detection analysis indicated that "respiratory drive," "lung injury," and "critically ill patients" are emerging research frontiers. Complementary analysis of 242 PubMed clinical studies confirmed these trends and highlighted growing clinical focus on "fluid responsiveness" and "amyotrophic lateral sclerosis."

CONCLUSION: Research on airway pressure-based indices has evolved from physiological studies into a crucial clinical tool for respiratory monitoring. The field exhibits strong international collaboration and emphasizes core areas, including acute respiratory failure and lung-protective ventilation. Analysis of clinical study data confirms these trends and highlights emerging applications in the assessment of fluid responsiveness and neuromuscular disorders. These findings support the ongoing development of personalized ventilation strategies based on monitoring respiratory effort.},
}

@article {pmid41601624,
year = {2025},
author = {Yang, J and Song, X and Yan, S and Li, Q and Yang, W},
title = {The gut microbiota influences neurodegenerative diseases through the gut-brain axis: molecular mechanisms and effects on immune function.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1739329},
pmid = {41601624},
issn = {1664-3224},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Neurodegenerative Diseases/immunology/microbiology/therapy/metabolism/etiology ; Animals ; *Brain/immunology/metabolism ; *Brain-Gut Axis/immunology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Prebiotics ; },
abstract = {The pathogenesis of neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), is complex and multifactorial. Recent studies indicate that the microbiota-gut-brain axis (MGBA) plays a crucial role in the development and progression of NDDs. The MGBA concept reveals a complex bidirectional regulatory network between the gut microbiota and the central nervous system (CNS), linking them through immune, neural, endocrine, and metabolic pathways. This review summarizes the components of the MGBA, communication pathways between gut microbiota and the brain, and mechanisms by which gut microbiota influence the onset and progression of NDDs. Finally, preclinical therapeutic approaches for NDDs are discussed, evaluating preclinical trial data for probiotics, prebiotics, and fecal microbiota transplantation.},
}

Humans
*Gastrointestinal Microbiome/immunology
*Neurodegenerative Diseases/immunology/microbiology/therapy/metabolism/etiology
Animals
*Brain/immunology/metabolism
*Brain-Gut Axis/immunology
Fecal Microbiota Transplantation
Probiotics/therapeutic use
Prebiotics

@article {pmid41599691,
year = {2026},
author = {Zhao, X and Zheng, Y and Cai, X and Yao, Y and Qin, D},
title = {The Expanding Role of Non-Coding RNAs in Neurodegenerative Diseases: From Biomarkers to Therapeutic Targets.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {19},
number = {1},
pages = {},
pmid = {41599691},
issn = {1424-8247},
support = {Y202248634//Zhejiang Provincial Department of Education Project/ ; Y202454271//Zhejiang Provincial Department of Education Project/ ; },
abstract = {Non-coding RNAs have emerged as central regulators of gene expression in neurodegenerative diseases, offering new opportunities for diagnosis and therapy. This review synthesizes current knowledge on microRNAs, long non-coding RNAs, and circular RNAs in Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, emphasizing their roles in synaptic function, proteostasis, mitochondrial biology, and neuroinflammation. We evaluate evidence supporting non-coding RNAs as circulating and tissue-based biomarkers for early detection, disease monitoring, and patient stratification, and we compare analytical platforms and biofluid sources. Mechanistic insights reveal how non-coding RNAs modulate pathogenic protein aggregation, neuronal excitability, immune cell crosstalk, and blood-brain barrier integrity. Translational efforts toward RNA-targeted interventions are reviewed, including antisense oligonucleotides, small interfering RNAs, miRNA mimics and inhibitors, circular RNA decoys, and extracellular vesicle-mediated delivery systems. We discuss pharmacological modulation, delivery challenges, safety concerns, and strategies to enhance specificity and CNS penetration. Finally, we outline emerging computational and multi-omics approaches to prioritize therapeutic targets and propose a roadmap for advancing non-coding RNA research from preclinical models to clinical trials. Addressing biological heterogeneity and delivery barriers will be pivotal to realizing the diagnostic and therapeutic promise of the non-coding transcriptome in neurodegenerative disease. Collaboration across disciplines and rigorous clinical validation are urgently needed.},
}

@article {pmid41599368,
year = {2026},
author = {Niziński, P and Szalast, K and Makuch-Kocka, A and Paruch-Nosek, K and Ciechanowska, M and Plech, T},
title = {Experimental Models and Translational Strategies in Neuroprotective Drug Development with Emphasis on Alzheimer's Disease.},
journal = {Molecules (Basel, Switzerland)},
volume = {31},
number = {2},
pages = {},
pmid = {41599368},
issn = {1420-3049},
support = {2022/47/O/NZ7/00155//National Science Centre/ ; },
mesh = {Humans ; *Alzheimer Disease/drug therapy/metabolism/pathology ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Drug Development ; Animals ; *Translational Research, Biomedical ; Disease Models, Animal ; Induced Pluripotent Stem Cells ; },
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), are becoming more prevalent and still lack effective disease-modifying therapies (DMTs). However, translational efficiency remains critically low. For example, a ClinicalTrials.gov analysis of AD programs (2002-2012) estimated ~99.6% attrition, while PD programs (1999-2019) achieved an overall success rate of ~14.9%. In vitro platforms are assessed, ranging from immortalized neuronal lines and primary cultures to human-induced pluripotent stem cell (iPSC)-derived neurons/glia, neuron-glia co-cultures (including neuroinflammation paradigms), 3D spheroids, organoids, and blood-brain barrier (BBB)-on-chip systems. Complementary in vivo toxin, pharmacological, and genetic models are discussed for systems-level validation and central nervous system (CNS) exposure realism. The therapeutic synthesis focuses on AD, covering symptomatic drugs, anti-amyloid immunotherapies, tau-directed approaches, and repurposed drug classes that target metabolism, neuroinflammation, and network dysfunction. This review links experimental models to translational decision-making, focusing primarily on AD and providing a brief comparative context from other NDDs. It also covers emerging targeted protein degradation (PROTACs). Key priorities include neuroimmune/neurovascular human models, biomarker-anchored adaptive trials, mechanism-guided combination DMTs, and CNS PK/PD-driven development for brain-directed degraders.},
}

Humans
*Alzheimer Disease/drug therapy/metabolism/pathology
*Neuroprotective Agents/pharmacology/therapeutic use
*Drug Development
Animals
*Translational Research, Biomedical
Disease Models, Animal
Induced Pluripotent Stem Cells

@article {pmid41599225,
year = {2026},
author = {Bernatoniene, J and Kopustinskiene, DM and Casale, R and Medoro, A and Davinelli, S and Saso, L and Petrikonis, K},
title = {Nrf2 Modulation by Natural Compounds in Aging, Neurodegeneration, and Neuropathic Pain.},
journal = {Pharmaceutics},
volume = {18},
number = {1},
pages = {},
pmid = {41599225},
issn = {1999-4923},
support = {S-A-UEI-23-7//Research Council of Lithuania (LMTLT)/ ; },
abstract = {This review summarizes the role of nuclear factor erythroid 2-related factor 2 (Nrf2) as a common link between aging, neurodegeneration, and neuropathic pain. Aging is characterized by oxidative stress and constant inflammation, which coincides with reduced Nrf2 activity and weaker antioxidant responses, increasing vulnerability to diseases. In neurodegenerative disorders-including Alzheimer's, Parkinson's, Huntington's disease, and amyotrophic lateral sclerosis-evidence indicates that impaired Nrf2 signaling contributes to oxidative damage, neuroinflammation, and mitochondrial dysfunction. Furthermore, in neuropathic pain, similar mechanisms are involved, and Nrf2 could play a role as a potential analgesic target because of its role in regulating cellular defense pathways. We also review natural Nrf2 modulators (e.g., flavonoids, other polyphenols, terpenoids, alkaloids), discussing their benefits alongside common translational limitations such as poor solubility, low oral bioavailability, rapid metabolism, and potential safety issues, including possible pro-oxidant effects and chemoresistance. We also outline future directions that should prioritize improving delivery systems, addressing NRF2/KEAP1 gene variations, evaluating combinations with standard therapies, exploring preventive applications, and defining dosing, treatment duration, and long-term safety. Overall, current evidence indicates that Nrf2 modulation is a practical, cross-cutting approach relevant to healthy aging and disease management.},
}

@article {pmid41599185,
year = {2026},
author = {Benech, H and Flament, V and Lhotellier, C and Roucairol, C and Joudinaud, T},
title = {New Insights into Drug Development via the Nose-to-Brain Pathway: Exemplification Through Dodecyl Creatine Ester for Neuronal Disorders.},
journal = {Pharmaceutics},
volume = {18},
number = {1},
pages = {},
pmid = {41599185},
issn = {1999-4923},
abstract = {Brain disorders remain a major global health challenge, highlighting the urgent need for innovative therapeutic strategies and efficient drug-delivery approaches. Among alternative routes, intranasal administration has garnered significant interest over recent decades, not only for its systemic delivery but also for its unique ability to bypass the bloodstream and the blood-brain barrier via the Nose-to-Brain (NtB) pathway. While numerous reviews have explored the opportunities and challenges of this route, industrial considerations-critical for successful clinical implementation and commercial development-remain insufficiently addressed. This review provides a comprehensive and critical assessment of the NtB pathway from a drug development and chemistry, manufacturing, and controls perspective, addressing key constraints in pre-clinical-clinical extrapolation, formulation design, device selection, dose feasibility, chronic safety, and regulatory requirements. We also discuss recent advances in neuronal targeting mechanisms, also with a focus on the role of trigeminal nerves. Dodecyl creatine ester (DCE), a highly unstable in plasma creatine prodrug developed by Ceres Brain Therapeutics, is presented as an illustrative case study. Delivered as a nasal spray, DCE enables direct neuronal delivery, exemplifying the potential of the NtB pathway for disorders characterized by neuronal energy deficiency, including creatine transporter deficiency and mitochondrial dysfunction. Overall, the NtB pathway-or, more precisely, the "Nose-to-Neurons" pathway-offers distinct advantages for unstable molecules and metabolic supplementation, particularly in neuron-centric diseases. Its successful implementation will depend on rational molecule design, optimized nasal formulations, appropriate devices, and early integration of industrial constraints to ensure feasibility, scalability, and safety for long-term treatment.},
}

@article {pmid41596533,
year = {2026},
author = {Bogus, K and Marchesi, N and Campagnoli, LIM and Pascale, A and Pałasz, A},
title = {Glial Cells as Key Mediators in the Pathophysiology of Neurodegenerative Diseases.},
journal = {International journal of molecular sciences},
volume = {27},
number = {2},
pages = {},
pmid = {41596533},
issn = {1422-0067},
mesh = {Humans ; *Neurodegenerative Diseases/pathology/metabolism/physiopathology ; *Neuroglia/metabolism/pathology ; Animals ; Microglia/metabolism/pathology ; Astrocytes/metabolism/pathology ; },
abstract = {Neurodegenerative disorders are characterized by progressive neuronal loss and dysfunction, yet increasing evidence indicates that glial cells are central mediators of both disease initiation and progression. Astrocytes, microglia, and oligodendrocyte lineage cells modulate neuronal survival by regulating neuroinflammation, metabolic support, synaptic maintenance, and proteostasis. However, dysregulated glial responses, including chronic microglial activation, impaired phagocytosis, altered cytokine production, and mitochondrial dysfunction, contribute to persistent inflammation and structural degeneration observed across Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease and multiple sclerosis. Recent advances in single-cell and spatial omics have revealed extensive glial heterogeneity and dynamic shifts between neuroprotective and neurotoxic phenotypes, emphasizing the context-dependent nature of glial activity. This review summarizes current knowledge regarding the multifaceted involvement of glial cells in neurodegenerative disorders.},
}

Humans
*Neurodegenerative Diseases/pathology/metabolism/physiopathology
*Neuroglia/metabolism/pathology
Animals
Microglia/metabolism/pathology
Astrocytes/metabolism/pathology

@article {pmid41596063,
year = {2025},
author = {Herbert, A},
title = {G-Quadruplexes Abet Neuronal Burnout in ALS and FTD.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {15},
number = {1},
pages = {},
pmid = {41596063},
issn = {2076-3921},
abstract = {Expansion of d(GGGGC)n repeat in the C9ORF72 gene is causal for Amyotrophic Lateral Sclerosis (ALS) and Frontal Temporal Dementia (FTD). Proposed mechanisms include Repeat-Associated Non-AUG translation or the formation of G-quadruplexes (GQ) that disrupt translation, induce protein aggregation, sequester RNA processing factors, or alter RNA editing. Here, I show, using AlphaFold V3 (AF3) modeling, that the TAR DNA-binding protein (TDP-43) docks to a complex of GQ and hemin. TDP-43 methionines lie over hemin and likely squelch the generation of superoxide by the porphyrin-bound Fe. These TDP-43 methionines are frequently altered in ALS patients. Tau protein, a variant of which causes ALS, also binds to GQ and heme and positions methionines to detoxify peroxides. Full-length Tau, which is often considered prone to aggregation and a prion-like disease agent, can bind to an array composed of multiple GQs as a fully folded protein. In ALS and FTD, loss-of-function variants cause an uncompensated surplus of superoxide, which sparks neuronal cell death. In Alzheimer's Disease (AD) patients, GQ and heme complexes bound by β-amyloid 42 (Aβ4) are also likely to generate superoxides. Collectively, these neuropathologies have proven difficult to treat. The current synthesis provides a framework for designing future therapeutics.},
}

@article {pmid41595662,
year = {2026},
author = {Stoian, II and Nistor, D and Levai, MC and Popa, DI and Popescu, R},
title = {Directional Modulation of the Integrated Stress Response in Neurodegeneration: A Systematic Review of eIF2B Activators, PERK-Pathway Agents, and ISR Prolongers.},
journal = {Biomedicines},
volume = {14},
number = {1},
pages = {},
pmid = {41595662},
issn = {2227-9059},
abstract = {Background and Objectives: The integrated stress response (ISR) is a convergent node in neurodegeneration. We systematically mapped open-access mammalian in vivo evidence for synthetic ISR modulators, comparing efficacy signals, biomarker engagement, and safety across mechanisms and disease classes. Methods: Following PRISMA 2020, we searched PubMed (MEDLINE), Embase, and Scopus from inception to 22 September 2025. Inclusion required mammalian neurodegeneration models; synthetic ISR modulators (eIF2B activators, PERK inhibitors or activators, GADD34-PP1 ISR prolongers); prespecified outcomes; and full open access. Extracted data included model, dose and route, outcomes, translational biomarkers (ATF4, phosphorylated eIF2α), and safety. Results: Twelve studies met the criteria across tauopathies and Alzheimer's disease (n = 5), prion disease (n = 1), amyotrophic lateral sclerosis and Huntington's disease (n = 3), hereditary neuropathies (n = 2), demyelination (n = 1), and aging (n = 1). Among interpretable in vivo entries, 10 of 11 reported benefit in at least one domain. By class, eIF2B activation with ISRIB was positive in three of four studies, with one null Alzheimer's hAPP-J20 study; PERK inhibition was positive in all three studies; ISR prolongation with Sephin1 or IFB-088 was positive in both studies; and PERK activation was positive in both studies. Typical regimens included ISRIB 0.1-2.5 mg per kg given intraperitoneally (often two to three doses) with reduced ATF4 and phosphorylated eIF2α; oral GSK2606414 50 mg per kg twice daily for six to seven weeks, achieving brain-level exposures; continuous MK-28 delivery at approximately 1 mg per kg; and oral IFB-088 or Sephin1 given over several weeks. Safety was mechanism-linked: systemic PERK inhibition produced pancreatic and other exocrine toxicities at higher exposures, whereas ISRIB and ISR-prolonging agents were generally well-tolerated in the included reports. Conclusions: Directional ISR control yields consistent, context-dependent improvements in behavior, structure, or survival, with biomarker evidence of target engagement. Mechanism matching (down-tuning versus prolonging the ISR) and exposure-driven safety management are central for translation.},
}

@article {pmid41594924,
year = {2026},
author = {Bao, Y and Miao, G and He, N and Bao, X and Shi, Z and Hu, C and Liu, X and Wang, B and Sun, C},
title = {Melatonin as a Guardian of Mitochondria: Mechanisms and Therapeutic Potential in Neurodegenerative Diseases.},
journal = {Biology},
volume = {15},
number = {2},
pages = {},
pmid = {41594924},
issn = {2079-7737},
abstract = {Mitochondrial dysfunction is a key early pathological process in neurodegenerative diseases (NDs), leading to oxidative stress, impaired energy metabolism, and neuronal apoptosis prior to the onset of clinical symptoms. Although mitochondria represent important therapeutic targets, effective interventions targeting mitochondrial function remain limited. This review summarizes current evidence regarding the mechanisms by which melatonin protects mitochondria and evaluates its therapeutic relevance, with a primary focus on Alzheimer's disease, Parkinson's disease, and Huntington's disease-the major protagonists of NDs-while briefly covering other NDs such as amyotrophic lateral sclerosis, multiple sclerosis, and prion diseases. Melatonin selectively accumulates in neuronal mitochondria and exerts neuroprotection through multiple pathways: (1) direct scavenging of reactive oxygen species (ROS); (2) transcriptional activation of antioxidant defenses via the SIRT3 and Nrf2 pathways; (3) regulation of mitochondrial dynamics through DRP1 and OPA1; and (4) promotion of PINK1- and Parkin-mediated mitophagy. Additionally, melatonin exhibits context-dependent pleiotropy: under conditions of mild mitochondrial stress, it restores mitochondrial homeostasis; under conditions of severe mitochondrial damage, it promotes pro-survival autophagy by inhibiting the PI3K/AKT/mTOR pathway, thereby conferring stage-specific therapeutic advantages. Overall, melatonin offers a sophisticated mitochondria-targeting strategy for the treatment of NDs. However, successful clinical translation requires clarification of receptor-dependent signaling pathways, development of standardized dosing strategies, and validation in large-scale randomized controlled trials.},
}

@article {pmid41594611,
year = {2026},
author = {Dong, C and Lv, D and Dong, Y and Zhang, Z and Li, Q and Chen, Z},
title = {Advances in Cardiolipin Analysis: Applications in Central Nervous System Disorders and Nutrition Interventions.},
journal = {Biomolecules},
volume = {16},
number = {1},
pages = {},
pmid = {41594611},
issn = {2218-273X},
support = {2022CXPT037//the Key R&D Program of Shandong Province, China/ ; 5501290015//the Advanced Researcher Fund of Jiangsu University/ ; 202510299087//National Training Program of Innovation and Entrepreneurship for Undergraduates/ ; },
mesh = {*Cardiolipins/metabolism/analysis ; Humans ; *Central Nervous System Diseases/metabolism/diet therapy ; Animals ; Mitochondria/metabolism ; },
abstract = {Cardiolipin (CL), a unique dimeric phospholipid predominantly enriched in the inner mitochondrial membrane, is a crucial determinant of mitochondrial structure and function. Its content, fatty acyl composition, and oxidation state are associated with mitochondrial bioenergetics, dynamics, and cellular signaling. Disruptions in CL metabolism are increasingly implicated in the pathogenesis of various central nervous system (CNS) disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, epilepsy, and traumatic brain injury. This narrative review summarizes recent advances in the analytical techniques employed for CL analysis. The principles and applications of mass spectrometry-based platforms, nuclear magnetic resonance, Fourier-transform infrared spectroscopy, atomic force microscopy-infrared spectroscopy, and fluorescent probes were discussed, with an emphasis on their strengths in revealing the structure, composition, dynamics, and spatial distribution of CL. Furthermore, the evidence of CL abnormalities in various CNS disorders was assessed, often showing decreased CL levels, loss of polyunsaturated species, and increased oxidation associated with mitochondrial dysfunction and neuronal apoptosis. Furthermore, the nutritional interventions for CL modulation were discussed, such as polyunsaturated fatty acids, polyphenols, carotenoids, retinoids, alkaloids, and triterpenoids, which summarize their potential health-beneficial effects in remodeling the CL acyl chain, preventing oxidation, and regulating mitochondrial homeostasis. Overall, this review provided insight into integrating CL analysis and dietary modulation in understanding CL-related pathologies in CNS disorders.},
}

*Cardiolipins/metabolism/analysis
Humans
*Central Nervous System Diseases/metabolism/diet therapy
Animals
Mitochondria/metabolism

@article {pmid41593859,
year = {2026},
author = {Pathak, K and Kumari, T and Aggarwal, L and Singh, V},
title = {Preventive dietary and lifestyle strategies for neurodegenerative diseases: a comprehensive review.},
journal = {Nutritional neuroscience},
volume = {},
number = {},
pages = {1-26},
doi = {10.1080/1028415X.2026.2615456},
pmid = {41593859},
issn = {1476-8305},
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's, Parkinson's, Huntington's disease, and amyotrophic lateral sclerosis, are rising sharply across the globe. These incurable and progressive conditions lead to severe cognitive and motor impairments, diminish the quality of life, and place a substantial burden on healthcare systems. In response to this growing challenge, the present review offers an integrative and forward-thinking perspective focused on modifiable daily habits that have the potential to preserve brain health and reduce the risk of neurodegeneration. Mounting evidence reveals that everyday lifestyle choices, including food habits, physical activity, sleep, and stress, profoundly shape long-term cognitive outcomes. Neuroprotective diets such as the Mediterranean and ketogenic diets reduce oxidative stress, enhance mitochondrial efficiency, and promote neurogenesis, whereas the Western diet accelerates cognitive decline. Intermittent fasting and caloric restriction trigger autophagy and ketone production, offering metabolic resilience. Functional foods such as berries, walnuts, and leafy greens combat inflammation and oxidative damage. Physical activity and resistance training boost synaptic plasticity and neurotransmitter balance. In addition, high-quality sleep and effective stress control help preserve neuronal integrity and lower neuroinflammatory markers. By integrating insights from neuroscience, nutrition, and behavioral medicine, this review highlights how multiple modifiable factors, when adopted consistently, can work in synergy to preserve cognitive health, delay disease onset, and reduce progression.},
}

@article {pmid41592170,
year = {2026},
author = {Allen, MD and Diab, V and Lezaic, N and Binet, M and Gentil, BJ and Blanchard, O and Genge, A and Massie, R},
title = {The genetics of autosomal recessive ALS: a review of the common forms and their phenotypes.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/21678421.2026.2615110},
pmid = {41592170},
issn = {2167-9223},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease marked by progressive degeneration of upper and lower motor neurons. Most forms of ALS associated with a suspected causal variant are inherited in an autosomal dominant manner. However, there is an important subset of autosomal recessive (AR) variants, often associated with early-onset or atypical clinical features. Advances in genetic sequencing have led to increased recognition of AR ALS. In this review, we focus on four key confirmed AR ALS-associated genes, which appear to be most common-ALS2, SPG11, OPTN, and the D90A variant of SOD1-reviewing their pathophysiology and unique clinical manifestations. We also highlight very rare AR mutations implicated in ALS, including SYNE1, ATP13A2, and FUS, and some associated with overlap syndromes or debated pathogenicity including SIGMAR1, ERLIN1, and ERLIN2. These genes are involved in an array of processes including axonal transport, endosomal trafficking, oxidative stress response, and autophagy, suggesting distinct mechanisms of motor neuron degeneration. Some forms of AR ALS more frequently present with juvenile onset and slower progression, but other genes are associated with broader phenotypic spectra. This includes overlap with hereditary spastic paraplegia (HSP) and hereditary ataxias. Understanding these AR forms of ALS may enhance diagnostic precision, improve prognostication, and may pave the way for targeted gene therapies. This review underscores the emerging significance of AR inheritance in ALS and calls for deeper investigation into its molecular and clinical dimensions.},
}

@article {pmid41585268,
year = {2025},
author = {Srivastav, J and Sharma, S},
title = {Viral and non-viral cellular therapies for neurodegeneration.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1718669},
pmid = {41585268},
issn = {2296-858X},
abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) are characterized by progressive loss of neurons and still lack curative treatment options. In this review, we describe current and developing therapeutic strategies that include viral vector-based gene delivery, antisense oligonucleotide (ASO) and RNA interference methods, stem cell transplantation, and genome editing technologies. Adeno-associated viruses (AAVs) and lentiviruses have been used for gene delivery in preclinical and clinical studies, while ASOs are under development to reduce expression of pathogenic proteins such as tau, α-synuclein, and mutant huntingtin. Cellular therapies, including mesenchymal stem cell (MSC)-based paracrine support and transplantation of neurons derived from induced pluripotent stem cells (iPSCs), are being evaluated, particularly in PD and AD. We also discuss important gene targets such as APOE4, GBA1, SCNA, and MAPT, and how treatment strategies may differ between monogenic and polygenic forms of these disorders. Lastly, we highlight recent efforts focused on genes like TREM2, PINK1, and progranulin, and examine their role in the future development of gene- and cell-based interventions.},
}

