@article {pmid41160352,
year = {2026},
author = {Bae, K and Park, Y and Ryu, H and Lee, J and Park, SW},
title = {A Longitudinal Study of the Relationship between Identity Development Processes and Self-Esteem among Korean College Freshmen.},
journal = {Journal of youth and adolescence},
volume = {55},
number = {3},
pages = {780-794},
pmid = {41160352},
issn = {1573-6601},
support = {NRF-2023S1A5A2A01078792//the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea/ ; },
abstract = {Self-esteem may serve both as a psychological resource that facilitates personal identity development processes and as an outcome of a consolidated identity. However, longitudinal evidence remains limited. This study tracked 641 South Korean first-year college students (48.0% women; Mage = 19.13) across four waves spaced three months apart during their first academic year to test bidirectional links between Luyckx et al.’s (2008) five dimensions of personal identity processes (exploration in breadth, exploration in depth, commitment making, identification with commitment, ruminative exploration) and self-esteem. Random-intercept cross-lagged panel models were used to examine how changes in each of the processes may follow and be followed by changes in self-esteem. Results highlight initial volatility and gradually increasing engagement in personal identity development processes. Higher self-esteem predicted greater engagement in identity processes, and a stronger sense of identification with commitment predicted higher self-esteem later in the year but not earlier. By demonstrating that self-esteem is not merely an outcome of identity development but also a psychological resource facilitating identity development, these findings contribute to the literature on the development of the self-system in youth.},
}

@article {pmid41267135,
year = {2025},
author = {Zreik, M and Redding, A and Santarossa, S},
title = {From engagement to evidence: a scoping review of qualitative and quantitative measures of adult patient engagement in research.},
journal = {Research involvement and engagement},
volume = {11},
number = {1},
pages = {136},
pmid = {41267135},
issn = {2056-7529},
support = {SOE-2022C2-28911/PCORI/Patient-Centered Outcomes Research Institute/United States ; },
abstract = {BACKGROUND: Patient engagement in research has been found to improve the quality and relevance of research findings. Quantifying levels of patient engagement may be beneficial in measuring engagement quality, yet tools for this purpose remain scarce. A scoping review was conducted to summarize and analyze existing tools used to measure patient engagement in research for the purpose of assessing the content validity of Hamilton et al.’s Patient Engagement In Research Scale (PEIRS). METHODS: The electronic database Ovid MEDLINE was used to conduct a search related to keywords and controlled vocabulary from 2017 - November 10, 2023, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews checklist. Articles were included if they quantitatively or qualitatively measured any outcome of patient engagement in research, exclusively with patients as participants. Data extraction, completed in Microsoft Excel, included the name of the research engagement tool, the type of tool (i.e., questionnaire, survey, or scale), sample size, source, and characteristics, and time frame of data collection. RESULTS: Five articles were ultimately included in this scoping review after an initial search returned 1719 citations. The most common reason for exclusion during the full text review stage was that articles were review articles. Of selected articles that included demographic data, the majority of participants were women and White. Articles highlighted areas for improvement in existing tools, including the need for patient collaboration at each stage of the research process and stronger communication between researchers and patient partners. CONCLUSIONS: Efforts to effectively measure patient engagement in research remain scant. Included studies were limited by inconsistency in defining “patient engagement” and a lack of demographic data collection.},
}

@article {pmid41372737,
year = {2025},
author = {Shah, A and Doshi, G},
title = {Stress and neurodegeneration: mechanistic insights and therapeutic opportunities for preserving brain resilience.},
journal = {Acta neurologica Belgica},
volume = {},
number = {},
pages = {},
pmid = {41372737},
issn = {2240-2993},
abstract = {Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and Amyotrophic Lateral Sclerosis are strongly influenced by persistent stress, which accelerates both their onset and progression. This review explores the intricate interplay between chronic stressors, oxidative and metabolic imbalances, protein misfolding, inflammatory responses, and psychosocial adversity, and their cumulative impact on the aging brain’s capacity for homeostasis. The loss of cellular resilience due to prolonged stress leads to maladaptive outcomes, including mitochondrial dysfunction, sustained neuroinflammation, breakdown in proteostasis, and disruption of hypothalamic-pituitary-adrenal axis signaling, all of which amplify neuronal vulnerability. The detailed molecular pathways that underlie these phenomena, the article identifies key mediators such as Reactive Oxygen species, mitochondrial regulators, heat shock proteins, and proinflammatory cytokines that drive neurodegeneration. A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar up to 2025. Eligible publications included original research articles, clinical studies, and systematic reviews focusing on stress-related molecular pathways, oxidative metabolism, proteostasis, neuroinflammation, and therapeutic interventions in aging and neurodegenerative diseases. A qualitative synthesis of these studies was performed to identify key mechanisms, biomarkers, and emerging treatment strategies relevant to stress-induced neurodegeneration. Further, the review evaluates both established and emerging interventions aimed at mitigating these stress-driven processes. Lifestyle modifications such as aerobic exercise, calorie restriction, and cognitive behavioural therapies complement pharmacological agents like antioxidants, chaperone modulators, and anti-inflammatory drugs to enhance brain resilience and delay disease onset. Recent advances in the field, including integrated multi-omics profiling, biomarker discovery, and medicine approaches, promise to refine our ability to satisfy patients and deliver targeted therapies based on individual stress profiles. Additionally, the article discusses the neuroimmune-gut axis and the potential for interventions targeting microbiome-related inflammation. Early detection of stress-related biomarkers and personalized strategies holds considerable promise for improving clinical outcomes, enabling earlier diagnosis, and fostering tailored therapies that preserve cognitive function and independence in aging populations.},
}

@article {pmid41511493,
year = {2026},
author = {Yu, J and Zhang, J and Jiang, Y and Ma, C and Wang, W and Zhang, K and Tian, R and Chen, H and Han, H and Sun, H and Peng, C and Zhang, H and Xu, X},
title = {Identification of a novel nonsense variant in ARR3 in a family with early-onset high myopia.},
journal = {Genes & genomics},
volume = {48},
number = {3},
pages = {409-418},
pmid = {41511493},
issn = {2092-9293},
support = {81873677//Natural Science Foundation of China/ ; },
abstract = {BACKGROUNDS: Early-onset high myopia (EoHM) is a severe refractive error that can result in significant vision loss. A known genetic cause involves mutations in the X-linked Arrestin-3 (ARR3) gene, which typically presents with a female-limited inheritance pattern, in which asymptomatic fathers transmit the variant to their affected daughters. OBJECTIVE: This study aims to present a unique case of EoHM characterized by paternal transmission of a novel ARR3 variant and to explore potential underlying molecular mechanisms through an exploratory bioinformatic analysis. METHODS: We collected the clinical phenotypes for the family and sequenced the blood using NGS and Sanger sequencing. Bioinformatic analysis of the GSE5338 dataset revealed a potential interaction network involving ARR3, NR2E3 (a photoreceptor development regulator), and OPN1MW (a cone opsin gene). RESULTS: The proband exhibited severe EoHM with stretched axial lengths (ALs) (24.09 and 24.43 mm) and pronounced myopic astigmatism. The asymptomatic father passed on a new nonsense variation in the ARR3 gene, c.7A > T (p.K3Ter). Exploratory bioinformatic analysis of a murine retinal dataset hinted at a possible regulatory relationship, wherein overexpression of the photoreceptor transcription factor Nr2e3 might be linked to the downregulation of Arr3 and the cone opsin gene Opn1mw. CONCLUSIONS: This study reports a novel ARR3 mutation within a family affected by EoHM, expanding the known mutational spectrum of this disease and offering vital insights for genetic counseling. Furthermore, our bioinformatic analysis has generated a hypothesis that NR2E3-mediated downregulation of both ARR3 and OPN1MW may contribute to the disease phenotype, a link that warrants future investigation in human models.},
}

@article {pmid41530568,
year = {2026},
author = {Qingqing, Z and Ruiyi, L and Zaijun, L},
title = {Graphene-oxide dual-stabilized Mg0.3AlVCuZn lightweight high-entropy alloy nanoparticles with ultrahigh catalytic activity, selectivity and stability for electrochemical detection of doxorubicin in human urine.},
journal = {Mikrochimica acta},
volume = {193},
number = {2},
pages = {90},
pmid = {41530568},
issn = {1436-5073},
support = {2021YFA0910200//National Key Research and Development Program of China,China/ ; 2021YFA0910200//National Key Research and Development Program of China,China/ ; },
abstract = {The practical applications of lightweight high-entropy alloys (HEAs) in catalysis and electrochemical sensors are hindered by inadequate chemical stability and catalytic activity. This study presents one groundbreaking synthesis strategy for fabricating Mg0.3AlVCuZn HEA nanoparticles by integrating histidine/serine-functionalized boron-doped graphene quantum dot (HSB-GQD). Mg2+, Al3+, V5+, Cu2+ and Zn2+ are coordinated with HSB-GQD to Me-HSB-GQD complex,followed by thermal annealing and controlled oxidative post-treatment. The resulting Mg0.3AlVCuZn shows single-phase octahedral morphology with a small size of about 50 nm and dual graphene-oxide shielding. Unique structure fully exposes active sites and enhances structural and chemical stability across acidic/alkaline media, interface electron transfer, and improves the affinity with polar electrolyte. The s-p-d orbital hybridization among Mg/Al (s, p) and V/Cu/Zn (s, d) induces electron redistribution to optimize adsorption energetics and catalytic specificity. Mg0.3AlVCuZn shows ultrahigh catalytic activity that is more than 2-fold that of Au nanoparticles. The electrochemical sensor with Mg0.3AlVCuZn exhibits a broad linear range (0.01–100 µM), ultra-low detection limit (0.0057 µM, S/N = 3), and robust selectivity and long-term stability for electrochemical detection of doxorubicin in human urine. This study also offers a generalizable platform for engineering lightweight HEAs with tailored stability and multifunctional efficacy, bridging advances in catalysis, sensing and energy storage.},
}

@article {pmid41697604,
year = {2026},
author = {Tutan, MB and Tutan, D},
title = {A bibliometric analysis of diverticulitis: global trends and future directions.},
journal = {Updates in surgery},
volume = {},
number = {},
pages = {},
pmid = {41697604},
issn = {2038-3312},
abstract = {Diverticulitis, an inflammation of colonic diverticula, poses significant clinical challenges due to its rising global incidence and potential complications. Modern dietary habits, sedentary lifestyles, and aging populations contribute to its increasing prevalence, with a notable rise among younger adults. Despite extensive research, a comprehensive assessment of global research trends remains limited. This study conducts a bibliometric and statistical analysis of diverticulitis research (1980–2024) to identify key trends, influential studies, international collaborations, and the correlation between national GDP and research output while projecting future publication trends. A bibliometric analysis of the Web of Science database identified 4459 publications, with 3653 articles, reviews, and meeting abstracts included. The United States led global research contributions (34.22%), followed by Italy and Germany. A strong positive correlation was found between national GDP and research productivity (r = 0.900, P < 0.001). Future projections estimate 289 publications in 2025. The most cited study was Rafferty et al.‘s 2006 “Practice parameters for sigmoid diverticulitis.” Citation analysis revealed growing academic interest, particularly in the past two decades. Diverticulitis has become a global health concern, driven by lifestyle changes and aging demographics, with an increasing incidence among younger populations. This study highlights a marked rise in research activity, predominantly in economically developed nations, and underscores the need for further investigation into prevention, diagnosis, and management strategies. These findings offer valuable insights for clinicians and researchers, guiding future research directions in diverticulitis.},
}

@article {pmid41840453,
year = {2026},
author = {Morgan, TL and Carroll, K and Waqar, A and Hudek, N and Mosa, M and Richards, DP and Meeking, K and Granieri, M and Smith, M and Walz, M and Etherington, C and Marlin, S and Gillies, K and Presseau, J and Brehaut, JC},
title = {A meta-review of patient engagement, shared decision-making, and factors influencing equity-deserving populations' participation in clinical trials.},
journal = {Research involvement and engagement},
volume = {12},
number = {1},
pages = {},
pmid = {41840453},
issn = {2056-7529},
support = {PJT-169055/CAPMC/CIHR/Canada ; PJT-169055/CAPMC/CIHR/Canada ; },
abstract = {BACKGROUND: Many equity-deserving populations, including those facing structural health inequities, lack support to participate in clinical trials while facing barriers to participation. Two approaches—patient engagement (PE) and shared decision-making (SDM)—can help trialists better understand and address such barriers. PE can improve the relevance of trials to silenced communities while SDM can align participation decisions among socially disadvantaged groups with their values, needs, and preferences, which may help overcome health inequities. Further, Indigenous community engagement is vital to address the effects of colonialism and promote Indigenous self-determination and health equity. The extent to which existing reviews have identified common barriers, enablers, and strategies across equity-deserving groups and discussed PE and SDM concepts is unclear. PURPOSE: (1) To describe which equity-deserving populations have been the focus of reviews on clinical trial participation and which barriers, enablers, and strategies are relevant to them (2) to explore the extent to which PE and SDM are discussed in these reviews. METHODS: We searched for English-language reviews (including any study design) summarizing trial participation barriers, enablers, and/or strategies among equity-deserving populations in five peer-reviewed databases. We coded data on the (1) equity-deserving population(s) of focus, (2) barriers, enablers, or interventions/strategies mentioned, (3) PE reported, (4) Indigenous community engagement reported, and (5) SDM outcomes discussed. RESULTS: Findings from 100 reviews showed that some equity-deserving populations have been represented more than others (e.g., 76% on racially, ethnically, culturally, or linguistically diverse populations; 29% on sex and gender populations; 2% on educationally disadvantaged populations). More reviews described barriers (84%) than enablers (31%) or strategies to improve participation (69%). Forty-five reviews (45%) reported PE while 11 (11%) reported Indigenous community engagement. Many reviews (74%) mentioned SDM outcomes (i.e., 9/11 [81.8%] outcomes from Gillies et al.’s internationally agreed core outcome set); however, few reviews (29%) discussed SDM outcomes in detail. CONCLUSIONS: Our findings suggest that PE and SDM could be more broadly applied among multiple equity-deserving groups to better serve disadvantaged communities. We advocate for an expanded focus on less-researched equity-deserving groups, improved PE reporting, prioritization of patient outcomes, and engagement with patients and Indigenous communities.},
}

@article {pmid41863721,
year = {2026},
author = {Maidh, A and Kalra, P and Khan, H and Silakari, P and Grewal, AK},
title = {Circadian disruption as a driver and target in neurodegenerative diseases: from molecular mechanisms to chronotherapeutic strategies.},
journal = {Metabolic brain disease},
volume = {41},
number = {1},
pages = {},
pmid = {41863721},
issn = {1573-7365},
abstract = {The Circadian System is a complex network of coordinated clocks that regulates the organism’s internal clock in synchronisation with the outside world. These rhythms are controlled by genetically controlled positive and negative transcriptional-translational feedback loops (TTFL) that generate 24-hour oscillations in the protein level and mRNA of core circadian components. Circadian disruption is recognised as a significant contributor to the molecular pathogenesis of neurodegenerative illnesses, as disease-specific alterations in clock gene expression and melatoninergic signalling have been identified as possible early-stage molecular indicators. Emerging evidence suggests a link between dysregulated circadian rhythms and neurodegenerative diseases, implying that the changes in circadian function may play a critical role in the development and progression of neurodegenerative diseases. The correlation between circadian rhythm and neurodegeneration is highly promising for developing treatment and promoting healthy lifestyle measures. This review article primarily focuses on how abnormalities in circadian rhythms may increase the risk of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and Amyotrophic Lateral Sclerosis (ALS). Applying knowledge from pre-clinical and translational research on neurodegenerative diseases is crucial for lowering the risks of neurodegeneration and improving the symptoms and quality of life of people with neurodegenerative diseases through approaches that restore circadian rhythm in the context of precision medicine. Understanding this interaction holds promise for developing therapeutic approaches to support a healthy lifestyle.},
}

@article {pmid41870724,
year = {2026},
author = {Darwish, S and Ballout, S and Shi, L and Negron, R and Cooley, ME},
title = {Social Ties and Behavioral Diffusion of Tobacco Use in Arab American Networks.},
journal = {Journal of immigrant and minority health},
volume = {},
number = {},
pages = {},
pmid = {41870724},
issn = {1557-1920},
abstract = {Arab Americans (AAs) exhibit elevated rates of tobacco use, often influenced by their social networks (SN). Despite this, research has not comprehensively explored the mechanisms through which these relationships sustain tobacco use, and broader studies on social SNs provide limited insight into the influential SN attributes and interactions affecting AA communities. Guided by Berkman et al.’s (2000) SN and health framework, this study examined associations between SN structure, composition, relational and communication dynamics, and tobacco use among AAs. Variables included network size, density, SN compositional and demographic characteristics, contact modality and frequency, and relationship closeness. Data were collected through a cross-sectional survey of 178 AA adults in Massachusetts and analyzed using multivariate logistic regression. Overall, 51.7% of participants were current tobacco users; 45.5% reported hookah use, 13.5% cigarette use, and 18.5% used multiple products. Features of SNs associated with decreased odds of tobacco use included having larger SNs (OR = 0.38, 95% CI: 0.20–0.70), higher proportions of non-tobacco users (OR = 0.98), frequent in-person interactions with non-tobacco users (OR = 0.71), and stronger ties to non-tobacco users (OR = 0.074). Networks with greater Arab representation initially appeared protective but, in adjusted models, were associated with higher use (OR = 1.45), suggesting cultural identity and affiliation may reinforce smoking norms. Gender patterns also differed : networks with more women initially appeared protective, but after adjustment this association reversed (OR = 1.53), highlighting nuanced sociocultural impacts on behavioral change among Arab men and women following migration. Conversely, increased tobacco use was associated with greater contact with tobacco users, particularly through virtual modalities (OR = 1.027), and closer relationships with tobacco users (OR = 5.54). The findings suggest that tobacco use is propagated through both imitation and social reinforcement within strongly connected, homogenous networks. The study offers valuable insights into overlooked SN attributes and relational mechanisms relevant to understanding the transmission of tobacco use behaviors within AA populations. Identifying specific relational attributes may inform culturally tailored cessation interventions that leverage influential network members and key actors, strong social ties, and targeted modes of interaction, both in-person and digital, to enhance tobacco control strategies in AA communities.},
}

@article {pmid41894075,
year = {2026},
author = {Kuwar, OK and Tejpal, S and Sharma, V and Sharma, A and Rao, A and Attri, M and Pallavi, and Dhingra, MS},
title = {Therapeutic potential of sulforaphane in neurodegenerative diseases: mechanistic Insights into Nrf2, NF-κB, TrkB, SIRT1, MAPK, and JAK/STAT signalling pathways.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {},
pmid = {41894075},
issn = {1573-4978},
abstract = {Neurodegenerative diseases, including Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis, are chronic and progressive disorders distinguished by neuronal dysfunction, oxidative stress, neuroinflammation, and abnormal protein aggregation. Due to the multifactorial nature of these disorders, current pharmacotherapies provide limited symptomatic relief without altering disease progression. Sulforaphane, a naturally occurring isothiocyanate abundant in cruciferous vegetables like broccoli, has emerged as a potent neuroprotective compound owing to its pleiotropic effects on key cellular signalling pathways. This review provides a thorough overview of the mechanistic insights underlying SFN’s neuroprotective potential, with a focus on the modulation of key signalling pathways such as Nrf2/ARE, NFĸB, BDNF/TrkB, SIRT1, MAPK, and JAK/STAT. Through the activation of antioxidant defenses and suppression of inflammatory cascades, SFN effectively mitigates neuronal damage and supports cellular homeostasis. Preclinical studies consistently demonstrate SFN’s ability to attenuate oxidative stress, inhibit apoptosis, preserve mitochondrial function, and improve neurobehavioral outcomes. While limited clinical evidence supports its safety and bioactivity, further investigations are needed to establish its therapeutic utility in human populations. Overall, SFN represents a promising natural compound with significant potential for the prevention and management of neurodegenerative diseases through multi-targeted pathway modulation.},
}

@article {pmid42009918,
year = {2026},
author = {G Diebo, B and E Nassar, J and Lafage, R and Challier, V and Pesenti, S and Lafage, V},
title = {Distinguishing reactive scoliosis: clinical presentation, pathophysiology and a proposed clinical framework.},
journal = {European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society},
volume = {},
number = {},
pages = {},
pmid = {42009918},
issn = {1432-0932},
abstract = {Purpose: This study introduces "reactive scoliosis" as an umbrella term formalizing various scoliosis subtypes that arise secondary to lumbar disc herniation, spondylolisthesis, and benign tumors. It aims to synthesize current evidence on the clinical presentations, pathophysiology, and surgical management of these subtypes, and to propose a preliminary clinical framework to guide their differentiation and treatment.Methods: A comprehensive literature search was conducted in PubMed/MEDLINE, Embase, and Scopus from inception through October 2025, following PRISMA guidelines. Search terms included combinations of "scoliosis" with "lumbar disc herniation", "spondylolisthesis", "osteoid osteoma", "osteoblastoma", and "ganglioneuroma". Studies were included if they addressed pathophysiology, clinical presentation, radiographic features, or surgical outcomes of reactive scoliosis subtypes. Two independent reviewers extracted data on curve magnitude, vertebral rotation, trunk shift, and surgical response.Results: Each reactive scoliosis subtype demonstrates distinct clinical and radiographic characteristics. Spasm scoliosis from lumbar disc herniation presents with short lumbosacral curves, minimal apical rotation, and significant coronal imbalance, typically resolving after discectomy. Pure spasm scoliosis from spondylolisthesis similarly resolves following fusion alone, while olisthetic scoliosis, characterized by vertebral rotation at the slip site rather than the curve apex, requires additional rotational correction. Tumor-driven scoliosis, including osteoid osteomas, osteoblastomas, and ganglioneuromas, demands individualized imaging and surgical strategies, with staged approaches warranted in structurally destructive cases.Conclusion: Accurate identification of reactive scoliosis subtypes is critical for surgical planning. The proposed expanded clinical framework, building upon Guo et al.'s modified Crostelli classification, offers surgeons a structured approach to differentiate these etiologies and optimize management. Prospective studies are needed to validate the algorithm and refine its clinical applicability.Keywords: Reactive scoliosis; Spasm scoliosis; Olisthetic scoliosis; Spondylolisthesis; Lumbar disc herniation},
}

