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

@article {pmid40881531,
year = {2025},
author = {Chase, RC and Cortes, P and Lamb, CJ and Francis, D and DeVault, KR and Pang, M},
title = {Factors That Predict Endoscopic Evaluation and Gastrostomy Placement in Patients With Neurologic Disorders and Dysphagia.},
journal = {Cureus},
volume = {17},
number = {7},
pages = {e88853},
doi = {10.7759/cureus.88853},
pmid = {40881531},
issn = {2168-8184},
abstract = {BACKGROUND: Although patients with neurologic disorders commonly develop dysphagia, there remains little consensus on the role of initial esophagogastroduodenoscopy (EGD) or temporal guidance on gastrostomy placement. We aimed to characterize the predictors associated with EGD and gastrostomy recommendation at the initial gastroenterology consultation in patients with progressive neurologic disorders.

METHODS: This retrospective study spanned from December 31, 2010, to December 31, 2021, and included patients with both dysphagia and neurologic disorders. Multivariate logistic regression determined the predictors for EGD and gastrostomy recommendation after the initial visit.

RESULTS: Out of 273 patients, EGD was recommended for 163 (59.7%) at the initial evaluation. A diagnosis of amyotrophic lateral sclerosis (ALS) (odds ratio: 0.20; 95% confidence interval (CI): 0.07-0.52; P=0.001) and being referred by a neurologist (odds ratio: 0.37; 95% CI: 0.17-0.84; P<0.02) were the negative predictors of an initial EGD recommendation. Gastrostomy was recommended for 38 patients (13.9%) at the initial consultation. Dysphagia to both liquids and solids, body mass index, diagnosis of ALS, and clinical frailty scale scores were associated with gastrostomy (P≤0.01). A model of six variables had high predictive accuracy for EGD recommendation (area under the receiver operating characteristic curve: 0.7741).

CONCLUSIONS: This study proposes a predictive model for initial EGD recommendation. We suggest that when considered in conjunction with the predictive clinical features of ALS diagnosis and dysphagia to both solids and liquids, the clinical frailty scale and American Society of Anesthesiologists physical status classification system scores may help clinicians anticipate gastrostomy when applied to patients with any neurologic disorder.},
}

@article {pmid40881516,
year = {2025},
author = {Swarnakar, R},
title = {Brain-Computer Interfaces in Rehabilitation: Implementation Models and Future Perspectives.},
journal = {Cureus},
volume = {17},
number = {7},
pages = {e88873},
doi = {10.7759/cureus.88873},
pmid = {40881516},
issn = {2168-8184},
abstract = {Brain-computer interfaces (BCIs) represent an emerging advancement in rehabilitation, enabling direct communication between the brain and external devices to aid recovery in individuals with neurological impairments. BCIs can be classified into invasive, semi-invasive, non-invasive, or hybrid types. By interpreting neural signals and converting them into control commands, BCIs can bypass damaged pathways, offering therapeutic potential for conditions such as stroke, spinal cord injury, traumatic brain injury, and neurodegenerative diseases such as amyotrophic lateral sclerosis. BCIs' current applications, such as motor restoration via robotic exoskeletons and functional electrical stimulation, cognitive enhancement through neurofeedback and attention training, and communication tools for individuals with severe physical limitations, are largely being explored within research settings and are not yet part of routine clinical practice. Advances in EEG signal acquisition, machine learning, wearable and wireless systems, and integration with virtual reality are enhancing the clinical utility of BCIs by improving accuracy, adaptability, and usability. However, widespread clinical adoption faces challenges, including signal variability, training complexity, data privacy, and ethical and regulatory issues. Ethical challenges in BCI include issues related to the ownership and misuse of brain data, risks of neural interference, threats to autonomy and personal identity, as well as concerns around data privacy, user consent, emotional manipulation, and accountability in neural interventions. In this context, this editorial has also proposed one model (NEURO model checklist) for BCI implementation in rehabilitation. The future of BCIs in rehabilitation lies in developing personalized, closed-loop, and home-based systems, enabled by interdisciplinary collaboration among clinicians, engineers, neuroscientists, and policymakers. With continued research and ethical implementation, BCIs have the potential to transform neurorehabilitation and greatly enhance patient outcomes and quality of life.},
}

@article {pmid40879853,
year = {2025},
author = {Tu, JY},
title = {Letter to the Editor- The association between sarcopenic obesity and depression in middle-aged and elderly U.S. adults: insights from the NHANES study.},
journal = {Aging clinical and experimental research},
volume = {37},
number = {1},
pages = {260},
pmid = {40879853},
issn = {1720-8319},
mesh = {Humans ; *Sarcopenia/complications/psychology/epidemiology ; *Obesity/complications/epidemiology/psychology ; Aged ; *Depression/epidemiology/complications ; Middle Aged ; Nutrition Surveys ; United States/epidemiology ; Male ; Female ; },
abstract = {After reading "The association between sarcopenic obesity and depression in middle-aged and elderly U.S. adults: insights from the NHANES study", we sincerely appreciate Zhang et al.'s exploration of the relationship between sarcopenic obesity and depression in middle-aged and elderly populations, which provides new clinical perspectives for preventing sarcopenic obesity and depression. However, to more rigorously and clearly elucidate this relationship, several concerns must be addressed.},
}

Humans
*Sarcopenia/complications/psychology/epidemiology
*Obesity/complications/epidemiology/psychology
Aged
*Depression/epidemiology/complications
Middle Aged
Nutrition Surveys
United States/epidemiology
Male
Female

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

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

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

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

@article {pmid40879079,
year = {2025},
author = {Talbot, K and Thompson, AG},
title = {Unpacking the relationship between exercise and amyotrophic lateral sclerosis.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awaf310},
pmid = {40879079},
issn = {1460-2156},
}

@article {pmid40878928,
year = {2025},
author = {Chakraborty, A and Benassy, MN and Weil, D and Kundu, B},
title = {Optineurin Localization at the Centrosome, Spindle, and Midbody Implies Its Role in Cell Division.},
journal = {Cytoskeleton (Hoboken, N.J.)},
volume = {},
number = {},
pages = {},
doi = {10.1002/cm.70015},
pmid = {40878928},
issn = {1949-3592},
abstract = {Optineurin (OPTN), a multifunctional cytosolic protein, is recognized as an autophagy adaptor. Its association with neurodegenerative diseases, like ALS, triggered extensive research. OPTN has been found in intracellular organelles, including the mitochondria, Golgi body, endosomes, microtubules, and the nucleus. The report of mitotic defects and delayed cell division in OPTN-depleted cells prompted us to explore OPTN's exact localization in the cell that could interfere with cell division assemblies. We used three distinct human cell lines, HeLa, HEK293, and SH-SY5Y, and probed them for OPTN localization using both centrosomal (Aurora A kinase, pericentrin, PCM1, Cep170, and γ-tubulin) and mitotic spindle markers (β-tubulin). Our immunofluorescence-based detection using wide-field fluorescence, confocal, and structured illumination microscopy (SIM) placed OPTN at the centrosome, which remained associated with the centriole after duplication and their migration during mitosis. OPTN was also observed at the junction of daughter cells during cytokinesis. Our finding reveals unmapped localizations of OPTN with key cytosolic assemblies that are directly involved in cell division.},
}

@article {pmid40878817,
year = {2025},
author = {Lester, DG and Talbot, K and Turner, MR and Thompson, AG and , },
title = {A Validated Model to Predict Severe Weight Loss in Amyotrophic Lateral Sclerosis.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.70129},
pmid = {40878817},
issn = {2328-9503},
support = {Lester/2450/795/MNDA_/Motor Neurone Disease Association/United Kingdom ; Thompson/Jan20/952-795/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/T006927/1/MRC_/Medical Research Council/United Kingdom ; MR/Y001095/1/MRC_/Medical Research Council/United Kingdom ; },
abstract = {Severe weight loss in amyotrophic lateral sclerosis (ALS) is common, multifactorial, and associated with shortened survival. Using longitudinal weight data from over 6000 patients with ALS across three cohorts, we built an accelerated failure time model to predict the risk of future severe (≥ 10%) weight loss using five single-timepoint clinical predictors: symptom duration, revised ALS Functional Rating Scale, site of onset, forced vital capacity, and age. Model performance and generalisability were evaluated using internal-external cross-validation and random-effects meta-analysis. The overall concordance statistic was 0.71 (95% CI 0.63-0.79), and the calibration slope and intercept were 0.91 (0.69-1.13) and 0.05 (-0.11-0.21). This study highlights clinical factors most associated with severe weight loss in ALS and provides the basis for a stratification tool.},
}

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

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

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

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

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

@article {pmid40877115,
year = {2025},
author = {Hu, N and Ding, J and Tian, H and Shen, D and Yang, X and Niu, J and Liu, M and Cui, L},
title = {Impacts of oral supplementation of vitamin B12 and plasma levels of homocysteine on progression and survival in a Chinese ALS cohort.},
journal = {Neurological research},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/01616412.2025.2553147},
pmid = {40877115},
issn = {1743-1328},
abstract = {OBJECTIVE: We investigate the impact of plasma levels of folate, vitamin B12 (VB12), homocysteine (HCY) and oral supplementation of folate and VB12 on amyotrophic lateral sclerosis (ALS) progression and survival.

METHODS: Patients with sporadic ALS were consecutively enrolled and regularly followed up. Oral supplementation of folate and VB12 was recommended to all involved patients. Tests of plasma levels of folate, VB12 and HCY were conducted before or after medication.

RESULTS: A total of 120 sporadic ALS patients with results of plasma folate, VB12 or HCY were finally included. Oral supplementation of VB12 significantly increased the plasma levels of folate (p < 0.01) and VB12 (p < 0.01), and lower HCY (p < 0.001). The progression rate of ALS patients in the first 3-6 months was negatively related to the plasma level of VB12 (p = 0.008). After taking VB supplements, the progression rate in the first 3-6 months was comparable to previous progression rate (p = 0.102) and significantly lower than that in the 9-12 month follow-up (p < 0.01). There was no significant difference in survival time between the two groups that took VB12 and those who did not take it neither between patients with high and low serum levels of folate, VB12 or HCY.

CONCLUSION: Oral intake of VB12 supplements may significantly increase plasma levels of folate and VB12 and decrease plasma levels of HCY in ALS patients. Oral supplementation of folate and VB12, and subsequent high levels of VB12 in serum, may lower the ALS progression at the early stages but show no significant impact on ALS survival time.},
}

@article {pmid40876628,
year = {2025},
author = {Pytel, D and Longo, JF},
title = {The Proteostasis Network in Proteinopathies: Mechanisms and Interconnections.},
journal = {The American journal of pathology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajpath.2025.07.011},
pmid = {40876628},
issn = {1525-2191},
abstract = {Proteinopathies are neurodegenerative disorders that are characterized by accumulation of misfolded toxic protein aggregates that lead to synaptic and neuronal dysfunction. Though genetically, clinically and pathologically distinct, a common feature of these diseases is disruption of protein homeostasis (proteostasis), which causes accumulation of misfolded proteins. The machinery mediating proteostasis exquisitely balances and interlaces protein synthesis, protein folding and trafficking, and protein degradation processes within the proteostasis network to maintain homeostasis. The proteostasis network governs a functional and dynamic proteome by modulating the timing, location, and stoichiometry of protein expression, surveillance and maintenance of protein folding and removal of misfolded or excess proteins. Although a functional proteome is essential for the health of all cell types, this is especially true for neurons which are prone to enhanced cellular stress. Aging is the most important risk factor for proteostasis decline and the development of proteinopathies. However, germline and somatic mutations can also functionally impair components of the proteostasis network. Post-mitotic cells, particularly neurons, are rendered further susceptible to proteostasis dysfunction due to their extended lifespan. This review discusses the interconnections between the functional components mediating proteostasis in neuronal cells and how aberrations in proteostasis contribute to neuronal dysfunction and disease.},
}

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

@article {pmid40875997,
year = {2025},
author = {Kaufman Goldberg, T and Hadlock, TA},
title = {Invited Commentary on: Frants et al.'s "Dual Innervation of the Depressor Labii Inferioris and Implications for Deep Plane Facelift and Structural Neck Contouring": Converging Evidence for Cervical Branch Innervation of the Depressor Labii Inferioris.},
journal = {Facial plastic surgery & aesthetic medicine},
volume = {27},
number = {5},
pages = {406-407},
doi = {10.1177/26893614251370279},
pmid = {40875997},
issn = {2689-3622},
}

@article {pmid40875690,
year = {2025},
author = {Abdallah, W and Picard-Turcot, MA and Lafontaine-Trudel, I and Codsi, E and Wavrant, S and Carmant, L and Raboisson, MJ and Khalil, A and Audibert, F},
title = {Prediction of dual twin survival after laser for twin-to-twin transfusion syndrome.},
journal = {Fetal diagnosis and therapy},
volume = {},
number = {},
pages = {1-14},
doi = {10.1159/000547995},
pmid = {40875690},
issn = {1421-9964},
abstract = {OBJECTIVES: To evaluate the predictive value of sonographic parameters at diagnosis of Twin-to-Twin Transfusion Syndrome (TTTS) treated with fetoscopic laser photocoagulation for post-natal dual twin survival, and to validate Krispin et al's calculator.

METHODS: This is a retrospective cohort study of cases of TTTS treated by FLPC. The primary outcome was dual survival 30 days after delivery. The calculator used preoperative variables: donor's estimated fetal weight (EFW)<10th centile, intertwin growth discordance >25%, anterior placenta, pulsatility index (PI) in the umbilical artery (UA), ductus venosus (DV) and middle cerebral artery (MCA), with scores ranging 0-300.

RESULTS: Among 157 patients, 84 (53.5%) had dual twin survival (A), compared to 73 (46.5%) with one or no survivors (B). No significant differences were seen in donor's EFW <10th centile (57.1%(A) vs. 57.5%(B), p=0.96), intertwin growth discordance (26.2%(A) vs. 38.4%(B) p=0.95), rates of PI>95th centile in the donor's UA and DV, and PI<5th centile in the MCA (p>0.05). However, a significant difference was found for anterior placenta (38.1% (A) vs. 58.9% (B), p=0.009). The observed dual survival was higher than predicted for scores ≥100.

CONCLUSIONS: We did not externally validate the calculator of dual survival after laser for TTTS, especially for elevated scores.},
}

@article {pmid40875372,
year = {2025},
author = {Ghaffari, LT and Welebob, EA and Newton, SEB and Boehringer, AV and Cyliax, KL and Pasinelli, P and Trotti, D and Haeusler, AR},
title = {Neuronal Activity-Dependent Gene Dysregulation in C9orf72 i[3]Neuronal Models of ALS/FTD Pathogenesis.},
journal = {American journal of physiology. Cell physiology},
volume = {},
number = {},
pages = {},
doi = {10.1152/ajpcell.00238.2025},
pmid = {40875372},
issn = {1522-1563},
support = {RF1NS114128//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01NS114128//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01NS109150//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; NA//Farber Family Foundation/ ; NA//Aldrich Foundation/ ; },
abstract = {The GGGGCC nucleotide repeat expansion (NRE) mutation in the C9orf72 (C9) gene is the most common cause of ALS and FTD. Neuronal activity plays an essential role in shaping biological processes within both healthy and neurodegenerative disease scenarios. Here, we show that at baseline conditions, C9-NRE iPSC-cortical neurons display aberrations in several pathways, including synaptic signaling and transcriptional machinery, potentially priming diseased neurons for an altered response to neuronal stimulation. Indeed, exposure to two pathophysiologically relevant stimulation modes, prolonged membrane depolarization, or a blockade of K[+] channels, followed by RNA sequencing, induces a temporally divergent activity-dependent transcriptome of C9-NRE cortical neurons compared to healthy controls. This study provides new insights into how neuronal activity influences the ALS/FTD-associated transcriptome, offering a dataset that enables further exploration of pathways necessary for conferring neuronal resilience or degeneration.},
}

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

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

@article {pmid40875336,
year = {2025},
author = {Yuan, Z and Yin, J and Sun, J},
title = {The paradox of team conflict revisited: An updated meta-analysis of the team conflict-team performance relationships.},
journal = {The Journal of applied psychology},
volume = {},
number = {},
pages = {},
doi = {10.1037/apl0001315},
pmid = {40875336},
issn = {1939-1854},
abstract = {The possibility that team conflict, especially task conflict, might improve team performance has stimulated a large body of empirical research that continues to grow to this day. Nevertheless, 12 years has passed since de Wit et al.'s (2012) comprehensive meta-analysis. To synthesize the even larger body of empirical evidence now available, we provide an updated meta-analysis of the team conflict-team performance relationships by revisiting the population average estimates and their effect size heterogeneity. Given the recent developments in the team conflict literature, we also incorporate status conflict into our synthesis. Moreover, to shed light on the contextual factors that may help explain the heterogeneous team conflict-team performance relationships, we examine a host of moderators pertaining to national culture, team features, and research methods. Our results based on psychometric meta-analysis indicate that all four team conflict dimensions (i.e., task conflict, relationship conflict, process conflict, and status conflict) are negatively related to team performance. Moreover, the relationships of task conflict and relationship conflict with team performance have substantial cross-situation heterogeneity. Examining the contingencies of these heterogeneous relationships, our metaregression analyses reveal that national culture (e.g., individualism), team features (e.g., team performance facet), and methodological factors (e.g., team conflict scale) all play important roles in helping to explain the mixed effects of team conflict on team performance. Based on our quantitative synthesis, we discuss the implications for the next waves of team conflict research. (PsycInfo Database Record (c) 2025 APA, all rights reserved).},
}

@article {pmid40874900,
year = {2025},
author = {Shive, M and Hawryluk, E and Drucker, AM and Frazer-Green, L},
title = {Response to Chu et al's "Atopic dermatitis (eczema) guidelines: 2023 American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters GRADE- and Institute of Medicine-based recommendations".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.07.061},
pmid = {40874900},
issn = {1097-6787},
}