@article {pmid41581940,
year = {2026},
author = {Behera, P and Rangappa, N and Chandrashekar, M and Mishra, A and Chinnathambi, S and Mishra, M},
title = {The multifaceted role of antimicrobial peptides in neurodegeneration: Insights from Drosophila and beyond.},
journal = {Advances in protein chemistry and structural biology},
volume = {149},
number = {},
pages = {419-444},
doi = {10.1016/bs.apcsb.2025.08.003},
pmid = {41581940},
issn = {1876-1631},
mesh = {Animals ; Humans ; *Neurodegenerative Diseases/immunology/metabolism/pathology ; *Antimicrobial Peptides/metabolism/immunology ; *Drosophila ; Disease Models, Animal ; Immunity, Innate ; },
abstract = {Antimicrobial peptides (AMPs) are tiny proteins essential for innate immunity in various taxa, including mammals and insects. They provide defence against a wide range of pathogens, including bacteria, viruses, fungi, and parasites. Apart from their antimicrobial properties, new studies have revealed the roles of AMPs in brain ageing, neurodegeneration, and neuroinflammation. With an emphasis on their dysregulation in glial and neuronal tissues and their role in neuroinflammation, mitochondrial dysfunction, and neuronal loss, we reviewed the new function of AMPs beyond their antimicrobial activity. Findings from Drosophila models of Huntington's disease, Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, and Ataxia-telangiectasia show that immune pathways, like Toll and immune deficiency, drive persistent or ectopic AMP expression, which is similar to the inflammatory processes seen in human neurodegenerative diseases. Furthermore, the dual function of AMPs as mediators of sterile inflammation and protective immunological agents reveals a universal paradox. The translational relevance of these findings is further supported by comparisons with human AMPs, such as LL-37 and β-defensins. LL-37 and β-defensins levels were found to be increased in the cerebrospinal fluid of patients suffering from meningitis. LL-37 is released from neurons and activates glial cells, boosting the production of inflammatory cytokines and decreasing neuronal survival. This chapter redefines AMPs as not only sentinels of microbial defence but also as important participants in preserving or disturbing brain homeostasis by establishing them as a link between immunity and neurobiology.},
}

Animals
Humans
*Neurodegenerative Diseases/immunology/metabolism/pathology
*Antimicrobial Peptides/metabolism/immunology
*Drosophila
Disease Models, Animal
Immunity, Innate

@article {pmid41575675,
year = {2026},
author = {Kopalli, SR and Wankhede, N and Rahangdale, SR and Sammeta, S and Aglawe, M and Koppula, S and Taksande, B and Upaganlawar, A and Umekar, M and Kale, M},
title = {Age-driven dysbiosis: gut microbiota in the pathogenesis and treatment of aging disorders.},
journal = {Biogerontology},
volume = {27},
number = {1},
pages = {42},
pmid = {41575675},
issn = {1573-6768},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/therapy/microbiology ; *Aging/physiology ; Animals ; Probiotics/therapeutic use ; },
abstract = {Aging, a complex physiological and molecular process, has undergone significant changes, of which gut microbiome composition has surfaced as an important key in the maintenance of neurological health. Recent studies have revealed the significant impact of age-related gut dysbiosis in the induction of neuroinflammation, metabolic syndrome, disruptions in gut-brain axis, and age-related neurological decline. Although significant studies have revealed the impact of the microbiome-gut-brain axis in individual neurological diseases, an aging-focused holistic synthesis has not yet been adequately developed. This review provides a critical assessment of the involvement of age-related dysbiosis of gut microbiota in the development and progression of neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and cognitive aging of the elderly, and to focus on age-related microbial patterns and mechanisms of dysbiosis related to neurological aging, including inflammation and immune system dysregulation, metabolic changes, oxidative stress, barrier dysfunction, and gut-brain communication through enteroendocrine, enteric neural, and vagal mechanisms, and to emphasize disease-specific and common microbial patterns of dysbiosis and beneficial and harmful microbial roles in aging diseases. This review assesses some of the latest promising therapies aimed at the microbiota, such as probiotics, prebiotics, dietary therapies, fecal microbiota transplantation, as well as pharmacological therapies, and critically discusses their limitations in terms of interindividual variability and their generalisation and applicability. Focusing on mechanistic, comparative, and translation aspects, this review offers a comprehensive approach to neurological aging due to gut microbiota and identifies gaps for future precision microbiome-based interventions.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Dysbiosis/therapy/microbiology
*Aging/physiology
Animals
Probiotics/therapeutic use

@article {pmid41572495,
year = {2026},
author = {Zaman, A and Drake, SS and Fournier, AE},
title = {Extracellular Vesicle-Derived microRNAs as Fluid Biomarkers in Neurodegenerative Diseases: A Systematic Review.},
journal = {Journal of neurochemistry},
volume = {170},
number = {1},
pages = {e70323},
pmid = {41572495},
issn = {1471-4159},
support = {//MS Canada/ ; /CAPMC/CIHR/Canada ; //Fonds de Recherche du Québec - Santé/ ; //Myelin Repair Foundation/ ; //Fonds de recherche du Québec/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/diagnosis/genetics/cerebrospinal fluid/blood/metabolism ; *Extracellular Vesicles/metabolism/genetics ; *MicroRNAs/cerebrospinal fluid/metabolism/blood ; Biomarkers/cerebrospinal fluid/blood/metabolism ; Animals ; },
abstract = {Given the absence of curative treatments for neurodegenerative diseases, early detection and therapeutic intervention are critical to slowing disease progression. Extracellular vesicles (EVs) have emerged as promising biomarkers for neurodegeneration, owing to their accessibility in bodily fluids and dynamic molecular cargo, including microRNAs (miRNAs). The last decade has seen accumulating evidence for miRNA dysregulation in circulating EVs from people with neurodegenerative diseases; however, assessing reproducibility between studies remains challenging, largely due to clinical and methodological heterogeneity. In this systematic review, we comprehensively searched the MEDLINE database for studies investigating miRNA expression in biofluids from people with neurodegenerative diseases. We extracted miRNA expression data from 185 peer-reviewed publications, published until June of 2025, reporting altered miRNA levels in fluid-derived EVs from people with neurodegenerative diseases. We consolidated results between studies to identify the most frequently dysregulated miRNAs across diseases, with a focus on Alzheimer's disease, Parkinson's disease, mild cognitive impairment, multiple sclerosis, amyotrophic lateral sclerosis, frontotemporal dementia, stroke, traumatic brain injury, and schizophrenia. Evaluating tissue specificity of frequently dysregulated miRNAs revealed enrichment of select miRNAs in the nervous system relative to blood and immune compartments. Summarizing miRNA regulation across biofluids emphasized consistencies between cerebrospinal fluid and plasma, but not serum. We highlight circulating miRNAs that may be reflective of neuropathology, including miR-143-3p, miR-127-3p, miR-9-5p, miR-15a-5p, and miR-125b-5p. Finally, we provide a repository of miRNA expression data from over 30 neurodegenerative conditions which can be exploited to further investigate miRNA regulation in diseases of interest.},
}

Humans
*Neurodegenerative Diseases/diagnosis/genetics/cerebrospinal fluid/blood/metabolism
*Extracellular Vesicles/metabolism/genetics
*MicroRNAs/cerebrospinal fluid/metabolism/blood
Biomarkers/cerebrospinal fluid/blood/metabolism
Animals

@article {pmid41571168,
year = {2026},
author = {Malvandi, AM and Gerosa, L and Maroni, P and Orlando, ME and Mohammadipour, A and Lombardi, G},
title = {miRNA-206 in muscle and central nervous system crosstalk during exercise: A double-edged sword with therapeutic potential.},
journal = {Neuroscience and biobehavioral reviews},
volume = {183},
number = {},
pages = {106569},
doi = {10.1016/j.neubiorev.2026.106569},
pmid = {41571168},
issn = {1873-7528},
abstract = {Physical activity triggers complex molecular responses in skeletal muscle, with increasing evidence showing systemic signaling roles for muscle-derived microRNAs (myomiRs). Among these, miR-206 has attracted attention for its dual function: promoting muscle regeneration but potentially harming the central nervous system (CNS). This review examines how miR-206 expression is regulated during exercise and its effects on muscle biology-such as fiber-type specification, mitochondrial changes, and neuromuscular junction (NMJ) repair. It also explores the paradoxical effects of high miR-206 levels in the CNS, where it targets brain-derived neurotrophic factor (BDNF), reducing neuroplasticity and increasing vulnerability to neuropsychiatric and neurodegenerative diseases. The review highlights disease-specific aspects, showing miR-206 as harmful in Alzheimer's, stroke, and depression, but potentially protective in amyotrophic lateral sclerosis (ALS). We discuss its potential as a biomarker and therapeutic target, stressing tissue-specific regulation approaches. Overall, miR-206 plays a key role in muscle-brain communication, with important implications for exercise, aging, and CNS disorders.},
}

@article {pmid41570741,
year = {2026},
author = {Genin, EC and Paquis-Flucklinger, V},
title = {ALS-related proteinopathies: From TDP-43 to mitochondrial proteinopathies.},
journal = {Current opinion in neurobiology},
volume = {97},
number = {},
pages = {103163},
doi = {10.1016/j.conb.2025.103163},
pmid = {41570741},
issn = {1873-6882},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive loss of motor neurons. ALS often overlaps clinically and pathologically with frontotemporal dementia (FTD), the second most common form of dementia. Like many neurodegenerative disorders, both ALS and FTD share a crucial pathological hallmark, the aggregation of misfolded proteins into insoluble inclusions in degenerating neurons. This process is referred to as proteinopathy. This review focuses on the proteinopathies associated with ALS, including aggregates of TDP-43, SOD1, FUS, and CHCHD10, which disrupt critical cellular processes such as RNA metabolism, mitochondrial function, and protein homeostasis. The review highlights to the identification of new types of mitochondrial and cytosolic aggregates linked to CHCHD10-related ALS. Although the precise pathological mechanisms remain to be fully elucidated, strategies aimed at restoring proteostasis and reducing protein aggregation may be promising therapeutic approaches for treating ALS, as they directly target fundamental pathogenic mechanisms.},
}

@article {pmid41567979,
year = {2025},
author = {Hamdalla, RH and Bhaskar, VB and Tian, C},
title = {Brain-derived extracellular vesicles potentially mediate crosstalk with peripheral organs in neurodegenerative diseases.},
journal = {Frontiers in cell and developmental biology},
volume = {13},
number = {},
pages = {1710150},
pmid = {41567979},
issn = {2296-634X},
abstract = {Brain-Derived Extracellular vesicles (BDEVs) are emerging mediators of intra- and interorgan communication in neurodegenerative diseases (NDs) such as Alzheimer's Disease (AD) and Parkinson's Disease (PD). A growing body of evidence suggests that BDEVs play an important role in modulating intercellular communication within the central nervous system in the pathogenesis of many NDs. By transporting non-coding RNAs (e.g., miRNAs) and important pathological proteins, BDEVs also influence peripheral organs and contribute to the progression of disease in the central nervous system (CNS). This review extends the understanding of NDs beyond solely brain dysfunction and gives a novel framework for the progression of these diseases, uniquely emphasizing the currently underexplored mechanisms by which BDEV-mediated communication exacerbates or potentially initiates peripheral dysfunction or complications. It maps and clarifies the specific and potential mechanisms by which CNS-originating EV activity proliferates systemic dysfunction, presenting new opportunities and areas for therapeutic and diagnostic treatments for NDs. These findings are contextualized across multiple NDs, including Amyotrophic Lateral Sclerosis (ALS), Huntington's Disease (HD), and Multiple Sclerosis (MS), by incorporating data on dysregulated BDEV miRNAs and toxic proteins to map the pathway of BDEV-mediated disease spread.},
}

@article {pmid41565509,
year = {2026},
author = {Lee, NC and Lin, CH and Chien, YH and Hwu, WL},
title = {Genetic testing for adult-onset neurodegenerative diseases: A clinical perspective.},
journal = {Journal of the Formosan Medical Association = Taiwan yi zhi},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jfma.2026.01.021},
pmid = {41565509},
issn = {0929-6646},
abstract = {Adult-onset neurodegenerative diseases (AOND), such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia, severely affect patients' quality of life. Pathogenic single-nucleotide variations (SNVs) and small insertions and deletions (indels) can disrupt genes involving ANOD, and expansion of short tandem repeats such as trinucleotide repeats is an important etiology of hereditary ataxia. Variations in more than one gene combined to create polygenic risk scores (PRS) for multifactorial types of AOND. Recently, genome structural variations (SVs) like copy number variations (CNVs) and expansion of long repeats are increasingly identified as the etiologies of AOND. Tools for molecular diagnosis of AOND have evolved from Sanger sequencing to next-generation sequencing (NGS) such as short-read whole-exome sequencing (WES) and whole-genome sequencing (WGS), and long-read sequencing is especially helpful in solving SVs and expansions of long repeats. Patients might have affected and/or at-risk family members at the time of diagnosis, so genetic counseling for risk handling and birth planning need to be conducted with caution. This review will help readers to better understand the genetic testing for AOND.},
}

@article {pmid41563518,
year = {2026},
author = {Boomsma, A and Doyle, C and Sai, N and Rogers, ML and Lee, SH and Benyamin, B},
title = {The differences in sex ratio between sporadic and familial amyotrophic lateral sclerosis: a systematic review.},
journal = {Journal of neurology},
volume = {273},
number = {2},
pages = {92},
pmid = {41563518},
issn = {1432-1459},
support = {Research Training Program//Australian Government/ ; DIS-202303-00932//FightMND/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/genetics ; *Sex Ratio ; Male ; Female ; *Sex Characteristics ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is more prevalent in males than in females. However, it is unclear whether the difference in sex ratio is observed similarly in sporadic compared to familial ALS. Here, we conducted a systematic review to investigate the differences in sex ratio between familial and sporadic ALS. Following the meta-analysis of observational studies in epidemiology (MOOSE) guidelines, this study searched Ovid MEDLINE, Embase, Emcare, SCOPUS and Cochrane databases. We used a random-effects meta-analysis to estimate sex ratios in a total of 9269 ALS patients (4135 female, 5134 male) across 20 included studies. We confirmed that ALS is more prevalent in males than in females (sex ratio: 1.25 (95%CI 1.14-1.37). However, when we stratified the analyses, the sex ratio was only different in sporadic ALS. Male-to-female ratios were 1.29 (95% CI 1.16-1.42) for sporadic ALS and 1.05 (95% CI 0.93-1.18) for familial ALS. A further analysis showed a pooled risk ratio of 1.07 (95% CI 1.00-1.15), indicating a 7% higher likelihood of males being diagnosed with sporadic rather than familial ALS. These findings highlight the importance of considering sex-specific factors in ALS research and clinical practice.},
}

Humans
*Amyotrophic Lateral Sclerosis/epidemiology/genetics
*Sex Ratio
Male
Female
*Sex Characteristics

@article {pmid41562880,
year = {2026},
author = {Fiorella, ML and Ballini, L and Lavermicocca, V and Ragno, MS and Restivo, DA and Marchese-Ragona, R},
title = {Dysphagia and Dysarthria in Neurodegenerative Diseases: A Multisystem Network Approach to Assessment and Management.},
journal = {Audiology research},
volume = {16},
number = {1},
pages = {},
pmid = {41562880},
issn = {2039-4330},
abstract = {Dysphagia and dysarthria are common, co-occurring manifestations in neurodegenerative diseases, resulting from damage to distributed neural networks involving cortical, subcortical, cerebellar, and brainstem regions. These disorders profoundly affect patient health and quality of life through complex sensorimotor impairments. Objective: The aims was to provide a comprehensive, evidence-based review of the neuroanatomical substrates, pathophysiology, diagnostic approaches, and management strategies for dysphagia and dysarthria in neurodegenerative diseases with emphasis on their multisystem nature and integrated treatment approaches. Methods: A narrative literature review was conducted using PubMed, Scopus, and Web of Science databases (2000-2024), focusing on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), progressive supranuclear palsy (PSP), and multiple system atrophy (MSA). Search terms included "dysphagia", "dysarthria", "neurodegenerative diseases", "neural networks", "swallowing control" and "speech production." Studies on neuroanatomy, pathophysiology, diagnostic tools, and therapeutic interventions were included. Results: Contemporary neuroscience demonstrates that swallowing and speech control involve extensive neural networks beyond the brainstem, including bilateral sensorimotor cortex, insula, cingulate gyrus, basal ganglia, and cerebellum. Disease-specific patterns reflect multisystem involvement: PD affects basal ganglia and multiple brainstem nuclei; ALS involves cortical and brainstem motor neurons; MSA causes widespread autonomic and motor degeneration; PSP produces tau-related damage across multiple brain regions. Diagnostic approaches combining fiberoptic endoscopic evaluation, videofluoroscopy, acoustic analysis, and neuroimaging enable precise characterization. Management requires multidisciplinary Integrated teams implementing coordinated speech-swallowing therapy, pharmacological interventions, and assistive technologies. Conclusions: Dysphagia and dysarthria in neurodegenerative diseases result from multifocal brain damage affecting distributed neural networks. Understanding this multisystem pathophysiology enables more effective integrated assessment and treatment approaches, enhancing patient outcomes and quality of life.},
}

@article {pmid41562832,
year = {2026},
author = {Aranda-Abreu, GE and Rojas-Durán, F and Hernández-Aguilar, ME and Herrera-Covarrubias, D and Tlapa-Monge, LR and Mestizo-Gutiérrez, SL},
title = {The Molecular Architecture of Neurodegeneration: An Integrative Overview of Convergent Mechanisms.},
journal = {NeuroSci},
volume = {7},
number = {1},
pages = {},
pmid = {41562832},
issn = {2673-4087},
abstract = {Neurodegenerative diseases such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and Huntington's disease represent a major challenge in neuroscience due to their complex, multifactorial nature and the absence of curative treatments. These disorders share common molecular mechanisms, including oxidative stress, mitochondrial dysfunction, proteostasis collapse, calcium dyshomeostasis, chronic neuroinflammation, and the prion-like propagation of misfolded proteins. Together, these processes trigger a cascade of cellular damage that culminates in synaptic dysfunction and programmed neuronal death. This review integrates current evidence on the sequential stages of neurodegeneration, emphasizing the convergence of oxidative, inflammatory, and proteotoxic pathways that drive neuronal vulnerability. Moreover, it explores emerging therapeutic strategies aimed at restoring cellular homeostasis, such as Nrf2 activation, modulation of the unfolded protein response (UPR), enhancement of autophagy, immunotherapy against pathological proteins, and gene therapy approaches. The dynamic interplay among mitochondria, endoplasmic reticulum, and glial cells is highlighted as a central element in disease progression. Understanding these interconnected mechanisms provides a foundation for developing multi-targeted interventions capable of halting or delaying neuronal loss and improving clinical outcomes in neurodegenerative disorders. This work provides an integrative and introductory overview of the convergent mechanisms underlying neurodegeneration rather than an exhaustive mechanistic analysis.},
}

@article {pmid41561436,
year = {2025},
author = {Ishaq, SM and Russell, AP},
title = {Potential role of stress granules and myogranules in amyotrophic lateral sclerosis.},
journal = {Frontiers in molecular neuroscience},
volume = {18},
number = {},
pages = {1686230},
pmid = {41561436},
issn = {1662-5099},
abstract = {Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of upper and lower motor neurones, leading to muscle wasting, paralysis and respiratory failure. Pathological cytoplasmic aggregation of the RNA-binding protein transactive response DNA-binding protein 43 (TDP-43) protein occurs in neural tissues in ~97% of all ALS cases, and is also observed in skeletal muscle. Cytoplasmic aggregation of TDP-43 is believed to contribute to ALS pathogenesis; however, its precise mechanistic role/s continues to elude the field. This mini review explores the potential role and regulation of two TDP-43-associated RNA-protein assemblies, stress granules (SGs) and myogranules (MGs). We review the current understanding of SG and MG formation and their potential role in ALS-related neurodegeneration and muscle pathology. We also highlight limitations and strengths and suggest future directions for research.},
}

@article {pmid41553588,
year = {2026},
author = {Bjørklund, G and Butnariu, M and Caunii, A and Peana, M},
title = {Metallothioneins in Neurodegenerative Diseases: Metal Homeostasis, Autoimmunity, and Therapeutic Potential.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {373},
pmid = {41553588},
issn = {1559-1182},
mesh = {Humans ; *Homeostasis/physiology ; *Metallothionein/metabolism ; *Neurodegenerative Diseases/metabolism/immunology/drug therapy/therapy ; *Autoimmunity/physiology ; Animals ; *Metals/metabolism ; },
abstract = {Neurodegenerative diseases, including multiple sclerosis, Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss and are frequently linked to metal dysregulation, oxidative stress, and immune dysfunction. Metallothioneins (MTs), a family of cysteine-rich, metal-binding proteins, are critical in maintaining metal homeostasis, mitigating oxidative damage, and modulating immune responses, functions highly relevant in these pathologies. MTs regulate essential metals like copper and iron by preventing their participation in harmful redox reactions and control zinc availability for enzymatic and signaling processes. They also detoxify neurotoxic metal(oid)s such as cadmium, mercury, lead, and arsenic, thereby reducing their adverse neurological and immunological effects. In autoimmune neurodegeneration, MTs modulate pro- and anti-inflammatory cytokines (e.g., IL-6, TNF-α, IL-10) and influence immune cell activity, particularly microglia and T cells, which are central to neuroinflammation and autoimmunity. Through these mechanisms, MTs play a dual role in sustaining immune homeostasis and counteracting oxidative stress. Their capacity to integrate metal regulation with immune modulation positions them as promising therapeutic targets, with preclinical and some clinical evidence supporting strategies to enhance MT expression or develop MT-mimetic agents to address both metal dysregulation and immune imbalance. Additionally, MTs show emerging utility as biomarkers, as alterations in MT isoform expression and metal-bound complexes in biofluids have been associated with disease onset, progression, and therapeutic response in specific neurodegenerative conditions. This article reviews the multifaceted roles of MTs in neurodegenerative diseases, emphasizing their function in metal and immune regulation and their emerging potential as therapeutic targets and clinical biomarkers.},
}

Humans
*Homeostasis/physiology
*Metallothionein/metabolism
*Neurodegenerative Diseases/metabolism/immunology/drug therapy/therapy
*Autoimmunity/physiology
Animals
*Metals/metabolism

@article {pmid41552817,
year = {2025},
author = {Chen, Y and Xiao, W and Qian, C and Huang, L and Lv, J and Wang, Z and Luo, Y},
title = {System Xc-pathway as a potential regulatory target in neurological disorders.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1701320},
pmid = {41552817},
issn = {1663-9812},
abstract = {The System Xc-pathway is composed of the 12-transmembrane transporter protein SLC7A11 (xCT) and the single-channel transmembrane protein SLC3A2 (CD98hc). We detail the pathway's characteristics and distribution within the central nervous system, as well as its canonical role in maintaining glutathione synthesis and inhibiting ferroptosis, and its emerging non-canonical functions in metabolic coupling and neuroimmunity. A core theme is the pathway's context-dependent and often paradoxical role across major neurological disorders, including ischemic stroke, Alzheimer's disease, multiple sclerosis, Parkinson's disease, and amyotrophic lateral sclerosis. Critically, we analyze how pathological activation of N-methyl-D-aspartate receptors (NMDARs) can dysregulate System Xc-through mechanisms involving calcium overload, reactive oxygen species, and specific signaling axes (e.g., Nrf2, PP2A/AMPK/HMGB1), thereby exacerbating excitotoxicity and oxidative damage. Conversely, System Xc-dysfunction can further fuel NMDAR-mediated injury, creating vicious pathogenic cycles. This analysis reveals that System Xc-is not a unitary target but a dynamic node within a complex network. Consequently, effective therapeutic strategies must move beyond broad inhibition and instead aim for nuanced, cell-type-specific, and disease-stage-precise modulation. This approach will selectively correct the dysfunction of System Xc-while preserving its essential physiological roles. It presents both a significant challenge and a promising frontier for future neuroprotective drug development.},
}

@article {pmid41552526,
year = {2026},
author = {Turcatel, GA and Moura, S},
title = {Glutamate Receptor Agonists as Triggers of Neurotoxicity: Decoding Pathways of Five Neurotoxins and Potential Therapeutic Targets.},
journal = {ACS omega},
volume = {11},
number = {1},
pages = {70-81},
pmid = {41552526},
issn = {2470-1343},
abstract = {l-Glutamate (l-Glu) is one of the primary excitatory neurotransmitters in the nervous system, functioning through both ionotropic and metabotropic receptors. The release of l-Glu into the synaptic cleft, its interaction with receptors, and its reuptake are meticulously regulated by excitatory amino acid transporters. The structural similarity of various compounds to l-glutamate is crucial to their ability to interact with NMDA, AMPA, and kainate receptors. These interactions can significantly influence neural communication and function. Overstimulation of these receptors, which operate as ion channels, results in an increased level of calcium ion influx, a phenomenon known as excitotoxicity, which is often linked to neurodegeneration. Many neurodegenerative conditions are linked to both acute and chronic exposures to neurotoxins, whether they originate within the body (endogenous) or from external sources (exogenous). These neurotoxins often function as l-glutamate receptor agonists, potentially contributing to the progression of these diseases. This perspective focuses on key neurotoxins, including β-N-methylamino-l-alanine (l-BMAA), quinolinic acid (QUIN), domoic acid, β-N-oxalyl-l-α,β-diaminopropionic acid (β-ODAP), homocysteine (Hcy), and l-homocysteate, all of which exhibit complementary mechanisms of action. We will explore their structural characteristics and mechanisms through which they induce neurotoxicity. Understanding the neurotoxic mechanisms of these compounds is essential for elucidating the pathology of neurodegenerative diseases, such as amyotrophic lateral sclerosis, neurolathyrism, and amnesic shellfish poisoning. This review summarizes the findings of 64 studies to clarify these relationships involving classic events associated with neurodegeneration such as mitochondrial damage, oxidative stress, and activation of proapoptotic pathways. In summary, the distinctive properties of these neurotoxins provide valuable insights that could help in the development of future therapeutic drugs aimed at treating and alleviating the effects of neurodegenerative diseases. Understanding how these neurotoxins interact with neuronal pathways can guide researchers in designing more effective interventions.},
}