@article {pmid42036486,
year = {2026},
author = {Assefa, M and Tsegaye, A and Addissie, A and Worku, A},
title = {Establishing population-based reference intervals for hematological parameters among apparently healthy adults in Northwest Ethiopia, 2023.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-50237-3},
pmid = {42036486},
issn = {2045-2322},
support = {VPRTT/PY-002/20021//Addis Ababa University Thematic Research Fund/ ; VPRTT/PY-002/20021//Addis Ababa University Thematic Research Fund/ ; VPRTT/PY-002/20021//Addis Ababa University Thematic Research Fund/ ; VPRTT/PY-002/20021//Addis Ababa University Thematic Research Fund/ ; },
abstract = {Ethiopian diagnostic facilities currently use Western hematological reference ranges, lacking national standardization. This study establishes hematological reference values for healthy adults in Northwest Ethiopia through a population-based cross-sectional study conducted from June to August 2023. Whole blood samples from 759 participants were analyzed using the Siemens ADVIA-560 hematology analyzer. Data were processed with Stata 17.0, and reference intervals (RIs) were calculated for the central 95% of the distribution, with gender & altitude differences assessed via the Mann-Whitney U test (p < 0.05). Sex and altitude based partitioning was done using Harris & Boyd’s Z-test and Lahti et al.’s proportion criteria. Results showed significant variations by sex and altitude, with males exhibiting higher median values for several hematological parameters. The combined 95% reference intervals (RIs) were: WBC (3.11–9.89 × 10[9]/L), NEU (0.96–6.54 × 10[9]/L), LYM (0.69–2.89 × 10[9]/L), MON (0.31–1.46 × 10[9]/L), and BAS (0.05–0.42 × 10[9]/L), with corresponding differential percentages also established. Sex-specific RIs were defined for key parameters. In men: RBC (4.54–6.39 × 10[12]/L), HGB (13.68–19.21 g/dL), HCT (41.39–57.01%), MCHC (32.01–34.91 g/dL), and PLT (127.10–367.10 × 10[9]/L); and in women: RBC (4.17–5.55 × 10[12]/L), HGB (12.51–16.39 g/dL), HCT (37.91–48.89%), MCHC (31.51–34.70 g/dL), and PLT (146.22–411.00 × 10[9]/L). Altitude-based stratification further revealed higher values at high altitude. In men, monocytes, eosinophils, RBC, HGB, HCT, and PLT were elevated, while in women, higher values were observed for neutrophils, monocytes, basophils, HGB, HCT, MCV, and MCH. These findings demonstrate that hematological reference intervals vary by sex and altitude among healthy adults in Northwest Ethiopia. The study highlights the potential value of using locally derived and context-specific reference intervals to improve interpretation of laboratory results. Further multicenter validation studies across diverse Ethiopian populations are recommended to support their application in clinical practice and research.},
}

@article {pmid42260986,
year = {2026},
author = {Sun, X and Dong, J and Liang, X and Peng, J and Chen, Y and Yin, R and Tan, T and Bai, L and Lan, K},
title = {PFN1 inhibits lytic replication of Kaposi sarcoma-associated herpesvirus through SQSTM1/p62-mediated selective autophagy targeting the KSHV helicase.},
journal = {Autophagy},
volume = {},
number = {},
pages = {1-16},
doi = {10.1080/15548627.2026.2686417},
pmid = {42260986},
issn = {1554-8635},
abstract = {Kaposi sarcoma-associated herpesvirus (KSHV), an oncogenic virus associated with several malignancies, including Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease, harbors a DNA replication helicase encoded by ORF44 that is crucial for viral replication and pathogenesis. In this study, we identified the host PFN1 (profilin 1), a well-known actin-binding factor, as an inhibitor of KSHV lytic replication functioning via the macroautophagy/autophagy-lysosomal degradation pathway targeting ORF44. Mechanistic analyses revealed that PFN1 interacts with ORF44, leading to enhanced polyubiquitination of PFN1. Notably, the E3 ubiquitin ligase TRIM37 (tripartite motif containing 37) facilitates the polyubiquitination of lysine residues at position 116 of PFN1, which serves as a critical recognition motif for the cargo receptor SQSTM1/p62 (sequestosome 1), which is pivotal for the subsequent autophagic degradation of ORF44. Overall, our findings revealed a previously uncharacterized antiviral function of PFN1, highlighting its potential as a novel therapeutic avenue for the treatment of KSHV-associated malignancies.Abbreviations: ALS: amyotrophic lateral sclerosis; Baf A1: bafilomycin A1; co-IP: co-immunoprecipitation; KSHV: Kaposi sarcoma-associated herpes virus; LIR: LC3-interacting region; PFN1: profilin 1; SQSTM1/p62: sequestosome 1; TRIM37: tripartite motif containing 37; UBA: ubiquitin-associated domain.},
}

@article {pmid42282797,
year = {2026},
author = {Yusuf, IO and Silva, RLA and Amoako, GG and Thompson, PR and Xu, Z},
title = {PAD2 knockout reduces myelin protein aggregates, modulates neuroinflammation and protects motor neurons, axons and neuromuscular junction in a SOD1-ALS mouse model.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.05.30.729013},
pmid = {42282797},
issn = {2692-8205},
abstract = {BACKGROUND: Dysregulated peptidyl deiminase 2 (PAD2) and aberrant protein citrullination (PC), a posttranslational modification (PTM), are involved in various inflammatory and neurodegenerative diseases. We previously showed in transgenic mice and postmortem human tissues that PC and PAD2 are altered in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by motor neurons loss, paralysis, and death. Herein, we investigated the role of PAD2 in ALS by PAD2 knockout in a SOD1-ALS mouse model.

METHODS: To investigate the role of PAD2-induced citrullination in ALS pathogenesis, we generated PAD2 knockout (PAD2KO) in SOD1 [G93A] ALS mouse model and investigated the consequent modulation on the neuropathology and clinical symptoms, using molecular biology techniques such as qPCR, Western blotting, confocal microscopy, and electron microscopy. Additionally, we identified C3 as being citrullinated in human ALS using ionFinder.

RESULTS: Our results show that PAD2KO blocked the increased PC and reduced myelin basic protein (MBP) aggregates in the ALS model. PAD2KO also improved motor neuron survival and the integrity of myelin, axons, and neuromuscular junctions, and reduced microgliosis in the white matter and C3 protein levels in astrocytes. Clinically, data from monitoring the body weight changes suggests that PAD2KO modulates the course of the disease in the ALS mouse model, accelerating the onset while slowing the progression after the onset, and modestly extending the survival of male mice.

CONCLUSION: These results show that PAD2 is responsible for the increased PC in ALS and PC contributes to neuroinflammation and degeneration of motor neurons and myelinated axons. The modest modulation of the disease phenotype suggests that the role of PC in ALS is complex, involving altered PC in numerous proteins and in multiple cell types. Future studies are needed to investigate how PC modulates individual protein functions in various cell types to understand the contribution of PC to ALS pathogenesis.},
}

@article {pmid42283221,
year = {2026},
author = {Scozzari, S and Columbro, SF and Favagrossa, M and Tortarolo, M and Cagnotto, A and Salmona, M and De Marco, G and Bendotti, C and Calvo, A and Pasetto, L and Bonetto, V},
title = {Effects of Lysine Deacetylation Inhibition Alone or in Combination With Arimoclomol on TDP-43 Proteinopathy.},
journal = {Journal of neurochemistry},
volume = {170},
number = {6},
pages = {e70493},
pmid = {42283221},
issn = {1471-4159},
support = {RF-2018-12365614//Ministero della Salute/ ; GATTALS//AriSLA/ ; },
mesh = {Animals ; *Histone Deacetylase Inhibitors/administration & dosage/pharmacology ; Humans ; Mice ; Acetylation/drug effects ; *Lysine/metabolism/antagonists & inhibitors ; *TDP-43 Proteinopathies/drug therapy/metabolism/pathology ; Mice, Transgenic ; Vorinostat/administration & dosage ; *DNA-Binding Proteins/metabolism ; Male ; },
abstract = {Cytoplasmic inclusions containing TAR DNA-binding protein 43 kDa (TDP-43) are recognized as a major pathological feature of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Peptidyl-prolyl cis-trans isomerase A (PPIA) interacts with TDP-43 and influences its aggregation and function. This interaction is facilitated by PPIA Lys-acetylation. Here, we investigated whether restoring lysine acetylation homeostasis exerts protective effects on TDP-43 proteinopathy in vitro and in vivo and how this relates with PPIA. We found that vorinostat/SAHA, a broad-spectrum histone deacetylase (HDAC) inhibitor that increases PPIA acetylation, is able to reverse TDP-43 mislocalization in a cellular model of TDP-43 proteinopathy. We confirmed its effects in peripheral blood mononuclear cells from ALS patients and explored its impact on TDP-43 proteinopathy and PPIA acetylation in the Thy1-hTDP-43 mouse model. Thy1-hTDP-43 mice treated with SAHA showed a delayed onset of TDP-43 pathology, associated with PPIA nucleus-cytoplasm redistribution, lower neurodegeneration and neuroinflammation, and improved neuromuscular function markers. However, these effects were transient. When combined with arimoclomol, a heat shock protein co-inducer, a mitigation of the neurodegeneration was sustained. A synergistic effect was observed in periphery, greatly enhancing tubulin acetylation and reducing phosphorylated TDP-43 accumulation in the sciatic nerve and acetylcholine receptor γ-subunit expression in gastrocnemius muscle. This study suggests that HDAC inhibition could be beneficial in restoring TDP-43 localization and function through multiple mechanisms, including modulation of PPIA acetylation. The combination of lysine deacetylation inhibition and arimoclomol shows a synergistic effect in vivo and has potential as a therapeutic approach for patients.},
}

Animals
*Histone Deacetylase Inhibitors/administration & dosage/pharmacology
Humans
Mice
Acetylation/drug effects
*Lysine/metabolism/antagonists & inhibitors
*TDP-43 Proteinopathies/drug therapy/metabolism/pathology
Mice, Transgenic
Vorinostat/administration & dosage
*DNA-Binding Proteins/metabolism
Male

@article {pmid42283246,
year = {2026},
author = {Fikry, H and Saleh, LA and Sadek, DR},
title = {Histological and Tissue-Level Outcomes of Stem Cell Therapies in Neurodegenerative Disorders: A Systematic Review.},
journal = {Clinical anatomy (New York, N.Y.)},
volume = {},
number = {},
pages = {},
doi = {10.1002/ca.70147},
pmid = {42283246},
issn = {1098-2353},
abstract = {Neurodegenerative diseases, which afflict millions worldwide and threaten public health, have no cure. Neurodegenerative diseases lack effective therapies, burdening society and the economy. Over the past 20 years, regenerative cell therapy (stem cell therapy) has advanced, opening novel neurodegenerative disease treatments. Thus, the current review aimed to systematically highlight experimental and clinical studies of potentially effective therapeutic strategies for stem cells and report histological, cellular, or ultrastructural outcomes following stem cell interventions in neurodegenerative diseases. PRISMA-compliant computerized literature searches of PubMed, Scopus, and Web of Science identified studies on embryonic, induced pluripotent, mesenchymal, or neural stem cells (NSCs) in neurodegenerative disease models and histological and tissue-level outcomes. Search terms included nervous system diseases, histology, neuron regeneration, stem cells, stem cell treatment, and transplantation. Peer-reviewed articles published between 2000 and 2025 were selected. Experimental animal and clinical studies that reported histological or tissue-level results after stem cell treatments were included. Eighty-six studies met the eligibility criteria, covering models of Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and Huntington's disease. Across these studies, stem cell therapies were linked to improved neuron survival, better synaptic structure, diminished gliosis, and some restoration of tissue structure. These effects depended on the type of stem cell used, the disease model, and how the treatment was given. Overall, the evidence suggests that stem cell therapies can lead to significant histological and tissue-level improvements in neurodegenerative diseases, supporting their potential for regeneration. Further standardized and translational studies are needed to clarify the underlying mechanisms and improve treatment strategies.},
}

@article {pmid42283497,
year = {2026},
author = {Turner, ED and Twelvetrees, AE},
title = {The Long Haul: Microtubule Motors as the Essential Supply Line for Neuronal Longevity.},
journal = {Journal of neurochemistry},
volume = {170},
number = {6},
pages = {e70496},
pmid = {42283497},
issn = {1471-4159},
support = {220192/Z/20/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; *Microtubules/metabolism/physiology ; Animals ; *Neurons/metabolism/physiology ; *Molecular Motor Proteins/metabolism/genetics ; Mutation ; },
abstract = {The extreme morphology and polarised architecture of neurons require the highly sophisticated microtubule transport system for both construction and lifelong survival. Genomic evidence from an expanding landscape of human mutations supports the essential role of the microtubule transport machinery. During neurodevelopment, mutations disrupt the proliferation and migration of neuronal precursors, as well as the initial establishment of polarity. In the mature nervous system, the reliance on microtubule transport shifts to the long-term maintenance of axon integrity and synaptic proteostasis. Across the motor proteins responsible for long distance transport in neurons, mutations highlight a specific vulnerability of long axons to transport failure in Hereditary Spastic Paraplegia (HSP), Charcot Marie Tooth disease Type 2 (CMT2), Spinal Muscular Atrophy (SMA), Perry Syndrome, and Amyotrophic Lateral Sclerosis (ALS) amongst others. Due to the role of microtubule motors in development and maintenance, there is frequently a phenotypic spectrum within a single gene of the microtubule transport system. For example, mutations in dynein motors are linked both to malformations of cortical development and specific motor neuron loss in SMA-LED (Spinal Muscular Atrophy with Lower Extremity Predominance). By synthesising genetic evidence, this review illustrates how specific molecular failures, ranging from motor-domain kinetics to cargo binding, can inform our understanding of neuronal homeostasis. Ultimately, we argue that microtubule transport is not merely a cellular utility, but a key determinant of neuronal longevity.},
}

Humans
*Microtubules/metabolism/physiology
Animals
*Neurons/metabolism/physiology
*Molecular Motor Proteins/metabolism/genetics
Mutation

@article {pmid42283699,
year = {2026},
author = {El-Wahsh, S and Bogart, E and Bonnor, S and El-Wahsh, S and Graco, M and Hogden, A and Paynter, C and Raykar, V and Signorelli, M and Thomson, E and Vucic, S and White, S},
title = {Supporting gastrostomy decision-making in motor neurone disease (MND): an Australian survey of healthcare professionals' beliefs, practices, and needs.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/17582024.2026.2687483},
pmid = {42283699},
issn = {1758-2032},
abstract = {INTRODUCTION: Gastrostomy decision-making for people living with motor neurone disease (MND) is complex. While international studies report healthcare professionals' (HCPs) beliefs and practices in this area, little is known about the Australian context.

AIM: To examine Australian HCPs' beliefs, clinical practices, and support needs regarding gastrostomy decision-making in MND.

METHODS: A national cross-sectional online survey of Australian HCPs involved in gastrostomy discussions (n = 123) was conducted, exploring five domains: 1) initiating discussions and timing; 2) patient education; 3) multidisciplinary coordination; 4) guideline use; 5) and professional development needs. Descriptive statistics were applied.

RESULTS: Most HCPs initiated discussions about gastrostomy (74%), commonly prompted by swallowing difficulty, weight loss, or patient request. Although 72% believed discussions should occur before clinical indications, only 40% reported doing so. Earlier placement was favored in the context of respiratory decline compared with swallowing impairment, and 56% considered gastrostomy to be performed too late. Almost 40% used no formal guidelines, and 74% wanted further professional development.

CONCLUSION: Australian HCPs valued person-centered practice, but belief-practice gaps highlight opportunities to improve consistency, timing, and quality of gastrostomy decision-making support. Enhanced national guidelines, improved multidisciplinary communication, and targeted professional development may help reduce delays and better align practice with evidence-based recommendations.},
}

@article {pmid42285406,
year = {2026},
author = {Mendoza-Camacho, DM and Espinoza-Gutiérrez, HA and Viveros-Paredes, JM and Flores-Soto, ME and Tejeda-Martínez, AR},
title = {Recent advances in neurodegenerative diseases therapeutics: The inhibition of monoacylglycerol lipase strategy.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2026.06.011},
pmid = {42285406},
issn = {1873-7544},
abstract = {Neurodegenerative diseases share common pathophysiological mechanisms, including chronic neuroinflammation, glutamatergic excitotoxicity, oxidative stress, mitochondrial dysfunction, and disruptions in synaptic and lipid homeostasis. In this context, the endocannabinoid system has emerged as a key modulator of neuroimmune communication and neuronal survival. Within this system, Monoacylglycerol Lipase (MAGL) plays a central role by regulating the levels of the endocannabinoid 2-Arachidonoylglycerol (2-AG) while simultaneously contributing to the generation of arachidonic acid and pro-inflammatory eicosanoids. Pharmacological or genetic inhibition of MAGL increases 2-AG levels and concurrently reduces the biosynthesis of pro-inflammatory lipid mediators, thereby modulating microglial activation, astrocytic responses, and neuronal excitotoxicity. Preclinical studies in models of Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis consistently demonstrate that MAGL blockade attenuates neuroinflammation, preserves synaptic and neuronal integrity, improves motor and cognitive function, and, in some cases, delays disease progression. Although clinical evidence remains limited, the available data position MAGL as a metabolic convergence point between inflammation and neurodegeneration, suggesting that its modulation may represent a therapeutic strategy with disease-modifying potential.},
}

@article {pmid42286474,
year = {2026},
author = {Seuren, LM and Versloot, J and Taneja, S and Zeeshan, MF and Wodchis, WP},
title = {Adoption and sustainability of a virtual interprofessional team for primary care in Ontario: a qualitative study.},
journal = {BMC primary care},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12875-026-03411-5},
pmid = {42286474},
issn = {2731-4553},
abstract = {BACKGROUND: Primary care providers across Canada face challenges caring for patients with increasingly complex care needs. Team-based care has been identified as an approach to improve care for patients with complex needs. The Mississauga Ontario Health Team recently adopted SCOPE, a telephone-based support line to improve care coordination between primary care, hospital and community services. To understand how Mississauga Health SCOPE supports primary care providers and how it can be improved, this study addresses the following research question: why do primary care providers adopt or not adopt Mississauga Health SCOPE, and what motivates sustained use or abandonment?

METHODS: Semi-structured interviews were conducted over Zoom with three stakeholder groups: primary care providers (n = 20), general internal medicine physicians (n = 3), and members of the project team (n = 6). Interviews focused on the adoption and continued use of Mississauga Health SCOPE. Data were analyzed inductively, using Proctor et al.'s Adoption and Sustainability concepts.

RESULTS: Within the broad concepts of Adoption and Sustainability, we identified seven themes that shaped whether PCPs would use and continue to use MHSCOPE: Broken healthcare system, Awareness of Mississauga Health SCOPE, Service misalignment, Useful and usable, Trying it out, Breaking the habit, and Making PCPs feel heard.

CONCLUSIONS: Telemedicine support services like Mississauga Health SCOPE can help primary care providers deliver appropriate and timely care to patient in the community. Succcesful implementation requires that clinicians feel supported in using the intervention, have a clear understanding of procedures and benefits, and are prepared to take time to learn to work with new tools to overcome hurdle of initial adoption.},
}

@article {pmid42286604,
year = {2026},
author = {Forster, L and Byrne, S and Spielmann-Burkard, H and Weber, S and von Strachwitz, M and Kuehlmeyer, K and Kugler, C},
title = {Linguistic and psychometric validation of a German version of the measure of moral distress for healthcare professionals (MMD-HP GER): results of a study with intensive care nurses.},
journal = {BMC medical ethics},
volume = {27},
number = {1},
pages = {},
pmid = {42286604},
issn = {1472-6939},
mesh = {Humans ; Ethical Dilemmas ; Germany ; *Psychometrics ; Female ; Adult ; Surveys and Questionnaires ; Male ; Reproducibility of Results ; Translating ; *Critical Care Nursing/ethics ; *Stress, Psychological/diagnosis ; *Morals ; Middle Aged ; },
abstract = {BACKGROUND: Moral distress is an increasingly studied phenomenon in nursing science and ethics. It refers to the psychological discomfort experienced when an individual is prevented from acting on a course of action that they recognize as ethically correct. Nurses who work in intensive care are at high risk of experiencing moral distress. Various instruments to assess moral distress, most recently Epstein et al.'s measure of moral distress for health care professionals (MMD-HP), have been developed. At present, there is no validated German language version of the instrument for assessing moral distress in Germany. Therefore, this study aimed, at (1) translating and linguistically validating the instrument, as well as (2) psychometrically validating it among intensive care nurses in Germany.