@article {pmid40873038,
year = {2025},
author = {Dulski, J and Boddapati, AK and Risi, B and Iruzubieta, P and Orlacchio, A and Fernández-Torrón, R and Castillo-Triviño, T and López de Munain, A and Vucic, S and Padovani, A and Kaat, LD and Barakat, TS and Petrucelli, L and Prudencio, M and Landers, JE and Weishaupt, JH and Prokop, A and Filosto, M and Wszolek, ZK and Pant, DC},
title = {Targeted plasma proteomics uncover proteins associated with KIF5A-linked SPG10 and ALS spectrum disorders.},
journal = {HGG advances},
volume = {},
number = {},
pages = {100498},
doi = {10.1016/j.xhgg.2025.100498},
pmid = {40873038},
issn = {2666-2477},
abstract = {KIF5A (Kinesin family member 5A) is a motor protein that functions as a key component of the axonal transport machinery. Variants in KIF5A are linked to several neurodegenerative diseases, mainly spastic paraplegia type 10 (SPG10), Charcot-Marie-Tooth disease type 2 (CMT2), and amyotrophic lateral sclerosis (ALS). These diseases share motor neuron involvement but vary significantly in clinical presentation, severity, and progression. KIF5A variants are mainly categorized into N-terminal variants associated with SPG10/CMT2 and C-terminal variants linked to ALS. This study utilized a multiplex NULISA targeted platform to analyze plasma proteome from KIF5A-linked SPG10, ALS individuals and compared to healthy controls. Our results revealed distinct proteomic signatures, with significant alterations in proteins related to synaptic function, and inflammation. Notably, neurofilament light polypeptide, a biomarker for neurodegenerative diseases, was elevated in KIF5A ALS but not in SPG10 individuals. Moreover, these findings can now be taken forward to gain mechanistic understanding of axonopathies linking to N- versus C-terminal KIF5A variants affecting both central and peripheral nervous systems.},
}

@article {pmid40872233,
year = {2025},
author = {Garcia-Sherman, MC and Hamid, SA and Jackson, DN and Thomas, J and Lipke, PN},
title = {Functional Amyloids in Adhesion of Non-albicans Candida Species.},
journal = {Pathogens (Basel, Switzerland)},
volume = {14},
number = {8},
pages = {},
doi = {10.3390/pathogens14080723},
pmid = {40872233},
issn = {2076-0817},
support = {1R01GM098616-01/NH/NIH HHS/United States ; },
mesh = {Humans ; *Cell Adhesion ; *Candida/physiology/metabolism ; *Amyloid/metabolism ; Biofilms/growth & development ; Fungal Proteins/metabolism ; Candida albicans ; Candidiasis/microbiology ; Epithelial Cells/microbiology ; },
abstract = {Candida fungal species are the most common fungal opportunistic pathogens. Their ability to form antifungal resistant biofilms contributes to their increasing clinical frequency. These fungi express surface-anchored adhesins including members of the Als family. These adhesins mediate epithelial adhesion, aggregation, and biofilm formation. Many of the adhesins contain cross-β core sequences that form amyloid-like protein aggregates on the fungal surface. The aggregates mediate high-avidity bonding that contributes to biofilm establishment and persistence. Accordingly, autopsy sections from individuals with candidiasis and other mycoses have amyloids within abscesses. An amyloid-forming peptide containing a sequence from Candida albicans Als5 bound to C. albicans, C. tropicalis, and C. parapsilosis. C. albicans and C. tropicalis aggregated with beads coated with serum albumin, and the aggregates stained with the amyloid-binding dye thioflavin T. Additionally, an Als5-derived amyloid-inhibiting peptide blocked cell aggregation. The amyloid-inhibiting peptide also blocked C. albicans, C. tropicalis, and C. parapsilosis adhesion to monolayers of FaDu epithelial cells. These results show the involvement of amyloid-like interactions in pathogenesis in several Candida species.},
}

Humans
*Cell Adhesion
*Candida/physiology/metabolism
*Amyloid/metabolism
Biofilms/growth & development
Fungal Proteins/metabolism
Candida albicans
Candidiasis/microbiology
Epithelial Cells/microbiology

@article {pmid40871062,
year = {2025},
author = {Yang, HM},
title = {Overcoming the Blood-Brain Barrier: Advanced Strategies in Targeted Drug Delivery for Neurodegenerative Diseases.},
journal = {Pharmaceutics},
volume = {17},
number = {8},
pages = {},
doi = {10.3390/pharmaceutics17081041},
pmid = {40871062},
issn = {1999-4923},
support = {03-2025-0200//Seoul National University Hospital/ ; },
abstract = {The increasing global health crisis of neurodegenerative diseases such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and Huntington's disease is worsening because of a rapidly increasing aging population. Disease-modifying therapies continue to face development challenges due to the blood-brain barrier (BBB), which prevents more than 98% of small molecules and all biologics from entering the central nervous system. The therapeutic landscape for neurodegenerative diseases has recently undergone transformation through advances in targeted drug delivery that include ligand-decorated nanoparticles, bispecific antibody shuttles, focused ultrasound-mediated BBB modulation, intranasal exosomes, and mRNA lipid nanoparticles. This review provides an analysis of the molecular pathways that cause major neurodegenerative diseases, discusses the physiological and physicochemical barriers to drug delivery to the brain, and reviews the most recent drug targeting strategies including receptor-mediated transcytosis, cell-based "Trojan horse" approaches, gene-editing vectors, and spatiotemporally controlled physical methods. The review also critically evaluates the limitations such as immunogenicity, scalability, and clinical translation challenges, proposing potential solutions to enhance therapeutic efficacy. The recent clinical trials are assessed in detail, and current and future trends are discussed, including artificial intelligence (AI)-based carrier engineering, combination therapy, and precision neuro-nanomedicine. The successful translation of these innovations into effective treatments for patients with neurodegenerative diseases will require essential interdisciplinary collaboration between neuroscientists, pharmaceutics experts, clinicians, and regulators.},
}

@article {pmid40870776,
year = {2025},
author = {Semyalo, D and Joshi, R and Kim, Y and Omia, E and Alal, LB and Kim, MS and Baek, I and Cho, BK},
title = {Short-Wavelength Infrared Hyperspectral Imaging and Spectral Unmixing Techniques for Detection and Distribution of Pesticide Residues on Edible Perilla Leaves.},
journal = {Foods (Basel, Switzerland)},
volume = {14},
number = {16},
pages = {},
doi = {10.3390/foods14162864},
pmid = {40870776},
issn = {2304-8158},
support = {N/A//Chungnam National University/ ; },
abstract = {Pesticide residue analysis of agricultural produce is vital because of associated health concerns, highlighting the need for effective non-destructive techniques. This study introduces a method that combines short-wavelength infrared hyperspectral imaging with spectral unmixing to detect chlorfenapyr and azoxystrobin residues on perilla leaves. Sixty-six leaves were treated with pesticides at concentrations between 0 and 0.06%. The study utilized multicurve resolution-alternating least squares (MCR-ALS), a spectral unmixing method, to identify and visualize the distribution of pesticide residues. This technique achieved lack-of-fit values of 1.03% and 1.78%, with an explained variance of 99% for both pesticides. Furthermore, a quantitative model was developed that integrates insights from MCR-ALS with Gaussian process regression to estimate chlorfenapyr residue concentrations, resulting in a root mean square error of double cross-validation (RMSEV) of 0.0012% and a double cross-validation coefficient of determination (R[2]v) of 0.99. Compared to other chemometric approaches, such as partial least squares regression and support vector regression, the proposed integrated method decreased RMSEV by 67.57% and improved R[2]v by 2.06%. The combination of hyperspectral imaging with spectral unmixing offers advancements in the real-time monitoring of agricultural product safety, supporting the delivery of high-quality fresh vegetables to consumers.},
}

@article {pmid40870005,
year = {2025},
author = {Jeong, J and Kim, J and Kim, MS},
title = {Dual Nature of Mitochondrial Integrated Stress Response: Molecular Switches from Protection to Pathology.},
journal = {Genes},
volume = {16},
number = {8},
pages = {},
doi = {10.3390/genes16080957},
pmid = {40870005},
issn = {2073-4425},
mesh = {Humans ; *Mitochondria/metabolism/pathology/genetics ; *Stress, Physiological ; Animals ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology/genetics ; },
abstract = {BACKGROUND: The mitochondrial integrated stress response (ISR) represents a fundamental cellular adaptation mechanism with dual protective and pathological roles. We critically analyzed current literature on ISR mechanisms, focusing on recent paradigm shifts including the 2020 discovery of the OMA1-DELE1-HRI axis, emerging controversies over context-dependent activation patterns, and the January 2025 clinical trial failures that have reshaped the therapeutic landscape.

METHODS: We reviewed recent literature (2020-2025) examining ISR mechanisms, clinical trials, and therapeutic developments through comprehensive database searches.

RESULTS: The field has evolved from simple linear pathway models to recognition of complex, context-dependent networks. Recent findings reveal that ISR activation mechanisms vary dramatically based on cellular metabolic state, with distinct pathways operating in proliferating versus differentiated cells. The "dark microglia" phenotype in neurodegeneration and DR5-mediated apoptotic switches exemplify pathological ISR manifestations, while adaptive responses include metabolic reprogramming and quality control enhancement.

CONCLUSIONS: The 2025 failures of DNL343 and ABBV-CLS-7262 in ALS trials underscore the need for precision medicine approaches that account for context-dependent ISR functions, temporal dynamics, and disease-specific mechanisms.},
}

Humans
*Mitochondria/metabolism/pathology/genetics
*Stress, Physiological
Animals
*Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology/genetics

@article {pmid40869392,
year = {2025},
author = {Șerban, M and Toader, C and Covache-Busuioc, RA},
title = {Blueprint of Collapse: Precision Biomarkers, Molecular Cascades, and the Engineered Decline of Fast-Progressing ALS.},
journal = {International journal of molecular sciences},
volume = {26},
number = {16},
pages = {},
doi = {10.3390/ijms26168072},
pmid = {40869392},
issn = {1422-0067},
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology/diagnosis ; Humans ; *Biomarkers/metabolism ; Disease Progression ; Animals ; Mitochondria/metabolism ; Precision Medicine ; Neurofilament Proteins/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is still a heterogeneous neurodegenerative disorder that can be identified clinically and biologically, without a strong set of biomarkers that can adequately measure its fast rate of progression and molecular heterogeneity. In this review, we intend to consolidate the most relevant and timely advances in ALS biomarker discovery, in order to begin to bring molecular, imaging, genetic, and digital areas together for potential integration into a precision medicine approach to ALS. Our goal is to begin to display how several biomarkers in development (e.g., neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), TDP-43 aggregates, mitochondrial stress markers, inflammatory markers, etc.) are changing our understanding of ALS and ALS dynamics. We will attempt to provide a framework for thinking about biomarkers in a systematic way where our candidates are not signals alone but part of a tethered pathophysiological cascade. We are particularly interested in the fast progressor phenotype, a devastating and under-characterized subset of ALS due to a rapid axonal degeneration, early respiratory failure, and very short life span. We will try to highlight the salient molecular features of this ALS subtype, including SOD1 A5V toxicity, C9orf72 repeats, FUS variants, mitochondrial collapse, and impaired autophagy mechanisms, and relate these features to measurable blood and CSF (biomarkers) and imaging platforms. We will elaborate on several interesting tools, for example, single-cell transcriptomics, CSF exosomal cargo analysis, MRI techniques, and wearable sensor outputs that are developing into high-resolution windows of disease progression and onset. Instead of providing a static catalog, we plan on providing a conceptual roadmap to integrate biomarker panels that will allow for earlier diagnosis, real-time disease monitoring, and adaptive therapeutic trial design. We hope this synthesis will make a meaningful contribution to the shift from observational neurology to proactive biologically informed clinical care in ALS. Although there are still considerable obstacles to overcome, the intersection of a precise molecular or genetic association approach, digital phenotyping, and systems-level understandings may ultimately redefine how we monitor, care for, and treat this challenging neurodegenerative disease.},
}

*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology/diagnosis
Humans
*Biomarkers/metabolism
Disease Progression
Animals
Mitochondria/metabolism
Precision Medicine
Neurofilament Proteins/metabolism

@article {pmid40869205,
year = {2025},
author = {Lewandowski, D and Konieczny, M and Różycka, A and Chrzanowski, K and Owecki, W and Kalinowski, J and Stepura, M and Jagodziński, P and Dorszewska, J},
title = {Cathepsins in Neurological Diseases.},
journal = {International journal of molecular sciences},
volume = {26},
number = {16},
pages = {},
doi = {10.3390/ijms26167886},
pmid = {40869205},
issn = {1422-0067},
mesh = {Humans ; *Cathepsins/metabolism ; Animals ; *Nervous System Diseases/metabolism/pathology ; Lysosomes/metabolism ; Biomarkers/metabolism ; },
abstract = {Cathepsins, a family of lysosomal proteases, play critical roles in maintaining cellular homeostasis through protein degradation and modulation of immune responses. In the central nervous system (CNS), their functions extend beyond classical proteolysis, influencing neuroinflammation, synaptic remodeling, and neurodegeneration. Emerging evidence underscores the crucial role of microglial cathepsins in the pathophysiology of several neurological disorders. This review synthesizes current knowledge on the involvement of cathepsins in a spectrum of CNS diseases, including Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, epilepsy, Huntington's disease, and ischemic stroke. We highlight how specific cathepsins contribute to disease progression by modulating key pathological processes such as α-synuclein and amyloid-β clearance, tau degradation, lysosomal dysfunction, neuroinflammation, and demyelination. Notably, several cathepsins demonstrate both neuroprotective and pathogenic roles depending on disease context and expression levels. Additionally, the balance between cathepsins and their endogenous inhibitors, such as cystatins, emerges as a critical factor in CNS pathology. While cathepsins represent promising biomarkers and therapeutic targets, significant gaps remain in our understanding of their mechanistic roles across diseases. Future studies focusing on their regulation, substrate specificity, and interplay with genetic and epigenetic factors may yield novel strategies for early diagnosis and disease-modifying treatments in neurology.},
}

Humans
*Cathepsins/metabolism
Animals
*Nervous System Diseases/metabolism/pathology
Lysosomes/metabolism
Biomarkers/metabolism

@article {pmid40868609,
year = {2025},
author = {Lisiecka, D and Dyson, N and Malpress, K and Smith, A and McNeice, E and Shack, P and Hutchinson, K},
title = {'Finally, in Hands I Can Trust': Perspectives on Trust in Motor Neurone Disease Care.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {16},
pages = {},
doi = {10.3390/healthcare13161994},
pmid = {40868609},
issn = {2227-9032},
abstract = {Integrated multidisciplinary care is recognised as essential for people living with motor neurone disease (PlwMND) and their families. The values underpinning integrated care, such as person-centredness, respect, empowerment, and co-production, are central to delivering meaningful and comprehensive support. Trust is an essential yet often overlooked element of effective person- and family-centred integrated care, particularly for PlwMND. While specialist multidisciplinary MND clinics represent the benchmark for evidence-based care, many PlwMND and their families depend significantly on local and community-based support services to maintain quality of life. Trust directly influences their engagement with these services and the continuity of care provided. Trust enables understanding of personal priorities and how they change as the disease progresses, ultimately allowing for person-centred care to happen. Trust is necessary to enable service co-production, which is a strong value of integrated care. Research highlights seven key domains of support essential to PlwMND and their carers: practical, social, informational, psychological, physical, emotional, and spiritual. Effective integrated care requires strong relationships built upon trust, shared decision-making, respect for individuality, and clear communication. Furthermore, due to the rapidly progressive nature of MND, care priorities and perceived symptom burdens may shift significantly over short periods, making flexible, temporally sensitive approaches critical. A dynamic, inclusive model of decision-making that fosters autonomy within and regular co-review of needs is recommended. This perspective paper examines how person- and family-centred integrated care is currently being delivered, what is working well, and how these practices can be further strengthened to enhance the care experiences of PlwMND, their families, and the health and social care providers involved. This paper builds on both theoretical knowledge and clinical experience to offer our perspective on the critical role of trust in co-producing integrated care for PlwMND. It brings together the voices of clinicians and researchers, alongside those with lived experience of MND. We propose a diagram of care that embeds the core values of integrated, person-centred care within the specific context of MND. Our aim is to enhance collaborative practices, strengthen cross-sector partnerships, and ultimately improve the care experiences for professionals, PlwMND, and their families.},
}