@article {pmid41548740,
year = {2026},
author = {Qaisar, R},
title = {Fiber-type-specific architecture and pathophysiology of the neuromuscular junction.},
journal = {Neuroscience},
volume = {597},
number = {},
pages = {13-26},
doi = {10.1016/j.neuroscience.2026.01.015},
pmid = {41548740},
issn = {1873-7544},
abstract = {The neuromuscular junction (NMJ) is a specialized synapse essential for translating neuronal signals into muscle contraction. This review examines the complex structural, functional, and molecular differences in NMJs that innervate fast- and slow-twitch skeletal muscle fibers. Fast-twitch fibers, optimized for rapid and powerful contractions, possess elaborate NMJs with deep folds, high neurotransmitter turnover, and greater vulnerability to synaptic fatigue and degeneration. In contrast, slow-twitch fiber NMJs exhibit simpler but more stable architectures that support sustained, fatigue-resistant activity. These differences are not fixed but subject to activity-dependent plasticity and pathological remodeling. Chronic stimulation, injury, and aging influence NMJ morphology, with fast-twitch junctions more prone to degeneration in conditions such as ALS, myasthenia gravis, and diabetic neuropathy. Slow-twitch NMJs often resist early deterioration due to superior trophic support, metabolic stability, and more robust expression of synaptic organizers, such as agrin and PGC-1α. Several key signaling pathways, including agrin-MuSK-LRP4, Wnt/β-catenin, and neuregulin/ErbB, govern NMJ maintenance with fiber-type-specific nuances. These insights underscore the importance of tailoring therapeutic strategies to the muscle fiber phenotype. Gene therapies, neuromuscular electrical stimulation, and biomaterial scaffolds are emerging as promising modalities for preserving or restoring NMJ integrity, especially in fast-twitch fibers at higher risk of degeneration. Understanding fiber-type-specific NMJ biology enhances our understanding of motor control, muscle aging, and neuromuscular disease progression, and it opens pathways for precision therapeutics that target vulnerable synapses with structural and functional specificity. This review introduces a novel perspective by emphasizing fiber-type-specific NMJ differences and their implications for targeted therapies.},
}

@article {pmid41548719,
year = {2026},
author = {Li, X and Wan, R and Zhao, Y and Wu, Y and Chen, X and Li, Q and Luo, C},
title = {Decoding synaptic imbalance in neurodegenerative diseases: From pathological analysis to targeted intervention.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {103028},
doi = {10.1016/j.arr.2026.103028},
pmid = {41548719},
issn = {1872-9649},
abstract = {Synapses serve as the central functional components mediating information transmission, integration, and storage within the central nervous system (CNS). Their functionality depends on the synergistic interplay of the presynaptic membrane, synaptic cleft, and postsynaptic membrane-three structures that collectively sustain neurotransmitter secretion, postsynaptic signaling, and synaptic plasticity. Of note, synaptic impairment represents an early, shared pathological hallmark across aging and age-related neurodegenerative disorders like Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic lateral sclerosis (ALS). This damage emerges prior to the demise of neuronal cell bodies and the manifestation of clinical symptoms, with its location and severity directly shaping disease phenotypes. Importantly, such synaptic dysfunction is closely linked to the pathological proteins specific to each disorder. This review comprehensively synthesizes current research advances regarding synaptic impairment in age-related neurodegenerative diseases. It elaborates on the location-specific pathological features of synaptic damage in AD, PD, HD, and ALS, with particular emphasis on their associations with disease-related pathological markers. Additionally, the work unpacks five core mechanisms driving synaptic dysfunction: the toxic effects of pathological proteins, dysregulated synaptic protein homeostasis, excitotoxicity coupled with disrupted calcium balance, oxidative stress and inflammatory responses, and deficiencies in neurotrophic factors. Ultimately, it summarizes potential biomarkers and targeted intervention strategies, aiming to provide a systematic reference for mechanistic investigations, early diagnosis, and clinical management of neurodegenerative diseases.},
}

@article {pmid41547243,
year = {2026},
author = {Dorothy Wong, ZY and Kang, X and Shi, Y and Fan, R and Zhang, C and Min, D and Sun, N and Ma, Y and Tang, ML},
title = {Autophagy-tethering compounds (ATTECs) as an emerging and potentially transformative drug discovery approach.},
journal = {European journal of medicinal chemistry},
volume = {305},
number = {},
pages = {118585},
doi = {10.1016/j.ejmech.2026.118585},
pmid = {41547243},
issn = {1768-3254},
mesh = {Humans ; *Autophagy/drug effects ; *Drug Discovery ; Lysosomes/metabolism/drug effects ; Proteolysis/drug effects ; Molecular Structure ; Animals ; },
abstract = {Targeted protein degradation (TPD) strategies leveraging the ubiquitin-proteasome system (UPS), such as proteolysis-targeting chimeras (PROTACs), have gained wide recognition. While the UPS predominantly degrades short-lived soluble proteins, the lysosome-mediated system (LMS) excels at processing larger substrates, including protein aggregates, organelles, and macromolecular complexes. Recently, autophagy-tethering compounds (ATTECs) have emerged as a promising strategy for targeted degradation, harnessing the autophagy-lysosome system (ALS) to enable proximity-induced degradation. These heterobifunctional molecules, composed of LC3-binding warheads and TOI (target of interest) ligands linked together, provide therapeutic potential against disease-causing targets. This review outlines the therapeutic applications of ATTECs in human diseases, highlights recent progress in their development, and explores future opportunities for expanding this emerging class of degradation technologies through ALS from medicinal chemistry perspective.},
}

Humans
*Autophagy/drug effects
*Drug Discovery
Lysosomes/metabolism/drug effects
Proteolysis/drug effects
Molecular Structure
Animals

@article {pmid41396532,
year = {2025},
author = {Sabey, TB and Shanklin, BC and Colquitt, JA and Baer, MD},
title = {The approach-inhibition theory of power: A meta-analytic test and synthesis.},
journal = {Psychological bulletin},
volume = {151},
number = {10},
pages = {1245-1279},
doi = {10.1037/bul0000500},
pmid = {41396532},
issn = {1939-1455},
mesh = {Humans ; *Inhibition, Psychological ; *Psychological Theory ; *Power, Psychological ; *Cognition ; *Affect/physiology ; },
abstract = {Keltner et al. (2003) presented an integrative theory of the social implications of possessing power. Their theory-the approach-inhibition theory of power-quickly became the dominant lens for empirical investigations of how power influences a person's cognition, affect, and behavior. Despite the many benefits of Keltner et al.'s theory, the past 20 years of research have surfaced several potential issues with the theory, including empirical dissensus, mediational ambiguity, and questions about cognitive versus affective primacy. The purpose of this study is to resolve these issues by conducting the first meta-analytic synthesis of the literature on the outcomes of power. Specifically, we tested Keltner et al.'s propositions that power is positively related to the approach-oriented outcomes of attention to rewards, automatic cognition, positive affect, and disinhibited behavior and negatively related to the inhibition-oriented outcomes of attention to threats, controlled cognition, negative affect, and inhibited behavior. Our meta-analysis included a final set of 1,712 effect sizes from 813 independent samples of 432 manuscripts with 269,534 participants. Our analysis demonstrates that the theory is well-supported; approach associations are larger than inhibition associations; power influences behavior indirectly through attention, cognition, and affect; and those indirect effects are largely conveyed through affect. Based on these findings, we suggest several future directions that scholars can take as the literature on power continues to evolve. (PsycInfo Database Record (c) 2025 APA, all rights reserved).},
}

Humans
*Inhibition, Psychological
*Psychological Theory
*Power, Psychological
*Cognition
*Affect/physiology

@article {pmid41365015,
year = {2026},
author = {Svendsen, O and Stevens, MWR and Hamamura, T and Harpas, I and Radunz, M and King, DL},
title = {Reporting quality standards in gaming disorder treatment evidence: A systematic review.},
journal = {Acta psychologica},
volume = {262},
number = {},
pages = {106063},
doi = {10.1016/j.actpsy.2025.106063},
pmid = {41365015},
issn = {1873-6297},
mesh = {Humans ; *Video Games ; *Psychotherapy/standards ; Randomized Controlled Trials as Topic/standards ; *Internet Addiction Disorder/therapy ; *Research Design/standards ; },
abstract = {BACKGROUND: The treatment evidence base for gaming disorder (GD) has grown steadily over the past two decades. A systematic review by King et al. (2017) of 30 studies reported that GD treatment studies tended to favor psychotherapy approaches, but the research was limited by poor reporting standards as assessed by the Consolidated Standards of Reporting Trials (CONSORT) framework. This systematic review aimed to conduct a follow up evaluation of the reporting quality of subsequent GD treatment studies.

METHODS: A literature search of six databases yielded 51,056 records, which resulted in 31 eligible studies after screening. Each study's reporting quality was assessed using the CONSORT statement, and then these assessments were compared to King et al.'s (2017) review.

RESULTS: This review identified several methodological improvements since 2017: 61 % of studies were randomized controlled trials (vs. 40 % in 2017), 90 % included control groups (vs. 63 %), and follow-up duration increased to 6.1 months (vs. 3.5 months; p = .032). Reporting improved for participant flow (87.1 % vs. 43.3 %; p = .001) and group-level statistics (74.2 % vs. 36.7 %; p = .003), but some areas showed no improvement.

DISCUSSION: There have been several improvements in GD treatment study design and reporting, including controls, randomization and follow up, reflecting an increasing number of higher quality trials for the condition. Most of the studies with higher reporting quality (i.e., scoring ≥30/46 on the CONSORT framework) were psychotherapy-based. Future research should employ designs with longer follow-ups, broader assessment of outcomes, and standardized ICD-11-aligned tools. Pharmacological treatments, including novel pharmacotherapies for other addictions (e.g., Naltrexone), are underexplored and lack high quality evidence.},
}

Humans
*Video Games
*Psychotherapy/standards
Randomized Controlled Trials as Topic/standards
*Internet Addiction Disorder/therapy
*Research Design/standards

@article {pmid41354105,
year = {2026},
author = {Mendes Araújo, L and Chianca, T and Persaud, C and Hartung, P and Soares, Y and Almirón, G and João, R},
title = {Respiratory strength training for patients with amyotrophic lateral sclerosis: A meta-analysis of randomized controlled trials.},
journal = {Respiratory medicine},
volume = {251},
number = {},
pages = {108560},
doi = {10.1016/j.rmed.2025.108560},
pmid = {41354105},
issn = {1532-3064},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/rehabilitation/therapy ; Randomized Controlled Trials as Topic ; *Breathing Exercises/methods ; Male ; Middle Aged ; Respiratory Muscles/physiopathology ; *Resistance Training/methods ; Female ; Treatment Outcome ; Aged ; Maximal Respiratory Pressures ; },
abstract = {INTRODUCTION: Respiratory strength training (RST) has been considered as a possible add-on treatment for amyotrophic lateral sclerosis (ALS). However, the benefits of RST are still controversial. We performed a meta-analysis of randomized controlled trials (RCTs) on the efficacy of RST in patients with ALS.

METHODS: PubMed, Embase and Cochrane Central were searched for RCTs comparing the use of RST with sham therapy or minimal device load in patients with ALS. The main outcomes were maximal expiratory pressure (MEP), maximal inspiratory pressure (MIP) and the ALS functioning rating scale (ALSFRS-R) score. Statistical analysis was performed using R software and heterogeneity was assessed with I[2] statistics.

RESULTS: Four RCTs were included with a total of 138 patients. RST was used to treat 69 (50 %) patients. The mean age was 60.2 ± 10.4 years, with 82 (62.3 %) male patients. Follow-up ranged from 2 to 8 months. Subgroup analysis of expiratory muscle training protocols showed a statistically significant improvement in MEP (MD 20.22 cmH2O; 95 % CI 2.66-37.77; p = 0.04). In overall analyses, there was no difference between groups regarding MEP (MD 9.40 cmH2O; 95 % CI -11.57-30.37; p = 0.25), MIP (MD 3.26 cmH2O; 95 % CI -9.23-15.75; p = 0.38), FVC (MD 4.05 %predicted; 95 % CI -0.91-9.01; p = 0.08) and ALSFRS-R score (MD 0.01 points; 95 % CI -0.29-0.32; p = 0.85).

CONCLUSION: In this meta-analysis of RCTs including patients with ALS, expiratory muscle training was associated with increased MEP compared with sham or minimal load. However, no statistically significant associations were found for overall RST in MIP, FVC, MEP, and ALSFRS-R.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/rehabilitation/therapy
Randomized Controlled Trials as Topic
*Breathing Exercises/methods
Male
Middle Aged
Respiratory Muscles/physiopathology
*Resistance Training/methods
Female
Treatment Outcome
Aged
Maximal Respiratory Pressures

@article {pmid41307543,
year = {2026},
author = {Macpherson, CE and Wani, DK and Li, H and Rana, V and Blacutt, M and Bello-Haas, VD and Quinn, L},
title = {Physical Therapist Interventions for People With Amyotrophic Lateral Sclerosis Across Disease Stages: A Systematic Review of Efficacy.},
journal = {Physical therapy},
volume = {106},
number = {1},
pages = {},
doi = {10.1093/ptj/pzaf142},
pmid = {41307543},
issn = {1538-6724},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/rehabilitation/therapy/physiopathology ; *Physical Therapy Modalities ; Exercise Therapy/methods ; Vital Capacity ; },
abstract = {IMPORTANCE: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease causing declines in muscular strength that affect respiratory function and functional independence. Although physical therapist interventions have been studied in ALS, their efficacy and evidence quality have not been systematically assessed across disease stages.

OBJECTIVE: The objective of this study was to examine the efficacy of physical therapist interventions on clinical outcomes across ALS disease stages.

DESIGN: This study was a systematic review using Joanna Briggs Institute methodology.

SETTING: Multiple settings were used.

PARTICIPANTS: The participants were adults (>18 years old) with ALS or motor neuron disease.

INTERVENTIONS: Physical therapist interventions within the professional scope of practice included therapeutic exercise, pulmonary training, manual therapy, and multimodal approaches.

OUTCOME MEASURES: Outcome measures included effect sizes (ESs) and 95% CIs calculated for forced vital capacity (FVC) and the Amyotrophic Lateral Sclerosis Rating Scale (ALSFRS) or the ALSFRS revised (ALSFRS-R).

RESULTS: Six databases were searched from inception to January 2025. Thirty-nine studies were included (25 experimental, 14 observational). Outcomes were heterogeneous, with 94 measures across studies: 23 included the ALSFRS or ALSFRS-R, and 16 included FVC. Most interventions targeted early-stage ALS (n = 27), limiting comparisons across stages. Multimodal training had moderate-quality evidence, with moderate effects on the ALSFRS-R (ES = 0.56 [95% CI = 0.09-1.03]), and low-quality evidence, with negligible effects on FVC (ES = -0.03 [95% CI = -1.47 to 1.41]). Pulmonary interventions had moderate-quality evidence, with small effects on FVC (ES = 0.40 [95% CI = -0.18 to 0.98]), and low-quality evidence, with negligible effects on the ALSFRS-R (ES = 0.04 [95% CI = -0.25 to 0.33]).

CONCLUSIONS: A range of physical therapist interventions for ALS were assessed, although most were early phase or low quality. Multimodal and pulmonary interventions showed modest benefits in the ALSFRS-R and FVC, respectively. However, variability in outcome measures and limited research beyond early-stage disease highlight the need for stage-specific trials using consistent functional outcomes.

RELEVANCE: This review highlights the breadth of studies of physical therapy in ALS and underscores the need for more rigorous, targeted research.},
}

Humans
*Amyotrophic Lateral Sclerosis/rehabilitation/therapy/physiopathology
*Physical Therapy Modalities
Exercise Therapy/methods
Vital Capacity

@article {pmid41261682,
year = {2025},
author = {Huang, X and Wang, X and Yang, Y and Chen, H},
title = {Assessing the potential causal influence of myasthenia gravis on neurodegenerative diseases via multivariable Mendelian randomization.},
journal = {Medicine},
volume = {104},
number = {44},
pages = {e45340},
pmid = {41261682},
issn = {1536-5964},
mesh = {Humans ; Alzheimer Disease/epidemiology/genetics ; Amyotrophic Lateral Sclerosis/epidemiology/genetics ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Myasthenia Gravis/epidemiology/genetics ; *Neurodegenerative Diseases/epidemiology/genetics ; Parkinson Disease/epidemiology/genetics ; Risk Factors ; },
abstract = {Myasthenia gravis (MG), an autoimmune condition known for impairing neuromuscular signaling, has increasingly been implicated in broader neurological dysfunctions. Recent studies point toward a possible connection between autoimmune and neurodegenerative processes. However, whether MG contributes causally to the onset of major neurodegenerative disorders such as Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS) remains unclear. This study utilizes Mendelian randomization (MR) to explore the potential causal influence of MG on these disorders from a genetic standpoint. A univariable Mendelian randomization (UVMR) framework was employed using summary-level data from genome-wide association studies (GWAS) to evaluate the effect of MG on the risk of AD, PD, and ALS. To confirm the robustness of the association between MG and AD, 2 independent AD GWAS datasets were incorporated for external replication, followed by a meta-analysis to combine the evidence. Additionally, multivariable Mendelian randomization (MVMR) was conducted to adjust for smoking behavior as a potential confounding factor. The UVMR analysis revealed a statistically significant causal relationship between MG and increased susceptibility to AD (odds ratio (OR): 1.037; 95% confidence interval (CI): 1.007-1.068; P = .016). No significant causal effects were observed for PD (OR: 1.019; 95% CI: 0.964-1.077; P = .509) or ALS (OR: 1.055; 95% CI: 0.977-1.140; P = .171). The association between MG and AD was consistently validated in 2 independent datasets (ieu-a-297: OR = 1.084; 95% CI: 1.017-1.156; P = .013; ieu-b-2: OR = 1.054; 95% CI: 1.006-1.104; P = .027). Meta-analysis reinforced the evidence supporting MG as a risk factor for AD (OR: 1.047; 95% CI: 1.023-1.072; P < .001). Furthermore, MVMR adjusting for smoking confirmed that MG independently contributes to AD risk (OR: 1.037; 95% CI: 1.006-1.069; P = .020). This study provides robust genetic evidence suggesting that MG is a causal and independent risk factor for AD. These findings highlight a novel link between autoimmunity and neurodegeneration, offering new directions for mechanistic and therapeutic research.},
}

Humans
Alzheimer Disease/epidemiology/genetics
Amyotrophic Lateral Sclerosis/epidemiology/genetics
Genetic Predisposition to Disease
Genome-Wide Association Study
Mendelian Randomization Analysis
*Myasthenia Gravis/epidemiology/genetics
*Neurodegenerative Diseases/epidemiology/genetics
Parkinson Disease/epidemiology/genetics
Risk Factors

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

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

@article {pmid41016645,
year = {2025},
author = {Thumbadoo, KM and Nementzik, LR and Swanson, MEV and Dieriks, BV and Dragunow, M and Faull, RLM and Curtis, MA and Blair, IP and Nicholson, GA and Williams, KL and Scotter, EL},
title = {A meta-analysis of genetic variant pathogenicity and sex differences in UBQLN2-linked amyotrophic lateral sclerosis and frontotemporal dementia.},
journal = {Neurobiology of disease},
volume = {216},
number = {},
pages = {107127},
doi = {10.1016/j.nbd.2025.107127},
pmid = {41016645},
issn = {1095-953X},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Frontotemporal Dementia/genetics ; *Autophagy-Related Proteins/genetics ; *Adaptor Proteins, Signal Transducing/genetics ; Male ; Female ; *Genetic Variation/genetics ; *Sex Characteristics ; *Cell Cycle Proteins/genetics ; *Ubiquitins/genetics ; },
abstract = {Ubiquilin 2, encoded by the X-linked UBQLN2 gene, is a ubiquitin-binding quality control protein. Pathogenic UBQLN2 genetic variants cause X-linked dominant amyotrophic lateral sclerosis and/or frontotemporal dementia (ALS/FTD), however, clinical phenotypes from these variants show striking inter- and intra-familial heterogeneity. Further, there are many UBQLN2 variants whose significance to disease is uncertain. Here, we examine the pathogenic potential of UBQLN2 variants reported in individuals with ALS/FTD and their non-symptomatic relatives. Meta-analysis from 27 published studies identified 186 affected individuals and 51 asymptomatic carriers, each harbouring one of 43 unique UBQLN2 coding variants. Features of identified variants, including evolutionary conservation, minor allele frequencies, localisation to protein domains, and in silico predictions of pathogenicity were compiled. Per biological sex, clinical features were compared between UBQLN2 variants segregated by pathogenicity. Pathogenic UBQLN2 variant carriers, most of whom are familial ALS cases, showed a sex-specific difference in age at onset wherein males developed disease on average 18.15 years prior to females (29.54 ± 11.9 versus 47.69 ± 13.4 years, p < 0.0001), with no change in disease duration (p = 0.2091). UBQLN2 variants of uncertain significance showed a bimodal distribution of onset age per sex suggesting a mixture of true benign and true pathogenic variants. In human brain tissue, two male UBQLN2 p.Thr487Ile (ALS-FTD and ALS) cases showed a greater burden of ubiquilin 2 aggregates than a related female case (ALS-FTD). These robust sex-specific differences in ALS/FTD presentation in carriers of pathogenic UBQLN2 variants may improve predictions of ALS/FTD risk in carriers, aiding in diagnosis and disease management.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics
*Frontotemporal Dementia/genetics
*Autophagy-Related Proteins/genetics
*Adaptor Proteins, Signal Transducing/genetics
Male
Female
*Genetic Variation/genetics
*Sex Characteristics
*Cell Cycle Proteins/genetics
*Ubiquitins/genetics

@article {pmid40983380,
year = {2025},
author = {Schellenberg, KL and Caspar-Bell, G and Ellis, C and Johnston, W and King, A and King, M and Korngut, L and Kushneriuk, B and Lavoie, AJ and McGonigle, R and Newton, J and O'Connell, C and Shoesmith, C and Suchowersky, O and Warman-Chardon, J and Wunder, S and Pfeffer, G},
title = {Best practice recommendations for the clinical care of spinal bulbar muscular atrophy.},
journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne},
volume = {197},
number = {31},
pages = {E987-E999},
pmid = {40983380},
issn = {1488-2329},
mesh = {Humans ; Canada ; *Bulbo-Spinal Atrophy, X-Linked/therapy/diagnosis ; Male ; },
abstract = {BACKGROUND: Although rare in the general population, spinal bulbar muscular atrophy (SBMA) is an X-linked recessive neuromuscular condition that is highly prevalent in people identifying as First Nations and Métis in western Canada. The aim of this guideline is to improve and standardize care of SBMA, and to increase awareness of the condition.

METHODS: Our interdisciplinary working group conducted a needs assessment survey to aid in the development of guideline topic questions, followed by a literature search, evidence review, and external review by health practitioners and people with lived experience. We followed the ADAPTE framework to evaluate the only pre-existing SBMA guideline (2020 French national protocol) and the 2020 Canadian amyotrophic lateral sclerosis guideline for appropriateness of adaptation. Our process adhered to the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool; used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach; and followed the Guidelines International Network-McMaster Guideline Development Checklist. Indigenous community engagement was led by the Pewaseskwan Indigenous Research Group, who participated in the development of the guideline.

RECOMMENDATIONS: We developed 41 recommendations to address the continuum of care in SBMA, including diagnosis; multidisciplinary teams; management of limb and bulbar symptoms, respiratory and cardiac complications, and multisystem symptoms; female carriers; emotional supports; and considerations for Indigenous people. Spinal bulbar muscular atrophy is best managed by multidisciplinary teams that can address both its motor and nonmotor manifestations, including cardiac involvement, sensory symptoms, and metabolic dysfunction. Concerns for female carriers may include symptom management and genetic counselling. Providers should ensure culturally appropriate care for Indigenous people.

INTERPRETATION: In this guideline, we provide health care professionals with a culturally responsive standard of care for SBMA, and hope this will translate into improved quality of life for people affected by SBMA.},
}

Humans
Canada
*Bulbo-Spinal Atrophy, X-Linked/therapy/diagnosis
Male

@article {pmid40971912,
year = {2026},
author = {Zhang, G and Ma, Y and Liu, Z and Jin, L and Zheng, D and Zhang, X and Jin, G},
title = {Intraocular lens power calculation formula accuracy in 1178 eyes with short axial length: systematic review and network meta-analysis.},
journal = {Journal of cataract and refractive surgery},
volume = {52},
number = {2},
pages = {202-207},
pmid = {40971912},
issn = {1873-4502},
mesh = {Humans ; *Axial Length, Eye/pathology ; *Biometry/methods ; *Lens Implantation, Intraocular ; *Lenses, Intraocular ; *Optics and Photonics ; *Refraction, Ocular/physiology ; },
abstract = {TOPIC: To systematically review the literature and conduct a comprehensive quantitative analysis to compare the accuracy of different intraocular lens (IOL) calculation formulas in eyes with short axial lengths (ALs).