METHODS: According to the ISPOR (International Society for Pharmacoeconomics and Outcomes Research) guidelines, the MMD‑HP was translated, linguistically validated, and psychometrically tested. The German version of the moral distress thermometer (MDT) and the German Nursing Workload Scale (NWS) were used to measure the construct validity of the translated instrument. Institutional ethics review boards of two universities approved the study protocols.

RESULTS: A total of 187 questionnaires of intensive care nurses remained for analysis after listwise deletion. The mean sum‑score was 106.9 (± 62) (minimum = 3, maximum = 325; range = 0-400). Criterion validity was supported by a high positive correlation between the German version of the MMD‑HP and the validated German-language moral distress thermometer (ρ = 0.598, p = 0.001, n = 168). Factor analyses revealed a four‑factor solution with correlating factors for the German version. The instrument showed high reliability (ωH = 0.91, 95 % CI = 0.88-0.93).

CONCLUSIONS: Our findings demonstrate that the German adaptation of the MMD-HP shows potential for measuring moral distress among intensive care nurses in Germany. In addition, its psychometric properties preliminarily support its reliability and validity in this cultural context. Further independent validation studies are needed to provide support for the proposed four-factor model.},
}

Humans
Ethical Dilemmas
Germany
*Psychometrics
Female
Adult
Surveys and Questionnaires
Male
Reproducibility of Results
Translating
*Critical Care Nursing/ethics
*Stress, Psychological/diagnosis
*Morals
Middle Aged

@article {pmid42286839,
year = {2026},
author = {Wheeler, A and Mehta, K and Sanders, D and Chin, C and Zivalic, H and Carey, J and McCaffrey, A and Pant, P and Lewenhaupt, C and Luppino, S and Jacobs, G and Golden, S and Gifford, R and Scirocco, E and Keegan, M and Hatem, M and Yazdanian, T and Uysal, SP and Susco, N and Schwartzman, S and Branch, K and Hall, KE and Barnas, J and Lam, J and Hagar, J and Hannan, CA and Paganoni, S and Berry, JD and Garret, M and Scalia, J and Babu, S},
title = {Optimizing Research Operations and Resource Utilization in ALS Care: Insights From the Tofersen Antisense Oligonucleotide Expanded Access Protocol.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70310},
pmid = {42286839},
issn = {1097-4598},
abstract = {INTRODUCTION/AIMS: Tofersen is a gene-targeted therapy for individuals with superoxide dismutase 1 (SOD1) (+) amyotrophic lateral sclerosis (ALS). Prior to U.S. Food and Drug Administration (FDA) approval, tofersen was made available through expanded access protocol. This study describes the clinical and operational experience of administering tofersen through expanded access protocols at a single academic medical center in the U.S.

METHODS: Individuals with symptomatic SOD1(+) ALS (≥ 18 years), who were ineligible for traditional ALS clinical trials, received tofersen via bedside lumbar punctures at Massachusetts General Hospital. Treatment was provided through single-patient and intermediate-sized expanded access protocols prior to FDA approval. Demographic and clinical characteristics, referral-to-treatment timelines, safety outcomes, and operational costs were collected.

RESULTS: Eleven individuals with SOD1(+) ALS received monthly intrathecal tofersen over a two-year period (July 2021 to July 2023). Most participants were female, and 81.8% had leg-onset ALS. The mean (SD) referral-to-first dose duration was 36 (22.4) days. A total of 120 doses were administered over a two-year period. Tofersen was safe and well tolerated, with no treatment-related serious adverse events. Operational costs totaled $336,620, supported by philanthropy and insurance. The company provided the drug for free.

DISCUSSION: This experience demonstrates the feasibility of implementing a resource-intensive expanded access protocol within an academic medical center using a mixed funding model to facilitate early access to emerging ALS therapies.},
}

@article {pmid42287757,
year = {2026},
author = {Jaberi, KR and Haghighi, MR and Aligholi, H and Takallu, S and Asadi, P and Mirzaei, E and Jaberi, AR and Sahraian, A},
title = {Focused ultrasound-mediated nanocarrier delivery across the blood-brain barrier for neurodegenerative diseases.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {201},
number = {},
pages = {119622},
doi = {10.1016/j.biopha.2026.119622},
pmid = {42287757},
issn = {1950-6007},
abstract = {The development of effective therapies for neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis remains a major challenge due to the restrictive nature of the blood-brain barrier (BBB). Conventional systemic drug delivery strategies often fail to achieve sufficient central nervous system (CNS) penetration while avoiding peripheral toxicity. Focused ultrasound (FUS), particularly when combined with microbubbles or nanocarriers, has emerged as a non-invasive approach to transiently and precisely open the BBB, enabling targeted delivery of therapeutics to the brain parenchyma. This review provides a comprehensive overview of the mechanisms by which FUS enhances CNS drug delivery, with a dedicated focus on its integration with nanoparticle-based systems, including liposomes, polymeric nanoparticles, dendrimers, metallic nanoparticles, and exosomes. We discuss how these nanocarriers can be engineered for improved stability, targeting specificity, and stimulus-responsive release upon FUS exposure. Recent advances in ultrasound technology, image guidance (particularly MRI), and therapeutic formulations are summarized, along with preclinical and clinical evidence across key neurodegenerative conditions. Despite promising results, several challenges remain, including long-term BBB stability, regulatory standardization, and scalability for broad clinical application. By integrating principles from acoustics, pharmacology, and nanotechnology, FUS-mediated drug delivery, especially in combination with smart nano systems, represents a significant advancement in precision neurotherapeutics, offering new hope for previously untreatable CNS diseases.},
}

@article {pmid42287763,
year = {2026},
author = {Mah, SJ and Bergeron, AM and Hanley, G and Yang, I and Bogach, J and Nguyen, L and Huerne, K and Morais, M and Stuart, H},
title = {Opportunistic salpingectomy during non-gynecologic surgery: Canadian surgeons' experience, barriers and facilitators.},
journal = {Gynecologic oncology},
volume = {211},
number = {},
pages = {1-7},
doi = {10.1016/j.ygyno.2026.06.005},
pmid = {42287763},
issn = {1095-6859},
abstract = {BACKGROUND: Opportunistic salpingectomy during concurrent abdominopelvic surgery has been shown to significantly reduce ovarian cancer risk. Uptake by non-gynecologic surgeons could increase population impact. We conducted a national survey of general and urologic surgeons using Michie et al.'s implementation framework of Capability, Motivation, Opportunity-Behaviour to understand understand current experience with opportunistic salpingectomy, and facilitators and barriers to adoption.

METHODS: An online survey was administered to Canadian general and urologic surgeons and postgraduate trainees from January-June 2024. A multivariable logistic regression model assessed relationship between demographic factors and motivation to adopt opportunistic salpingectomy.

RESULTS: 269 surveys were completed by 226 general surgeons and 43 urologists. Although 88% reported motivation to perform opportunistic salpingectomy for cancer prevention, practice duration ≥21 years and province of practice were associated with decreased motivation. Only 44% were aware of recommendations endorsing the procedure, and 19% had performed it. Commonly reported barriers to adoption were Capability (consenting patients regarding permanent contraception and ovarian function, and intraoperative technique/complications), and Opportunity (reimbursement). A surgical video was the preferred method to learn salpingectomy by 94%, and patient consent handouts and intraoperative training by a gynecologist were facilitators. Most (92%) stated that opportunistic salpingectomy training should be offered to postgraduate trainees.

DISCUSSION: Most general and urologic surgeons in Canada were unaware of and have not performed opportunistic salpingectomy but were motivated to offer it. Providing consent resources and training opportunities with gynecologist support, and addressing cultural and regulatory factors may improve uptake by surgeons and decrease ovarian cancer incidence.},
}

@article {pmid42288074,
year = {2026},
author = {Tackaert, T and Hemeryck, J and Duchatelet, C and Vanwulpen, M and Hachimi-Idrissi, S},
title = {Mean airway pressure as the missing link in CPR physiology: A prehospital comparison of manual and mechanical chest compressions.},
journal = {The American journal of emergency medicine},
volume = {108},
number = {},
pages = {80-85},
doi = {10.1016/j.ajem.2026.06.012},
pmid = {42288074},
issn = {1532-8171},
abstract = {BACKGROUND: The impact of manual versus mechanical chest compressions on mean airway pressure (mPAW) during cardiopulmonary resuscitation (CPR) is poorly understood. This exploratory pilot study assessed intratracheal airway pressures during prehospital CPR in out-of-hospital cardiac arrest (OHCA).

METHODS: Adult OHCA patients treated by the prehospital Medical Emergency Team of the Ghent University Hospital (Belgium) were prospectively enrolled. Intratracheal pressure was recorded immediately after intubation, mPAW was calculated for both the first and last minutes of advanced life support (ALS). The results were compared between mechanical compressions using the Stryker LUCAS3® device and manual chest compressions (with chest compression feedback).

RESULTS: Nineteen patients were included (manual n = 10; mechanical n = 9). Initial median mPAW was low (7.74 mbar) and showed a slight increase over time. Mechanical compressions generated higher early mPAW than manual compressions (8.96 vs. 6.54 mbar). mPAW increased over time with manual compressions and decreased with mechanical compressions. Patients who achieved return of spontaneous circulation (ROSC) showed higher mPAW, though this difference was not statistically significant.

CONCLUSIONS: Prehospital mPAW values were substantially lower than those reported in previous ED-based studies. While airway pressure patterns differed between compression modalities, overall pressures were similar. These findings highlight complex airway mechanics during CPR and support further research into whether higher airway pressures could improve airway patency, oxygenation, and hemodynamics in selected OHCA patients.},
}

@article {pmid42288493,
year = {2026},
author = {Wang, N and Li, Y and Li, N and Shen, L and Wang, C and Zhu, H and Zhou, Z and Ding, Y and Zhang, J and Fang, L and Bai, B},
title = {Quantitative Proteomics Unveils Comprehensive Tissue-Specific VCP Interaction Networks in Mice.},
journal = {Scientific data},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41597-026-07626-0},
pmid = {42288493},
issn = {2052-4463},
support = {32071256//National Natural Science Foundation of China/ ; 82172354//National Natural Science Foundation of China/ ; },
abstract = {Valosin-containing protein (VCP), a conserved AAA ATPase hexamer, participates in multiple biological processes including ERAD, ubiquitin-dependent degradation by extracting misfolded proteins for proteasomal degradation. Although its interactions with cofactors are well-characterized, and its dysregulation is implicated in multisystem proteinopathy, amyotrophic lateral sclerosis, and cancer, the tissue-specific VCP interactomes underlying its functional versatility remain elusive. Here, we generated HA-N-tagged VCP knock-in mice via CRISPR/Cas9 strategy and performed affinity purification coupled with data-independent acquisition (DIA) mass spectrometry to systematically profile VCP interactors across eight mouse tissues, yielding a high-confidence dataset. We identified 923 robust VCP-binding partners, including established interactors (UBX2B, UFD1, proteasomal subunits) and novel candidates implicated in energy metabolism (TCA cycle, oxidative phosphorylation) and protein quality control (proteasome, ERAD). Notably, we validated the interaction of VCP to two hepatic candidate proteins, DAXX and PRKAG2 (AMPK γ2 regulatory subunit), using HepG2 cells. This study establishes the first in vivo atlas of the VCP interaction network, providing mechanistic insights into its tissue-specific roles and highlighting potential therapeutic avenues for VCP-related disorders.},
}

@article {pmid42289132,
year = {2026},
author = {Jamil, V and Aldoski, M and Selivany, B and Jameel, D},
title = {MORPHOLOGY AND PREVALENCE OF C-SHAPED CANALS IN MANDIBULAR FIRST MOLARS OF AN IRAQI KURDISTAN REGION POPULATION: A CONE-BEAM COMPUTED TOMOGRAPHY ASSESSMENT.},
journal = {Georgian medical news},
volume = {},
number = {373},
pages = {215-218},
pmid = {42289132},
issn = {1512-0112},
mesh = {Humans ; Female ; Male ; *Cone-Beam Computed Tomography ; Iraq/epidemiology ; *Molar/diagnostic imaging/anatomy & histology ; Adult ; Adolescent ; Middle Aged ; *Dental Pulp Cavity/diagnostic imaging/anatomy & histology ; *Tooth Root/diagnostic imaging/anatomy & histology ; Retrospective Studies ; *Mandible/diagnostic imaging/anatomy & histology ; Young Adult ; Prevalence ; },
abstract = {BACKGROUND: Root canal morphology variations, particularly C-shaped canal configurations, pose substantial challenges to successful endodontic therapy. Accurate preoperative assessment of these complex anatomical patterns remains essential, with cone-beam computed tomography (CBCT) offering superior three-dimensional visualization compared to conventional radiography.

OBJECTIVES: This study aimed to determine the prevalence and morphological characteristics of C-shaped canals and comprehensively evaluate root and canal configurations of mandibular first molars within an Iraqi Kurdish population using CBCT imaging.

METHODS: In this retrospective analysis, CBCT images from 323 patients (186 males, 137 females; aged 18-50 years) originating from Duhok, Erbil, and Suleimani underwent evaluation. Two calibrated endodontists independently examined axial, sagittal, and coronal reconstructions to document root numbers, canal counts, and configurations. Root canal morphology was classified according to Vertucci's system, while Fan et al.'s classification was applied only to confirmed true C-shaped canals. Chi-square analysis assessed gender-based differences, with statistical significance set at p≤0.05.

RESULTS: Two-rooted molars predominated (94.1%), typically exhibiting three (64.4%) or four canals (28.8%). Gender differences proved non-significant for root (p=0.653) and canal numbers (p>0.05). Mesial roots consistently demonstrated Vertucci Type IV morphology (90.1%), while distal roots displayed greater diversity: Type I (58.5%), Type IV (20.1%), and Type II (18.6%). Cross-sectional morphology was not analyzed using Fan classification for non-C-shaped canals. True C-shaped canal configurations were rare (0.6%; 2/323 teeth), with no significant gender association (p>0.05).

CONCLUSION: Iraqi Kurdish mandibular first molars typically exhibit predictable mesial root Type IV anatomy alongside variable distal root morphology requiring careful clinical exploration. The low true C-shaped canal prevalence (0.6%) underscores ethnicity-specific anatomical patterns. These findings advocate judicious CBCT utilization for complex endodontic cases while emphasizing systematic distal canal detection protocols.},
}

Humans
Female
Male
*Cone-Beam Computed Tomography
Iraq/epidemiology
*Molar/diagnostic imaging/anatomy & histology
Adult
Adolescent
Middle Aged
*Dental Pulp Cavity/diagnostic imaging/anatomy & histology
*Tooth Root/diagnostic imaging/anatomy & histology
Retrospective Studies
*Mandible/diagnostic imaging/anatomy & histology
Young Adult
Prevalence

@article {pmid42289668,
year = {2026},
author = {Pillay, S and Head, J and Horn, A and de Wet, W and Davidge, R and Dickson-Hall, M and Felix, G and Kali, G and Khan, W and Klein, B and Nakwa, F and Venter, M and Vlok, N and Wege, M and Stassen, W},
title = {The development of a consensus-based curriculum for a Bespoke Online Neonatal Education for Transfers (BONNETs) course.},
journal = {BMC medical education},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12909-026-09377-3},
pmid = {42289668},
issn = {1472-6920},
abstract = {BACKGROUND: High neonatal mortality in Sub-Saharan Africa (SSA) is driven by multiple systemic barriers, including insufficient neonatal transport infrastructure and limited provider training. Although specially trained neonatal retrieval teams are recommended for interfacility neonatal transfers, resource constraints lead to non-specialist emergency medical services (EMS) cadres performing these roles, potentially compromising the safe transport of critically ill neonates.

OBJECTIVE: To develop a bespoke, online neonatal interfacility transfer curriculum, informed by expert consensus and South African research to address critical gaps in provider knowledge and confidence, thereby improving neonatal transfer outcomes.

METHODS: Building on Kern's Six-Step Framework for curriculum development, an initial curriculum was derived through a comprehensive literature review, a retrospective chart analysis of neonatal cases in South Africa, and detailed interviews with experts and learners. Consequently, consensus on this curriculum was sought using a virtual, modified Nominal Group Technique (NGT) over two consensus rounds. A refined course curriculum is proposed.

RESULTS: Fourteen expert participants (neonatologists, paediatricians, neonatal nurses, and Advanced Life Support (ALS) providers with ≥ 3 years of experience) allocated potential outcomes to Core, Extended, or Advanced tiers based on EMS scope of practice. A 75% consensus threshold was applied. Eleven experts completed both rounds (21% attrition). Most were ALS providers (43%), largely employed in the public sector (71%). The final curriculum consists of three sequential courses (Core, Extended, Advanced) which scaffolds learning. The Core course consists of five modules, with each curriculum item achieving > 90% agreement on foundational skills including basic assessment, recognition of critical instability, and escalation pathways. This open-access online course is tailored to resource-limited settings.

CONCLUSION: A consensus-driven neonatal interfacility transfer curriculum for South Africa was successfully developed, providing a tiered, evidence-based approach to reinforce provider knowledge and confidence. By leveraging expanding internet accessibility, the Bespoke Online NeoNatal Education for Transfers (BONNETs) framework mitigates geographic disparities while integrating best practices for safe neonatal transfer. However, rigorous validation across diverse contexts and attention to broader systemic challenges, is essential to achieving sustained improvements. Future research should assess the curriculum's performance in improving knowledge and confidence, as well as long-term clinical impact on neonatal outcomes.},
}

@article {pmid42290091,
year = {2026},
author = {Khamies, MS and Mortada-Mahmoud, A and Laklouk, M},
title = {Naviculectomy combined with 'à la carte' soft-tissue releases: is it a practical solution for congenital vertical talus in adolescence?.},
journal = {Journal of pediatric orthopedics. Part B},
volume = {},
number = {},
pages = {},
doi = {10.1097/BPB.0000000000001364},
pmid = {42290091},
issn = {1473-5865},
abstract = {Neglected congenital vertical talus in adolescents often necessitates extensive soft-tissue dissection, leading to increased surgical trauma and worsening outcomes. We propose that excising the navicular bone can shorten the foot's medial column and loosen the ligaments around the talonavicular joint, thus improving reduction. This study aimed to evaluate whether naviculectomy and 'à la carte' soft-tissue releases could enhance the outcomes in these patients or not. A retrospective case series study was conducted on 15 adolescent patients (average age 10.67 years) with neglected congenital vertical talus from June 2020 to 2025, with a median follow-up of 24 months. All cases were idiopathic, neglected, virginal feet that had not undergone any manipulative casting before. Clinical assessments followed Zorer et al.'s criteria, and pain levels were evaluated using the visual analog scale (VAS). There were 11 boys and 4 girls. The median Zorer score increased from 2 preoperatively to 11 postoperatively, with a mean difference of 10 (P < 0.001), reflecting marked functional recovery. The median VAS score showed significant improvement at the final follow-up from 7 to 2 (P < 0.001). Significant improvement was observed in all radiographic measurements. Naviculectomy combined with 'à la carte' soft-tissue releases could be a practical, effective solution for adolescents with neglected congenital vertical talus in terms of pain relief, clinical, and radiological improvement while reducing complications associated with extensive surgical soft-tissue releases on short-term outcomes.},
}

@article {pmid42290559,
year = {2026},
author = {Martyniuk, О and Mushii, O and Pavlova, A},
title = {Integrated Analysis of hsa-miR-26b-5p and hsa-miR-186-5p in Blood Serum and Tumor Tissue Reveals their Prognostic and Predictive Significance in Breast Cancer.},
journal = {Experimental oncology},
volume = {48},
number = {1},
pages = {31-39},
doi = {10.15407/exp-oncology.2026.01.031},
pmid = {42290559},
issn = {2312-8852},
mesh = {Humans ; *MicroRNAs/genetics/blood ; Female ; *Breast Neoplasms/genetics/blood/pathology/mortality ; Prognosis ; *Biomarkers, Tumor/genetics/blood ; Middle Aged ; Adult ; Gene Expression Regulation, Neoplastic ; },
abstract = {BACKGROUND: Breast cancer (BC) heterogeneity signifi antly complicates diagnosis, prognosis, and prediction of treatment response. MicroRNAs (miRNAs) have emerged as promising biomarkers due to their involvement in tu- mor progression and in regulating therapy sensitivity. however, the combined clinical signifi ance of circulating and tumor-associated miRNAs, such as hsa-miR-26b-5p and hsa-miR-186-5p, remains insuffi tly elucidated. Materi- als and Methods. Expression levels of hsa-miR-26b-5p and hsa-miR-186-5p were analyzed in serum and tumor tis- sue of 124 BC patients. Associations with clinicopathological parameters were assessed. The prognostic signifi ance was evaluated based on disease progression and recurrence within 3 years. The predictive value was determined in patients receiving neoadjuvant chemotherapy (4AC regimen) using response assessment and ROC analysis. Re- sults. young BC patients (≤45 years) demonstrated signifi antly lower circulating levels of both miRNAs. Serum hsa-miR-186-5p expression was associated with early-stage disease, tumor size, lymph node status, and molecular subtype. Increased circulating hsa-miR-26b-5p levels were linked to disease progression, whereas decreased hsa- miR-186-5p levels were observed in patients with unfavorable outcomes. In tumor tissue, hsa-miR-26b-5p expres- sion correlated with tumor grade, size, and metastatic status, showing elevated levels in poorly differentiated tumors and reduced expression in metastatic disease. In contrast, hsa-miR-186-5p was associated with the molecular sub- type and lymph node involvement, with the highest expression observed in hER2-positive tumors and in patients with recurrence. Elevated levels of hsa-miR-186-5p in both serum and tumor tissue were associated with reduced sensitivity to doxorubicin-based neoadjuvant chemotherapy. ROC analysis confi med its predictive value (AUC = 0.750 for serum and 0.818 for tumor tissue). No signifi ant association between hsa-miR-26b-5p and chemothe- rapy response was observed.