@article {pmid40868276,
year = {2025},
author = {Voicu, V and Toader, C and Șerban, M and Covache-Busuioc, RA and Ciurea, AV},
title = {Systemic Neurodegeneration and Brain Aging: Multi-Omics Disintegration, Proteostatic Collapse, and Network Failure Across the CNS.},
journal = {Biomedicines},
volume = {13},
number = {8},
pages = {},
doi = {10.3390/biomedicines13082025},
pmid = {40868276},
issn = {2227-9059},
abstract = {Neurodegeneration is increasingly recognized not as a linear trajectory of protein accumulation, but as a multidimensional collapse of biological organization-spanning intracellular signaling, transcriptional identity, proteostatic integrity, organelle communication, and network-level computation. This review intends to synthesize emerging frameworks that reposition neurodegenerative diseases (ND) as progressive breakdowns of interpretive cellular logic, rather than mere terminal consequences of protein aggregation or synaptic attrition. The discussion aims to provide a detailed mapping of how critical signaling pathways-including PI3K-AKT-mTOR, MAPK, Wnt/β-catenin, and integrated stress response cascades-undergo spatial and temporal disintegration. Special attention is directed toward the roles of RNA-binding proteins (e.g., TDP-43, FUS, ELAVL2), m6A epitranscriptomic modifiers (METTL3, YTHDF1, IGF2BP1), and non-canonical post-translational modifications (SUMOylation, crotonylation) in disrupting translation fidelity, proteostasis, and subcellular targeting. At the organelle level, the review seeks to highlight how the failure of ribosome-associated quality control (RQC), autophagosome-lysosome fusion machinery (STX17, SNAP29), and mitochondrial import/export systems (TIM/TOM complexes) generates cumulative stress and impairs neuronal triage. These dysfunctions are compounded by mitochondrial protease overload (LONP1, CLPP), UPR maladaptation, and phase-transitioned stress granules that sequester nucleocytoplasmic transport proteins and ribosomal subunits, especially in ALS and FTD contexts. Synaptic disassembly is treated not only as a downstream event, but as an early tipping point, driven by impaired PSD scaffolding, aberrant endosomal recycling (Rab5, Rab11), complement-mediated pruning (C1q/C3-CR3 axis), and excitatory-inhibitory imbalance linked to parvalbumin interneuron decay. Using insights from single-cell and spatial transcriptomics, the review illustrates how regional vulnerability to proteostatic and metabolic stress converges with signaling noise to produce entropic attractor collapse within core networks such as the DMN, SN, and FPCN. By framing neurodegeneration as an active loss of cellular and network "meaning-making"-a collapse of coordinated signal interpretation, triage prioritization, and adaptive response-the review aims to support a more integrative conceptual model. In this context, therapeutic direction may shift from damage containment toward restoring high-dimensional neuronal agency, via strategies that include the following elements: reprogrammable proteome-targeting agents (e.g., PROTACs), engineered autophagy adaptors, CRISPR-based BDNF enhancers, mitochondrial gatekeeping stabilizers, and glial-exosome neuroengineering. This synthesis intends to offer a translational scaffold for viewing neurodegeneration as not only a disorder of accumulation but as a systems-level failure of cellular reasoning-a perspective that may inform future efforts in resilience-based intervention and precision neurorestoration.},
}

@article {pmid40868211,
year = {2025},
author = {Flor, J and Silveira, AT and Martins, IA and Otero, LB and Silva, FM and Vizuete, AFK and Wink, MR and Rigatto, K},
title = {Biological Actions of Alamandine: A Scoping Review.},
journal = {Biomedicines},
volume = {13},
number = {8},
pages = {},
doi = {10.3390/biomedicines13081957},
pmid = {40868211},
issn = {2227-9059},
abstract = {Objective: This scoping review aims to comprehensively map the existing literature on the mechanisms of action of Alamandine (ALA), a peptide within the renin-angiotensin system, and its effects across various physiological systems. Materials and Methods: Utilizing the Joanna Briggs Institute methodology, a thorough search of databases including PubMed, Embase, Scopus, and Web of Science was conducted up to 30 January 2025. The review focused on identifying studies that explore the biological and therapeutic roles of ALA in different contexts, incorporating in vivo, in vitro, and in silico research. Results: A total of 590 records were initially identified, with 25 meeting the eligibility criteria for inclusion in this review. China emerged as the leading contributor to the research in this area, with a significant focus on the cardiovascular system. The studies revealed that ALA exhibits a range of beneficial effects, including anti-inflammatory, vasodilatory, antifibrotic, and antiapoptotic actions. These effects are primarily mediated through the inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway and modulation of the nitric oxide pathway. The review also highlighted AL's potential in mitigating oxidative stress and its implications in treating cardiovascular diseases, fibrosis, and cancer. Conclusions: The findings suggest that ALA holds significant therapeutic potential, offering antihypertensive, anti-inflammatory, antifibrotic, and anticancer benefits without notable adverse effects, warranting further research to explore its full potential and mechanism of action.},
}

@article {pmid40866928,
year = {2025},
author = {Tsang, VSK and Malaspina, A and Henson, SM},
title = {The metabolic intersection between immunosenescence and neuroinflammation in amyotrophic lateral sclerosis.},
journal = {Journal of inflammation (London, England)},
volume = {22},
number = {1},
pages = {36},
pmid = {40866928},
issn = {1476-9255},
support = {BBX009610/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motor neurons. Although it is traditionally viewed as a neuron-centric disease, neurodegeneration is increasingly linked to immunosenescence and age-related immune dysfunction, but the mechanisms connecting immune ageing to neurodegeneration remain poorly understood. In this review, we explore how metabolic reprogramming, especially the loss of metabolic plasticity in senescent immune cells, drives neuroinflammation in ALS. Senescent immune cells, including microglia and T cells, exhibit mitochondrial dysfunction, redox imbalance, impaired autophagy, and altered nutrient-sensing pathways that impair their homeostatic and reparative capacities. These cells adopt a metabolically demanding pro-inflammatory phenotype, sustaining an inflammatory secretome while promoting glial activation and neuronal damage. Finally, we discuss how targeting immunometabolic pathways may offer new therapeutic opportunities to restore immune balance, mitigate neuroinflammation, and potentially slow ALS progression. Understanding the metabolic basis of immune ageing is essential for developing effective, age-tailored interventions for ALS.},
}

@article {pmid40866479,
year = {2025},
author = {Waheed, ZA and Colagar, AH and Seyedalipour, B and Baziyar, P},
title = {Uncovering the protein aggregation process through effect of G41D mutant SOD1 charge variation in ALS disease.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {31661},
pmid = {40866479},
issn = {2045-2322},
abstract = {Neurodegenerative disorders are a group of hereditary and sporadic conditions that are characterized by progressive nervous system dysfunctions. Mutations in the gene encoding human superoxide dismutase 1 (hSOD1) were among the first to be proposed in line with the protein aggregation theory for ALS disease. This study aimed to characterize the (G41D) mutation/charge effects on the biochemical and biophysical properties of the SOD1 structure through computational and experimental methods. The computed average values of RMSD, RMSF, and Rg demonstrate that mutation results in a loss of conformational stability, increased flexibility, and greater compactness, all supporting the observed aggregation. The G41D mutant revealed distinct changes in β-sheet content compared to WT-SOD1 under amyloidogenic conditions, as confirmed by FTIR spectroscopy. Furthermore, the formation of amyloid/amorphous species was identified using ThT/ANS fluorescence and confirmed by TEM analysis. Mutations that alter the net negative charge of the SOD1 protein are crucial in misfolding and shortening the lag phase in SOD1 aggregation. Our results provide supporting evidence that these charge alterations, alongside amyloid-inducing agents at near-physiological pH, significantly contribute to the formation of amyloid-like species. Therefore, studying the G41D mutation may provide valuable insights into the mechanisms of fALS-associated aggregate formation, which holds promise for the development of highly effective inhibitors in reducing aggregates and therapeutic potential.},
}

@article {pmid40865732,
year = {2025},
author = {Deighen, MR and Fakult, NJ and Mani, KA and Cullison, CR and Wang, M and Bordeaux, JS and Carroll, BT and Rothermel, LD and Zaorsky, NG},
title = {Response to Sheu et al., "Comments on Fakult et al.'s 'Epidemiology of Merkel Cell Carcinoma in the United States'".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.08.055},
pmid = {40865732},
issn = {1097-6787},
}

@article {pmid40865726,
year = {2025},
author = {Li, Y and Wang, Y and Li, Y and Jia, X and Du, X},
title = {[Response][to][Pavlović] '[s] "[Response][to][Li][et][al.'s] '[Therapeutic efficacy of platelet-rich plasma combining with microneedling and topical minoxidil in refractory severe androgenic alopecia]'".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.08.056},
pmid = {40865726},
issn = {1097-6787},
}

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

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

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

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

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

@article {pmid40864790,
year = {2025},
author = {Du, Y and Fan, SS and Wu, H and He, J and He, Y and Meng, XY and Xu, X},
title = {Convergent and Divergent Mitochondrial Pathways as Causal Drivers and Therapeutic Targets in Neurological Disorders.},
journal = {Current issues in molecular biology},
volume = {47},
number = {8},
pages = {},
doi = {10.3390/cimb47080636},
pmid = {40864790},
issn = {1467-3045},
support = {0801059201//the Research Fund for the Doctoral Program of Anhui Medical University/ ; 82303057//National Natural Science Foundation of China/ ; 2023AFB521//Natural Science Foundation of Hubei Province of China/ ; },
abstract = {Mitochondrial dysfunction is implicated across a spectrum of neurological diseases, yet its causal role and mechanistic specificity remain unclear. This study employed a multi-modal integrative analysis of mitochondrial gene expression in Alzheimer's Disease (AD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), and Parkinson's Disease (PD) to address these gaps. We combined machine learning for predictive modeling with genetic causal inference methods (Mendelian Randomization, colocalization, PheWAS), followed by drug enrichment analysis and molecular docking. Our machine learning models, particularly Support Vector Machine and Multi-layer Perceptron, effectively classified these conditions, with MS exhibiting the highest predictability (mean Accuracy: 0.758). Causal inference analyses identified specific gene-disease links; for instance, genetically predicted increased expression of PDK1 was causally associated with an elevated risk for both AD (OR = 1.041) and ALS (OR = 1.037), identifying pyruvate metabolism as a shared vulnerability. In contrast, genes like SLC25A38 emerged as highly predictive specifically for PD. We also observed evidence of potential brain-periphery interaction, such as a bidirectional causal relationship between red blood cell indices and MS risk. Finally, drug enrichment analysis highlighted Celecoxib, and subsequent molecular docking predicted a strong binding affinity to PDK1 (docking score S = -6.522 kcal/mol), generating hypotheses for potential metabolic modulation. Taken together, this study provides a computational hypothesis framework suggesting mitochondrial pathways and targets that warrant future biological validation. This study provides specific, genetically supported evidence for the causal role of mitochondrial pathways in neurological diseases and identifies tangible targets for future therapeutic development.},
}

@article {pmid40864664,
year = {2025},
author = {Popoli, R and Wells, TL and Akay, T},
title = {Unlocking new mechanisms for future ALS therapies: early interventions with cholinergic antagonists reduce neuromuscular decline.},
journal = {Journal of neurophysiology},
volume = {},
number = {},
pages = {},
doi = {10.1152/jn.00306.2025},
pmid = {40864664},
issn = {1522-1598},
support = {2017//ALS Society of Canada (ALS Canada)/ ; 162357//Canadian Government | Canadian Institutes of Health Research (CIHR)/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by motor neuron loss, leading to muscle paralysis and death. C-boutons have been shown to be part of the compensatory mechanism behind delayed symptom onset, and are most active during vigorous exercises, like swimming. When mutant mice with silenced C-boutons perform this exercise, disease progression and behavioral performance drastically improve. Genetic manipulation of C-boutons in human patients remains limited, therefore, we sought to manipulate these synapses using cholinergic antagonists in the presence and absence of exercise in a mouse model of ALS. We demonstrate that atropine and methoctramine administration yield significant improvements in human endpoints, weight maintenance, treadmill performance, and grip strength. Most remarkably, muscle innervation was greatly enhanced at humane endpoints compared to controls, suggesting these drugs provide a protective effect against loss of motor control. We found that methoctramine provided greater benefits in the absence of exercise, hinting at the presence of novel cholinergic mechanisms that can be manipulated in order to preserve motor function. Moreover, we provide evidence that these results are independent of C-boutons, and that methoctramine does not appear to cross the blood-brain barrier. Our results reveal pharmacological mechanisms by which muscle denervation can be reduced, thereby decreasing the rate of disease progression. We have uncovered a promising avenue for improving ALS symptoms by pharmacologically manipulating cholinergic transmission. This mechanism presents as a possible therapy translatable to the clinical setting, which has the potential to prevent the loss of motor control in patients with ALS.},
}

@article {pmid40864229,
year = {2025},
author = {Xu, Y and Raban, MZ and Li, L and Nguyen, AD and Silva, SSM and Huang, G and Arnolda, G and Westbrook, JI and Wabe, N},
title = {Anticholinergic medication use and falls in Australian residential aged care: a retrospective multisite cohort study.},
journal = {Aging clinical and experimental research},
volume = {37},
number = {1},
pages = {257},
pmid = {40864229},
issn = {1720-8319},
support = {APP1170898//Australian National Health and Medical Research Council/ ; APP1170898//Australian National Health and Medical Research Council/ ; },
mesh = {Humans ; *Accidental Falls/statistics & numerical data/prevention & control ; *Cholinergic Antagonists/adverse effects/therapeutic use ; Female ; Male ; Aged ; Retrospective Studies ; Aged, 80 and over ; *Homes for the Aged/statistics & numerical data ; Australia ; New South Wales ; },
abstract = {BACKGROUND: Associations between anticholinergic load and falls remain understudied in residential aged care facilities (RACFs).

AIMS: To examine associations between anticholinergic load and falls in the first year after entry to an RACF.

METHODS: We aggregated routinely collected data from 27 RACFs in New South Wales, Australia. Anticholinergic load and falls were repeatedly measured for one year after residents first entered an RACF. Thirteen 28-day review periods were set. Associations between anticholinergic load in a review period and any falls in the next review period were examined, comprising 12 repeated measurements of associations. We included new residents aged ≥ 65 years, who entered an RACF between 1 July 2014 and 2 September 2021. Six scales were used: Anticholinergic Cognitive Burden (ACB), Anticholinergic Drug Scale (ADS), Anticholinergic Loading Scale (ALS), Anticholinergic Risk Scale (ARS), Chew's list, and Clinician-rated Anticholinergic Score (CrAS). We used mixed-effect logistic regression models, adjusting for potential confounders. Facility was used as a cluster variable.

RESULTS: For the 2300 residents (67.7% females), there were steady increases in mean anticholinergic load from the first to the 12th review period. Per one-point higher anticholinergic load was associated with an increased risk of falls, adjusted odds ratios: 1.08 (95% confidence interval[CI] 1.04, 1.12) using ACB, 1.11 (95%CI 1.06, 1.15) using ADS, 1.15 (95%CI 1.10, 1.21) using ALS, 1.10 (95%CI 1.04, 1.17) using ARS, 1.18 (95%CI 1.09, 1.27) using Chew's list, and 1.14 (95%CI 1.10, 1.19) using CrAS.

CONCLUSION: Anticholinergic scales may be useful to inform falls prevention programs for new RACF residents.},
}

Humans
*Accidental Falls/statistics & numerical data/prevention & control
*Cholinergic Antagonists/adverse effects/therapeutic use
Female
Male
Aged
Retrospective Studies
Aged, 80 and over
*Homes for the Aged/statistics & numerical data
Australia
New South Wales

@article {pmid40864161,
year = {2025},
author = {Zhu, Y and Cho, K and Lacin, H and Zhu, Y and DiPaola, JT and Wilson, BA and Patti, G and Skeath, JB},
title = {Loss of dihydroceramide desaturase drives neurodegeneration by disrupting endoplasmic reticulum and lipid droplet homeostasis in glial cells.},
journal = {eLife},
volume = {13},
number = {},
pages = {},
pmid = {40864161},
issn = {2050-084X},
support = {NS036570/NS/NINDS NIH HHS/United States ; NS122903/NS/NINDS NIH HHS/United States ; ES2028365/ES/NIEHS NIH HHS/United States ; },
mesh = {Animals ; *Endoplasmic Reticulum/metabolism ; *Neuroglia/metabolism/pathology ; *Lipid Droplets/metabolism ; *Oxidoreductases/metabolism/genetics ; Homeostasis ; *Drosophila Proteins/metabolism/genetics ; Ceramides/metabolism ; *Drosophila melanogaster/genetics ; },
abstract = {Dihydroceramide desaturases convert dihydroceramides to ceramides, the precursors of all complex sphingolipids. Reduction of DEGS1 dihydroceramide desaturase function causes pediatric neurodegenerative disorder hypomyelinating leukodystrophy-18 (HLD-18). We discovered that infertile crescent (ifc), the Drosophila DEGS1 homolog, is expressed primarily in glial cells to promote CNS development by guarding against neurodegeneration. Loss of ifc causes massive dihydroceramide accumulation and severe morphological defects in cortex glia, including endoplasmic reticulum (ER) expansion, failure of neuronal ensheathment, and lipid droplet depletion. RNAi knockdown of the upstream ceramide synthase schlank in glia of ifc mutants rescues ER expansion, suggesting dihydroceramide accumulation in the ER drives this phenotype. RNAi knockdown of ifc in glia but not neurons drives neuronal cell death, suggesting that ifc function in glia promotes neuronal survival. Our work identifies glia as the primary site of disease progression in HLD-18 and may inform on juvenile forms of ALS, which also feature elevated dihydroceramide levels.},
}

Animals
*Endoplasmic Reticulum/metabolism
*Neuroglia/metabolism/pathology
*Lipid Droplets/metabolism
*Oxidoreductases/metabolism/genetics
Homeostasis
*Drosophila Proteins/metabolism/genetics
Ceramides/metabolism
*Drosophila melanogaster/genetics

@article {pmid40863128,
year = {2025},
author = {Pawłowska, M and Kruszka, J and Porzych, M and Garbarek, J and Nuszkiewicz, J},
title = {Ketogenic Metabolism in Neurodegenerative Diseases: Mechanisms of Action and Therapeutic Potential.},
journal = {Metabolites},
volume = {15},
number = {8},
pages = {},
pmid = {40863128},
issn = {2218-1989},
abstract = {Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss and share key pathological features such as oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation. Recent research has highlighted the potential of ketogenic metabolism, particularly the use of ketone bodies like β-hydroxybutyrate, as a therapeutic approach targeting these shared mechanisms. This review provides a comprehensive synthesis of current knowledge on the neuroprotective effects of ketogenic interventions, including both dietary strategies and exogenous ketone supplementation. We discuss how ketone bodies improve mitochondrial function, reduce reactive oxygen species, modulate inflammatory pathways, and influence neurotransmission and synaptic plasticity. Additionally, we examine experimental and clinical evidence supporting the application of ketogenic therapies in neurodegenerative diseases, highlighting disease-specific findings, benefits, and limitations. While preclinical data are robust and suggest meaningful therapeutic potential, clinical studies remain limited and heterogeneous, with challenges related to adherence, safety, and patient selection. The review also addresses the translational relevance of ketogenic strategies, considering their feasibility, combination with other therapies, and the need for personalized approaches based on genetic and metabolic profiles. By critically evaluating existing data, this article aims to clarify the mechanisms through which ketogenic metabolism may exert neuroprotective effects and to outline future directions for research and clinical application in the context of neurodegenerative disorders.},
}

@article {pmid40862353,
year = {2025},
author = {Harji, ZA and Rampal, CJ and Rodríguez, EC and Petel Légaré, V and Lissouba, A and Semmler, S and Liao, M and Ross, JP and Rouleau, GA and Vande Velde, C and Armstrong, GAB},
title = {TARDBP (TDP-43) Knock-in Zebrafish Display a Late-Onset Motor Phenotype and Loss of Large Spinal Cord Motor Neurons.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78012},
pmid = {40862353},
issn = {1531-8249},
support = {/CAPMC/CIHR/Canada ; //ALS Society of Canada/ ; //Weston Family Foundation/ ; //Fonds de Recherche du Québec/ ; },
abstract = {OBJECTIVE: Mutations in TARDBP (encoding TDP-43) are associated with the neurodegenerative disease amyotrophic lateral sclerosis (ALS) and include familial missense mutations where there are a lack of models and mechanisms examining how they are pathogenic.