CLINICAL RELEVANCE: The precision of the IOL formulas decreases when applied in eyes with short AL (AL <22 mm), and many new formulas for calculating IOL power have been proposed in the past few decades. However, the accuracy of these formulas has not been systematically compared when applied in eyes with short AL.

METHODS: This study systematically searched PubMed, Embase, Web of Science, and Cochrane Library databases to collect relevant research literature published between January 2003 and September 2023. Included were prospective or retrospective clinical studies involving cataract patients with short AL (AL <22 mm) and reporting the following outcomes: mean absolute error, median absolute error (MedAE), and percentage of eyes with a prediction error (PE) within ±0.25 diopters (D), ±0.50 D, and ±1.00 D. A network meta-analysis was performed using R software (v. 4.2.1).

RESULTS: 15 prospective or retrospective studies involving 1178 eyes and 12 calculation formulas were included in this study. The network meta-analysis showed that compared with the widely used Haigis formula, the Kane formula had a higher percentage of eyes with PE within the range of ±0.25 D, ±0.50 D, and ±1.00 D (all odds ratio >1, but P > .05). In addition, based on the surface under the cumulative ranking area (SUCRA), the Kane formula had the highest probability of predicting the PE of the eyes within the range of ±0.25 D, with its SUCRA value of 95.74%, followed by Haigis formula (94.79%) and Olsen Standalone formula (84.04%). The Kane and Olsen Standalone formulas had the lowest MedAE.

CONCLUSIONS: The Kane, Haigis, and Olsen Standalone formulas may perform better than other formulas in calculating the IOLs power in eyes with short AL. Nonetheless, significant uncertainty remains in this area. The accuracy of these formulas in patients with short AL needs to be verified by large multicenter registry studies.},
}

Humans
*Axial Length, Eye/pathology
*Biometry/methods
*Lens Implantation, Intraocular
*Lenses, Intraocular
*Optics and Photonics
*Refraction, Ocular/physiology

@article {pmid40875341,
year = {2025},
author = {Dang, J and Xiao, S},
title = {A meta-analytic reassessment of the vicious cycle of psychopathology and stressful life events: Commentary on Rnic et al. (2023).},
journal = {Psychological bulletin},
volume = {151},
number = {7},
pages = {930-939},
doi = {10.1037/bul0000475},
pmid = {40875341},
issn = {1939-1455},
mesh = {Humans ; *Stress, Psychological/psychology ; *Life Change Events ; *Mental Disorders/psychology/epidemiology ; Psychopathology ; },
abstract = {Rnic et al. (2023) conducted a comprehensive multilevel meta-analysis examining the stress generation hypothesis across various forms of psychopathology. They utilized the bivariate correlation between psychopathology at Time 1 and stress at Time 2 to estimate effect sizes. To address potential confounding from baseline stress assessments, we reanalyzed the data by (a) using the cross-lagged association in a multilevel meta-analysis to examine longitudinal links between Time 1 psychopathology and Time 2 stress and (b) incorporating Time 1 stress as a control variable in a meta-analytic structural equation model. Based on a subset of Rnic et al.'s original data set (33 studies with 18,684 participants and 126 effect sizes), our findings revealed cross-lagged associations of rC.L = .12 for the predictive effect of baseline psychopathology, especially internalizing psychopathology, on subsequent dependent stress and rC.L = .06 for independent stress. These effects were homogeneous across diverse samples, measures, and contexts. Moreover, even after controlling for Time 1 stress, dependent stress continued to mediate the relationship between baseline psychopathology and subsequent symptoms, whereas independent stress did not mediate, underscoring the role of dependent stress in perpetuating the cycle of stress and psychopathology. (PsycInfo Database Record (c) 2025 APA, all rights reserved).},
}

Humans
*Stress, Psychological/psychology
*Life Change Events
*Mental Disorders/psychology/epidemiology
Psychopathology

@article {pmid40875336,
year = {2026},
author = {Yuan, Z and Yin, J and Sun, J},
title = {The paradox of team conflict revisited: An updated meta-analysis of the team conflict-team performance relationships.},
journal = {The Journal of applied psychology},
volume = {111},
number = {2},
pages = {195-224},
doi = {10.1037/apl0001315},
pmid = {40875336},
issn = {1939-1854},
mesh = {Humans ; *Conflict, Psychological ; *Group Processes ; *Interpersonal Relations ; *Work Performance ; *Cooperative Behavior ; *Employment/psychology ; },
abstract = {The possibility that team conflict, especially task conflict, might improve team performance has stimulated a large body of empirical research that continues to grow to this day. Nevertheless, 12 years has passed since de Wit et al.'s (2012) comprehensive meta-analysis. To synthesize the even larger body of empirical evidence now available, we provide an updated meta-analysis of the team conflict-team performance relationships by revisiting the population average estimates and their effect size heterogeneity. Given the recent developments in the team conflict literature, we also incorporate status conflict into our synthesis. Moreover, to shed light on the contextual factors that may help explain the heterogeneous team conflict-team performance relationships, we examine a host of moderators pertaining to national culture, team features, and research methods. Our results based on psychometric meta-analysis indicate that all four team conflict dimensions (i.e., task conflict, relationship conflict, process conflict, and status conflict) are negatively related to team performance. Moreover, the relationships of task conflict and relationship conflict with team performance have substantial cross-situation heterogeneity. Examining the contingencies of these heterogeneous relationships, our metaregression analyses reveal that national culture (e.g., individualism), team features (e.g., team performance facet), and methodological factors (e.g., team conflict scale) all play important roles in helping to explain the mixed effects of team conflict on team performance. Based on our quantitative synthesis, we discuss the implications for the next waves of team conflict research. (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}

Humans
*Conflict, Psychological
*Group Processes
*Interpersonal Relations
*Work Performance
*Cooperative Behavior
*Employment/psychology

@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 = {25},
number = {13},
pages = {965-974},
pmid = {40849781},
issn = {1875-5607},
support = {1142025//School of Theoretical Modeling, Washington, DC, USA/ ; },
mesh = {*Calmodulin/metabolism/chemistry/antagonists & inhibitors ; Humans ; *Neurodegenerative Diseases/metabolism/drug therapy/pathology ; Animals ; *Neuroprotection ; *Neuroprotective Agents/pharmacology/chemistry ; Calcium/metabolism ; },
abstract = {Intracellular calcium (Ca[2+]) 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.},
}

*Calmodulin/metabolism/chemistry/antagonists & inhibitors
Humans
*Neurodegenerative Diseases/metabolism/drug therapy/pathology
Animals
*Neuroprotection
*Neuroprotective Agents/pharmacology/chemistry
Calcium/metabolism

@article {pmid40646421,
year = {2025},
author = {McCormick, CR and Christie, J},
title = {Assessing Posner's theory of alerting: A meta-analysis of speed-accuracy effects.},
journal = {Attention, perception & psychophysics},
volume = {87},
number = {6},
pages = {2007-2028},
pmid = {40646421},
issn = {1943-393X},
mesh = {Humans ; *Reaction Time ; *Attention ; *Pattern Recognition, Visual ; *Psychological Theory ; *Orientation ; Cues ; Psychomotor Performance ; Discrimination, Psychological ; },
abstract = {Posner and his colleagues proposed a seminal theory of how alerting influenced information processing over 50 years ago (Posner et al., Memory & Cognition, 1, 2-12, 1973). In this study, participants were presented with warning signals at varying intervals before a target, and participants were asked to produce a spatial discrimination response. Trials in which participants were played a warning signal were compared to trials without a warning signal to understand the effect of phasic alerting using reaction time (RT) and error rate (ER). Posner and colleagues observed a general speed-accuracy trade-off (SAT) across conditions, in which faster RTs led to higher ER, and concluded that phasic alertness shifts response criteria without improving the efficiency of information processing. More recent research has questioned whether this theory of alerting applies generally across all time-courses and conditions. The current meta-analysis aimed to test Posner's theory of alerting (1975) using all available data in the field that closely matches the methodology used in Posner et al.'s Memory & Cognition, 1, 2-12, (1973) influential study. After including data from 16 published experiments across three different signal-target foreperiod durations, our conclusions support that while a speed-accuracy trade-off is likely present at shorter foreperiods (50 ms), the longer foreperiods (200 and 400 ms) show evidence of an increase in the rate of information processing when the participant was alerted.},
}

Humans
*Reaction Time
*Attention
*Pattern Recognition, Visual
*Psychological Theory
*Orientation
Cues
Psychomotor Performance
Discrimination, Psychological

@article {pmid40300556,
year = {2025},
author = {Zhou, S and Zhou, P and Yang, T and Si, J and An, W and Jiang, Y},
title = {Glucosamine supplementation contributes to reducing the risk of type 2 diabetes: Evidence from Mendelian randomization combined with a meta-analysis.},
journal = {The Journal of international medical research},
volume = {53},
number = {4},
pages = {3000605251334460},
pmid = {40300556},
issn = {1473-2300},
mesh = {Humans ; *Diabetes Mellitus, Type 2/genetics/prevention & control/epidemiology ; *Glucosamine/administration & dosage/therapeutic use ; Mendelian Randomization Analysis ; *Dietary Supplements ; Genome-Wide Association Study ; Risk Factors ; Polymorphism, Single Nucleotide ; },
abstract = {ObjectiveObservational studies on glucosamine supplementation and type 2 diabetes risk have shown inconsistent results, necessitating the use of Mendelian randomization to clarify the true causal relationship.MethodsThe glucosamine supplementation-related genome-wide association study dataset was obtained from the MRC Integrative Epidemiology Unit consortium, whereas type 2 diabetes-related genome-wide association study datasets were obtained from the FinnGen consortium (discovery) and Xue et al.'s meta-analysis (validation). Two-sample Mendelian randomization analyses were performed separately in the discovery and validation datasets, followed by meta-analysis and multivariable Mendelian randomization analyses to verify the robustness of the results of two-sample Mendelian randomization. The estimation of the causal relationship was conducted through the inverse variance weighted method.ResultsGlucosamine supplementation exhibited a significant protective effect against type 2 diabetes, as identified by two-sample Mendelian randomization analysis in the FinnGen consortium (odds ratio: 0.13, 95% confidence interval: 0.02-0.89) and validated in Xue et al.'s meta-analysis (odds ratio: 0.06, 95%; confidence interval: 0.01-0.29). A combined meta-analysis (odds ratio: 0.08, 95%; confidence interval: 0.02-0.27) of the results of two-sample Mendelian randomization confirmed the robustness of these findings. Additionally, multivariable Mendelian randomization analysis (odds ratio: 0.12, 95%; confidence interval: 0.02-0.94), after adjusting for confounding factors, supported the results of two-sample Mendelian randomization. No evidence of heterogeneity or pleiotropy was observed.ConclusionOverall, our results revealed that genetically predicted glucosamine supplementation was inversely associated with the risk of type 2 diabetes, highlighting the potential importance of glucosamine supplementation in preventing type 2 diabetes.},
}

Humans
*Diabetes Mellitus, Type 2/genetics/prevention & control/epidemiology
*Glucosamine/administration & dosage/therapeutic use
Mendelian Randomization Analysis
*Dietary Supplements
Genome-Wide Association Study
Risk Factors
Polymorphism, Single Nucleotide

@article {pmid39904709,
year = {2025},
author = {Vahey, N and Nicholson, E and Barnes-Holmes, D},
title = {A decade on: Reflecting on the limitations of the first meta-analysis of the Implicit Relational Assessment Procedure's (IRAP) criterion validity in the clinical domain.},
journal = {Journal of behavior therapy and experimental psychiatry},
volume = {87},
number = {},
pages = {102016},
doi = {10.1016/j.jbtep.2024.102016},
pmid = {39904709},
issn = {1873-7943},
mesh = {Humans ; *Meta-Analysis as Topic ; Reproducibility of Results ; },
abstract = {Hussey (in press) recently conducted a detailed critical reanalysis of Vahey, Nicholson and Barnes-Holmes' (2015) meta-analysis. Its stated purpose was to (a) examine the extent to which Vahey et al.'s (2015) meta-analysis contains errors; and (b) to test how computationally reproducible it is by current standards of best practice. Hussey identified a small number of minor numerical errors, but crucially was unable to exactly replicate the original meta-effect of r‾ = .45. Six different variations of the meta-analysis reported by Vahey et al. were used and obtained meta-effects that deviated from the original by Δr‾ = .01-.02. Hussey also reported corresponding 95% credibility intervals that were all of zero width. These discrepancies prompted the present authors to conduct a detailed audit of the original meta-analysis. This revealed one minor transposing error in addition to three identified by Hussey. Once corrected this resulted in a marginally increased Hunter and Schmidt meta-analytic effect of r‾ = .46 without a credibility interval, and a Hedges-Vevea meta-effect of r‾ = .47 with 95% confidence interval (.40, .54). This correction was too small to have any bearing on Vahey et al.'s supplementary analyses regarding publication bias or statistical power. Vahey et al. contained a much lower proportion of transposing errors than is typical of meta-analyses even still (cf. Kadlec, Sainani, & Nimphius, 2023; Lakens et al., 2016; Lakens et al., 2017). Nonetheless, Hussey highlighted important ambiguities about the theoretical and practical meaning of the meta-effect reported by Vahey et al. We clarify our position on these matters in summary, and in so doing explain why we believe that the wider IRAP literature would undoubtedly benefit from increased adoption of contemporary open science standards.},
}

Humans
*Meta-Analysis as Topic
Reproducibility of Results

@article {pmid39786806,
year = {2025},
author = {Yang, S and Song, J and Deng, M and Cheng, S},
title = {Identification of Drug-Targetable Genes for Eczema and Dermatitis Using Integrated Genomic and Proteomic Approaches.},
journal = {Dermatitis : contact, atopic, occupational, drug},
volume = {36},
number = {4},
pages = {369-381},
doi = {10.1089/derm.2024.0429},
pmid = {39786806},
issn = {2162-5220},
mesh = {Humans ; *Eczema/genetics/drug therapy ; Proteomics ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; Quantitative Trait Loci ; Mendelian Randomization Analysis ; Genomics ; *Dermatitis/genetics/drug therapy ; },
abstract = {Background: Eczema and dermatitis are common inflammatory skin conditions with significant morbidity. Identifying drug-targetable genes can facilitate the development of effective treatments. Methods: This study analyzed data obtained by meta-analysis of 2 genome-wide association studies on eczema/dermatitis (57,311 cases and 896,779 controls, European ancestry). We identified drug-targetable genes from the Drug-Gene Interaction Database and Finan et al's findings. Cis-expression quantitative trait loci (eQTL) data from human blood and skin tissues were used for Mendelian randomization (MR) analysis. Bayesian colocalization, proteomic MR, and meta-analysis validated the causal relationships. Finally, protein-protein interactions (PPIs) and correlation analysis of potential drug targets and cytokines were performed. Results: We identified 2532 drug-targetable genes; 3378 Single Nucleotide Polymorphism (SNPs) were associated with 1531 genes in blood cis-eQTLs, 664 SNPs with 667 genes in sun-exposed skin eQTLs, and 572 SNPs with 574 genes in nonsun-exposed skin eQTLs. Five genes (SLC22A5, NOTCH4, AGER, HLA-DRB5, and EHMT2) showed causal relationships with eczema/dermatitis across multiple datasets. Single-variable and multi-variable Mendelian randomization (SMR) and multi-SNP SMR analysis identified 8 genes (PIK3R4, DHODH, CXCR2, Interleukin (IL)18, LGALS9, RPS6KB2, SLC22A5, and AGER) across all tissues. Functional Summary Information for Variants in the Online Network (FUSION) analysis confirmed associations for SLC22A5 and AGER. Bayesian colocalization indicated AGER (PPH4: 0.95) as a shared causal variant. Proteomic MR and meta-analysis showed that increased AGER protein levels were associated with a lower risk of eczema or dermatitis (odds ratio: 0.995, 95% confidence interval: 0.997-0.993, P = 0.0002). A PPI network revealed interactions of AGER with NOTCH4 and multiple cytokines, whereas SLC22A5 showed no cytokine interactions. Conclusions: This study identified potential drug-targetable genes, with AGER showing strong potential as a target for reducing eczema/dermatitis risk. These findings provide a basis for developing targeted therapies.},
}

Humans
*Eczema/genetics/drug therapy
Proteomics
Polymorphism, Single Nucleotide
Genome-Wide Association Study
Quantitative Trait Loci
Mendelian Randomization Analysis
Genomics
*Dermatitis/genetics/drug therapy

@article {pmid39496035,
year = {2024},
author = {Xu, W and Zhao, X and Wang, J and Guo, Y and Ren, Z and Cai, L and Wu, S and Zhou, M},
title = {Different intensities of physical activity for amyotrophic lateral sclerosis and Parkinson disease: A Mendelian randomization study and meta-analysis.},
journal = {Medicine},
volume = {103},
number = {44},
pages = {e40141},
pmid = {39496035},
issn = {1536-5964},
support = {ZYYLJRC201911//the Anhui Province Traditional Chinese Medicine Leading Talents Construction Project/ ; },
mesh = {Humans ; *Mendelian Randomization Analysis ; *Amyotrophic Lateral Sclerosis/genetics ; *Parkinson Disease/genetics/epidemiology ; *Exercise ; Genome-Wide Association Study ; },
abstract = {BACKGROUND: The causal relationships between amyotrophic lateral sclerosis (ALS), Parkinson disease and different intensities of physical activity (PA) are still inconclusive. To evaluate the causal impact of PA on ALS and Parkinson disease (PD), this study integrates evidence from Mendelian randomization (MR) using a meta-analysis approach.

METHODS: MR analyses on genetically predicted levels of PA (compose of self-reported moderate-to-vigorous physical activity [MVPA], self-reported vigorous physical activity [VPA], and strenuous sports or other exercises [SSOE]) regarding ALS and PD published up to July 27, 2024, were obtained from PubMed, Scopus, Web of Science, and Embase. De novo MR studies were analyzed utilizing publicly accessible datasets from genome-wide association studies and then meta-analyses were performed to pool the results.

RESULTS: Meta-analyses of results of 12 de novo MR studies analyses and 2 published MR studies indicated that genetic predicted levels of MVPA (odds ratio [OR]: 1.22, 95% confidence interval [CI]: 1.08-1.38), VPA (OR: 1.32, 95% CI: 1.08-1.60), and SSOE (OR: 1.35, 95% CI: 1.07-1.70) were related to a raised risk of ALS, but not causally with PD.

CONCLUSION: Our findings showed no causal relationships between MVPA, VPA, SSOE, and PD, while MVPA, VPA, and SSOE were associated with increased ALS risk, highlighting the need for targeted PA recommendations for disease management.},
}

Humans
*Mendelian Randomization Analysis
*Amyotrophic Lateral Sclerosis/genetics
*Parkinson Disease/genetics/epidemiology
*Exercise
Genome-Wide Association Study

@article {pmid39378530,
year = {2025},
author = {Meng, T and Wu, W and Wang, B and Li, C and Li, J and Liu, J and Wang, J and Qie, R},
title = {Treating chronic pulmonary heart disease with traditional Chinese medicine: Systematic evaluation and mechanistic insights into the resolving phlegm and activating blood approach.},
journal = {Heart & lung : the journal of critical care},
volume = {69},
number = {},
pages = {111-126},
doi = {10.1016/j.hrtlng.2024.09.017},
pmid = {39378530},
issn = {1527-3288},
mesh = {Humans ; Chronic Disease ; *Drugs, Chinese Herbal/therapeutic use/pharmacology ; *Medicine, Chinese Traditional/methods ; *Pulmonary Heart Disease/drug therapy ; Randomized Controlled Trials as Topic ; },
abstract = {BACKGROUND: Chronic Pulmonary Heart Disease (CPHD) significantly impacts global health, especially among middle-aged and older adults. In China, the Traditional Chinese Medicine (TCM) technique of Resolving Phlegm and Activating Blood (RPAB) is widely used to treat CPHD, although high-quality evidence supporting its efficacy remains limited.

OBJECTIVES: The purpose of this study was to rigorously assess the clinical efficacy of RPAB for CPHD and elucidate the mechanisms underlying its primary herbal components.

METHODS: Through a detailed search of literature in both Chinese and English and strict inclusion and exclusion criteria, 18 randomized controlled trials (RCTs) were selected for meta-analysis. We identified RPAB's core herbal combinations using association rule analysis. This method statistically analyzes the frequency and correlation of herbal medicine usage. We then analyzed the chemical components of these combinations and investigated their potential intervention mechanisms on CPHD through network pharmacology.

RESULTS: The combination of RPAB with Western medicine was superior to Western medicine alone in improving blood gas analysis and pulmonary function and reducing plasma viscosity in CPHD patients. The core herbal combination identified was Astragalus membranaceus (Fisch.) Bunge, Ligusticum chuanxiong Hort. ex S. H. Qiu & al., and Stellaria alsine Grimm (ALS). This combination targeted 588 therapeutic and 27 core targets. It influenced ten core compounds across 34 pathways, primarily through the chemokine signaling pathway and the JAK-STAT signaling pathway.

CONCLUSION: RPAB with Western medicine significantly improves CPHD treatment outcomes. The study highlights the therapeutic potential of the ALS combination, which operates through multiple pathways to remodel pulmonary arteries, decrease inflammation, and lessen oxidative stress. These insights support the clinical application of RPAB in CPHD treatment and open new avenues for research and therapeutic development.},
}

Humans
Chronic Disease
*Drugs, Chinese Herbal/therapeutic use/pharmacology
*Medicine, Chinese Traditional/methods
*Pulmonary Heart Disease/drug therapy
Randomized Controlled Trials as Topic

@article {pmid39122262,
year = {2024},
author = {Wang, S and Jiang, Q and Zheng, X and Wei, Q and Lin, J and Yang, T and Xiao, Y and Li, C and Shang, H},
title = {Genotype-phenotype correlation of SQSTM1 variants in patients with amyotrophic lateral sclerosis.},
journal = {Journal of medical genetics},
volume = {61},
number = {10},
pages = {966-972},
doi = {10.1136/jmg-2023-109569},
pmid = {39122262},
issn = {1468-6244},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/genetics/pathology/epidemiology ; Frontotemporal Dementia/genetics/pathology ; Gene Frequency ; *Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Mutation ; Phenotype ; *Sequestosome-1 Protein/genetics ; Young Adult ; Aged, 80 and over ; },
abstract = {BACKGROUND: Several variants of sequestosome 1 (SQSTM1) were screened in patients with amyotrophic lateral sclerosis (ALS), while the pathogenicity and genotype-phenotype correlation remains unclear.

METHODS: We screened variants of SQSTM1 gene in 2011 Chinese patients with ALS and performed a burden analysis focusing on the rare variants. Furthermore, we conducted a comprehensive analysis of patients with variants of SQSTM1 gene in patients with ALS from our cohort and published studies.

RESULTS: In our cohort, we identified 32 patients with 25 different SQSTM1 variants with a mutant frequency of 1.6%. Notably, 26% (5/19) of the patients with ALS with SQSTM1 variant in our cohort had comorbid cognitive impairment and 43% (3/7) of them had behavioural variant frontotemporal dementia (FTD). Our meta-analysis found a total frequency of SQSTM1 variants in 7183 patients with ALS was 2.4%; burden analysis indicated that patients with ALS had enrichment of ultra-rare (minor allele frequency<0.01%) probably pathogenic variants in SQSTM1. Most variants were missense variants and distributed in various domains of p62 protein, some of which might be related to comorbidities of Paget's disease of bone and FTD.

CONCLUSION: Our study established the largest cohort of patients with ALS with SQSTM1 variants, expanded the mutation spectrum and investigated the genotype-phenotype correlations of SQSTM1 variants.},
}

Adult
Aged
Female
Humans
Male
Middle Aged
*Amyotrophic Lateral Sclerosis/genetics/pathology/epidemiology
Frontotemporal Dementia/genetics/pathology
Gene Frequency
*Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Mutation
Phenotype
*Sequestosome-1 Protein/genetics
Young Adult
Aged, 80 and over

@article {pmid39085618,
year = {2024},
author = {Müller, KJ and Schmidbauer, ML and Schönecker, S and Kamm, K and Pelz, JO and Holzapfel, K and Papadopoulou, M and Bakola, E and Tsivgoulis, G and Naumann, M and Hermann, A and Walter, U and Dimitriadis, K and Reilich, P and Schöberl, F},
title = {Diagnostic accuracy and confounders of vagus nerve ultrasound in amyotrophic lateral sclerosis-a single-center case series and pooled individual patient data meta-analysis.},
journal = {Journal of neurology},
volume = {271},
number = {9},
pages = {6255-6263},
pmid = {39085618},
issn = {1432-1459},
support = {DFG TRR 338//Deutsche Forschungsgemeinschaft/ ; DFG TRR 274//Deutsche Forschungsgemeinschaft/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/diagnostic imaging/diagnosis ; Humans ; Male ; Aged ; Female ; Middle Aged ; *Ultrasonography ; *Vagus Nerve/diagnostic imaging ; },
abstract = {BACKGROUND: Several single-center studies proposed utility of vagus nerve (VN) ultrasound for detecting disease severity, autonomic dysfunction, and bulbar phenotype in amyotrophic lateral sclerosis (ALS). However, the resulting body of literature shows opposing results, leaving considerable uncertainty on the clinical benefits of VN ultrasound in ALS.