CONCLUSIONS: hsa-miR-26b-5p and hsa-miR-186-5p demonstrate complementary roles in BC biology. hsa-miR-26b-5p is primarily associated with tumor aggressiveness and cancer progression, whereas hsa-miR-186-5p refl cts its molecular characteristics and response to chemotherapy. Their combined assessment in serum and tumor tissue represents a promising approach for improving prognostic stratifi ation and predicting treatment effi acy in BC patients.},
}

Humans
*MicroRNAs/genetics/blood
Female
*Breast Neoplasms/genetics/blood/pathology/mortality
Prognosis
*Biomarkers, Tumor/genetics/blood
Middle Aged
Adult
Gene Expression Regulation, Neoplastic

@article {pmid42290625,
year = {2026},
author = {Tenenbein, M},
title = {Author response to: Mullins et al. comment on, "We need a standardized North American acetylcysteine dosing regimen for the treatment of paracetamol (acetaminophen) poisoning".},
journal = {Clinical toxicology (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/15563650.2026.2679164},
pmid = {42290625},
issn = {1556-9519},
abstract = {INTRODUCTION: I have reviewed Mullins et al's critique of my commentary "We need a standardized North American acetylcysteine dosing regimen for the treatment of paracetamol (acetaminophen) poisoning".

DISCUSSION: I concur regarding this need, and I agree that the original three-bag regimen should be retired. However, we disagree upon its replacement. They challenge my recommendation for a two-bag regimen, and they favour the one-bag two-step approach. The impetus for a replacement acetylcysteine regimen is to decrease the adverse effects and errors associated with the three-bag protocol. However, the one-bag two-step regimen was not designed to decrease adverse effects, and their published reports do not find a decrease of errors. And a fatal adverse effect, acetylcysteine overdose, has emerged with use experience of this regimen.

CONCLUSIONS: The one-bag two-step regimen should be dismissed from the quest for a standardized North American acetylcysteine dosing regimen for the treatment of paracetamol (acetaminophen) poisoning.},
}

@article {pmid42293320,
year = {2026},
author = {Novikova, L and Lang, C and Tumani, H and Klose, V and Kassubek, J and Dreyhaupt, J and Dupuis, L and Wabitsch, M and Ludolph, A},
title = {Thyroid hormones and energy metabolism in amyotrophic lateral sclerosis.},
journal = {Brain communications},
volume = {8},
number = {3},
pages = {fcag198},
pmid = {42293320},
issn = {2632-1297},
abstract = {Weight loss, partially caused by hypermetabolism, represents a well-documented and therapeutically relevant feature of the amyotrophic lateral sclerosis phenotype worldwide. In this study, we retrospectively analysed the association between thyroid function and clinical, prognostic and metabolic parameters in a cohort of patients with amyotrophic lateral sclerosis in an experienced centre in Germany (n = 1754). Specifically, we examined the relationship between thyroid stimulating hormone levels, age, glucose and body mass index and-in subgroups-phosphorylated neurofilament heavy chain levels in CSF. There was no association between thyroid stimulating hormone levels and body mass index in patients with amyotrophic lateral sclerosis (n = 954). In contrast with other cohorts, thyroid stimulating hormone levels decreased with age in patients with amyotrophic lateral sclerosis indicating hypothalamic deficiency in the ageing patients. There was no association between thyroid stimulating hormone and phosphorylated neurofilament heavy chain (prognostic marker) in CSF of a subcohort (n = 646). Thyroid stimulating hormone levels correlated with glucose levels, an effect more pronounced in male patients. In conclusion, our results suggest that thyroid metabolism does not significantly contribute to amyotrophic lateral sclerosis-related weight loss or disease prognosis as estimated by phosphorylated neurofilament heavy chain; thyroid dysfunction is unlikely to be a primary driver of the metabolic dysregulation observed in amyotrophic lateral sclerosis. Most interestingly, thyroid stimulating hormone levels show an unexpected negative relation to age in patients with amyotrophic lateral sclerosis.},
}

@article {pmid42293321,
year = {2026},
author = {Ma, M and Zhao, B and Gao, N and Sun, X and Shao, K and Lin, P and Li, W and Zhao, Y and Yu, D and Yan, C and Liu, S and Yun, Y},
title = {Quantitative susceptibility mapping reveals widespread brain iron abnormalities in sporadic patients with early-stage amyotrophic lateral sclerosis.},
journal = {Brain communications},
volume = {8},
number = {3},
pages = {fcag190},
pmid = {42293321},
issn = {2632-1297},
abstract = {In the present study, using the novel quantitative susceptibility mapping technique, we aimed to systematically investigate brain iron alterations in a large group of sporadic early-stage amyotrophic lateral sclerosis patients and their correlation with clinical disability. In this study, amyotrophic lateral sclerosis patients at King's stage 1 were defined as early-stage amyotrophic lateral sclerosis patients, and 53 newly diagnosed early-stage amyotrophic lateral sclerosis patients and 50 healthy controls were included. Voxel-based whole-brain quantitative susceptibility mapping analysis was used to explore brain iron alterations. Voxel-based morphometry analysis was also performed. Longitudinal follow-up was performed in amyotrophic lateral sclerosis patients, and the follow-up progression rate was calculated. We found that, compared with healthy controls, early-stage amyotrophic lateral sclerosis patients presented significantly increased susceptibility values, mainly in the motor cortex, prefrontal cortex, hippocampus and cerebellar regions, while volumetric alterations were not detected. Moreover, motor and extra-motor cortex susceptibility values were significantly correlated with upper motor neuron scores and follow-up progression rate (r = 0.452-0.504, P < 0.01) in early-stage amyotrophic lateral sclerosis patients. We demonstrated a clear profile of early motor and extra-motor iron depositions and their important roles in early-stage amyotrophic lateral sclerosis patients. We suggest that quantitative susceptibility mapping is likely a promising neuroimaging approach for assessing early upper motor neuron damage and detecting early extra-motor alterations in amyotrophic lateral sclerosis patients.},
}

@article {pmid42281996,
year = {2026},
author = {Cooper-Knock, J and Bonsall, S and Kazu, R and King, M and Leung, D and Mahiddine, F and Highley, J and Strange, A and Chen, Y and Sassani, M and Eldahshoury, M and Boyne, J and Collins, M and Monte, E and Harvey, C and Gornall, S and Jangid, A and Treanor, C and Moll, T and van Dijk, C and Cabras, S and Urban, A and Bowden, K and Wareing, H and Huang, Y and Shaw, P and West, R and Kenna, K and Hornstein, E and Zhang, S and Zhou, J and Snyder, M},
title = {Single-nucleus multiomic atlas of ALS primary motor cortex nominates neuroprotective WDR49-expressing astrocytes.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-9853460/v1},
pmid = {42281996},
issn = {2693-5015},
abstract = {Amyotrophic lateral sclerosis (ALS) causes selective neurodegeneration in primary motor cortex, yet cell-type-specific molecular changes driving this vulnerability remain poorly understood. We present an integrated single-nucleus RNA- and ATAC-sequencing atlas of 778,330 nuclei from the primary motor cortex of 140 genetically characterised donors. ALS is associated with widespread transcriptional reprogramming driven by a common set of transcription factors (TFs) across multiple cell-types. Astrocytes harbour the most differentially expressed genes. Within astrocytes, a WDR49-expressing subpopulation is spatially associated with TDP-43 pathology, and genetic variants within WDR49 confer risk for both sporadic and monogenic autosomal dominant ALS. In patient-derived induced astrocytes, WDR49 protein abundance predicts the survival of co-cultured neurons. WDR49 localises to PML nuclear bodies, where it regulates astrocyte reactivity and secretion of EVs containing protein chaperones. Together, these in vivo and in vitro findings suggest that WDR49+ astrocytes mount a compensatory secretory response to extracellular protein aggregates, and that loss of this capacity lowers the threshold for ALS pathogenesis.},
}

@article {pmid42282536,
year = {2026},
author = {Cortez, JD and Avalos, JL},
title = {Heterologous iron-sulfur cluster biogenesis and delivery for cytosolic isobutanol and isopentanol production in Saccharomyces cerevisiae.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.05.29.728687},
pmid = {42282536},
issn = {2692-8205},
abstract = {Saccharomyces cerevisiae is an excellent microbial platform for sustainable production of next generation biofuels such as the branched chain higher alcohols (BCHAs) isobutanol and isopentanol. A cytosolic pathway for BCHA production is generated from expression of prokaryotic orthologs of branched-chain amino acid (BCAA) enzymes acetolactate synthase (ALS), mutant NADH-dependent ketol-acid reductoisomerase (KARI [P2D1-A1]), and dihydroxy-acid dehydratase (DHAD). The potential for this pathway has been hindered by the availability of iron-sulfur clusters, particularly the 2Fe-2S cluster, required for DHAD to function in the cytosol. ILV3 , the endogenous yeast DHAD located in the mitochondria, can be deleted to create a valine auxotroph. In this study we use bioinformatics, heterologous gene library synthesis, and a valine complementation assay to find prokaryotic iron-sulfur cluster biosynthetic gene clusters (BGC) and accessory genes that aid DHAD function in the yeast cytosol. This work presents, to our knowledge, the first functional BGC that enhances the cytosolic activity of prokaryotic DHADs in S. cerevisiae . The SUF BGC from Bacillus subtilis combined with a ferritin-like protein (FTNB) from Escherichia coli and the Lactococcus lactis DHAD enhanced the production of BCHAs. Combined expression gave an average isobutanol titer of 412mg/L, 1.8-fold greater than L. lactis DHAD expressed alone. This work establishes a blueprint for better biofuel production by improving iron-sulfur cluster dependent enzyme activity in the yeast cytosol.},
}

@article {pmid42282588,
year = {2026},
author = {Kochen, NN and Zafari, S and Renaud, A and Schneider, N and Vunnam, N and Liao, EE and Dutton, JR and Braun, AR and Sachs, JN},
title = {From anti-fungal to potential neurotherapeutic: Posaconazole as an effective inhibitor of cellular TDP-43 pathology.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.06.01.728552},
pmid = {42282588},
issn = {2692-8205},
abstract = {Recently, we showed that ketoconazole, a known anti-fungal inhibitor of CYP51, stabilized TAR DNA-binding protein 43 (TDP-43) native self-interactions, reduced TDP-43 pathology and rescued TDP-43-induced SREBP2 downregulation. Despite its promising effects, ketoconazole is not viable for repurposing for ALS due to liver toxicity side effects that occur when orally delivered. To address this, we tested the activities of seven additional known azole-based CYP51 inhibitors in order identify a viable alternative to ketoconazole. Using our established TDP-43 mislocalization and aggregation assay in HEK293T cells, we identified posaconazole, an FDA-approved, CNS-penetrant and orally delivered anti-fungal, as the strongest inhibitor of TDP-43 pathology. Posaconazole was able to reduce insoluble TDP-43 and restore SREBP2 levels, outperforming ketoconazole. Mechanism of action (MOA) experiments suggest posaconazole is able to outperform ketoconazole by inducing a significantly stronger activation of autophagy and upregulation of heat shock proteins known to clear TDP-43. Further MOA experiments show that the effects of posaconazole on TDP-43 are dependent on its known ability to lower cellular cholesterol levels. By correlating our experimental results on the eight CYP51 inhibitors tested, we show that predicted affinity towards human CYP51 strongly correlates with the inhibitors' ability to lower TDP-43 aggregation and mislocalization. Finally, we tested posaconazole in a low dose sodium arsenite ALS model in iPSC-derived motor neurons, showing that it is efficacious at inhibiting TDP-43 pathology in the nanomolar range. Altogether, these results support the repurposing of posaconazole for ALS/FTD as a means to prevent TDP-43 pathology.},
}

@article {pmid42274592,
year = {2026},
author = {Sgalletta, B and Agostini, F and Bisaglia, M},
title = {The Role of Iron in Neuronal Homeostasis: A Double-Edged Sword.},
journal = {Cells},
volume = {15},
number = {11},
pages = {},
pmid = {42274592},
issn = {2073-4409},
mesh = {Humans ; *Iron/metabolism ; *Homeostasis ; Animals ; *Neurons/metabolism ; Neurodegenerative Diseases/metabolism/pathology ; Neurogenesis ; Neurodevelopment ; Brain/metabolism ; },
abstract = {Iron is an essential micronutrient that plays a central role in numerous biological processes. Despite its relatively low abundance in the human body, iron is particularly critical for brain function. Systemic and cerebral iron homeostasis is tightly regulated through coordinated mechanisms involving absorption, transport, storage, and recycling. Within the brain, iron metabolism is further controlled by the blood-brain barrier and specialized neural cell populations, including neurons, astrocytes, oligodendrocytes, and microglia. Iron is indispensable for neurodevelopment, supporting neurogenesis, myelination, and neurotransmitter synthesis. However, both iron deficiency and iron overload have detrimental consequences. Early-life iron deficiency disrupts neural development and leads to long-lasting cognitive, motor, and behavioral impairments, whereas excessive iron accumulation promotes oxidative stress, ferroptosis, and neuroinflammation. These mechanisms have been described to contribute to the pathogenesis of major neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, neurodegeneration with brain iron accumulation, and amyotrophic lateral sclerosis. This review first outlines systemic and brain iron metabolism, highlighting how neural cells regulate homeostasis. Next, it examines iron's physiological roles, particularly in neurogenesis and neurodevelopment. Finally, it explores iron's involvement in neurodegenerative diseases, emphasizing neuroinflammation as a primary mechanism of iron toxicity.},
}

Humans
*Iron/metabolism
*Homeostasis
Animals
*Neurons/metabolism
Neurodegenerative Diseases/metabolism/pathology
Neurogenesis
Neurodevelopment
Brain/metabolism

@article {pmid42274906,
year = {2026},
author = {He, Y and Yi, T and Min, M and Xu, K and Lin, H and Xu, R and Deng, D and Xiao, X},
title = {Environmental Factors Drive Neurodegenerative Diseases Through Glutamate Excitotoxicity: A Convergent Mechanistic Pathway.},
journal = {Neuroscience bulletin},
volume = {},
number = {},
pages = {},
pmid = {42274906},
issn = {1995-8218},
abstract = {This review illustrates how environmental stressors disrupt glutamate homeostasis via specific mechanisms: lead-induced thiol modification, manganese mediated yin yang 1 (YY1)-histone deacetylases (HDAC) repression, PM2.5-triggered microglia-astrocyte crosstalk, and advanced glycation end products (AGEs)-receptor for advanced glycation end products (RAGE)-nuclear factor kappa-B (NF-κB) signaling from high-sugar diets. Together with genetic susceptibility and pigment epithelium-derived factor (PEDF), these factors impair astrocytic glutamate uptake, promoting synaptic glutamate accumulation. Subsequent N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor overactivation triggers calcium overload, mitochondrial dysfunction, oxidative stress, and neuroinflammation-termed "degenerative excitotoxicity". Excitotoxicity manifests in Alzheimer's disease (amyloid-beta-excitatory amino acid transporter 2 (EAAT2) interplay), Parkinson's disease (subthalamic nucleus-driven excitatory storm), and amyotrophic lateral sclerosis (astrocytic failure versus neuronal cell-autonomous mechanisms). Future interventions need multi-target strategies, emerging technologies, and lifestyle modifications. This convergent framework offers a unified understanding linking environmental exposure to neurodegeneration and charts a roadmap toward mechanism-based prevention and treatment.},
}

@article {pmid42274979,
year = {2026},
author = {Ojha, GJ and Talwar, T},
title = {Exploring the Role of Spirituality in Neuropalliative Care: An Integrative Review.},
journal = {Journal of religion and health},
volume = {},
number = {},
pages = {},
pmid = {42274979},
issn = {1573-6571},
abstract = {Neuropalliative care aims to address the physical, psychosocial and spiritual needs of persons with progressive and life-limiting neurological conditions, while spiritual care fosters hope and meaning in life. Progressive neurological disorders with an uncertain disease trajectory present a set of complex challenges that have far-reaching consequences on the patient's self-belief, questioning the very existence, self-identity, and belongingness. A typical neuropalliative care team consists of neurologists, nurses, psychologists, occupational therapists, and spiritual care providers. Previous research indicates that spiritual care improves coping and quality of life in persons with Parkinson's disease and Amyotrophic lateral sclerosis. This study aimed to explore how spiritual needs are addressed in the area of neuropalliative care, examining the theoretical frameworks and empirical studies that incorporate spirituality as a component of neuropalliative care. The databases PubMed, PsycINFO, Cochrane Library, Scopus and two peer-reviewed journals were searched using a strategy based on three sets of terms "spirituality," "progressive neurological conditions" and "neuropalliative care." Articles included were in the English language, and mentioned spirituality in the context of neuropalliative care or palliative care for neurological conditions. Initial screening yielded 744 articles, of which 29 were selected for synthesis. Results highlighted the various challenges in ascertaining and meeting the spiritual needs in neuropalliative care. The review concludes that palliative services should be initiated early following the diagnosis of a progressive neurological condition so that the patient and family have enough time to reflect, create memories, and prepare in advance for the inevitable through dignity and resilience.},
}

@article {pmid42275159,
year = {2026},
author = {Ito, D and Iida, M and Iguchi, Y and Hashizume, A and Yamada, S and Kishimoto, Y and Komori, S and Obara, K and Nishisaki, S and Yokoi, S and Shimamura, T and Takemoto, Y and Nakatochi, M and Akashi, T and Hinohara, K and Lee-Okada, HC and Okada, Y and Niwa, J and Sobue, G and Tanaka, S and Takashina, K and Yokomizo, T and Katsuno, M},
title = {Fatty acid amide hydrolase inhibition for treatment of amyotrophic lateral sclerosis.},
journal = {JCI insight},
volume = {},
number = {},
pages = {},
doi = {10.1172/jci.insight.198842},
pmid = {42275159},
issn = {2379-3708},
abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease caused by the selective loss of upper and lower motor neurons. There is a considerable variability in the disease progression of sporadic ALS, but the molecular basis for phenotypic heterogeneity remains largely unknown. ALS patients often manifest systemic metabolic abnormalities such as glucose intolerance and hypermetabolic state. We conducted reverse translational research to explore therapeutic targets in ALS based on the systemic metabolic alterations in patients and identified several metabolites associated with the disease progression, including metabolites involved in the expanded endocannabinoid system (ECS). In particular, the levels of N-acyl taurines (NATs) were correlated with the longitudinal change in the revised ALS functional rating scale and survival. Experiments with ALS cellular models, iPS cells derived from ALS patients and SOD1G93A transgenic mice revealed that PF-04457845, a fatty acid amide hydrolase inhibitor, upregulated the expanded ECS, particularly the levels of NATs and ameliorated motor neuron degeneration through the regulation of microglial environment, synapse plasticity, and neuronal development. These results collectively indicate that dysregulation of NATs is associated with ALS progression and PF-04457845 may represent a potential disease-modifying therapy for ALS.},
}

@article {pmid42276279,
year = {2026},
author = {Gurung, N and Choi, DY and Park, PH},
title = {Naringenin as a Multi-Target Neuroprotective Agent in Neurodegenerative Diseases.},
journal = {Neurochemistry international},
volume = {},
number = {},
pages = {106203},
doi = {10.1016/j.neuint.2026.106203},
pmid = {42276279},
issn = {1872-9754},
abstract = {Neurodegenerative diseases (ND) such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS) are characterized by progressive neuronal loss driven by complex and multifactorial pathogenic mechanisms. Naringenin (NAR), a citrus-derived flavanone, has attracted considerable interest as a neuroprotective molecule due to its pleiotropic pharmacological activities such as antioxidant, anti-inflammatory and ability to modulate multiple cellular targets. This review provides a comprehensive overview of NAR pharmacokinetic profile, mechanistic actions, and therapeutic potential across major ND. We highlight how NAR's multi-target effects-including redox homeostasis maintenance, suppression of neuroinflammation, protein aggregation inhibition, and modulation of signaling pathways-contribute to neuroprotection in various experimental models of AD, PD, HD, ALS, and MS. Preclinical studies demonstrate that NAR can ameliorate cognitive and motor deficits in toxin and transgenic models of neurodegeneration, attenuate pathological hallmarks such as amyloid-beta toxicity, dopaminergic neuronal loss, and neuroinflammation, and induce cytoprotective pathways including Nrf2-mediated antioxidant response and autophagy. However, NAR's clinical translation is challenged by poor bioavailability; thus, novel delivery systems are being explored to enhance brain uptake. NAR emerges as a promising multi-functional neuroprotective agent that can simultaneously target diverse pathogenic processes in ND. Further research including advanced formulation development and well-designed clinical trials is warranted to fully establish NAR's therapeutic efficacy and safety in humans.},
}