METHODS: In this study, we developed 2 tardbp (Tdp-43) knock-in (KI) zebrafish mutant models encoding the analogous A382T and G348C variants and investigated their degenerative phenotypes.

RESULTS: We show that both models display reduced survival as well as an age-dependent motor phenotype that manifests at 1.5 years. Both variants in either the heterozygous or homozygous state did not impact protein expression levels of Tdp-43 in the central nervous system. However, homozygous G347C zebrafish displayed reduced expression levels of the tardbp transcript. We observed muscle cell atrophy starting at 1 year of age and loss of large spinal cord motor neurons in both KI models in older fish (2.35-3 years of age). We did not observe Tdp-43 aggregates. However, we did observe increased cytoplasmic Tdp-43 localization in spinal cord motor neurons in A379T zebrafish. At 1 year of age, whole spinal cord RNA-sequencing revealed an upregulation of neuroinflammatory transcripts in both models, as well as the selective downregulation of transcripts involved with synaptic function in G347C zebrafish, including syn2a, syn2b, syt2a, and stxbp1a.

INTERPRETATION: These novel models of common TDP-43 disease variants provide a unique opportunity to further our understanding of neurodegeneration in vivo and demonstrate that mutations in the same protein and domain can manifest with different phenotypes. ANN NEUROL 2025.},
}

@article {pmid40861195,
year = {2025},
author = {Chapman, LR and Shepheard, S and Verber, N and Turner, MR and Malaspina, A and Rogers, ML and Shaw, PJ},
title = {Urinary P75: a promising biomarker for amyotrophic lateral sclerosis.},
journal = {BMJ neurology open},
volume = {7},
number = {2},
pages = {e001088},
pmid = {40861195},
issn = {2632-6140},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease. The urinary neurotrophin receptor p75 extracellular domain (p75[ECD]) has previously been reported as a potential disease biomarker for diagnosis, severity assessment and monitoring therapeutic response.

METHODS: This study measured urinary p75[ECD] using an enzyme-linked immunoassay and normalised the results against urinary creatinine. Participants were recruited via A Multicentre Biomarker Resource Strategy in ALS (AMBroSIA) programme. Study participants included 97 ALS patients, 24 of whom were studied longitudinally, and 27 healthy controls. The study focused on urinary p75[ECD] and its potential association with different subtypes of ALS, change over time, disease progression, severity of symptoms and survival from symptom onset.

RESULTS: Confirming previous findings, urinary p75[ECD] levels were significantly higher in patients with ALS (median 6.78 ng/mg, 95% CI (5.12 to 9.23)) compared with controls (4.57 ng/mg, 95% CI (3.35 to 5.89)) at first study visit. There was a significant negative correlation between absolute change in the Revised ALS Functional Rating Scale score and p75[ECD] levels (Spearman's rho=-0.371, p≤0.0004, 95% CI (-0.543 to -0.169)), indicating that an increase in the severity of motor neuron injury correlated with an increase in p75[ECD] levels. There was a significant increase in p75[ECD] between first and second samples in the same participants, indicating an increase in the level of this biomarker longitudinally during the disease course (moderate effect size of -0.3).

CONCLUSIONS: Urinary p75[ECD] is a promising candidate as a biomarker, which increases with disease progression and has the potential to serve as a pharmacodynamic biomarker.},
}

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

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

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

@article {pmid40859014,
year = {2025},
author = {Zhang, MY and Ma, Y and Wang, LQ and Xia, W and Li, XN and Zhao, K and Chen, J and Li, D and Zou, L and Wang, Z and Liu, C and Liang, Y},
title = {Distinct amyloid fibril structures formed by ALS-causing SOD1 mutants G93A and D101N.},
journal = {EMBO reports},
volume = {},
number = {},
pages = {},
pmid = {40859014},
issn = {1469-3178},
support = {32271326//MOST | National Natural Science Foundation of China (NSFC)/ ; 32201040//MOST | National Natural Science Foundation of China (NSFC)/ ; 32071212//MOST | National Natural Science Foundation of China (NSFC)/ ; 22425704//MOST | National Natural Science Foundation of China (NSFC)/ ; 82188101//MOST | National Natural Science Foundation of China (NSFC)/ ; 12272276//MOST | National Natural Science Foundation of China (NSFC)/ ; 2024YFA1307301//MOST | National Key Research and Development Program of China (NKPs)/ ; 2023ZD0507202//National Science and Technology Major Project ()/ ; 2021TQ0252//China Postdoctoral Science Foundation (China Postdoctoral Foundation Project)/ ; 2021M700103//China Postdoctoral Science Foundation (China Postdoctoral Foundation Project)/ ; JCYJ20200109144418639//| Science and Technology Planning Project of Shenzen Municipality (Science and Technology Planning Project of Shenzhen of China)/ ; },
abstract = {Two hundred eight genetic mutations in SOD1 have been linked to amyotrophic lateral sclerosis (ALS). Of these, the G93A and D101N variants maintain much of their physiological function, closely resembling that of wild-type SOD1, and the SOD1-G93A transgenic mouse is the most extensively used mouse line in the study of ALS. In this study, we report two cryo-EM structures of amyloid fibrils formed by G93A and D101N mutants of SOD1 protein. These mutations give rise to amyloid fibrils with distinct structures compared to native SOD1 fibrils. The fibril core displays a serpentine configuration featuring four β-strands, held together by two hydrophobic cavities and a salt bridge between Arg143 and Asp96 in the G93A fibril, and by a hydrophobic cavity and a salt bridge between Arg143 and Asp132 in the D101N fibril, demonstrating unique structural features for each mutant. Moreover, our results show that G93A fibrils are significantly more toxic than those formed by D101N, which do not show a marked increase in toxicity compared to wild-type SOD1 fibrils. This study sheds light on the structural mechanisms through which SOD1 mutants aggregate and induce cytotoxicity in ALS.},
}

@article {pmid40858858,
year = {2025},
author = {Loo, YS and Yusoh, NA and Yap, K and Ng, CS},
title = {Programmable self-replicating JEV nanotherapeutics redefine RNA delivery in ALS.},
journal = {Communications biology},
volume = {8},
number = {1},
pages = {1282},
doi = {10.1038/s42003-025-08579-7},
pmid = {40858858},
issn = {2399-3642},
support = {PM010CNI000148//International Brain Research Organization (IBRO)/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration, leading to paralysis and respiratory failure. Current therapies offer limited benefits, highlighting the need for novel therapeutic strategies. Antisense oligonucleotides (ASO) and CRISPR/Cas9 gene editing hold promise, but their effective delivery to the central nervous system (CNS) remains a significant challenge. Here, a potential approach involves utilizing engineered Japanese encephalitis virus (JEV) as a self-replicating nanocarrier for targeted ASO delivery to motor neurons. By leveraging JEV's natural neurotropism and "Trojan horse" mechanism of immune cell-mediated CNS entry, this strategy overcomes the blood-brain and blood-spinal cord barriers (BBB/BSCB). Incorporation of ASO sequences within the JEV genome facilitates co-packaging and sustained therapeutic delivery, while microRNA (miRNA)-mediated attenuation may enhance safety and CNS specificity. This theoretical framework offers a potential paradigm shift in CNS gene therapy for ALS and other neurodegenerative diseases by enabling efficient, targeted, and sustained ASO delivery. However, experimental validation remains critical to assess its safety and therapeutic efficacy.},
}

@article {pmid40858618,
year = {2025},
author = {Lenoel, I and Ribon, M and Lorenc, F and Diebold, A and Philibert, CE and Robaldo, D and Badsi, M and Perronnet, J and Lameth, J and Berriat, F and Misawa, H and Coutelier, M and Cassel, R and Sarrazin, N and Jost-Mousseau, C and Bohl, D and Millecamps, S and Mallat, M and Brenner, D and Weishaupt, JH and Boillée, S and Lobsiger, CS},
title = {ALS/FTD-linked TBK1 deficiency in microglia induces an aged-like microglial signature and drives social recognition deficits in mice.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {7951},
pmid = {40858618},
issn = {2041-1723},
abstract = {TANK-Binding Kinase 1 (TBK1) is involved in autophagy and immune signaling. Dominant loss-of-function mutations in TBK1 have been linked to Amyotrophic Lateral Sclerosis (ALS), Fronto-temporal dementia (FTD), and ALS/FTD. However, pathogenic mechanisms remain unclear, particularly the cell-type specific disease contributions of TBK1 mutations. Here, we show that deleting Tbk1 from mouse motor neurons does not induce transcriptional stress, despite lifelong signs of autophagy deregulations. Conversely, Tbk1 deletion in microglia alters their homeostasis and reactive responses. In both spinal cord and brain, Tbk1 deletion leads to a pro-inflammatory, primed microglial signature with features of ageing and neurodegeneration. While it does not induce or modify ALS-like motor neuron damage, microglial Tbk1 deletion is sufficient to cause early FTD-like social recognition deficits. This phenotype is linked to focal microglial activation and T cell infiltration in the substantia nigra pars reticulata and pallidum. Our results reveal that part of TBK1-linked FTD disease originates from microglial dysfunction.},
}

@article {pmid40858507,
year = {2025},
author = {Barajas, CB and Young, MT and Bustamante, AV and Padilla-Frausto, I and Garcia, RE and Langellier, BA and Roby, DH and Stimpson, JP and Ponce, NA and Eberth, JM and Stehr, M and Ortega, AN},
title = {Organizational Perspectives on the Public Charge Rule and Health Care Access for Latino Immigrants in California.},
journal = {Health services research},
volume = {},
number = {},
pages = {e70032},
doi = {10.1111/1475-6773.70032},
pmid = {40858507},
issn = {1475-6773},
support = {R01MD014146/MD/NIMHD NIH HHS/United States ; R01MD018727/MD/NIMHD NIH HHS/United States ; },
abstract = {OBJECTIVE: To examine how mis- and disinformation about the Public Charge Ground of Inadmissibility final rule ("public charge rule") influences health care access for Latino immigrants in California as seen through the perspectives of leaders in health-serving organizations.

STUDY SETTING AND DESIGN: This qualitative study included semi-structured interviews with healthcare and community-based organizational leaders serving Latino immigrants in California. Viswanath et al.'s structural influence model of communication and equity guided the analyses and interpretation of the findings.

Between May 2024 and April 2025, primary data were collected from 31 organizations, resulting in 32 semi-structured interviews with 38 participants. Interviews were conducted via Zoom and transcribed verbatim. Researchers coded the data based on recurring themes using Dedoose software.

PRINCIPAL FINDINGS: Participants identified the public charge rule as a significant barrier to health care access for Latino immigrants. The policy has discouraged many Latinos from accessing public benefits, particularly the state's Medicaid and Supplemental Nutrition Assistance Program. In addition, immigrants' trusted sources of information (e.g., family, friends, and attorneys) were often misinformed about the policy, which amplified confusion and fear. Organizations respond by providing accurate information and connecting individuals with reliable resources to clarify that using public benefits would not necessarily result in being classified as a public charge. However, most efforts focused on education rather than directly countering mis- and disinformation.

CONCLUSIONS: Healthcare and community-based organizations offer unique perspectives as trusted intermediaries who help Latino immigrant families navigate health care and public benefits. Their close daily interactions reveal how misinformation about the public charge rule deters families from accessing essential services and makes it more challenging for organizations to fulfill their missions. These insights underscore the need for culturally responsive outreach and policy solutions that address information gaps and the climate of fear affecting community health.},
}

@article {pmid40858416,
year = {2025},
author = {Hao, R and He, C and Cheng, Y and Sang, S and Bai, Y},
title = {A plug-and-play data processing module for complex faults diagnosis.},
journal = {ISA transactions},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.isatra.2025.07.061},
pmid = {40858416},
issn = {1879-2022},
abstract = {Intelligent fault diagnosis technology is a vital approach to detect and sustain contemporary equipment. Although it is widely utilized for equipment monitoring, the limited number of samples available in the industry and complex faults restrict its further development. This paper presents a plug-and-play data processing module to expand the number of samples and improve the internal relationship between them to improve the overall performance of the deep learning model. an Amplitude-phase composite data enhancement (APCUP) method for expanding training samples is designed in the module, which uses Discrete Fourier Transform to randomly fuse multiple fault types in proportion to generate new fault samples, achieving the goal of expanding the training dataset. Based on the interdependence of faults in real scenes, the module also designs an adjacent label smoothing (ALS) strategy to process the original label data, which smoothen the label over, prevents the excessive absolute classification and improves the robustness of the model. The efficacy and viability of the module have been demonstrated through comprehensive experimentation on the cutting-edge industrial robot arm platform and two public datasets. The incorporation of a data processing module has markedly enhanced the model's capacity to diagnose intricate faults. As the module processes the input, there is a significant increase in accuracy and a reduction in errors.},
}

@article {pmid40858193,
year = {2025},
author = {Wu, Q and Liu, X and Zhang, T and Cui, S and Huang, B and Huang, C and Cao, Q and Xia, XG and Zhou, H},
title = {Astrocytes Expressing Mutant hnRNPA1 Induce Non-cell-autonomous Motor Neuron Death.},
journal = {Brain research bulletin},
volume = {},
number = {},
pages = {111522},
doi = {10.1016/j.brainresbull.2025.111522},
pmid = {40858193},
issn = {1873-2747},
abstract = {Pathogenic mutation of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is causative to amyotrophic lateral sclerosis (ALS). Neuron death resulting from pathogenic hnRNPA1 may not require its presence across all pertinent cells types, including neurons, glia, and muscles. Rather, the exclusive presence of pathogenic hnRNPA1 in a specific cell type, such as astrocytes, may suffice to substantially alter cellular functions. Consequently, this alteration initiates abnormal interaction within intricate neuron-glia networks, culminating in non-cell-autonomous motor neuron death. To investigate the pivotal role of non-cell-autonomous neuron death in hnRNPA1-associated ALS, we developed transgenic rats overexpressing mutant hnRNPA1 in specifically astrocytes. The confined overexpression of pathogenic hnRNPA1 in astrocytes instigated a sequence of events resulting in motor neuron death and subsequent muscle atrophy. These findings underscore the critical, non-cell-autonomous contribution of astrocytes to hnRNPA1-induced neurodegeneration in ALS, and point toward astrocytic pathways as potential therapeutic targets.},
}

@article {pmid40857498,
year = {2025},
author = {Zhao, B and Huggins, JE and Kang, J},
title = {Bayesian Inference on Brain-Computer Interfaces via GLASS.},
journal = {Journal of the American Statistical Association},
volume = {},
number = {},
pages = {},
doi = {10.1080/01621459.2025.2498088},
pmid = {40857498},
issn = {0162-1459},
abstract = {Brain-computer interfaces (BCIs), particularly the P300 BCI, facilitate direct communication between the brain and computers. The fundamental statistical problem in P300 BCIs lies in classifying target and non-target stimuli based on electroencephalogram (EEG) signals. However, the low signal-to-noise ratio (SNR) and complex spatial/temporal correlations of EEG signals present challenges in modeling and computation, especially for individuals with severe physical disabilities-BCI's primary users. To address these challenges, we introduce a novel Gaussian Latent channel model with Sparse time-varying effects (GLASS) under a Bayesian framework. GLASS is built upon a constrained multinomial logistic regression particularly designed for the imbalanced target and non-target stimuli. The novel latent channel decomposition efficiently alleviates strong spatial correlations between EEG channels, while the soft-thresholded Gaussian process (STGP) prior ensures sparse and smooth time-varying effects. We demonstrate GLASS substantially improves BCI's performance in participants with amyotrophic lateral sclerosis (ALS) and identifies important EEG channels (PO8, Oz, PO7, and Pz) in parietal and occipital regions that align with existing literature. For broader accessibility, we develop an efficient gradient-based variational inference (GBVI) algorithm for posterior computation and provide a user-friendly Python module available at https://github.com/BangyaoZhao/GLASS.},
}

@article {pmid40857153,
year = {2025},
author = {Szewczyk, B and Zimyanin, V and Japtok, J and Held, A and Pal, A and Großmann, D and Glaß, H and Jürs, AV and Dash, BP and Bak, M and Naumann, M and Hartmann, C and Kuksenko, O and Günther, R and Kao, TT and Sameith, K and Dahl, A and Sterneckert, J and Aronica, E and Shneider, NA and Büttner, A and Catanese, A and Phatnani, H and Kipp, M and Wainger, BJ and Goswami, A and Hermann, A},
title = {Activation of polo-like kinase 1 correlates with selective motor neuron vulnerability in familial ALS.},
journal = {Cell reports},
volume = {44},
number = {9},
pages = {116113},
doi = {10.1016/j.celrep.2025.116113},
pmid = {40857153},
issn = {2211-1247},
abstract = {Mutations in the Fused in Sarcoma (FUS) gene cause familial amyotrophic lateral sclerosis (ALS), characterized by selective degeneration of spinal motor neurons (sMNs) with relative sparing of cortical neurons (CNs). The mechanisms underlying this cell-type vulnerability remain unclear. Here, we compare CNs and sMNs derived from FUS-ALS models to assess differential responses to FUS mutations. We find that CNs are less affected than sMNs in DNA damage repair, axonal organelle trafficking, and stress granule dynamics. RNA sequencing (RNA-seq) reveals distinct transcriptomic signatures, with sMNs uniquely activating DNA damage responses involving cell cycle regulators, particularly polo-like kinase 1 (PLK1). PLK1 is highly expressed in sMNs but not CNs, correlating with greater nuclear FUS loss and splicing defects in sMNs. Cross-comparison with other familial ALS RNA-seq datasets highlights PLK1 upregulation as a shared molecular feature. These findings identify intrinsic differences between CNs and sMNs in FUS-ALS and suggest PLK1 as a potential driver of sMN vulnerability.},
}

@article {pmid40857025,
year = {2025},
author = {Ercan, V and Kuas, C and Cetin, M},
title = {Commentary on Sheppard et al.'s Study of First Trimester POCUS Behaviors.},
journal = {Academic emergency medicine : official journal of the Society for Academic Emergency Medicine},
volume = {},
number = {},
pages = {},
doi = {10.1111/acem.70130},
pmid = {40857025},
issn = {1553-2712},
}

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

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

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

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

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

@article {pmid40856961,
year = {2025},
author = {Solh Dost, L and Guignard, B and Gastaldi, G and Hasan Hamzo, A and Nendaz, M and Audétat, MC and Schneider, MP},
title = {Community pharmacists' practices and clinical reasoning towards hospital discharge prescription: a study using simulations and retrospective think-aloud methodology.},
journal = {International journal of clinical pharmacy},
volume = {},
number = {},
pages = {},
doi = {10.1007/s11096-025-01978-0},
pmid = {40856961},
issn = {2210-7711},
abstract = {BACKGROUND: The roles of community pharmacists have evolved from dispensing medications to clinical decision makers. This shift requires a clearer understanding of pharmacists' clinical reasoning. Managing hospital discharge prescriptions requires analytical reasoning to ensure patient safety through medication reconciliation and patient education.

