@article {pmid41503832,
year = {2026},
author = {Tuli, S and Patel, P and Shethji, A and Gau, D},
title = {Mitochondria and the Actin Cytoskeleton in Neurodegeneration.},
journal = {Cytoskeleton (Hoboken, N.J.)},
volume = {},
number = {},
pages = {},
doi = {10.1002/cm.70095},
pmid = {41503832},
issn = {1949-3592},
support = {CA267180/NH/NIH HHS/United States ; TL1 TR001858/NH/NIH HHS/United States ; },
abstract = {Mitochondrial dysfunction and cytoskeletal disorganization are widely recognized hallmarks of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Although these disorders differ in clinical presentation and etiology, accumulating evidence points to a shared cellular vulnerability at the intersection of mitochondrial dynamics and actin cytoskeletal regulation. In this review, we examine the emerging role of actin-mitochondria crosstalk as a convergent mechanism in neurodegeneration. We discuss how disruptions in actin filament remodeling, mitochondrial fission and fusion, organelle transport, and mitophagy contribute to neuronal dysfunction and loss across these diseases. Particular attention is given to disease-specific pathways, including cofilin-actin rod formation in AD, α-synuclein-driven actin disruption in PD, mutant huntingtin's effects on mitochondrial fragmentation in HD, and profilin-1-associated mitochondrial defects in ALS. By synthesizing findings from diverse models, we highlight how perturbations in the cytoskeleton-mitochondria interface may act as an upstream trigger and amplifier of neurodegenerative cascades. We also outline key knowledge gaps and propose future directions for research, with an emphasis on targeting actin-mitochondrial interactions as a potential therapeutic strategy across multiple neurodegenerative conditions.},
}

@article {pmid41499987,
year = {2026},
author = {Poulidou, V and Tseriotis, VS and Bombaci, A and Vucic, S and Pavey, N and Papagiannopoulos, S and Kimiskidis, VK and Arnaoutoglou, M},
title = {The split elbow sign in amyotrophic lateral sclerosis: A systematic review and meta-analysis.},
journal = {Neurophysiologie clinique = Clinical neurophysiology},
volume = {56},
number = {2},
pages = {103134},
doi = {10.1016/j.neucli.2025.103134},
pmid = {41499987},
issn = {1769-7131},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) patients can exhibit split phenomena, with preferential weakness of specific muscle groups. The aim of this review is to investigate the split elbow (SE) phenomenon (different weakness/wasting pattern between biceps and triceps) as a potential clinical and neurophysiological feature in ALS.

METHODS: Our study was reported according to the PRISMA statement and registered in PROSPERO (CRD42024528359). MEDLINE, SCOPUS, Web of Science, and grey literature sources were searched using the terms "split elbow" and "amyotrophic lateral sclerosis" up to April 2025. English-written peer-reviewed, randomized, non-randomized, observational, diagnostic accuracy, and case-control studies were included. Study quality was assessed using Joanna Briggs Institute critical appraisal tool. Regarding muscle strength, we pooled the standardized mean difference of normalized Medical Research Council (MRC) scores using random effects. We used a bivariate random-effects model to evaluate SE index (SEICMAP, compound muscle action potential of biceps/triceps) in distinguishing ALS from controls.

RESULTS: Seven studies with 1941 ALS patients (61.8 % male) met inclusion criteria. Pooled standardized mean difference (triceps - biceps MRC scores) was -0.17 [95 % CI, -1.03 to 0.69], p = 0.63, indicating no significant difference in muscle strength between elbow flexion and extension. Between-study heterogeneity was high (I[2] = 97.1 % [95.5 %; 98.2 %], p < 0.0001). The SEICMAP demonstrated only moderate accuracy in distinguishing ALS from controls (pooled sensitivity, specificity, and AUC of 0.789 [0.655-0.880], 0.580 [0.487-0.668], and 0.661, respectively).

CONCLUSIONS: Current evidence does not support a consistent SE pattern in ALS. Methodological variability and small sample sizes limit the generalizability of available findings, indicating that the SE is unlikely to provide meaningful diagnostic utility in routine clinical practice.},
}

@article {pmid41498587,
year = {2026},
author = {Maskell, KG and Cook, AL and King, AE and Dickson, TC and Blizzard, CA},
title = {Modeling amyotrophic lateral sclerosis (ALS) in vitro: from mechanistic studies to translatable drug discovery.},
journal = {Lab on a chip},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5lc00577a},
pmid = {41498587},
issn = {1473-0189},
abstract = {Amyotrophic lateral sclerosis is a rapidly progressing, fatal neurodegenerative disease that causes selective degeneration of the corticomotor system. Currently, ALS remains incurable, and the available treatment options offer little in the way of extending life or improving quality of life. This is due, at least in part, to a lack of representative disease models. In vitro modeling offers rapid, experimentally accessible platforms for mechanistic discovery research and drug screening, but modeling the complexity of ALS - a multicellular, multisystem disease - in a dish, is not without its challenges. Here, we review the current landscape of in vitro pre-clinical ALS research, with emphasis on the development of compartmentalised culture and the promise this holds for translatable modeling of ALS.},
}

@article {pmid41498352,
year = {2026},
author = {Hewitt-Dean, J and Tebbutt, J and Hobson, E},
title = {The impact of motor neurone disease on oral health: a scoping review.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/21678421.2025.2603312},
pmid = {41498352},
issn = {2167-9223},
abstract = {OBJECTIVE: To identify current evidence on oral health-related quality of life in people with Motor Neurone Disease (MND), as well as identify barriers to oral health and care, and establish priorities for future research.

METHODS: A scoping review was conducted. Electronic databases and grey literature sources were searched from 2000 to 2024. Articles discussing oral health in adults with MND were included. Findings were supplemented by stakeholder consultation with people with MND, caregivers, clinicians, and researchers.

RESULTS: Fourteen articles met inclusion criteria, comprising eight cross-sectional studies, one prospective quality improvement project, one single center observational and four review articles. Five key themes emerged: dental status and oral hygiene activities, orofacial function, secretion management, service delivery and Oral health-related quality of life (OHRQoL). Studies indicated that MND negatively impacts oral health through impaired ability to perform oral hygiene and altered orofacial functioning. Only one study examined oral health-related quality of life. Stakeholder consultation highlighted additional concerns including challenges with service access, the impact of MND on oral health, and difficulties maintaining oral hygiene due to physical limitations.

CONCLUSIONS: Oral health remains an under-researched area in MND care despite its potential impact on quality of life and overall wellbeing. Future research priorities should include investigating relationships between oral health and MND outcomes, improving service delivery models, and increasing dental professional awareness. Active involvement of people with MND in research design and implementation is essential for developing effective interventions.},
}

@article {pmid41498289,
year = {2025},
author = {Ram, J and Glickman, MH},
title = {The many faces of p97/Cdc48 in mitochondrial homeostasis.},
journal = {Essays in biochemistry},
volume = {69},
number = {5},
pages = {},
doi = {10.1042/EBC20253045},
pmid = {41498289},
issn = {1744-1358},
mesh = {Humans ; *Valosin Containing Protein/metabolism/genetics ; *Mitochondria/metabolism ; *Homeostasis ; Animals ; *Adenosine Triphosphatases/metabolism/genetics ; Nuclear Proteins ; },
abstract = {Through its various roles in protein quality control, membrane dynamics, and cellular survival pathways, the AAA+ ATPase p97/valosin-containing protein emerges as a significant regulator of mitochondrial homeosta sis. This review comprehensively examines the multifaceted functions of p97 in mitochondrial biology, spanning from mitochondria-associated degradation to newly discovered functions in organellar cross-talk and disease pathogenesis. Underlying its cellular importance, p97 mutations are found in amyotrophic lateral sclerosis and frontotemporal dementia. To elucidate its mechanistic contribution to these processes, we provide a detailed table (Table 1) listing all known mitochondrial Cdc48/p97 substrates and associ ated proteins, categorized by their respective pathways. Recruitment to most of these substrates occurs by specialized adaptors, including Doa1/phospholipase A-2-activating protein, UBXD8, and UBXN1. p97 orchestrates the extraction and proteasomal degradation of outer mitochondrial membrane proteins, which are essential for maintaining mitochondrial integrity. For example, by controlling the turnover of fusion factors MFN1/2 and fission machinery, p97 regulates mitochondrial dynamics. p97 also governs apoptotic signaling through the regulated degradation of anti-apoptotic factors, such as myeloid cell leukemia-1 and VDAC, thereby modulating mitochondrial permeability. In mitophagy, p97 enables the clearance of damaged organelles by extracting ubiquitinated substrates and recruiting autophagy machinery. Beyond proteolysis, p97 facilitates recycling of endoplasmic reticulum-mitochondria contact sites through regulation of UBXD8-dependent lipid metabolism. Recent discoveries have revealed p97's involvement in pathogen host interactions and circular RNA-mediated regulation, thereby expanding our understanding of its cellular functions. The emerging picture positions p97 as an integrative hub co-ordinating mitochondrial protein homeostasis, organellar dynamics, and cell fate decisions, with therapeutic potential for metabolic and neurodegenerative disorders.},
}

Humans
*Valosin Containing Protein/metabolism/genetics
*Mitochondria/metabolism
*Homeostasis
Animals
*Adenosine Triphosphatases/metabolism/genetics
Nuclear Proteins

@article {pmid41498281,
year = {2026},
author = {Santamaria, MP and Mathias-Santamaria, IF and Tavelli, L and Barootchi, S and Prato, GPP},
title = {An updated evidence-based recommendation for the treatment of gingival recession associated with non-carious cervical lesions.},
journal = {Journal of periodontology},
volume = {},
number = {},
pages = {},
doi = {10.1002/jper.70049},
pmid = {41498281},
issn = {1943-3670},
abstract = {BACKGROUND: Approximately 50% of the gingival recessions (GRs) are associated with non-carious cervical lesions (NCCLs), forming what are known as combined defects (CDs), which often require specific treatment protocols that differ from those used for GRs on teeth with an intact and sound surface. This narrative review aims to evaluate the current and relevant literature on the treatment of CDs and update the latest decision-making process with the new literature.

METHODS: Medline/PubMed, Embase, BIREME, and Google Scholar databases were searched. The NCCL portion of the CDs was classified according to Pini-Prato et al.'s classification (2010). The GR portion of the CDs was classified according to Cairo et al.'s classification (2011) and gingival phenotype. Based on these, a decision tree, supported by the current literature, was proposed.

RESULTS: Several approaches associating different surgical techniques/graft materials with different NCCL restoration protocols and materials are available. When A-, A+, and B- NCCL are present, only a surgical procedure for root coverage is needed based on GR characteristics. When either B+ or V-shaped NCCL is present, a composite restorative protocol and a root coverage procedure should be considered.

CONCLUSIONS: CDs are characterized by the coexistence of gingival recession and a non-carious cervical lesion. This updated decision-making process incorporated current literature, including new evidence on soft tissue grafts, which can guide clinicians in the treatment of CDs.

PLAIN LANGUAGE SUMMARY: Gum recession often occurs alongside defects in the tooth that are not caused by cavities. These two conditions can appear on the same tooth in about half of the cases. When that happens, treatment becomes more complex and requires careful planning. Choosing the best approach depends on the shape and severity of the tooth defect. This recommendation helps dentists and patients understand how to manage these combined problems. Most cases fall into mild categories (A-, A+, and B-; i.e., shallow tooth defects) and can be treated with standard procedures for gum recession alone. However, about 25% of cases have a more advanced defect (B+; i.e., deep tooth defects), which requires both a tooth restoration and gum surgery. The way gum recession is treated also depends on how thick the gum tissue is. If the tissue is thin, using the patient's own tissue for a graft usually gives the best results. If the tissue is already thick, a graft may not be necessary. In moderate cases, a graft using either patient tissue or commercial materials can improve long-term success. This recommendation summarizes the latest research and provides practical guidance to improve treatment outcomes for both patients and clinicians.},
}

@article {pmid41496184,
year = {2026},
author = {Portaro, S and Latella, D and Manuli, A and Calderone, A and Calabrò, RS},
title = {Bridging the gap in sexuality and neuromuscular disorders: a scoping review of an overlooked but crucial topic.},
journal = {Sexual medicine reviews},
volume = {14},
number = {1},
pages = {},
doi = {10.1093/sxmrev/qeaf076},
pmid = {41496184},
issn = {2050-0521},
support = {//Current Research Funds 2024-2025/ ; //Ministry of Health, Italy/ ; },
mesh = {Humans ; *Neuromuscular Diseases/psychology ; *Quality of Life/psychology ; *Sexuality/psychology ; *Sexual Dysfunction, Physiological/psychology ; Social Stigma ; Female ; *Sexual Health ; },
abstract = {INTRODUCTION: Neuromuscular disorders (NMDs) comprise a group of conditions affecting the muscles and/or the nerves controlling them, resulting in progressive muscle weakness. Beyond the physical limitations, NMDs can significantly impact quality of life (QoL), including sexuality. Sexuality, as defined by the World Health Organization, encompasses physical, psychological, and social dimensions. However, research exploring the multifaceted impact of NMDs on sexual well-being remains limited, despite the potential influence of physical impairments, psychological distress, and social stigma.

OBJECTIVES: This scoping review aims to synthesize the existing literature on sexuality in individuals with NMDs, identifying the interplay of physical, psychological, and social factors affecting sexual QoL, highlighting research gaps, and informing future research and clinical practice.

METHODS: A scoping review was conducted using PubMed, Web of Science, Cochrane Library, Embase, and Scopus databases (up to May 15, 2025) to identify studies examining sexuality in individuals with NMDs. Studies addressing physical, psychological, and social factors influencing sexual health in NMD patients were included. Data were extracted using a standardized form and synthesized narratively. The review was registered on Open OSF (DOI https://doi.org/10.17605/OSF.IO/RP9U2).

RESULTS: Fourteen studies with various conditions such as Duchenne muscular dystrophy, amyotrophic lateral sclerosis (ALS), myotonic dystrophy type 1, myasthenia gravis, and Charcot-Marie-Tooth disease were included, from interviews to surveys. One key theme that emerged was the extent to which personal narratives reveal the emotional weight of stigma, the struggle with body image, and how intimacy is peripheral in medical institutions. In surveys, many said their sexual activity had declined, particularly among people with progressive diseases like ALS and myotonic dystrophy. Many of these studies also pointed to how sexual health was directly associated with QoL, a good reminder that it's an important aspect of well-being that we need to pay more attention to in care and support.

CONCLUSION: This scoping review highlights a significant gap in research regarding sexuality in individuals with NMDs. The limited number of studies identified underscores the need for further research to understand the complex interplay of physical, psychosocial, and social factors affecting sexual well-being in this population.},
}

Humans
*Neuromuscular Diseases/psychology
*Quality of Life/psychology
*Sexuality/psychology
*Sexual Dysfunction, Physiological/psychology
Social Stigma
Female
*Sexual Health

@article {pmid41493706,
year = {2026},
author = {Hashemi, M and Shafiei Asheghabadi, P and Moassesfar, M and Mashhadikhan, S and Nasirzade, S and Vasheghani Farahani, A and Mehdizadeh, S and Minaei, S and Rahmani, M and Jamshidian, F and Farahani, N and Reiter, RJ and Taheriazam, A and Hasani Sadi, F and Hushmandi, K and Alimohammadi, M and Rahimzadeh, P and Entezari, M},
title = {MicroRNAs and Long Non-Coding RNAs Affect the Mechanisms Involved in Age-Related Neurodegeneration in a Manner Depending on RNA-Binding Proteins.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {343},
pmid = {41493706},
issn = {1559-1182},
mesh = {Humans ; *RNA, Long Noncoding/metabolism/genetics ; *MicroRNAs/genetics/metabolism ; Animals ; *RNA-Binding Proteins/metabolism/genetics ; *Aging/genetics/pathology/metabolism ; *Neurodegenerative Diseases/genetics/metabolism/pathology ; },
abstract = {Neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), are marked by progressive neuronal loss and aberrant protein aggregation, presenting substantial global healthcare challenges. Recent research has illuminated the pivotal roles of RNA-binding proteins (RBPs) and non-coding RNAs (ncRNAs), notably microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in the molecular pathogenesis of age-related neurodegeneration. RBPs orchestrate RNA metabolism and engage extensively with miRNAs and lncRNAs to modulate gene expression at the post-transcriptional level. Dysregulation of these interactions precipitates pathological phenomena such as protein misfolding, stress granule formation, and disrupted RNA processing, thereby exacerbating neuronal dysfunction and death. Specific miRNAs have been implicated in regulating key neurodegenerative biomarkers, including tau and amyloid-β in AD, motor neuron maintenance in ALS, and survival pathways in HD. Elucidating the intricate interplay between RBPs and ncRNAs holds significant promise for the development of therapeutic strategies aimed at ameliorating RNA-mediated mechanisms in neurodegenerative disorders.},
}

Humans
*RNA, Long Noncoding/metabolism/genetics
*MicroRNAs/genetics/metabolism
Animals
*RNA-Binding Proteins/metabolism/genetics
*Aging/genetics/pathology/metabolism
*Neurodegenerative Diseases/genetics/metabolism/pathology

@article {pmid41488323,
year = {2025},
author = {Lotlikar, MS and Zellmer, JC and Bhattacharyya, R},
title = {Sigma receptors and mitochondria-associated ER membranes are converging therapeutic targets for Alzheimer's disease.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1733659},
pmid = {41488323},
issn = {1662-4548},
abstract = {Alzheimer's disease (AD) begins decades before clinical symptoms emerge. The "amyloid hypothesis" suggests that amyloid-β (Aβ) deposition initiates a cascade of tau hyperphosphorylation, neuroinflammation, and neuronal loss leading to cognitive decline. The recent success of anti-Aβ therapies such as Leqembi in prodromal or mild cognitive impaired patients underscores the importance of early intervention and Aβ clearance. However, safety and cost limitations highlight the need for alternative therapeutic strategies. Small-molecule modulators of Sigma-1 and Sigma-2 receptors (σ1R and σ2R) have emerged as promising candidates for AD treatment. σ1R agonists exhibit neuroprotective and anti-amnestic effects under pathological conditions without affecting normal cognition. Beyond AD, σ1R is implicated in several neurodegenerative diseases including ALS (amyotrophic lateral sclerosis), Parkinson's, and Huntington's diseases, stroke, and epilepsy. σ1R plays a key role at mitochondria-associated ER membranes (MAMs)-specialized lipid raft-like domains that form functional membrane contact sites between the endoplasmic reticulum (ER) and mitochondria. β-secretase (BACE1), γ-secretase, and their substrates APP and palmitoylated APP (palAPP) localize in the MAMs, promoting amyloidogenic Aβ production. MAMs serve as dynamic hubs for inter-organelle communication, calcium signaling, and lipid metabolism. The "MAM hypothesis" proposes that MAM dysregulation drives early AD pathology and persists throughout disease progression, contributing to neurofibrillary tangle formation, calcium imbalance, and neuroinflammation. This review aims to summarize the current understanding of σ1R-mediated regulation of MAMs and its neuroprotective mechanisms, highlighting potential therapeutic opportunities for targeting σ1R in AD and other neurodegenerative disorders.},
}

@article {pmid41481411,
year = {2026},
author = {Ortholand, J and Gensollen, N and Durrleman, S and Du Montcel, ST},
title = {Joint model with latent disease age: Overcoming the need for reference time.},
journal = {Statistical methods in medical research},
volume = {},
number = {},
pages = {9622802251399917},
doi = {10.1177/09622802251399917},
pmid = {41481411},
issn = {1477-0334},
abstract = {Heterogeneity of the progression of neurodegenerative diseases is one of the main challenges faced in developing therapies. Thanks to the increasing number of clinical databases, progression models have allowed a better understanding of this heterogeneity. Joint models have proven their effectiveness by combining longitudinal and survival data. Nevertheless, they require a reference time, which is ill-defined for neurodegenerative diseases, where biological underlying processes start before the first symptoms. In this work, we propose a joint non-linear mixed-effect model with a latent disease age, to overcome this need for a precise reference time. We used a longitudinal model with a latent disease age as a longitudinal sub-model. We associated it with a survival sub-model that estimates a Weibull distribution from the latent disease age. We validated our model on simulated data and benchmarked it with a state-of-the-art joint model on data from patients with Amyotrophic Lateral Sclerosis (ALS). Finally, we showed how the model could be used to describe ALS heterogeneity. Our model got significantly better results than the state-of-the-art joint model for absolute bias on ALS functional rating scale revised score (4.21(SD 4.41) versus 4.24(SD 4.14)(p-value=1.4×10-17)), and mean-cumulative-AUC for right-censored events on death (0.67(0.07) versus 0.61(0.09)(p-value=1.7×10-03)). To conclude, we propose a new model better suited in the context of unreliable reference time.},
}

@article {pmid41480618,
year = {2025},
author = {Hu, G and Gogzheyan, C and Panja, S and Sil, S and Gendelman, HE},
title = {Extracellular vesicle-based therapies for neurodegenerative diseases.},
journal = {NeuroImmune pharmacology and therapeutics},
volume = {4},
number = {4},
pages = {377-390},
pmid = {41480618},
issn = {2750-6665},
abstract = {Extracellular vesicles (EVs) are mediators of neurodegeneration and emerging therapeutic tools for central nervous system disorders. On the one hand, they help spread beta amyloid, tau, α-synuclein, TDP-43, and mutant SOD1, contributing to the signs and symptoms of Alzheimer's, Parkinson's, Amyotrophic lateral sclerosis, and Huntington's Diseases. By activating glial cells, they promote chronic neuroinflammation through carrying cytokines, inflammasomes, and chemokines. On the other hand, EVs' ability to transport neuroregulatory products and cross the blood-brain barrier makes them ideal vehicles for drug delivery. Their function can be surface-modified to deliver targeted therapies, including anti-inflammatory and neuroprotective regulatory RNAs, proteins, and lipids, as well as factors that help maintain neural homeostasis. Notably, we suggest that colostrum-derived EVs, enriched with growth factors and immune-regulatory microRNAs, offer a natural, scalable, and biocompatible source for neuroprotective treatment. Although EVs can act as "Janus-faced" entities - serving both as disease initiators and versatile therapeutic vehicles - controlling their activity can enable immune-based therapeutics for neurodegenerative diseases.},
}

@article {pmid41479097,
year = {2026},
author = {Stamatelopoulos, D and Papakonstantinou, E and Bacopoulou, F and Vlachakis, D},
title = {Polyphenols from Olive Oil: A Promising Therapeutic Approach for Neurodegenerative Diseases.},
journal = {Advances in experimental medicine and biology},
volume = {1490},
number = {},
pages = {343-349},
pmid = {41479097},
issn = {0065-2598},
mesh = {*Olive Oil/chemistry/therapeutic use ; Humans ; *Polyphenols/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology ; *Neuroprotective Agents/therapeutic use ; Animals ; Oxidative Stress/drug effects ; Antioxidants/therapeutic use ; Diet, Mediterranean ; Anti-Inflammatory Agents/therapeutic use ; },
abstract = {Neurodegenerative diseases such as Alzheimer's, Parkinson's, ALS, and Huntington's disease pose a growing global health challenge due to their prevalence in aging populations and their devastating impact on cognitive and motor functions. Current treatments focus on symptom management, with no options available to reverse neuronal damage. Emerging evidence highlights the potential role of extra virgin olive oil (EVOO) polyphenols in neuroprotection, particularly in the context of the Mediterranean diet, which is associated with lower rates of neurodegenerative disorders. EVOO's rich polyphenolic compounds, including hydroxytyrosol, oleuropein, tyrosol, and oleocanthal, exhibit potent antioxidant, anti-inflammatory, and neuroprotective properties. These bioactive molecules have shown potential in modulating disease-specific pathways, such as reducing oxidative stress, inhibiting abnormal protein aggregation, and regulating neuroinflammation. This paper explores the therapeutic potential of olive oil polyphenols for neurodegenerative diseases, detailing their mechanisms of action across different conditions. Our findings suggest that incorporating EVOO into dietary and medical interventions could serve as a promising strategy for mitigating neurodegenerative disease progression and enhancing cognitive health.},
}

*Olive Oil/chemistry/therapeutic use
Humans
*Polyphenols/therapeutic use/pharmacology
*Neurodegenerative Diseases/drug therapy/metabolism/pathology
*Neuroprotective Agents/therapeutic use
Animals
Oxidative Stress/drug effects
Antioxidants/therapeutic use
Diet, Mediterranean
Anti-Inflammatory Agents/therapeutic use

@article {pmid40990470,
year = {2026},
author = {Siu, MC and Selinopoulou, M and Abarca Salazar, S and Sturgeon, JP and Huynh, J and Basu Roy, R},
title = {Diagnostic Performance of Host-based Gene Expression Diagnostics in Children With Extrapulmonary Tuberculosis: A Systematic Review.},
journal = {The Pediatric infectious disease journal},
volume = {45},
number = {2},
pages = {140-146},
doi = {10.1097/INF.0000000000004998},
pmid = {40990470},
issn = {1532-0987},
mesh = {Humans ; Child ; *Tuberculosis/diagnosis/genetics ; Child, Preschool ; Adolescent ; Sensitivity and Specificity ; Infant ; Mycobacterium tuberculosis/genetics ; *Gene Expression Profiling ; Infant, Newborn ; Tuberculosis, Extrapulmonary ; },
abstract = {BACKGROUND: Diagnosing extrapulmonary tuberculosis (EPTB) in children is challenging due to nonspecific presentations and poor diagnostic yield from conventional microbiologic tests. Host gene expression signatures offer a non-sputum-based diagnostic alternative. This systematic review evaluates their diagnostic performance in pediatric EPTB.