METHODS: Relevant studies were identified up to 04/2024 and individual patient data (IPD) obtained from the respective authors were pooled with a so far unpublished cohort (from Munich). An IPD meta-analysis of 109 patients with probable or definite ALS (El Escorial criteria) and available VN cross-sectional area (CSA) was performed, with age, sex, ALS Functional Rating Scale-revised (ALSFRS-R), disease duration, and bulbar phenotype as independent variables.

RESULTS: Mean age was 65 years (± 12) and 47% of patients (± 12) had bulbar ALS. Mean ALSFRS-R was 38 (± 7), and mean duration was 18 months (± 18). VN atrophy was highly prevalent [left: 67% (± 5), mean CSA 1.6mm[2] (± 0.6); right: 78% (± 21), mean CSA 1.8 mm[2] (± 0.7)]. VN CSA correlated with disease duration (mean slope: left - 0.01; right - 0.01), but not with ALSFRS-R (mean slope: left 0.004; mean slope: right - 0.002). Test accuracy for phenotyping bulbar vs. non-bulbar ALS was poor (summary receiver operating characteristic area under the curve: left 0.496; right 0.572).

CONCLUSION: VN atrophy in ALS is highly prevalent and correlates with disease duration, but not with ALSFRS-R. VN CSA is insufficient to differentiate bulbar from non-bulbar ALS phenotypes. Further studies are warranted to analyze the link between VN atrophy, autonomic impairment, and survival in ALS.},
}

*Amyotrophic Lateral Sclerosis/diagnostic imaging/diagnosis
Humans
Male
Aged
Female
Middle Aged
*Ultrasonography
*Vagus Nerve/diagnostic imaging

@article {pmid38968276,
year = {2024},
author = {El Ouardi, L and Yeou, M},
title = {Are Personal and Reflexive Pronouns Dissociated in Agrammatic Comprehension? An Individual Participant Meta-Analysis With Clinical Implications.},
journal = {American journal of speech-language pathology},
volume = {33},
number = {6S},
pages = {3218-3235},
pmid = {38968276},
issn = {1558-9110},
mesh = {Humans ; Aphasia, Broca/physiopathology ; *Comprehension/physiology ; Semantics ; },
abstract = {PURPOSE: This study had three objectives: (a) to verify if Grodzinsky et al.'s (1993) findings of worse comprehension of personal than reflexive pronouns can be replicated in a larger meta-analysis of individual participant data, (b) to examine if the heterogeneity found in the patterns of pronoun comprehension in agrammatism can be attributed to task effects, and (c) to evaluate the risk of bias in the reviewed studies.

METHOD: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic literature search was performed to identify studies examining the personal-reflexive pronoun dissociation in agrammatic comprehension. Seven studies met the search criteria and were included in the meta-analysis. For each participant, individual accuracy scores for the comprehension of personal and reflexive pronouns were extracted in addition to information on the study methods. Individual accuracy data were analyzed using the Fisher's exact test and the binomial test. The risk of bias in the studies was assessed using an adapted version of the Newcastle-Ottawa Quality Assessment Scale.

RESULTS: The meta-analysis had three main findings: (a) The majority of the persons with agrammatic aphasia (89%) had no dissociation between the comprehension of personal and reflexive pronouns; (b) 8% revealed a pattern consistent with a neuropsychological dissociation, faring worse on the comprehension of personal than reflexive pronouns; and (c) 2% performed worse on reflexive than personal pronouns. The type of the task used affected pronoun comprehension accuracy and accounted for the heterogeneity in the patterns of pronoun comprehension attested across the different participants.

CONCLUSIONS: Taken together, the meta-analysis did not support a dissociation between personal and reflexive pronoun comprehension in agrammatic comprehension. When confirmed, the dissociation was driven by task effects. The clinical implications of these findings were discussed together with implications to minimize the risk of bias in future examinations of the topic.},
}

Humans
Aphasia, Broca/physiopathology
*Comprehension/physiology
Semantics

@article {pmid38937912,
year = {2024},
author = {Verde, F and Licaj, S and Soranna, D and Ticozzi, N and Silani, V and Zambon, A},
title = {Cerebrospinal fluid and blood neurofilament light chain levels in amyotrophic lateral sclerosis and frontotemporal degeneration: A meta-analysis.},
journal = {European journal of neurology},
volume = {31},
number = {9},
pages = {e16371},
pmid = {38937912},
issn = {1468-1331},
support = {//Ministero della Salute/ ; //BIBLIOSAN/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/cerebrospinal fluid/blood ; Humans ; *Neurofilament Proteins/blood/cerebrospinal fluid ; *Frontotemporal Lobar Degeneration/blood/cerebrospinal fluid ; Biomarkers/cerebrospinal fluid/blood ; Frontotemporal Dementia/cerebrospinal fluid/blood ; },
abstract = {BACKGROUND AND PURPOSE: Neurofilament light chain (NFL) has been shown to be increased in amyotrophic lateral sclerosis (ALS) and, to a lesser extent, in frontotemporal dementia (FTD). A meta-analysis of NFL in ALS and FTD was performed.

METHODS: Available studies comparing cerebrospinal fluid and blood NFL levels in ALS versus neurologically healthy controls (NHCs), other neurological diseases (ONDs) and ALS mimics, as well as in FTD and related entities (behavioural variant of FTD and frontotemporal lobar degeneration syndromes) versus NHCs, ONDs and other dementias were evaluated.

RESULTS: In ALS, both cerebrospinal fluid and blood levels of NFL were higher compared to other categories. In FTD, behavioural variant of FTD and frontotemporal lobar degeneration syndromes, NFL levels were consistently higher compared to NHCs; however, several comparisons with ONDs and other dementias did not demonstrate significant differences.

DISCUSSION: Amyotrophic lateral sclerosis is characterized by higher NFL levels compared to most other conditions. In contrast, NFL is not as good at discriminating FTD from other dementias.},
}

*Amyotrophic Lateral Sclerosis/cerebrospinal fluid/blood
Humans
*Neurofilament Proteins/blood/cerebrospinal fluid
*Frontotemporal Lobar Degeneration/blood/cerebrospinal fluid
Biomarkers/cerebrospinal fluid/blood
Frontotemporal Dementia/cerebrospinal fluid/blood

@article {pmid38924633,
year = {2024},
author = {Wolf, J and Buckley, GJ and Rozanski, EA and Fletcher, DJ and Boller, M and Burkitt-Creedon, JM and Weigand, KA and Crews, M and Fausak, ED and , },
title = {2024 RECOVER Guidelines: Advanced Life Support. Evidence and knowledge gap analysis with treatment recommendations for small animal CPR.},
journal = {Journal of veterinary emergency and critical care (San Antonio, Tex. : 2001)},
volume = {34 Suppl 1},
number = {},
pages = {44-75},
doi = {10.1111/vec.13389},
pmid = {38924633},
issn = {1476-4431},
support = {//Zoetis Animal Health/ ; //Boehringer Ingelheim Animal Health/ ; },
mesh = {Animals ; Dogs ; Cats ; *Dog Diseases/therapy/drug therapy ; Cardiopulmonary Resuscitation/veterinary/standards ; Cat Diseases/therapy/drug therapy ; Veterinary Medicine/standards ; Heart Arrest/veterinary/therapy ; },
abstract = {OBJECTIVE: To systematically review the evidence and devise clinical recommendations on advanced life support (ALS) in dogs and cats and to identify critical knowledge gaps.

DESIGN: Standardized, systematic evaluation of literature pertinent to ALS following Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Prioritized questions were each reviewed by Evidence Evaluators, and findings were reconciled by ALS Domain Chairs and Reassessment Campaign on Veterinary Resuscitation (RECOVER) Co-Chairs to arrive at treatment recommendations commensurate to quality of evidence, risk:benefit relationship, and clinical feasibility. This process was implemented using an Evidence Profile Worksheet for each question that included an introduction, consensus on science, treatment recommendations, justification for these recommendations, and important knowledge gaps. A draft of these worksheets was distributed to veterinary professionals for comment for 4 weeks prior to finalization.

SETTING: Transdisciplinary, international collaboration in university, specialty, and emergency practice.

RESULTS: Seventeen questions pertaining to vascular access, vasopressors in shockable and nonshockable rhythms, anticholinergics, defibrillation, antiarrhythmics, and adjunct drug therapy as well as open-chest CPR were reviewed. Of the 33 treatment recommendations formulated, 6 recommendations addressed the management of patients with nonshockable arrest rhythms, 10 addressed shockable rhythms, and 6 provided guidance on open-chest CPR. We recommend against high-dose epinephrine even after prolonged CPR and suggest that atropine, when indicated, is used only once. In animals with a shockable rhythm in which initial defibrillation was unsuccessful, we recommend doubling the defibrillator dose once and suggest vasopressin (or epinephrine if vasopressin is not available), esmolol, lidocaine in dogs, and/or amiodarone in cats.

CONCLUSIONS: These updated RECOVER ALS guidelines clarify the approach to refractory shockable rhythms and prolonged CPR. Very low quality of evidence due to absence of clinical data in dogs and cats continues to compromise the certainty with which recommendations can be made.},
}

Animals
Dogs
Cats
*Dog Diseases/therapy/drug therapy
Cardiopulmonary Resuscitation/veterinary/standards
Cat Diseases/therapy/drug therapy
Veterinary Medicine/standards
Heart Arrest/veterinary/therapy

@article {pmid38924627,
year = {2024},
author = {Burkitt-Creedon, JM and Boller, M and Fletcher, DJ and Brainard, BM and Buckley, GJ and Epstein, SE and Fausak, ED and Hopper, K and Lane, SL and Rozanski, EA and Wolf, J},
title = {2024 RECOVER Guidelines: Updated treatment recommendations for CPR in dogs and cats.},
journal = {Journal of veterinary emergency and critical care (San Antonio, Tex. : 2001)},
volume = {34 Suppl 1},
number = {},
pages = {104-123},
doi = {10.1111/vec.13391},
pmid = {38924627},
issn = {1476-4431},
support = {//Boehringer Ingelheim Animal Health/ ; //Zoetis Animal Health/ ; },
mesh = {Dogs ; Animals ; Cats ; *Cardiopulmonary Resuscitation/veterinary/standards/methods ; *Cat Diseases/therapy ; Dog Diseases/therapy ; Heart Arrest/veterinary/therapy ; },
abstract = {OBJECTIVE: After the 2012 Reassessment Campaign on Veterinary Resuscitation (RECOVER) CPR Guidelines, this is an update of evidence-based consensus guidelines for Basic Life Support (BLS), advanced life support (ALS), and periarrest monitoring.

DESIGN: These RECOVER CPR Guidelines were generated using a modified version of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system for evidence evaluation and translation of this evidence into clear and actionable clinical instructions. Prioritized clinical questions in the Population, Intervention, Comparator, and Outcome (PICO) format were used as the basis to conduct systematic literature searches by information specialists, to extract information from relevant publications, to assess this evidence for quality, and finally to translate the findings into treatment recommendations. These recommendations were reviewed by the RECOVER writing group and opened for comment by veterinary professionals for 4 weeks.

SETTING: Transdisciplinary, international collaboration in university, specialty, and emergency practice.

RESULTS: A total of 40 worksheets were prepared to evaluate questions across the 3 domains of BLS, ALS and Monitoring, resulting in 90 individual treatment recommendations. High-dose epinephrine is no longer recommended, and atropine, if used, is only administered once. Bag-mask ventilation is prioritized over mouth-to-nose ventilation in nonintubated animals. In addition, an algorithm for initial assessment, an updated CPR algorithm, a rhythm diagnosis tool, and an updated drug dosing table are provided.

CONCLUSIONS: While the majority of the BLS and ALS recommendations remain unchanged, some noteworthy changes were made due to new evidence that emerged over the past 10 years. Indirectness of evidence remains the largest impediment to the certainty of guidelines formulation and underscores an urgent need for more studies in the target species of dogs and cats.},
}

Dogs
Animals
Cats
*Cardiopulmonary Resuscitation/veterinary/standards/methods
*Cat Diseases/therapy
Dog Diseases/therapy
Heart Arrest/veterinary/therapy

@article {pmid38627298,
year = {2024},
author = {Hamad, AA and Amer, BE},
title = {Safety of masitinib in patients with neurodegenerative diseases: a meta-analysis of randomized controlled trials.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {45},
number = {7},
pages = {3503-3507},
pmid = {38627298},
issn = {1590-3478},
mesh = {Humans ; *Randomized Controlled Trials as Topic ; *Thiazoles/adverse effects/administration & dosage/therapeutic use ; *Neurodegenerative Diseases/drug therapy ; *Piperidines/adverse effects/therapeutic use/administration & dosage ; *Benzamides/adverse effects/administration & dosage ; *Pyridines/adverse effects/administration & dosage/therapeutic use ; Protein Kinase Inhibitors/adverse effects/administration & dosage ; },
abstract = {OBJECTIVES: This meta-analysis aimed to examine the safety of masitinib in patients with neurodegenerative diseases.

METHODS: We considered randomized controlled trials (RCTs) comparing different doses of masitinib versus placebo. We performed our analysis using the R (v.4.3.0) programming language and the incidence of adverse events was pooled using risk ratio (RR) and 95% confidence interval (CI).

RESULTS: We included five RCTs, focusing on multiple sclerosis (MS), Alzheimer's disease (AD), and amyotrophic lateral sclerosis. The meta-analysis revealed a significantly higher incidence of adverse events in the masitinib group compared to the control group, regardless of adverse event grade and masitinib dose (RR = 1.12, 95% CI [1.07 to 1.17], P < 0.01). Adverse events categorized as severe, non-fatal serious, leading to dose reduction, and leading to permanent discontinuation also showed a higher incidence in the masitinib group (P ≤ 0.01). Subgroup analysis for AD and MS supported these findings. The pooled incidence of adverse events, regardless of their grade, was higher in the masitinib group for both the 3 mg/kg/d dose (RR = 1.13, P = 0.01) and the 4.5 mg/kg/d dose (RR = 1.11, P < 0.01). However, there was no significant difference between masitinib 3 mg/kg/d dose and placebo regarding severe and non-fatal serious adverse events for the.

CONCLUSION: Masitinib use in neurodegenerative diseases presents safety concerns that may impact patients' quality of life and require management. Further research is recommended to determine the optimal dose with minimal safety concerns in this patient population.},
}

Humans
*Randomized Controlled Trials as Topic
*Thiazoles/adverse effects/administration & dosage/therapeutic use
*Neurodegenerative Diseases/drug therapy
*Piperidines/adverse effects/therapeutic use/administration & dosage
*Benzamides/adverse effects/administration & dosage
*Pyridines/adverse effects/administration & dosage/therapeutic use
Protein Kinase Inhibitors/adverse effects/administration & dosage

@article {pmid38522911,
year = {2024},
author = {Urushitani, M and Warita, H and Atsuta, N and Izumi, Y and Kano, O and Shimizu, T and Nakayama, Y and Narita, Y and Nodera, H and Fujita, T and Mizoguchi, K and Morita, M and Aoki, M},
title = {The clinical practice guideline for the management of amyotrophic lateral sclerosis in Japan-update 2023.},
journal = {Rinsho shinkeigaku = Clinical neurology},
volume = {64},
number = {4},
pages = {252-271},
doi = {10.5692/clinicalneurol.cn-001946},
pmid = {38522911},
issn = {1882-0654},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/diagnosis ; Disease Progression ; Evidence-Based Medicine ; Japan ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is an adult-onset intractable motor neuron disease characterized by selective degeneration of cortical neurons in the frontotemporal lobe and motor neurons in the brainstem and spinal cord. Impairment of these neural networks causes progressive muscle atrophy and weakness that spreads throughout the body, resulting in life-threatening bulbar palsy and respiratory muscle paralysis. However, no therapeutic strategy has yet been established to halt ALS progression. Although evidence for clinical practice in ALS remains insufficient, novel research findings have steadily accumulated in recent years. To provide updated evidence-based or expert consensus recommendations for the diagnosis and management of ALS, the ALS Clinical Practice Guideline Development Committee, approved by the Japanese Society of Neurology, revised and published the Japanese clinical practice guidelines for the management of ALS in 2023. In this guideline, disease-modifying therapies that have accumulated evidence from randomized controlled trials were defined as "Clinical Questions," in which the level of evidence was determined by systematic reviews. In contrast, "Questions and Answers" were defined as issues of clinically important but insufficient evidence, according to reports of a small number of cases, observational studies, and expert opinions. Based on a literature search performed in February 2022, recommendations were reached by consensus, determined by an independent panel, reviewed by external reviewers, and submitted for public comments by Japanese Society of Neurology members before publication. In this article, we summarize the revised Japanese guidelines for ALS, highlighting the regional and cultural diversity of care processes and decision-making. The guidelines cover a broad range of essential topics such as etiology, diagnostic criteria, disease monitoring and treatments, management of symptoms, respiration, rehabilitation, nutrition, metabolism, patient instructions, and various types of care support. We believe that this summary will help improve the daily clinical practice for individuals living with ALS and their caregivers.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/diagnosis
Disease Progression
Evidence-Based Medicine
Japan

@article {pmid38470068,
year = {2024},
author = {Van Damme, P and Al-Chalabi, A and Andersen, PM and Chiò, A and Couratier, P and De Carvalho, M and Hardiman, O and Kuźma-Kozakiewicz, M and Ludolph, A and McDermott, CJ and Mora, JS and Petri, S and Probyn, K and Reviers, E and Salachas, F and Silani, V and Tysnes, OB and van den Berg, LH and Villanueva, G and Weber, M},
title = {European Academy of Neurology (EAN) guideline on the management of amyotrophic lateral sclerosis in collaboration with European Reference Network for Neuromuscular Diseases (ERN EURO-NMD).},
journal = {European journal of neurology},
volume = {31},
number = {6},
pages = {e16264},
pmid = {38470068},
issn = {1468-1331},
support = {//ERN Euro-NMD/ ; //European Academy of Neurology/ ; //ALS Liga Belgium/ ; //EUpALS/ ; //ENCALS/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; Europe ; Neurology/standards/methods ; Neuromuscular Diseases/therapy ; },
abstract = {BACKGROUND: This update of the guideline on the management of amyotrophic lateral sclerosis (ALS) was commissioned by the European Academy of Neurology (EAN) and prepared in collaboration with the European Reference Network for Neuromuscular Diseases (ERN EURO-NMD) and the support of the European Network for the Cure ALS (ENCALS) and the European Organization for Professionals and Patients with ALS (EUpALS).

METHODS: Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the effectiveness of interventions for ALS. Two systematic reviewers from Cochrane Response supported the guideline panel. The working group identified a total of 26 research questions, performed systematic reviews, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available.

RESULTS: A guideline mapping effort revealed only one other ALS guideline that used GRADE methodology (a National Institute for Health and Care Excellence [NICE] guideline). The available evidence was scarce for many research questions. Of the 26 research questions evaluated, the NICE recommendations could be adapted for 8 questions. Other recommendations required updates of existing systematic reviews or de novo reviews. Recommendations were made on currently available disease-modifying treatments, multidisciplinary care, nutritional and respiratory support, communication aids, psychological support, treatments for common ALS symptoms (e.g., muscle cramps, spasticity, pseudobulbar affect, thick mucus, sialorrhea, pain), and end-of-life management.

CONCLUSIONS: This update of the guideline using GRADE methodology provides a framework for the management of ALS. The treatment landscape is changing rapidly, and further updates will be prepared when additional evidence becomes available.},
}

*Amyotrophic Lateral Sclerosis/therapy
Humans
Europe
Neurology/standards/methods
Neuromuscular Diseases/therapy

@article {pmid38381392,
year = {2024},
author = {Miah, MM and Zinnia, MA and Tabassum, N and Islam, ABMMK},
title = {Association between DPP6 gene rs10260404 polymorphism and increased risk of sporadic amyotrophic lateral sclerosis (sALS): a meta-analysis.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {45},
number = {7},
pages = {3225-3243},
pmid = {38381392},
issn = {1590-3478},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology ; *Genetic Predisposition to Disease/genetics ; *Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/genetics ; *Polymorphism, Single Nucleotide ; Case-Control Studies ; Nerve Tissue Proteins ; Potassium Channels ; },
abstract = {BACKGROUND: Sporadic amyotrophic lateral sclerosis (sALS) is a severe neurodegenerative disease characterized by continuous diminution of motor neurons in the brain and spinal cord. Earlier studies indicated that the DPP6 gene variant has a role in the development of sALS. This meta-analysis was designed to uncover the role of rs10260404 polymorphism of the DPP6 gene and its association with sALS.

METHODS: All case-control articles published prior to October 2022 on the association between DPP6 (rs10260404) polymorphism and sALS risk were systematically extracted from different databases which include PubMed, PubMed Central, and Google Scholar. Overall odds ratios (ORs) and "95% confidence intervals (CIs)" were summarized for various genetic models. Subgroup and heterogeneity assessments were performed. Egger's and "Begg's tests were applied to evaluate publication bias. Trial sequential analysis (TSA) and false-positive report probability (FPRP) were performed.

RESULTS: Nine case-control studies containing 4202 sALS cases and 4444 healthy controls were included in the meta-analysis. A significant association of the DPP6 (rs10260404) variant with an increased sALS risk in overall pooled subjects under allelic model [C allele vs. T allele, OR = 1.149, 95% CI (1.010-1.307), p-value = 0.035], dominant model [CC + CT vs. TT, OR = 1.165, 95% CI (1.067-1.273), p-value = 0.001], and homozygote comparison [CC vs. TT, OR = 1.421, 95% CI (1.003-2.011), p-value = 0.048] were observed. Moreover, in subgroup analysis by nationality, remarkable associations were detected in Dutch, Irish, American, and Swedish under allelic, dominant, and homozygote models. Additionally, stratification analysis by ethnicity exhibited an association with sALS risk among Caucasians and Americans under different genetic models. Interestingly, none of the models found any significant association with Asians.

CONCLUSION: The present meta-analysis indicates that DPP6 (rs10260404) polymorphism could be a candidate risk factor for sALS predisposition.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/epidemiology
*Genetic Predisposition to Disease/genetics
*Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/genetics
*Polymorphism, Single Nucleotide
Case-Control Studies
Nerve Tissue Proteins
Potassium Channels

@article {pmid37930481,
year = {2024},
author = {Domi, T and Schito, P and Sferruzza, G and Russo, T and Pozzi, L and Agosta, F and Carrera, P and Riva, N and Filippi, M and Quattrini, A and Falzone, YM},
title = {Unveiling the SOD1-mediated ALS phenotype: insights from a comprehensive meta-analysis.},
journal = {Journal of neurology},
volume = {271},
number = {3},
pages = {1342-1354},
pmid = {37930481},
issn = {1432-1459},
mesh = {Humans ; Superoxide Dismutase-1/genetics ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics ; Phenotype ; Genetic Testing ; Mutation ; C9orf72 Protein/genetics ; RNA-Binding Protein FUS/genetics ; },
abstract = {BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis associated with mutations in SOD1 (SOD1-ALS) might be susceptible to specific treatment. The aim of the study is to outline the clinical features of SOD1-ALS patients by comparing them to patients without ALS major gene variants and patients with variants in other major ALS genes. Defining SOD1-ALS phenotype may assist clinicians in identifying patients who should be prioritized for genetic testing.

METHODS: We performed an extensive literature research including original studies which reported the clinical features of SOD1-ALS and at least one of the following patient groups: C9ORF72 hexanucleotide repeat expansion (C9-ALS), TARDBP (TARDBP-ALS), FUS (FUS-ALS) or patients without a positive test for a major-ALS gene (N-ALS). A random effects meta-analytic model was applied to clinical data extracted encompassing sex, site and age of onset. To reconstruct individual patient survival data, the published Kaplan-Meier curves were digitized. Data were measured as odds ratio (OR) or standardized mean difference (SMD) as appropriate. Median survival was compared between groups.

RESULTS: Twenty studies met the inclusion criteria. We identified 721 SOD1-ALS, 470 C9-ALS, 183 TARDBP-ALS, 113 FUS-ALS and 2824 N-ALS. SOD1-ALS showed a higher rate of spinal onset compared with N-ALS and C9-ALS (OR = 4.85, 95% CI = 3.04-7.76; OR = 10.47, 95% CI = 4.32-27.87) and an earlier onset compared with N-ALS (SMD = - 0.45, 95% CI = - 0.72 to - 0.18). SOD1-ALS had a similar survival compared with N-ALS (p = 0.14), a longer survival compared with C9-ALS (p < 0.01) and FUS-ALS (p = 0.019) and a shorter survival compared with TARDBP-ALS (p < 0.01).