AIM: This study assessed community pharmacists' practices and their clinical reasoning towards hospital discharge prescriptions.

METHOD: This mixed-method study consisted of two phases. First, community pharmacists participated in a simulated encounter in their pharmacy, where a patient presented a discharge prescription. Their practices and the structure of the encounter were assessed using a structured checklist of practices adapted from the MEDICODE checklist. Following the simulation, participants verbalised their thought processes in a retrospective think-aloud session. These semi-structured interviews were transcribed and analysed using both inductive and deductive qualitative methods. Charlin et al.'s model was used to assess clinical reasoning, while the Calgary-Cambridge model evaluated communication structure.

RESULTS: Among 14 participating pharmacists, 13 performed medication reconciliation, and 10 contacted the simulated prescriber to address discrepancies. While most provided adherence aids, only seven assessed non-adherence, and five actively collaborated with the patient. Pharmacists exhibited diverse interview structures, often revisiting previous discussion points. Clinical reasoning misconceptions, such as assumptions or premature closure, were observed at multiple stages of the clinical reasoning process.

CONCLUSION: Community pharmacists demonstrate strong medication-related skills but face challenges in clinical reasoning for discharge prescriptions. Clinical reasoning training, semi-structured consultations, and greater patient engagement would help tailor and improve post-discharge care.},
}

@article {pmid40856865,
year = {2025},
author = {Shandilya, C and Mani, S},
title = {Rho kinase isoforms in neurodegeneration: from cellular functions to therapeutic targets.},
journal = {Molecular biology reports},
volume = {52},
number = {1},
pages = {846},
pmid = {40856865},
issn = {1573-4978},
mesh = {Humans ; *rho-Associated Kinases/metabolism/antagonists & inhibitors/genetics ; *Neurodegenerative Diseases/metabolism/drug therapy ; Mitochondria/metabolism ; Animals ; Mitophagy ; Neurons/metabolism ; Protein Isoforms/metabolism ; Signal Transduction ; Reactive Oxygen Species/metabolism ; Mitochondrial Dynamics ; Isoenzymes/metabolism ; Oxidative Stress ; },
abstract = {Mitochondria serve as an important cellular organelle for maintaining neurotransmission and synaptic plasticity in neuronal cells by playing a key role in ATP generation, maintaining calcium homeostasis, and regulating the levels of reactive oxygen species (ROS), etc. The regulation of the dynamic nature of mitochondria, including their fission, fusion, and removal of damaged mitochondria by mitophagy, is also very important for neuronal health. Abnormalities in mitochondrial processes, including but not limited to fission, fusion, and mitophagy, are known to be associated with numerous neurodegenerative diseases (NDDs), such as Parkinson's disease (PD), Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). In the recent past, the Rho kinase (ROCK) isoforms, particularly ROCK1 and ROCK2, have gained a lot of attention in NDDs, mainly for their role in regulating the dynamics of the mitochondria, mitophagy, and other cell signalling pathways. By adding phosphate groups to Drp1, ROCK1 is crucial in supporting excessive mitochondrial fission, causing the death of neuronal cells. On the other hand, ROCK2 inhibits Parkin-dependent mitophagy by inhibiting the PTEN protein, the activator of Parkin-dependent mitophagy. This impaired mitochondrial quality control via reduced mitophagic flux leads to oxidative stress and neuronal degeneration, the central pathological feature of NDDs. The inhibition of ROCK isoforms has shown great promise in neuroprotective effects, controlling the dynamics of mitochondria in neuronal cells, lowering inflammation, and improving motor and cognitive functions in preclinical models of different NDDs, indicating ROCK isoforms as an attractive therapeutic target in different NDDs. This review aims to highlight the therapeutic significance of targeting ROCK isoforms in different NDDs.},
}

Humans
*rho-Associated Kinases/metabolism/antagonists & inhibitors/genetics
*Neurodegenerative Diseases/metabolism/drug therapy
Mitochondria/metabolism
Animals
Mitophagy
Neurons/metabolism
Protein Isoforms/metabolism
Signal Transduction
Reactive Oxygen Species/metabolism
Mitochondrial Dynamics
Isoenzymes/metabolism
Oxidative Stress

@article {pmid40856243,
year = {2025},
author = {Seven, YB and Seven, ES and Kirbas Cilingir, E and Parikh, K and Aydin, M and Luca, EK and Nair, J and Leblanc, RM},
title = {Rapid mapping of spinal and supraspinal connectome via self-targeting glucose-based carbon dots.},
journal = {Nanoscale},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5nr02670a},
pmid = {40856243},
issn = {2040-3372},
abstract = {The spinal cord is a highly dynamic network, playing significant roles in the vital functions of the brain. Disorders of the spinal cord, such as spinal cord injury and amyotrophic lateral sclerosis (ALS), are associated with neurodegeneration, often resulting in morbidity and mortality. The blood-brain barrier (BBB) poses a major challenge to imaging and therapeutic agents because less than 2% of small-molecule drugs and almost no large-molecule drugs can cross the BBB. Furthermore, spatial spectroscopy studies have shown highly heterogeneous BBB crossing with significant accumulation at the unintended brain regions. Thus, targeting systems that can cross the BBB at the spinal cord and precisely target specific cell types/populations are vitally needed. Carbon dots can be custom-designed to accumulate at the spinal cord; thus, they offer great potential as delivery platforms for imaging and therapeutic approaches. Since neurons are metabolically highly active and rely on glucose, we designed glucose-based carbon dots (GluCDs) with a diameter of ∼4 nm and glucose-like surface groups. We determined the CNS distribution of GluCDs on three scales: 1. brain regional distribution, 2. cellular tropism (e.g. neurons vs. glia), and 3. intracellular localization. We found that GluCDs (1) crossed the BBB at the spinal cord level, localized primarily to the spinal cord, and were quickly transported to higher centers in the brain, revealing supraspinal connectome within 4 hours after systemic delivery (minimally invasive and significantly faster than the available technologies); (2) almost exclusively localized to neurons without the need for a targeting ligand (neuronal self-targeting), and (3) were confined to late endosomal/lysosomal compartments in the neurons. Then, we verified our findings in a cervical spinal cord contusion injury model with GluCDs targeting the neurons at the injury epicenter. Therefore, GluCDs can be used as robust imaging agents to obtain rapid snapshots of the spinal/supraspinal network. GluCD nanoconjugates can open new avenues for targeted imaging of spinal cord injury. These findings can be extended to other spinal disorders such as ALS, spinal muscular atrophy, and spinal stroke.},
}

@article {pmid40856102,
year = {2025},
author = {Göksun, T and Aktan-Erciyes, A},
title = {Diversity as a Core Feature of Language Acquisition: A Commentary on Scaff et al. (2025).},
journal = {Developmental science},
volume = {28},
number = {5},
pages = {e70064},
doi = {10.1111/desc.70064},
pmid = {40856102},
issn = {1467-7687},
support = {//James S. McDonnell Foundation Human Cognition Scholar Award/ ; },
mesh = {Humans ; *Language Development ; *Multilingualism ; *Child Language ; Child ; Language ; },
abstract = {This commentary builds on Scaff et al.'s (2025) systematic review of the CHILDES database, highlighting persistent biases in child language corpora and research. We expand the discussion, emphasizing three key areas: (1) the need to diversify naturalistic data across languages to strengthen language acquisition theories; (2) the importance of including diverse child and parent demographics within specific language environments; and (3) the underrepresentation of bilingual samples from non-WEIRD, non-Indo-European contexts. We argue that these limitations not only hinder generalizability but also shape prevalent theoretical assumptions. Promoting inclusive, globally representative corpora is important for advancing a fair and accurate understanding of child language acquisition. SUMMARY: Diversification of naturalistic data across languages strengthens language acquisition theories. Child and parent characteristics within specific language environments should be included in child language research. Bilingual samples in CHILDES corpora should be evaluated on their generalizability.},
}

Humans
*Language Development
*Multilingualism
*Child Language
Child
Language

@article {pmid40856010,
year = {2025},
author = {Boyanova, S and Banks, G and Lipina, TV and Bains, RS and Forrest, H and Stewart, M and Carcolé, M and Milioto, C and Isaacs, AM and Wells, SE and Wiseman, FK},
title = {Multi-modal comparative phenotyping of knock-in mouse models of frontotemporal dementia/amyotrophic lateral sclerosis.},
journal = {Disease models & mechanisms},
volume = {18},
number = {8},
pages = {},
doi = {10.1242/dmm.052324},
pmid = {40856010},
issn = {1754-8411},
support = {UKDRI-1014//UK Dementia Research Institute/ ; UKDRI-CIP0202//UK Dementia Research Institute/ ; UKDRI-1203//UK Dementia Research Institute/ ; ARUK-SRF2018A-001//Alzheimer's Research UK/ ; Isaacs/Apr20/876-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; A410-53658/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/physiopathology/genetics/pathology ; *Frontotemporal Dementia/physiopathology/genetics/pathology ; Disease Models, Animal ; Phenotype ; *Gene Knock-In Techniques ; C9orf72 Protein ; Mice ; Behavior, Animal ; Aging/pathology ; DNA-Binding Proteins/genetics/metabolism ; Male ; Mice, Transgenic ; Memory, Short-Term ; Mice, Inbred C57BL ; Female ; },
abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive adult-onset neurodegenerative diseases with overlapping pathological and genetic origins. They are caused by multiple underlying mechanisms leading to a common collection of clinical features that occur in a spectrum. Here, we report side-by-side longitudinal behavioural, cognitive and sensory phenotyping of two mouse models of ALS/FTD, to determine which aspects of the disease they recapitulate. We used knock-in models, in which the endogenous mouse orthologues of the C9orf72 and TARDBP (encoding TDP-43) genes have been altered to model specific molecular aspects of ALS/FTD. We found that the C9orf72GR400/+ model exhibits age-related deficit in short-term memory and that parental genotype affects exploration activity in offspring. In the TardbpQ331K/Q331K model, we found age-related changes in weight, fat mass, locomotion and marble burying. In both models, we found no evidence of deficits in vision or olfactory habituation-dishabituation. These data provide new insight into genotype-phenotype relationships in these ALS/FTD mice, which can be used to inform model choice and experimental design in future research studies.},
}

Animals
*Amyotrophic Lateral Sclerosis/physiopathology/genetics/pathology
*Frontotemporal Dementia/physiopathology/genetics/pathology
Disease Models, Animal
Phenotype
*Gene Knock-In Techniques
C9orf72 Protein
Mice
Behavior, Animal
Aging/pathology
DNA-Binding Proteins/genetics/metabolism
Male
Mice, Transgenic
Memory, Short-Term
Mice, Inbred C57BL
Female

@article {pmid40855953,
year = {2025},
author = {Logroscino, G and Giannoni-Luza, S and Urso, D and Hamdi, N},
title = {Heterogeneity of frequencies of motor neuron disease across ethnicities and geographical areas: focus on Arabic countries in the Mediterranean area.},
journal = {Current opinion in neurology},
volume = {},
number = {},
pages = {},
doi = {10.1097/WCO.0000000000001415},
pmid = {40855953},
issn = {1473-6551},
abstract = {PURPOSE OF REVIEW: Although amyotrophic lateral sclerosis (ALS) epidemiology has been increasingly characterized in many regions, data from Arabic countries remain limited. This review aims to summarize the current knowledge on the burden of ALS in Arabic Mediterranean countries, with a particular focus on Egypt.

RECENT FINDINGS: ALS exhibits significant geographic and ethnic variability in terms of incidence, phenotype, and genetic background. Data from the Global Burden of Disease Study 2021 show that Egypt has one of the lowest age-standardized rates of ALS incidence, prevalence, and mortality in the Mediterranean basin. During the past three decades, Egypt has seen a notable decline in ALS-related Disability-Adjusted Life Years and deaths, in contrast to neighboring countries. A national registry has recently been initiated to enhance epidemiological surveillance in the country.

SUMMARY: ALS in Arabic Mediterranean countries presents a distinct epidemiological profile. These differences likely reflect a combination of genetic, demographic, and healthcare-related factors. Strengthening national registries and promoting regional collaborations will be crucial for gaining a deeper understanding of the determinants of ALS in these underrepresented populations.},
}

@article {pmid40855203,
year = {2025},
author = {Ferreira, J},
title = {Lymphatic system role in ALS.},
journal = {Lab animal},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41684-025-01610-8},
pmid = {40855203},
issn = {1548-4475},
}

@article {pmid40854500,
year = {2025},
author = {Sheu, KL and Chen, CC and Chen, SC},
title = {Comments on Fakult et al.'s "Epidemiology of Merkel Cell Carcinoma in the United States".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.06.080},
pmid = {40854500},
issn = {1097-6787},
}

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

@article {pmid40853517,
year = {2025},
author = {Kokotis, P and Bakola, E and Schmelz, M and Rentzos, M and Papagiannopoupou, G and Tsivgoulis, G},
title = {Motor neuron axonal excitability changes in the clinical course of amyotrophic lateral sclerosis.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {},
number = {},
pages = {},
pmid = {40853517},
issn = {1590-3478},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by slowly progressive degeneration of upper motor neurons (UMNs) and lower motor neurons (LMNs). Although the pathogenesis of sporadic form of ALS has not been fully elucidated, the initial damage mostly leads to hyperexcitability of the central and peripheral motor neuron. The results of our study aimed to confirm the changes in the excitability of the peripheral motor axon and contribute to the emergence of these measurements as potential biomarkers for disease progression. A total of 56 ALS patients [24 women (43%), median age 62.5 (interquartile range: 53.75-70.25) years] were finally included in the study. Twenty-four healthy controls that were age- and sex-matched to the cases [12 women (50%), mean age 58.46 ± 8.84] were recruited. The first main finding of our study is the fact that abnormalities of the voltage gated K[+] ion channels were constantly present in ALS patients than in the controls. The multivariate analysis revealed that Superexcitability 7ms lower than - 21.06%, related to shorter survival. Additionally using receiver operating characteristic (ROC) curves, the c-statistic showed Superexcitability 7ms moderate predictive ability. The clinical significance of our results is that Superexcitability 7ms can be used as a biomarker not only for survival but also for disease progression.},
}

@article {pmid40852304,
year = {2025},
author = {Yang, JE and Lee, JH and Boya, BR and Kim, YG and Byun, Y and Lee, J},
title = {Novel Pyrone-Based Biofilm Inhibitors against Azole-Resistant.},
journal = {ACS omega},
volume = {10},
number = {32},
pages = {36441-36454},
pmid = {40852304},
issn = {2470-1343},
abstract = {is an opportunistic fungus that is pathogenic in immunocompromised patients with life-threatening diseases such as HIV and cancer. is the most common fungal species isolated from biofilms formed on implanted medical devices or on human tissue. Biofilm development of is mainly driven by a transition from yeast to hyphal form involving core proteins such as HWP and ALS. We designed and synthesized novel α-pyrone-based analogues to investigate their potential in inhibiting biofilm formation and hyphal development of . Among the synthesized compounds, three compounds (6f, 6j, and 6n) significantly inhibited biofilm formation and reduced cell aggregation and hyphal formation in a dose-dependent manner. These compounds had minimal effects on planktonic cell growth while significantly reducing biofilm formation at 20-50 μg/mL, suggesting novel candidate compounds for managing drug-resistant strains of . The three compounds may represent promising therapeutic options with potential synergistic effects when combined with existing antifungal agents.},
}