METHODS: We systematically reviewed host-based gene expression diagnostics for pediatric EPTB. PubMed, Embase and Cochrane Library (January 1965-May 2025) were searched for studies in children (0-18 years) with EPTB. Exclusions were adult-only studies, mixed data on pulmonary TB and EPTB without disaggregation, pulmonary TB-only studies, reviews and abstracts. Two reviewers screened data, resolving disagreements by discussion.

RESULTS: Of 830 records, 2 studies met the inclusion criteria: Pan et al. (2017) and Olbrich et al. (2024), both in low and middle-income countries, enrolling a total of 891 children under 15 years. Olbrich et al.'s 3-gene MTB-HR prototype showed 59.8% sensitivity against a strict culture-confirmed reference standard and 50.0% in isolated EPTB with a low risk of bias. Using a microbiologic, clinical and radiologic composite standard, Pan et al.'s miRNA-29a assay achieved 67.2% sensitivity, 88.5% specificity in peripheral blood mononuclear cells; 81.1% sensitivity, 90.0% specificity in cerebrospinal fluid; 84.4% sensitivity, 95.4% specificity in combined peripheral blood mononuclear cell/cerebrospinal fluid with a high risk of bias.

CONCLUSIONS: Evidence for host gene expression diagnostics in pediatric EPTB is limited by few studies, small sample sizes, bias and lack of disaggregated data, with accuracy falling short of the World Health Organization targets.},
}

Humans
Child
*Tuberculosis/diagnosis/genetics
Child, Preschool
Adolescent
Sensitivity and Specificity
Infant
Mycobacterium tuberculosis/genetics
*Gene Expression Profiling
Infant, Newborn
Tuberculosis, Extrapulmonary

@article {pmid40631493,
year = {2026},
author = {Li, W and Gillies, RM and Sun, H and Khan, A},
title = {Career indecision among medical students: A scoping review of contributing sources, associated factors, and support strategies.},
journal = {Medical teacher},
volume = {48},
number = {1},
pages = {42-60},
doi = {10.1080/0142159X.2025.2520927},
pmid = {40631493},
issn = {1466-187X},
mesh = {Humans ; *Students, Medical/psychology ; *Career Choice ; *Decision Making ; Self Efficacy ; Adaptation, Psychological ; },
abstract = {BACKGROUND: While career indecision is well-studied in vocational psychology, its application in medical education remains limited. This scoping review examined sources of indecision, associated factors, and strategies to support medical students' career decision-making.

METHODS: A systematic search of PubMed, Scopus, CINAHL, and ERIC identified relevant studies published from January 2014 to December 2024. Two reviewers independently screened articles and data were charted. Eligible articles were synthesised using directed qualitative content analysis with inductive expansion, guided by Kulcsár et al.'s career decision-making taxonomy.

RESULTS: Ninety-three studies were included. Most studies focused on the career aspect of specialty selection. Career decision-making difficulties were categorised into Readiness (dysfunctional beliefs, career decision-making self-efficacy, willingness, general indecisiveness), Lack of Information (about self, about world of work, about how to make career decisions) and Use of Information (unreliable information, internal conflicts, external conflicts). Personal coping strategies and institutional support recommendations were identified. Influencing factors included demographics, personal traits, educational experiences, attitudes, and macro-level disruptions.

CONCLUSIONS: This review maps medical students' career decision-making difficulties to a structured framework and outlines support strategies and influencing factors. Findings underscore the value of integrating career psychology into medical education and addressing structural barriers to better support students' career development.},
}

Humans
*Students, Medical/psychology
*Career Choice
*Decision Making
Self Efficacy
Adaptation, Psychological

@article {pmid39871563,
year = {2025},
author = {Guo, J and Liu, XY and Yang, SS and Li, Q and Duan, Y and Zhu, SS and Zhou, K and Yan, YZ and Zeng, P},
title = {Roles of C/EBPβ/AEP in Neurodegenerative Diseases.},
journal = {Current topics in medicinal chemistry},
volume = {25},
number = {20},
pages = {2440-2452},
pmid = {39871563},
issn = {1873-4294},
support = {82301506//National Natural Science Foundation of China/ ; 220XQD090//Research Foundation of Scientific Research Program of University of South China/ ; 2023JJ40560//Provincial Natural Science Foundation of Hunan/ ; S202410555234, S202410555259, S202410555262//Science and Technology Innovation Project for College Students/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/metabolism/drug therapy/pathology ; *CCAAT-Enhancer-Binding Protein-beta/metabolism/antagonists & inhibitors/chemistry ; Animals ; Small Molecule Libraries/chemistry/pharmacology ; },
abstract = {In recent years, an increasing number of studies have shown that increased activation of aspartic endopeptidases (AEPs) is a common symptom in neurodegenerative diseases (NDDs). AEP cleaves amyloid precursor protein (APP), tau (microtubule-associated protein tau), α- synuclein (α-syn), SET (a 39-KDa phosphoprotein widely expressed in various tissues and localizes predominantly in the nucleus), and TAR DNA-binding protein 43 (TDP-43), and promotes their aggregation, contributing to Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) pathogenesis. Abundant evidence supports the notion that CCAAT/enhancer-binding protein β (C/EBPβ)/AEP may play an important role in NDDs. Developing its small molecule inhibitors is a promising treatment of NDDs. However, current research suggests that the pathophysiological mechanism of the C/EBPβ/AEP pathway is very complex in NDDs. This review summarizes the structure of C/EBPβ and AEP, their major physiological functions, potential pathogenesis, their small molecule inhibitors, and how C/EBPβ/AEP offers a novel pathway for the treatment of NDDs.},
}

Humans
*Neurodegenerative Diseases/metabolism/drug therapy/pathology
*CCAAT-Enhancer-Binding Protein-beta/metabolism/antagonists & inhibitors/chemistry
Animals
Small Molecule Libraries/chemistry/pharmacology

@article {pmid41477139,
year = {2025},
author = {Syamal, M},
title = {Treatment of Neurogenic Voice Disorders.},
journal = {World journal of otorhinolaryngology - head and neck surgery},
volume = {11},
number = {4},
pages = {541-547},
pmid = {41477139},
issn = {2589-1081},
abstract = {This overview serves as a foundational resource for clinicians caring for neurologically complex patients presenting with voice complaints. Neurogenic voice disorders are diverse in their clinical presentations and therapeutic approaches. A thorough medical history, including family history, detailed laryngeal examination, voice assessments, and neuroimaging, are imperative, as well as a multidisciplinary, collaborative approach with neurologists, speech language pathologists, and patient caregivers. Disorders such as amyotrophic lateral sclerosis (ALS), cerebrovascular accidents (strokes), Huntington's disease, myasthenia gravis (MG), Parkinson's disease (PD), and voice tremor should be understood by otolaryngologists. Each condition presents unique challenges and requires tailored treatment strategies ranging from supportive therapies and pharmacological interventions to surgery. Voice management techniques, including the use of botulinum toxin for hyperkinetic disorders and deep brain stimulation for refractory cases, are highlighted as promising interventions.},
}

@article {pmid41476438,
year = {2025},
author = {Oza, R},
title = {Physical Activity as an Intervention for Frailty Syndrome: A Narrative Review.},
journal = {Cureus},
volume = {17},
number = {12},
pages = {e100293},
pmid = {41476438},
issn = {2168-8184},
abstract = {Frailty is a geriatric syndrome characterised by a decline in functional reserves as the body ages, resulting in increased disability, comorbidity, and mortality. With trends towards ageing populations, frailty syndrome becomes more clinically relevant, highlighting the importance of appropriately preventing and managing the characteristics of frailty syndrome. Risk factor modification is recommended to delay or prevent the onset of frailty, including physical activity alongside other modifiable behaviours such as diet. Ageing is associated with chronic low-grade inflammation, resulting in reduced muscle protein synthesis and increased resistance to insulin, which both contribute to sarcopenia. Sarcopenia underpins key characteristics of frailty, including weakness and slow speed. Physical activity stimulates anabolic pathways and improves insulin resistance, reducing sarcopenia. Moreover, aerobic exercise is responsible for increasing the VO2 peak, whilst resistance exercise improves muscle strength, both of which are known to decrease in frail elders. This narrative review primarily explored the effectiveness of physical activity in reducing the risk of the onset of frailty syndrome through a narrative review of the relevant literature concerning this subject. A secondary focus of this narrative review is to compare the success of alternative interventions for preventing frailty, relative to physical activity. Physical activity interventions have been shown to improve components of frailty scoring and selected biological markers of frailty, with evidence suggesting physical activity is an effective single-domain intervention for frailty; however, multidomain approaches may result in a greater overall improvement in frailty prevention. Further research is required to identify the types of exercise that modify specific aspects of Fried et al.'s frailty criteria (FFC), as well as what interventions can be used alongside physical activity, to holistically treat all characteristics of frailty syndrome.},
}

@article {pmid37827930,
year = {2023},
author = {Cassereau, J and Bernard, E and Genestet, S and Chebbah, M and Le Clanche, S and Verschueren, A and Couratier, P},
title = {Management of amyotrophic lateral sclerosis in clinical practice: Results of the expert consensus using the Delphi methodology.},
journal = {Revue neurologique},
volume = {179},
number = {10},
pages = {1134-1144},
doi = {10.1016/j.neurol.2023.07.011},
pmid = {37827930},
issn = {0035-3787},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/therapy ; Riluzole/therapeutic use ; Motor Neurons ; Diagnosis, Differential ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a rare disease characterized by a progressive and irreversible degeneration of upper and lower motor neurons leading to death. In France, limited data exist describing the criteria used in clinical practice for diagnosis and follow-up, and how novel therapies may fit in. The objective of this Delphi panel was to obtain an overview of current French practices in ALS diagnosis, management, and follow-up by determining the scales and criteria used in clinical practice outside of clinical trials, as well as the place of a future treatment like AMX0035, acting on endoplasmic reticulum (ER) stress and mitochondrial dysfunction, in the current therapeutic strategies. A questionnaire was administered to 24 ALS healthcare providers practicing in ALS centers in France. Two rounds of remote voting were organized, before proposition of final consensus statements. Consensus was considered reached when at least 66% of the voters agreed. Consensus were obtained to define the new Gold Coast criteria as the ones used in clinical practice to establish the diagnosis of ALS, thus replacing the revised El Escorial criteria, considered too complex and now mainly used to characterize the patient populations to be included in clinical trials. The clinical factors considered to establish ALS diagnosis are mainly the demonstration of progression of the motor deficit and elimination of differential diagnoses. The ALSFRS-R scale is used in daily clinical practice to assess patient's functional impairment in terms of number of points lost, with the bulbar, respiratory, and fine motor subscores being the most important to evaluate independently. A critical medical need was identified regarding the provision of new therapeutic alternatives in ALS. The panel members would support the earliest management of patients. In this landscape, based on data from a very encouraging phase II (Centaur trial), AMX0035 represents a new tool of choice in current treatment strategies for all patients for whom experts are confident in the diagnosis of ALS, in combination with riluzole. These results will need to be confirmed by the ongoing phase III trial (Phoenix trial).},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/therapy
Riluzole/therapeutic use
Motor Neurons
Diagnosis, Differential

@article {pmid41471389,
year = {2025},
author = {Gershoni Emek, N and Tan, AM and Geva, M and Fekete, A and Abate, C and Hayden, MR},
title = {Pridopidine, a Potent and Selective Therapeutic Sigma-1 Receptor (S1R) Agonist for Treating Neurodegenerative Diseases.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {12},
pages = {},
pmid = {41471389},
issn = {1424-8247},
abstract = {Pridopidine is a highly selective sigma-1 receptor (S1R) agonist in clinical development for Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). The S1R is a ubiquitous chaperone protein enriched in the central nervous system and regulates multiple pathways critical for neuronal cell function and survival, including cellular stress responses, mitochondrial function, calcium signaling, protein folding, and autophagy. S1R has a crucial role in the ER mitochondria-associated membrane (MAM), whose dysfunction is implicated in several neurodegenerative diseases. By activating the S1R, pridopidine corrects multiple cellular pathways necessary to the cell's ability to respond to stress, which are disrupted in neurodegenerative diseases. Pridopidine restores MAM integrity; rescues Ca[2+] homeostasis and autophagy; mitigates ER stress, mitochondrial dysfunction, and oxidative damage; and enhances brain-derived neurotrophic factor (BDNF) axonal transport and secretion, synaptic plasticity, and dendritic spine density. Pridopidine demonstrates neuroprotective effects in in vivo models of neurodegenerative diseases (NDDs). Importantly, pridopidine demonstrates the biphasic dose response characteristic of S1R agonists. In clinical trials in HD and ALS, pridopidine has shown benefits across multiple endpoints. Pridopidine's mechanism of action, modulating core cellular survival pathways, positions it as a promising candidate for disease modification for different nervous system disorders. Its broad therapeutic potential includes neurodevelopmental disorders, and rare diseases including Wolfram syndrome, Rett syndrome, and Vanishing White Matter Disease. Here, we review the experimental data demonstrating pridopidine's S1R-mediated neuroprotective effects. These findings underscore the therapeutic relevance of S1R activation and support further investigation of pridopidine for the treatment of different neurodegenerative diseases including ALS and HD.},
}

@article {pmid41468784,
year = {2025},
author = {Palanivel, V and Salkar, A and Shenoy, A and Eva, TA and Perera, R and Chitranshi, N and Gupta, V and You, Y and Mirzaei, M and Graham, SL and Gupta, V and Basavarajappa, D},
title = {Neuropeptide Y at the crossroads of neurodegeneration: Mechanistic insights and emerging therapeutic strategies.},
journal = {Neuropeptides},
volume = {115},
number = {},
pages = {102583},
doi = {10.1016/j.npep.2025.102583},
pmid = {41468784},
issn = {1532-2785},
abstract = {Neuropeptide Y (NPY), a widely distributed and highly conserved neuropeptide, plays a central role in the regulation of diverse physiological processes, including stress responses, energy homeostasis, vascular tone, and immune modulation, via activation of its receptor subtypes. Beyond its physiological roles, the dysregulation of NPY expression has been documented in several neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Machado-Joseph disease, and retinal disorders such as diabetic retinopathy and glaucoma. These alterations in NPY levels and receptor activity highlight its potential not only as a biomarker for disease progression but also as a promising therapeutic target. Previous evidence revealed that NPY exerts neuroprotection by alleviating excitotoxicity, oxidative stress, mitochondrial dysfunction, and neuroinflammation while concurrently facilitating neurogenesis, synaptic plasticity, and cellular resilience. NPY activates receptor-mediated intracellular signaling cascades like PI3K/Akt, MAPK/ERK, and p38K, that control cellular survival, proteostasis, and inflammation and thereby influence disease trajectories. Understanding NPY operation with these mechanisms can unveil new avenues for targeted therapy. Current insights into the complex roles of NPY in neurodegeneration are discussed in this review, and their implications in diagnostic and treatment strategies are addressed.},
}

@article {pmid41465514,
year = {2025},
author = {Riku, Y and Brion, JP and Ando, K and Uchihara, T and Iwasaki, Y},
title = {The Determinant of Tau Spreading in Alzheimer's Disease: Dependent on Senile Plaque, Neural Circuits, or Spatial Proximity?.},
journal = {International journal of molecular sciences},
volume = {26},
number = {24},
pages = {},
pmid = {41465514},
issn = {1422-0067},
support = {JPMH23FC1008//MHLW Research on rare and intractable diseases Program/ ; 23K06935, 25K22597, and 25K10781//JSPS-KAKENHI/ ; },
mesh = {Humans ; *Alzheimer Disease/metabolism/pathology ; *tau Proteins/metabolism ; *Plaque, Amyloid/metabolism/pathology ; Animals ; Neurofibrillary Tangles/metabolism/pathology ; Amyloid beta-Peptides/metabolism ; Brain/metabolism/pathology ; },
abstract = {Alzheimer's disease (AD) is neuropathologically characterized by tau-immunopositive neurofibrillary tangles (NFTs) and amyloid-β (Aβ)-immunopositive senile plaques. According to the widely accepted amyloid cascade hypothesis, Aβ pathology represents the upstream event in AD pathophysiology and induces tau aggregation. However, numerous studies have suggested that tau aggregates correlate more closely with neuronal loss and regional brain atrophy than with Aβ depositions. Tau aggregation in AD demonstrates a hierarchical spreading pattern beginning in the transentorhinal cortex, but the mechanisms underlying this spreading manner of lesions remain to be elucidated. This review aims to address current controversies regarding tau pathology in AD from the perspectives of both the 'amyloid cascade' and 'tauopathy' hypotheses. From the 'amyloid cascade' viewpoint, Aβ deposition prominently involves distal axon and axon terminals, and in some regions, there are anatomical correspondences between axonal Aβ pathology and cytoplasmic tau aggregations (e.g., a close relationship between senile plaques in the molecular layer of the hippocampal dentate gyrus and NFTs in the transentorhinal cortex). Nevertheless, this model cannot explain the whole body of hierarchical spreading of tau aggregation because notable spaciotemporal discrepancies also exist in many regions. From the 'tauopathy' perspective, the distribution of tau aggregates in AD involves key nodes within the memory circuits. Also, experimental studies have suggested that patient-derived tau exhibits seeding and neuron-to-neuron propagation properties. Interestingly, tau aggregation in AD appears to spread laterally in a proximity-dependent, cortico-cortical fashion rather than along long-range memory circuits. This contrasts with the system-selective, poly-nodal degenerations seen in four-repeat tauopathies, amyotrophic lateral sclerosis, or spinocerebellar degenerations. Moreover, the proportions of three-repeat and four-repeat isoforms shift during the maturation of NFTs in AD. Overall, spreading patterns of tau-pathology in AD cannot be fully explained by Aβ pathology and also differ from the system degeneration seen in other tauopathies.},
}

Humans
*Alzheimer Disease/metabolism/pathology
*tau Proteins/metabolism
*Plaque, Amyloid/metabolism/pathology
Animals
Neurofibrillary Tangles/metabolism/pathology
Amyloid beta-Peptides/metabolism
Brain/metabolism/pathology

@article {pmid41065069,
year = {2026},
author = {Shan, Y and Jing, W and Zhang, H and Liu, Y and Wei, S and Wu, F and Pan, W},
title = {Amyotrophic lateral sclerosis rehabilitation management and non-pharmacological symptomatic treatment: A review.},
journal = {International journal of clinical pharmacology and therapeutics},
volume = {64},
number = {1},
pages = {38-46},
doi = {10.5414/CP204744},
pmid = {41065069},
issn = {0946-1965},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/rehabilitation/physiopathology/diagnosis/psychology/therapy ; Quality of Life ; Treatment Outcome ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that lacks effective treatment options for the prevention of progression. Relieving swallowing difficulties, reducing breathing difficulties, and alleviating muscle spasms are essential to improving the quality of life in patients with ALS. Many symptoms can be treated clinically with medication; however, the evidence level of related research is relatively low. Rehabilitation management can aid in improving various functional impairments and enhancing quality of life. This review introduces and describes the relevant evaluations of rehabilitation and nonpharmacological symptomatic treatment methods for functional disorders from the perspectives of motor and nonmotor symptoms. This review may promote the popularization of ALS rehabilitation management and provide an additional reference for ALS treatment.},
}

Humans
*Amyotrophic Lateral Sclerosis/rehabilitation/physiopathology/diagnosis/psychology/therapy
Quality of Life
Treatment Outcome

@article {pmid41465278,
year = {2025},
author = {Marzetti, E and Di Lorenzo, R and Calvani, R and Coelho-Júnior, HJ and Landi, F and Pesce, V and Picca, A},
title = {Linking Cell Architecture to Mitochondrial Signaling in Neurodegeneration: The Role of Intermediate Filaments.},
journal = {International journal of molecular sciences},
volume = {26},
number = {24},
pages = {},
pmid = {41465278},
issn = {1422-0067},
support = {D1.2024//Università Cattolica del Sacro Cuore/ ; D1.2025//Università Cattolica del Sacro Cuore/ ; Ricerca Corrente 2025//Italian Ministry of Health/ ; DM 1557 11.10.2022//European Commission/ ; 2022YNENP3//Italian Ministry of University and Research/ ; },
mesh = {Humans ; *Mitochondria/metabolism/pathology ; Animals ; *Neurodegenerative Diseases/metabolism/pathology ; *Intermediate Filaments/metabolism/pathology ; *Signal Transduction ; Neurons/metabolism/pathology ; },
abstract = {Mitochondrial dysfunction is a pivotal contributor to neurodegeneration. Neurons heavily rely on mitochondrial oxidative metabolism and therefore need highly efficient quality control mechanisms, including proteostasis, mitochondrial biogenesis, fusion-fission dynamics, and mitophagy, to sustain bioenergetics and synaptic function. With aging, deterioration of mitochondrial quality control pathways leads to impaired oxidative phosphorylation, excessive reactive oxygen species generation, calcium imbalance, and defective clearance of damaged organelles, ultimately compromising neuronal viability. Pathological protein aggregates, such as α-synuclein in Parkinson's disease, β-amyloid and tau in Alzheimer's disease, and misfolded superoxide dismutase 1 and transactive response DNA-binding protein 43 in amyotrophic lateral sclerosis, further aggravate mitochondrial stress, establishing self-perpetuating cycles of neurotoxicity. Such mitochondrial defects underscore mitochondria as a convergent pathogenic hub and a promising therapeutic target for neuroprotection. Intermediate filaments (IFs), traditionally viewed as passive structural elements, have recently gained attention for their roles in cytoplasmic organization, mitochondrial positioning, and energy regulation. Emerging evidence indicates that IF-mitochondria interactions critically influence organelle morphology and function in neurons. This review highlights the multifaceted involvement of mitochondrial dysfunction and IF dynamics in neurodegeneration, emphasizing their potential as targets for novel therapeutic strategies.},
}

Humans
*Mitochondria/metabolism/pathology
Animals
*Neurodegenerative Diseases/metabolism/pathology
*Intermediate Filaments/metabolism/pathology
*Signal Transduction
Neurons/metabolism/pathology

@article {pmid41464650,
year = {2025},
author = {Sonaglioni, A and Nicolosi, GL and Lombardo, M and Baravelli, M and Muti, P},
title = {Comparative Meta-Analysis of Left Ventricular Mechanics in Takotsubo Syndrome and Anterior STEMI Due to Left Anterior Descending Artery Occlusion.},
journal = {Journal of clinical medicine},
volume = {14},
number = {24},
pages = {},
pmid = {41464650},
issn = {2077-0383},
support = {N/A//Ministero della Salute/ ; },
abstract = {Background: Takotsubo syndrome (TTS) often mimics anterior ST-elevation myocardial infarction (STEMI) caused by left anterior descending (LAD) occlusion, yet the two entities differ fundamentally in pathophysiology and mechanical behavior. Two-dimensional speckle-tracking echocardiography (2D-STE) enables detailed assessment of left ventricular (LV) deformation beyond conventional ejection fraction (LVEF). This meta-analysis compared global and regional LV strain patterns in TTS versus LAD-related anterior STEMI during the acute phase. Methods: A systematic search of PubMed, Embase, and Scopus through October 2025 identified observational case-control studies directly comparing TTS and angiographically confirmed anterior STEMI, with LV mechanics assessed by 2D-STE. Random-effects models were used to pool standardized mean differences (SMDs) for LVEF; global longitudinal strain (GLS); apical, mid-ventricular, and basal longitudinal strain (ALS, MLS, BLS); and global radial strain (GRS). Heterogeneity (I[2]), publication bias (funnel plots, Egger's test), meta-regression, and leave-one-out sensitivity analyses were performed. Results: Six studies comprising 221 TTS and 290 anterior STEMI patients met the inclusion criteria. TTS patients were older, predominantly female, and had fewer metabolic risk factors, while LV size was comparable. LVEF was significantly lower in TTS (SMD -1.149; 95% CI -2.20 to -0.10; p = 0.032), with stable findings across sensitivity analyses and no evidence of publication bias. GLS, ALS, MLS, and BLS showed only a non-significant trend toward greater impairment in TTS, and these comparisons were limited by marked inter-study heterogeneity. In contrast, GRS was significantly and consistently more reduced in TTS (SMD -1.284; 95% CI -1.59 to -0.98; p < 0.001), indicating more profound global radial dysfunction. Meta-regression showed no significant influence of demographic factors or vendor-specific software on LVEF or GLS differences. Conclusions: Compared with LAD-related anterior STEMI, TTS is associated with more severely depressed LVEF and markedly impaired radial strain, while longitudinal strain differences remain inconclusive and suggest only a potential trend toward greater dysfunction, reflecting the limited and heterogeneous evidence. These findings are consistent with diffuse, stress-induced myocardial stunning in TTS and suggest that 2D-STE may aid differentiation between stress cardiomyopathy and ischemic infarction in the acute setting, although longitudinal strain parameters should be interpreted cautiously and regarded as hypothesis-generating.},
}