@article {pmid42276329,
year = {2026},
author = {Abzhanova, E and Kawae, Y and Mizuno, H and Umemoto, T and Ciftci, H and Tsuboi, M and Hirabayashi, Y and Mizuno, H},
title = {ALS-associated protein TDP-43 disturbs axonal projections in the somatosensory cortex.},
journal = {Neuroscience research},
volume = {},
number = {},
pages = {105079},
doi = {10.1016/j.neures.2026.105079},
pmid = {42276329},
issn = {1872-8111},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by loss of upper and lower motor neurons that gradually causes muscle weakness and paralysis, eventually resulting in death. While ALS was once believed to specifically target motor neurons, recent clinical studies have revealed sensory involvement. The pathological hallmark of ALS is TAR DNA-binding protein 43 (TDP-43) aggregation in cytoplasm, with increasing evidence of its presence in both motor and sensory neurons. However, sensory abnormalities remain poorly characterized. To address this research gap, we analyzed the effects of TDP-43 expression on layer 2/3 (L2/3) pyramidal neurons of the primary somatosensory cortex in mice projecting through corpus callosum. In utero electroporation (IUE) was performed to express GFP alone (control) or in combination with TDP-43. Compared with the control, mice co-expressing GFP and TDP-43 showed disturbed callosal axonal projections of L2/3 neurons. Mutant TDP-43 variants displayed a more pronounced phenotype, indicating pathogenic role during fetal cortical development. To distinguish developmental from maintenance effects, tamoxifen-inducible TDP-43 expression was used to initiate postnatal TDP-43 expression. Postnatal induction resulted in shorter axonal length and reduced branching rather than gross projections disturbance. Taken together, these results demonstrate that TDP-43 expression can disturb the integrity of axonal projections, such as callosal projections of L2/3 neurons in the somatosensory cortex.},
}

@article {pmid42276614,
year = {2026},
author = {Karthikeyan, K and Velmurugan, G and Upadhyay, R and Sevanan, M and Chinnathambi, S},
title = {Glutamate and glutamine metabolism in neurodegenerative diseases.},
journal = {International review of neurobiology},
volume = {186},
number = {},
pages = {1-24},
doi = {10.1016/bs.irn.2026.01.008},
pmid = {42276614},
issn = {2162-5514},
mesh = {Humans ; *Glutamic Acid/metabolism ; *Glutamine/metabolism ; *Neurodegenerative Diseases/metabolism/drug therapy ; Animals ; },
abstract = {Glutamate is known as the most important excitatory neurotransmitter in brain. Glutamate and glutamine recycling is very essential to maintain the nitrogen metabolism. Despite of its major functions, its dysregulation is a basic pathology which is common to neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), and Amyotrophic lateral sclerosis (ALS). Amyloid-β and Tau in AD disrupt glutamate uptake and the glutamate-glutamine cycle, accelerating synaptic failure, whereas loss of astrocytic EAAT2 in ALS generates unrelenting excitotoxicity and motor neuron demise. Toxic α-synuclein aggregation in PD exacerbates dopamine-glutamate imbalance through destabilizing corticostriatal transmission. This review explores on the key mechanisms by which glutamate impairment leads to the pathogenies of neurogenerative disorders and also about current medications like amantadine, memantine, and riluzole which are glutamate antagonists, are shown to partially alleviative but cannot halt the advancement of the disease. One of the potential targets for disease-modifying treatments could be the receptor modulation, astrocytic function, and elimination of excess glutamate.},
}

Humans
*Glutamic Acid/metabolism
*Glutamine/metabolism
*Neurodegenerative Diseases/metabolism/drug therapy
Animals

@article {pmid42276630,
year = {2026},
author = {McRae, M and Hart, L and Wolf, L},
title = {Accreditation as opportunity: Preparing future nursing leaders through faculty collaboration and succession planning.},
journal = {Journal of professional nursing : official journal of the American Association of Colleges of Nursing},
volume = {65},
number = {},
pages = {137-141},
doi = {10.1016/j.profnurs.2026.04.007},
pmid = {42276630},
issn = {1532-8481},
abstract = {Preparing for Commission on Collegiate Nursing Education (CCNE) accreditation requires extensive faculty engagement, yet the literature offers limited guidance on operational strategies to cultivate collaboration and mentorship during this process. This article describes the Keigwin School of Nursing's adaptation of Benner's novice to expert framework and Haverkamp et al.'s (2018) "map for accreditation" to design a collaborative approach for developing the self-study report and preparing for a site visit. Junior faculty were paired with experienced mentors in dyads, assigned to analyze key elements of the CCNE Standards, and reported findings back to cross-program Standard Teams. This structure fostered faculty development, enhanced understanding of accreditation processes, and promoted succession planning. Standardized meeting minutes, end-of-year committee reports, and the use of stoplight tracking tools provided systematic evidence of continuous quality improvement. Faculty-wide meetings and individualized support further strengthened readiness and confidence for site visit engagement. The outcome was full faculty participation, successful alignment of undergraduate and graduate program reaccreditation cycles, and no accreditation compliance concerns reported for any program. These results underscore the value of mentorship, collaboration, and succession planning in accreditation preparation and highlight the potential to address national challenges in faculty shortages, destabilization of higher education, and the need for a unified nursing faculty voice in academic advocacy.},
}

@article {pmid42276908,
year = {2026},
author = {Covas Moschovas, M and Falagario, U and Pellegrino, F and Wiklund, P and Patel, V},
title = {Reply to Alexander Light, Max Peters, Manit Arya, et al's Salvage Focal Therapy vs Radical Prostatectomy for Localized Radiorecurrent Prostate Cancer. JAMA Oncol 2026;12:364-73. https://doi.org/10.1001/jamaoncol.2025.6448.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2026.05.031},
pmid = {42276908},
issn = {1873-7560},
}

@article {pmid42279231,
year = {2026},
author = {Mesches, MH and Granholm, AC and Paredes, D and Mesches, K and Oguma, Y and Dezawa, M},
title = {Stem Cell Therapy for Parkinson's Disease: A Mechanistically Distinct Role for Muse Cells.},
journal = {Journal of clinical medicine},
volume = {15},
number = {11},
pages = {},
doi = {10.3390/jcm15114370},
pmid = {42279231},
issn = {2077-0383},
abstract = {Cell replacement therapy is a promising investigational approach for Parkinson's disease (PD), a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra. Although current PD therapies provide symptomatic relief, none halt or reverse disease progression. Early transplantation studies using fetal dopaminergic neurons provided proof of concept for PD cell replacement, with recent efforts focusing on pluripotent stem cell-derived dopaminergic progenitors that are now entering clinical testing. These strategies face challenges, however, including immune compatibility, tumorigenic risk, and the need for controlled differentiation and functional integration. Multi-lineage differentiating stress-enduring (Muse) cells are endogenous, non-tumorigenic pluripotent-like stem cells that home to sites of tissue injury and differentiate in response to the host microenvironment. A targeted literature search of PubMed and Scopus, however, did not identify prior reviews specifically addressing Muse cells in the context of PD, highlighting a gap in the literature. Here, we examine current limitations of established cell-replacement approaches and consider whether Muse cells may represent a mechanistically distinct cell source. Early clinical studies of Muse cell therapy in stroke and amyotrophic lateral sclerosis suggest an encouraging safety profile and preliminary signals of potential therapeutic benefit, although these findings are based on small, early-stage trials and require confirmation. The evidence supporting Muse cell therapy in PD is currently limited to a single preclinical animal study, supported by mechanistic in vitro findings and indirect evidence from other neurologic disease models; therefore, its relevance to PD remains to be established, and current evidence is insufficient to support conclusions regarding clinical efficacy. Together, these observations provide a rationale for further targeted preclinical investigation and support the systematic evaluation of Muse cells as a mechanistically distinct candidate for regenerative therapy in PD.},
}

@article {pmid42280649,
year = {2026},
author = {Liu, Q and Zhang, R and Sun, L and Lu, X and Xu, G and Tong, H and Zhang, B and Liu, X and Du, S},
title = {Mechanism of Echinochloa crus-galli Resistance to the ALS-Inhibiting Herbicide Pyrazosulfuron-ethyl in China.},
journal = {Plants (Basel, Switzerland)},
volume = {15},
number = {11},
pages = {},
doi = {10.3390/plants15111611},
pmid = {42280649},
issn = {2223-7747},
abstract = {Rice (Oryza sativa L.) is a staple food crop, feeding more than 3.5 billion people. With the increasing demand for food in the 21st century, weed infestation poses the most significant biotic threat to global food security, and herbicides remain the most effective and economic way to manage it in field. However, weeds can rapidly adapt under herbicide selection pressure due to their high competitiveness, rapid growth, and reproductive capacity. Hence, we collected Echinochloa crus-galli populations from Heilongjiang and Hebei provinces in China and investigated their resistance mechanisms to pyrazosulfuron-ethyl (PSE), a sulfonylurea herbicide that inhibits acetolactate synthase (ALS). Dose-response experiments confirm that the resistant (R) population exhibits 52.9-fold resistance to PSE compared with the susceptible (S) population. Inhibitor bioassays with malathion and NBD-Cl, together with ALS activity assays, ALS gene sequencing, and molecular docking, collectively suggest that resistance is strongly associated with the ALS Trp-574-Leu target-site substitution, with a possible additional contribution from enhanced herbicide metabolism. However, because the S and R populations originate from geographically distinct locations, some of the observed physiological and molecular differences may also reflect inherent population variation. Specifically, the ALS W574L substitution is predicted to reduce key interactions between ALS and PSE. This study provides valuable evidence for the risk of PSE resistance evolution in E. crus-galli and elucidates the molecular mechanism conferring resistance to ALS inhibitors.},
}

@article {pmid42281786,
year = {2026},
author = {Tsai, AC},
title = {Defining a shift estimand on forgivingness without domesticating forgiveness: Comment on Cowden et al.},
journal = {SSM. Mental health},
volume = {9},
number = {},
pages = {},
pmid = {42281786},
issn = {2666-5603},
abstract = {This commentary responds to Cowden et al.'s (2026) careful epidemiologic study of the population-wide changes in well-being that might follow from two explicitly defined "shift" scenarios applied to a three-item forgivingness measure. I value the paper's candor about its counterfactual aim: it is not asking whether forgiveness is good in the abstract, but what could plausibly happen if the distribution of measured forgivingness were moved in specified ways. I argue that Cowden et al.'s (2026) methodological clarity surfaces what remains ethically and theologically decisive. In Christian thought, forgiveness is not simply an emotion-regulation technique or a general prosocial disposition; it is a demanding practice formed by grace and ordered toward truth, justice, mercy, and (where possible) repair. When we compress that "thick" practice into a several-item scale for administration in population surveys, we risk treating qualitatively different moral realities as interchangeable. This thinning is subject to the same critique when applied to intervention: a shift estimand tells us what might follow from a distributional change but not how to bring it about; and different ways of cultivating forgiveness may not be morally or practically interchangeable, even if they produce the same numerical shift. While the rigor Cowden et al. (2026) bring to this literature is commendable, the remaining challenge is to connect distributional shifts in forgivingness scores to the concrete practices and communal disciplines that form forgiveness as a moral reality rather than a psychological technique.},
}

@article {pmid42265995,
year = {2026},
author = {Ozlu, C and Schwaede, A and McGowan, B and Zhang, L and Finch, M and Wolfe, LF and Ajroud-Driss, S and Franz, C and Kuntz, N},
title = {Two Patients With Juvenile-Onset, Rapidly Progressive Amyotrophic Lateral Sclerosis Associated With an SOD1 Variant (p.Asp125Gly) With Incomplete Penetrance.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70314},
pmid = {42265995},
issn = {1097-4598},
abstract = {INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) patients are rarely encountered before age 25 years, often associated with genetic variants. SOD1 gene variants are well-known to account for a subset of adult-onset ALS but have only been described in a handful of early onset patients. Variants affecting residue 125 in SOD1 have been described in adult-onset ALS patients with a rapid progression. Here we report two such patients.

METHODS: The clinical, genetic, and electrodiagnostic findings of two unrelated adolescents with juvenile onset rapidly progressive SOD1-ALS are described.

RESULTS: Patient 1 presented at 16 and patient 2 at 15 years-of-age with lower limb onset of weakness, lower motor neuron examination findings, and rapid progression over months to involve all body regions. Both patients underwent extensive laboratory, electrophysiologic, and radiologic testing ruling out any alternate etiologies. For both patients, whole-exome sequencing revealed the pathogenic variant p.Asp125Gly in the SOD1 gene inherited from asymptomatic fathers.

DISCUSSION: These two patients expand the phenotypic spectrum of SOD1-ALS, demonstrating a rapidly progressive juvenile lower limb onset phenotype associated with the p.Asp125Gly variant inherited with incomplete penetrance. Recognition and further characterization of juvenile SOD1-ALS are important in light of the advances in targeted therapies.},
}

@article {pmid42266360,
year = {2026},
author = {Ilczak, T and Ćwiertnia, M and Sumera, K and Babik, P and Białoń, P and Dutka, M and Malinowska-Lipień, I and Augustyn, M and Majewski, M and Lis, A and Leszczyński, P and Stasicki, A and Abramczyk, P and Kukla, P and Pollok-Waksmańska, W and Trojak-Piętka, J and Kawecki, M},
title = {Nontechnical Skills (NTS) and the Quality of Conducting Prehospital Advanced Cardiopulmonary Resuscitation Among Paramedics.},
journal = {Emergency medicine international},
volume = {2026},
number = {},
pages = {2207053},
pmid = {42266360},
issn = {2090-2840},
abstract = {INTRODUCTION: It is common knowledge that the correct application of cardiopulmonary resuscitation (CPR) requires technical skills such as defibrillation, high-quality chest compressions, and efficient airway management. However, scientific research is increasingly underlining the role of appropriate training in nontechnical skills (NTS).

RESEARCH AIM: This exploratory study aimed to assess the relationship between NTS and the quality of advanced CPR among paramedics.

MATERIALS AND METHODS: The research involved 51 paramedics randomly assigned to 17 three-person teams. Each team participated in a 15-min cardiac arrest scenario. After the first session, the teams were divided into two groups: the intervention group (Group 1), which underwent specialized NTS training, and the control group (Group 2), which did not receive the initial training. Directly after the training phase, all teams from both groups carried out a second attempt during a simulated sudden cardiac arrest (SCA) scenario identical to the first one.

RESULTS: The lowest CPR result in the intervention group (Group 1) was Min = -3.00, and the highest Max = 13.00, while in the control group (Group 2), the lowest result was Min = -42.00, and the highest Max = 8.00 (p < 0.05). In Group 1, a statistically significant correlation (p < 0.05) was noted between the change in the NTS score and the change in the CPR result. A higher NTS score was accompanied by a higher CPR score.

CONCLUSIONS: A short NTS training session was associated with improved NTS application by paramedic resuscitation teams. Furthermore, higher chest compression quality positively correlated with NTS proficiency.},
}

@article {pmid42267592,
year = {2026},
author = {Malik, MMUD},
title = {Moral Injury, Peer Support and Allied Health Integration: Three Extensions to Gilmore et al.'s Account of Mental Health Crisis Care in Homelessness.},
journal = {Journal of psychiatric and mental health nursing},
volume = {},
number = {},
pages = {},
doi = {10.1111/jpm.70156},
pmid = {42267592},
issn = {1365-2850},
}

@article {pmid42267597,
year = {2026},
author = {Held-Bradford, EC and DeMarco, E and Zocher, S and Weaver, K and Forsman, K and Hayat, G and Subramaniam, DS and Doherty, M},
title = {Functional Motor Change Across Time and Phenotypes in Patients With Amyotrophic Lateral Sclerosis: A Descriptive Study.},
journal = {Neurorehabilitation and neural repair},
volume = {},
number = {},
pages = {15459683261445435},
doi = {10.1177/15459683261445435},
pmid = {42267597},
issn = {1552-6844},
abstract = {PURPOSE: Progressive disability occurs in persons with amyotrophic lateral sclerosis (pALS), but change over time across phenotypes remains understudied, limiting clinical decision-making. This descriptive study describes functional motor change with detailed measures across ALS phenotypes to enhance clinical decision making.

MATERIALS AND METHODS: Electronic health record data from an interdisciplinary ALS clinic (n = 109 pALS, 2018-2022) including demographics, disability (ALS Functional Rating Scale-[ALSFRS-R]), and functional motor scores (10 m Walk, Handheld dynamometry [grip and ankle]) was utilized. Phenotype groups were defined by site of onset (bulbar, limb onset; upper limb or lower limb). Analysis was conducted using R and included changes scores and measures of central tendency in 3-month intervals.

RESULTS: PALS included n = 43 bulbar, n = 32 upper limb, n = 34 lower limb onset, age 65, 60 to 71 (median, interquartile range). ALFSRS-R decline was greatest in bulbar, and similar in upper and lower limb. Patterns of change within motor scores suggest greatest loss of grip strength in bulbar and upper limb, ankle strength in upper limb, walking speed in lower limb, and preservation of community ambulation in upper limb.

CONCLUSION: While ALSFRS-R scores were similar in upper and lower limb, detailed functional motor measures indicated differences in groups. These patterns provide insight to guide clinical decision making and future research to enhance care in pALS.},
}

@article {pmid42267908,
year = {2026},
author = {Donati Della Lunga, I and Cerutti, L and Barabino, V and Figus, GG and Callegari, F and Oneto, L and Tedesco, M and Bacchetti, F and Milanese, M and Massobrio, P and Brofiga, M},
title = {Developmental circuit instability in amyotrophic lateral sclerosis: from hyperexcitability to network collapse.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag185},
pmid = {42267908},
issn = {1460-2156},
abstract = {Amyotrophic lateral sclerosis (ALS) is traditionally viewed as a late-onset motor neuron disease, yet how cortical dysfunction originates and contributes to pathogenesis remains unresolved. In this study, we reconstruct the developmental trajectory of cultured cortical networks derived from SOD1G93A mouse embryos using a multimodal approach, by combining morphometric, electrophysiological, pharmacological, molecular, computational, and machine-learning techniques. We prove that ALS neurons fail to acquire mature polarization and connectivity, displaying a transient phase of hyperexcitability that precedes a progressive collapse of network organization. Astrocytic dysfunction emerges early and impairs synchronization, establishing a causal link between glial dysfunction and neuronal instability. The analysis of synaptic transmission reveals an excitatory bias followed by maladaptive inhibitory recruitment and GABA/glutamate co-release, causing fragmented and inefficient network topologies. Finally, in silico modelling identified deficient intrinsic adaptation as a key driver of hyperexcitability. Together, our findings position ALS as a developmentally rooted disorder of cultured cortical network homeostasis, driven by glial, synaptic, and intrinsic adaptation failures. By demonstrating that cortical dysfunction is embedded before degeneration, this work provides a unifying framework connecting early network instability to disease progression and establishes electrophysiological network signatures, detected by machine learning classifiers, as candidate biomarkers for early diagnosis and therapeutic screening.},
}

@article {pmid42268433,
year = {2026},
author = {Sytwu, HP and Jih, KY and Tsai, YS and Fang, SY and Liao, YC and Lee, YC},
title = {FUS-associated ALS in Taiwan: genetic spectrum, clinical features, and a founder haplotype of p.H517D.},
journal = {Journal of neurology},
volume = {273},
number = {7},
pages = {},
pmid = {42268433},
issn = {1432-1459},
support = {112-2314-B-075-034-MY3//National Science and Technology Council/ ; 114-2314-B-075-021-MY3//National Science and Technology Council/ ; 113-2314-B-075-018-MY3//National Science and Technology Council/ ; },
abstract = {OBJECTIVE: To characterize the genetic spectrum and clinical features of FUS-associated amyotrophic lateral sclerosis (ALS) in a Taiwanese cohort and to investigate whether the recurrent p.H517D variant represents a founder mutation.

METHODS: All coding exons and flanking intronic regions of FUS were analyzed by Sanger sequencing in 650 unrelated Taiwanese patients with ALS. Clinical characteristics of patients carrying FUS variants were evaluated. Haplotype analysis using polymorphic microsatellite markers flanking FUS was performed to assess a potential founder effect of the p.H517D variant.

RESULTS: Eight distinct heterozygous pathogenic FUS variants were identified in 11 probands and five affected relatives, including six missense and two frameshift variants. The most frequent variant was p.H517D, detected in four probands. A novel frameshift variant, p.G499Vfs*30, was identified as a de novo mutation in a juvenile-onset ALS patient. Compared with the non FUS-associated ALS cohort, patients with FUS-associated ALS had a significantly younger mean age at onset (40.1 vs 56.6 years) and more frequent bulbar onset (50% vs 19%). Haplotype analysis suggested a common founder for the p.H517D variant.