@article {pmid40852180,
year = {2025},
author = {Corcia, P and Stenson, K and Doutriaux, A and Hadjrabia, H and Boer, F and Issa, S and Marguet, S and Bernard, F and Nasanbat, E and Nowacki, G and de Pouvourville, G and Couratier, P},
title = {Epidemiology, disease evolution and economic burden of amyotrophic lateral sclerosis in France using the French national health data system.},
journal = {Brain communications},
volume = {7},
number = {4},
pages = {fcaf292},
pmid = {40852180},
issn = {2632-1297},
abstract = {Amyotrophic lateral sclerosis is a rare neurodegenerative disease that requires multidisciplinary care, resulting in extensive healthcare resource utilization. No study has explored the prevalence of amyotrophic lateral sclerosis or characterized associated healthcare resource utilization in France, despite its high burden on people living with amyotrophic lateral sclerosis, caregivers and the healthcare system. Herein, we conducted a France-wide retrospective study to describe the epidemiology, disease course and economic burden of amyotrophic lateral sclerosis. People living with amyotrophic lateral sclerosis were identified from the French population from 2012 to 2019 using the French national health data system. A milestone and symptom-based staging algorithm was developed to categorize the incident cohort into early, mid and late stages. Data were extracted on epidemiology, demographic and clinical characteristics and clinical treatments. Healthcare resource utilization and costs were analysed for amyotrophic lateral sclerosis cases and matched non-amyotrophic lateral sclerosis controls and at disease stages. Events of interests were identified, and a competing risk analysis was conducted. Comparative statistics were performed using paired t-test, ANOVA and χ[2] test. We identified 18 289 incident amyotrophic lateral sclerosis cases, 56.1% of whom were male. The average age at diagnosis was 68.4 (± 12.5) years. In 2019, the estimated incidence and prevalence were 3.5/100 000 person-years and 11.0/100 000 persons, respectively. All-cause hospitalizations were higher among people at mid stage (1.66 person-years) and late stage (2.82 person-years) than among people at early stage (1.46 person-years) and for the amyotrophic lateral sclerosis cases (1.98 person-years) than for the matched non-amyotrophic lateral sclerosis controls (0.45 person-years). Home hospitalization and rehabilitation admission were more prevalent among people in later stages. The rate of out-patient and ambulatory consultations to all specialties was 13.8 person-years for people at early and mid stages and 11.1 person-years for people at late stage and 13.0 and 8.7 person-years for the amyotrophic lateral sclerosis cases and the matched non-amyotrophic lateral sclerosis controls, respectively. Direct costs increased as the disease progressed and were also higher for the amyotrophic lateral sclerosis cases than for the matched non-amyotrophic lateral sclerosis controls. Amyotrophic lateral sclerosis imposes a significant health burden through incremental healthcare resource utilization across all stages that increases with disease progression. Out-patient and ambulatory resource consumption decreased as the disease progressed to a more severe form, accompanied by a corresponding increase in in-patient services. These findings shed light on the complex needs of people living with amyotrophic lateral sclerosis and the continued need for more efficacious treatments.},
}

@article {pmid40851522,
year = {2025},
author = {Morgan, KH and Havranek, K and Horn, C and Lee, ML and Thomas, S},
title = {You look at life through a different lens: a phenomenological study of living with amyotrophic lateral sclerosis.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/17582024.2025.2546761},
pmid = {40851522},
issn = {1758-2032},
abstract = {AIMS: Amyotrophic lateral sclerosis (ALS) is a motor neuron disease that progresses without periods of remission; few live more than five years beyond diagnosis. In this study we investigated the lived experiences of people diagnosed with ALS in the United States, in South Central Appalachia.

PATIENTS & METHODS: We selected the philosophical and methodological approach of existential phenomenology of Merleau-Ponty to identify what was most important or figural to participants, within the contexts of Body, Other People, World, and Time.

RESULTS: Through phenomenological interviews with 10 people living with ALS, six themes and 17 subthemes were identified covering the process of diagnosis, loss and devastation, support from others, assistive devices, a new purpose, and a change in perspective.

CONCLUSIONS: These themes offer insight into life with an ALS diagnosis so that this unique patient population may be better understood from a physical, medical, emotional, and spiritual standpoint.},
}

@article {pmid40851455,
year = {2025},
author = {Ido, BJF and Dabilgou, AA and Doulgou, AS and Carama, EA and Ganame, MKL and Napon, C},
title = {Epidemiology, clinical features, and management of amyotrophic lateral sclerosis in the neurology department of the Bogodogo University Hospital in Ouagadougou, Burkina Faso.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/21678421.2025.2549323},
pmid = {40851455},
issn = {2167-9223},
abstract = {Objective: To describe the epidemiology, the clinical features, and the management of amyotrophic lateral sclerosis (ALS) in the neurology department of the Bogodogo University Hospital. Methods: This was a retrospective study including patients followed in the neurology department of the Bogodogo University Hospital between April 15, 2017 and December 31, 2024 for ALS. The socio-demographic, clinical and follow-up data of these patients were studied. Results: During our study period, 14 patients were followed for ALS, an average of 2 cases per year. The mean age of patients at symptom onset was 38.50 ± 14.23 years. The mean time to diagnosis was 19.71 ± 5.27 months. Four patients underwent no spinal cord magnetic resonance imaging (MRI). Riluzole was prescribed in 02 patients (14.29%). No patient benefited from noninvasive ventilation or gastrostomy. Six patients (42.85%) were discharged against medical advice. On December 31, 2024, there were 2 patients alive (14.29%), 5 patients who died (14.29%) and 7 patients (50%) who were lost to follow-up. Conclusion: Our cohort is characterized by a low hospital incidence, a young age of patients and difficulties in the care and follow-up of patients.},
}

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

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

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

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

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

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

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

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

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

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

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

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

@article {pmid40848497,
year = {2025},
author = {Jiang, W and Su, Y and Guo, M and Wang, X and Liu, H and Liu, X and Zhang, Y},
title = {Detection of aging-induced vascular remodeling based on Raman imaging and deep learning.},
journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy},
volume = {345},
number = {},
pages = {126832},
doi = {10.1016/j.saa.2025.126832},
pmid = {40848497},
issn = {1873-3557},
abstract = {Vascular aging-related remodeling is a common pathological basis for many chronic diseases, so early detection of physical arterial aging is important for their prevention and control. Existing staining methods can only analyze a limited number of tissue components at a time and often suffer from inaccuracies caused by over- or under-staining. In this study, we performed high-quality Raman imaging to simultaneously analyze five components in mouse aortic sections: elastic fibers, types I and III collagen fibers, nuclei, and cytoplasm of vascular smooth muscle cells (VSMCs), detailing their content and distribution changes. Despite subtle differences in Raman spectra, young and aged aortic tissues were successfully distinguished using multivariate curve resolution-alternating least squares (MCR-ALS) analysis and deep learning, achieving an AUC of 0.986 (95 % CI: 0.979-0.992). Additionally, Raman imaging and metabolomics revealed metabolic changes in arterial aging related to collagen synthesis and post-modifications, offering new potential therapeutic targets. Thus we show that Raman imaging combined with advanced algorithms is potentially useful in detecting vascular-aging remodeling, as well as monitoring the aging process.},
}

@article {pmid40848171,
year = {2025},
author = {Xu, H and Shao, Y and Zhang, J and Ni, Y and Xu, G and Liu, C and Liang, Y and Le, W},
title = {HSF-1 Regulates Autophagy to Govern Motor Function and Facilitate Toxic Protein Clearance in a C. elegans Model of Amyotrophic Lateral Sclerosis.},
journal = {Neuroscience bulletin},
volume = {},
number = {},
pages = {},
pmid = {40848171},
issn = {1995-8218},
abstract = {Heat shock factor-1 (HSF-1) plays a crucial role in orchestrating stress responses across diverse organisms and disease conditions. Here, we investigate how the HSF-1 signaling pathway influences the degradation of toxic proteins and neuropathological changes in the Caenorhabditis elegans model of amyotrophic lateral sclerosis (ALS). We found that overexpressing HSF-1 improves locomotor ability and increases the survival rate of ALS C. elegans. Moreover, we observed a deceleration of motor neuron degeneration, demonstrating the protective effect of HSF-1 on neurodegenerative processes. Transcriptomic analysis revealed notable changes in genes associated with autophagy and neurodegeneration, underscoring HSF-1's critical involvement in ALS pathology. In addition, metabolomic profiling further highlighted the involvement of this pathway in metabolic reprogramming. Overall, our study underscores the critical role of the HSF-1 signaling pathway in improving survival rate, movement velocity, cellular integrity, and metabolic adaptation, providing new insights into the mechanisms underlying ALS and potential targets for therapeutic intervention.},
}

@article {pmid40847753,
year = {2025},
author = {Yang, M and Wang, Q and Yan, R and Wang, X and Gu, J},
title = {Dimer-Specific FokT-seq Reveals DNA-Binding Dimerization and Novel Genomic Targets of TDP-43.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e08902},
doi = {10.1002/advs.202508902},
pmid = {40847753},
issn = {2198-3844},
support = {32171258//National Natural Science Foundation of China/ ; 82330041//National Natural Science Foundation of China/ ; 92049107//National Natural Science Foundation of China/ ; 2022-72-18//Department of Science and Technology of Hubei Province/ ; },
abstract = {In postmortem brain tissues of patients with sporadic amyotrophic lateral sclerosis (ALS), the dimerization ability of TAR DNA-binding protein 43 (TDP-43) is impaired, accompanied by an accumulation of insoluble TDP-43. Thus, the loss of TDP-43 dimerization may play a critical driving role in ALS pathogenesis, although its underlying mechanism remains unclear. In this study, the FokT (FokI-TDP-43) system is developed, which fuses TDP-43 protein with FokI nuclease. By restoring TDP-43 dimerization, this system reactivates FokI nuclease activity, enabling the cleavage of DNA targets bound by TDP-43. Additionally, the FokT-seq (FokT combined with genome-wide unbiased identification of DNA double-strand breaks enabled by sequencing, Guide-seq) method is established, allowing genome-wide detection of DNA sites bound by dimerized TDP-43. These findings reveal the essential role of TDP-43 dimerization in DNA binding, identify a series of related targets. Furthermore, this study offers a powerful tool for investigating dimerized transcription factors.},
}

@article {pmid40847737,
year = {2025},
author = {Novikov, V and Timothy, LTC and Fan, J and Sadek, K and Cowan, MF and Onuska, KM and Duennwald, M and Prado, VF and Prado, MAM},
title = {A Longitudinal Study of Sex Differences in a TDP-43 Mouse Model Reveals STI1 Regulation of TDP-43 Proteinopathy and Motor Deficits.},
journal = {Journal of neurochemistry},
volume = {169},
number = {8},
pages = {e70204},
doi = {10.1111/jnc.70204},
pmid = {40847737},
issn = {1471-4159},
support = {03592-2021 RGPIN//Natural Sciences and Engineering Research Council of Canada/ ; 06577-2018 RGPIN//Natural Sciences and Engineering Research Council of Canada/ ; //Canadian Institutes of Health Research CGS-D/ ; //ALS Society of Canada/ ; PJT 159781/CAPMC/CIHR/Canada ; PJT 162431/CAPMC/CIHR/Canada ; //Canadian Institutes of Health Research CGS-M/ ; },
mesh = {Animals ; Mice ; Male ; Female ; *DNA-Binding Proteins/genetics/metabolism ; *Sex Characteristics ; Mice, Transgenic ; *TDP-43 Proteinopathies/metabolism/genetics/pathology ; Disease Models, Animal ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Longitudinal Studies ; Humans ; *HSP90 Heat-Shock Proteins/metabolism/genetics ; Mice, Inbred C57BL ; Spinal Cord/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a disease influenced by a complex interplay of age, genetics, and sex. Most ALS cases are sporadic, and individuals with this disease show elevated levels of TDP-43 in their central nervous system and aggregated cytoplasmic inclusions containing TDP-43 in neurons. Misfolded and aggregated proteins like TDP-43 can be refolded or marked for degradation by molecular chaperones and their co-chaperone partners. In this study, we use a mouse model of ALS that mildly overexpresses human wild-type TDP-43 in neurons to explore how aging affects the onset of motor abnormalities and proteinopathy in male and female mice. We found that the age-dependent onset of motor symptoms is more pronounced in male mice, despite both sexes sharing similar TDP-43 pathology. Further, we found that reducing the activity of STI1, an Hsp90 co-chaperone, was associated with reduced mislocalized TDP-43 in the brain and spinal cord and partially rescued some motor deficits. By contrast, overexpressing STI1 seemed to be deleterious, exacerbating the levels of C-terminal TDP-43 fragments in the cytoplasm, worsening motor abnormalities and reducing lifespan. Our findings reveal that sex is a key biological factor in an ALS mouse model of TDP-43 overexpression and provide novel insights on the role of STI1 and proteostasis in mediating TDP-43 pathology.},
}

Animals
Mice
Male
Female
*DNA-Binding Proteins/genetics/metabolism
*Sex Characteristics
Mice, Transgenic
*TDP-43 Proteinopathies/metabolism/genetics/pathology
Disease Models, Animal
*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology
Longitudinal Studies
Humans
*HSP90 Heat-Shock Proteins/metabolism/genetics
Mice, Inbred C57BL
Spinal Cord/metabolism

@article {pmid40847590,
year = {2025},
author = {Spillinger, A and Ellefson, J and Yang, Q and Yin, LX and Stokken, JK and Pasic, T and Koszewski, IJ and Lin, SY},
title = {External Validation of a Multivariable Diagnostic Prediction Model for Acute Invasive Fungal Rhinosinusitis in Tertiary Care Settings.},
journal = {International forum of allergy & rhinology},
volume = {},
number = {},
pages = {},
doi = {10.1002/alr.70024},
pmid = {40847590},
issn = {2042-6984},
abstract = {BACKGROUND: Prompt detection and intervention are crucial for improving outcomes in acute invasive fungal rhinosinusitis (AIFS). Diagnostic prediction models assist in risk-stratification, but their accuracy requires testing through external validation. This study aims to validate a previously published diagnostic prediction model for AIFS in an independent cohort.

METHODS: A retrospective chart review was conducted at a tertiary care center (2008-2023) to identify patients with an otolaryngology consult for suspected AIFS. Of 65 patients identified, 11 (16.9%) were diagnosed with AIFS based on histopathology. Risk was calculated using Yin et al.'s predictive model. Predictive performance was assessed by calibration and discrimination.

RESULTS: Patients had significantly higher rates of diabetes (46.2% vs. 26.1%, p = 0.002), long-term steroid use (60% vs. 28.2%, p < 0.0001), and solid organ transplantation (38.5% vs. 8.5%, p < 0.001), compared with the development cohort, with conversely lower rates of hematologic malignancy (29.2% vs. 58.7, p < 0.001) and neutropenia (19.4% vs. 41%, p = 0.001). Despite these differences, both the three-variable (C-index: 0.844; 95% CI, 0.736-0.952) and four-variable models (C-index: 0.963; 95% CI, 0.919-1) showed adequate discrimination. Both models exhibited slight overprediction of risk, with a calibration-in-the-large predicted risk of 24.1% (95% CI, 13.68-34.46) for the three-variable model and 24.2% (95% CI, 13.76-34.57) for the four-variable model. Calibration plots confirmed overprediction.

CONCLUSION: The AIFS diagnostic model demonstrates acceptable discrimination and calibration on external validation, with generalizability to patients with different comorbidities. Larger studies are recommended to further test the model's predictive performance and clinical applicability.},
}

@article {pmid40846833,
year = {2025},
author = {Won, W and Lee, EH and Gotina, L and Chun, H and Lee, JH and Bhalla, M and Park, U and Kim, D and Kim, TY and Choi, JW and Kim, Y and Park, SJ and Lim, J and Park, JH and Kim, HJ and Heo, JY and Chung, W and Oh, MJ and An, HJ and Lee, J and Oh, SJ and Ryu, H and Pae, AN and Park, KD and Lee, CJ},
title = {Hemoglobin as a pseudoperoxidase and drug target for oxidative stress-related diseases.},
journal = {Signal transduction and targeted therapy},
volume = {10},
number = {1},
pages = {270},
pmid = {40846833},
issn = {2059-3635},
support = {IBS-R001-D2//Institute for Basic Science (IBS)/ ; },
mesh = {*Oxidative Stress/drug effects/genetics ; Humans ; Hydrogen Peroxide/metabolism ; Animals ; *Hemoglobins/metabolism/genetics ; *Alzheimer Disease/drug therapy/genetics/pathology/metabolism ; Astrocytes/metabolism/drug effects/pathology ; Mice ; *Parkinson Disease/drug therapy/genetics/pathology/metabolism ; Dopaminergic Neurons/metabolism/pathology/drug effects ; },
abstract = {Hemoglobin (Hb) is well known for transporting oxygen in the blood, but its role in the brain remains poorly understood. Here, we identified Hb in the cytosol, mitochondria, and nuclei of hippocampal and substantia nigra astrocytes and dopaminergic neurons. As a pseudoperoxidase, Hb decomposes hydrogen peroxide (H2O2) and mitigates H2O2-induced oxidative damage. However, in Alzheimer's disease, Parkinson's disease, and aging, excessive H2O2 diminishes astrocytic Hb, perpetuating a vicious cycle of oxidative stress and neurodegeneration. To counter the harmful effects of aberrant H2O2 production in diseases, we developed KDS12025, a BBB-permeable small molecule that enhances Hb pseudoperoxidase activity 100-fold, even at a low level of Hb. KDS12025 and its analogs achieve this enhancement through its electron-donating amine group, possibly stabilizing the complex between Hb, H2O2, and KDS12025. KDS12025 reduces astrocytic H2O2, alleviates astrogliosis, normalizes Hb, and reverts to a virtuous cycle of redox balance, preventing neurodegeneration without altering the oxygen-transport function of Hb. Gene silencing of Hb abrogates the impact of KDS12025 in both culture and animal models, confirming the necessity of Hb for the effects of KDS12025. KDS12025 extends survival and improves motor function even in severe amyotrophic lateral sclerosis and aging. Furthermore, the enrichment of astrocytic Hb in the nucleolus highlights a novel antioxidative mechanism potentially protecting against nuclear oxidative damage. Our findings suggest that Hb is a new therapeutic target for neurodegenerative diseases, with KDS12025 emerging as a first-in-class approach that enhances Hb pseudoperoxidase activity to reduce H2O2. Increasing Hb pseudoperoxidase activity with KDS12025 mitigates oxidative stress and alleviates neurodegeneration in AD, PD, and ALS patients and increases the degree of aging, with broad applicability for numerous oxidative-stress-driven diseases.},
}