@article {pmid41464612,
year = {2025},
author = {Klumb, S and Haley, L and Hathaway, C and Irby, J and Cheng, J and Rumley, J},
title = {Degenerative Cervical Myelopathy Diagnosis and Its Differentiation from Neurological Mimics, MS and ALS: A Literature Review.},
journal = {Journal of clinical medicine},
volume = {14},
number = {24},
pages = {},
doi = {10.3390/jcm14248711},
pmid = {41464612},
issn = {2077-0383},
abstract = {Multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and degenerative cervical myelopathy (DCM) share features that may confound diagnosis. DCM is caused by degenerative changes in the cervical spine leading to spinal cord compression and injury, resulting in significant disability. Misdiagnosis of DCM for a similar neurological condition can lead to further spinal cord damage from delayed surgical treatment. Here we review the diagnostic criteria, clinical signs and symptoms, and imaging typical for DCM, and two of its clinical mimics, MS and ALS. Shared motor symptoms of all three conditions can make diagnosis difficult, especially early in disease course. Noteworthy differences include neck and shoulder pain in DCM, visual disturbances in MS, and bulbar symptoms and the absence of sensory deficits in ALS. In DCM and MS, MRI is used to support the diagnosis, with specific findings on MRI that differentiate DCM versus MS. In ALS, MRI is used to rule out differential diagnoses. Applying the diagnostic criteria for MS and ALS, as well as understanding the typical presentation and MRI findings of DCM, is crucial. Through discussion of these conditions, this review aims to help limit misdiagnosis rates, allowing for early management, which can improve long-term patient outcomes.},
}

@article {pmid41463333,
year = {2025},
author = {Tendero-Lopez, D and Dominguez, M and Aguilar-Aragon, M},
title = {Modelling Neural Disorders with the D. melanogaster Larval Peripheral and Adult Dopaminergic Systems.},
journal = {Biomolecules},
volume = {15},
number = {12},
pages = {},
doi = {10.3390/biom15121677},
pmid = {41463333},
issn = {2218-273X},
mesh = {Animals ; *Drosophila melanogaster/metabolism ; Larva/metabolism ; *Disease Models, Animal ; Humans ; *Dopamine/metabolism ; *Dopaminergic Neurons/metabolism/pathology ; *Nervous System Diseases/metabolism ; Parkinson Disease/metabolism ; },
abstract = {The increasing prevalence of neurological disorders highlights the need for disease animal models to elucidate the underlying biomolecular and cellular mechanisms of disease and to facilitate studies aimed at developing effective treatments. The fruit fly Drosophila melanogaster, at both larval and adult stages, can serve as an effective model for different human-relevant neurological diseases. Larvae are particularly suited for studying peripheral nervous system disorders, such as Charcot-Marie-Tooth and amyotrophic lateral sclerosis, while adults enable investigations of higher-order cognitive functions and age-related conditions, including Parkinson's disease and depression-like behaviours. Combining larval and adult models offers a complementary framework to dissect the biomolecular pathways of neurological disorders and accelerate preclinical research.},
}

Animals
*Drosophila melanogaster/metabolism
Larva/metabolism
*Disease Models, Animal
Humans
*Dopamine/metabolism
*Dopaminergic Neurons/metabolism/pathology
*Nervous System Diseases/metabolism
Parkinson Disease/metabolism

@article {pmid41462890,
year = {2025},
author = {Fajkić, A and Belančić, A and Lam, YW and Rački, V and Pilipović, K and Janković, T and Mežnarić, S and Mršić-Pelčić, J and Vitezić, D},
title = {Novel Translational Concept: Axon-to-Muscle Exosomal Signaling as an Emerging Therapeutic Target in Spinal Muscular Atrophy.},
journal = {Biomedicines},
volume = {13},
number = {12},
pages = {},
doi = {10.3390/biomedicines13122876},
pmid = {41462890},
issn = {2227-9059},
abstract = {Spinal muscular atrophy (SMA) has transitioned from a uniformly fatal disease to a treatable condition, yet incomplete neuromuscular recovery underscores the limits of current SMN-restorative therapies. Emerging data implicate disrupted axon-to-muscle exosomal signaling as an important, overlooked driver of residual dysfunction. Exosomes, nanovesicles mediating bidirectional neuronal-muscular communication, carry synaptic organizers, trophic factors, and microRNAs essential for neuromuscular junction integrity. SMN deficiency alters exosomal biogenesis and cargo, leading to loss of agrin-MuSK signaling, impaired β-actin transport, and muscle atrophy. Comparative insights from amyotrophic lateral sclerosis and muscular dystrophy reveal that stem-cell-derived or engineered exosomes restore synaptic stability, enhance regeneration, and cross biological barriers safely. Thus, we speculate herein on a translational model integrating exosome-based therapies with existing genetic interventions to achieve durable, systems-level recovery in SMA. Exosomal profiling may further yield minimally invasive biomarkers for disease monitoring and treatment optimization, establishing vesicle-mediated communication as a novel therapeutic axis in neuromuscular medicine.},
}

@article {pmid41459056,
year = {2025},
author = {Auclair-Ouellet, N and Kassem, O and Bronner, S and Oula, ML and Binda, S},
title = {Leveraging microbiome-based interventions to improve the management of neurodegenerative diseases: evidence for effects along the microbiota-gut-brain axis.},
journal = {Frontiers in nutrition},
volume = {12},
number = {},
pages = {1699884},
pmid = {41459056},
issn = {2296-861X},
abstract = {The microbiota-gut-brain axis (MGBA) has recently emerged as a useful model for the understanding of the onset and progression of neurodegenerative diseases (NDDs). Microbiome-based interventions using biotic supplements (probiotics, prebiotics, synbiotics, postbiotics) can modulate the MGBA and constitute relevant solutions to help reduce the risk of neurological changes associated with NDDs and manage symptoms. This narrative review provides a summary of the functioning of the MGBA and of its interactions with disease processes involved in the onset and progression of NDDs. Microbiome-based interventions and their mechanisms of action are reviewed, and important considerations for the design of interventions are discussed. Next, preclinical and clinical studies on the potential of microbiome-based interventions in Alzheimer's disease (AD), Parkinson's disease (PD), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and Huntington's disease (HD) are reviewed. Evidence related to biomarkers of pathology (e.g., beta-amyloid or alpha-synuclein protein depositions), neuroinflammation, and metabolic activity is summarized, along with emerging evidence for the improvement of clinical symptoms and disease trajectories. Overall, preclinical studies show that microbiome-based supplements have significant positive effects on mechanisms and pathways involved in the pathophysiology of NDDs. Clinical studies show that these interventions provide important benefits both in terms of biomarkers and clinical symptoms. However, evidence is limited in some key clinical areas, such as mental wellbeing in AD and cognition in PD, and for the management of clinical symptoms in ALS and HD overall. Gaps in knowledge and open questions as well as perspectives for future research are discussed.},
}

@article {pmid41458376,
year = {2025},
author = {Qian, G and Ding, L and Tan, C and Wang, L and Long, C},
title = {Mucosal immune response modulated by secreted and membrane-bound hydrolases of Candida albicans in vulvovaginal candidiasis.},
journal = {Frontiers in fungal biology},
volume = {6},
number = {},
pages = {1692795},
pmid = {41458376},
issn = {2673-6128},
abstract = {Vulvovaginal candidiasis (VVC) affects the physical and mental health of millions of women worldwide. The leading cause of VVC, Candida albicans, can induce a strong mucosal inflammatory reaction during the VVC infection, where secreted and membrane-bound adhesion and hydrolases seem to be the key virulent factors to promote the mucosal antifungal immunity and immunopathology. Several hydrolases, such as Saps, Als, candidalysin, lipases, and phospholipases, have been identified in vaginal secretions isolated from VVC patients; however, the immune impacts of some hydrolases have not been well documented. In this review, we focus on the literature that addresses the immunopathogenic roles of the Als adhesin family or proteinase, such as Sap and candidalysin, in VVC. Our goal is to expand our knowledge of VVC pathogenesis in order to provide new strategies for VVC treatment.},
}

@article {pmid41456636,
year = {2025},
author = {Koppali, SR and Vadia, N and Varma, P and Mishra, S and Joshi, N and Bansal, P and Al-Hasnaawei, S and Chauhan, AS and Jain, H and Nathiya, D and Devi, A and Jayasingh Chellammal, HS and Gupta, P and Wal, P and Koppula, S},
title = {Neurodevelopmental origins of neurodegeneration: a lifespan perspective on brain vulnerability.},
journal = {Brain research},
volume = {},
number = {},
pages = {150134},
doi = {10.1016/j.brainres.2025.150134},
pmid = {41456636},
issn = {1872-6240},
abstract = {Neurodegenerative disorders-including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis-are increasingly understood to have origins in early neurodevelopmental disturbances. This review examines how genetic, epigenetic, and environmental factors impact brain development during critical periods, predisposing individuals to neurodegeneration later in life. Prenatal and early-life exposures such as maternal stress, malnutrition, infection, and environmental toxins can alter key developmental processes, leading to long-term vulnerability. Mechanistic pathways linking early-life disruptions to neurodegenerative outcomes include persistent mitochondrial dysfunction, chronic neuroinflammation, increased oxidative stress, and aberrant synaptic pruning, all of which contribute to progressive neuronal damage and dysfunction. The gut-brain axis is also discussed as a key intermediary, where early microbiota dysbiosis alters neuroimmune signaling and inflammatory responses, modulating susceptibility to age-related neurological disorders. In this context, the review highlights emerging molecular and imaging biomarkers capable of detecting subtle neurodevelopmental deviations that may precede clinical symptoms by decades. The paper emphasizes the need for early-life interventions, including maternal nutritional optimization, management of prenatal stress, and microbiome-targeted strategies, as potential tools to reduce long-term neurological risk. Furthermore, it proposes the integration of precision medicine approaches aimed at individualized risk assessment and therapeutic targeting of developmental pathways. Adopting a lifespan perspective, this review argues for a paradigm shift from reactive to preventive strategies in neurology. Understanding the developmental roots of neurodegeneration opens new avenues for research and intervention, enabling resilience and reducing disease burden through early diagnostics and tailored therapeutics across the lifespan.},
}

@article {pmid41455134,
year = {2025},
author = {Du, O and Wu, YJ and Li, MY and Du, JR},
title = {The role of HMGB1 in central nervous system (CNS) diseases: mechanisms and therapeutic perspectives.},
journal = {Cytokine},
volume = {198},
number = {},
pages = {157099},
doi = {10.1016/j.cyto.2025.157099},
pmid = {41455134},
issn = {1096-0023},
abstract = {Central nervous system (CNS) diseases represent a major global health burden and are among the leading causes of disability and mortality worldwide. The pathological mechanisms underlying CNS disorders are complex and multifactorial, involving processes such as neuroinflammation, oxidative stress, neuronal damage, and synaptic dysfunction. High-mobility group box 1 (HMGB1), a member of the high-mobility group box (HMGB) protein family, is predominantly localized in the nucleus under physiological conditions, where it contributes to DNA repair, transcriptional regulation, and other cellular functions. However, in various CNS pathologies-including stroke, traumatic brain injury (TBI), Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), glioblastoma (GBM), epilepsy, depression, multiple sclerosis (MS), and schizophrenia-HMGB1 is released or secreted into the extracellular space. There, it plays a key role in regulating neuroinflammation, cell death, cell migration, and tissue damage and repair, thereby contributing to disease pathogenesis and progression. HMGB1 not only functions as a critical regulator in the progression of CNS diseases but also serves as a biomarker for predicting poor clinical outcomes. Moreover, a growing body of evidence indicates that therapeutic strategies targeting HMGB1 can significantly alleviate pathological damage in various CNS disorders, highlighting its potential as a promising therapeutic target. This review comprehensively summarizes the structure, post-translational modifications, release mechanisms, and receptor systems of HMGB1, along with its roles and mechanisms in CNS diseases. It also discusses the potential of HMGB1 as a biomarker and examines emerging HMGB1-targeted therapeutic strategies, aiming to provide a theoretical foundation for the treatment and drug development of CNS disorders.},
}

@article {pmid41454317,
year = {2025},
author = {Abdi, M and Sooudi, OK and Milota, M},
title = {Professional identity formation for underrepresented groups in medicine: challenges and interventions for Dutch medical schools: a systematic scoping review.},
journal = {BMC medical education},
volume = {25},
number = {1},
pages = {1715},
pmid = {41454317},
issn = {1472-6920},
mesh = {Humans ; Netherlands ; *Schools, Medical/organization & administration ; *Students, Medical/psychology ; *Social Identification ; *Minority Groups/psychology/education ; Cultural Diversity ; *Ethnicity ; },
abstract = {BACKGROUND: The concept of intersectionality is important when considering the professional identity formation (PIF) of students who are racially and ethnically underrepresented in medicine (URiM), as they must navigate race and ethnicity within the medical landscape. Despite a growing body of studies that shed light on the challenges that URiM students face in their PIF, there remains a notable lack of practical interventions for medical schools to address these challenges. Our objective is to highlight the challenges faced by URiM students and identify interventions in the literature that would be most suitable for Dutch medical schools to address them.

METHODS: This study builds upon Teo et al.'s (2022) scoping review. We examined articles from January 1, 2000, to December 31, 2021, and conducted an extended search from January 1, 2022, to November 30, 2023. Our focus was on articles exploring the intersectionality of PIF, perspectives of minoritized groups, and diversity, equity, and inclusion (DEI) within the context of PIF in medical education. We used the Systematic Evidence-Based Approach (SEBA) guided systematic scoping review, encompassing four stages: Systematic Approach, Structured Summary and Synthesis, Jigsaw Perspective, and Literature Analysis.

RESULTS: A total of 692 abstracts were reviewed, 36 full-text articles were evaluated, and 22 articles were included. URiM students encounter multiple challenges in their PIF journeys such as a lack of role models and representation, experiences of microaggressions, and pressure to assimilate into the majority culture. The proposed interventions for medical schools included diversifying recruitment practices to create more role models, developing curricula to address these challenges, and establishing a supportive network for URiM students.

CONCLUSIONS: Our study highlights the pressing need for Dutch medical schools to address the challenges faced by URiM students in PIF. The identified interventions offer actionable strategies to cultivate a more supportive and equitable learning environment. The implementation of these interventions has the potential to enhance URiM students' educational experiences, reduce disparities, and promote diversity within the medical profession. These findings underscore the importance of ongoing efforts to prioritize inclusivity and equity in medical education.},
}

Humans
Netherlands
*Schools, Medical/organization & administration
*Students, Medical/psychology
*Social Identification
*Minority Groups/psychology/education
Cultural Diversity
*Ethnicity

@article {pmid41438688,
year = {2026},
author = {Su, T and Li, Z and Yang, Y and Dai, Y and Li, Y and Zhao, H},
title = {In vitro 3D models of neuron-astrocyte interactions.},
journal = {Biochemistry and biophysics reports},
volume = {45},
number = {},
pages = {102400},
pmid = {41438688},
issn = {2405-5808},
abstract = {The pathological processes of neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis) also include relationships between neuron and glia cells. Conventional two-dimensional (2D) cell cultures have limitations to mimic the microenvironment of cells inside living organisms because of flaws in intercellular relationships investigated using 2D cell cultures. Recent advances have introduced three-dimensional (3D) cell cultures that have the capability to create 3D cellular architecture to mimic advanced platforms for scientific inquiries into neurodegenerative diseases, simulating microenvironments inside living organisms.This review provides a brief overview of the development of in vitro 3D cell culture models of astrocytes and attempts to highlight the role of astrocytes in crucial pathophysiologic events occurring in 3D cultures. Studies have shown the use of in vitro 3D cultures to better represent the dual functions of astrocytes in neurodegenerative disorders. Looking ahead to the future, novel advances in microfluidics and multi-omics analysis promise to further improve 3D cultures and push forward new insights into neurological dysfunction to spark innovative advances for treatment strategies.},
}

@article {pmid41438236,
year = {2025},
author = {Li, T and Gao, Y and Zhou, J and Chen, Y and Zhang, S and Gong, X and Liu, Y},
title = {Advancements in the application of brain-computer interfaces based on different paradigms in amyotrophic lateral sclerosis.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1658315},
pmid = {41438236},
issn = {1662-4548},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurological condition that leads to the gradual loss of movement and communicative abilities, significantly diminishing the quality of life for affected individuals. Recent advancements in neuroscience and engineering have propelled the swift evolution of brain-computer interfaces (BCIs), which are now extensively utilised in medical rehabilitation, military applications, assistive technologies, and various other domains. As a communication medium facilitating direct interaction between the brain and the external world independent of the peripheral nervous system, BCI provides ALS patients with an innovative method for communication and control, offering unparalleled prospects for improving their quality of life. Recent collaborative endeavours among several specialists have markedly enhanced the precision and velocity of diverse BCI paradigms, signifying a breakthrough in BCI applications for ALS. Nonetheless, obstacles and constraints remain. This study methodically extracted pertinent literature from the Web of Science and PubMed databases in accordance with PRISMA guidelines. Following stringent inclusion and exclusion criteria, 23 studies were identified. This data allows us to summarise the application results and current limitations of several BCI paradigms in motor control and communication, while delineating prospects in multimodal fusion and adaptive calibration. This review presents evidence-based references for the effective translation and application of BCI technology in ALS rehabilitation.},
}

@article {pmid41431371,
year = {2025},
author = {Dobbertin, T and Schirmer, L},
title = {Spatially Resolved Profiling of Compartmentalized Muscle and Brain Inflammation.},
journal = {European journal of immunology},
volume = {55},
number = {12},
pages = {e70119},
pmid = {41431371},
issn = {1521-4141},
support = {P1180016//Gemeinnützige Hertie-Stiftung/ ; GRK2727(InCheck)//Deutsche Forschungsgemeinschaft/ ; FOR2690(SCHI1330/7-2)//Deutsche Forschungsgemeinschaft/ ; SPP2395(SCHI1330/10-1)//Deutsche Forschungsgemeinschaft/ ; FOR5705(SCHI1330/13-1)//Deutsche Forschungsgemeinschaft/ ; SCHI1330/2-1//Deutsche Forschungsgemeinschaft/ ; SCHI1330/4-1//Deutsche Forschungsgemeinschaft/ ; SCHI1330/11-1//Deutsche Forschungsgemeinschaft/ ; 950584//H2020 European Research Council/ ; },
mesh = {Humans ; Animals ; *Muscle, Skeletal/immunology/pathology/metabolism ; Proteomics/methods ; *Brain/immunology/pathology ; Inflammation/immunology ; *Neuroinflammatory Diseases/immunology ; *Encephalitis/immunology ; Transcriptome ; },
abstract = {Spatial omics technologies enable high-resolution mapping of transcriptomic, proteomic, and metabolic profiles within intact tissues, revealing how immune, stromal, and parenchymal cells interact in situ during inflammation. Chronic inflammation in skeletal muscle and the central nervous system is spatially organized within defined niches that shape disease progression and therapeutic response. In skeletal muscle, spatial analyses have uncovered fiber-type-specific vulnerability, regenerative trajectories, and immune-stromal crosstalk in disorders such as Duchenne muscular dystrophy and inclusion body myositis. In the central nervous system, these approaches have revealed compartmentalized neuroinflammation in multiple sclerosis, innate immune activation in amyotrophic lateral sclerosis, and immune evasion in glioma. Integration with single-cell gene expression enables inference of cell-cell communication networks and identification of spatial gradients of immune activation and tissue remodeling. Despite major advances, clinical translation remains limited by small cohorts, methodological variability, and insufficient functional validation. As spatial profiling becomes more accessible, standardized, and scalable, it promises to stratify inflammatory disease states, identify tissue-resident immune programs, and guide mechanism-based therapies. Hence, spatial omics provide an unprecedented opportunity to resolve the cellular architecture of inflammation, revealing not only where immune activity occurs, but how it is orchestrated within complex tissue microenvironments.},
}

Humans
Animals
*Muscle, Skeletal/immunology/pathology/metabolism
Proteomics/methods
*Brain/immunology/pathology
Inflammation/immunology
*Neuroinflammatory Diseases/immunology
*Encephalitis/immunology
Transcriptome

@article {pmid41428942,
year = {2025},
author = {Sannes, A and Rognli, EW and Hanssen-Bauer, K and Torp, NC and Storfossen, SK and Høstaker, MN and Aalberg, M},
title = {Barriers to and Facilitators of Implementation of Internet-Delivered Therapist-Guided Therapy in Child and Adolescent Mental Health Services: Systematic Review and Bayesian Meta-Analysis.},
journal = {Journal of medical Internet research},
volume = {27},
number = {},
pages = {e83543},
pmid = {41428942},
issn = {1438-8871},
mesh = {Adolescent ; Child ; Humans ; *Adolescent Health Services ; Bayes Theorem ; *Child Health Services ; *Internet ; *Mental Health Services ; *Psychotherapy/methods ; },
abstract = {BACKGROUND: Internet-delivered therapist-guided therapy (e-therapy) represents a promising approach for enhancing accessibility, treatment fidelity, and scalability within child and adolescent mental health services (CAMHS).

OBJECTIVE: This systematic review aimed to (1) identify and synthesize determinants of implementation, specifically barriers to and facilitators of e-therapy in CAMHS structured according to the Consolidated Framework of Implementation Research (CFIR); and (2) provide pooled benchmark estimates of key implementation outcomes for fidelity, cost-effectiveness, and acceptability.

METHODS: A PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)-compliant systematic review was performed across PsycINFO, MEDLINE, Web of Science, CINAHL, Embase, Cochrane, and ProQuest Dissertations & Thesis on June 6, 2025-to identify peer-reviewed studies assessing implementation outcomes or determinants of e-therapy in the context of outpatient CAMHS (ages 8-18 years). Barriers and facilitators were synthesized qualitatively with thematic analysis applying CFIR. A parallel quantitative synthesis of Proctor et al's taxonomy of implementation outcomes was performed using Bayesian multilevel random-effects meta-analyses to estimate pooled effect sizes and 95% credible intervals (CIs). By combining quantitative benchmarks of implementation success with qualitative insights into contextual determinants, the review provides an integrated understanding of what drives effective e-therapy implementation in CAMHS. Study quality was assessed using the CASP (Critical Appraisal Skills Programme) checklist, Cochrane Risk of Bias tool, and Risk Of Bias In Non-randomized Studies-of Interventions tool. Small study effects were evaluated using funnel plots, sensitivity analyses, and the Egger test.

RESULTS: From 50,026 screened reports, 50 studies published between 2007 and 2025 were included: 18 randomized controlled trials, 17 cohort, and 15 qualitative or mixed methods studies. Most studies originated from Western Europe (n=34), Northern America (n=11), and Oceania (n=5), targeting anxiety (n=24) and depression (n=9), through cognitive behavioral therapy-based programs (n=47), with parallel parent content (n=31). Therapist guidance was primarily asynchronous (n=43). Among the 39 studies reporting determinants, common barriers and facilitators were identified across intervention, organization, therapist, and patient domains, structured via CFIR. Pooled implementation outcomes showed modest dropout rates (~20%, CI 14%-27%), high module completion (~68%, CI 60%-75%), low therapist time (24 min per wk per patient, 95% CI 19-28), and high patient satisfaction (24/32 on Client Satisfaction Questionnaire-8, 95% CI 22-27; and 76% satisfaction rate, 95% CI 62%-87%), suggesting e-therapy is resource efficient and acceptable if implemented successfully.

CONCLUSIONS: This review provided the first integrated synthesis of pooled benchmarks for implementation outcomes of e-therapy in CAMHS and modifiable determinants to inform future service planning and scale-up. These findings highlighted service-level enablers, such as leadership anchoring, targeted use, technical stability, structured patient flow, and therapist training, that organizations could prioritize to strengthen sustainable e-therapy implementation in CAMHS.},
}

Adolescent
Child
Humans
*Adolescent Health Services
Bayes Theorem
*Child Health Services
*Internet
*Mental Health Services
*Psychotherapy/methods

@article {pmid41426554,
year = {2025},
author = {Liang, L and Zhang, Y and Zhang, X and Guo, X and Yan, Y},
title = {Historical evolution, research hotspots and emerging trends of pediatric hand, foot, and mouth disease: a bibliometric worldview since the 21st century.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1722750},
pmid = {41426554},
issn = {2296-858X},
abstract = {BACKGROUND: Hand, foot, and mouth disease (HFMD) poses a significant challenge to global public health. Primarily caused by enterovirus and coxsackievirus infections, the disease has a particularly pronounced impact in the Asia-Pacific region. However, systematic analysis and discussion regarding the developmental trajectory, core research entities, current status, key research directions, and future prospects of pediatric HFMD research remain lacking.

METHODS: This study collected and analyzed papers and reviews on pediatric HFMD published between January 1, 2000, and February 1, 2025, from the Web of Science Core Collection and PubMed. Key research indicators were analyzed through bibliometric visualization, using tools including Excel, CiteSpace, VOSviewer, and BibliomeTools (an R-based tool in R-Studio).

RESULTS: Since the start of the 21 st century, academic publications in pediatric HFMD have steadily increased, with a cumulative total of 2,034 papers published by February 1, 2025. Global research distribution exhibits uneven patterns, with China emerging as core contributors. Specifically, Lin, Tzou-Yien from China, has published the largest number of papers, while Chang, Luan-Yin is the co-cited author with the highest citation rate. Solomon T et al.'s "Virology," Epidemiology, Pathogenesis, and Control of Enterovirus 71" being the most cited study in the field. Research on pediatric HFMD is closely integrated with disciplines such as virology and epidemiology, forming core research themes around "HFMD," "enterovirus 71," and "enteroviruses." Recent research has focused on the pathogenesis, epidemiology, novel therapeutic discoveries and vaccine development for pediatric HFMD. Looking ahead, it is essential to delve deeper into the molecular mechanisms underlying the interaction between the human HFMD virus and its host, and to develop multivalent vaccines targeting multiple serotypes.