DISCUSSION: This study indicates the presence of a specific SOD1-ALS phenotype. Insights in SOD1-ALS clinical features are important in genetic counseling, disease prognosis and support patients' stratification in clinical trials.},
}

Humans
Superoxide Dismutase-1/genetics
*Amyotrophic Lateral Sclerosis/diagnosis/genetics
Phenotype
Genetic Testing
Mutation
C9orf72 Protein/genetics
RNA-Binding Protein FUS/genetics

@article {pmid37806668,
year = {2023},
author = {Marchand, GJ and Masoud, A},
title = {Response to Dr. Somovilla del Saz's letter to the editor regarding "Risk of all-cause and cardiac-related mortality after vaccination against COVID-19: A meta-analysis of self-controlled case series studies".},
journal = {Human vaccines & immunotherapeutics},
volume = {19},
number = {3},
pages = {2264599},
pmid = {37806668},
issn = {2164-554X},
abstract = {This is a response to Dr. Somovilla del Saz's letter to the editor regarding Marchand et al.'s article, "Risk of all-cause and cardiac-related mortality after vaccination against COVID-19: A meta-analysis of self-controlled case series studies." The response is on behalf of all authors clarifying misconceptions about the work.},
}

@article {pmid37735015,
year = {2023},
author = {Corcia, P and Vourc'h, P and Bernard, E and Cassereau, J and Codron, P and Fleury, MC and Guy, N and Mouzat, K and Pradat, PF and Soriani, MH and Couratier, P},
title = {French National Protocol for genetic of amyotrophic lateral sclerosis.},
journal = {Revue neurologique},
volume = {179},
number = {9},
pages = {1020-1029},
doi = {10.1016/j.neurol.2023.05.005},
pmid = {37735015},
issn = {0035-3787},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/genetics ; Mutation ; },
abstract = {Relationships between genes and amyotrophic lateral sclerosis (ALS) have been widely accepted since the first studies highlighting pathogenic mutations in the SOD1 gene 30years ago. Over the last three decades, scientific literature has clearly highlighted the central role played by genetic factors in the disease, in both clinics and pathophysiology, as well as in therapeutics. This implies that health professionals who care for patients with ALS are increasingly faced with patients and relatives eager to have answers to questions related to the role of genetic factors in the occurrence of the disease and the risk for their relatives to develop ALS. In order to address these public health issues, the French ALS network FILSLAN proposed to the Haute Autorité de santé (HAS) the drafting of a French National Protocol (PNDS) on ALS genetics. This PNDS was developed according to the "method for developing a national diagnosis and care protocol for rare diseases" published by the HAS in 2012 (methodological guide for PNDS available on the HAS website: http://www.has-sante.fr/). This document aims to provide the most recent data on the role of genes in ALS and to detail the implications for diagnosis and care.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/genetics
Mutation

@article {pmid37688479,
year = {2024},
author = {Li, Z and Tian, M and Jia, H and Li, X and Liu, Q and Zhou, X and Li, R and Dong, H and Liu, Y},
title = {Genetic variation in targets of lipid-lowering drugs and amyotrophic lateral sclerosis risk: a Mendelian randomization study.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {25},
number = {1-2},
pages = {197-206},
doi = {10.1080/21678421.2023.2255622},
pmid = {37688479},
issn = {2167-9223},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/epidemiology/genetics ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Cholesterol, LDL ; Apolipoproteins B/genetics ; Genetic Variation ; Polymorphism, Single Nucleotide/genetics ; },
abstract = {BACKGROUND: The use of lipid-lowering drugs is still highly controversial in patients with amyotrophic lateral sclerosis (ALS). We performed a drug-target Mendelian randomization (MR) analysis to investigate the effect of targeted lipid-lowering drugs on the risk of ALS.

METHODS: First, we evaluated the causal relationship between HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase (HMGCR) inhibitors-taking trait and ALS using a bidirectional two-sample MR study. Second, we investigated the causal relationship between lipid-lowering drugs and ALS through a drug-target MR approach. The summary data for HMGCR inhibitors-taking traits were extracted from a genome-wide association study (GWAS) of medication use and associated disease in the UK Biobank. The summary data for low-density lipoprotein cholesterol and apolipoprotein B (apoB) were extracted from a meta-analysis of GWAS in individuals of European ancestry in the UKB. The GWAS summary data of ALS were obtained from the Project MinE.

RESULTS: Our bidirectional two-sample MR showed that genetically determined increased HMGCR inhibitors-taking trait was an independent risk factor for ALS (odds ratio [OR] = 1.090, 95% confidence interval [CI] = 1.035-1.150, p = 0.001). The results of drug-target MR showed that the increased expression of the HMGCR gene in blood with the higher risk of ALS (OR = 1.21, 95% CI = 1.01-1.46; p = 0.042) through SMR method and the apoB level mediated by the APOB gene increased the risk of ALS (OR = 1.15; 95% CI =1.05-1.25; p = 0.001) through inverse-variance weighted MR method.

CONCLUSION: This present study provides genetic support for a positive causal effect of HMGCR inhibitors-taking trait and ALS. The reason for this may be due to the underlying disease condition behind the medication, rather than the medication itself. Our findings also suggested that HMGCR and apoB inhibitors may have potential protective effects on ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy/epidemiology/genetics
Mendelian Randomization Analysis
Genome-Wide Association Study
Cholesterol, LDL
Apolipoproteins B/genetics
Genetic Variation
Polymorphism, Single Nucleotide/genetics

@article {pmid37647907,
year = {2023},
author = {Gondim, FAA and Pinto, WBVR and Chieia, MAT and Correia, CDC and Cunha, FMB and Dourado, MET and França Júnior, MC and Marques Júnior, W and Oliveira, ASB and Rodrigues, CL and Silva, DJD and Dias-Tosta, E},
title = {Definitions, phenomenology, diagnosis, and management of the disorders of laughter and crying in amyotrophic lateral sclerosis (ALS): Consensus from ALS and Motor Neuron Disease Scientific Department of the Brazilian Academy of Neurology.},
journal = {Arquivos de neuro-psiquiatria},
volume = {81},
number = {8},
pages = {764-775},
pmid = {37647907},
issn = {1678-4227},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/therapy ; Brazil ; *Laughter ; Crying ; *Motor Neuron Disease ; *Neurology ; },
abstract = {The spectrum of neuropsychiatric phenomena observed in amyotrophic lateral sclerosis (ALS) is wide and not fully understood. Disorders of laughter and crying stand among the most common manifestations. The aim of this study is to report the results of an educational consensus organized by the Brazilian Academy of Neurology to evaluate the definitions, phenomenology, diagnosis, and management of the disorders of laughter and crying in ALS patients. Twelve members of the Brazilian Academy of Neurology - considered to be experts in the field - were recruited to answer 12 questions about the subject. After exchanging revisions, a first draft was prepared. A face-to-face meeting was held in Fortaleza, Brazil on 9.23.22 to discuss it. The revised version was subsequently emailed to all members of the ALS Scientific Department from the Brazilian Academy of Neurology and the final revised version submitted for publication. The prevalence of pseudobulbar affect/pathological laughter and crying (PBA/PLC) in ALS patients from 15 combined studies and 3906 patients was 27.4% (N = 1070), ranging from 11.4% to 71%. Bulbar onset is a risk factor but there are limited studies evaluating the differences in prevalence among the different motor neuron diseases subtypes, including patients with and without frontotemporal dementia. Antidepressants and a combination of dextromethorphan and quinidine (not available in Brazil) are possible therapeutic options. This group of panelists acknowledge the multiple gaps in the current literature and reinforces the need for further studies.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/therapy
Brazil
*Laughter
Crying
*Motor Neuron Disease
*Neurology

@article {pmid37516812,
year = {2023},
author = {Yin, Z and Chen, J and Xia, M and Zhang, X and Li, Y and Chen, Z and Bao, Q and Zhong, W and Yao, J and Wu, K and Zhao, L and Liang, F},
title = {Assessing causal relationship between circulating cytokines and age-related neurodegenerative diseases: a bidirectional two-sample Mendelian randomization analysis.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {12325},
pmid = {37516812},
issn = {2045-2322},
mesh = {Humans ; Cytokines/genetics ; *Neurodegenerative Diseases/genetics ; Mendelian Randomization Analysis ; *Amyotrophic Lateral Sclerosis/genetics ; Fibroblast Growth Factor 2 ; Genome-Wide Association Study ; *Alzheimer Disease ; *Parkinson Disease/genetics ; },
abstract = {Numerous studies have reported that circulating cytokines (CCs) are linked to age-related neurodegenerative diseases (ANDDs); however, there is a lack of systematic investigation for the causal association. A two-sample bidirectional Mendelian Randomisation (MR) method was utilized to evaluate the causal effect. We applied genetic variants correlated with concentrations of CCs from a genome-wide association study meta-analysis (n = 8293) as instrumental variables. Summary data of three major ANDDs [Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS)] were identified from the IEU OpenGWAS platform (n = 627, 266). Inverse-variance weighted method is the main approach to analyse causal effect, and MR results are verified by several sensitivity and pleiotropy analyses. In directional MR, it suggested that several CCs were nominally correlated with the risk of ANDDs, with a causal odds ratio (OR) of Interleukin (IL)-5 of 0.909 for AD; OR of IL-2 of 1.169 for PD; and OR of Beta nerve growth factor of 1.142 for ALS). In reverse MR, there were some suggestively causal effects of ANDDs on CCs (AD on increased Basic fibroblast growth factor and IL-12 and decreased Stem cell growth factor beta; PD on decreased Monokine induced by interferon-gamma; ALS on decreased Basic fibroblast growth factor and IL-17). The findings were stable across sensitivity and pleiotropy analyses. However, after Bonferroni correction, there is no statistically significant association between CCs and ANDDs. Through the genetic epidemiological approach, our study assessed the role and presented possible causal associations between CCs and ANDDs. Further studies are warranted to verify the causal associations.},
}

Humans
Cytokines/genetics
*Neurodegenerative Diseases/genetics
Mendelian Randomization Analysis
*Amyotrophic Lateral Sclerosis/genetics
Fibroblast Growth Factor 2
Genome-Wide Association Study
*Alzheimer Disease
*Parkinson Disease/genetics

@article {pmid37211659,
year = {2023},
author = {O'Keefe, DJ},
title = {Commentary on "Do Vaping Prevention Messages Impact Adolescents and Young Adults? A Meta-Analysis of Experimental Studies".},
journal = {Health communication},
volume = {38},
number = {8},
pages = {1723-1726},
doi = {10.1080/10410236.2023.2212467},
pmid = {37211659},
issn = {1532-7027},
mesh = {Humans ; Adolescent ; Young Adult ; *Vaping/prevention & control ; },
abstract = {Preventing vaping by adolescents and young adults is unquestionably an important goal. Ma et al.'s meta-analysis invites the conclusion that vaping prevention messages are effective. This commentary discusses two concerns about that conclusion and the affiliated meta-analysis: (1) None of the analyzed effect sizes describes the effectiveness of vaping prevention messages; the effect sizes describe the difference in effectiveness (the difference on an outcome variable) between the two conditions being compared. (2) As the two conditions being compared vary, so do the relevant conclusions--but the review combines different kinds of comparisons.},
}

Humans
Adolescent
Young Adult
*Vaping/prevention & control

@article {pmid37171577,
year = {2023},
author = {Zhao, B and Jiang, Q and Lin, J and Wei, Q and Li, C and Hou, Y and Cao, B and Zhang, L and Ou, R and Liu, K and Yang, T and Xiao, Y and Huang, R and Shang, H},
title = {Genetic and Phenotypic Spectrum of Amyotrophic Lateral Sclerosis Patients with CCNF Variants from a Large Chinese Cohort.},
journal = {Molecular neurobiology},
volume = {60},
number = {7},
pages = {4150-4160},
pmid = {37171577},
issn = {1559-1182},
support = {2020YJ0457//Sichuan Science and Technology Program/ ; 2022ZDZX0023//Sichuan Science and Technology Program/ ; 82101485//National Natural Science Foundation of China/ ; 2021-YF05-00242-SN//Science and Technology commission foundation of Chengdu City/ ; },
mesh = {Humans ; Male ; Female ; *Amyotrophic Lateral Sclerosis/genetics ; East Asian People ; *Frontotemporal Dementia/genetics ; Genetic Association Studies ; Mutation, Missense/genetics ; Mutation ; Cyclins ; },
abstract = {Cyclin F (CCNF) variants have been found to be associated with amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). However, the genetic and clinical characteristics of ALS patients who carry CCNF variants are largely unknown. Genetic analysis was performed for 1587 Chinese ALS patients, and missense variants were predicted by software analyses. Additionally, we searched PubMed, Embase, and Web of Science for relevant literature and conducted a meta-analysis of the frequency of variants. In our ALS cohort, we identified 29 nonsynonymous variants in 41 ALS patients. Among these ALS patients, 18 (1.1%) were carriers of 15 rare missense variants that were considered probably pathogenic variants, and 11 of 15 variants were novel. Seven relevant studies were identified, and a total of 43 CCNF variants in 59 ALS patients with a frequency of 0.8% were reported. The ratio of males to females in our cohort (10/8) was similar to that in Caucasian populations (4/7) and significantly higher than that in Asian populations (10/1). The proportion of bulbar onset in Caucasian CCNF carriers was similar to our cohort (25.0 vs. 27.8%); however, bulbar onset had never been reported in previous Asian studies (0/11). FTD was not found in CCNF carriers in previous Asian studies and our cohort, but it has been reported in a FALS cohort (1/75) of Caucasian individuals. There were some differences in the clinical characteristics among different ethnic ALS populations. More basic scientific studies are needed to elucidate the pathogenic mechanisms and genotype-phenotype associations of CCNF variants.},
}

Humans
Male
Female
*Amyotrophic Lateral Sclerosis/genetics
East Asian People
*Frontotemporal Dementia/genetics
Genetic Association Studies
Mutation, Missense/genetics
Mutation
Cyclins

@article {pmid36835433,
year = {2023},
author = {Vasilopoulou, C and McDaid-McCloskey, SL and McCluskey, G and Duguez, S and Morris, AP and Duddy, W},
title = {Genome-Wide Gene-Set Analysis Identifies Molecular Mechanisms Associated with ALS.},
journal = {International journal of molecular sciences},
volume = {24},
number = {4},
pages = {},
pmid = {36835433},
issn = {1422-0067},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Genome-Wide Association Study ; Genotype ; Motor Neurons ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal late-onset motor neuron disease characterized by the loss of the upper and lower motor neurons. Our understanding of the molecular basis of ALS pathology remains elusive, complicating the development of efficient treatment. Gene-set analyses of genome-wide data have offered insight into the biological processes and pathways of complex diseases and can suggest new hypotheses regarding causal mechanisms. Our aim in this study was to identify and explore biological pathways and other gene sets having genomic association to ALS. Two cohorts of genomic data from the dbGaP repository were combined: (a) the largest available ALS individual-level genotype dataset (N = 12,319), and (b) a similarly sized control cohort (N = 13,210). Following comprehensive quality control pipelines, imputation and meta-analysis, we assembled a large European descent ALS-control cohort of 9244 ALS cases and 12,795 healthy controls represented by genetic variants of 19,242 genes. Multi-marker analysis of genomic annotation (MAGMA) gene-set analysis was applied to an extensive collection of 31,454 gene sets from the molecular signatures database (MSigDB). Statistically significant associations were observed for gene sets related to immune response, apoptosis, lipid metabolism, neuron differentiation, muscle cell function, synaptic plasticity and development. We also report novel interactions between gene sets, suggestive of mechanistic overlaps. A manual meta-categorization and enrichment mapping approach is used to explore the overlap of gene membership between significant gene sets, revealing a number of shared mechanisms.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics
Genome-Wide Association Study
Genotype
Motor Neurons

@article {pmid36613659,
year = {2022},
author = {Ciuro, M and Sangiorgio, M and Leanza, G and Gulino, R},
title = {A Meta-Analysis Study of SOD1-Mutant Mouse Models of ALS to Analyse the Determinants of Disease Onset and Progression.},
journal = {International journal of molecular sciences},
volume = {24},
number = {1},
pages = {},
pmid = {36613659},
issn = {1422-0067},
mesh = {Mice ; Animals ; *Amyotrophic Lateral Sclerosis/pathology ; Superoxide Dismutase-1/genetics/therapeutic use ; Superoxide Dismutase/genetics ; Mice, Transgenic ; Mutation ; Disease Models, Animal ; Disease Progression ; },
abstract = {A complex interaction between genetic and external factors determines the development of amyotrophic lateral sclerosis (ALS). Epidemiological studies on large patient cohorts have suggested that ALS is a multi-step disease, as symptom onset occurs only after exposure to a sequence of risk factors. Although the exact nature of these determinants remains to be clarified, it seems clear that: (i) genetic mutations may be responsible for one or more of these steps; (ii) other risk factors are probably linked to environment and/or to lifestyle, and (iii) compensatory plastic changes taking place during the ALS etiopathogenesis probably affect the timing of onset and progression of disease. Current knowledge on ALS mechanisms and therapeutic targets, derives mainly from studies involving superoxide dismutase 1 (SOD1) transgenic mice; therefore, it would be fundamental to verify whether a multi-step disease concept can also be applied to these animal models. With this aim, a meta-analysis study has been performed using a collection of primary studies (n = 137), selected according to the following criteria: (1) the studies should employ SOD1 transgenic mice; (2) the studies should entail the presence of a disease-modifying experimental manipulation; (3) the studies should make use of Kaplan-Meier plots showing the distribution of symptom onset and lifespan. Then, using a subset of this study collection (n = 94), the effects of treatments on key molecular mechanisms, as well as on the onset and progression of disease have been analysed in a large population of mice. The results are consistent with a multi-step etiopathogenesis of disease in ALS mice (including two to six steps, depending on the particular SOD1 mutation), closely resembling that observed in patient cohorts, and revealed an interesting relationship between molecular mechanisms and disease manifestation. Thus, SOD1 mouse models may be considered of high predictive value to understand the determinants of disease onset and progression, as well as to identify targets for therapeutic interventions.},
}

Mice
Animals
*Amyotrophic Lateral Sclerosis/pathology
Superoxide Dismutase-1/genetics/therapeutic use
Superoxide Dismutase/genetics
Mice, Transgenic
Mutation
Disease Models, Animal
Disease Progression

@article {pmid36504126,
year = {2023},
author = {Gautam, AS and Pulivarthi, CB and Singh, RK},
title = {Proinflammatory IL-17 levels in serum/cerebrospinal fluid of patients with neurodegenerative diseases: a meta-analysis study.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {396},
number = {3},
pages = {577-588},
pmid = {36504126},
issn = {1432-1912},
mesh = {Humans ; *Neurodegenerative Diseases ; *Alzheimer Disease ; *Amyotrophic Lateral Sclerosis ; Interleukin-17 ; Leukocytes, Mononuclear ; *Parkinson Disease ; Cytokines ; *Multiple Sclerosis ; },
abstract = {IL-17 is one of the major proinflammatory cytokine implicated in the pathophysiology of various chronic inflammatory diseases. However, a clear association between the levels of IL-17 and various neurodegenerative diseases is inconclusive due to lack of consistent results reported in several studies. Therefore, we designed and performed a meta-analysis study to assess the levels of IL-17 cytokine in various neurodegenerative diseases. The aim of this meta-analysis study was to assess the level of IL-17 in cerebrospinal fluid/serum of the patients with neurodegenerative diseases such as Alzheimer's disease, Parkinson disease, multiple sclerosis, and amyotrophic lateral sclerosis. An extensive search was performed on electronic databases including PubMed, Cochrane, and Google Scholar to find out the relevant studies for analysis. The quality of selected studies was assessed by Newcastle-Ottawa scale for cohort and case control studies. The standardized mean difference of level of IL-17 in patients with neurodegenerative diseases and control was calculated using RevMan 5 software. A significant increase in the level of serum IL-17 was found to in the patients with neurodegenerative diseases like Alzheimer's disease (p = 0.001) and amyotrophic lateral sclerosis (p = 0.009), whereas IL-17 level in serum of Parkinson's disease (p = 0.22), multiple sclerosis (p = 0.09), and in peripheral blood mononuclear cells of MS patients (p = 0.34) was not found to be significant. IL-17 may be involved in regulation of neuronal inflammation during the pathogenesis of these neurodegenerative disease, and its specific inhibition could be a potential therapeutic target.},
}

Humans
*Neurodegenerative Diseases
*Alzheimer Disease
*Amyotrophic Lateral Sclerosis
Interleukin-17
Leukocytes, Mononuclear
*Parkinson Disease
Cytokines
*Multiple Sclerosis

@article {pmid36460467,
year = {2023},
author = {Janse van Mantgem, MR and van Rheenen, W and Hackeng, AV and van Es, MA and Veldink, JH and van den Berg, LH and van Eijk, RPA},
title = {Association Between Serum Lipids and Survival in Patients With Amyotrophic Lateral Sclerosis: A Meta-analysis and Population-Based Study.},
journal = {Neurology},
volume = {100},
number = {10},
pages = {e1062-e1071},
pmid = {36460467},
issn = {1526-632X},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism ; Genome-Wide Association Study ; Triglycerides ; Cholesterol, HDL ; Biomarkers ; },
abstract = {BACKGROUND AND OBJECTIVE: To explore the association between lipids, polygenic profile scores (PPS) for biomarkers of lipid metabolism, markers of disease severity, and survival in patients with amyotrophic lateral sclerosis (ALS).

METHODS: We meta-analyzed the current literature on the prognostic value of lipids in patients with ALS. Subsequently, we evaluated the relationship between lipid levels at diagnosis, clinical disease stage, and survival in all consecutive patients diagnosed in the Netherlands. We determined the hazard ratio (HR) of each lipid for overall survival, defined as death from any cause. A subset of patients was matched to a previous genome-wide association study; data were used to calculate PPS for biomarkers of lipid metabolism and to determine the association between observed lipid levels at diagnosis and survival.

RESULTS: Meta-analysis of 4 studies indicated that none of the biomarkers of the lipid metabolism were statistically significantly associated with overall survival; there was, however, considerable heterogeneity between study results. Using individual patient data (N = 1,324), we found that increased high-density lipoprotein (HDL) cholesterol was associated with poorer survival (HR of 1.33 (95% CI 1.14-1.55, p < 0.001)). The correlation between BMI and HDL cholesterol (Pearson r -0.26, 95% CI -0.32 to -0.20) was negative and between BMI and triglycerides (TG) positive (Pearson r 0.18, 95% CI 0.12-0.24). Serum concentrations of total cholesterol and LDL cholesterol were lower in more advanced clinical stages (both p < 0.001). PPS for biomarkers of lipid metabolism explained 1.2%-13.1% of their variance at diagnosis. None of the PPS was significantly associated with survival (all p > 0.50).

DISCUSSION: Lipids may contain valuable information about disease severity and prognosis, but their main value may be driven as a consequence of disease progression. Our results underscore that gaining further insight into lipid metabolism and longitudinal data on serum concentrations of the lipid profile could improve the monitoring of patients and potentially further disentangle ALS pathogenesis.},
}

Humans
*Amyotrophic Lateral Sclerosis/metabolism
Genome-Wide Association Study
Triglycerides
Cholesterol, HDL
Biomarkers

@article {pmid36252825,
year = {2022},
author = {Román-Caballero, R and Lupiáñez, J},
title = {Suggestive but not conclusive: An independent meta-analysis on the auditory benefits of learning to play a musical instrument. Commentary on.},
journal = {Neuroscience and biobehavioral reviews},
volume = {142},
number = {},
pages = {104916},
doi = {10.1016/j.neubiorev.2022.104916},
pmid = {36252825},
issn = {1873-7528},
mesh = {Humans ; *Music ; Auditory Perception ; Learning ; },
abstract = {The literature on musical training suggests benefits of this activity on auditory skills (i.e., near transfer) and general cognitive abilities (i.e., far transfer). However, other positions have taken those results more skeptically, rather arguing that studies with positive outcomes suffer from methodological issues that impede inferences of causality. In the context of this debate, we conducted an independent meta-analysis similar to one recently published by Neves et al.'s, also showing auditory benefits of musical training. Our meta-analysis suggests that the available evidence is not sufficient to reach firm conclusions as interventions with design-quality features (randomization and active control) are still scarce. Moreover, the reviewed studies measured auditory skills with tests based on same/different judgments that rely on short-term memory, therefore being less sensitive to changes produced by musicmaking experiences. Although the evidence is not conclusive, the results are in line with those observed with other cognitively stimulating activities and suggest a positive impact of musical training on auditory skills. Thus, the available evidence does not support extreme versions of skepticism.},
}

Humans
*Music
Auditory Perception
Learning

@article {pmid36116424,
year = {2022},
author = {Lu, WZ and Lin, HA and Hou, SK and Lee, CF and Bai, CH and Lin, SF},
title = {Split-hand index for amyotrophic lateral sclerosis diagnosis: A frequentist and Bayesian meta-analysis.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {143},
number = {},
pages = {56-66},
doi = {10.1016/j.clinph.2022.08.020},
pmid = {36116424},
issn = {1872-8952},
mesh = {*Amyotrophic Lateral Sclerosis/diagnosis ; Bayes Theorem ; Hand ; Humans ; Muscle, Skeletal ; ROC Curve ; },
abstract = {OBJECTIVE: Preferential wasting of the thenar muscles, the split-hand sign, may be used for early diagnosis of amyotrophic lateral sclerosis (ALS).

METHODS: Electronic databases were searched for studies assessing the split-hand index (SHI) and the compound muscle action potential (CMAP) amplitudes of abductor pollicis brevis (APB), first dorsal interosseous (FDI), and abductor digiti minimi (ADM). The SHI was obtained by multiplying CMAP amplitudes of APB and FDI and dividing the product by the CMAP amplitude of ADM. The Bayesian analysis was used for validation.