*Oxidative Stress/drug effects/genetics
Humans
Hydrogen Peroxide/metabolism
Animals
*Hemoglobins/metabolism/genetics
*Alzheimer Disease/drug therapy/genetics/pathology/metabolism
Astrocytes/metabolism/drug effects/pathology
Mice
*Parkinson Disease/drug therapy/genetics/pathology/metabolism
Dopaminergic Neurons/metabolism/pathology/drug effects

@article {pmid40846160,
year = {2025},
author = {Chen, J and Liu, J},
title = {Navigating the paradoxes and potential of digital phenotyping for bipolar relapse prediction.},
journal = {Journal of affective disorders},
volume = {},
number = {},
pages = {120116},
doi = {10.1016/j.jad.2025.120116},
pmid = {40846160},
issn = {1573-2517},
abstract = {This commentary responds to the important study by Ludwig et al. on using smartphone data and critical slowing down (CSD) to predict bipolar disorder (BD) relapse. While commending the study's methodological rigor, we highlight a key paradoxical finding: a decrease in activity variance preceding manic episodes, which challenges the classic CSD model. We posit this may not be a failure of the theory but instead reveals a distinct pre-manic signature of behavioral 'rigidification' rather than instability. Furthermore, we discuss the ambiguity of the 'euthymic' baseline in a clinically complex, medicated population, suggesting that unmeasured pharmacological effects may confound the detected signals. The commentary argues that the limited individual-level predictive power underscores the need to shift from searching for universal nomothetic signals to developing personalized, idiographic (N-of-1) models. Ultimately, we conclude that Ludwig et al.'s work is pivotal in reframing the research agenda towards more nuanced, individualized, and clinically translatable digital phenotyping for BD.},
}

@article {pmid40845103,
year = {2025},
author = {Neeves, J and Petrić Howe, M and Ziff, OJ and Callaghan, B and Jutzi, D and Pal, K and Roumeliotis, TI and Choudhary, J and Isaacs, AM and Rigo, F and Bennett, CF and Ruepp, MD and Patani, R},
title = {An alternative cytoplasmic SFPQ isoform with reduced phase separation potential is up-regulated in ALS.},
journal = {Science advances},
volume = {11},
number = {34},
pages = {eadt4814},
doi = {10.1126/sciadv.adt4814},
pmid = {40845103},
issn = {2375-2548},
mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Humans ; *Cytoplasm/metabolism ; Protein Isoforms/genetics/metabolism ; *Alternative Splicing ; *PTB-Associated Splicing Factor/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Cell Nucleus/metabolism ; *Up-Regulation ; Animals ; Phase Separation ; },
abstract = {Splicing factor proline- and glutamine-rich (SFPQ) is an RNA binding protein that broadly regulates RNA metabolism. Although its nuclear roles are well studied, evidence of SFPQ's cytoplasmic functionality is emerging. Altered expression and nuclear-to-cytoplasmic redistribution of SFPQ have been recognized in amyotrophic lateral sclerosis (ALS) pathology, yet the mechanistic bases for these phenomena remain undetermined. We identified altered SFPQ splicing in ALS, increasing the expression of an alternative mRNA isoform lacking a nuclear localization sequence, which we termed "altSFPQ." We find that altSFPQ mRNA contributes to SFPQ autoregulation and is highly unstable yet exhibits context-specific translation with cytoplasm-predominant localization. Notably, reduced canonical SFPQ coincides with increased altSFPQ transcript expression in familial and sporadic ALS models, providing a mechanistic basis for SFPQ nuclear-to-cytoplasmic redistribution in patients with ALS. Last, we observe that the altSFPQ protein has reduced phase separation potential and differential protein binding compared to its canonical counterpart, providing insight into its mechanistic relevance to physiology and ALS pathogenesis.},
}

*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology
Humans
*Cytoplasm/metabolism
Protein Isoforms/genetics/metabolism
*Alternative Splicing
*PTB-Associated Splicing Factor/genetics/metabolism
RNA, Messenger/genetics/metabolism
Cell Nucleus/metabolism
*Up-Regulation
Animals
Phase Separation

@article {pmid40844868,
year = {2025},
author = {Ramgopal, S and Cash, R and Martin-Gill, C},
title = {Agency-Level Factors Associated with EMS Volume for High-impact Clinical Conditions and Patient Populations.},
journal = {Prehospital emergency care},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/10903127.2025.2550598},
pmid = {40844868},
issn = {1545-0066},
abstract = {BACKGROUND: Emergency medical services (EMS) agencies play a crucial role in delivering prehospital care, yet significant variability exists in EMS call volume and the conditions encountered. Variation in EMS call volume across agencies (i.e., high- vs. low-frequency) for specific patient populations and clinical presentations across EMS agencies can have substantial impact on implementation strategies for new guidelines and performance measures. We sought to evaluate agency-level factors associated with EMS volume of specific clinical presentations to inform the planning of targeted quality improvement efforts and resource allocation related to specific high-impact clinical categories.

METHODS: We conducted a retrospective analysis of the 2022 and 2023 National EMS Information System datasets, identifying EMS agencies that consistently reported patient encounters over a two-year period. We categorized encounters by key patient populations and clinical presentations, including cardiac arrest, trauma, stroke, pediatric cases, advanced airway management, and non-transport disposition. We used negative binomial regression to assess factors associated with EMS volumes.

RESULTS: We included 7,230 EMS agencies, with 55,705,469 encounters. The median number of encounters by EMS agency was 1,988 encounters averaged per year (IQR 706-5,584 encounters averaged per year). Cardiac arrest was more frequent in mixed/volunteer agencies and less common in for-profit, non-hospital, and tribal-based EMS services. Trauma volume was higher in advanced life support (ALS) and critical care agencies, the West (relative to Midwest), and mixed/volunteer agencies (relative to non-volunteer agencies). Stroke volume was linked to greater ALS/critical care agencies and mixed/volunteer agencies but was lower in urban areas. Pediatric encounters were more common in urban, mixed/volunteer agencies, and tribal services but less frequent in for-profit and hospital-based agencies. Airway interventions were associated with ALS/critical care agencies, but were less frequent in tribal agencies. Non-transport occurred more commonly in ALS agencies and tribal agencies.

CONCLUSIONS: Distinct patterns of agency-level characteristics appear to exist in relation to the volume of EMS responses for specific patient populations and clinical presentations. These findings can inform agency-specific strategic planning for guideline implementation, resource allocation, and quality improvement in prehospital care.},
}

@article {pmid40844737,
year = {2025},
author = {Manini, A and Brusati, A and Grassano, M and Scacciatella, G and Peverelli, S and Spagliardi, J and Pensato, V and Doretti, A and Vasta, R and Manera, U and Canosa, A and Brunetti, M and Gentilini, D and Messina, S and Verde, F and Moglia, C and Morelli, C and Dalla Bella, E and Keagle, PJ and Landers, JE and Gellera, C and Lauria Pinter, G and Chiò, A and Ratti, A and Calvo, A and Silani, V and Ticozzi, N},
title = {Whole genome sequencing analysis in primary lateral sclerosis (PLS) patients reveals mutations in neurological diseases-causing genes.},
journal = {Journal of neurology},
volume = {272},
number = {9},
pages = {587},
pmid = {40844737},
issn = {1432-1459},
support = {RF-2021-12374238//Ministero della Salute/ ; RF-2018-12367768//Ministero della Salute/ ; },
mesh = {Humans ; Male ; Female ; Middle Aged ; Aged ; *Motor Neuron Disease/genetics ; Adult ; *Mutation/genetics ; Whole Genome Sequencing ; },
abstract = {BACKGROUND: Primary Lateral Sclerosis (PLS) is a rare, adult-onset neurodegenerative disease that predominantly affects upper motor neurons. Despite being considered mostly sporadic, familial cases and rare genetic variants in genes associated with amyotrophic lateral sclerosis, hereditary spastic paraplegia and other neurological disorders have been reported in some PLS cases. Due to its rare prevalence among general population, large genetic studies of PLS are lacking.

METHODS: Fifty patients diagnosed with PLS based on consensus criteria were enrolled between 2013 and 2022 for comprehensive phenotypic and genotypic analysis using whole genome sequencing. We analyzed rare single nucleotide variants (SNVs), deemed pathogenic, likely pathogenic or of uncertain significance (VUS) based on the American College of Medical Genetics and Genomics criteria, and repeat expansions (REs) exceeding the pathogenic threshold, in 290 genes involved in neurological disorders.

RESULTS: We identified mutations in 7 patients (13.7%), specifically SNVs in CAPN1 (Spastic paraplegia 76), TBK1 (amyotrophic lateral sclerosis/frontotemporal dementia, ALS4/FTD), LITAF (Charcot-Marie-Tooth disease 1C), POLG (chronic progressive external ophthalmoplegia), APP (Alzheimer's disease) and OPTN (ALS12 ± FTD), and one RE in ATXN8OS (spinocerebellar ataxia 8). Additionally, two VUS were found in ANTXR2, a candidate gene for PLS recently identified via truncating variant collapsing analysis, but none of them was loss-of-function (one synonymous and one in-frame insertion).

CONCLUSIONS: Our study demonstrates a notable genetic intersection between PLS and various neurological disorders, including motor neuron diseases, neuropathies, mitochondrial disorders, ataxias, and dementias. These findings underscore the relevance of further investigation in larger cohorts to fully elucidate PLS genetic architecture and highlight the need to reconsider the role of genetic testing in its diagnostic criteria.},
}

Humans
Male
Female
Middle Aged
Aged
*Motor Neuron Disease/genetics
Adult
*Mutation/genetics
Whole Genome Sequencing

@article {pmid40843943,
year = {2025},
author = {Musson, LS and Baxter, SK and Norman, P and O'Brien, D and Elliott, M and Bianchi, S and Kaltsakas, G and Mcdermott, CJ and Hobson, EV and Stavroulakis, T},
title = {Perceptions of healthcare professionals on optimal delivery of noninvasive ventilation care to people living with motor neuron disease.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/21678421.2025.2539896},
pmid = {40843943},
issn = {2167-9223},
abstract = {Background: Patients with motor neuron disease (MND) often do not experience the full survival and quality of life benefits of noninvasive ventilation (NIV). Successful delivery of NIV is challenging to multiple healthcare professionals involved in the respiratory care patient journey and considering their perspectives is crucial in order to understand how to deliver optimal care. Objective: To identify the factors that influence NIV delivery in MND from a healthcare professional perspective and understand how obstacles can be overcome to optimize care. Methods: Qualitative focus group discussions with healthcare professionals delivering respiratory care and support to MND patients in the UK and charity representatives. Results: Thirty healthcare professionals and three charity representatives participated in five focus groups. A range of factors that influence the delivery of NIV across the entire respiratory care pathway were identified. These were grouped under four main themes: multidisciplinary working; NIV service structure; professional further education and training; and good use of NIV and effective ventilation. Conclusions: There is a need for specific resources to support service delivery; frequent, funded, and structured training to support healthcare professionals to deliver good care; as well as ways to encourage optimal staff practice so patients get the best care.},
}

@article {pmid40843685,
year = {2025},
author = {Epplen, ASC and Stahlke, S and Theiss, C and Matschke, V},
title = {Which One Would You Choose?-Investigation of Widely Used Housekeeping Genes and Proteins in the Spinal Cord of an Animal Model of Amyotrophic Lateral Sclerosis.},
journal = {NeuroSci},
volume = {6},
number = {3},
pages = {},
doi = {10.3390/neurosci6030069},
pmid = {40843685},
issn = {2673-4087},
abstract = {Amyotrophic lateral sclerosis (ALS) remains a progressive neurodegenerative disease, lacking effective causal therapies. The Wobbler mouse model harboring a spontaneous autosomal recessive mutation in the vacuolar protein sorting associated protein (Vps54), has emerged as a valuable model for investigating ALS pathophysiology and potential treatments. This model exhibits cellular and phenotypic parallels to human ALS, including protein aggregation, microglia and astrocyte activation, as well as characteristic disease progression at distinct stages. Exploring the underlying pathomechanisms and identifying therapeutic targets requires a comprehensive analysis of gene and protein expression. In this study, we examined the expression of three well-established housekeeping genes and proteins-calnexin, ß-actin, and ßIII-tubulin-in the cervical spinal cord of the Wobbler model. These candidates were selected based on their demonstrated stability across various systems like animal models or cell culture. Calnexin, an integral protein of the endoplasmic reticulum, ß-actin, a structural component of the cytoskeleton, and ß-tubulin III, a component of microtubules, were quantitatively assessed using quantitative reverse transcription-polymerase chain reaction (RT-PCR) for gene expression and Western blotting for protein expression. Our results revealed no significant differences in the expression of CANX, ACTB, and TUBB3 between spinal cords of wild-type and Wobbler mice at the symptomatic stage (p40) at both the gene and protein levels. These findings suggest that the pathophysiological alterations induced by the Wobbler mutation do not significantly affect the expression of these crucial housekeeping genes and proteins at p40. Overall, this study provides a basis for further investigations using the Wobbler mouse model, while highlighting the potential use of calnexin, ß-actin, and ßIII-tubulin as reliable reference genes and proteins in future research to aid in the discovery for effective therapeutic interventions.},
}

@article {pmid40843608,
year = {2025},
author = {Marshall, A and Goul, R and Dodson, B and Sakidja, R and Peelaers, H and Seacat, S and Bray, K and Ewing, D and Walsh, M and Wu, JZ},
title = {Probing the Effects of the First Atomic Layer on the Dynamic Behavior of Sub-2 nm MgO/Al2O3 Memristors.},
journal = {ACS applied materials & interfaces},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsami.5c04654},
pmid = {40843608},
issn = {1944-8252},
abstract = {As electronic devices continue to scale down from the current sub-5 nm range, atomic-scale control of defects becomes increasingly crucial to suppressing their impact on the physical properties of the devices. Memristors present an excellent example of a nonlinear and dynamic device with high speed and endurance required for electronic applications ranging from neuromorphic computing to nonvolatile memories. Herein we investigate the impact of atomic defects in sub-2 nm thick MgO/Al2O3 atomic layer stack (ALS) memristors that use an M1 (switching layer)/M2 (oxygen vacancy reservoir layer) bilayer structure grown using in vacuo atomic layer deposition (iALD). Intriguingly, we revealed a direct correlation of the atomic defects in the M2 layer with the memristor dynamic behavior using combined analysis of in situ scanning tunneling spectroscopy (iSTS) on the M2 layer and ex situ characterization on the memristors. Specifically, incomplete coverage of the first ALD atomic layer of M2 on the electrode yields defects at the M2/electrode interface. Despite the monotonic increase of ALD coverage, by almost 3-fold from ∼30% to >90%, at completion of the M2 layer of ∼0.7 nm in thickness, the impact of the defects on the M2/electrode interface has been found to be detrimental to both memristor switching speed and endurance. Guided by atomistic simulation, we addressed the issue of interface defects via tuning of the Al surface hydroxylation to increase the first atomic layer ALD coverage to ∼75%, leading to improved memristor switching speed and endurance by several orders of magnitude. These findings shed light on the correlation between the atomic defects and the dynamic behavior of sub-2 nm memristors and the importance of minimizing the atomic defects in memristors for future electronic applications.},
}

@article {pmid40842350,
year = {2025},
author = {Long, JW and Hankins, DL and Adams, MM},
title = {Indigenous Fire Stewardship to Revitalize Disrupted Ecosystems.},
journal = {Global change biology},
volume = {31},
number = {8},
pages = {e70411},
doi = {10.1111/gcb.70411},
pmid = {40842350},
issn = {1365-2486},
mesh = {*Conservation of Natural Resources/methods ; *Wildfires ; *Ecosystem ; *Fires ; Australia ; Biodiversity ; },
abstract = {This commentary highlights the significance of Bowd et al.'s (2025) study with Wiradjuri and Ngunnawal community members in quantifying the effects of Indigenous Fire Stewardship on plant biocultural diversity in southeastern Australia's box-gum grassy woodlands. Their work is a model for bridging ecological science and Indigenous stewardship in restoring fire-adapted ecosystems. Accelerating and scaling such efforts can counter the disruption of Indigenous practices, the spread of nonnative species, the intensification of wildfires, and other global changes.},
}

*Conservation of Natural Resources/methods
*Wildfires
*Ecosystem
*Fires
Australia
Biodiversity

@article {pmid40841847,
year = {2025},
author = {Du, C},
title = {Selection bias, overfitting, and generalisability in predicting postoperative complications: insights from Fang et al.'s work.},
journal = {Journal of robotic surgery},
volume = {19},
number = {1},
pages = {504},
pmid = {40841847},
issn = {1863-2491},
}