CONCLUSION: This study employs bibliometric methods to visualize research in the field of pediatric hand, foot, and mouth disease, revealing trends and frontiers in this area. It will provide valuable reference for scholars seeking key research questions and potential collaborators.},
}

@article {pmid41420832,
year = {2025},
author = {Wang, X and Wei, M and Qiao, Y},
title = {Modulation of Liquid-to-Solid Phase Transition in Coacervates for Neurodegenerative Disease Treatments.},
journal = {Chembiochem : a European journal of chemical biology},
volume = {},
number = {},
pages = {e202500795},
doi = {10.1002/cbic.202500795},
pmid = {41420832},
issn = {1439-7633},
support = {2023YFC2507000//National Key R&D Program of China/ ; 22272183//National Natural Science Foundation of China/ ; T2425001//National Natural Science Foundation of China/ ; },
abstract = {Coacervates formed through liquid-liquid phase separation represent a fundamental model for protocell and serve as a membraneless organelle in living cells, modulating various biological processes. During aging or under stress, protein misfolding and oligomerization trigger aberrant liquid-to-solid phase transition (LSPT), a process driven by multivalent interactions. These phase transitions disrupt cellular equilibrium, leading to neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The regulatory strategies is summarize to enhance molecular interactions in coacervate LSPT into three categories, including physical stimulation, molecular modulation, and sequence regulation. This review aims to establish a conceptual framework for modulating coacervate LSPT and further explores potential clinical treatments for neurodegenerative diseases.},
}

@article {pmid41419286,
year = {2025},
author = {Phillips, G and Sharma, D and O'Reilly, G and Romero, L and Cameron, P},
title = {Developing emergency care systems in low-income and middle-income countries: a scoping review to examine the role of leadership and governance.},
journal = {BMJ open},
volume = {15},
number = {12},
pages = {e102624},
pmid = {41419286},
issn = {2044-6055},
mesh = {Humans ; *Developing Countries ; *Leadership ; *Emergency Medical Services/organization & administration ; },
abstract = {BACKGROUND: More knowledge and resources are required to strengthen 'leadership and governance' (L+G) as a central building block to further develop emergency care (EC) systems in low-income and middle-income countries (LMICs).

OBJECTIVES: This scoping review aimed to examine and map the impact of individual, collective or institutional L+G on the development of EC systems (prehospital and facility-based) in LMICs.

ELIGIBILITY CRITERIA: English language publications from January 2005 to April 2024 that linked any L+G action with the development and capacity of everyday EC in LMICs, specifically excluding disaster responses.

SOURCES OF EVIDENCE: Medline (Ovid), Embase (Ovid), CINAHL, Web of Science (Clarivate), Central (Cochrane Central Register of Controlled Trials), Global Health (Ovid) and select grey literature.

CHARTING METHODS: Data from all eligible papers were jointly extracted using a piloted tool developed from the literature and WHO's EC Systems Framework. L+G descriptors included level (from clinical to national) and components (informed by Siddiqi et al's LMIC health system 'good governance' framework and a synthesis of EC policy documents). Impact of L+G on EC systems and key lessons were extracted from each publication.

RESULTS: From an initial 9713 items, 129 papers were included for final analysis and divided by EC component: prehospital (n=35), facility-based (n=53) and 'whole of EC system' (n=41). Qualitative and descriptive papers were most common, and 72 out of a possible 131 LMICs were represented. Findings were heterogeneous across all building blocks of EC systems and for different components of leadership and/or governance. Cross-cutting L+G themes were identified that demonstrated consistent impact across all EC systems development: government recognition, vision and human rights framing; coalition-building for effective partnerships and trained, empowered EC clinicians demonstrating emotionally intelligent, transformational leadership.

CONCLUSIONS: Applying new models such as Theories of Change and Social Network Analysis concepts may assist to illuminate how effective L+G is attained, what are the essential components and how these influence EC systems for better patient-centred outcomes. Further understanding the role of L+G for EC systems has utility for future EC clinician leadership training and policy-maker awareness, to strengthen resilience of overall health systems against likely future shocks.},
}

Humans
*Developing Countries
*Leadership
*Emergency Medical Services/organization & administration

@article {pmid41417080,
year = {2025},
author = {Zafar, U and Abdullah, M and Butt, TN and Uddin, MMZ and Masood, MH and Chu, LC and Zaheer, A},
title = {A bibliometric analysis of the 100 most cited radiology papers on pancreatic diseases (1990-Present).},
journal = {Abdominal radiology (New York)},
volume = {},
number = {},
pages = {},
pmid = {41417080},
issn = {2366-0058},
abstract = {PURPOSE: To map the intellectual evolution of pancreatic radiology through a comprehensive bibliometric analysis of the 100 most-cited articles, identifying influential contributors and publications, geographical and institutional patterns, and delineating the thematic and technological trends shaping research from 1990 to the present.

METHODS: A systematic search of the Scopus database, conducted on May 11, 2025, identified the top 1,000 most-cited pancreatic radiology records between 1990 and 2025. Two reviewers independently screened articles for a primary focus on pancreatic imaging within core radiology journals. The final 100 articles were analyzed using the Bibliometrix R package to evaluate publication trends, contributor influence, and collaborative networks. The conceptual structure and thematic evolution of the field were mapped using VOSviewer (version 1.6.20).

RESULTS: The median citation count was 223 (IQR: 190.2-264.5). A significant temporal bias was evident: the most-cited article was Balthazar et al.'s 1990 study on CT in pancreatitis (1,424 citations), while a 2015 deep learning paper achieved the highest citation velocity (58.5 citations/year). Analysis of research topics revealed a strong oncologic focus, with pancreatic neoplasms accounting for 51% of all articles. CT was the predominant imaging modality (55%), followed by MRI (24%). The research ecosystem was concentrated, with the United States contributing 46 articles and Radiology publishing 44 of the top 100 papers. Leading institutions included Johns Hopkins University and the Mayo Clinic. Co-authorship network analysis identified Megibow AJ as the researcher with the highest network centrality, highlighting the importance of collaborative hubs.

CONCLUSION: This bibliometric analysis charts the field's evolution from foundational CT/MRI applications to the current AI frontier. Our findings serve as a guide to the characteristics of high-impact research, highlighting a consistent focus on oncology, driven by key authors and US institutions. While historical benchmarks focused on morphological assessment, citation metrics confirm computational methods as the principal driver of future innovation.},
}

@article {pmid41417044,
year = {2025},
author = {Rott, N and Reinsch, L and Dirks, B and Böttiger, BW},
title = {[The new European Resuscitation Council (ERC) guidelines 2025-Overview of the most important changes; the first 3-5 min are decisive].},
journal = {Die Anaesthesiologie},
volume = {},
number = {},
pages = {},
pmid = {41417044},
issn = {2731-6866},
abstract = {In October 2025 the new resuscitation guidelines of the European Resuscitation Council (ERC) were published. In the chapter on advanced life support (ALS) for adults the update emphasizes topics such as efficient ventilation with adequate chest compressions, early defibrillation, identification and treatment of reversible causes as rapidly as possible and the administration of epinephrine in cases of non-defibrillatable cardiac arrest. The aim of the guidelines is to sustainably improve survival rates after cardiac arrest through structured and evidence-based care systems.},
}

@article {pmid41385186,
year = {2025},
author = {Mitsiadou, D and Xirodimas, DP and Polanowska, J},
title = {NEDD8, stress granules, and amyotrophic lateral sclerosis: unveiling the therapeutic potential of the NEDP1 protease.},
journal = {Essays in biochemistry},
volume = {69},
number = {5},
pages = {},
doi = {10.1042/EBC20253036},
pmid = {41385186},
issn = {1744-1358},
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/drug therapy ; Humans ; Animals ; *Stress Granules/metabolism ; *NEDD8 Protein/metabolism ; },
abstract = {Protein quality control (PQC) systems are crucial for maintaining cellular proteostasis, particularly under stress that promotes misfolded protein accumulation. A central component of this response is the assembly of stress granules (SGs), cytoplasmic condensates of RNA and proteins that temporarily stall translation. Aberrant SG dynamics, often linked to mutations in SG proteins, contribute to neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), where persistent protein aggregates are hallmarks. This review examines the emerging role of the ubiquitin-like modifier NEDD8 and its deconjugating enzyme NEDP1 in regulating SG homeostasis. Recent studies identify NEDP1 as a critical factor controlling SG clearance. Inhibition of NEDP1 enhances SG turnover, prevents pathological solidification, and promotes the disassembly of toxic aggregates through hyper-NEDDylation of PARP1, a DNA repair enzyme that also governs SG dynamics. Unlike broad-spectrum PARP1 inhibitors, which can impair DNA repair and cause cytotoxicity, NEDP1 inhibition offers a stress-specific approach that preserves normal cellular functions. Encouragingly, NEDP1 inhibition effectively causes aggregate elimination in ALS patient-derived fibroblasts and restores motility in Caenorhabditis elegans disease models. Altogether, these findings highlight NEDP1 as a key regulator of SG regulation and a promising therapeutic target for ALS and related neurodegenerative disorders.},
}

*Amyotrophic Lateral Sclerosis/metabolism/drug therapy
Humans
Animals
*Stress Granules/metabolism
*NEDD8 Protein/metabolism

@article {pmid41415845,
year = {2025},
author = {Harsa, HS and González Domenech, CM and Prvulović, M and Agirbasli, Z and Bagherzadehsurbagh, E and Simeunović, V and Naziri, E and Adesemoye, E and Yigit Cinar, A and Mukherjee, A and Laranjo, M and Vidović, B and Alves, E and Vukojević, A and Özmen Toğay, S and Düven, G and Saar, H and Salminen, S and Matalas, A and Paveljšek, D and Schneider, E and Liwinski, T and Chassard, C and Vergères, G and Bär, C and Praćer, S},
title = {The effects of Lactobacillus and/or Bifidobacterium in fermented foods on cognitive health: a systematic review.},
journal = {Frontiers in nutrition},
volume = {12},
number = {},
pages = {1682419},
pmid = {41415845},
issn = {2296-861X},
abstract = {BACKGROUND: Psychobiotics are microorganisms that modulate brain function via the gut-brain axis and are increasingly studied for their cognitive benefits. Lactobacillus and Bifidobacterium species, widely present in fermented foods, are considered safe and may influence cognition by modulating neuroinflammation, neurotransmitters, and gut barrier integrity. This systematic review examined the effects of foods fermented with these species on cognitive performance in healthy adults and individuals with mild cognitive impairment.

METHODS: We conducted the systematic review following EFSA guidelines, Cochrane methodology, and a PROSPERO protocol, using CADIMA for study selection and data extraction. PubMed, Scopus, and Cochrane Library were searched (1 January 1970-31 August 2023) for human intervention and observational studies assessing cognitive outcomes after ingestion of foods fermented with Lactobacillus or Bifidobacterium. Eligible populations included healthy adults and individuals with mild cognitive impairment; studies involving disease were excluded. Screening, data extraction, and bias assessment followed Muka et al.'s 24-step guide using ROBINS and Cochrane/CADIMA frameworks. Evidence was synthesized narratively, while a non-systematic component examined food characteristics, potential mechanisms, and factors affecting bioavailability of bioactive constituents.

RESULTS: We included 21 studies (8 interventional, 13 observational). The majority of studies reported benefits, particularly in episodic memory, executive functions, and global cognition, but evidence was limited by inadequate controls, small sample sizes, short interventions, inconsistent domain assessment, and incomplete food characterization. Observational studies had larger populations and longer follow-ups but were limited by exposure assessment and depth of cognitive testing.

CONCLUSION: Consumption of foods fermented with Lactobacillus and/or Bifidobacterium species may offer promising cognitive benefits. However, following EFSA's guidance on the substantiation of health claims, the current evidence is "neither convincing nor sufficient" to establish a causal relationship. Well-designed studies with thorough product characterization are needed to substantiate effects and support potential health claims.

This study was registered at the Open Science Framework (10.17605/OSF.IO/Z6GRW).},
}

@article {pmid41411702,
year = {2025},
author = {Lebkuecher, AL and Coslett, HB and Buxbaum, LJ},
title = {The cognitive neuropsychology of action semantics: A review.},
journal = {Cortex; a journal devoted to the study of the nervous system and behavior},
volume = {194},
number = {},
pages = {159-190},
doi = {10.1016/j.cortex.2025.11.008},
pmid = {41411702},
issn = {1973-8102},
abstract = {The conceptual knowledge that mediates our ability to use familiar objects, understand viewed actions, and engage in communication about actions is often termed "action semantics". The underlying format, cognitive organization, and neural substrates of these representations are matters of active scientific investigation. This review synthesizes the large and diverse literature on action semantics in individuals with neurological disorders characterized by prominent motor deficits (e.g., Parkinson's disease and Amyotrophic lateral sclerosis), as well as those for whom motor deficits are often less prominent (e.g., Alzheimer's disease, Frontotemporal Dementia, stroke). Research in these two groups of disorders is strikingly "siloed" and offers many contradictory findings with respect to whether action semantic representations are abstract (i.e., "disembodied") or grounded in sensory and motor features that reflect the way knowledge was acquired. Findings across these populations also disagree as to whether action semantic representations are organized somatotopically or with a semantic feature-based architecture, and mediated by anterior motor-related or relatively posterior sensory-related brain regions. Many of these disparate findings can be reconciled with consideration of a multidimensional, multimodal representational architecture mediated by a distributed left-lateralized network of brain regions. We provide suggestions for specific methodological approaches for research with neurological populations that may further our understanding of the format, organization, and neural substrates of action semantics.},
}

@article {pmid41408263,
year = {2025},
author = {Doughty, J and Booth, J and Smith, M and Saini, K and Paisi, M and Rodriguez, A and Levine, A and Bedos, C and Muirhead, V and Martins de Barros, C and Freeborn, C},
title = {Unmasking oral health stigma: a qualitative scoping review.},
journal = {BMC oral health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12903-025-07329-9},
pmid = {41408263},
issn = {1472-6831},
abstract = {INTRODUCTION: Health-related stigma can limit access to care, impair adherence to treatment, and negatively impact mental health and quality-of-life. Oral health stigma, defined as stigma arising from oral conditions that diverge from sociocultural norms, operates through labelling, stereotyping, othering, and exclusion. Oral health stigma can lead to shame, diminished self-confidence, and avoidance of dental care, creating a self-perpetuating cycle of poor oral health and reinforcing internalised and anticipated stigma. While previous research has explored the social implications of oral appearance, little is known about the broader concept of oral health stigma or strategies to mitigate it.

METHODS: This scoping review adopted Levac et al.'s six-stage framework. The review utilised data from qualitative studies to explore lived experiences of oral health stigma and consider ways to mitigate it. Patient and public involvement (PPI) informed the development of the research question, search strategy, and interpretation of findings.

RESULTS: Seventy-two qualitative studies were included, comprising 2,455 participants. Themes included stigma associated with physical appearance and attractiveness, judgement, labelling, and stereotyping. Consequences included low self-esteem, social exclusion, impacts to care seeking behaviours, and efforts to conceal oral appearance. Participants highlighted the transformative value of dental care and described coping strategies to build resilience. Other proposed solutions included fostering social connection and implementing trauma-informed, non-judgemental dental care.

CONCLUSION: Oral health stigma has significant social and psychological consequences and impacts on care-seeking behaviours. Addressing it requires targeted interventions at multiple levels, including individual, community, professionals and wider system / policy.},
}

@article {pmid41407165,
year = {2025},
author = {Ghosh, N and Ghosh, J and Ghosh, S and Sinha, K and Sil, PC},
title = {Nutraceutical interventions for neuroprotection: a comprehensive review.},
journal = {Biochemical pharmacology},
volume = {245},
number = {},
pages = {117637},
doi = {10.1016/j.bcp.2025.117637},
pmid = {41407165},
issn = {1873-2968},
abstract = {Nutraceuticals, bioactive compounds derived from food sources, are emerging as promising agents for neuroprotection, particularly through their modulation of gut health. Unlike conventional single-molecule therapeutics that often target isolated pathways, nutraceuticals offer a multi-targeted approach by influencing the gut-brain axis, a bidirectional communication network linking the gut microbiota and the central nervous system. Key nutraceuticals such as probiotics, prebiotics, polyphenols, omega-3 fatty acids, and vitamins have been shown to beneficially alter microbiota composition, reduce intestinal inflammation, and strengthen gut barrier integrity. These changes can significantly influence brain function by modulating neurotransmitter activity and systemic immune responses. This review compares the holistic action of nutraceuticals with the more focused effects of single-molecules, particularly in the context of neurodegenerative diseases like Alzheimer's, Parkinson's, Huntington's Disease and Motor Neuron Diseases like amyotrophic lateral sclerosis. It discusses how nutraceuticals may mitigate key pathological features of these conditions-including neuroinflammation, oxidative stress, and mitochondrial dysfunction, through gut-mediated pathways. Despite their potential, challenges remain regarding the standardization of formulations, bioavailability, dosage optimization, and long-term safety. Further clinical research is needed to validate the efficacy of nutraceuticals as complementary or alternative strategies to traditional neuroprotective agents.},
}

@article {pmid41402228,
year = {2025},
author = {Vovard, B and Faure-de Baets, J and Codron, P and Allain, P and Cassereau, J},
title = {Assessment of social cognition impairments in patients with amyotrophic lateral sclerosis: How can it be improved? A systematic review.},
journal = {Revue neurologique},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neurol.2025.11.003},
pmid = {41402228},
issn = {0035-3787},
abstract = {OBJECTIVES: The aim of this review was to evaluate the current evidence on which part of social cognition is impaired in amyotrophic lateral sclerosis (ALS) patients among emotion recognition, affective empathy and Theory of Mind (ToM) and to suggest improvements in social cognition testing protocols.

METHODS: A systematic review was conducted according to PRISMA guidelines. We included controlled cross-sectional or longitudinal studies published in English before September 1, 2024, that assessed social cognition in non-demented ALS patients. Searches were performed in Medline, Embase, Web of Science, and PsycINFO using specific MeSH terms. Studies using social cognition tests as a primary or secondary outcome were included.

RESULTS: Thirty-four studies were analyzed. Impairments in emotion recognition - especially for negative emotions - were frequently reported, even in cognitively preserved ALS patients. Results for cognitive ToM were mixed and may be confounded by executive dysfunction or test limitations. In contrast, affective ToM deficits were more consistently identified. However, no included study directly assessed affective empathy. Tests used in the reviewed studies were often overly specific and lacked ecological validity, which may explain inconsistent results across domains and weak correlations with imaging or executive function.

CONCLUSION: Social cognition is increasingly recognized as a key non-motor domain affected in ALS. However, current assessment tools may lack the sensitivity and ecological validity needed to capture real-life deficits. The implementation of dynamic, multimodal assessments such as real-life social interaction tests or tests like the Movie Assessment for Social Cognition (MASC) could improve detection and guide clinical interventions but remain to be validated for ALS patients.},
}

@article {pmid40473505,
year = {2026},
author = {Song, W and Huang, Q and Jiang, Z},
title = {Clinical efficacy of athletic taping-assisted physiotherapy for plantar fasciitis: A systematic evaluation and meta-analysis.},
journal = {Foot and ankle surgery : official journal of the European Society of Foot and Ankle Surgeons},
volume = {32},
number = {1},
pages = {11-25},
doi = {10.1016/j.fas.2025.05.013},
pmid = {40473505},
issn = {1460-9584},
mesh = {Humans ; *Fasciitis, Plantar/therapy ; *Athletic Tape ; Randomized Controlled Trials as Topic ; Pain Measurement ; Treatment Outcome ; *Physical Therapy Modalities ; },
abstract = {BACKGROUND: Plantar fasciitis is a common sports injury with long-term chronic pain in the heel as the main symptom, and athletic taping has achieved certain therapeutic effects to improve it, but the clinical efficacy of the problem is still controversial, which was evaluated by Meta-analysis to evaluate the clinical efficacy of the athletic taping technique on patients with plantar fasciitis.

METHODS: The Cochrane Library, Embase, PubMed, Web of Science, CNKI, Wanfang, and Vip databases were searched by computer for randomized controlled trial on the clinical efficacy of exercise taping in patients with PF from the time of construction to 1 September 2024, and the PRISMA 2020 checklist was strictly followed. Quality was assessed using the cochrane 2.0 randomized controlled trials scale by two independent reviewers. Endings were meta-analysis using RevMan 5.4.1 analysis software to analyse the data.

RESULTS: Eleven randomized controlled trial with a total of 395 patients were included. On VAS scores, KT effectively reduced VAS pain scores (MD=-0.79,95 % CI -1.10,-0.48, P < 0.00001); on AOFAS scores, KT improved AOFAS function scores (MD=6.58, 95 % CI 5.03,8.13, P < 0.00001) and the results remained consistent across intervention durations; on plantar fascia thickness measurements, KT significantly reduced plantar fascia thickness (MD=-0.33, 95 % CI -0.56,-0.10, P = 0.005); on BBS scores, KT significantly improved BBS scores [MD= 4.75, 95 % CI (3.17, 6.32), P < 0.00001]; on FFI-FPS scores, KT effectively improved FFI-FPS scores [MD = -2.59, 95 % CI (-3.50, -1.69), P < 0.00001]; on FFI-FDS scores, there was a significant improvement on FFI-FDS scores; on FFI-ALS scores, KT had a significant improvement on the FFI-ALS score had a significant effect [MD= -11.03, 95 % CI (-14.79, -7.27), P < 0.00001]; and on VAS scores after follow-up, the pain relief effect was sustained (MD=-1.03, 95 % CI -1.21, -0.85, P < 0.00001).

CONCLUSION: Based on the available evidence, preliminary analyses suggest that KT combined with conventional rehabilitation may have some advantages in improving pain, ankle-hindfoot function, and plantar fascia thickness in patients with plantar fasciitis, and some of the efficacy is short-term sustained. However, due to the heterogeneity and sample size of the included studies, the above conclusions need to be further validated by more high-quality studies.},
}

Humans
*Fasciitis, Plantar/therapy
*Athletic Tape
Randomized Controlled Trials as Topic
Pain Measurement
Treatment Outcome
*Physical Therapy Modalities

@article {pmid41399798,
year = {2025},
author = {Ghosh, S and Debnath, I and Bhunia, S and Nandi, S and Ashique, S and Nayak, A and Mallick, S and Basak, S},
title = {Decoding natural products for neuroprotection: Pathway networks and structural insights for drug development.},
journal = {Chinese herbal medicines},
volume = {17},
number = {4},
pages = {643-672},
pmid = {41399798},
issn = {2589-3610},
abstract = {Neurodegenerative diseases (NDs), including Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis, are progressive disorders marked by neuronal dysfunction and death, driven by pathological mechanisms such as oxidative stress, mitochondrial dysfunction, neuroinflammation, apoptosis, and protein misfolding. Despite scientific advances, current treatments remain largely palliative, underscoring the need for multitargeted therapeutic strategies. This narrative review synthesizes preclinical and clinical evidence to explore the neuroprotective potential of natural products, with a focus on their ability to modulate key molecular pathways implicated in NDs. A comprehensive literature search across Scopus, ScienceDirect, PubMed, MDPI, and Web of Science identified relevant studies. Bioactive compounds such as curcumin, resveratrol, ginsenosides, quercetin, and marine-derived molecules like fucoxanthin and phlorotannin demonstrated antioxidant, anti-inflammatory, anti-amyloidogenic, and mitochondrial-protective effects by modulating pathways including PI3K/Akt, NF-κB, and Nrf2/ARE, thereby mitigating neuronal damage and promoting cell survival. Natural products from diverse sources, including honey, ginseng, marine macroalgae, and cyanobacteria, exhibited broad-spectrum neuroprotective properties, with advances in nano-formulations improving bioavailability and brain penetration. Furthermore, emerging approaches such as gene-drug interaction studies and scaffold-based drug design offer promising avenues for enhancing clinical translation. While natural products provide a holistic, multitargeted approach to combat NDs, challenges related to bioavailability and therapeutic translation persist, necessitating future research that integrates advanced drug delivery systems, precision medicine, and synthetic modifications to develop innovative and effective treatment paradigms.},
}

@article {pmid41395267,
year = {2025},
author = {Roy, T and Al-Chalabi, A and Iacoangeli, A and Al Khleifat, A},
title = {Biomarkers in ALS trials: from discovery to clinical utility.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1636303},
pmid = {41395267},
issn = {1662-4548},
abstract = {INTRODUCTION: Motor neuron disease (MND), also known as amyotrophic lateral sclerosis (ALS), is a progressive neurodegenerative disorder characterized by motor neuron degeneration, leading to muscle weakness, paralysis, and eventual respiratory failure. Despite advances in understanding its pathology, effective therapies remain limited, underscoring the need for reliable biomarkers to aid early diagnosis, monitor disease progression, and optimize clinical trials. This systematic review explores the role of biomarkers in ALS, focusing on their application in clinical trials to accelerate therapeutic development and enhance patient care.

METHODS: A comprehensive search of PubMed, EMBASE, MedLine, and Google Scholar identified 93 studies investigating various biomarkers, including neurofilament light chain (NFL), inflammatory markers, genetic markers like SOD1 and C9orf72, and imaging modalities.