CONCLUSIONS: FUS mutations accounted for 1.7% of ALS cases in this Taiwanese cohort. The recurrent p.H517D variant appears to represent a population-specific founder mutation. Patients with FUS variants presented with earlier disease onset and heterogeneous clinical phenotypes, and de novo variants contributed to juvenile-onset disease.},
}

@article {pmid42268660,
year = {2026},
author = {Roy, É and Blais, M and Dion, P and Rouleau, GA and Dupré, N and Picher-Martel, V},
title = {Oligogenic variants in NEK1 and ATXN2 in amyotrophic lateral sclerosis: report of two cases and review of the literature.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/21678421.2026.2685158},
pmid = {42268660},
issn = {2167-9223},
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that affects the upper and lower motor neurons and leads to progressive paralysis. More than 40 genes have been implicated in familial ALS, which represents about 10% of ALS cases. Some genes, including C9orf72, SOD1, FUS and TARDBP are undoubtedly considered causative, but many others have uncertain pathogenicity and low penetrance. Here, we described the cases of two siblings affected by ALS and carrying both an ATXN2 heterozygous 32 CAG trinucleotide repeat expansion and a novel NEK1 heterozygous c.1674_1677dup. The segregation of both variants in this large family with thirteen siblings may support a role for these variants as susceptibility alleles within an oligogenic model. Our review of the literature suggests that NEK1 variants are frequently found in combination with other variants and repeats expansion in the ATXN2 gene appears to be more associated with monogenic ALS, but also frequently combined with C9orf72 repeat expansion.},
}

@article {pmid42269975,
year = {2026},
author = {Ma, M and Cui, B and Sun, X and Liu, S and Shao, K and Liu, F and Lin, P and Li, W and Zhao, Y and Yu, D and Lou, J and Yun, Y},
title = {Progressive choroid plexus enlargement across disease stages in patients with sporadic amyotrophic lateral sclerosis.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107481},
doi = {10.1016/j.nbd.2026.107481},
pmid = {42269975},
issn = {1095-953X},
abstract = {BACKGROUND: The choroid plexus (CP), a key structure involved in cerebrospinal fluid homeostasis and glymphatic function, is increasingly recognized as an interface for neuroimmune communication. Recent studies have identified CP abnormalities as potential neuroimaging markers in several neurodegenerative disorders, including sporadic amyotrophic lateral sclerosis (sALS). However, whether CP enlargement occurs early and progresses across clinical stages or over time in patients with sALS remains unclear. Given the role of the CP in peripheral-central nervous system immune crosstalk, the association between neuroinflammation and CP abnormalities in sALS also requires clarification. In this prospective study, we used structural MRI to examine cross-sectional and longitudinal CP volume changes in patients with sALS and to evaluate their associations with CSF inflammatory markers.

METHODS: This prospective study included 161 newly diagnosed patients with sALS who underwent genetic testing and structural MRI, and 64 healthy controls (HCs) who underwent structural MRI. Disease stage in patients with sALS was assessed using the King's staging system. Longitudinal MRI was performed in a subset of 42 patients, of whom 38 also underwent baseline CSF inflammatory protein assessment.

RESULTS: Compared with HCs, patients with sALS at all King's stages showed significantly larger CP volumes after Bonferroni correction (all p < 0.05). CP volumes were significantly greater in patients at King's stage 3 than in those at King's stage 1 or stage 2 after Bonferroni correction (all p < 0.05). In the longitudinal subgroup, CP volume increased significantly from baseline to follow-up. Multivariable analysis showed that higher CSF CHIT1 and IL-6 levels were independently associated with larger CP volume in patients with sALS (β = 0.348-0.456; p < 0.01).

CONCLUSIONS: Our findings provide evidence that CP enlargement occurs early and progresses across disease stages and over time in patients with sALS. Higher CSF CHIT1 and IL-6 levels were associated with larger CP volume, supporting a potential link between neuroinflammation and CP abnormalities in sALS. These findings support CP enlargement as a promising neuroimaging marker for monitoring disease progression and neuroinflammatory processes in patients with sALS.},
}

@article {pmid42270846,
year = {2026},
author = {Wood, H and Hamdi, N},
title = {Advancing amyotrophic lateral sclerosis research in Egypt.},
journal = {Nature reviews. Neurology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41582-026-01230-x},
pmid = {42270846},
issn = {1759-4766},
}

@article {pmid42271582,
year = {2026},
author = {Ito, M},
title = {[Re-evaluating ALS Medical Care in Japan: An International Comparison of Japan, Europe, the United States, and Canada-Insights from Mechanical Ventilation, Support for Social Participation, End-of-Life Care Options, Approved Drugs, and Precision Medicine].},
journal = {Brain and nerve = Shinkei kenkyu no shinpo},
volume = {78},
number = {6},
pages = {654-657},
doi = {10.11477/mf.188160960780060654},
pmid = {42271582},
issn = {1881-6096},
abstract = {Amyotrophic lateral sclerosis (ALS) care in Japan should be re-evaluated not simply as a matter of clinical choice but as a function of the public support system structure. In Japan, care is distinguished by a publicly funded model that supports home-based living and social participation following tracheostomy invasive ventilation. In contrast, Europe reflects a model centered on non-invasive ventilation and palliative care, and the United States reflects a system in which precision therapies are approved earlier but access remains highly unequal. Further, Canada reflects a model integrating multidisciplinary ALS clinics with Medical Assistance in Dying within a shared policy framework. These differences extend beyond treatment preferences and instead reflect broader social, institutional, and ethical configurations that shape the future of individuals with ALS. As access to emerging disease-modifying therapies increasingly depends on genetic testing, the central challenge in ALS care is shifting from end-of-life decision-making to the equitable distribution of precision medicine. Comparative reappraisal of national care models is therefore critical for understanding ALS not only as a neurological disease but also as a condition shaped by welfare systems, care infrastructure, and policy design.},
}

@article {pmid42271589,
year = {2026},
author = {Kunieda, K},
title = {[Clinical Management of Dysphagia and Nutritional Disorders in Neurodegenerative Diseases].},
journal = {Brain and nerve = Shinkei kenkyu no shinpo},
volume = {78},
number = {6},
pages = {695-700},
doi = {10.11477/mf.188160960780060695},
pmid = {42271589},
issn = {1881-6096},
abstract = {Dysphagia is common in patients with neuro degenerative diseases. It is associated with aspiration pneumonia, malnutrition, and reduced quality of life. Swallowing assessment should incorporate therapeutic perspectives, including the use of compensatory strategies. In conditions such as amyotrophic lateral sclerosis, weight loss is associated with a poor prognosis, and nutritional therapy may function as a disease-modifying intervention. Clinical ethical issues may arise, including decisions regarding gastrostomy or care for patients with impaired decision-making capacity. A multidisciplinary team approach is essential for managing dysphagia and nutritional problems in these patients.},
}

@article {pmid42272352,
year = {2026},
author = {Lizio, A and Farè, M and Gerardi, F and Collesi, M and Sansone, VA and Lunetta, C and Diamanti, L and Cerri, F},
title = {Impact of treatment burden on medication adherence and quality of life in amyotrophic lateral sclerosis: a prospective multicentre study.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/21678421.2026.2683691},
pmid = {42272352},
issn = {2167-9223},
abstract = {BACKGROUND: Patients with amyotrophic lateral sclerosis (ALS) face substantial barriers to medication adherence as disease progression necessitates complex drug formulation adjustments, such as crushing tablets, mixing with liquids, or delivering via feeding tubes. These modifications may not only increase the time and effort required but could also impact drug efficacy and safety.

OBJECTIVE: To evaluate the prevalence and the impact of treatment burden on medication adherence and patient-reported quality of life (QoL) in ALS.

METHODS: This prospective multicenter study enrolled ALS patients across three Italian reference centers, with assessments at baseline, 6, and 12 months. Key measures included the Multimorbidity Treatment Burden Questionnaire (MTBQ), ALSFRS-R, DYALS (dysphagia), Morisky Medication Adherence Scale, SSS-8 (somatic symptoms), INQoL (QoL), SWAMECO (swallowing/medication difficulties), alongside comorbidities and current therapies. Associations between treatment burden, QoL, and adherence were analyzed using multivariable models.

RESULTS: A total of 114 consecutive ALS patients were enrolled. Clinically significant treatment burden was observed in 69.3% of patients, with over half reporting moderate-to-high levels according to the MTBQ classification. Elevated burden was independently related to greater somatic symptom severity and formulation modification needs. Moreover, higher burden associated with poorer QoL and diminished adherence after confounder adjustment. Longitudinally, patients experiencing worsening burden over 1 year showed accelerated QoL decline compared to those remaining stable, though adherence trajectories were unaffected.

CONCLUSION: Treatment burden, particularly driven by drug formulation complexities and somatic symptoms, emerges as a pivotal, modifiable determinant of adherence and QoL in ALS. Targeted interventions to alleviate modifiable burden components hold promise for optimizing clinical outcomes and enhancing patient-centred care.},
}

@article {pmid42272365,
year = {2025},
author = {Mishra, V and Shekhar, S and Bisht, S and Chatterjee, R and Pandey, L and Pandey, A},
title = {Incidental Radiation Exposure to the Internal Mammary Lymph Nodes in Breast Cancer Patients Undergoing Intensity-Modulated Radiation Therapy: A Retrospective Analysis.},
journal = {The Gulf journal of oncology},
volume = {1},
number = {49},
pages = {16-21},
pmid = {42272365},
issn = {2521-3881},
mesh = {Humans ; Female ; *Radiotherapy, Intensity-Modulated/methods/adverse effects ; Retrospective Studies ; Middle Aged ; Adult ; *Breast Neoplasms/radiotherapy/pathology ; *Lymph Nodes/radiation effects/pathology ; *Radiation Exposure ; Radiotherapy Planning, Computer-Assisted/methods ; Radiotherapy Dosage ; },
abstract = {BACKGROUND: Breast cancer (BC) remains the most common malignancy among Indian women, with Stage III being the most frequent at diagnosis. While radiation therapy (RT) plays a pivotal role in the adjuvant treatment of breast cancer, the inclusion of internal mammary lymph nodes (IMLNs) in the radiation field remains controversial due to potential cardiopulmonary toxicity. However, the extent of incidental radiation to the IMLNs, especially with forward planning intensity-modulated radiation therapy (IMRT), remains under-explored.

OBJECTIVE: This study aimed to evaluate the incidental radiation dose received by the IMLNs in patients with leftsided breast cancer treated with forward planning IMRT.

MATERIALS AND METHODS: A total of 36 left-sided breast cancer patients, aged 35-60 years, who underwent modified radical mastectomy followed by adjuvant RT using IMRT, were retrospectively analyzed. CT-based planning and contouring were performed according to RTOG guidelines, with IMLNs contoured retrospectively using Jetwa et al.'s method. Dosimetric parameters for the planning target volume (PTV) and IMLNs were extracted and analyzed using dose-volume histograms. Statistical comparisons were made using the dependent Student's t-test.

RESULTS: The PTV received effective radiation coverage with a mean D95 of 38.47 Gy and a mean Dmean of 40.10 Gy. The IMLNs, although not directly targeted, received significant incidental radiation, with a mean D95 of 8.49 Gy, D50 of 21.59 Gy, and Dmean of 21.40 Gy. The maximum dose to the IMLNs (Dmax) reached 38.14 Gy. Comparative analysis revealed statistically significant differences in both Dmax and Dmean between PTV and IMLNs (p = 0.004 and p < 0.001, respectively).

CONCLUSION: Forward planning IMRT provides substantial incidental radiation exposure to the IMLNs, which may have therapeutic implications in reducing recurrence risk. However, this exposure also necessitates careful consideration of potential long-term toxicities to adjacent organs. Further prospective studies are warranted to evaluate the clinical outcomes associated with incidental IMLN irradiation.},
}

Humans
Female
*Radiotherapy, Intensity-Modulated/methods/adverse effects
Retrospective Studies
Middle Aged
Adult
*Breast Neoplasms/radiotherapy/pathology
*Lymph Nodes/radiation effects/pathology
*Radiation Exposure
Radiotherapy Planning, Computer-Assisted/methods
Radiotherapy Dosage

@article {pmid42274555,
year = {2026},
author = {Khan, MS and Zafar, I and Noman, M and Yang, G and Kang, KS and Bopassa, JC},
title = {Polypharmacology of Pathway Crosstalk in Neurodegenerative Diseases: Chemical Modulation of Interconnected Signaling Networks.},
journal = {Cells},
volume = {15},
number = {11},
pages = {},
pmid = {42274555},
issn = {2073-4409},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology ; *Signal Transduction/drug effects ; *Polypharmacology ; Animals ; Oxidative Stress ; Mitochondria/metabolism ; },
abstract = {Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), arise from highly interconnected molecular and cellular abnormalities that progressively lead to neuronal dysfunction, synaptic failure, and cell death. This review provides a unified framework to understand the interrelated molecular mechanisms driving these diseases, with a focus on identifying key disease-specific intervention nodes. Core contributors include oxidative stress, mitochondrial dysfunction, protein aggregation, neuroinflammation, and emerging roles of peroxisomal dysfunction in redox imbalance, lipid dysregulation, and inflammatory amplification. Single-target therapies often show limited efficacy due to the complex, interconnected nature of these pathways. In contrast, polypharmacology, which targets multiple disease-relevant mechanisms simultaneously, offers a more promising therapeutic strategy. This review critically examines how pathway crosstalk drives neurodegenerative progression, with particular emphasis on mitochondrial-ROS-inflammatory signaling, aggregation-proteostasis failure, synaptic-neuroimmune dysfunction, and gut-brain communication. It evaluates various multi-node intervention strategies, including multi-target-directed ligands (MTDLs), molecular hybrids, natural products, drug repurposing, and nanocarrier-based delivery systems. Advances in network pharmacology, artificial intelligence (AI), bioinformatics, and multi-omics have enhanced the identification of actionable therapeutic nodes, candidate compounds, and brain-targeted delivery platforms. Notably, the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathways-play distinct roles in neuroinflammation, amplifying neuronal damage by releasing inflammatory cytokines and inducing mitochondrial dysfunction. However, successful translation into clinical practice remains constrained by challenges such as blood-brain barrier penetration, patient heterogeneity, and biomarker limitations. The review advocates for a shift towards mechanism-informed, patient-stratified polypharmacological strategies to better address the network pathology of neurodegeneration, despite significant translational hurdles.},
}

Humans
*Neurodegenerative Diseases/drug therapy/metabolism/pathology
*Signal Transduction/drug effects
*Polypharmacology
Animals
Oxidative Stress
Mitochondria/metabolism

@article {pmid42274577,
year = {2026},
author = {Schuldt, ON and Leitch, SR and Jones, LK and Buckley, PR and Morrison, BE},
title = {Neuroinflammatory Remodeling by Type 2 Immune Pathways Links Allergic Signaling to Neurodegenerative Disease.},
journal = {Cells},
volume = {15},
number = {11},
pages = {},
pmid = {42274577},
issn = {2073-4409},
support = {R15HL165397//National Heart Lung and Blood Institute/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/immunology/pathology ; Animals ; *Signal Transduction/immunology ; *Hypersensitivity/immunology ; *Neuroinflammatory Diseases/immunology ; },
abstract = {The hallmarks of allergic diseases are Type 2 immunity, including IL-4 and IL-13 production, IgE antibody generation, mast cell and basophil activation, histamine release, and eosinophil activation. There are many routes by which such mediators can influence CNS biology, including cytokine entry or signaling via brain barrier receptors; leukocyte trafficking across activated barriers; cytokine signaling via circumventricular organ sites or dural immune compartments; vagus nerve afferent signaling; mast cell degranulation; and histamine neuromodulation. Neuroinflammation is a common hallmark of many neurodegenerative diseases, but whether and to what degree allergic/type 2 immune biology may be involved depends on the specific disease stage and pathology. Here, we assess studies connecting the roles of IL-4/IL-13 signaling, IgE/mast cell activation, eosinophil-attractive chemokines, and histamines in Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, dementia with Lewy bodies, Huntington's disease, prion disease, and tauopathy/atypical parkinsonism. Mechanisms appear most clear in the case of Parkinson's disease, where epidemiology suggests an important role in dementia/Alzheimer's disease, while for other neurodegenerative conditions the evidence is less compelling and may be either mechanistic or modulatory. Confounding issues include sex differences, drug exposures, comorbid conditions, socioeconomic factors, and coexisting inflammatory diseases. Finally, we suggest a strategy based on longitudinal immune phenotyping, CNS biomarkers, and pathway manipulation to assess the relationship between allergic immune signaling and neurodegeneration.},
}

Humans
*Neurodegenerative Diseases/immunology/pathology
Animals
*Signal Transduction/immunology
*Hypersensitivity/immunology
*Neuroinflammatory Diseases/immunology

@article {pmid42261159,
year = {2026},
author = {Shirbhate, E and Singh, V and Mishra, OK and Koch, B and Tiwari, AK and Yasin, HKA and Rajak, H},
title = {The Pivotal Role of HDAC6 in Amyotrophic Lateral Sclerosis: Neuroprotective Protagonist or Degenerative Adversary?.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X462214260429080002},
pmid = {42261159},
issn = {1875-6190},
abstract = {The review specifically examines the pivotal role of HDAC6 in the pathophysiological pathway of Amyotrophic Lateral Sclerosis (ALS), an escalating neurodegenerative ailment marked by the discerning damage to motor neurons. Several lines of evidence implicate inadequate proteostasis in significantly influencing neuronal degeneration. The accumulation of misfolded proteins and proteotoxicity are highlighted as significant factors in ALS pathophysiology. Key pathological hallmarks include ubiquitin-positive inclusions, disrupted RNA metabolism, cytoskeletal perturbations, and compromised axonal transport systems. HDAC6 dysregulation disrupts axonal transport, impairing mitochondrial function and increasing oxidative stress, leading to rapid motor neuron damage and cell death. The enzyme's aberrant deacetylation of α-tubulin destabilizes microtubules and impairs intracellular trafficking. Despite HDAC6's participation in these unfavorable processes, it also exerts neuroprotective properties. It deacetylates tubulin, promoting efficient axonal transport and autophagic clearance. HDAC6 helps form aggresomes and stress granules, which are essential for cellular defence against proteotoxic stress. Through its zinc finger ubiquitin-binding domain, HDAC6 interacts with polyubiquitinated proteins, facilitating their autophagic degradation. HDAC6 inhibition can boost autophagic flux and reduce protein aggregation, while its activation may amplify the protective effects. This dichotomous behaviour of HDAC6 may pose an obstacle to the design of targeted therapy. Illuminating the complex mechanisms through which HDAC6 influences neurodegeneration and neuroprotection is important before constructing effective treatments for ALS. The review provides a clear understanding of the complex role of HDAC6 in ALS pathogenesis and highlights potential strategies to improve the prognosis of people affected by this neurological illness.},
}

@article {pmid42262533,
year = {2026},
author = {Korade, G and Kharat, S and Rathi, K},
title = {Nitric oxide in neuroinflammation and neurodegeneration: dual roles, inflammasome crosstalk, and biomarker opportunities.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {42262533},
issn = {1432-1912},
abstract = {Nitric oxide is a short-lived gas that plays a critical role in numerous physiological processes, including vascular regulation, neurotransmission, and immune responses. In the CNS NO's role is complex, as it can both protect and damage neurons. Microglia, the brain's resident macrophages, produce excessive NO in response to stimuli like endotoxins and cytokines, leading to chronic inflammation and neuronal damage associated with neurodegenerative diseases such as Alzheimer's, Parkinson's, multiple sclerosis, and amyotrophic lateral sclerosis. NO's dual role as a pro-inflammatory and anti-inflammatory mediator is intricately linked to its impact on neuronal health and disease progression. This review is aimed at summarizing and critically discussing the roles of NO in neuroinflammation, neurodegeneration, inflammasome regulation, and related therapeutic perspectives. A narrative literature review was conducted using electronic databases (e.g. PubMed and Google Scholar) to identify experimental and clinical studies on NO, neuroinflammation, neurodegenerative diseases, inflammasomes, and related biomarkers and therapies, with emphasis on mechanistic and translational work. Research into NO's effects on inflammasomes, key components of the innate immune system, reveals that NO can inhibit inflammasome activation, influencing inflammatory responses. Despite progress, challenges remain, including the need for cell-type-specific models, advanced technological approaches, and the development of selective NO modulators. Overall, current evidence indicates that NO exerts both neuroprotective and neurotoxic effects in the CNS, mediated by its complex interactions with neural, glial, and immune pathways. Future research should focus on the dual nature of NO, explore lesser-known inflammasomes, and incorporate human-centric models to develop targeted therapies.},
}

@article {pmid42262640,
year = {2026},
author = {Tavassoli, T and Marco, EJ and Puts, N},
title = {Sensory Reactivity in Autism: Integrating Behavioural, Affective, Physiological, and Neural Dimensions.},
journal = {Current psychiatry reports},
volume = {28},
number = {1},
pages = {},
pmid = {42262640},
issn = {1535-1645},
abstract = {PURPOSE OF REVIEW: The goal of this paper is to synthesise recent research on sensory reactivity differences in autism across the lifespan, using He et al.'s sensory taxonomy as an organising framework. The review aims to address how behavioural, affective, perceptual, physiological, and neural levels of processing contribute to sensory reactivity differences, and how these differences relate to broader outcomes such as mental health, adaptive functioning, and quality of life.