RESULTS: In total, 17 studies and 1635 patients were included. Our meta-analysis revealed that ALS patients had significantly decreased SHI (standardized mean difference [SMD], -1.60, P < 0.001), CMAP of the APB (SMD, -1.67, P < 0.001), FDI (SMD, -1.12, P < 0.001), and ADM (SMD, -1.09, P < 0.001). The binormal receiver operating characteristic curve analysis showed a threshold of < 7.4 for SHI, and cutoff values of < 6.4 mV for APB and < 8.4 mV for FDI, respectively. The Bayesian analysis validated decreased SHI in ALS patients (posterior mean difference of - 5.91).

CONCLUSIONS: An SHI of < 7.4 can be used facilitating earlier diagnosis of ALS.

SIGNIFICANCE: SHI can be used as a standard neurophysiological biomarker for early diagnosis.},
}

*Amyotrophic Lateral Sclerosis/diagnosis
Bayes Theorem
Hand
Humans
Muscle, Skeletal
ROC Curve

@article {pmid35946434,
year = {2022},
author = {Cao, MC and Scotter, EL},
title = {Transcriptional targets of amyotrophic lateral sclerosis/frontotemporal dementia protein TDP-43 - meta-analysis and interactive graphical database.},
journal = {Disease models & mechanisms},
volume = {15},
number = {9},
pages = {},
pmid = {35946434},
issn = {1754-8411},
mesh = {*Amyotrophic Lateral Sclerosis/pathology ; DNA-Binding Proteins/genetics/metabolism ; *Frontotemporal Dementia/genetics/pathology ; Humans ; RNA ; },
abstract = {TDP-43 proteinopathy is the major pathology in amyotrophic lateral sclerosis (ALS) and tau-negative frontotemporal dementia (FTD). Mounting evidence implicates loss of normal TDP-43 RNA-processing function as a key pathomechanism. However, the RNA targets of TDP-43 differ by report, and have never been formally collated or compared between models and disease, hampering understanding of TDP-43 function. Here, we conducted re-analysis and meta-analysis of publicly available RNA-sequencing datasets from six TDP-43-knockdown models, and TDP-43-immunonegative neuronal nuclei from ALS/FTD brain, to identify differentially expressed genes (DEGs) and differential exon usage (DEU) events. There was little overlap in DEGs between knockdown models, but PFKP, STMN2, CFP, KIAA1324 and TRHDE were common targets and were also differentially expressed in TDP-43-immunonegative neurons. DEG enrichment analysis revealed diverse biological pathways including immune and synaptic functions. Common DEU events in human datasets included well-known targets POLDIP3 and STMN2, and novel targets EXD3, MMAB, DLG5 and GOSR2. Our interactive database (https://www.scotterlab.auckland.ac.nz/research-themes/tdp43-lof-db/) allows further exploration of TDP-43 DEG and DEU targets. Together, these data identify TDP-43 targets that can be exploited therapeutically or used to validate loss-of-function processes. This article has an associated First Person interview with the first author of the paper.},
}

*Amyotrophic Lateral Sclerosis/pathology
DNA-Binding Proteins/genetics/metabolism
*Frontotemporal Dementia/genetics/pathology
Humans
RNA

@article {pmid35820692,
year = {2022},
author = {de Jong, VMT and Rousset, RZ and Antonio-Villa, NE and Buenen, AG and Van Calster, B and Bello-Chavolla, OY and Brunskill, NJ and Curcin, V and Damen, JAA and Fermín-Martínez, CA and Fernández-Chirino, L and Ferrari, D and Free, RC and Gupta, RK and Haldar, P and Hedberg, P and Korang, SK and Kurstjens, S and Kusters, R and Major, RW and Maxwell, L and Nair, R and Naucler, P and Nguyen, TL and Noursadeghi, M and Rosa, R and Soares, F and Takada, T and van Royen, FS and van Smeden, M and Wynants, L and Modrák, M and , and Asselbergs, FW and Linschoten, M and , and Moons, KGM and Debray, TPA},
title = {Clinical prediction models for mortality in patients with covid-19: external validation and individual participant data meta-analysis.},
journal = {BMJ (Clinical research ed.)},
volume = {378},
number = {},
pages = {e069881},
pmid = {35820692},
issn = {1756-1833},
mesh = {*COVID-19 ; Data Analysis ; Hospital Mortality ; Humans ; *Models, Statistical ; Prognosis ; },
abstract = {OBJECTIVE: To externally validate various prognostic models and scoring rules for predicting short term mortality in patients admitted to hospital for covid-19.

DESIGN: Two stage individual participant data meta-analysis.

SETTING: Secondary and tertiary care.

PARTICIPANTS: 46 914 patients across 18 countries, admitted to a hospital with polymerase chain reaction confirmed covid-19 from November 2019 to April 2021.

DATA SOURCES: Multiple (clustered) cohorts in Brazil, Belgium, China, Czech Republic, Egypt, France, Iran, Israel, Italy, Mexico, Netherlands, Portugal, Russia, Saudi Arabia, Spain, Sweden, United Kingdom, and United States previously identified by a living systematic review of covid-19 prediction models published in The BMJ, and through PROSPERO, reference checking, and expert knowledge.

Prognostic models identified by the living systematic review and through contacting experts. A priori models were excluded that had a high risk of bias in the participant domain of PROBAST (prediction model study risk of bias assessment tool) or for which the applicability was deemed poor.

METHODS: Eight prognostic models with diverse predictors were identified and validated. A two stage individual participant data meta-analysis was performed of the estimated model concordance (C) statistic, calibration slope, calibration-in-the-large, and observed to expected ratio (O:E) across the included clusters.

MAIN OUTCOME MEASURES: 30 day mortality or in-hospital mortality.

RESULTS: Datasets included 27 clusters from 18 different countries and contained data on 46 914patients. The pooled estimates ranged from 0.67 to 0.80 (C statistic), 0.22 to 1.22 (calibration slope), and 0.18 to 2.59 (O:E ratio) and were prone to substantial between study heterogeneity. The 4C Mortality Score by Knight et al (pooled C statistic 0.80, 95% confidence interval 0.75 to 0.84, 95% prediction interval 0.72 to 0.86) and clinical model by Wang et al (0.77, 0.73 to 0.80, 0.63 to 0.87) had the highest discriminative ability. On average, 29% fewer deaths were observed than predicted by the 4C Mortality Score (pooled O:E 0.71, 95% confidence interval 0.45 to 1.11, 95% prediction interval 0.21 to 2.39), 35% fewer than predicted by the Wang clinical model (0.65, 0.52 to 0.82, 0.23 to 1.89), and 4% fewer than predicted by Xie et al's model (0.96, 0.59 to 1.55, 0.21 to 4.28).

CONCLUSION: The prognostic value of the included models varied greatly between the data sources. Although the Knight 4C Mortality Score and Wang clinical model appeared most promising, recalibration (intercept and slope updates) is needed before implementation in routine care.},
}

*COVID-19
Data Analysis
Hospital Mortality
Humans
*Models, Statistical
Prognosis

@article {pmid35789175,
year = {2022},
author = {Walsh, CJ and Batt, J and Herridge, MS and Mathur, S and Bader, GD and Hu, P and Khatri, P and Dos Santos, CC},
title = {Comprehensive multi-cohort transcriptional meta-analysis of muscle diseases identifies a signature of disease severity.},
journal = {Scientific reports},
volume = {12},
number = {1},
pages = {11260},
pmid = {35789175},
issn = {2045-2322},
support = {MOP-137002//CIHR/Canada ; MOP-106545//CIHR/Canada ; },
mesh = {*Amyotrophic Lateral Sclerosis/genetics ; Cohort Studies ; Humans ; *Muscular Diseases/genetics ; Quadriceps Muscle ; Severity of Illness Index ; },
abstract = {Muscle diseases share common pathological features suggesting common underlying mechanisms. We hypothesized there is a common set of genes dysregulated across muscle diseases compared to healthy muscle and that these genes correlate with severity of muscle disease. We performed meta-analysis of transcriptional profiles of muscle biopsies from human muscle diseases and healthy controls. Studies obtained from public microarray repositories fulfilling quality criteria were divided into six categories: (i) immobility, (ii) inflammatory myopathies, (iii) intensive care unit (ICU) acquired weakness (ICUAW), (iv) congenital muscle diseases, (v) chronic systemic diseases, (vi) motor neuron disease. Patient cohorts were separated in discovery and validation cohorts retaining roughly equal proportions of samples for the disease categories. To remove bias towards a specific muscle disease category we repeated the meta-analysis five times by removing data sets corresponding to one muscle disease class at a time in a "leave-one-disease-out" analysis. We used 636 muscle tissue samples from 30 independent cohorts to identify a 52 gene signature (36 up-regulated and 16 down-regulated genes). We validated the discriminatory power of this signature in 657 muscle biopsies from 12 additional patient cohorts encompassing five categories of muscle diseases with an area under the receiver operating characteristic curve of 0.91, 83% sensitivity, and 85.3% specificity. The expression score of the gene signature inversely correlated with quadriceps muscle mass (r = -0.50, p-value = 0.011) in ICUAW and shoulder abduction strength (r = -0.77, p-value = 0.014) in amyotrophic lateral sclerosis (ALS). The signature also positively correlated with histologic assessment of muscle atrophy in ALS (r = 0.88, p-value = 1.62 × 10[-3]) and fibrosis in muscular dystrophy (Jonckheere trend test p-value = 4.45 × 10[-9]). Our results identify a conserved transcriptional signature associated with clinical and histologic muscle disease severity. Several genes in this conserved signature have not been previously associated with muscle disease severity.},
}

*Amyotrophic Lateral Sclerosis/genetics
Cohort Studies
Humans
*Muscular Diseases/genetics
Quadriceps Muscle
Severity of Illness Index

@article {pmid35703478,
year = {2022},
author = {Li, Z and Zheng, Y and Li, D and Wang, X and Cheng, S and Luo, X and Wen, A},
title = {Low-Dose NOACs Versus Standard-Dose NOACs or Warfarin on Efficacy and Safety in Asian Patients with NVAF: A Meta-Analysis.},
journal = {Anatolian journal of cardiology},
volume = {26},
number = {6},
pages = {424-433},
pmid = {35703478},
issn = {2149-2271},
mesh = {Administration, Oral ; Anticoagulants/therapeutic use ; *Atrial Fibrillation/complications ; Gastrointestinal Hemorrhage/complications/drug therapy ; Humans ; Intracranial Hemorrhages/complications/drug therapy ; *Stroke/complications/prevention & control ; Treatment Outcome ; Warfarin/therapeutic use ; },
abstract = {BACKGROUND: The meta-analysis of randomized controlled trials has illustrated that the efficacy of low-dose non-vitamin K antagonist oral anticoagulants is inferior compared with standard-dose non-vitamin K antagonist oral anticoagulants, though they are still frequently prescribed for Asian patients with non-valvular atrial fibrillation. We aimed to further investigate the efficacy and safety of low-dose non-vitamin K antagonist oral anticoagulants by carrying out a meta-analysis of all relevant randomized controlled tri- als and cohort studies.

METHODS: Cochrane Central Register of Controlled Trials, Embase, and MEDLINE were sys- tematically searched from the inception to September 9, 2021, for randomized controlled trials or cohorts that compared the efficacy and/or safety of low-dose non-vitamin K antagonist oral anticoagulants in Asian patients with non-valvular atrial fibrillation. The primary outcomes were stroke and major bleeding, and the secondary outcomes were mortality, intracranial hemorrhage, and gastrointestinal hemorrhage. Hazard ratios and 95% CIs were estimated using the random-effect model.

RESULTS: Nineteen publications involving 371 574 Asian patients with non-valvular atrial fibrillation were included. Compared with standard-dose non-vitamin K antagonist oral anticoagulants, low-dose non-vitamin K antagonist oral anticoagulants showed compa- rable risks of stroke (hazard ratio, 1.18; 95% CI 0.98 to 1.42), major bleeding (hazard ratio, 1.00; 95% CI 0.83 to 1.21), intracranial hemorrhage (hazard ratio, 1.13; 95% CI 0.92 to 1.38), and gastrointestinal hemorrhage (hazard ratio, 1.07; 95% CI 0.87 to 1.31), though had a higher risk of mortality (hazard ratio, 1.34; 95% CI 1.05 to 1.71). Compared with warfarin, low-dose non-vitamin K antagonist oral anticoagulants were associated with lower risks of stroke (hazard ratio, 0.73; 95% CI 0.67 to 0.79), mortality (hazard ratio, 0.69; 95% CI 0.60 to 0.81), major bleeding (hazard ratio, 0.62; 95% CI 0.51 to 0.75), intracranial hemor- rhage (hazard ratio, 0.48; 95% CI 0.33 to 0.69), and gastrointestinal hemorrhage (hazard ratio, 0.78; 95% CI 0.65 to 0.93).

CONCLUSION: Low-dose non-vitamin K antagonist oral anticoagulants were superior to warfarin, and comparable to standard-dose non-vitamin K antagonist oral anticoagu- lants considering risks of stroke, major bleeding, intracranial hemorrhage, and gastroin- testinal hemorrhage. Further, high qualified studies are warranted.},
}

Administration, Oral
Anticoagulants/therapeutic use
*Atrial Fibrillation/complications
Gastrointestinal Hemorrhage/complications/drug therapy
Humans
Intracranial Hemorrhages/complications/drug therapy
*Stroke/complications/prevention & control
Treatment Outcome
Warfarin/therapeutic use

@article {pmid35363117,
year = {2023},
author = {Medrano, NW and Villarreal, CL and Mann, NC and Price, MA and Nolte, KB and MacKenzie, EJ and Bixby, P and Eastridge, BJ and , },
title = {Activation and On-Scene Intervals for Severe Trauma EMS Interventions: An Analysis of the NEMSIS Database.},
journal = {Prehospital emergency care},
volume = {27},
number = {1},
pages = {46-53},
doi = {10.1080/10903127.2022.2053615},
pmid = {35363117},
issn = {1545-0066},
mesh = {Humans ; Databases, Factual ; *Emergency Medical Services ; Information Systems ; Retrospective Studies ; Time Factors ; },
abstract = {Objective: Time to care is a determinant of trauma patient outcomes, and timely delivery of trauma care to severely injured patients is critical in reducing mortality. Numerous studies have analyzed access to care using prehospital intervals from a Carr et al. meta-analysis of studies from 1975 to 2005. Carr et al.'s research sought to determine national mean activation and on-scene intervals for trauma patients using contemporary emergency medical services (EMS) records. Since the Carr et al. meta-analysis was published, the National Highway Traffic Safety Administration (NHTSA) created and refined the National Emergency Medical Services Information System (NEMSIS) database. We sought to perform a modern analysis of prehospital intervals to establish current standards and temporal patterns.Methods: We utilized NEMSIS to analyze EMS data of trauma patients from 2016 to 2019. The dataset comprises more than 94 million EMS records, which we filtered to select for severe trauma and stratified by type of transport and rurality to calculate mean activation and on-scene intervals. Furthermore, we explored the impact of basic life support (BLS) and advanced life support (ALS) of ground units on activation and on-scene time intervals.Results: Mean activation and on-scene intervals for ground transport were statistically different when stratified by rurality. Urban, suburban, and rural ground activation intervals were 2.60 ± 3.94, 2.88 ± 3.89, and 3.33 ± 4.58 minutes, respectively. On-scene intervals were 15.50 ± 10.46, 17.56 ± 11.27, and 18.07 ± 16.13 minutes, respectively. Mean helicopter transport activation time was 13.75 ± 7.44 minutes and on-scene time was 19.42 ± 16.09 minutes. This analysis provides an empirically defined mean for activation and on-scene times for trauma patients based on transport type and rurality. Results from this analysis proved to be significantly longer than the previous analysis, except for helicopter transport on-scene time. Shorter mean intervals were seen in ALS compared to BLS for activation intervals, however ALS on-scene intervals were marginally longer than BLS.Conclusions: With the increasing sophistication of geospatial technologies employed to analyze access to care, these intervals are the most accurate and up-to-date and should be included in access to care models.},
}

Humans
Databases, Factual
*Emergency Medical Services
Information Systems
Retrospective Studies
Time Factors

@article {pmid35264038,
year = {2022},
author = {Erazo, D and Luna, J and Preux, PM and Medina, MT and Magne, J and Boumediene, F and Couratier, P},
title = {Amyotrophic lateral sclerosis mortality rates in Latin America and the Caribbean: a meta-analysis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {23},
number = {7-8},
pages = {608-619},
doi = {10.1080/21678421.2022.2048310},
pmid = {35264038},
issn = {2167-9223},
mesh = {Humans ; Latin America/epidemiology ; *Amyotrophic Lateral Sclerosis/epidemiology ; Ethnicity ; Caribbean Region ; Europe ; },
abstract = {Background: Recent studies have described a low occurrence of Amyotrophic Lateral Sclerosis (ALS) in Latin America. Significant differences in ALS risk have been reported among ethnic populations in the region. We conducted a meta-analysis using population-based data to describe ALS mortality rates in Latin America. We explored sources of heterogeneity among key covariates.Methods: National mortality registries from Latin American countries were searched to identify ALS deaths according to the International Classification of Diseases (ICD-9: code 335.2 and ICD-10: code G12.2). Crude and standardized mortality rates were calculated. A random-effect meta-analysis was conducted to estimate pooled mortality rates. Subgroup analysis was performed as a means of investigating heterogeneity.Results: Overall, 28,548 ALS deaths and 819 million person-years of follow-up (PYFU) from ten Latin American countries were considered. Standardized mortality varied among countries. The highest mortality rates were observed in Uruguay and Costa Rica at 1.3 and 1.2 per 100,000 PYFU, respectively. The pooled crude mortality rate was 0.38 (95%CI: 0.28-0.53) and the pooled standardized mortality was 0.62 (95%CI: 0.49-0.77) per 100,000 PYFU. Heterogeneity was high (I2: 99.9%, Cochran's Q p < 0.001). Subgroup analysis showed a higher mortality rate among countries with a higher proportion of Caucasian populations and higher income levels.Conclusion: There is a lower ALS occurrence in Latin America compared to Europe and North America. This meta-analysis supports the hypothesis of a higher ALS risk among the Caucasian population. Further studies are needed to investigate the role of ancestral origins in ALS, taking socioeconomic status into consideration.},
}

Humans
Latin America/epidemiology
*Amyotrophic Lateral Sclerosis/epidemiology
Ethnicity
Caribbean Region
Europe

@article {pmid35179485,
year = {2022},
author = {Lidborg, LH and Cross, CP and Boothroyd, LG},
title = {A meta-analysis of the association between male dimorphism and fitness outcomes in humans.},
journal = {eLife},
volume = {11},
number = {},
pages = {},
pmid = {35179485},
issn = {2050-084X},
mesh = {*Choice Behavior ; Female ; Humans ; Male ; Masculinity ; *Sex Characteristics ; Sexual Behavior ; Testosterone ; },
abstract = {Humans are sexually dimorphic: men and women differ in body build and composition, craniofacial structure, and voice pitch, likely mediated in part by developmental testosterone. Sexual selection hypotheses posit that, ancestrally, more 'masculine' men may have acquired more mates and/or sired more viable offspring. Thus far, however, evidence for either association is unclear. Here, we meta-analyze the relationships between six masculine traits and mating/reproductive outcomes (96 studies, 474 effects, N = 177,044). Voice pitch, height, and testosterone all predicted mating; however, strength/muscularity was the strongest and only consistent predictor of both mating and reproduction. Facial masculinity and digit ratios did not significantly predict either. There was no clear evidence for any effects of masculinity on offspring viability. Our findings support arguments that strength/muscularity may be sexually selected in humans, but cast doubt regarding selection for other forms of masculinity and highlight the need to increase tests of evolutionary hypotheses outside of industrialized populations.},
}

*Choice Behavior
Female
Humans
Male
Masculinity
*Sex Characteristics
Sexual Behavior
Testosterone

@article {pmid35169211,
year = {2022},
author = {Zhang, L and Tang, L and Huang, T and Fan, D},
title = {Association between type 2 diabetes and amyotrophic lateral sclerosis.},
journal = {Scientific reports},
volume = {12},
number = {1},
pages = {2544},
pmid = {35169211},
issn = {2045-2322},
mesh = {Amyotrophic Lateral Sclerosis/*epidemiology ; Case-Control Studies ; Diabetes Mellitus, Type 2/*epidemiology ; Genome-Wide Association Study ; Humans ; },
abstract = {Type 2 diabetes (T2D) and amyotrophic lateral sclerosis (ALS) are associated consistently. However, it is currently unknown whether this association is causal. We aimed to estimate the unconfounded, causal association between T2D on ALS using a two-sample Mendelian randomization approach both in European and East Asian ancestry. Genetic variants strongly associated with T2D and each T2D markers were used to investigate the effect of T2D on ALS risk in European (involving 20,806 ALS cases and 59,804 controls) and East Asian (involving 1234 ALS cases and 2850 controls) ancestry. We found that the OR of ALS per 1 SD increase in T2D was estimated to be 0.96 [95% confidence interval (CI) 0.92-0.996; p = 0.03] in European populations. Similarly, all 8 SNPs were associated with T2D in East Asian ancestry, the OR of ALS per 1 SD increase in T2D was estimated to be 0.83 [95% CI 0.70-0.992; p = 0.04] in East Asian populations. Examining the intercept estimates from MR-Egger regression also leads to the same conclusion, in that horizontal pleiotropy unlikely influences the results in either population. We found that genetically predicted T2D was associated with significantly lower odds of amyotrophic lateral sclerosis both in European and East Asian populations. It is now critical to identify a clear molecular explanation for this association between T2D and ALS and to focus on its potential therapeutic implications.},
}

Amyotrophic Lateral Sclerosis/*epidemiology
Case-Control Studies
Diabetes Mellitus, Type 2/*epidemiology
Genome-Wide Association Study
Humans

@article {pmid34963663,
year = {2022},
author = {Ziff, OJ and Clarke, BE and Taha, DM and Crerar, H and Luscombe, NM and Patani, R},
title = {Meta-analysis of human and mouse ALS astrocytes reveals multi-omic signatures of inflammatory reactive states.},
journal = {Genome research},
volume = {32},
number = {1},
pages = {71-84},
pmid = {34963663},
issn = {1549-5469},
support = {MR/S006591/1/MRC_/Medical Research Council/United Kingdom ; MR/L016311/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; 103760/Z/14/Z/WT_/Wellcome Trust/United Kingdom ; MR/M02492X/1/MRC_/Medical Research Council/United Kingdom ; FC010110/CRUK_/Cancer Research UK/United Kingdom ; },
mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; Animals ; Astrocytes/metabolism ; Disease Models, Animal ; Humans ; *Induced Pluripotent Stem Cells ; Mice ; Mice, Transgenic ; Motor Neurons/metabolism ; Mutation ; },
abstract = {Astrocytes contribute to motor neuron death in amyotrophic lateral sclerosis (ALS), but whether they adopt deleterious features consistent with inflammatory reactive states remains incompletely resolved. To identify inflammatory reactive features in ALS human induced pluripotent stem cell (hiPSC)-derived astrocytes, we examined transcriptomics, proteomics, and glutamate uptake in VCP-mutant astrocytes. We complemented this by examining other ALS mutations and models using a systematic meta-analysis of all publicly-available ALS astrocyte sequencing data, which included hiPSC-derived astrocytes carrying SOD1, C9orf72, and FUS gene mutations as well as mouse ALS astrocyte models with SOD1[G93A] mutation, Tardbp deletion, and Tmem259 (also known as membralin) deletion. ALS astrocytes were characterized by up-regulation of genes involved in the extracellular matrix, endoplasmic reticulum stress, and the immune response and down-regulation of synaptic integrity, glutamate uptake, and other neuronal support processes. We identify activation of the TGFB, Wnt, and hypoxia signaling pathways in both hiPSC and mouse ALS astrocytes. ALS changes positively correlate with TNF, IL1A, and complement pathway component C1q-treated inflammatory reactive astrocytes, with significant overlap of differentially expressed genes. By contrasting ALS changes with models of protective reactive astrocytes, including middle cerebral artery occlusion and spinal cord injury, we uncover a cluster of genes changing in opposing directions, which may represent down-regulated homeostatic genes and up-regulated deleterious genes in ALS astrocytes. These observations indicate that ALS astrocytes augment inflammatory processes while concomitantly suppressing neuronal supporting mechanisms, thus resembling inflammatory reactive states and offering potential therapeutic targets.},
}

*Amyotrophic Lateral Sclerosis/genetics/metabolism
Animals
Astrocytes/metabolism
Disease Models, Animal
Humans
*Induced Pluripotent Stem Cells
Mice
Mice, Transgenic
Motor Neurons/metabolism
Mutation

@article {pmid34874217,
year = {2022},
author = {Sferruzza, G and Bosco, L and Falzone, YM and Russo, T and Domi, T and Quattrini, A and Filippi, M and Riva, N},
title = {Neurofilament light chain as a biological marker for amyotrophic lateral sclerosis: a meta-analysis study.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {23},
number = {5-6},
pages = {446-457},
doi = {10.1080/21678421.2021.2007952},
pmid = {34874217},
issn = {2167-9223},
mesh = {*Amyotrophic Lateral Sclerosis/diagnosis ; Biomarkers ; Enzyme-Linked Immunosorbent Assay ; Humans ; Intermediate Filaments ; Neurofilament Proteins ; },
abstract = {Aim: The aim of the present metanalysis is to evaluate blood and CSF Neurofilament light chain (NfL) concentrations in ALS patients, compared to healthy controls, ALS mimic disorders (ALSmd) and other neurological diseases (OND), and to evaluate their diagnostic yield against ALSmd. Methods: Search engines were systematically investigated for relevant studies. A random effect model was applied to estimate the pooled standard mean difference in NfL levels between ALS and controls and a bivariate mixed-effects model was applied to estimate their diagnostic accuracy on blood and CSF. Results and conclusions: NfL CSF levels were higher in ALS compared with all other control groups. On blood, NfL levels were significantly higher in ALS patients compared with healthy controls and ALSmd. In a subgroup analysis, the use of SIMOA yielded to a better differentiation between ALS and controls on blood, compared with ELISA. Studies performed on CSF (AUC = 0.90) yielded to better diagnostic performances compared with those conducted on blood (AUC = 0.78). Further prospective investigations are needed to determine a diagnostic cutoff, exploitable in clinical practice.},
}

*Amyotrophic Lateral Sclerosis/diagnosis
Biomarkers
Enzyme-Linked Immunosorbent Assay
Humans
Intermediate Filaments
Neurofilament Proteins

@article {pmid34864363,
year = {2021},
author = {Su, WM and Cheng, YF and Jiang, Z and Duan, QQ and Yang, TM and Shang, HF and Chen, YP},
title = {Predictors of survival in patients with amyotrophic lateral sclerosis: A large meta-analysis.},
journal = {EBioMedicine},
volume = {74},
number = {},
pages = {103732},
pmid = {34864363},
issn = {2352-3964},
mesh = {Amyotrophic Lateral Sclerosis/*mortality ; Female ; Humans ; Life Style ; Male ; Prognosis ; Risk Assessment ; Survival Analysis ; Young Adult ; },
abstract = {BACKGROUND: The survival time of amyotrophic lateral sclerosis (ALS) is greatly variable and protective or risk effects of the potential survival predictors are controversial. Thus, we aim to undertake a comprehensive meta-analysis of studies investigating non-genetic prognostic and survival factors in patients with ALS.