RESULTS: NFL emerged as a robust biomarker, strongly correlating with disease progression and therapeutic response, and was frequently used in trials like RESCUE-ALS and CENTAUR. Genetic biomarkers, such as C9orf72 and SOD1 mutations, provided insights into ALS mechanisms and informed targeted therapeutic approaches. Emerging biomarkers, such as retroviral elements, show potential but require further validation. Included studies span key trials such as Lighthouse-II, MIROCALS, and MND-SMART.

DISCUSSION: This systematic review evaluates which biomarkers are currently validated for monitoring disease progression and therapeutic response in ALS clinical trials, including protein, genetic, inflammatory, metabolic, and imaging markers. It also highlights the critical role of biomarkers in advancing MND clinical trials by enabling adaptive trial designs, patient stratification, and the use of surrogate endpoints, thereby reducing trial duration and improving efficiency. The review also highlights the translational gap between biomarker discovery and clinical application, emphasizing their potential to optimize trial design and patient stratification. While biomarkers like NFL have transformed trial methodologies, challenges such as disease specificity and inter-patient heterogeneity persist. Future efforts should focus on multimodal biomarker approaches to achieve comprehensive disease assessment and advance personalized therapeutic strategies, ultimately improving outcomes for patients with MND.},
}

@article {pmid41386298,
year = {2025},
author = {Ealy, A and Serapiglia, AM and Panicker, N},
title = {Sterile Innate Immune Mechanisms in Neurodegenerative diseases.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {111039},
doi = {10.1016/j.jbc.2025.111039},
pmid = {41386298},
issn = {1083-351X},
abstract = {Neurodegenerative diseases are characterized by the dysfunction and death of susceptible neuronal populations. Increasing evidence has demonstrated that sustained neuroinflammation and activation of innate immune complexes underlie neurodegeneration, worsening disease progression and outcomes. Sterile inflammation (which occurs in the absence of infection) can be triggered by neurodegenerative disease-associated misfolded proteins. These studies highlight the need to decipher the complexities of innate immune signaling mechanisms and their contribution to neuropathology. In this review, we focus on major neurodegenerative diseases that have a well-documented neuroinflammatory component: Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS) and Frontotemporal Dementia (FTD). In the context of these diseases, we discuss recent advances in innate-immune mechanisms that have been demonstrated to partake in disease progression and neurodegeneration. These include evolutionarily conserved innate-immune signaling complexes whose uncontrolled activation amplifies neurodegeneration, damaging lipid droplets that accumulate within myeloid cells and prevent their ability to clear toxic protein aggregates, as well as genome-wide studies implicated genes/proteins. The individual and/or concerted actions of these pathways could be leveraged to rationally target the pathogenesis or progression of neurodegenerative diseases.},
}

@article {pmid33557659,
year = {2021},
author = {Lyng, J and Adelgais, K and Alter, R and Beal, J and Chung, B and Gross, T and Minkler, M and Moore, B and Stebbins, T and Vance, S and Williams, K and Yee, A},
title = {Recommended Essential Equipment for Basic Life Support and Advanced Life Support Ground Ambulances 2020: A Joint Position Statement.},
journal = {Prehospital emergency care},
volume = {25},
number = {3},
pages = {451-459},
doi = {10.1080/10903127.2021.1886382},
pmid = {33557659},
issn = {1545-0066},
mesh = {Allied Health Personnel ; Ambulances ; Certification ; *Emergency Medical Services ; *Emergency Medical Technicians ; Humans ; },
abstract = {In continued support of establishing and maintaining a foundation for standards of care, our organizations remain committed to periodic review and revision of this position statement. This latest revision was created based on a structured review of the National Model EMS Clinical Guidelines Version 2.2 in order to identify the equipment items necessary to deliver the care defined by those guidelines. In addition, in order to ensure congruity with national definitions of provider scope of practice, the list is differentiated into BLS and ALS levels of service utilizing the National Scope of Practice-defined levels of Emergency Medical Responder (EMR) and Emergency Medical Technician (EMT) as BLS, and Advanced EMT (AEMT) and Paramedic as ALS. Equipment items listed within each category were cross-checked against recommended scopes of practice for each level in order to ensure they were appropriately dichotomized to BLS or ALS levels of care. Some items may be considered optional at the local level as determined by agency-defined scope of practice and applicable clinical guidelines. In addition to the items included in this position statement our organizations agree that all EMS service programs should carry equipment and supplies in quantities as determined by the medical director and appropriate to the agency's level of care and available certified EMS personnel and as established in the agency's approved protocols.},
}

Allied Health Personnel
Ambulances
Certification
*Emergency Medical Services
*Emergency Medical Technicians
Humans

@article {pmid41384353,
year = {2025},
author = {Yu, H and Zhang, X and Liu, Z and Zhang, L},
title = {Explaining Isoform Selectivity of c-Jun N-Terminal Kinase 3 (JNK3) Inhibitors through Its Development and Structural Insights.},
journal = {Journal of medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jmedchem.5c01488},
pmid = {41384353},
issn = {1520-4804},
abstract = {c-Jun N-terminal kinase 3 (JNK3), a member of the mitogen-activated protein kinase (MAPK) family, is selectively enriched in the brain. It plays a significant role in the pathogenesis of neurodegenerative disorders, glaucoma, amyotrophic lateral sclerosis, and cancer, which makes it a promising drug target. However, the advancement of JNK3 inhibitors has been challenged by limited isoform selectivity. This article explains the pathway regulated by JNK3 and the unique functions of JNK3. A detailed structural analysis of JNK3 complexes with ligands is presented to uncover the molecular basis of binding interactions. The inhibitors are systematically classified according to their chemical scaffolds, and the reason for their isoform selectivity was discussed, providing a structural rationale for the evolution of JNK3 inhibitor design. The perspective concludes with an exploration of the challenges in the discovery of selective JNK3 inhibitors and proposes innovative strategies to surmount these obstacles.},
}

@article {pmid41379273,
year = {2025},
author = {Zhang, R and Gao, B and Li, R and Zhou, R},
title = {Meta-analysis of the effects of dance- and movement-based kinesthetic games on cognitive function in older adults with cognitive impairment (CI) under different intervention periods.},
journal = {Aging clinical and experimental research},
volume = {37},
number = {1},
pages = {343},
pmid = {41379273},
issn = {1720-8319},
support = {24YJC890031//he Ministry of Education 's Youth Fund Project for Humanities and Social Sciences/ ; 22PJC094//Shanghai Pujiang Program/ ; },
mesh = {Humans ; *Cognitive Dysfunction/therapy/psychology ; Aged ; *Cognition/physiology ; *Video Games ; *Dancing ; *Dance Therapy/methods ; Male ; Randomized Controlled Trials as Topic ; *Exercise Therapy/methods ; Female ; },
abstract = {OBJECTIVE: To evaluate the effects of different types and durations of exergame interventions on cognition in elderly individuals with cognitive impairment (CI) through a meta-analysis.

METHODS: A computerized search was conducted in databases including Cochrane Library, PubMed, Web of Science, Embase, and CNKI from database inception to September 2025. Quality assessment and data extraction were performed on the included studies. Results measures included the MoCA , MMSE, etc. The study designs were randomized controlled trials or qua-si-experimental studies. The Cochrane Handbook's risk of bias tool was used for quality assessment, and Rev Man 5.0 software was employed to conduct meta-analyses on the ef-fects of dance-based and movement-based exergames on cognitive function in elderly CI patients.

RESULTS: A total of 13 studies involving 433 CI patients were included. Analysis of the 13 studies showed that dance-based exergaming was significantly superior to exercise-based exergaming in cognitive ability (SMD = 0.73, P < 0.01); interventions lasting ≥8 weeks were more effective than those lasting <8 weeks (SMD = 1.01, P = 0.02).

CONCLUSION: Dance-based exergames significantly improve cognition in elderly individu-als with CI, with better effects observed in long-term interventions. However, more high-quality studies are needed to verify these findings and to supplement analyses on ex-ercise dose effects.},
}

Humans
*Cognitive Dysfunction/therapy/psychology
Aged
*Cognition/physiology
*Video Games
*Dancing
*Dance Therapy/methods
Male
Randomized Controlled Trials as Topic
*Exercise Therapy/methods
Female

@article {pmid41375912,
year = {2025},
author = {Sancho, J and Ferrer, S and Signes-Costa, J},
title = {Noninvasive Ventilation Effectiveness in Amyotrophic Lateral Sclerosis.},
journal = {Journal of clinical medicine},
volume = {14},
number = {23},
pages = {},
pmid = {41375912},
issn = {2077-0383},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons; respiratory problems are the leading cause of death and hospital admissions and are secondary to progressive weakness of the respiratory muscles and upper airway. Noninvasive ventilation (NIV) can increase survival, alleviate symptoms, reduce hospital admissions, and improve the quality of life of these patients. The key factor in respiratory management of patients with ALS is achieving effective NIV; ineffective NIV has a negative impact on survival, with a reduction of up to 50% compared to patients with an effective technique. The most common cause of ineffective NIV is air leaks; other causes include upper airway obstruction events, residual hypoventilation, hyperventilation, and upper airway obstruction secondary to an oronasal mask. Regular monitoring of the effectiveness of NIV is essential given its impact on survival; the key tools that detect the main problems are the presence of hypoventilation symptoms, arterial blood gases, nocturnal oximetry and capnography, and built-in ventilator software. Different measures have been proposed to address the ineffectiveness of NIV, such as fitting the mask to reduce air leaks, increasing ventilatory support for residual hypoventilation, decreasing ventilatory support for hyperventilation, or a trial with a nasal mask to address oronasal interface effects. In the case of obstruction, the most common measure is to increase positive expiratory pressure during NIV. These measures enable NIV to be effective in 58% of cases, achieving a survival rate similar to that of patients who have effective NIV from the outset.},
}

@article {pmid41205880,
year = {2026},
author = {Cho, H and Lee, B and Son, C and Choi, J and Eom, S and Park, J},
title = {ERLIN1: A central regulator of protein quality control, lipid homeostasis, and cellular signaling at the endoplasmic reticulum.},
journal = {Cellular signalling},
volume = {138},
number = {},
pages = {112224},
doi = {10.1016/j.cellsig.2025.112224},
pmid = {41205880},
issn = {1873-3913},
mesh = {Humans ; *Endoplasmic Reticulum/metabolism ; *Membrane Proteins/metabolism/genetics ; Homeostasis ; *Signal Transduction ; Animals ; *Lipid Metabolism ; Endoplasmic Reticulum-Associated Degradation ; Cholesterol/metabolism ; Nerve Tissue Proteins ; },
abstract = {Endoplasmic reticulum lipid raft-associated protein 1 (ERLIN1) is an endoplasmic reticulum (ER)-resident stomatin/prohibitin/flotillin/HflK/C (SPFH) family protein that assembles into oligomeric complexes within detergent-resistant membrane domains. ERLIN1 regulates multiple cellular functions, including protein quality control, calcium signaling, and lipid metabolism. Together with ERLIN2, it forms ER-associated degradation (ERAD) nanodomains through interactions with RING finger protein 170 (RNF170) and transmembrane and ubiquitin-like domain-containing 1 (TMUB1). These specialized domains facilitate the degradation of inositol 1,4,5-trisphosphate receptor type 1 (IP3R) via the ERAD pathway. ERLIN1 also controls cholesterol metabolism by inhibiting sterol regulatory element-binding protein (SREBP) activation and promoting 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) degradation. In addition, it blocks cholesterol esterification, thereby enhancing cholesterol transport to the Golgi apparatus. ERLIN1 further regulates cell fate by promoting autophagy and suppressing apoptosis; in complex with ERLIN2, it interacts with activating molecule in Beclin 1-regulated autophagy protein 1 (AMBRA1) at mitochondria-associated membranes to initiate autophagy and binds phosphatidylinositol 3-phosphate to stabilize autophagy signaling. Its overexpression enhances tumor progression, whereas silencing triggers apoptosis in colorectal cancer. Mutations in ERLIN1 are linked to neurodegenerative diseases such as hereditary spastic paraplegia type 62 and atypical amyotrophic lateral sclerosis. The ERLIN1/2 complex also influences immune responses and viral replication through cholesterol regulation. Collectively, these diverse and integrated functions highlight the potential of ERLIN1 as a therapeutic target in cancer, metabolic, neurodegenerative, and infectious diseases.},
}

Humans
*Endoplasmic Reticulum/metabolism
*Membrane Proteins/metabolism/genetics
Homeostasis
*Signal Transduction
Animals
*Lipid Metabolism
Endoplasmic Reticulum-Associated Degradation
Cholesterol/metabolism
Nerve Tissue Proteins

@article {pmid41375893,
year = {2025},
author = {Gratzer, A and Gdynia, N and Sasse, N and Beese, R and Winterholler, C and Bauer, Y and Schröter, C and Gdynia, HJ},
title = {Rehabilitation in Amyotrophic Lateral Sclerosis: Recommendations for Clinical Practice and Further Research.},
journal = {Journal of clinical medicine},
volume = {14},
number = {23},
pages = {},
pmid = {41375893},
issn = {2077-0383},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative condition characterized by the degeneration of upper and lower motor neurons. This degeneration leads to a gradual muscle weakness, dysarthria, dysphagia, respiratory insufficiency, and, in some patients, alterations in cognitive and behavioral performance. Regardless of advancements made in pharmacological and gene-targeted interventions, a definitive curative treatment remains elusive. Consequently, rehabilitation plays a pivotal role in preserving autonomy, participation, and overall quality of life. This review outlines the current evidence and clinical approaches related to multidisciplinary rehabilitation in ALS. It covers physical and occupational therapy, respiratory, speech and language, psychological, and palliative care domains. Evidence supports moderate tailored exercise programs, early respiratory therapy, and structured management of mobility deficits, spasticity, pain, dysphagia, and communication impairments as key elements of symptomatic treatment. Psychological and social support, which includes the involvement of caregivers and relatives, enhances emotional well-being and coping resilience. Even with progressive development of gene-targeted and disease-modifying therapies, rehabilitation will stay relevant for maintaining long-term motor function. This review highlights the need for standardized, evidence-based rehabilitation protocols and intensified neurorehabilitation research to strengthen clinical outcomes and quality of life as key therapeutic goals in ALS management.},
}

@article {pmid41373784,
year = {2025},
author = {Basavarajappa, BS and Subbanna, S},
title = {From Synaptic Plasticity to Neurotoxicity: Endocannabinoid Influence on Addiction and Neurodegeneration.},
journal = {International journal of molecular sciences},
volume = {26},
number = {23},
pages = {},
pmid = {41373784},
issn = {1422-0067},
mesh = {Humans ; *Endocannabinoids/metabolism ; *Neuronal Plasticity ; Animals ; *Neurodegenerative Diseases/metabolism ; *Substance-Related Disorders/metabolism ; Receptors, Cannabinoid/metabolism ; },
abstract = {The endocannabinoid system (eCBS) is a versatile neuromodulatory network that orchestrates synaptic plasticity, reward processing, and neuronal homeostasis. Increasing evidence implicates eCBS dysregulation in both addiction and neurodegenerative (ND) disorders, suggesting overlapping molecular and cellular mechanisms underlying these conditions. This review synthesizes recent advances in understanding how eCBS components-cannabinoid receptors (CB1 and CB2), endogenous ligands (anandamide and 2-arachidonoylglycerol), and their metabolic enzymes-modulate dopaminergic and glutamatergic signaling within reward and reinforcement circuits. Chronic exposure to drugs of abuse, including alcohol, opioids, cocaine, and methamphetamine, perturbs eCBS homeostasis, promoting oxidative stress, neuroinflammation, excitotoxicity, mitochondrial dysfunction, and protein aggregation-pathological features common to Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis. These overlapping mechanisms disrupt neuronal integrity and contribute to progressive neurotoxicity, highlighting shared pathogenic pathways between addiction and neurodegeneration. Despite these advances, critical gaps remain in delineating how substance-induced eCBS alterations precipitate neurodegenerative cascades. Addressing these gaps will be essential for harnessing the eCBS as a therapeutic target to mitigate addiction-driven neurotoxicity and age-related cognitive decline.},
}

Humans
*Endocannabinoids/metabolism
*Neuronal Plasticity
Animals
*Neurodegenerative Diseases/metabolism
*Substance-Related Disorders/metabolism
Receptors, Cannabinoid/metabolism

@article {pmid41373533,
year = {2025},
author = {Apolloni, S and Tortoriello, S and Milani, M and Rossi, S},
title = {Extracellular Matrix Remodeling in Motor Neuron Diseases.},
journal = {International journal of molecular sciences},
volume = {26},
number = {23},
pages = {},
doi = {10.3390/ijms262311376},
pmid = {41373533},
issn = {1422-0067},
support = {GR-2021-12375436//Ministero della Salute/ ; PNRR project "Rome Technopole - Innovation Ecosystem"//European Union/ ; },
mesh = {Humans ; *Extracellular Matrix/metabolism/pathology ; *Motor Neuron Disease/metabolism/pathology ; Animals ; Amyotrophic Lateral Sclerosis/metabolism/pathology ; Motor Neurons/metabolism/pathology ; },
abstract = {The extracellular matrix (ECM) constitutes a dynamic scaffold composed of both cellular and non-cellular elements that not only ensure tissue integrity but also regulate signaling events crucial for development and homeostasis. While its dysregulation has long been investigated in cancer, fibrosis, and autoimmunity, increasing evidence implicates ECM remodeling in neurodegenerative diseases, including motor neuron diseases (MNDs). Amyotrophic lateral sclerosis and spinal muscular atrophy, the most studied MNDs, both exhibit profound ECM alterations that influence synaptic connectivity, glial reactivity, and neuroinflammation. This review outlines recent data on ECM dynamics in MNDs, highlighting shared and disease-specific mechanisms, their potential as biomarkers, and therapeutic opportunities targeting the ECM environment to preserve neuronal function and slow disease progression.},
}

Humans
*Extracellular Matrix/metabolism/pathology
*Motor Neuron Disease/metabolism/pathology
Animals
Amyotrophic Lateral Sclerosis/metabolism/pathology
Motor Neurons/metabolism/pathology

@article {pmid41373461,
year = {2025},
author = {Butcher, EL and Arthur, S},
title = {Emerging Roles of Bile Acids in Neuroinflammation.},
journal = {International journal of molecular sciences},
volume = {26},
number = {23},
pages = {},
doi = {10.3390/ijms262311301},
pmid = {41373461},
issn = {1422-0067},
mesh = {Humans ; *Bile Acids and Salts/metabolism ; *Neuroinflammatory Diseases/metabolism/pathology ; Animals ; Gastrointestinal Microbiome ; Signal Transduction ; Biomarkers/metabolism ; Blood-Brain Barrier/metabolism ; Inflammation/metabolism ; Central Nervous System/metabolism ; },
abstract = {Bile acids, once considered mere digestive detergents, have emerged as multifaceted signaling molecules with systemic influence extending far beyond the gastrointestinal tract. Recent discoveries reveal their capacity to modulate immune responses, cross the blood-brain barrier, and interact with central nervous system (CNS) cells through their receptors. Neuroinflammation, a key driver of neurodegenerative and neuroimmune disorders, is increasingly linked to bile acid signaling pathways that regulate glial activation, cytokine production, and neuronal survival. This review compiles the current evidence connecting bile acids to CNS inflammation, highlighting mechanistic insights, disease-specific alterations, and the gut-microbiome-bile acid-brain axis. It also explores the therapeutic potential of bile acid derivatives and receptor modulators, as well as their emerging role as biomarkers in conditions such as Alzheimer's disease, multiple sclerosis, and hepatic encephalopathy. Despite promising advances, critical gaps remain, including the need for bile receptor mapping in human CNS cells, standardized CNS bile acid profiling, and longitudinal metabolomic studies. Bridging these gaps may unlock new strategies for targeting neuroinflammation through bile acid-immune crosstalk.},
}

Humans
*Bile Acids and Salts/metabolism
*Neuroinflammatory Diseases/metabolism/pathology
Animals
Gastrointestinal Microbiome
Signal Transduction
Biomarkers/metabolism
Blood-Brain Barrier/metabolism
Inflammation/metabolism
Central Nervous System/metabolism

@article {pmid41366852,
year = {2025},
author = {Barahona-López, C and Plans-Beriso, E and Diez-Echave, P and Hernández, O and de Larrea, NF and Craciun, O and García-Ovejero, E and Petrova, D and Fernández-Martínez, NF and Arruabarrena-Blanco, E and Babb-de-Villiers, C and Turner, H and Jimenez, RC and Erady, C and Wilson, H and Fernández-Navarro, P and García-Esquinas, EG and Kuhn, I and Sánchez, P and Rodríguez-Artalejo, F and Sánchez, MJ and Moreno, V and Blackburn, L and Pollán, M and Kroese, M and Perez-Gomez, B},
title = {Personalized prevention of neurodegenerative diseases: scoping review and evidence gap map.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {12},
pages = {e70980},
pmid = {41366852},
issn = {1552-5279},
support = {101057721//Horizon Europe / H2020 Health/ ; 10040946//UKRI/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/prevention & control/genetics ; Biomarkers ; *Precision Medicine/methods ; Evidence Gaps ; },
abstract = {Neurodegenerative diseases represent a major public health challenge due to their high prevalence and poor prognosis. Identifying biomarkers to stratify individuals by their risk of developing these diseases may help to define new personalized prevention interventions. The objective of this study was to conduct a scoping review of biomarkers for primary and secondary personalized prevention of neurodegenerative diseases. The search targeted biomarkers in adults or high-risk subpopulations in clinical or public health settings for Alzheimer's disease, vascular dementia, Lewy body disease, frontotemporal dementia, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis. Ultimately, 286 papers were included in the review and the interactive gap map. There is a strong focus on Alzheimer's disease, and most papers included -omics-based biomarkers and/or used artificial intelligence. Genetics/genomics are at the forefront of current scientific research, although there is a notable gap in studying gene-environment interactions, and studies in clinical settings are still scarce. HIGHLIGHTS: Research indicates a strong focus on Alzheimer´s disease and limited research in other diseases. Genetics and genomics are at the forefront of current scientific research. We found biomarkers for predicting progression in mild cognitive decline. There is a notable gap in studying gene-environment interactions. Studies investigating biomarkers in a clinical context are still scarce.},
}

Humans
*Neurodegenerative Diseases/prevention & control/genetics
Biomarkers
*Precision Medicine/methods
Evidence Gaps

@article {pmid41366746,
year = {2025},
author = {Huang, J and Liu, Y and Li, M and He, R and Tang, Z and Lei, Y and Zha, Y and Wei, J},
title = {Safety and efficacy of botulinum toxin injection for sialorrhea in amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {BMC neurology},
volume = {25},
number = {1},
pages = {496},
pmid = {41366746},
issn = {1471-2377},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, with 80% of ALS patients experiencing bulbar weakness at some stage of the disease. ALS patients with bulbar weakness often suffer from troublesome sialorrhea. Botulinum toxin injection, as a neuromuscular blocker, has been widely used in the treatment of sialorrhea. This paper evaluates the safety and efficacy of botulinum toxin injections for the treatment of sialorrhea in ALS patients through a systematic review and meta-analysis.

METHODS: A systematic review and meta-analysis was conducted by searching eight databases, including PubMed, EMBASE, and CNKI, up to April 13, 2025. Eligible randomized controlled trials and quasi-experimental studies were analyzed using Review Manager 5.4 and Stata software.

RESULTS: Thirteen studies (2 RCTs, 11 quasi-experimental studies) with 130 ALS patients were included. Botulinum toxin significantly reduced sialorrhea and improved quality of life (Z = 10.98, p < 0.00001; RD = 0.82, 95% CI: 0.67–0.97). The treatment effect was independent of toxin type (p = 0.48), injection site (p = 0.17), and ultrasound guidance use (p = 0.44).

CONCLUSION: Botulinum toxin appears to be a safe and effective option for managing sialorrhea in ALS patients, regardless of injection technique. However, given that most included studies were observational, further validation through high-quality RCTs is warranted.