RECENT FINDINGS: Across behavioural studies, autistic youth show elevated and variable sensory responsivity, with hypersensitivity predicting internalising symptoms and sensory seeking linked to externalising behaviours. Affective reactivity is consistently elevated across cultures, associated with anxiety and caregiver stress, and sensory seeking may function as a coping mechanism. Psychophysical research reveals domain‑specific perceptual differences-such as reduced tactile adaptation, altered motion noise exclusion, and enhanced pitch discrimination-rather than overarching hyper‑ or hyposensitivity. These perceptual findings often show limited correspondence with questionnaire‑based measures. Physiologically, autonomic dysregulation is implicated, or pharmacological approaches show emerging promise. Neuroimaging evidence highlights excitation-inhibition imbalance and altered connectivity, including dissociations between exogenous and endogenous networks in sensory‑reactive autistic children. Across multiple levels of processing, sensory reactivity differences in autism are robust, heterogeneous, and meaningfully linked to mental health and daily functioning. Key conclusions include: • Sensory hyperreactivity predicts internalising challenges, while sensory seeking may reflect regulatory strategies. • Perceptual differences are domain‑specific • Physiological and neural evidence converges on autonomic dysregulation and differences in connectivity patterns.},
}

@article {pmid42262849,
year = {2026},
author = {Deleu, B and Dupont, P and Bracaval, K and Ombelet, F and Hobin, F and Lamaire, N and Van Laere, K and Van Damme, P and De Vocht, J},
title = {[18]F FDG-PET correlates of motor neuron disease motor variants.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-5},
doi = {10.1080/21678421.2026.2682820},
pmid = {42262849},
issn = {2167-9223},
abstract = {While [18]F-fluorodeoxyglucose positron emission tomography (FDG-PET) is an established biomarker in amyotrophic lateral sclerosis (ALS), the metabolic correlates of motor neuron disease (MND) motor variants remain poorly defined. This is why we investigated patterns of cerebral glucose metabolism across the spectrum of MNDs, including progressive muscular atrophy (PMA), primary lateral sclerosis (PLS), and ALS. We retrospectively included 18 PMA, 25 PLS, and 43 matched non-hereditary ALS patients according to most recent diagnostic criteria. FDG-PET imaging revealed similar widespread hypometabolism in PMA, as in ALS, whereas PLS showed a more focal motor cortical pattern of hypometabolism. Despite clinical differences between MND subtypes, PMA and ALS showed similar FDG-PET metabolic patterns, whereas PLS exhibited a more restricted cortical signature in this retrospective study.},
}

@article {pmid42262924,
year = {2026},
author = {Mastromarco, GJ and Earnshaw, R and Moore, G and Xu, XYS and Sadek, NH and Cui, F and Lo, N and Lee, HO},
title = {Human J-domain proteins promote stress granule disassembly and suppress neurodegeneration-linked protein aggregation.},
journal = {Cell reports},
volume = {45},
number = {6},
pages = {117326},
doi = {10.1016/j.celrep.2026.117326},
pmid = {42262924},
issn = {2211-1247},
abstract = {Stress granules are conserved biomolecular condensates that form under stress and rapidly disassemble during recovery. Stress granules have been linked to pathological protein aggregation and their impaired disassembly reduces cell viability, yet the mechanisms governing their clearance and protein aggregation remain unclear. We find that human HSP70 and a subset of J-domain proteins (JDPs) localize to stress granules and that chemical or genetic inhibition of these chaperones markedly slows granule disassembly. Conversely, overexpressing these JDPs, particularly DNAJB1, accelerates disassembly without altering assembly. In vitro, HSP70 and DNAJB1 partition into G3BP1 condensates and reduce their size in an ATP-dependent manner. In cells expressing amyotrophic lateral sclerosis (ALS)-linked mutant FUS, DNAJB1 depletion further impairs stress granule clearance and promotes pre-amyloid accumulation, while depleting a non-stress granule JDP has no effect. Our findings demonstrate that specific JDP chaperones enhance stress granule disassembly and help limit aberrant protein aggregation.},
}

@article {pmid42263252,
year = {2025},
author = {Bétourné, A and Texakalidis, P and Raheb Khelo, R and Campbell, M and Sadiq, SA and Boulis, NM},
title = {Intrathecal Administration of Riluzole in Amyotrophic Lateral Sclerosis.},
journal = {Neurosurgery},
volume = {},
number = {},
pages = {},
doi = {10.1227/neu.0000000000003859},
pmid = {42263252},
issn = {1524-4040},
abstract = {BACKGROUND AND OBJECTIVES: Riluzole is the only treatment known to improve survival in amyotrophic lateral sclerosis (ALS) patients. However, its efficacy and dosing are limited by hepatic toxicity and interindividual pharmacokinetic variability. Recent experimental studies in hounds have shown that continuous intrathecal (IT) administration of riluzole is well tolerated and achieves significantly higher spinal cord tissue levels. We report the first 2 human ALS cases treated with IT riluzole.

METHODS: A catheter was inserted into the lumbar cistern and advanced to the midcervical region under fluoroscopic guidance and connected to a subcutaneous pump. Therapy was initiated at 0.1 mg/h of riluzole. The infusion rate was gradually increased until it reached a maximum of 4.8 mg/d.

RESULTS: The 2 patients tolerated dose escalation and treatment for over 2 years without apparent motor or sensory complications. Patients reported no asthenia, a central side effect often reported as a reason to abandon oral therapy.

CONCLUSION: This is the first report of chronic IT riluzole infusion in humans at a dose found to be safe in canines. A phase 1 study is planned to establish the maximum tolerated human dose, followed by a randomized placebo-controlled trial to determine the safety and tolerability of IT riluzole in patients with ALS.},
}

@article {pmid42263370,
year = {2026},
author = {Deveci, Ş and Matur, Z and Erzurumluoğlu, SS},
title = {Sensory abnormalities and entrapment neuropathies identified by nerve conduction studies in patients with amyotrophic lateral sclerosis.},
journal = {Neuromuscular disorders : NMD},
volume = {64},
number = {},
pages = {106463},
doi = {10.1016/j.nmd.2026.106463},
pmid = {42263370},
issn = {1873-2364},
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder primarily affecting motor neurons; however, non-motor symptoms, including sensory and autonomic disturbances, are increasingly recognized. This retrospective cross-sectional study evaluated the frequency of sensory and entrapment neuropathies in 114 patients with ALS using electrodiagnostic (EDX) studies. Demographic characteristics, comorbidities, and sensory and autonomic symptoms were documented. Electrophysiological evidence of sensory neuropathy was identified in 20 patients overall (20/114, 17.5%), including 10 patients without diabetes mellitus (DM), whereas entrapment neuropathy was detected in 28 patients overall (28/114, 24.6%), including 16 of those without DM or hypothyroidism. Sensory neuropathy was significantly associated with both DM and a history of chronic disease. In contrast, these comorbid conditions were not significantly associated with entrapment neuropathy. Furthermore, patient-reported symptoms showed no correlation with electrophysiological evidence of sensory involvement on EDX. Sensory neuropathy was more frequent in patients with spinal-onset than bulbar-onset disease, although the difference was not statistically significant. This study confirms that sensory involvement is not uncommon in ALS. Although clinical symptoms are poor predictors, electrophysiological abnormalities consistent with sensory and entrapment neuropathies are common. A significant proportion of these abnormalities are idiopathic and may directly reflect the disease process itself, particularly in spinal-onset cases.},
}

@article {pmid42263417,
year = {2026},
author = {Chung, J},
title = {A two-continua model of sleep health and sleep disorders: Why framework proliferation is a feature.},
journal = {Sleep medicine reviews},
volume = {88},
number = {},
pages = {102320},
doi = {10.1016/j.smrv.2026.102320},
pmid = {42263417},
issn = {1532-2955},
abstract = {Multi-dimensional sleep health (MDSH) frameworks emerged in the 2010s to articulate positive sleep health beyond the absence of sleep disorders. Meng et al. (2026) [1] provide the first systematic review directly comparing the two leading instruments, the Ru-SATED scale (Buysse, 2014; Ravyts et al., 2021) [2, 3] and the Sleep Health Index (SHI) (Knutson et al., 2017) [4], and surface two unresolved tensions: a conceptual question (what is the relationship between sleep health and sleep disorders?) and an operational question (will sleep science converge on a single MDSH framework?). This perspective elaborates Meng et al.'s brief observation that MDSH is orthogonal to sleep disorders into a Two-Continua Model (TCM), drawing on the dual-continua model of mental health. The TCM defines a sleep disorder continuum (X-axis) and an orthogonal sleep health continuum (Y-axis), generating a four-quadrant typology. Implications: the typology identifies under-attended populations for surveillance; MDSH complements rather than replaces disorder-focused science; joint-axis modeling integrating disorder and health information yields more powerfully predictive frameworks; and a proliferation of tailored MDSH frameworks is a feature of a maturing research program, not a defect.},
}

@article {pmid42263783,
year = {2026},
author = {Lai, TF and Liao, Y and Tzeng, PL and Wen, CJ and Chan, DC},
title = {Association of Brief Bouts of Vigorous Physical Activity and Frailty in Older Adults With Regular and Irregular Exercise Habits.},
journal = {Journal of aging and physical activity},
volume = {},
number = {},
pages = {1-7},
doi = {10.1123/japa.2024-0332},
pmid = {42263783},
issn = {1543-267X},
abstract = {Brief bouts of vigorous physical activity such as vigorous intermittent lifestyle physical activity (VILPA) have emerged as a flexible alternative to traditional structured exercise, requiring less time commitment, preparation, and access to facilities. This study explored the association between VILPA and the odds of prefrailty or frailty in 195 older adults aged 65 and above at National Taiwan University Hospital. Frailty status was evaluated using Fried et al.'s criteria, which include slowness, weakness, weight loss, exhaustion, and low physical activity. VILPA was measured using a waist-worn accelerometer. Multivariate binary logistic regression models revealed that meeting the VILPA duration or bouts thresholds was linked to lower odds of prefrailty or frailty. These associations were significant in those with irregular exercise habits, with adherence to VILPA duration or bouts thresholds correlating with reduced prefrailty or frailty likelihood (odds ratio = 0.21, 95% confidence interval [0.05, 0.89]). However, no significant associations were observed in individuals with regular exercise habits. Adhering to VILPA thresholds may be associated with lower frailty odds, particularly in older adults with irregular exercise habits. These findings suggest that promoting brief bouts of vigorous physical activity in daily life may have potential implications for frailty reduction in older adults, especially those who do not engage in regular exercise. This approach offers a potentially accessible and flexible alternative to structured exercise programs for maintaining health in aging populations.},
}

@article {pmid42264115,
year = {2026},
author = {Pynn, SR and Jørgensen, H and Vanstone, C and Mosewich, AD and Holt, NL and , },
title = {A narrative scoping review exploring parents' emotion knowledge and abilities in youth sport.},
journal = {Psychology of sport and exercise},
volume = {},
number = {},
pages = {103187},
doi = {10.1016/j.psychsport.2026.103187},
pmid = {42264115},
issn = {1878-5476},
abstract = {The purpose of this narrative scoping review was to explore how parents identify, express, use, understand, and manage their own and others' emotions in the context of youth sport. Mikolajczak's (2009) tripartite model of emotional intelligence (EI) was used as the conceptual lens for this review. Using Levac et al.'s (2010) framework for conducting scoping reviews, we reviewed 87 relevant sport parenting studies and conducted consultation focus groups with 10 sport parents and six former youth athletes. Qualitative data analysis techniques were used to map the findings into themes based on the dimensions of EI (i.e., identification and expression of emotions, using emotions, understanding emotions, and managing emotions). Findings indicated that parents identified and articulated their own emotions and empathised with their children in the sport context. This emotional awareness informed their emotionally supportive behaviours, such as providing encouragement and comfort. Parents' understanding of their children and sport shaped how and when they provided appropriate support in emotional situations. Parents also engaged in efforts to manage their own emotional reactions, drawing on self-awareness and knowledge of the sport environment to regulate their behaviour during competition. These findings provide insight into the specific aspects of youth sport parents' emotional competencies and can be used to inform sport parent education initiatives.},
}

@article {pmid42264185,
year = {2026},
author = {Baker, A and Okorie, M},
title = {UK Foundation Programme training needs a national minimum standard for advanced life support.},
journal = {Clinical medicine (London, England)},
volume = {},
number = {},
pages = {100605},
doi = {10.1016/j.clinme.2026.100605},
pmid = {42264185},
issn = {1473-4893},
abstract = {Since 2021, Advanced Life Support (ALS) has no longer been a mandatory requirement of the UK Foundation Programme. Although the shift towards capability rather than certification was educationally defensible, in practice it has created marked national variation in how resuscitation preparedness is developed, evidenced and signed off. Foundation doctors now enter emergencies with unequal access to funded ALS training, simulation and supervised assessment, while supervisors are left to judge equivalence without a consistent national threshold. This matters not because patient-level harm has been neatly proven, but because high-stakes clinical capability should not depend on local opportunity or variable interpretation. A capability-based curriculum and a national minimum standard are not mutually exclusive. The Foundation Programme should therefore restore a national ALS requirement, or a formally recognised equivalent standard, alongside funded access, blended delivery and transparent national evaluation of uptake, exemptions and outcomes.},
}

@article {pmid42264545,
year = {2026},
author = {Vishwakarma, H and Chauhan, A and Kaur, L and Awasthi, A},
title = {Nanotechnology-enabled targeting strategies for neurodegenerative disorders: role of functionalized nanoparticles.},
journal = {The Journal of pharmacy and pharmacology},
volume = {78},
number = {6},
pages = {},
doi = {10.1093/jpp/rgag060},
pmid = {42264545},
issn = {2042-7158},
abstract = {BACKGROUND: Neurodegenerative disorders comprise a diverse group of progressive neurological diseases characterized by the gradual loss of neuronal structure and function. Conditions such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis arise from multifactorial mechanisms involving genetic susceptibility, environmental factors, and age-related cellular decline.

PATHOPHYSIOLOGY: Key pathogenic processes include oxidative stress, mitochondrial dysfunction, protein misfolding and aggregation, impaired axonal transport, Golgi fragmentation, and chronic neuroinflammation, all of which disrupt neuronal homeostasis and synaptic communication, ultimately leading to neuronal death. Hormonal imbalances further exacerbate these effects by promoting oxidative damage, inflammation, and metabolic dysfunction.

CHALLENGES IN THERAPY: Despite advances in understanding disease mechanisms, effective drug delivery remains challenging due to the restrictive nature of the blood-brain barrier.

Recent developments highlight the potential of nanoparticle-based drug delivery systems to overcome these limitations. Functionalized nanoparticles enhance blood-brain barrier penetration, improve targeting specificity, and enable controlled drug release. These systems can deliver neuroprotective agents, antioxidants, peptides, and gene therapies directly to affected brain regions. Thus, integrating disease pathophysiology with nanotechnology-based strategies offers a promising approach for improving therapeutic outcomes and advancing precision treatment in neurodegenerative disorders.},
}

@article {pmid42264722,
year = {2026},
author = {He, S and Yu, H and Li, X and Chen, J and Liu, Z and Miao, D and Ren, M and Cui, H},
title = {Distribution of resistant Aegilops tauschii populations across China and its target-site resistance mechanism.},
journal = {Pesticide biochemistry and physiology},
volume = {221},
number = {},
pages = {107181},
doi = {10.1016/j.pestbp.2026.107181},
pmid = {42264722},
issn = {1095-9939},
abstract = {Aegilops tauschii is a notorious weed that poses a severe threat to wheat production. Recently, its resistance to mesosulfuron-methyl has been increasingly documented in some provinces of China. With Ae. tauschii rapidly expanding its distribution range throughout China, however, its nationwide resistance distribution and the underlying resistance molecular mechanisms remain poorly understood. To address this knowledge gap, 305 populations of Ae. tauschii were collected from eight major wheat-growing provinces of China to characterize their nationwide resistance profiles and target-site resistance mechanisms. Of the populations examined, 83 populations from Shanxi, Shaanxi, Henan, Hebei, Shandong, and Jiangsu provinces exhibited varying levels of resistance to mesosulfuron-methyl. Resistant populations were particularly widespread in Shanxi and Shaanxi compared with other regions. Forty-seven resistant populations were then selected for target-site mutation analysis. A Pro-197-Leu substitution in the acetolactate synthase (ALS) gene was identified in 14 resistant populations, whereas no known resistance-conferring amino acid alteration was detected in the remaining 33 populations. Resistant populations carrying the Pro-197-Leu mutation displayed a higher resistance level than resistant populations without ALS gene mutations. Furthermore, in vitro ALS activity assays showed that populations with the Pro-197-Leu substitution were highly resistant to mesosulfuron-methyl, with resistance index (RI) ranging from 32.95 to 33.12. In contrast, the RI values of resistant populations lacking target-site mutations were below 2.90. To the best of our knowledge, this study represents the first report of a target-site mutation (Pro-197-Leu) conferring resistance to mesosulfuron-methyl in Ae. tauschii.},
}

@article {pmid42264735,
year = {2026},
author = {Rojano-Delgado, AM and Sohrabi, S and Santana, APDS and Palma-Bautista, C and Domínguez-Valenzuela, JA and Gherekhloo, J and Alcántara-de la Cruz, R and De Prado, R},
title = {Herbicide metabolism and EPSPS Pro-106-Ser substitution confer multiple resistance in Chenopodium spp. from Southern Spain.},
journal = {Pesticide biochemistry and physiology},
volume = {221},
number = {},
pages = {107132},
doi = {10.1016/j.pestbp.2026.107132},
pmid = {42264735},
issn = {1095-9939},
abstract = {Long-term herbicide programs in Mediterranean perennial systems have imposed sustained selection pressure on weed populations, promoting the evolution of multiple resistance. We investigated resistance mechanisms in Chenopodium album (Ca) and C. vulvaria (Cv) from southern Spain following more than two decades of glyphosate-based management. We aimed to (i) confirm resistance to atrazine, tribenuron-methyl (TM), glyphosate, and 2,4-D; (ii) distinguish between target-site and metabolic resistance; and (iii) characterize the biochemical and molecular basis of cross- and multiple-herbicide resistance. Screening assays revealed high survival (78-100%) of resistant (R) populations to acetolactate synthase (ALS)-, photosystem II (PSII)-, auxinic-, and 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS)-inhibiting herbicides. Dose-response assays confirmed resistance, with resistance indices (RI) of 6.7 and 5.1 for atrazine, 19.0 and 17.3 for TM, 7.0 and 13.9 for glyphosate, and 6.0 and 6.9 for 2,4-D in CaR and CvR, respectively. Radiolabelled and analytical metabolism assays demonstrated enhanced herbicide metabolism in R populations: atrazine (94-95% vs. 13-16% in S), TM (68-69% vs. 24-25%), 2,4-D (64-65% vs. 2-4%), and glyphosate (39-43% vs. 8-9%). Malathion partially reversed resistance to atrazine, TM, and 2,4-D, supporting cytochrome P450 (CYP450) involvement. In contrast, glyphosate metabolism was independent of CYP450 or glutathione S-transferases inhibition. Biochemical assays showed no differences in PSII or ALS sensitivity (I50 RI ≈ 1), whereas EPSPS inhibition assays revealed a tenfold increase in I50 in CvR. Sequencing identified a Pro-106-Ser substitution in EPSPS exclusively in CvR. Enhanced metabolism predominates in the R Chenopodium spp. populations, with coexistence of metabolic and target-site mechanisms in CvR, increasing the risk of further cross-resistance under continued herbicide reliance.},
}

@article {pmid42265364,
year = {2026},
author = {Treittinger, K and Yang, S and Fischer, R and Dreisbach, G},
title = {The asymmetric list shift effect - flexible adaptation to new context demands?.},
journal = {Attention, perception & psychophysics},
volume = {88},
number = {5},
pages = {},
pmid = {42265364},
issn = {1943-393X},
abstract = {The list-wide proportion congruency effect describes how the congruency effect varies depending on the frequency of incongruent trials within a block. Specifically, the congruency effect is larger in mostly congruent (MC) blocks compared to mostly incongruent (MI) blocks. Research has shown that adaptation to these blocks does not change symmetrically when transitioning between them: moving from MC to MI leads to a rapid decrease in the congruency effect while transitioning from MI to MC results in little or no increase (Abrahamse et al., 2013). We aimed to investigate this asymmetric list shift (ALS) effect in a within-participants design where all participants experienced both transitions (MC-MI and MI-MC). Throughout Experiments 1-3 using a color-word Stroop task, we identified various forms of practice - including trial-type, stimulus-specific learning, general RT decrease, and a decrease in congruency effects over time (see Schmidt, 2016) - that can either facilitate or obscure the ALS effect, depending on the order in which participants experienced the transitions. In Experiment 4, using a face-name version of the Stroop task, where we minimized practice-related confounding factors by employing more complex stimuli and used a new stimulus set in the second transition, an ALS effect was observed regardless of the order of transition and for frequency-unbiased (i.e., 50% congruent) items. The role of practice effects and implications for the (in)-flexibility of control adaptations will be discussed.},
}