METHODS: A search of relevant literature from PubMed, Embase, Cochrane library and other citations from 1[st] January 1966 to 1[st] December 020 was conducted. Random-effects models were conducted to pool the multivariable or adjusted hazard ratios (HR) by Stata MP 16.0. PROSPERO registration number: CRD42021256923.

FINDINGS: A total of 5717 reports were identified, with 115 studies meeting pre-designed inclusion criteria involving 55,169 ALS patients. Five dimensions, including demographic, environmental or lifestyle, clinical manifestations, biochemical index, therapeutic factors or comorbidities were investigated. Twenty-five prediction factors, including twenty non-intervenable and five intervenable factors, were associated with ALS survival. Among them, NFL (HR:3.70, 6.80, in serum and CSF, respectively), FTD (HR:2.98), ALSFRS-R change (HR:2.37), respiratory subtype (HR:2.20), executive dysfunction (HR:2.10) and age of onset (HR:1.03) were superior predictors for poor prognosis, but pLMN or pUMN (HR:0.32), baseline ALSFRS-R score (HR:0.95), duration (HR:0.96), diagnostic delay (HR:0.97) were superior predictors for a good prognosis. Our results did not support the involvement of gender, education level, diabetes, hypertension, NIV, gastrostomy, and statins in ALS survival.

INTERPRETATION: Our study provided a comprehensive and quantitative index for assessing the prognosis for ALS patients, and the identified non-intervenable or intervenable factors will facilitate the development of treatment strategies for ALS.

FUNDING: This study was supported by the National Natural Science Fund of China (Grant No. 81971188), the 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (Grant No. 2019HXFH046), and the Science and Technology Bureau Fund of Sichuan Province (No. 2019YFS0216).},
}

Amyotrophic Lateral Sclerosis/*mortality
Female
Humans
Life Style
Male
Prognosis
Risk Assessment
Survival Analysis
Young Adult

@article {pmid34726989,
year = {2022},
author = {Shi, G and Shao, S and Zhou, J and Huang, K and Bi, FF},
title = {Urinary p75[ECD] levels in patients with amyotrophic lateral sclerosis: a meta-analysis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {23},
number = {5-6},
pages = {438-445},
doi = {10.1080/21678421.2021.1990345},
pmid = {34726989},
issn = {2167-9223},
mesh = {*Amyotrophic Lateral Sclerosis/diagnosis ; Case-Control Studies ; Humans ; },
abstract = {Objective: p75 neurotrophin receptor (p75[NTR]) is associated with the pathogenesis of amyotrophic lateral sclerosis (ALS). However, its role is not fully understood. The aim of this study was to evaluate the association between ALS and the extracellular domain of p75[NTR](p75[ECD]) in urine. Methods: We conducted a comprehensive literature search using keywords in the PubMed, Embase, Science, and the Cochrane Library, and identified five case control studies, with the latest date of search being 18 April 2021. Results: The results showed that urinary p75[ECD] levels were significantly higher in patients with ALS compared to non-neurological control (weighted mean difference (WMD) = 4.18, 95% CI [2.525, 6.990], p < 0.001), and other neurological diseases (WMD = 6.005, 95% CI [1.596, 10.414], p = 0.008). Increased urinary p75[ECD] levels were inversely associated with ALSFRS-R in ALS patients (r = -0.32, 95% CI [-0.43, -0.21], p < 0.001). Conclusions: Given the associations between p75[ECD] and ALS found in this meta-analysis, urinary p75[ECD] levels have potential to be used as a diagnostic biomarker and a progression indicator in the future.},
}

*Amyotrophic Lateral Sclerosis/diagnosis
Case-Control Studies
Humans

@article {pmid34502460,
year = {2021},
author = {Fernández-Beltrán, LC and Godoy-Corchuelo, JM and Losa-Fontangordo, M and Williams, D and Matias-Guiu, J and Corrochano, S},
title = {A Transcriptomic Meta-Analysis Shows Lipid Metabolism Dysregulation as an Early Pathological Mechanism in the Spinal Cord of SOD1 Mice.},
journal = {International journal of molecular sciences},
volume = {22},
number = {17},
pages = {},
pmid = {34502460},
issn = {1422-0067},
support = {2018-T1/BMD-10731//Consejería de Educación, Juventud y Deporte, Comunidad de Madrid/ ; },
mesh = {Amyotrophic Lateral Sclerosis/etiology/*metabolism ; Animals ; Disease Models, Animal ; Female ; *Lipid Metabolism ; Mice ; Spinal Cord/*metabolism ; Steroid Hydroxylases/genetics/metabolism ; *Transcriptome ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a multifactorial and complex fatal degenerative disorder. A number of pathological mechanisms that lead to motor neuron death have been identified, although there are many unknowns in the disease aetiology of ALS. Alterations in lipid metabolism are well documented in the progression of ALS, both at the systemic level and in the spinal cord of mouse models and ALS patients. The origin of these lipid alterations remains unclear. This study aims to identify early lipid metabolic pathways altered before systemic metabolic symptoms in the spinal cord of mouse models of ALS. To do this, we performed a transcriptomic analysis of the spinal cord of SOD1[G93A] mice at an early disease stage, followed by a robust transcriptomic meta-analysis using publicly available RNA-seq data from the spinal cord of SOD1 mice at early and late symptomatic disease stages. The meta-analyses identified few lipid metabolic pathways dysregulated early that were exacerbated at symptomatic stages; mainly cholesterol biosynthesis, ceramide catabolism, and eicosanoid synthesis pathways. We present an insight into the pathological mechanisms in ALS, confirming that lipid metabolic alterations are transcriptionally dysregulated and are central to ALS aetiology, opening new options for the treatment of these devastating conditions.},
}

Amyotrophic Lateral Sclerosis/etiology/*metabolism
Animals
Disease Models, Animal
Female
*Lipid Metabolism
Mice
Spinal Cord/*metabolism
Steroid Hydroxylases/genetics/metabolism
*Transcriptome

@article {pmid34431799,
year = {2021},
author = {Mavroudis, I and Knights, M and Petridis, F and Chatzikonstantinou, S and Karantali, E and Kazis, D},
title = {Diagnostic Accuracy of Anti-CN1A on the Diagnosis of Inclusion Body Myositis. A Hierarchical Bivariate and Bayesian Meta-analysis.},
journal = {Journal of clinical neuromuscular disease},
volume = {23},
number = {1},
pages = {31-38},
doi = {10.1097/CND.0000000000000353},
pmid = {34431799},
issn = {1537-1611},
mesh = {5'-Nucleotidase ; Autoantibodies ; Bayes Theorem ; Humans ; Male ; Muscle, Skeletal ; *Myositis ; *Myositis, Inclusion Body/diagnosis ; },
abstract = {Sporadic inclusion body myositis (IBM) is an acquired muscle disease and the most common idiopathic inflammatory myopathy over the age of 50. It is characterized by male predominance, with a prevalence rate between 1 and 71 cases per million, reaching 139 cases per million over the age of 50 globally. The diagnosis of IBM is based on clinical presentation and muscle biopsy findings. However, there is increasing evidence for the role of genetics and serum biomarkers in supporting a diagnosis. Antibodies against the cytosolic 5'-nucleotidase 1A (Anti-CN1A), an enzyme catalyzing the conversion of adenosine monophosphate into adenosine and phosphate and is abundant in skeletal muscle, has been reported to be present in IBM and could be of crucial significance in the diagnosis of the disease. In this study, we investigated the diagnostic accuracy of anti-CN1A antibodies for sporadic IBM in comparison with other inflammatory myopathies, autoimmune disorders, motor neurone disease, using a hierarchical bivariate approach, and a Bayesian model taking into account the variable prevalence. The results of the present analysis show that anti-CN1A antibodies have moderate sensitivity, and despite having high specificity, they are not useful biomarkers for the diagnosis of IBM, polymyositis or dermatomyositis, other autoimmune conditions, or neuromuscular disorders. Neither the hierarchical bivariate nor the Bayesian analysis showed any significant usefulness of anti-CN1A antibodies in the diagnosis of IBM.},
}

5'-Nucleotidase
Autoantibodies
Bayes Theorem
Humans
Male
Muscle, Skeletal
*Myositis
*Myositis, Inclusion Body/diagnosis

@article {pmid34397718,
year = {2021},
author = {Chang, MC and Kwak, SG and Park, JS and Park, D},
title = {Relationship between statins and the risk of amyotrophic lateral sclerosis: A PRISMA-compliant meta-analysis.},
journal = {Medicine},
volume = {100},
number = {30},
pages = {e26751},
pmid = {34397718},
issn = {1536-5964},
support = {NRF-2019M3E5D1A02068106//National Research Foundation of Korea grand funded by the Korean government/ ; },
mesh = {Amyotrophic Lateral Sclerosis/*chemically induced ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects ; },
abstract = {OBJECTIVE: Previous studies on overlapping surveillance databases have suggested that statin use was associated with the development of amyotrophic lateral sclerosis (ALS)-like syndrome. However, the association between statin use and ALS incidence has not been clearly elucidated. To further explore this issue, we performed a systemic review and meta-analysis of all available clinical studies on the association between statin use and ALS incidence.

METHODS: A comprehensive database search on PubMed, Embase, Cochrane Library, and SCOPUS was conducted. We included studies up to January 31, 2020 that fulfilled our inclusion and exclusion criteria. Statin use between the ALS and control groups was collected for the meta-analysis.

RESULTS: Three case-control studies and 1 cohort study, that related the risk of ALS to statin use, satisfied the inclusion criteria for the meta-analysis. There was no statistically significant difference in statin use between the ALS and control groups (odds ratio, 0.75 [95% confidence interval, 0.53-1.08]).

CONCLUSION: No definite association was found between statin use and the development of ALS. Further large-scale prospective randomized control studies are necessary to draw definite conclusions.},
}

Amyotrophic Lateral Sclerosis/*chemically induced
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects

@article {pmid33706058,
year = {2021},
author = {Haji, S and Sako, W and Murakami, N and Osaki, Y and Furukawa, T and Izumi, Y and Kaji, R},
title = {The value of serum uric acid as a prognostic biomarker in amyotrophic lateral sclerosis: Evidence from a meta-analysis.},
journal = {Clinical neurology and neurosurgery},
volume = {203},
number = {},
pages = {106566},
doi = {10.1016/j.clineuro.2021.106566},
pmid = {33706058},
issn = {1872-6968},
mesh = {Amyotrophic Lateral Sclerosis/*blood/*diagnosis ; Biomarkers/blood ; Humans ; Prognosis ; Sensitivity and Specificity ; Uric Acid/*blood ; },
abstract = {OBJECTIVE: To determine the value of uric acid (UA) as a prognostic biomarker for amyotrophic lateral sclerosis (ALS) using a meta-analysis of hazard ratio-based studies.

METHODS: We included data from Tokushima University (47 patients with ALS) and three previous studies (1835 patients with ALS) with a hazard ratio (HR) identified by a systematic computational search. A total of four studies and 1882 patients were enrolled in the pooled analysis. We pooled HRs of death or tracheostomy, which were estimated by a Cox proportional hazard model, using a random-effects model. Heterogeneity was assessed by Q statistic, and a p value < 0.1 was considered significant heterogeneity. Furthermore, sensitivity analysis was performed to assess the effect of each single study and the robustness of the summary effect. We evaluated publication bias by visual assessment of the funnel plot and Egger's test, and adjusted the bias using a trim-and-fill method.

RESULTS: This meta-analysis revealed that UA could be a prognostic factor for ALS (all, HR = 0.87, p < 0.001; men, HR = 0.83, p < 0.001; women, HR = 0.76, p < 0.001). The included studies were homogeneous (all, p = 0.43; men, p = 0.9; women, p = 0.49). Sensitivity analysis confirmed the robustness of these summary effects. Publication bias was detected, which was adjusted for by a trim-and-fill method. The adjusted results showed significant summary effects (all, HR = 0.88, p = 0.002; men, HR = 0.83, p < 0.001; women, HR = 0.77, p < 0.001).

CONCLUSION: The present meta-analysis suggests that the serum UA level could be a prognostic biomarker in patients with ALS. Sensitivity analyses and the trim-and-fill method supported the robustness of these results.},
}

Amyotrophic Lateral Sclerosis/*blood/*diagnosis
Biomarkers/blood
Humans
Prognosis
Sensitivity and Specificity
Uric Acid/*blood

@article {pmid33678061,
year = {2021},
author = {Spielmans, GI},
title = {Re-Analyzing Phase III Bremelanotide Trials for "Hypoactive Sexual Desire Disorder" in Women.},
journal = {Journal of sex research},
volume = {58},
number = {9},
pages = {1085-1105},
doi = {10.1080/00224499.2021.1885601},
pmid = {33678061},
issn = {1559-8519},
mesh = {Female ; Humans ; *Libido ; Peptides, Cyclic ; *Sexual Dysfunctions, Psychological/drug therapy ; alpha-MSH ; },
abstract = {Kingsberg et al. described results from two 24-week Phase III trials of bremelanotide for treating hypoactive sexual desire disorder (HSDD) in women. 72.72% of protocol-listed outcomes were not reported by Kingsberg et al., who provided results of 15 secondary measures which were not listed in the study protocols. None of their efficacy outcomes were reported in line with CONSORT data reporting standards and no secondary outcome had a stated rationale or cited evidence of validity. My meta-analysis of the trials' data, based on the FDA New Drug Application, found similar results to Kingsberg et al. However, Kingsberg et al. did not report that a) adverse event-induced study discontinuation was substantially higher on bremelanotide: OR = 11.98, 95% CI = 3.74-38.37, NNH: 6 or b) participants preferred placebo, measured by the combination of both 1) completing a clinical trial and 2) electing to participate in the follow-up open-label study (OR = 0.30, 95% CI = .24-.38, NNH: 4). Bremelanotide's modest benefits on incompletely reported post-hoc measures of questionable validity in combination with participants substantially preferring to take placebo suggest that the drug is generally not useful. Kingsberg et al.'s data reporting and measurement practices were incomplete and lacked transparency.},
}

Female
Humans
*Libido
Peptides, Cyclic
*Sexual Dysfunctions, Psychological/drug therapy
alpha-MSH

@article {pmid33199452,
year = {2020},
author = {Shoesmith, C and Abrahao, A and Benstead, T and Chum, M and Dupre, N and Izenberg, A and Johnston, W and Kalra, S and Leddin, D and O'Connell, C and Schellenberg, K and Tandon, A and Zinman, L},
title = {Canadian best practice recommendations for the management of amyotrophic lateral sclerosis.},
journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne},
volume = {192},
number = {46},
pages = {E1453-E1468},
pmid = {33199452},
issn = {1488-2329},
mesh = {Amyotrophic Lateral Sclerosis/*therapy ; Canada ; Humans ; *Patient Care Team ; Societies, Medical ; },
}

Amyotrophic Lateral Sclerosis/*therapy
Canada
Humans
*Patient Care Team
Societies, Medical

@article {pmid33113361,
year = {2020},
author = {Iacoangeli, A and Lin, T and Al Khleifat, A and Jones, AR and Opie-Martin, S and Coleman, JRI and Shatunov, A and Sproviero, W and Williams, KL and Garton, F and Restuadi, R and Henders, AK and Mather, KA and Needham, M and Mathers, S and Nicholson, GA and Rowe, DB and Henderson, R and McCombe, PA and Pamphlett, R and Blair, IP and Schultz, D and Sachdev, PS and Newhouse, SJ and Proitsi, P and Fogh, I and Ngo, ST and Dobson, RJB and Wray, NR and Steyn, FJ and Al-Chalabi, A},
title = {Genome-wide Meta-analysis Finds the ACSL5-ZDHHC6 Locus Is Associated with ALS and Links Weight Loss to the Disease Genetics.},
journal = {Cell reports},
volume = {33},
number = {4},
pages = {108323},
pmid = {33113361},
issn = {2211-1247},
support = {ALCHALABI-DOBSON/APR14/829-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; MC_PC_17214/MRC_/Medical Research Council/United Kingdom ; MR/L501529/1/MRC_/Medical Research Council/United Kingdom ; G0600974/MRC_/Medical Research Council/United Kingdom ; AL-CHALABI/APR15/844-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; ALCHALABI-TALBOT/APR14/926-794/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/R024804/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; },
mesh = {Acyltransferases/*adverse effects ; Amyotrophic Lateral Sclerosis/*complications/genetics ; Genetic Predisposition to Disease ; Genome-Wide Association Study/*methods ; Humans ; Polymorphism, Single Nucleotide/*genetics ; Weight Loss/*genetics ; },
abstract = {We meta-analyze amyotrophic lateral sclerosis (ALS) genome-wide association study (GWAS) data of European and Chinese populations (84,694 individuals). We find an additional significant association between rs58854276 spanning ACSL5-ZDHHC6 with ALS (p = 8.3 × 10[-9]), with replication in an independent Australian cohort (1,502 individuals; p = 0.037). Moreover, B4GALNT1, G2E3-SCFD1, and TRIP11-ATXN3 are identified using a gene-based analysis. ACSL5 has been associated with rapid weight loss, as has another ALS-associated gene, GPX3. Weight loss is frequent in ALS patients and is associated with shorter survival. We investigate the effect of the ACSL5 and GPX3 single-nucleotide polymorphisms (SNPs), using longitudinal body composition and weight data of 77 patients and 77 controls. In patients' fat-free mass, although not significant, we observe an effect in the expected direction (rs58854276: -2.1 ± 1.3 kg/A allele, p = 0.053; rs3828599: -1.0 ± 1.3 kg/A allele, p = 0.22). No effect was observed in controls. Our findings support the increasing interest in lipid metabolism in ALS and link the disease genetics to weight loss in patients.},
}

Acyltransferases/*adverse effects
Amyotrophic Lateral Sclerosis/*complications/genetics
Genetic Predisposition to Disease
Genome-Wide Association Study/*methods
Humans
Polymorphism, Single Nucleotide/*genetics
Weight Loss/*genetics

@article {pmid32968195,
year = {2020},
author = {Nakamura, R and Misawa, K and Tohnai, G and Nakatochi, M and Furuhashi, S and Atsuta, N and Hayashi, N and Yokoi, D and Watanabe, H and Watanabe, H and Katsuno, M and Izumi, Y and Kanai, K and Hattori, N and Morita, M and Taniguchi, A and Kano, O and Oda, M and Shibuya, K and Kuwabara, S and Suzuki, N and Aoki, M and Ohta, Y and Yamashita, T and Abe, K and Hashimoto, R and Aiba, I and Okamoto, K and Mizoguchi, K and Hasegawa, K and Okada, Y and Ishihara, T and Onodera, O and Nakashima, K and Kaji, R and Kamatani, Y and Ikegawa, S and Momozawa, Y and Kubo, M and Ishida, N and Minegishi, N and Nagasaki, M and Sobue, G},
title = {A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis.},
journal = {Communications biology},
volume = {3},
number = {1},
pages = {526},
pmid = {32968195},
issn = {2399-3642},
mesh = {Amyotrophic Lateral Sclerosis/ethnology/*genetics ; Asian People/genetics ; Case-Control Studies ; China ; Coenzyme A Ligases/*genetics/physiology ; Female ; Genes/*genetics ; Genetic Predisposition to Disease/*genetics ; Genome-Wide Association Study ; Humans ; Japan ; Male ; Polymorphism, Single Nucleotide/genetics ; White People/genetics ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating progressive motor neuron disease that affects people of all ethnicities. Approximately 90% of ALS cases are sporadic and thought to have multifactorial pathogenesis. To understand the genetics of sporadic ALS, we conducted a genome-wide association study using 1,173 sporadic ALS cases and 8,925 controls in a Japanese population. A combined meta-analysis of our Japanese cohort with individuals of European ancestry revealed a significant association at the ACSL5 locus (top SNP p = 2.97 × 10[-8]). We validated the association with ACSL5 in a replication study with a Chinese population and an independent Japanese population (1941 ALS cases, 3821 controls; top SNP p = 1.82 × 10[-4]). In the combined meta-analysis, the intronic ACSL5 SNP rs3736947 showed the strongest association (p = 7.81 × 10[-11]). Using a gene-based analysis of the full multi-ethnic dataset, we uncovered additional genes significantly associated with ALS: ERGIC1, RAPGEF5, FNBP1, and ATXN3. These results advance our understanding of the genetic basis of sporadic ALS.},
}

Amyotrophic Lateral Sclerosis/ethnology/*genetics
Asian People/genetics
Case-Control Studies
China
Coenzyme A Ligases/*genetics/physiology
Female
Genes/*genetics
Genetic Predisposition to Disease/*genetics
Genome-Wide Association Study
Humans
Japan
Male
Polymorphism, Single Nucleotide/genetics
White People/genetics

@article {pmid32901053,
year = {2020},
author = {Chang, MC and Kwak, SG and Park, JS and Park, D},
title = {The effectiveness of nonsteroidal anti-inflammatory drugs and acetaminophen in reduce the risk of amyotrophic lateral sclerosis? A meta-analysis.},
journal = {Scientific reports},
volume = {10},
number = {1},
pages = {14759},
pmid = {32901053},
issn = {2045-2322},
mesh = {Acetaminophen/*therapeutic use ; Amyotrophic Lateral Sclerosis/metabolism/pathology/*prevention & control ; Analgesics, Non-Narcotic/*therapeutic use ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use ; Drug Therapy, Combination ; Humans ; },
abstract = {To test the hypothesis that aspirin, non-aspirin nonsteroidal anti-infammatory drugs (NA-NSAIDs), or acetaminophen can reduce the risk of ALS, we conducted a systematic review and meta-analysis of related previous studies. A comprehensive search was conducted on the PubMed, Embase, Cochrane Library and SCOPUS databases. It included studies published up to 29 February 2020 that fulfilled our inclusion criteria. Aspirin, acetaminophen and NA-NSAIDs use information, between the ALS and control groups, was collected for the meta-analysis. Rates of aspirin, NA-NSAID, and acetaminophen use in ALS group, compared with control group were investigated. In the results, only three studies that relate the risk of ALS to aspirin, NA-NSAIDs and acetaminophen use satisfied the inclusion criteria for the meta-analysis. Regarding aspirin, the studies did not show any statistically significant difference in aspirin use between the ALS and control groups (Odds ratio, 1.04 [95% confidence interval, 0.90-1.21]). NA-NSAIDs and acetaminophen use, however, did show up statistically significant differences in between the ALS and control groups. (Odds ratio, 0.82 [95% confidence interval, 0.73-0.91]) and (Odds ratio, 0.80 [95% confidence interval, 0.69-0.93]). However, our study has some limitations. Firstly, we only included a small number of studies. Secondly, the included studies did not control for past medical history, which may have confounded their results, and in turn, could have caused bias in our study. Thirdly, in this meta-analysis, the ALS patients were not subdivided into sporadic or familial type. Lastly, the studies also did not consider the types of NSAIDs and dosages used of each drug. For more convincing evidence regarding the effectiveness of aspirin, NA-NSAIDs and acetaminophen to reduce the risk of ALS occurrence, more qualified prospective studies are required. In conclusion, the use of NA-NSAIDs and acetaminophen is associated with a decreased risk for the development of ALS. In contrast, aspirin did not have any effect on the reduction of the risk of ALS occurrence.},
}

Acetaminophen/*therapeutic use
Amyotrophic Lateral Sclerosis/metabolism/pathology/*prevention & control
Analgesics, Non-Narcotic/*therapeutic use
Animals
Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use
Drug Therapy, Combination
Humans