TRIAL REGISTRATION: This meta-analysis has been registered with Prospero, and the registration number is CRD420251029441. The registration period is April 9, 2025.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12883-025-04515-8.},
}

@article {pmid41356579,
year = {2025},
author = {Seyam, MK and Shaik, RA and Miraj, M and Alzahrani, NS and Shaik, AR and Ajmera, P and Kalra, S and Miraj, SA and Shawky, GM and Nurani, KM and A, P},
title = {Effect of mobile phone applications on medication adherence among patients with coronary artery diseases: A scoping review.},
journal = {World journal of cardiology},
volume = {17},
number = {11},
pages = {114140},
pmid = {41356579},
issn = {1949-8462},
abstract = {Patients with cardiovascular disease rely on medication to achieve favorable long-term clinical results. Poor adherence has been linked to a relative increase in mortality of 50%-80% as well as higher health care costs. This scoping review thus aimed to explore the evidence of the effects of mobile health care apps on medication adherence in patients with cardiovascular diseases. A comprehensive data search and extraction was done in line with the updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews checklist. A total of 10 studies were included for the review. The mean pooled improvement in adherence was found to be 18% and the most effective tool was the digital therapeutics app discussed in Li et al's study. Smartphones and apps enhance coronary artery disease management by promoting medication compliance. Challenges include data security and smartphone usage among the elderly. Tailored apps or voice assistants offer potential solutions.},
}

@article {pmid41354564,
year = {2025},
author = {Mouhi, S and Pio, T and Andersen, J},
title = {Revisiting oligodendrocytes in amyotrophic lateral sclerosis using human multicellular stem cell models.},
journal = {Trends in cell biology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tcb.2025.11.003},
pmid = {41354564},
issn = {1879-3088},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration, muscle wasting, and eventual paralysis. The clinical and genetic complexity along with rapid disease progression has hindered efforts to model the disease and develop effective treatments. Rodent models and human tissue studies point to dysfunction in oligodendrocyte lineage cells early in disease, although the underlying mechanisms remain unclear. Advances in stem cell research have introduced novel platforms to investigate cells in the oligodendrocyte lineage and their interactions with neurons and other glial cells in complex human genetic backgrounds. This Review summarizes the literature implicating oligodendrocyte lineage cells in ALS and discusses both the potential and limitations of in vitro-derived cultures to shed light on their vulnerabilities and cellular interactions.},
}

@article {pmid41352634,
year = {2025},
author = {Geleta, LA and Doyle, C and Garton, FC and Fowler, M and Carr, JM and Akkari, PA and McRae, AF and Rogers, ML and Madakkatel, I and Benyamin, B},
title = {The roles of human endogenous retrovirus in neurodegenerative diseases: A systematic review.},
journal = {Brain, behavior, and immunity},
volume = {132},
number = {},
pages = {106201},
doi = {10.1016/j.bbi.2025.106201},
pmid = {41352634},
issn = {1090-2139},
abstract = {BACKGROUND: Human endogenous retroviruses (HERVs) constitute ∼8 % of the human genome, far exceeding the 2 % occupied by protein-coding genes. Although most HERV sequences are inactive, some HERV elements can be reactivated under certain conditions and may contribute to neurodegenerative diseases (NDDs). However, the findings vary across different HERV families, disease models, and detection methods. Here, we systematically review and synthesize the available evidence on the role of HERVs in human NDDs and reconcile inconsistencies in the literature.

METHODS: We systematically searched MEDLINE, EMBASE, Cochrane Library, PsycINFO, Scopus, Web of Science, CINAHL, and Emcare to identify relevant studies. Two independent reviewers screened studies, assessed quality, and extracted data. Qualitative synthesis was conducted for all included NDDs, specifically Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Parkinson's disease (PD), and due to data availability, meta-analysis was used to assess the impact of HERVs antibodies on ALS only.

RESULTS: Twenty-six studies (N ranges: 6-485) met the inclusion criteria, with majority focusing on HERV-K and ALS. Across studies, the association between HERV expression and NDDs was inconsistent, particularly for ALS, PD, and FTD, whereas investigations in AD showed a more consistent upregulation of specific HERVs. Studies relying on polymerase chain reaction (PCR) (typically smaller) showed inconsistent associations (21 studies), while RNA sequencing studies reported consistent associations (9 studies). A preliminary meta-analysis revealed a fivefold increase [OR: 5.83; 95 % CI: 4.14, 8.18] in ALS risk among participants with positive HERV antibodies.

CONCLUSIONS: The inconsistencies in HERV involvement across NDDs highlight the need for further studies employing standardized methodologies. RNAseq findings on the association of HERVs expression and NDDs support the need for large-scale RNA sequencing studies (rather than small, PCR studies) and careful tissue selection to clarify HERVs' role in NDDs. The association of HERV-K antibodies with ALS risk and prognosis suggests a significant role in disease, which could help detect biomarkers and used as a target for treatment.},
}

@article {pmid40925732,
year = {2025},
author = {, },
title = {[Expert consensus on the diagnosis and treatment of sleep-disordered breathing related to neuromuscular diseases].},
journal = {Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases},
volume = {48},
number = {9},
pages = {815-830},
doi = {10.3760/cma.j.cn112147-20250614-00332},
pmid = {40925732},
issn = {1001-0939},
support = {82270107//National Natural Science Fundation of China/ ; },
mesh = {Humans ; *Neuromuscular Diseases/complications ; *Sleep Apnea Syndromes/diagnosis/therapy/etiology ; Consensus ; Noninvasive Ventilation ; Sleep Apnea, Obstructive/diagnosis/therapy ; China ; },
abstract = {Neuromuscular diseases are often accompanied by various types of sleep-related breathing disorders, which can exacerbate the underlying condition and are associated with a poor prognosis. Early identification is essential, and interventions such as non-invasive ventilation, oxygen therapy, and respiratory rehabilitation should be initiated promptly to mitigate disease progression and improve outcomes. Nevertheless, the rates of missed and misdiagnosed cases remain common in clinical practice. Currently, there are no standardized guidelines for the diagnosis and treatment of sleep-disordered breathing related to neuromuscular diseases in China. Therefore, based on the latest domestic and international research progress, and combined with domestic clinical diagnosis and treatment experience, the Sleep Disorder Group of Chinese Thoracic Society has brought together multidisciplinary experts to develop this expert consensus. This consensus provides a comprehensive overview of the epidemiology, clinical manifestations, diagnostic approaches, assessment strategies, and treatment of sleep-disordered breathing related to neuromuscular diseases. It formulates evidence-based recommendations to guide clinical practice, with the aim of providing standardized recommendations for their diagnosis and management.Statement 1: The neuromuscular disorders that are most frequently associated with sleep-disordered breathing include: myasthenia gravis (1A), amyotrophic lateral sclerosis (2B), post-polio syndrome (2B), myotonic dystrophy (2B), peripheral neuropathies (2C), and metabolic myopathies, among other neuromuscular conditions.Statement 2: Patients with neuromuscular disorders frequently develop multiple types of sleep-disordered breathing concurrently or sequentially, with obstructive sleep apnea (OSA) being the most prevalent manifestation. Distinct clinical manifestations of OSA are observed across different neuromuscular disease subtypes (1A).Statement 3: Neuromuscular disorders predispose to central sleep apnea (CSA), with clinical manifestations varying significantly across disease subtypes, stages of progression, and severity levels (1A).Recommendation 1: In patients with neuromuscular disorders exhibiting progressive hypercapnia or worsening hypoxemia, clinicians should investigate potential comorbid nocturnal alveolar hypoventilation and/or sleep-associated hypoxemia (1A).Recommendation 2: When sleep-disordered breathing is suspected, patients with neuromuscular disorders should be evaluated for symptoms of sleep-disordered breathing. Meanwhile, sleep monitoring, non-invasive CO2 monitoring, and related examinations should be actively performed according to the actual situation (1A). A polysomnography should be performed when there is a high clinical suspicion of sleep-disordered breathing but a negative result on a portable sleep monitor (1A).Recommendation 3: (1) Noninvasive positive pressure ventilation (NPPV) titration under polysomnography is the standard method to determine the effective treatment parameters for neuromuscular diseases with sleep-disordered breathing (1A). (2) Positive airway pressure titration in OSA patients with neuromuscular diseases should follow American Academy of Sleep Medicine (AASM) guidelines (1A). (3) For neuromuscular disorders with CSA or Cheyne-Stokes respiration, bi-level positive airway pressure (BPAP) with ST pattern is recommended (1A); When BPAP is not tolerated or accompanied by severe Cheyne-Stokes respiratory and heart failure in patients, adaptive support ventilation (ASV) should be used (2B). (4) Patients with neuromuscular disease and sleep-related alveolar hypoventilation should be treated with BPAP or variable assurance pressure support (VAPS) (1A). (5) BPAP with alternate frequency is preferred for neuromuscular disorders with "pseudo-central events" (1A).Recommendation 4: Oxygen therapy alone is not recommended for neuromuscular disease patients combined with sleep-disordered breathing (2D). Oxygen therapy with monitoring of CO2 level is recommended when non-invasive ventilation therapy cannot effectively correct hypoxemia (2C). Diaphragmatic pacing should not be routinely used in amyotrophic lateral sclerosis patients with respiratory failure (2B). Transvenous phrenic nerve stimulation is not currently applied to CSA caused by neuromuscular disorders (2D). Respiratory rehabilitation may improve respiratory muscle strength in a subset of patients with neuromuscular disorders (2B). Protiline can be used for REM-associated alveolar hypoventilation, and daytime sleepiness could be addressed with methylphenidate and modafinil (2C).Recommendation 5: Neuromuscular disease combined with sleep-disordered breathing is a chronic disease requiring patient-centered, individualized education and long-term follow-up management (1A).},
}

Humans
*Neuromuscular Diseases/complications
*Sleep Apnea Syndromes/diagnosis/therapy/etiology
Consensus
Noninvasive Ventilation
Sleep Apnea, Obstructive/diagnosis/therapy
China

@article {pmid41351663,
year = {2025},
author = {Amirian, R and Merati, A and Babamohamadi, M and Mirahmadi, Y and Esfahani, ML and Rahmani, S and Izadi, Z and Rezazadeh, D},
title = {Navigating the Autophagy Maze: ATG and Their Impact on Neurodegenerative Diseases.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {260},
pmid = {41351663},
issn = {1559-1182},
mesh = {*Autophagy/genetics/physiology ; Humans ; *Neurodegenerative Diseases/genetics/metabolism/pathology ; Animals ; *Autophagy-Related Proteins/metabolism/genetics ; Signal Transduction ; },
abstract = {Autophagy, a tightly regulated process essential for maintaining cellular homeostasis, plays a critical role in the pathogenesis and progression of neurodegenerative diseases (NDs). These disorders-marked by diverse mechanisms and clinical heterogeneity-pose significant challenges in developing effective therapies. Central to the autophagic machinery are autophagy-related genes (ATGs), whose functions and variants are increasingly recognized as pivotal in modulating disease-specific pathways. This review explores the intricate roles of ATGs in NDs, emphasizing the need for a comprehensive understanding of molecular signaling networks, protein-protein interactions, and regulatory checkpoints that may serve as therapeutic targets. We highlight recent advancements in disease modeling, autophagy assays, and biomarker identification that facilitate the translation of ATG-related discoveries into clinical practice. Furthermore, we underscore the importance of interdisciplinary collaboration across academia, industry, clinical medicine, and regulatory bodies to harness the therapeutic potential of autophagy. This article aims to serve as a detailed roadmap for understanding the role of ATGs in NDs and to illuminate promising avenues for future research and therapeutic development.},
}

*Autophagy/genetics/physiology
Humans
*Neurodegenerative Diseases/genetics/metabolism/pathology
Animals
*Autophagy-Related Proteins/metabolism/genetics
Signal Transduction

@article {pmid41349278,
year = {2025},
author = {García-Parra, B and Guiu, JM and Povedano, M and Modamio, P},
title = {Real-world evidence supporting orphan drugs approvals for rare neuromuscular disorders in the European Union and the United States: Review of public assessment reports (2015-2025).},
journal = {Current opinion in pharmacology},
volume = {86},
number = {},
pages = {102586},
doi = {10.1016/j.coph.2025.102586},
pmid = {41349278},
issn = {1471-4973},
abstract = {Real-world data (RWD) and real-world evidence (RWE) are becoming essential complements to conventional clinical trials for drug assessment, particularly for rare neuromuscular disorders where small patient populations heighten outcome uncertainty. Robust RWE could reduce that uncertainty and inform regulatory decisions on orphan drugs (ODs). To review how the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) have incorporated RWE into OD approvals for neuromuscular diseases from January 2015 to January 2025. We reviewed all publicly available EMA European Public Assessment Reports and FDA review packages for ODs targeting neuromuscular indications. Each document was screened for mention of RWD sources and by the regulatory weight assigned to the resulting RWE. We identified 14 OD approvals by the EMA and 13 by the FDA, with greater use of RWE by the FDA. Indications comprised spinal muscular atrophy (3/3 EMA/FDA), amyotrophic lateral sclerosis (1/3), amyloid neuropathies (2/2), Friedreich ataxia (1/1), Lambert-Eaton syndrome (1/1), myasthenia gravis (2/2), myotonic disorders (1/0), and Duchenne muscular dystrophy (2/1). Among 18 evaluable dossiers, clinical outcome assessments (COA) were reported as follows: patient-reported outcomes - 39.1%, clinician-reported outcomes - 34.7%, observer-reported outcomes - 13.1 %, and performance outcomes - 13.1%. Only tofersen incorporated all COA types. The use of RWE for the evaluation of ODs is increasing for both the FDA and the EMA, more so for the former than for the latter. Harmonized methodological standards and transparent reporting frameworks are urgently needed to generate quality evidence that benefits stakeholders.},
}

@article {pmid41345582,
year = {2025},
author = {Ebrahimian, A and Moradi, A and Athari, SZ and Farajdokht, F},
title = {Restless legs syndrome as a comorbidity in amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {BMC neurology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12883-025-04543-4},
pmid = {41345582},
issn = {1471-2377},
support = {74962//Student Research Committee, Tabriz University of Medical Sciences/ ; },
abstract = {BACKGROUND: Restless Legs Syndrome (RLS), characterized by an urge to move the legs, is linked to neurodegenerative diseases. Emerging evidence suggests a higher RLS prevalence in Amyotrophic Lateral Sclerosis (ALS), impacting quality of life. However, there is lack of comprehensive review addressing its prevalence and associated risk factors. This meta-analysis estimates RLS prevalence in ALS patients compared to healthy controls.

METHODS: We searched PubMed, Embase, Web of Science, and Scopus for studies assessing RLS in ALS patients versus controls, adhering to PRISMA guidelines. Two reviewers independently extracted data and assessed bias using Joanna Briggs Institute (JBI) checklist. Meta-analysis used Comprehensive Meta-Analysis software with a random-effects model due to heterogeneity. The certainty of evidence was appraised using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework.

RESULTS: Out of 291 studies, eight studies (792 ALS, 716 controls) were included. The pooled RLS prevalence in ALS was 17% (95% CI: 14.0%-21.1%; I²: 56.5%; p-value < 0.001). The fixed effect meta-analysis of four studies indicated that the difference of RLS prevalence was statically significant between patients with ALS and healthy controls (OR: 5.65; CI: 2.86-11.13; P-value < 0.001; I²: 28.7.).

CONCLUSION: RLS is significantly more prevalent in ALS patients, potentially worsening sleep and quality of life, mental health, and social well-being. Therefore, it is essential to draw clinicians' attention to RLS in ALS patients due to its potential impact on overall health.},
}

@article {pmid41345047,
year = {2025},
author = {Bahbah, EI},
title = {Tetramethylpyrazine nitrone: a multifaceted neuroprotective agent in neurodegenerative disorders.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-15},
doi = {10.1080/17582024.2025.2598227},
pmid = {41345047},
issn = {1758-2032},
abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) share key pathological features, including oxidative stress, mitochondrial dysfunction, and impaired protein homeostasis, yet remain without effective disease-modifying therapies. Tetramethylpyrazine nitrone (TBN), a synthetic derivative of tetramethylpyrazine bearing a free radical-scavenging nitrone moiety, has emerged as a promising multi-target neuroprotective agent. This review synthesizes preclinical and clinical data supporting TBN's therapeutic potential in AD, PD, and ALS. In AD models, TBN reduces amyloid-β accumulation and tau hyperphosphorylation, enhances autophagic clearance, preserves synaptic integrity, and improves cognitive performance. In PD models, TBN confers dopaminergic neuroprotection, restores motor function, and promotes α-synuclein degradation, effects mediated largely through activation of the PGC-1α/Nrf2 pathway and augmentation of the ubiquitin-proteasome system (UPS). In ALS models, TBN mitigates motor neuron loss, improves motor performance, and extends survival, likely via the PGC-1α/Nrf2/HO-1 axis and enhanced autophagic activity. Phase I studies have established TBN's favorable oral and intravenous pharmacokinetics, effective blood - brain barrier penetration, and overall safety and tolerability in healthy volunteers. Owing to its multi-pathway mechanism, principally engaging antioxidant/mitochondrial pathways and proteostasis (autophagy/UPS), TBN represents a compelling candidate for continued clinical development, either as monotherapy or in combination with disease-specific interventions.},
}

@article {pmid41175990,
year = {2025},
author = {Konopka, A},
title = {Perspectives on the utilization of cell-free DNA in amyotrophic lateral sclerosis (ALS) diagnostics and prognostics - insight from cancer research.},
journal = {Neurobiology of disease},
volume = {217},
number = {},
pages = {107167},
doi = {10.1016/j.nbd.2025.107167},
pmid = {41175990},
issn = {1095-953X},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/blood ; *Cell-Free Nucleic Acids/blood ; Prognosis ; Biomarkers/blood ; },
abstract = {Amyotrophic lateral sclerosis (ALS) remains a devastating neurodegenerative disease with limited diagnostic and prognostic tools. In recent years, cell-free DNA (cfDNA) has emerged as a promising non-invasive biomarker in various clinical settings, particularly in oncology. Despite its potential, the application of cfDNA in ALS is still in its early stages, and several critical gaps must be addressed. This discussion article reviews the current knowledge about cfDNA in ALS and explores its potential applications for disease diagnosis, monitoring, and prognosis. Drawing on the advances made in cancer research, it also examines the challenges that ALS research may face in cfDNA utilization, highlighting lessons learned from oncology. Taken together, these insights point to the urgent need for a comprehensive understanding of cfDNA characteristics specific to ALS. Given the current lack of reliable diagnostic and prognostic biomarkers in ALS, further investigation into cfDNA represents a valuable and necessary scientific endeavor with the potential to transform patient care and disease management.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/genetics/blood
*Cell-Free Nucleic Acids/blood
Prognosis
Biomarkers/blood

@article {pmid41341655,
year = {2025},
author = {Almalki, S and Salama, M and Taylor, MJ and Ahmed, Z and Tuxworth, RI},
title = {C9orf72-related amyotrophic lateral sclerosis-frontotemporal dementia and links to the DNA damage response: a systematic review.},
journal = {Frontiers in molecular neuroscience},
volume = {18},
number = {},
pages = {1671906},
pmid = {41341655},
issn = {1662-5099},
abstract = {The G4C2 repeat expansion in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). While healthy individuals have fewer than 30 repeats, affected patients may carry hundreds to thousands. This expansion accounts for approximately 40% of familial ALS and 25% of familial FTD cases, and between 5 and 10% cases of sporadic ALS and FTD. Three overlapping pathological mechanisms have been proposed for the C9orf72 expansion: loss of function due to protein deficiency, gain of function through RNA foci, and the production of toxic dipeptide repeat proteins (DPRs) via repeat-associated non-ATG (RAN) translation. This systematic review investigates the role of DNA damage in C9orf72-related ALS-FTD. Analysis of twelve peer-reviewed studies showed that C9orf72 repeat expansions and DPRs compromise genome stability across four experimental models: human cell lines, induced pluripotent stem cell-derived neurons, rodent neurons, and postmortem tissue. We identified four mechanisms underlying DNA damage accumulation: disruption of the ATM pathway, impairment of DNA repair efficiency, formation of R-loops, and mitochondrial dysfunction with oxidative stress. In addition, several consequences of DNA damage were identified, including misrepair-mediated repeat expansion and activation of STING pathway. These findings highlight the key role of DNA damage in C9orf72-related pathology. Consistent with this, targeting DNA damage response factors extended lifespan and improved motor function in mouse models. This review highlights the contribution of DNA damage to C9orf72 pathology and suggest new therapeutic avenues, including personalized approaches based on genetic background.},
}

@article {pmid41341510,
year = {2025},
author = {Yang, J and Yang, F and Chen, G and Liu, M and Yuan, S and Zhang, TE},
title = {Receptor-mediated mitophagy: a new target of neurodegenerative diseases.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1665315},
pmid = {41341510},
issn = {1664-2295},
abstract = {Neurodegenerative diseases are a category of neurological conditions with high prevalence that pose major treatment challenges. Common pathologies involve protein accumulation and mitochondrial damage. Mitophagy maintains cellular homeostasis by removing defective mitochondria, which are associated with the pathogenesis of neurodegenerative diseases. Although the ubiquitin-dependent mitophagy mediated by the PINK1-Parkin pathway has been extensively studied, growing evidence indicates that receptor-mediated mitophagy plays a crucial compensatory role in neurons, particularly when the PINK1-Parkin pathway is impaired. This review focuses on the emerging field of receptor-mediated mitophagy, systematically elaborating its role as a key homeostatic mechanism operating independently of the canonical PINK1/Parkin pathway. It provides a focused analysis of the specific functions and activation mechanisms of key receptors-including BNIP3, NIX, FUNDC1, and AMBRA1-in models of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Furthermore, this review explores the clinical potential of targeting these specific receptors for precise intervention, aiming to provide a new theoretical foundation and direction for developing therapeutic strategies against neurodegenerative diseases.},
}

@article {pmid41330444,
year = {2025},
author = {Rosso, F and Magdalena, R and Torazza, C and Bacchetti, F and Milanese, M and Poletti, A and Bonanno, G and Cristofani, R and Bonifacino, T},
title = {Non-cell autonomous autophagy in amyotrophic lateral sclerosis: A new promising target?.},
journal = {Neurobiology of disease},
volume = {218},
number = {},
pages = {107203},
doi = {10.1016/j.nbd.2025.107203},
pmid = {41330444},
issn = {1095-953X},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative non-cell-autonomous disease with no cure, thus research is intensely focused on identifying pharmacological targets. Several studies aimed to clarify the pathogenic mechanisms and involvement in various cell types. A crucial factor in ALS is autophagy, which plays a key role in degrading intracellular protein aggregates. The connection between ALS and autophagy is reinforced by the fact that several genes mutated in ALS are linked to fundamental aspects of autophagy. The blockage of the autophagic flux was observed in ALS motor neurons, where it occurs earlier than in glia. However, the inconsistent effects of autophagy modulators in preclinical and clinical studies indicate the need for a deeper understanding of the role of autophagy in other cell types, such as astrocytes, microglia, and oligodendrocytes. Astrocytes and microglia are significantly impacted by autophagy dysregulation, contributing to neurodegeneration in both mouse and human-derived models. Autophagy is overactivated early in the disease, even before symptoms appear. This overactivation is influenced by the timing and specific tissue involved. It can alter cells' immunophenotype, favouring proinflammatory responses and affecting the cellular environment and autophagy in the surrounding cells. In contrast, oligodendrocytes show mild autophagic alterations. Additionally, sex hormones may affect proper autophagy function and ALS progression. The lack of information on how sex influences autophagy in glia highlights the need for more nuanced investigation into this mechanism. Future research should focus on these aspects, paving the way for personalised pharmacological approaches that consider the roles of cell types, time of intervention, and sex.},
}

@article {pmid41328916,
year = {2025},
author = {Ahsan, A and Kar, O and Akter, K and Ta, HDK and Shen, CJ and Datta, K and Chatterjee, B and Huang, CC and Majumder, P},
title = {Regulatory Functions of TDP-43 and FMRP in Non-Neuronal Diseases: Are Co-Targeted mRNAs the Keys?.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {39},
number = {23},
pages = {e71292},
doi = {10.1096/fj.202502281R},
pmid = {41328916},
issn = {1530-6860},
support = {110-2320-B-038-090-MY3//National Science and Technology Council (NSTC)/ ; },
mesh = {Humans ; *Fragile X Mental Retardation Protein/metabolism/genetics ; *DNA-Binding Proteins/metabolism/genetics ; *RNA, Messenger/genetics/metabolism ; Animals ; *Neurodegenerative Diseases/metabolism/genetics ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Fragile X Syndrome/genetics/metabolism ; },
abstract = {RNA binding proteins (RBPs) act as the central nodal point in shaping the cellular transcriptome through their involvement in various aspects of RNA metabolism including stability, splicing, polyadenylation, modifications, translation and transport. Dysregulation in the function of various RBPs can be associated with different human pathophysiological conditions. Owing to their ability to regulate various RNA metabolism-associated processes, the same RBPs can functionally be involved in human pathologies with distinct underlying pathophysiological mechanisms. Two such important RBPs, namely TDP-43 and FMRP, have long been implicated respectively, in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) etc. and in neurodevelopmental diseases like fragile-X syndrome (FXS). However, numerous recent reports indicate that these ubiquitously expressed proteins can regulate important cellular functions and signaling cascades, misregulation which results in different disease phenotypes. In this review, the association of TDP-43 and FMRP with different non-neuronal disease mechanisms has been discussed. Furthermore, to anticipate yet-to-be-explored non-neuronal disease mechanisms involving mismanagement in co-regulation of spatial and temporal transport/translation processes of TDP-43 and FMRP targeted RNAs, as observed in neuronal diseases for example, autism, RNA target databases of these two proteins are compared followed by GO and KEGG analysis. The lists of RNAs co-targeted by TDP-43 and FMRP are presumably involved in different non-neuronal diseases and disease-associated mechanistic pathways and will open up new phases of research to establish new disease mechanism(s). Different disease mechanisms and their interconnections expectantly will also lead to the discovery of new drug targets.},
}

Humans
*Fragile X Mental Retardation Protein/metabolism/genetics
*DNA-Binding Proteins/metabolism/genetics
*RNA, Messenger/genetics/metabolism
Animals
*Neurodegenerative Diseases/metabolism/genetics
Amyotrophic Lateral Sclerosis/genetics/metabolism
Fragile X Syndrome/genetics/metabolism