@article {pmid40841608,
year = {2025},
author = {Snow, M and Cameron, B and Pond, R and Trudell, R and Snyder, S and Torres-Hernandez, L and Deschamps, D and Tulimaiau, D and Hawkinson, K and Russell, M and Horan, D and Walters, J and Fox, JH and Arlian, B and Chariot, A and Nguyen, L and George, L},
title = {An Elongator mouse model of ALS spotlights TDP-43 in the motor neuron nucleolus.},
journal = {Communications biology},
volume = {8},
number = {1},
pages = {1259},
pmid = {40841608},
issn = {2399-3642},
support = {R15NS090384//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; P20GM103474//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; },
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *Motor Neurons/metabolism/pathology ; *Cell Nucleolus/metabolism ; *DNA-Binding Proteins/metabolism/genetics ; Disease Models, Animal ; Mice ; Mice, Knockout ; Humans ; Spinal Cord/metabolism/pathology ; },
abstract = {Dysfunction of Elongator is associated with amyotrophic lateral sclerosis (ALS). Here, we describe mouse models in which either Elongator subunit 1(Elp1) or subunit 3 (Elp3) is selectively ablated in alpha motor neurons of the spinal cord. These mice exhibit a progressive loss of motor strength and motor neuron degeneration. To interrogate the molecular mechanisms that contribute to motor neuron cell death in these mice, we examine multiple disease pathways, including the expression of TDP-43 whose cytoplasmic aggregation is associated with the human disease. Although TDP-43 is a well-characterized nuclear protein functioning in RNA metabolism and gene transcription, here we document TDP-43's robust presence in the nucleolus of wild-type motor neurons and its clearance from both the nucleus and the nucleolus of motor neurons in Elp conditional knockout mice. Thus, this study directly links dysfunction of Elongator with nucleolar disruption and TDP-43 clearing, two hallmark cellular pathologies of ALS.},
}

Animals
*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology
*Motor Neurons/metabolism/pathology
*Cell Nucleolus/metabolism
*DNA-Binding Proteins/metabolism/genetics
Disease Models, Animal
Mice
Mice, Knockout
Humans
Spinal Cord/metabolism/pathology

@article {pmid40841583,
year = {2025},
author = {Watanabe, K and Ema, T and Shimizu, K and Yamada, K and Nakashima, M and Saitsu, H},
title = {A Japanese familial spastic paraplegia associated with a missense UBQLN2 variant.},
journal = {Journal of human genetics},
volume = {},
number = {},
pages = {},
pmid = {40841583},
issn = {1435-232X},
support = {JP23K27566//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; JP25ek0109760//Japan Agency for Medical Research and Development (AMED)/ ; JP25ek0109674//Japan Agency for Medical Research and Development (AMED)/ ; JP25ek0109637//Japan Agency for Medical Research and Development (AMED)/ ; },
abstract = {UBQLN2 is located on Xp11.21 and encodes the ubiquilin 2 protein involved in protein homeostasis. Heterozygous or hemizygous missense variants in UBQLN2 cause amyotrophic lateral sclerosis (ALS). In addition, rare cases of primary lateral sclerosis (PLS) and spastic paraplegia (SPG) associated with UBQLN2 variants have also been reported. Here, we report four male patients in a family with SPG carrying a hemizygous missense UBQLN2 variant (NM_013444.4:c.1442G>T, p.(Gly481Val)). These patients showed childhood-onset lower limb spasticity, progressing to gait disturbance. The mean onset age (11 years) was earlier than that of previous ALS (49.6 years), SPG (29 years) and PLS (25.5 years) cases, and their progression was slower than in ALS or PLS. Literature review reveals Pro506 missense variants are associated with various motor neuron disease phenotypes, with some SPG patients progressing to ALS. Therefore, we consider that careful follow-up is warranted for UBQLN2-related SPG patients.},
}

@article {pmid40841001,
year = {2025},
author = {Zheng, X and Jia, G and Zhao, Y and Yan, T},
title = {Involvement of four alga toxins in the risks of human neurodegenerative diseases: Toxicogenomic data mining and bioinformatics analysis.},
journal = {Journal of environmental sciences (China)},
volume = {158},
number = {},
pages = {151-164},
doi = {10.1016/j.jes.2025.02.036},
pmid = {40841001},
issn = {1001-0742},
mesh = {Humans ; *Neurodegenerative Diseases/chemically induced/epidemiology ; Computational Biology ; *Marine Toxins/toxicity ; Toxicogenetics ; Data Mining ; Amino Acids, Diamino/toxicity ; Okadaic Acid/toxicity ; Oxocins/toxicity ; Cyanobacteria Toxins ; Microcystins ; },
abstract = {Alga toxins have recently emerged as an environmental risk factor, especially to neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. However, the association between the alga toxins β-N-methylamino-L-alanine (BMAA), brevetoxin B, cyanoginosin LR, okadaic acid and neurodegenerative diseases remains inadequately investigated. Therefore, the aim of this study was to elucidate the potential associations. Four sets of differentially expressed genes related with BMAA, brevetoxin B, cyanoginosin LR and okadaic acid in Homo sapiens and genes linked to neurodegenerative disease development were respectively collected from the Comparative Toxicogenomic Database. Metascape analysis and cluster community analysis of four alga toxins highlighted protein-protein interaction enrichment and hub genes, while biological processes analysis showed that the dominant pathways involved in harmful effects triggered by four alga toxins were the apoptotic signaling pathway, regulation of amyloid protein formation, inflammatory response and endoplasmic reticulum stress. Genes related to the interactions between four alga toxins and neurodegenerative diseases were selected and analyzed, revealing that the relevant pathways and genes were those involved in apoptotic mitochondrial changes and neuroinflammatory response pathways. The adverse outcome pathway frameworks were constructed according to the analysis results for toxins and associated neurodegenerative diseases. These discoveries provide a new perspective for us to gain a deeper understanding of the neurotoxic effects of four alga toxins.},
}

Humans
*Neurodegenerative Diseases/chemically induced/epidemiology
Computational Biology
*Marine Toxins/toxicity
Toxicogenetics
Data Mining
Amino Acids, Diamino/toxicity
Okadaic Acid/toxicity
Oxocins/toxicity
Cyanobacteria Toxins
Microcystins

@article {pmid40840854,
year = {2025},
author = {Fernàndez-Bernal, A and Mota, N and Pamplona, R and Area-Gómez, E and Portero-Otin, M},
title = {Mission cholesterol: Uncovering its hidden role in ALS neurodegeneration.},
journal = {Biochimica et biophysica acta. Molecular basis of disease},
volume = {},
number = {},
pages = {168021},
doi = {10.1016/j.bbadis.2025.168021},
pmid = {40840854},
issn = {1879-260X},
abstract = {Cholesterol is a central determinant of membrane architecture, signaling, and cellular homeostasis in the central nervous system (CNS). While historically viewed as a structural component, emerging evidence highlights its dynamic regulatory role in neuronal function, particularly through its compartmentalized synthesis, trafficking, and turnover. This review examines the complex landscape of cholesterol metabolism in the CNS, emphasizing the cooperative roles of astrocytes and neurons, the partitioning of biosynthetic pathways, and the barriers that distinguish brain cholesterol pools from peripheral sources. We focus on mitochondria-associated endoplasmic reticulum membranes (MAMs) as key regulatory platforms for cholesterol sensing, esterification, and signaling, underscoring their emerging role in neurodegenerative diseases. Disruptions in MAM integrity, lipid raft composition, and transcriptional regulation of cholesterol-handling genes have been linked to pathologies such as amyotrophic lateral sclerosis (ALS), particularly through the actions of TDP-43. By consolidating recent findings from lipidomics, cell biology, and disease models, we propose that cholesterol dyshomeostasis constitutes a shared mechanistic axis across diverse neurodegenerative conditions. Understanding this axis offers novel insights into the metabolic vulnerability of neurons and highlights cholesterol metabolism as a promising target for therapeutic intervention.},
}

@article {pmid40839404,
year = {2025},
author = {Li, Z and Jiang, J and Song, J and Bai, L and Pan, L},
title = {One Glutathione S-Transferase Gene, GSTU163, Was Involved in Mesosulfuron-methyl Resistance in Alopecurus japonicus.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c08615},
pmid = {40839404},
issn = {1520-5118},
abstract = {Alopecurus japonicus, an annual grass damaging wheat and canola fields in China, has evolved resistance to mesosulfuron-methyl, an acetolactate synthase (ALS)-inhibiting herbicide commonly used for its control. In this study, the resistant population (R) exhibited 22.93-fold resistance to mesosulfuron-methyl, and single-dose screening revealed cross-resistance to five other ALS-inhibiting herbicides. ALS gene sequencing revealed no known resistance mutations. Pretreatment with the glutathione S-transferase (GST) inhibitor 4-chloro-7-nitrobenzoxadiazole (NBD-Cl) increased the sensitivity of the R population to mesosulfuron-methyl. RNA-seq and quantitative real-time polymerase chain reaction (RT-qPCR) identified significant upregulation of one cytochrome P450 gene, two GST genes, and three glycosyltransferase genes, with AjGSTU163 showing the highest upregulation in the R population. Heterologous expression of AjGSTU163 in yeast significantly enhanced growth on mesosulfuron-methyl-containing media by mitigating ROS accumulation. Knockout of rice homologue OsGSTU163 slightly increased sensitivity to mesosulfuron-methyl in rice. This study first reported that GST contributes to mesosulfuron-methyl resistance in A. japonicus.},
}

@article {pmid40839108,
year = {2025},
author = {Mukherjea, N and Khandelwal, A and Saluja, R and Kalra, N},
title = {The Role of the human microbiome in neurodegenerative diseases: A Perspective.},
journal = {Current genetics},
volume = {71},
number = {1},
pages = {17},
pmid = {40839108},
issn = {1432-0983},
mesh = {Humans ; *Neurodegenerative Diseases/microbiology ; *Microbiota ; Parkinson Disease/microbiology ; *Gastrointestinal Microbiome ; Alzheimer Disease/microbiology ; Inflammasomes ; Inflammation/microbiology ; },
abstract = {Advances in diagnostics, therapeutics, and large-scale clinical studies have significantly expanded our understanding how human health is shaped by the microorganisms that colonize the body since birth. This article explores the rapidly evolving field of human microbiome research, focusing upon how microbial communities influence neurological health and contribute to the development of neurodegenerative diseases (NDs). Multiple factors, including age, lifestyle, and immunological memory, are recognized as major determinants of an individual's microbiome composition, which in turn can influence the onset and the progression of disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. These conditions have been linked to mechanisms including the aggregation of pathogenic proteins (e.g., amyloid-β and α-synuclein), inflammation driven by activation of the Toll-like receptor (TLR) signaling pathway, the NLRP3 inflammasome, as well as the modulatory effect of microbial metabolites such as short-chain fatty acids (SCFAs) and lipopolysaccharides (LPS). The article also highlights ongoing research and emerging strategies aimed at leveraging the human microbiome for better diagnosis, and management of NDs.},
}

Humans
*Neurodegenerative Diseases/microbiology
*Microbiota
Parkinson Disease/microbiology
*Gastrointestinal Microbiome
Alzheimer Disease/microbiology
Inflammasomes
Inflammation/microbiology

@article {pmid40838943,
year = {2025},
author = {Hiraoka, T and Tamura, M and Moriguchi, Y and Kuji, R and Mino, T and Akiba, M and Takahashi, Y and Yoshino, K and Suzaki, A and Sugimoto, K and Oshika, T},
title = {Choroidal Thickness Distribution and Its Association With Axial Length and Spherical Equivalent in Schoolchildren Assessed by Wide-Field Swept-Source Optical Coherence Tomography.},
journal = {Translational vision science & technology},
volume = {14},
number = {8},
pages = {33},
doi = {10.1167/tvst.14.8.33},
pmid = {40838943},
issn = {2164-2591},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Child ; *Choroid/diagnostic imaging/anatomy & histology ; Adolescent ; Female ; Male ; Prospective Studies ; *Axial Length, Eye/diagnostic imaging ; Myopia ; },
abstract = {PURPOSE: The purpose of this study was to evaluate the distribution of choroidal thickness (ChT) in schoolchildren using wide-field swept-source optical coherence tomography (SS-OCT) and to investigate its association with axial length (AL) and spherical equivalent (SE).

METHODS: This prospective study included 176 eyes from 88 healthy Japanese schoolchildren aged 6 to 15 years (mean age = 9.9 ± 2.4 years). Wide-field SS-OCT was used to measure ChT across a 57 degrees × 57 degrees fundus area. After excluding poor-quality images, 169 eyes were included in the final analysis. The ChT distribution was evaluated by dividing the obtained images into a 3 × 3 grid comprising 9 sections. ChT measurements were performed automatically with custom-designed software. ChT values were compared among the nine regions, and correlations with AL and SE were assessed for each grid section. Additionally, the findings in schoolchildren were compared with historical data from adults.

RESULTS: Mean ChT values across the 9 regions ranged from 172 ± 29 µm in the nasal-inferior region to 307 ± 39 µm in the temporal region. The choroid was thicker in the temporal and macular regions and thinner around the optic disc and inferior regions. Significant negative correlations were found between ChT and AL across all regions (R = -0.50 to -0.23, P < 0.05), indicating that longer ALs were associated with thinner choroids. Similarly, significant positive correlations were observed between ChT and SE (R = 0.19 to 0.55, P < 0.05), demonstrating that higher degrees of myopia were associated with thinner choroids. Moreover, ChT in schoolchildren was generally thicker compared to that in adults.

CONCLUSIONS: This study provides a detailed analysis of ChT distribution in schoolchildren, revealing regional variability and a generally thicker choroid compared with adults. The significant correlations between ChT, AL, and SE across all regions suggest a potential role for ChT in ocular growth and myopia progression. These findings underscore the need for longitudinal studies to investigate causal relationships between ChT distribution and myopia development.

TRANSLATIONAL RELEVANCE: Wide-field choroidal mapping identifies early structural biomarkers for pediatric myopia progression and control.},
}

Humans
*Tomography, Optical Coherence/methods
Child
*Choroid/diagnostic imaging/anatomy & histology
Adolescent
Female
Male
Prospective Studies
*Axial Length, Eye/diagnostic imaging
Myopia

@article {pmid40838713,
year = {2025},
author = {Noor, SM and Reddy, DH and Srikanth, Y and Viswanadh, MK and Dumala, N and Chakravarthy, G and Nalluri, BN and Naryanarao, A and Duguluri, S and Yadagiri, G and Prasanna, VS and Sundaram, S and Gujjari, L and Ramakrishna, K},
title = {Morin hydrate: a comprehensive review on therapeutic potential in treating neurological diseases.},
journal = {Nutritional neuroscience},
volume = {},
number = {},
pages = {1-25},
doi = {10.1080/1028415X.2025.2544605},
pmid = {40838713},
issn = {1476-8305},
abstract = {Background: Morin hydrate is a polyphenolic flavonoid present in various vegetables, fruits, nuts, and sea products. It has been reported to offer multiple protective effects against a range of diseases, including cancer, cardiovascular, liver, neurological, metabolic, and renal disorders.Objective: This review highlights the molecular mechanisms and therapeutic potential of Morin in neurological diseases, including Parkinson's disease, Alzheimer's disease, traumatic brain injury, neuropathic pain, stroke, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, depression, anxiety, sleep, encephalopathy, schizophrenia, and psychosis, etc.Methods: The research and review articles were collected from the Pubmed, Scopus, Web of Science, and Google Scholar databases using 'Morin' and the above-mentioned neurological diseases as keywords.Results: The neuroprotective effects of Morin are primarily attributed to its ability to mitigate oxidative stress, inflammation, excitotoxicity, calcium dysregulation, mitochondrial dysfunction, neurotransmitter alterations, protein modifications, and enzymatic inhibition.Conclusion: Despite its promising pharmacological profile, the clinical adaptation of Morin for combating neurological diseases requires further validation through comprehensive preclinical and clinical investigations.},
}

@article {pmid40838580,
year = {2025},
author = {Tse, NY and Caga, J and Ahmed, RM and Mazumder, S and Nguyen, C and Huynh, W and Karjalainen, A and Timmins, HC and Ramsey, E and Talbot, DL and Halliday, GM and Kiernan, MC and Devenney, EM},
title = {Behavioral subtypes impact prognosis and survival in amyotrophic lateral sclerosis: a clustering-based approach.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/21678421.2025.2522402},
pmid = {40838580},
issn = {2167-9223},
abstract = {BACKGROUND: Behavioral impairments are well established in amyotrophic lateral sclerosis (ALS). A refined understanding of the contribution of delineated patterns of behavioral impairments to prognosis is vitally important.

METHODS: Leveraging data-driven two-step cluster analysis, we first stratified a large cross-sectional cohort of 170 ALS patients into distinct phenotypic subtypes based on their baseline behavioral profiles, as determined by the well-validated and informant-rated Motor Neuron Disease Behavioral Instrument (MiND-B). Mixed-effects model and multivariate Cox regression analyses were performed to compare rate of functional decline as measured by the revised ALS functional rating scale (ALSFRS-R) over follow-up assessments in 121 participants, as well as survival duration (n = 130), between the behavioral subtypes. Results: Clustering analysis yielded three behavioral phenotypes characterized by 1) intact behavioral functioning (n = 125), 2) apathy alone (n = 20), and 3) concurrent disinhibition and stereotypical behavior (n = 25). Apathy was associated with both significantly shorter survival (p = .003) and most rapid functional decline across follow-up assessments (both p <.001). Importantly, this pervasive effect was not observed in other behavioral cluster groups.

CONCLUSIONS: Extending previous cross-sectional work, current findings offer delineation of the trajectory of clinical outcomes associated with classic behavioral phenotypes of ALS. Converging with past evidence of unique disease and progression profile in ALS patients with apathy, our work provides strong support for behavioral change and in particular apathy as a reliable indicator of poor prognosis across cross-sectional and longitudinal markers of clinical outcomes.},
}

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

@article {pmid40837837,
year = {2025},
author = {Zhao, S and Chen, R and An, Y and Zhang, Y and Ma, C and Gao, Y and Lu, Y and Yang, F and Bai, X and Zhang, J},
title = {Correction: Optineurin overexpression ameliorates neurodegeneration through regulating neuroinflammation and mitochondrial quality in a murine model of amyotrophic lateral sclerosis.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1670545},
doi = {10.3389/fnagi.2025.1670545},
pmid = {40837837},
issn = {1663-4365},
abstract = {[This corrects the article DOI: 10.3389/fnagi.2025.1522073.].},
}