@article {pmid41126461,
year = {2025},
author = {Ayton, S and Moreau, C and Devos, D and Bush, AI},
title = {Iron on trial: recasting the role of iron in neurodegeneration.},
journal = {Brain : a journal of neurology},
volume = {148},
number = {12},
pages = {4241-4247},
doi = {10.1093/brain/awaf398},
pmid = {41126461},
issn = {1460-2156},
support = {//National Health & Medical Research Council of Australia/ ; //Florey Institute of Neuroscience/ ; },
mesh = {Humans ; *Iron/metabolism ; *Neurodegenerative Diseases/metabolism/drug therapy ; *Brain/metabolism ; Iron Chelating Agents/therapeutic use ; Animals ; Oxidative Stress/physiology ; },
abstract = {Iron is critical for numerous neurophysiological functions, while its dysregulation is potentially hazardous for neurodegeneration through oxidative stress and ferroptosis. For decades, elevated brain iron levels observed in neurodegenerative diseases such as Alzheimer's, Parkinson's and amyotrophic lateral sclerosis was presumed to drive disease progression; a hypothesis that propelled clinical trials of strong iron chelators like deferiprone. Results from these trials, however, have challenged this paradigm, with deferiprone markedly worsening outcomes in patients with Alzheimer's disease and, in certain contexts, patients with Parkinson's disease. These findings underscore the vital role of iron for brain health and suggest functional compensatory mechanisms that could become deleterious at the extremes of iron distribution (both low and high levels). Here, we outline an evolving understanding of iron's role in neurodegeneration, and we explore pathways for therapeutic development strategies that mitigate potential iron-mediated damage, while preserving its essential functions in the brain.},
}

Humans
*Iron/metabolism
*Neurodegenerative Diseases/metabolism/drug therapy
*Brain/metabolism
Iron Chelating Agents/therapeutic use
Animals
Oxidative Stress/physiology

@article {pmid41328354,
year = {2026},
author = {Huang, Q and Wang, S and Liu, Z and Rao, L and Cheng, K and Mao, X},
title = {Engineering exosomes for targeted neurodegenerative therapy: innovations in biogenesis, drug loading, and clinical translation.},
journal = {Theranostics},
volume = {16},
number = {1},
pages = {545-579},
pmid = {41328354},
issn = {1838-7640},
mesh = {Humans ; *Exosomes/metabolism ; *Neurodegenerative Diseases/drug therapy/therapy ; Animals ; *Drug Delivery Systems/methods ; Blood-Brain Barrier/metabolism ; Bioengineering/methods ; Translational Research, Biomedical ; },
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and multiple sclerosis (MS), are characterized by progressive neuronal dysfunction and limited therapeutic options, largely due to the restrictive nature of the blood-brain barrier (BBB). Exosomes, naturally occurring extracellular vesicles (EVs), have gained attention as innovative drug delivery vehicles owing to their intrinsic ability to cross the BBB, minimal immunogenicity, high biocompatibility, and capability to carry diverse therapeutic cargos such as proteins, nucleic acids, and small molecules. Furthermore, exosomes can be bioengineered to enhance drug-loading efficiency and targeting specificity, positioning them as a versatile and effective platform for treating NDDs. In this review, we summarize recent advances in exosome biogenesis, secretion, and engineering, with an emphasis on innovative strategies for exosome isolation, drug loading, and surface modification. We further explore their roles in modulating neuroinflammation, promoting neural regeneration, and enabling precise therapeutic delivery. Critical challenges associated with large-scale production, quality control, and regulatory compliance under Good Manufacturing Practices (GMP) are also discussed. Collectively, these developments underscore the transformative potential of engineered exosomes in advancing precision therapies for neurodegenerative disorders and offer strategic insights into their clinical translation.},
}

Humans
*Exosomes/metabolism
*Neurodegenerative Diseases/drug therapy/therapy
Animals
*Drug Delivery Systems/methods
Blood-Brain Barrier/metabolism
Bioengineering/methods
Translational Research, Biomedical

@article {pmid41327675,
year = {2025},
author = {Kiristioglu, MO and Akova, B and Sogutlu Sari, E and Baykara, M},
title = {Anterior segment optical coherence tomography in corneal diseases: A bibliometric analysis and visualization research of global research trends (1994-2024).},
journal = {Medicine},
volume = {104},
number = {48},
pages = {e45679},
doi = {10.1097/MD.0000000000045679},
pmid = {41327675},
issn = {1536-5964},
mesh = {*Tomography, Optical Coherence/methods/trends ; *Bibliometrics ; Humans ; *Corneal Diseases/diagnostic imaging ; *Biomedical Research/trends ; *Anterior Eye Segment/diagnostic imaging ; },
abstract = {PURPOSE: This study provides a bibliometric analysis of global research on anterior segment optical coherence tomography (AS-OCT) in corneal diseases, mapping key research trajectories, collaborations, and emerging trends.

METHODS: A systematic search in the Web of Science Core Collection on January 1, 2025, retrieved 3634 records (1994-2024). After excluding non-English publications, non-ophthalmology studies, and non-corneal research, 2079 publications were analyzed using VOSviewer and CiteSpace for citation networks, coauthorship trends, and keyword co-occurrence.

RESULTS: AS-OCT research has grown significantly (Mann-Kendall τ = 0.929, P < .001). The United States led in publications (639 papers, 19,594 citations), followed by China (333 papers, 4502 citations). The University of California was the most productive institution. The first AS-OCT study, published in the Archives of Ophthalmology (1994) by Izatt JA et al, marked the field's inception. The most cited article was Huang et al's 1991 Science paper on optical coherence tomography. Recent trends highlight the integration of artificial intelligence, deep learning, and optical coherence elastography in AS-OCT applications. The top 3 contributing journals were Cornea, Journal of Refractive Surgery, and Journal of Cataract and Refractive Surgery. Coauthorship analysis identified Jodhbir S. Mehta and David Huang as central figures in AS-OCT research collaborations.

CONCLUSION: AS-OCT research has expanded significantly, enhancing diagnostics, surgical planning, and disease monitoring. Artificial intelligence-driven analytics and optical coherence elastography are promising future directions. This bibliometric analysis guides advancing AS-OCT research and clinical applications.},
}

*Tomography, Optical Coherence/methods/trends
*Bibliometrics
Humans
*Corneal Diseases/diagnostic imaging
*Biomedical Research/trends
*Anterior Eye Segment/diagnostic imaging

@article {pmid41327179,
year = {2025},
author = {Eshak, D and Arumugam, M},
title = {Nanomaterials: an overview of current trends and future prospects in neurological disorder treatment.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {1366},
pmid = {41327179},
issn = {1479-5876},
mesh = {Humans ; *Nervous System Diseases/therapy/drug therapy ; *Nanostructures/therapeutic use/chemistry ; Animals ; Blood-Brain Barrier ; },
abstract = {The World Health Organization (WHO) has identified neurological disorders (NDs) as one of the major health concerns worldwide, resulting in high mortality rates. NDs are conditions affecting the central and peripheral nervous systems, including the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, neuromuscular junctions, and muscles. These neurological diseases include Alzheimer's disease, Parkinson's disease, glioma/brain cancer, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, neuroinfections, ischemic stroke, trauma, hypoxia/anoxia, and depression. Unfortunately, these disorders remain difficult to treat due to the limited ability of conventional drugs to cross the blood-brain barrier (BBB) and achieve significant pharmacological effects in the brain. There is an urgent need to develop methods that can enhance drug efficacy and bypass the BBB. The application of various nanomaterials represents a promising approach to address these neurological disorders. Drugs incorporated with nanomaterials help improve therapeutic outcomes, reduce toxicity, provide better stability, enable targeted delivery, and enhance drug loading capacity. Numerous types and morphologies of inorganic and organic nanomaterials are increasingly employed for treating NDs, including quantum dots, dendrimers, metal nanoparticles, polymeric nanoparticles, liposomes, carbon nanotubes, metal oxide nanoparticles, and micelles. Their exceptional properties such as sensitivity, selectivity, and potential to bypass the BBB make them suitable for both diagnosis and treatment of NDs. In this review article, we briefly summarize the etiology and pathophysiology of various NDs along with current literature highlighting the use of nanomaterials for treating neurological disorders.},
}

Humans
*Nervous System Diseases/therapy/drug therapy
*Nanostructures/therapeutic use/chemistry
Animals
Blood-Brain Barrier

@article {pmid41320876,
year = {2025},
author = {Tang, YB and Zhang, J and Liu, Q},
title = {tRNA-derived small noncoding RNAs: Roles in brain aging and neurodegenerative disorders.},
journal = {Zoological research},
volume = {46},
number = {6},
pages = {1575-1587},
doi = {10.24272/j.issn.2095-8137.2025.349},
pmid = {41320876},
issn = {2095-8137},
mesh = {*Aging/physiology ; *Neurodegenerative Diseases/genetics/metabolism ; Animals ; *Brain/physiology/metabolism ; *RNA, Transfer/metabolism/genetics ; *RNA, Small Untranslated/metabolism/genetics ; Humans ; },
abstract = {Transfer ribonucleic acid-derived small ribonucleic acids (tsRNAs) are an emerging class of regulatory noncoding RNAs produced through the precise cleavage of mature or precursor tRNAs (pre-tRNAs). Once considered degradation byproducts, tsRNAs are now recognized as key modulators of gene expression, epigenetic regulation, and cellular stress responses. In recent years, growing evidence has implicated tsRNAs in the aging process of the brain and in the pathogenesis of age-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). These small RNAs are involved in modulating synaptic function, neuronal survival, and neuroinflammation, and their expression profiles are dynamically altered in response to aging and disease-associated stressors. This review summarizes the biogenesis, classification, and molecular and cellular mechanisms of tsRNAs, with an emphasis on their subcellular locations and associated biological functions. We further explore their roles in brain aging and age-related neurodegenerative diseases and the emerging potential of tsRNAs as biomarkers and therapeutic targets for age-related neurological disorders while highlighting current challenges and future directions in this rapidly advancing field.},
}

*Aging/physiology
*Neurodegenerative Diseases/genetics/metabolism
Animals
*Brain/physiology/metabolism
*RNA, Transfer/metabolism/genetics
*RNA, Small Untranslated/metabolism/genetics
Humans

@article {pmid41109516,
year = {2026},
author = {Pandya, K and Kumar, D},
title = {CRISPR/cas genome editing for neurodegenerative diseases: Mechanisms, therapeutic advances, and clinical prospects.},
journal = {Ageing research reviews},
volume = {113},
number = {},
pages = {102922},
doi = {10.1016/j.arr.2025.102922},
pmid = {41109516},
issn = {1872-9649},
mesh = {Humans ; *Gene Editing/methods/trends ; *Neurodegenerative Diseases/genetics/therapy ; *CRISPR-Cas Systems/genetics ; Animals ; *Genetic Therapy/methods/trends ; },
abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), Spinocerebral Ataxia (SCA), and Huntington's disease (HD) are major global health challenges. Current treatments are only symptomatic and do not address the underlying pathogenic genetic mechanisms. The development of the CRISPR/Cas genome editing technologies, has increased possibilities for targeted repair of pathological mutations. CRISPR/Cas9, Cas12, and Cas13 systems enable targeted editing and transcriptome modulation in various preclinical models. CRISPR/Cas9 disruption of mutant APP, Tau, and LRRK2 genes, reducing toxic protein aggregration in AD models has restored normal genetic function. While correction of CAG nucleotide repeats in HD, and reduction of alpha-synuclein expression in PD. RNA targeting systems like Cas13 offers additional therapeutics potential by selectively degrading disease assciated transcript without altering genomic DNA. Advancements in engineered Cas variants with enhanced specificity, such as SpCas9-HF1, base editors and prime editors, with innovative delivery strategies including adeno-associated virus (AAVs) and nanoparticle-based systems, have improved genome editing. However, challenges remain, including off-target effects, mosaicism, and delivery across the BBB, and long-term safety. Ethical consideration focuses on somatic versus germline editing, equitable access, and regulatory oversight. While somatic editing shows acceptance in treating neurological disorders. Germline interventions face strict regulations due to potential multigeneration impacts. Collectively, these technologies are the vanguard of precision molecular medicine, advancing from symptom management towards potentially curative gene therapies for neurological disorders.},
}

Humans
*Gene Editing/methods/trends
*Neurodegenerative Diseases/genetics/therapy
*CRISPR-Cas Systems/genetics
Animals
*Genetic Therapy/methods/trends

@article {pmid41319477,
year = {2025},
author = {Benussi, A and Vucic, S},
title = {Emergent technologies and applications of TMS and TMS-EEG in clinical neurophysiology for early and differential diagnosis: IFCN handbook chapter.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {182},
number = {},
pages = {2111459},
doi = {10.1016/j.clinph.2025.2111459},
pmid = {41319477},
issn = {1872-8952},
abstract = {This chapter examines how emerging neurophysiological technologies are transforming the early and differential diagnosis of neurological disorders. While imaging and fluid biomarkers have greatly advanced the field, they remain limited by cost, invasiveness, and their inability to directly capture dynamic brain activity. Neurophysiological techniques, particularly transcranial magnetic stimulation (TMS) and TMS combined with EEG, offer a unique, non-invasive means of probing cortical excitability, connectivity, and plasticity with millisecond precision. Recent technological and analytical breakthroughs are moving these approaches from research laboratories into clinical practice. By detecting subtle network dysfunctions that precede structural degeneration, they open the possibility of identifying disease in its prodromal or even presymptomatic stages, when interventions may be most effective. This chapter outlines the principles of advanced TMS paradigms and TMS-EEG and explores their application across a range of conditions, including amyotrophic lateral sclerosis, dementias, and movement disorders. It also highlights how integrating neurophysiological measures with blood-based biomarkers and computational tools, such as machine learning, can enhance diagnostic accuracy and guide individualized treatment strategies. Together, these innovations establish neurophysiology as a cornerstone of precision neurology, linking mechanistic insights to clinical decision-making and enabling earlier diagnosis, improved patient stratification, and more targeted therapeutic interventions.},
}

@article {pmid41314748,
year = {2025},
author = {Quadri, SN and Tiwari, S and Siddiqi, B and Fatima, S and Khan, MA and Abdin, MZ},
title = {Advanced neuroimaging in precision neurology: Tools, trends, and translational impact.},
journal = {Progress in brain research},
volume = {297},
number = {},
pages = {221-246},
doi = {10.1016/bs.pbr.2025.08.005},
pmid = {41314748},
issn = {1875-7855},
mesh = {Humans ; *Neuroimaging/methods/trends ; *Neurodegenerative Diseases/diagnostic imaging ; *Precision Medicine/methods/trends ; Translational Research, Biomedical ; *Neurology/methods/trends ; Artificial Intelligence ; Machine Learning ; },
abstract = {Advances in neuroimaging are revolutionizing the landscape of precision neurology by enabling high-resolution, multimodal visualization of brain structure, function, and pathology. As traditional, symptom-based frameworks fall short in capturing the biological complexity of neurodegenerative diseases, imaging modalities such as structural MRI, diffusion tensor imaging, functional MRI, PET, and hybrid PET/MRI have emerged as essential tools for early diagnosis, patient stratification, and therapeutic monitoring. These technologies not only reveal hallmark features like hippocampal atrophy and disrupted neural networks but also uncover molecular signatures such as amyloid and tau deposition, synaptic density, and neuroinflammation. Integration with artificial intelligence (AI) and machine learning (ML) further enhances diagnostic precision by decoding subtle imaging patterns, facilitating subtype classification, and predicting disease progression. Despite transformative progress, disparities in access and implementation remain a critical challenge, particularly in low- and middle-income countries. This chapter provides a comprehensive overview of neuroimaging modalities, their diagnostic and prognostic relevance across major neurodegenerative conditions including Alzheimer's disease, Parkinson's disease, ALS, and frontotemporal dementia and the evolving role of hybrid platforms and AI integration in shaping the future of individualized neurological care.},
}

Humans
*Neuroimaging/methods/trends
*Neurodegenerative Diseases/diagnostic imaging
*Precision Medicine/methods/trends
Translational Research, Biomedical
*Neurology/methods/trends
Artificial Intelligence
Machine Learning

@article {pmid41314746,
year = {2025},
author = {Ceballos, MWG and Sy, FFA and Akbar, A and Taofiq, A},
title = {Multi-omics integration in disease research.},
journal = {Progress in brain research},
volume = {297},
number = {},
pages = {155-189},
doi = {10.1016/bs.pbr.2025.08.012},
pmid = {41314746},
issn = {1875-7855},
mesh = {Humans ; *Neurodegenerative Diseases/genetics/metabolism ; *Proteomics/methods ; *Genomics/methods ; *Metabolomics/methods ; Animals ; Multiomics ; },
abstract = {Neurodegenerative diseases, marked by complex molecular mechanisms and diverse clinical features, challenge conventional research approaches. This chapter emphasizes the value of multi-omics integration in understanding the biology of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). Genomic studies reveal risk variants such as APOE ε4 in Alzheimer's and rare mutations in familial forms. Transcriptomics highlights gene expression changes, including synaptic dysfunction in early Parkinson's and alternative splicing errors in TARDBP-related ALS. Proteomics identifies key protein aggregates like amyloid beta and alpha-synuclein, along with modifications such as hyperphosphorylated tau that correlate with cognitive decline. Metabolomics uncovers metabolic alterations, including mitochondrial dysfunction in Parkinson's and lipid peroxidation in ALS, which contribute to disease progression. By combining these layers with high-throughput tools like single-cell sequencing, spatial transcriptomics, and mass spectrometry, researchers can reconstruct molecular networks linking genetic risk, gene regulation, protein dysfunction, and metabolic imbalance. This approach enables patient stratification into molecular subtypes, such as neuroinflammatory clusters defined by microglial gene signatures and cytokine expression. Biomarkers from blood and cerebrospinal fluid allow for minimally invasive disease monitoring. Despite challenges such as data heterogeneity and limited standardization, multi-omics approaches support biomarker discovery and therapeutic development. Integrating these datasets with neuroimaging and digital tools enhances diagnostic precision and guides targeted interventions, such as antisense therapies for SOD1-linked ALS. Multi-omics integration is thus a critical foundation for advancing personalized strategies in neurodegenerative disease research.},
}

Humans
*Neurodegenerative Diseases/genetics/metabolism
*Proteomics/methods
*Genomics/methods
*Metabolomics/methods
Animals
Multiomics

@article {pmid41070448,
year = {2025},
author = {ElDabour, MA},
title = {Circumferential clues: strain patterns and arrhythmia risk in pulmonary regurgitation.},
journal = {Cardiology in the young},
volume = {35},
number = {11},
pages = {2332-2333},
doi = {10.1017/S1047951125110032},
pmid = {41070448},
issn = {1467-1107},
mesh = {Humans ; *Pulmonary Valve Insufficiency/physiopathology/complications/surgery ; *Tetralogy of Fallot/surgery/complications/physiopathology ; *Arrhythmias, Cardiac/etiology/physiopathology ; *Heart Ventricles/physiopathology/diagnostic imaging ; Risk Factors ; },
abstract = {Slim et al.'s paper provided an insight into the differences between repaired tetralogy of Fallot and isolated pulmonary regurgitation in their strain. Repaired tetralogy of Fallot had higher right ventricular circumferential strain, while isolated pulmonary regurgitation relied on longitudinal strain more. This allowed the authors to infer that repaired tetralogy of Fallot can withstand more chronic regurgitation before valve replacement is necessary. We highlighted new findings relevant to this paper. Arrhythmia in repaired tetralogy of Fallot is associated with a reduced global circumferential strain of the right ventricle. Specifically, a value of below -14% was associated with a 6.3 times increase in the risk for an arrhythmic event. We believe this would be beneficial for patients when considered for valve replacements, suggesting modification of current valve replacement guidelines to include strain thresholds alongside current volumetric thresholds. However, the data for isolated pulmonary regurgitation remains scarce. Further investigation is needed to provide clearer timelines for valve replacement. We emphasised the importance of exploring the underlying architecture of repaired tetralogy of Fallot patients' hearts and why they could generate more global circumferential strain. We acknowledged the broader effect of this paper and its specific benefit in our country, Egypt. This paper provided insights useful for broader global health impact, especially in low-income countries.},
}

Humans
*Pulmonary Valve Insufficiency/physiopathology/complications/surgery
*Tetralogy of Fallot/surgery/complications/physiopathology
*Arrhythmias, Cardiac/etiology/physiopathology
*Heart Ventricles/physiopathology/diagnostic imaging
Risk Factors

@article {pmid40296625,
year = {2025},
author = {Barabadi, T and Mirjalili, ES and Mohamadi-Zarch, SM and Rahimi, H and Keshmirshekan, F and Bagheri, SM},
title = {Cell-Free DNA, a Noninvasive Biomarker for Prediction and Detection of Neurodegenerative Diseases, New Insights, and Perspectives.},
journal = {CNS & neurological disorders drug targets},
volume = {24},
number = {10},
pages = {731-742},
pmid = {40296625},
issn = {1996-3181},
support = {18535//Shahid Sadoughi University of Medical Science and Health Services/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/diagnosis/blood ; Biomarkers/blood ; *Cell-Free Nucleic Acids/blood/metabolism ; Parkinson Disease/diagnosis ; Animals ; },
abstract = {Neurodegenerative diseases pose serious threats to public health worldwide. Biomarkers for neurodegenerative disorders are essential to enhance the diagnostic process in clinical settings and to aid in the creation and assessment of effective disease-modifying treatments. In recent times, affordable and readily available blood-based biomarkers identifying the same neurodegenerative disease pathologies have been created, potentially transforming the diagnostic approach for these disorders worldwide. Emerging relevant biomarkers for α-synuclein pathology in Parkinson's disease include blood-based indicators of overall neurodegeneration and glial activation. Cell-free DNA (cfDNA), an encouraging non-invasive biomarker commonly utilized in oncology and pregnancy, has demonstrated significant potential in clinical uses for diagnosing neurodegenerative disorders. In this section, we explore the latest cfDNA studies related to neurodegenerative disorders. Moreover, we present a perspective on the possible role of cfDNA as a diagnostic, therapeutic, and prognostic indicator for neurodegenerative disorders. This review provides a summary of the most recent progress in biomarkers for neurodegenerative disorders such as Alzheimer's, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and traumatic brain injury.},
}

Humans
*Neurodegenerative Diseases/diagnosis/blood
Biomarkers/blood
*Cell-Free Nucleic Acids/blood/metabolism
Parkinson Disease/diagnosis
Animals

@article {pmid40231507,
year = {2025},
author = {Tecalco-Cruz, AC and Ramirez-Jarquin, JO and Medina Abreu, KH and Palacios-Serrato, EG and Lopez-Canovas, L and Zepeda-Cervantes, J and Oropeza-Martínez, E},
title = {Molecular Interplay of ISG15/ISGylation in Neuropathologies.},
journal = {CNS & neurological disorders drug targets},
volume = {24},
number = {10},
pages = {723-730},
pmid = {40231507},
issn = {1996-3181},
support = {CCyT-2024-CON-07//CCyT-UACM/ ; },
mesh = {Humans ; *Ubiquitins/metabolism ; Animals ; *Cytokines/metabolism ; *Neurodegenerative Diseases/metabolism ; },
abstract = {ISG15 is a 15 kDa ubiquitin-like protein that covalently associates with its target proteins by a sequential enzymatic process known as ISGylation. Research on protein ISGylation has increased in recent years, and some studies have suggested that ISG15 is involved in neuroprotection and neurodegeneration mechanisms. This review outlines the current state of research on the implications of ISG15/ISGylation in other neuropathies such as malignant tumors, ataxia telangiectasia, ischemia, depression, and neurodegenerative diseases such as Alzheimer's, Parkinson's diseases, multiple sclerosis, and amyotrophic lateral sclerosis. Based on the studies reported to date, ISG15/ ISGylation promotes the progression of brain tumors such as glioblastoma. Moreover, ISG15/ ISGylation seems to play a dual role in neuropathies, demonstrating a neuroprotective effect when there is acute brain damage, but ISG15/ISGylation is associated with reduced neuroprotection when there is chronic damage, such as in neurodegenerative diseases.},
}

Humans
*Ubiquitins/metabolism
Animals
*Cytokines/metabolism
*Neurodegenerative Diseases/metabolism

@article {pmid41314745,
year = {2025},
author = {Fatima, S and Tiwari, S and Siddiqi, B and Quadri, SN and Abdin, MZ},
title = {Biomarkers: From early detection to treatment personalization.},
journal = {Progress in brain research},
volume = {297},
number = {},
pages = {131-153},
doi = {10.1016/bs.pbr.2025.08.008},
pmid = {41314745},
issn = {1875-7855},
mesh = {Humans ; *Biomarkers/metabolism ; *Neurodegenerative Diseases/diagnosis/therapy/metabolism ; *Precision Medicine/methods ; Early Diagnosis ; },
abstract = {Neurodegenerative disorders (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), present increasing issues associated with the unavoidable aging of the world's population. These challenges are further highlighted by the socioeconomic consequences of these diseases. The identification and use of biomarkers for prompt diagnosis, careful observation, and efficient treatment approaches is essential to overcoming these obstacles. The primary methods for diagnosing neurodegenerative illnesses are invasive procedures like lumbar punctures to measure CSF fluid or functional brain imaging methods. Biomarkers for underlying proteinopathy in blood serum and cerebral fluid have been the focus of recent biological research, particularly in vivo. With their ability to provide novel pathways for early detection, illness progression tracking, and individualized treatment plans, biomarkers have become essential instruments in precision medicine. The classification of biomarkers including fluid, digital imaging, and molecular biomarkers is examined in this chapter, with an emphasis on their function in neurodegenerative diseases. In neurodegenerative illnesses and the aging brain, tau, amyloid-β, α-synuclein, and TDP-43 are commonly seen to be deposited together rather than separately. These may be disregarded, and it might be challenging to determine their clinicopathological significance. An overview of illness pathophysiology, diagnostic implications, and the most recent molecular and ultrastructural categories for neurodegenerative disorders are given in this chapter. Addressing these issues through interdisciplinary research and technological advancements will be crucial for the future of biomarker-driven precision medicine. This chapter provides an in-depth overview of the evolving landscape of biomarkers and their transformative impact on the early detection and personalized treatment of neurodegenerative diseases.},
}

Humans
*Biomarkers/metabolism
*Neurodegenerative Diseases/diagnosis/therapy/metabolism
*Precision Medicine/methods
Early Diagnosis

@article {pmid41314744,
year = {2025},
author = {Gunasekaran, B and Arifin, AH and Yu, WH and Hanafi, S and Rao, KDK and Salvamani, S},
title = {Precision medicine in neurodegenerative diseases: From research to clinical practice.},
journal = {Progress in brain research},
volume = {297},
number = {},
pages = {1-52},
doi = {10.1016/bs.pbr.2025.08.006},
pmid = {41314744},
issn = {1875-7855},
mesh = {Humans ; *Precision Medicine/methods ; *Neurodegenerative Diseases/therapy/genetics/diagnosis ; Biomarkers ; },
abstract = {The chapter outlines how precision medicine is reshaping the way neurodegenerative diseases (NDs) which includes Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD) are understood, diagnosed, and treated. It discusses the limitations of current therapies, which mainly address symptoms without altering disease progression. Genetic and molecular factors that influence disease development are described, including distinctions between familial and sporadic forms. The chapter also covers the roles of epigenetic changes, gene expression, protein dysfunction, mitochondrial DNA, and non-coding RNAs in NDs. Biomarkers in blood and cerebrospinal fluid, along with imaging techniques and digital tools, are presented as key elements in early diagnosis and disease monitoring. Patient stratification based on clinical features, molecular profiles, and biomarkers helps guide treatment decisions and improve outcomes. The chapter reviews ongoing developments in genotype-based drug design, gene therapy, pharmacogenomics, and personalized lifestyle strategies. Clinical case studies show how these approaches are being used in practice. The chapter also discusses challenges in applying precision medicine, such as trial design, data integration, unequal access, and regulatory hurdles. Finally, it highlights the future tools like single-cell transcriptomics, digital twins, and global research collaborations that aim to bring precision approaches into everyday care.},
}

Humans
*Precision Medicine/methods
*Neurodegenerative Diseases/therapy/genetics/diagnosis
Biomarkers

@article {pmid41314255,
year = {2025},
author = {Odonchimed, S and Imamura, K and Inoue, H},
title = {Neurodegenerative Disease and Autophagy in iPSC models.},
journal = {Neuroscience research},
volume = {},
number = {},
pages = {104991},
doi = {10.1016/j.neures.2025.104991},
pmid = {41314255},
issn = {1872-8111},
abstract = {Neurodegenerative diseases are characterized by the gradual deterioration of specific neuronal populations, ultimately resulting in motor, cognitive, or behavioral impairments. Despite the worldwide increase in disease incidence, effective therapies remain unavailable. A common pathological hallmark of neurodegenerative diseases is the accumulation of misfolded protein aggregates, which impair normal cellular function. Accordingly, numerous studies and therapeutic strategies have focused on targeting these toxic aggregates and protein quality control via autophagy, a vital cellular recycling mechanism. Autophagy dysregulation has been implicated in the pathogenesis of several neurodegenerative diseases. Induced pluripotent stem cell (iPSC) technology has emerged as a powerful platform for modeling neurodegenerative diseases, and iPSC-derived models provide human-relevant systems for studying autophagic dysfunction in vitro. In this review, we discuss the key findings of recent studies investigating autophagy in iPSC-based models of neurodegenerative diseases, including Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and other diseases.},
}

@article {pmid41313410,
year = {2025},
author = {Goel, F and Singh, P and Rai, SN and Yadav, DK},
title = {Nrf2/Keap1 Signaling Axis in the Brain: Master Regulator of Oxidative Stress in Neurodegenerative and Psychiatric Disorders.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {197},
pmid = {41313410},
issn = {1559-1182},
mesh = {Humans ; *Kelch-Like ECH-Associated Protein 1/metabolism ; *NF-E2-Related Factor 2/metabolism ; *Signal Transduction/physiology ; *Oxidative Stress/physiology ; *Mental Disorders/metabolism/pathology ; Animals ; *Neurodegenerative Diseases/metabolism/pathology ; *Brain/metabolism/pathology ; },
abstract = {Oxidative stress is a crucial factor in the development of CNS disorders, including neurodegenerative and psychiatric conditions. The Nrf2/Keap1 signaling axis plays a central role in defending against oxidative damage by regulating antioxidant and cytoprotective gene expression. Beyond its antioxidant function, Nrf2 influences neurogenesis, synaptic plasticity, mitochondrial bioenergetics, and glial neuronal interactions, all of which are vital for maintaining neural integrity and cognitive performance. Dysregulation of this pathway through altered dimerization, post-translational modifications, or impaired regulation contributes to the pathophysiology of Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, leading to protein aggregation, mitochondrial dysfunction, and neuroinflammation. Emerging evidence also implicates aberrant Nrf2 activity in psychiatric disorders such as depression, schizophrenia, and bipolar disorder, where redox imbalance and neuroimmune activation disrupt neural function. This review summarizes the molecular structure and regulation of the Nrf2/Keap1 pathway, including basal and stress-induced activation, post-translational modifications, and cross-talk with PI3K/Akt, MAPK, and NF-κB signaling. We highlight cell-type-specific roles of Nrf2 in neurons, astrocytes, and microglia, and the gene expression networks that drive CNS antioxidant and detoxification responses. Recent therapeutic strategies include natural and synthetic Nrf2 activators, gene therapy approaches, and nanotechnology-based delivery systems. While the translational potential of Nrf2-targeted interventions is considerable, challenges remain, including risks of overactivation and oncogenicity, lack of reliable biomarkers, and barriers related to blood-brain barrier permeability, dose, timing, and bioavailability. By integrating advances in neuroscience, pharmacology, and molecular medicine, this review emphasizes the promise of Nrf2 as a unifying therapeutic target across diverse CNS pathologies. Future directions include precision modulation through epigenetic regulation and circRNAs, as well as personalized pharmacotherapy. The Nrf2/Keap1 axis represents a multidisciplinary platform for developing multimodal interventions to preserve brain health in neurodegenerative and psychiatric disorders.},
}

Humans
*Kelch-Like ECH-Associated Protein 1/metabolism
*NF-E2-Related Factor 2/metabolism
*Signal Transduction/physiology
*Oxidative Stress/physiology
*Mental Disorders/metabolism/pathology
Animals
*Neurodegenerative Diseases/metabolism/pathology
*Brain/metabolism/pathology

@article {pmid41309196,
year = {2025},
author = {Jamwal, RS and Sharma, B and Minerva, and Gupta, A and Misri, S and Shankaryan, R and Shah, R and Kumar, R},
title = {Protein misfolding and its dual role in neurodegeneration and cancer progression.},
journal = {Advances in protein chemistry and structural biology},
volume = {148},
number = {},
pages = {355-377},
doi = {10.1016/bs.apcsb.2025.10.001},
pmid = {41309196},
issn = {1876-1631},
mesh = {Humans ; *Neoplasms/metabolism/pathology ; *Protein Folding ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; Disease Progression ; Unfolded Protein Response ; },
abstract = {Protein misfolding is a fundamental biological process with profound implications for human health and disease. Typically, proteins assume precise three-dimensional structures to perform their functions, a process safeguarded by the proteostasis network, which comprises molecular chaperones, the ubiquitin-proteasome system (UPS), and autophagy. However, genetic mutations, oxidative stress, and environmental insults can disrupt folding, leading to the accumulation of non-functional or toxic conformations. In neurodegenerative diseases such as Huntington's disease (HD), Parkinson's disease (PD), Alzheimer's disease (AD), Amyotrophic lateral Sclerosis (ALS), chronic misfolding results in toxic protein aggregates like amyloid-β, tau, and α-synuclein. These disrupt synaptic function, induce oxidative and nitrosative stress, and trigger apoptosis, ultimately leading to progressive neuronal loss. Dysregulation of the unfolded protein response (UPR) and weakened proteostasis with aging exacerbate disease pathology. In contrast, cancer cells utilize protein misfolding to enhance their survival and progression. Misfolded oncoproteins, such as mutant p53, not only evade degradation but also acquire oncogenic properties. Tumor cells hijack the UPR and chaperone networks, upregulate heat shock proteins, and manipulate oxidative stress responses to withstand hypoxia, nutrient deprivation, and rapid proliferation. Cancer stem cells (CSCs) further adapt to proteotoxic stress, contributing to tumor heterogeneity, therapy resistance, and immune evasion. The dual role of protein misfolding, driving degeneration in neurons while supporting proliferation in tumors, underscores its centrality in disease biology. Future research should focus on identifying early biomarkers of proteostasis imbalance and exploiting shared molecular pathways for the development of novel therapeutic interventions.},
}

Humans
*Neoplasms/metabolism/pathology
*Protein Folding
*Neurodegenerative Diseases/metabolism/pathology
Animals
Disease Progression
Unfolded Protein Response

@article {pmid41303502,
year = {2025},
author = {Hassan, M and Shahzadi, S and Moustafa, AA and Kloczkowski, A},
title = {Neurodegeneration Through the Lens of Bioinformatics Approaches: Computational Mechanisms of Protein Misfolding.},
journal = {International journal of molecular sciences},
volume = {26},
number = {22},
pages = {},
pmid = {41303502},
issn = {1422-0067},
support = {1R01HG012117-04/NH/NIH HHS/United States ; },
mesh = {Humans ; *Computational Biology/methods ; *Neurodegenerative Diseases/metabolism ; *Protein Folding ; Animals ; Protein Aggregates ; Protein Aggregation, Pathological/metabolism ; },
abstract = {Protein and peptide aggregation has become a prominent focus in biomedical research due to its critical role in the development of neurodegenerative diseases (NDs) and its relevance to industrial applications. Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS) are closely associated with abnormal aggregation processes, highlighting the need for a deeper understanding of their molecular mechanisms. In recent years, a wide range of computational methods, bioinformatics tools, and curated databases have been developed to predict and analyze sequences and structures that are prone to aggregation. These in silico approaches offer valuable insights into the underlying principles of aggregation and contribute to the identification of potential therapeutic targets. This review provides a concise overview of the current bioinformatics resources and computational techniques available for studying protein and peptide aggregation, intending to guide future research efforts in the field of neurodegenerative disease modeling and drug discovery.},
}

Humans
*Computational Biology/methods
*Neurodegenerative Diseases/metabolism
*Protein Folding
Animals
Protein Aggregates
Protein Aggregation, Pathological/metabolism

@article {pmid41302089,
year = {2025},
author = {Anjum, F and Hulbah, MJ and Shamsi, A and Mohammad, T},
title = {Exploring TANK-Binding Kinase 1 in Amyotrophic Lateral Sclerosis: From Structural Mechanisms to Machine Learning-Guided Therapeutics.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {11},
pages = {},
doi = {10.3390/life15111665},
pmid = {41302089},
issn = {2075-1729},
support = {KSRG-2024-446//King Salman Center for Disability Research/ ; },
abstract = {TANK-binding kinase 1 (TBK1) has emerged as one of the most compelling genetic contributors to amyotrophic lateral sclerosis (ALS), with heterozygous loss-of-function and pathogenic missense variants identified in patients across the ALS-frontotemporal dementia (FTD) spectrum. TBK1 participates in various core cellular processes associated with motor neuron vulnerability, including autophagy, mitophagy, and innate immune regulation, indicating that TBK1 is likely a key determinant of ALS pathogenesis. Structurally, TBK1 exhibits a trimodular organization comprising a kinase domain, a ubiquitin-like domain, and a scaffold/dimerization domain. Multiple experimentally resolved conformations and inhibitor-bound complexes provide a foundation for structure-guided therapeutic design. Here, we synthesize current genetic and mechanistic evidence linking TBK1 dysfunction to ALS, emphasizing its dual roles in autophagy and neuroinflammation. We also summarize advances in structure-based and AI-assisted drug discovery approaches targeting TBK1. Finally, we outline key translational challenges, including isoform selectivity, biomarker validation, and central nervous system (CNS) delivery, highlighting TBK1 as a promising yet complex therapeutic target in ALS. By integrating computational modeling, machine learning frameworks, and experimental pharmacology, future research may accelerate the translation of TBK1 modulators into clinically effective therapies.},
}

@article {pmid41300346,
year = {2025},
author = {Yeasmin, A and Torrente, MP},
title = {Histone Post-Translational Modifications and DNA Double-Strand Break Repair in Neurodegenerative Diseases: An Epigenetic Perspective.},
journal = {Biology},
volume = {14},
number = {11},
pages = {},
doi = {10.3390/biology14111556},
pmid = {41300346},
issn = {2079-7737},
support = {1R15NS125394-01/NH/NIH HHS/United States ; },
abstract = {DNA damage is a hallmark of the fatal process of neurodegeneration in the central nervous system (CNS). As neurons are terminally differentiated, they accumulate metabolic and oxidative burdens over their whole life span. Unrepaired DNA develops into DNA double-strand breaks (DSBs), which are repaired through homologous recombination (HR) or non-homologous end joining (NHEJ). Being post-mitotic and unable to normally undergo HR, damage and defective repair is especially burdensome to CNS neurons. Current research has not produced treatment to prevent and halt progression of neurodegeneration. Hence, novel targeting strategies are desperately needed. Recent investigations in histone post-translational modifications (PTMs) reveal new mechanistic insight and highlight unexplored targets to ameliorate neurodegeneration. As various histone PTMs dictate and facilitate DSB repair, they represent an underexploited area in investigating DNA damage and incorrect repair aiding neurodegeneration. Here, we review the histone PTM alterations in several neurodegenerative diseases: Amyotrophic Lateral Sclerosis/Frontotemporal Dementia, Parkinson's Disease, Alzheimer's Diseases, Multiple Sclerosis, and Huntington's Disease. These findings emphasize that histone PTM alterations can enable an aberrant DNA damage response (DDR) leading to neurodegeneration. Further research into the connections between histone PTMs and DNA damage in decaying neurons will illuminate novel targets to dampen the aberrant DDR and promote neuronal survival.},
}

@article {pmid41299417,
year = {2025},
author = {Wang, J and Zhu, M and Smith, RD},
title = {Prevalence, incidence and risk factors of syphilis among men who have sex with men in China from 2013 to 2025: a systematic review and meta-analysis.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-025-12176-8},
pmid = {41299417},
issn = {1471-2334},
abstract = {BACKGROUND: Syphilis has re-emerged in China in recent decades, particularly among men who have sex with men (MSM). We aimed to assess the prevalence, incidence, and associated factors of syphilis among MSM in China.

METHODS: We systematically searched major English (MEDLINE via PubMed, Web of Science, Embase, Scopus, Cochrane Library) and Chinese (CNKI, Wanfang, CBM, VIP, Airiti Library) databases for studies on syphilis prevalence or incidence among MSM in China published from January 1, 2013 to March 1, 2025. Study qualities were evaluated using the Hoy et al.'s risk-of-bias tool and the Newcastle-Ottawa Scale. Random-effects meta-analysis models were used to estimate pooled syphilis prevalence (%) and incidence (per 100 person-years, PYs) with 95% confidence intervals (CIs). Meta-regression analyses were performed to assess differences across subgroups.

RESULTS: A total of 441 studies (429 prevalence and 33 incidence) were included. The pooled syphilis prevalence among general MSM was 8.8% (95% CI: 8.3-9.4). Study location (R²=0.13) and study year (R²=0.11) each contributed significantly to the high heterogeneity observed (I² = 98.5%) among the general MSM prevalence studies. MSM with high-risk sexual behaviors or related risk factors exhibited higher prevalence. The pooled incidence among all MSM was 7.8 per 100 PYs (95% CI: 6.0-9.8), with similarly high heterogeneity (I² = 96.4%). Both syphilis prevalence and incidence declined over time.

CONCLUSION: Syphilis prevalence and incidence remain high among high-risk MSM subgroups in China. More rigorous studies and targeted interventions are needed to obtain more accurate estimates and to further reduce syphilis infection rates.},
}

@article {pmid41295414,
year = {2025},
author = {Favari, E and Parolini, C},
title = {Marine Bioactive Components and Chronic Neuroinflammation: Focus on Neurodegenerative Disease.},
journal = {Marine drugs},
volume = {23},
number = {11},
pages = {},
pmid = {41295414},
issn = {1660-3397},
support = {NA//MUR Progetto Eccellenza/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; Animals ; *Neuroinflammatory Diseases/drug therapy ; *Aquatic Organisms/chemistry ; Oxidative Stress/drug effects ; Inflammation/drug therapy ; },
abstract = {Advances in neuroscience, immunology, and neuroimmunology have revealed that the nervous and immune systems form a bidirectional integrated network, ranging from regulating inflammation to directing stress responses, pivotal for the maintenance of the brain-body physiology. Like peripheral inflammation, neuroinflammation is a conserved process aimed at activating innate/adaptive immune and non-immune cells to effectively deal with bacteria, viruses, toxins, and injuries, and eventually at removing the microbial pathogens and supporting tissue repair and recovery. A failure of this process or the permanent release of pro-inflammatory mediators causes a condition called "chronic low-grade neuroinflammation" resulting in tissue damage and an increased risk of developing neurodegenerative diseases (NDD), such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). Marine-derived bioactive components are able to modulate lipid and glucose metabolism as well as inflammation and oxidative stress. In this review, we describe the neuroinflammatory process and its involvement in the pathogenesis and progression of AD, PD, MS, and ALS. Then, we discuss the potential therapeutic efficacy of select marine-derived bioactive components.},
}

Humans
*Neurodegenerative Diseases/drug therapy
Animals
*Neuroinflammatory Diseases/drug therapy
*Aquatic Organisms/chemistry
Oxidative Stress/drug effects
Inflammation/drug therapy

@article {pmid41294873,
year = {2025},
author = {Wang, S and Feng, Z and Wu, H and Wang, S and Qin, S and Wang, X and Zhou, F and Zheng, K and Huang, X and Liu, X},
title = {The m[6]A Modification in Neurodegenerative Disease: A Cellular Perspective.},
journal = {Cells},
volume = {14},
number = {22},
pages = {},
pmid = {41294873},
issn = {2073-4409},
support = {BK20231347//Natural Science Foundation of Jiangsu Province/ ; 81971179//National Natural Science Foundation of China/ ; Z2019035//Jiangsu Commission of Health/ ; 20KJA320004//Jiangsu Provincial Department of Education/ ; KC23242//Technology Innovation Foundation of Xuzhou City/ ; JBGS202202//Open Competition Grant of Xuzhou Medical University/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/genetics/metabolism/pathology ; *Adenosine/analogs & derivatives/metabolism/genetics ; Animals ; Neurons/metabolism ; },
abstract = {N6-methyladenosine (m[6]A) is the most abundant internal RNA modification in eukaryotes and plays a critical role in gene expression regulation by influencing RNA stability, splicing, nuclear export, and translation. Emerging evidence suggests that dysregulation of m[6]A contributes to neuroinflammation, neurotoxicity, and synaptic dysfunction-key features of neurodegenerative diseases. This review aims to examine the role of m6A modification in neurodegenerative diseases from a cell-type-specific perspective. We systematically reviewed recent studies investigating m[6]A modifications in neurons and glial cells. Data from transcriptomic, epitranscriptomic, and functional studies were analyzed to understand how m[6]A dynamics influence disease-related processes. Findings indicate that m[6]A modifications regulate neuroinflammation and immune responses in microglia, modulate astrocytic support functions, affect myelination through oligodendrocytes, and alter m[6]A patterns in neurons, impacting synaptic plasticity, stress responses, and neuronal survival. These cell-type-specific roles of m[6]A contribute to the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS). Understanding m[6]A-modulated mechanisms in specific neural cell types may facilitate the development of targeted interventions for neurodegenerative diseases.},
}

Humans
*Neurodegenerative Diseases/genetics/metabolism/pathology
*Adenosine/analogs & derivatives/metabolism/genetics
Animals
Neurons/metabolism

@article {pmid41294805,
year = {2025},
author = {Xu, H and Zhou, K and Xia, L and Ren, K and Xu, Y},
title = {In-Depth Study of Low-Complexity Domains: From Structural Diversity to Disease Mechanisms.},
journal = {Cells},
volume = {14},
number = {22},
pages = {},
doi = {10.3390/cells14221752},
pmid = {41294805},
issn = {2073-4409},
support = {31972537//National Natural Science Foundation of China/ ; },
mesh = {Humans ; Protein Domains ; Animals ; Neurodegenerative Diseases/metabolism ; Intrinsically Disordered Proteins/chemistry/metabolism ; },
abstract = {Low-complexity domains (LCDs) are protein regions characterized by a simple amino acid composition and low sequence complexity, as they are typically composed of repeats or a limited set of a few amino acids. Historically dismissed as "garbage sequences", these regions are now acknowledged as critical functional elements. This review systematically explores the structural characteristics, biological functions, pathological roles, and research methodologies associated with LCDs. Structurally, LCDs are marked by intrinsic disorder and conformational dynamics, with their amino acid composition (e.g., G/Y-rich, Q-rich, S/R-rich, P-rich) dictating structural tendencies (e.g., β-sheet formation, phase separation ability). Functionally, LCDs mediate protein-protein interactions, drive liquid-liquid phase separation (LLPS) to form biomolecular condensates, and play roles in signal transduction, transcriptional regulation, cytoskeletal organization, and nuclear pore transportation. Pathologically, LCD dysfunction-such as aberrant phase separation or aggregation-is implicated in neurodegenerative diseases (e.g., ALS, AD), cancer (e.g., Ewing sarcoma), and prion diseases. We also summarize the methodological advances in LCD research, including biochemical (CD, NMR), structural (cryo-EM, HDX-MS), cellular (fluorescence microscopy), and computational (MD simulations, AI prediction) approaches. Finally, we highlight current challenges (e.g., structural heterogeneity, causal ambiguity of phase separation) and future directions (e.g., single-molecule techniques, AI-driven LCD design, targeted therapies). This review provides a comprehensive perspective on LCDs, illuminating their pivotal roles in cellular physiology and disease, and offering insights for future research and therapeutic development.},
}

Humans
Protein Domains
Animals
Neurodegenerative Diseases/metabolism
Intrinsically Disordered Proteins/chemistry/metabolism

@article {pmid41294799,
year = {2025},
author = {Medigovic, G and Rachamala, HK and Dutta, SK and Pal, K},
title = {Structural and Functional Perspectives of Optineurin in Autophagy, Immune Signaling, and Cancer.},
journal = {Cells},
volume = {14},
number = {22},
pages = {},
doi = {10.3390/cells14221746},
pmid = {41294799},
issn = {2073-4409},
support = {W81XWH-21-1-0678//Department of Defense Congressionally Directed Medical Research Program/ ; R56HL160545//The National Heart, Lung, and Blood Institute/ ; },
mesh = {Humans ; *Autophagy ; *Neoplasms/immunology/metabolism/pathology ; *Membrane Transport Proteins/chemistry/metabolism ; *Signal Transduction ; *Cell Cycle Proteins/chemistry/metabolism ; Animals ; *Transcription Factor TFIIIA/metabolism/chemistry/genetics ; },
abstract = {Optineurin (OPTN) is a multifunctional adaptor protein that regulates diverse cellular processes, including inflammatory signaling, autophagy, vesicular trafficking, and immune responses. This multifaceted role of OPTN is made possible by the presence of a complex structure comprising multiple domains that interact with different proteins to exert various functions important for modulating key signaling processes. Mutations in OPTN are linked with several human pathologies including glaucoma, Paget's disease of bone, Crohn's disease, and neurodegenerative diseases such as amyotrophic lateral sclerosis, and dementia. Emerging evidence suggests that OPTN has a complex and context-dependent role in cancer biology as well. It is upregulated in pancreatic ductal adenocarcinoma and hepatocellular carcinoma but downregulated in lung and colorectal cancers, indicating its dual role as a potential oncogene or tumor suppressor depending on the cellular environment. Additionally, OPTN plays a critical role in preventing immune evasion in colorectal cancer by maintaining interferon-gamma receptor 1 (IFNGR1) expression and supporting dendritic cell-mediated T-cell priming, thereby enhancing antitumor immune responses. Despite its significance in oncogenic pathways and immune regulation, the therapeutic potential of targeting OPTN in cancer remains largely unexplored. This review aims to provide a comprehensive understanding of OPTN's pleiotropic functions, highlighting its role in autophagy, inflammation, immune surveillance, and cancer progression. By elucidating its diverse regulatory mechanisms, we seek to encourage further research into the therapeutic implications of OPTN in cancer treatment and immunotherapy.},
}

Humans
*Autophagy
*Neoplasms/immunology/metabolism/pathology
*Membrane Transport Proteins/chemistry/metabolism
*Signal Transduction
*Cell Cycle Proteins/chemistry/metabolism
Animals
*Transcription Factor TFIIIA/metabolism/chemistry/genetics