@article {pmid42265426,
year = {2026},
author = {Johannsen, L and Koger, A and Straub, ER and Stephan, DN and Kiesel, A and Koch, I and Müller, H},
title = {Contrasting cognitive control in the Simon and spatial Stroop tasks regarding their interference with the control of standing balance.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {42265426},
issn = {2045-2322},
abstract = {The scientific understanding of any interaction between cognition and balance control is advanced by methods that capture event-related effects of cognitive processes on balance with high temporal resolution and precision. We developed such an approach to examine how cognitive conflict interferes with the control of body balance during upright standing. Participants stood on a force plate while performing two cognitive conflict paradigms: a Simon task, which according to Kornblum et al.'s dimensional overlap model[41] mainly induces spatial stimulus-response conflict during response selection, and a Spatial Stroop task, which additionally elicits a stimulus-stimulus conflict during stimulus encoding. By aligning force plate time series data to the onset events of target and response across all trials, we assessed the temporal dynamics of spatial congruency effects on force moment variability as a marker of balance control activity. Across both experimental cognitive tasks, we observed strong congruency effects in cognitive task performance, when considering trials after previous congruent trials. Further, incongruent trials were associated with systematic transient reductions in force moment variability along the mediolateral axis in balance control. These observations are in line with the assumption that the recruitment of cognitive processes for conflict resolution temporarily inhibits, suppresses, or postpones balance adjustments. Importantly, regarding the impact of cognitive interference on body balance, data confirm our previous observations using improved methods and demonstrate that reduction in balance control activity during resolution of cognitive conflict generalizes to a task with multiple conflict loci (Spatial Stroop task). Thereby, this extended range of conflict does not result in correspondingly stronger interference effects in balance control. From a theoretical perspective, the results align with predictive models of postural regulation and intermittent, event-driven accounts of balance control.},
}

@article {pmid42265532,
year = {2026},
author = {Ella, A and Bar-Kalifa, E},
title = {Relational Memory Reconsolidation: A New Lens on Change Mechanisms in EFT for Couples.},
journal = {Family process},
volume = {65},
number = {2},
pages = {e70172},
doi = {10.1111/famp.70172},
pmid = {42265532},
issn = {1545-5300},
abstract = {This paper presents a new framework to account for change mechanisms in Emotion-Focused Therapy for Couples (EFT). Building on Lane et al.'s (2015) integrated memory model, the Relational Memory Reconsolidation model described here posits that EFT reshapes partners' relational memory structures through emotionally intense moments of expressed vulnerability and responsiveness. These vulnerability-responsiveness events allow partners to access and transform memories of past relational experiences (i.e., episodic memory) as well as associated beliefs about themselves and the relationship (i.e., semantic memory). This process of emotional activation and reconsolidation allows maladaptive interaction patterns, which are rigid and stressful, to evolve into more adaptive, emotionally responsive exchanges. These emotional moments activate and transform relational self-states that are responsive to interpersonal cues and can shape partners' self-concepts in a relational context. As therapy progresses and emotionally significant interactions are repeated, the coactivation of adaptive and maladaptive self-states updates neocortical memory traces, leading to changes in higher-order relational semantic structures (i.e., the relational self). These moments foster alignment in partners' perceptions of their shared reality, characterized by mutuality in feelings, practices, memories, goals, and identity. Clinically, the framework highlights the need to elicit one partner's core vulnerable emotions and, within the reconsolidation window, disconfirm related expectations (e.g., rejection) through the other partner's empathic and supportive response. This process may transform key components of partners' relational memory, including relational episodic memories, semantic structures, and procedural emotional responses.},
}

@article {pmid42265600,
year = {2026},
author = {Jiang, S and Chen, F and Ma, H and Wu, S and Tang, X and Pan, X and Li, Q and Tao, A and Xu, J and Qi, J and Fang, P and Chen, J and Zhang, L},
title = {Cloning and functional verification of endogenous U6 promoters for developing an efficient CRISPR/Cas9-mediated genome editing system in kenaf (Hibiscus cannabinus L.).},
journal = {BMC plant biology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12870-026-09228-9},
pmid = {42265600},
issn = {1471-2229},
support = {32472219//the National Natural Science Foundation of China/ ; 2023J01443//Fujian Provincial Natural Science Foundation of China/ ; CARS-16//China Agricultural Research System of MOF and MARA/ ; KFB23001//Science and Technology Innovation Project of Fujian Agriculture and Forestry University/ ; ASTIP-IBFC-01//Agriculture Science and Technology Innovation Program/ ; },
abstract = {BACKGROUND: The U6 promoter is a critical component of the CRISPR/Cas9 system, as it drives the transcription of single-guide RNAs (sgRNAs) to enable precise genome editing. Endogenous promoters typically exhibit higher transcriptional activity than their exogenous counterparts, which can significantly enhance editing efficiency. However, the endogenous U6 promoter in kenaf (Hibiscus cannabinus L.), an important fiber crop, has not yet been characterized.

METHODS: Using the Arabidopsis U6-26 (AtU6-26) promoter as a reference, we performed a homologous sequence search and identified two candidate U6 promoters in kenaf, designated HcU6-1 and HcU6-14. Promoter fragments were amplified from the kenaf cultivar 'Fuhong 952' and cloned into a β-glucuronidase (GUS) reporter vector. Histochemical GUS staining assays revealed that both HcU6 promoters were transcriptionally active, with HcU6-14 showing significantly stronger expression levels compared to HcU6-1.

RESULTS: To further evaluate the utility of these promoters for genome editing, we constructed CRISPR/Cas9 vectors targeting the kenaf acetolactate synthase (ALS) gene, driven by either HcU6-14P or the exogenous cotton GbU6-9P promoter. Agrobacterium rhizogenes K599-mediated transformation was used to induce hairy roots, and mutation analysis of the ALS gene was performed via Sanger sequencing. Notably, targeted mutations in the ALS gene were detected in hairy roots transformed with the HcU6-14P-driven CRISPR/Cas9 vector, whereas no mutations were observed in roots transformed with the exogenous GbU6-9P promoter. These results demonstrate that the endogenous HcU6-14 promoter confers superior genome editing efficiency compared to the heterologous promoter, which facilitates the development of improved varieties with enhanced agronomic traits.},
}

@article {pmid42256556,
year = {2026},
author = {Xiao, X and Hao, G and Wan, P and Hou, W},
title = {Safety evaluation of Tofersen in amyotrophic lateral sclerosis based on the FAERS database.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1843630},
pmid = {42256556},
issn = {1664-2295},
abstract = {BACKGROUND: This study utilizes data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) to conduct a post-marketing safety evaluation of Tofersen.

METHODS: A systematic search of the FAERS database was performed to identify adverse event (AE) reports from Q1 2023 to Q4 2025 was performed. Multi-dimensional disproportionality analyses were conducted using the ROR, PRR, BCPNN, and MGPS method.

RESULTS: A total of 409 Tofersen-related reports were identified, revealing significant signals across 22 System Organ Class (SOC) categories and 369 Preferred Terms (PTs). At the SOC level, the most prominent safety signals were observed in injury, poisoning and procedural complications, nervous system disorders, and musculoskeletal and connective tissue disorders. In contrast, ear and labyrinth disorders, as well as respiratory, thoracic and mediastinal disorders, were not listed in the current product labeling and may warrant further investigation. At the PT level, neurological procedural complication, CSF red blood cell count positive, CSF white blood cell count increased, and CSF cell count increased exhibited the strongest signals, primarily reflecting cerebrospinal fluid cytological and biochemical abnormalities, as well as procedural-related adverse events such as post-lumbar puncture syndrome, procedural pain, and procedural headache. Although central nervous system-related events (e.g., increased intracranial pressure, peroneal nerve palsy, papilloedema, and facial paralysis) and infectious or inflammatory events (e.g., radiculopathy, myelitis, aspiration pneumonia, and meningitis) were less frequently reported, their relatively high disproportionality signals warrant clinical attention and systematic monitoring. Notably, a newly identified signal of pulmonary embolism suggests a potential thromboembolic risk in specific patient populations.

CONCLUSION: These findings provide real-world evidence to inform the balance between the therapeutic potential and safety profile of Tofersen. Future clinical strategies should focus on mitigating central nervous system-related and procedure-related adverse events. Further mechanistic studies are crucial.},
}

@article {pmid42257176,
year = {2026},
author = {Villasi, W and Frederic, R and Qureshi, S and Zheng, B and Torrente, MP and Fisher, RMA},
title = {Histone H3 Post-Translational Modification Changes are Linked to Manganese and Copper Exposure in Saccharomyces cerevisiae.},
journal = {microPublication biology},
volume = {2026},
number = {},
pages = {},
pmid = {42257176},
issn = {2578-9430},
abstract = {Prolonged exposures to heavy metals are risk factors for chronic diseases, such as Amyotrophic Lateral Sclerosis and Frontotemporal dementia (ALS/FTD). ALS/FTD comprises a fatal neurodegenerative disease continuum and is linked to disruptions in the levels of histone post-translational modifications (PTMs). Epigenetic mechanisms can connect environmental exposures to disease occurrences. Here, we examine the effects of manganese and copper exposure on the H3 PTM landscape in yeast. Manganese exposure decreases H3K9ac, H3K14ac, and H3S10ph levels. Copper exposure increases H3S10ph and H3K14ac levels and decreases H3K36me3 levels. This provides a basis for linking environmental exposure to biological mechanisms of disease.},
}

@article {pmid42257870,
year = {2026},
author = {Nguyen, N and Lauinger, AR and Naik, A and Liu, R and Yolcu, Y and Arnold, PM},
title = {Clinical Research for the Use of 7 T Magnetic Resonance Imaging for Spinal Pathologies: a Scoping Review.},
journal = {Clinical neuroradiology},
volume = {},
number = {},
pages = {},
pmid = {42257870},
issn = {1869-1447},
abstract = {PURPOSE: Magnetic resonance imaging (MRI) at 7 T (7T) offers higher signal-to-noise ratio and improved spatial resolution compared to lower magnetic field strengths such as 1.5T and 3T, which may improve lesion detection and anatomical visualization for spinal cord pathology. This review summarizes current techniques and achievements in 7T spinal imaging and outlines associated technical barriers and future directions.

METHODS: A scoping review in accordance with PRISMA extension for scoping reviews guidelines was performed utilizing PubMed, Scopus, and Web of Science. Only studies related to 7T MRI of human subjects were included, after removing unrelated studies and those of non-human subjects.

RESULTS: Twenty-nine studies were included. Current literature supports 7T's superior resolution and signal-to-noise ratio in comparison to 1.5T and 3T MRI. These studies reported improved lesion detection and staging in multiple sclerosis (MS), spinal cord injury (SCI), and amyotrophic lateral sclerosis (ALS); however, the implications of results are limited by small sample sizes, technical heterogeneity, and inconsistent outcome measures. Additionally, the use of 7T spinal imaging remains limited by radiofrequency coil design, susceptibility artifacts, physiological noise, lack of FDA-clearance for spinal indications, and an absence of standardized imaging protocols. Future research aims to address these limitations.

CONCLUSION: Spinal cord imaging at 7T is challenging due to technical constraints and higher susceptibility to artifacts as a result of physiological noise (respiration, swallowing, and bulk movement). However, early studies' results using 7T imaging support improved ability, compared to 3T, to provide enhanced visualization of fine anatomical structures, such as nerve roots, and to improve spinal cord lesion detection.},
}

@article {pmid42257902,
year = {2026},
author = {Horiuchi, K and Nakamura, S and Ishikawa, K and Nunomura, S and Yamada, K and Inoue, T and Oiwa, K and Fujii, S and Oshima, Y and Kudo, A and Yabe, I},
title = {Early respiratory decline around diagnosis and short-term post-landmark outcomes in amyotrophic lateral sclerosis: a 6-month landmark cohort study.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {7},
pages = {},
pmid = {42257902},
issn = {1590-3478},
abstract = {BACKGROUND: In amyotrophic lateral sclerosis (ALS), respiratory decisions rely on serial trends rather than a single value. We evaluated whether early respiratory decline around diagnosis provides prognostic information in a real-world landmark framework.

METHODS: This single-center retrospective cohort screened 94 consecutive patients diagnosed between April 2019 and December 2025. A 6-month landmark was used. Early decline was estimated from %FVC values between - 30 and + 180 days around diagnosis. The primary model included age and early %FVC decline; robustness analyses included time-varying Cox, piecewise Cox, RMST, included-vs-excluded comparison, death-only analysis, and slope-quality filtering.

RESULTS: Of 94 screened patients, 62 met baseline eligibility, 56 had calculable early slope, and 45 entered the landmark cohort; 28 post-landmark composite events occurred. In the Cox model, faster early %FVC decline was associated with higher hazard of death or invasive mechanical ventilation via tracheostomy (HR 1.33 per 1%/month faster decline, 95% CI 1.14-1.55, p < 0.001). PH diagnostics suggested non-proportionality (%FVC p = 0.031; NIV p = 0.034 in the expanded model), so this HR was interpreted as an average follow-up association and complemented by PH-robust analyses. The signal was stronger early than late, remained consistent in a death-only analysis, and favored the slower-decline group by RMST at 24 and 36 months.

CONCLUSIONS: In this selected measurement-capable landmark cohort, early respiratory decline provided a clinically meaningful short-to-medium term prognostic signal for post-landmark adverse outcomes. External validation is required before broader generalization beyond measurement-capable landmark populations.},
}

@article {pmid42259179,
year = {2026},
author = {Nakasako, J and Yaguchi, R and Terayama, A and Kuwahara, M and Nishimoto, Y},
title = {Association of anti-glycolipid IgG with respiratory function decline in amyotrophic lateral sclerosis.},
journal = {Journal of the neurological sciences},
volume = {488},
number = {},
pages = {126039},
doi = {10.1016/j.jns.2026.126039},
pmid = {42259179},
issn = {1878-5883},
abstract = {OBJECTIVE: Effective treatments for amyotrophic lateral sclerosis (ALS) remain limited, underscoring the need to identify robust biomarkers associated with disease severity and prognosis. This study investigated whether immunoglobulin G (IgG) and immunoglobulin M (IgM) anti-glycolipid antibodies are associated with clinical manifestations of ALS, particularly decline in respiratory function.

METHODS: This was a retrospective observational cohort study of the patients with ALS. Among patients with definite or probable limb-onset ALS, 11 patients in the glycolipid IgG-positive group were compared with 15 patients in the IgG-negative group, and 5 patients in the glycolipid IgM-positive group were compared with 9 patients in the IgM-negative group, with adjustment for age. Associations between anti-glycolipid antibody status and respiratory function were assessed using Kaplan-Meier survival analysis and Cox proportional hazards models.

RESULTS: The time to decline of percent forced vital capacity (%FVC) below 80% and 60% was significantly shorter in the IgG-positive group than in the IgG-negative group (p = 0.002 and p = 0.025, respectively). Cox proportional hazards analysis demonstrated that IgG antibody positivity was an independent risk factor for earlier decline in %FVC to 80%.

INTERPRETATION: These findings suggest that anti-glycolipid IgG antibodies may be associated with respiratory function decline in ALS. Larger comprehensive studies will be required to validate these results and to elucidate the underlying pathophysiological mechanisms.},
}

@article {pmid42259250,
year = {2026},
author = {Creel, SC},
title = {A note of caution on tone language advantages for music.},
journal = {Current biology : CB},
volume = {36},
number = {11},
pages = {R467-R469},
doi = {10.1016/j.cub.2026.04.009},
pmid = {42259250},
issn = {1879-0445},
abstract = {Liu et al.[1] reported recently in Current Biology a large-scale citizen science replication of the tone-language advantage for musical pitch perception. Their 493,100 volunteers spoke 54 languages, including 19 tone languages, those in which a word's pitch pattern contributes to its meaning. For example, Mandarin ma with high pitch means 'mother', while ma with dipping pitch means 'horse'. Previous studies reported tone language advantages, but with far smaller and less linguistically diverse samples (mostly East Asian tone languages). I applaud the authors' exploration of diverse tone languages with disparate tonal properties, including varying numbers, types, and linguistic uses of tones, plus varying cultural factors. While I do not dispute the overall tone language advantage, I take issue with Liu et al.'s[1] inference that the effect is consistent across the varied tone languages tested: because of the properties of the models they used to estimate individual-language effects, their more-diverse tone languages spuriously appear to pattern consistently, when in actuality the data are too noisy to draw strong conclusions about tone languages as a unified group.},
}

@article {pmid42259394,
year = {2026},
author = {Zhang, K and Kong, S and Ma, Y and Kan, C and Zheng, T and Sun, X},
title = {Natural Monomer Compounds in Neurodegenerative Diseases: Targeting Ferroptosis and Neuroinflammation.},
journal = {Behavioural brain research},
volume = {},
number = {},
pages = {116319},
doi = {10.1016/j.bbr.2026.116319},
pmid = {42259394},
issn = {1872-7549},
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss driven by oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation. Ferroptosis, an iron-dependent and lipid peroxidation-associated form of regulated cell death, has recently been identified as a key contributor to neuronal vulnerability. Emerging evidence demonstrates that purified natural monomer compounds derived from medicinal plants exert potent neuroprotective effects by targeting ferroptosis and neuroinflammatory pathways. Representative agents such as curcumin, baicalin, resveratrol, and ginsenoside Rg1 activate nuclear factor E2-related factor-2 and glutathione peroxidase 4 signaling to preserve redox balance, while suppressing microglia-mediated inflammation through inhibition of toll-like receptor 4 pathways. This review highlights the interplay between ferroptosis and neuroinflammation in NDDs, summarizes the regulatory effects of bioactive herbal monomer compounds, and discusses recent advances in multi-omics profiling, nano-delivery strategies, and translational research. By modulating the ferroptosis-neuroinflammation axis, these compounds may represent promising therapeutic candidates for NDDs.},
}

@article {pmid42260601,
year = {2026},
author = {Yoshida, M},
title = {Development and validation of the creative personality and thinking styles scale: a multifaceted measure for assessing creativity-related individual differences.},
journal = {BMC psychology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40359-026-04959-8},
pmid = {42260601},
issn = {2050-7283},
abstract = {BACKGROUND: Creativity is the process of generating contextually useful novel outcomes by uniquely reconfiguring existing knowledge and information. While various measures examine specific aspects of creativity, multifaceted measures that holistically assess creativity as a domain-general factor are still needed. This study developed the Creative Personality and Thinking Styles Scale (C-PETS), which measures personality, thinking styles, and creativity-related motivation based on Plucker et al.'s theory of creativity.

METHODS: The initial C-PETS item pool was developed by referencing existing scales, followed by a qualitative screening process to ensure theoretical consistency. Exploratory factor analysis involving 572 participants was conducted to examine the underlying factor structure. Subsequently, confirmatory factor analysis and a higher-order model analysis involving 943 participants were performed to verify the model fit.

RESULTS: Exploratory factor analysis identified a five-factor, 16-item scale comprising Broad Thinking, Thorough Thinking, Information Manipulation, Challenge-Seeking, and Ambiguity Tolerance. The higher-order CFA model demonstrated an excellent fit (GFI = .97, CFI = .98, RMSEA = .02). Criterion-related validity was supported by significant correlations with the Short Scale of Creative Self-Efficacy (r = .75), Aesthetic Experiences Scale (r = .30), and Divergent Association Task (r = .18). Test-retest reliability after two weeks was strong (r = .87). Additionally, a positive correlation was observed with educational attainment.

CONCLUSIONS: The C-PETS represents a valuable contribution to creativity assessment by providing a multifaceted measure of creativity-related personality, thinking styles, and motivation.},
}

@article {pmid42261056,
year = {2026},
author = {Bromberg, MB},
title = {The Flail Limb Syndrome.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70307},
pmid = {42261056},
issn = {1097-4598},
abstract = {The flail limb syndrome is primarily a lower motor neuron disorder that initially affects proximal arm muscles (flail arm syndrome-FAS) or distal leg muscles (flail leg syndrome-FLS). Both were recognized early on (1886 for FAS and 1918 for FLS) as somewhat distinct from classic amyotrophic lateral sclerosis (ALS). Descriptions in the literature are case series with limited information on electrophysiologic features (central and peripheral), cognitive involvement, and genetic mutations. What follows is a compilation of these features. The flail limb syndromes are rare, representing ~7%-8% of ALS. They have a higher ratio of males to females compared to classic ALS. Both are defined by predominant focal arm or leg weakness for ~2 years before progression to other regions, although there can be early and mild clinical or electrophysiologic evidence for denervation and reinnervation in other regions during the initial period. Ultimately, there is progression to respiratory failure, but at a slower rate compared to classic ALS. Upper motor neuron clinical signs are variable, but transcortical magnetic stimulation paradigms and magnetic resonance imaging tractography support upper motor neuron loss. Tests of the split hand pattern show it is rare compared to ALS. Dementia is also rare. Genetic testing supports a spectrum of ALS-related gene mutations but at a lower frequency than with classic ALS, and no gene mutation is predominant. Diagnosis requires ~2 years of regional stability to predict the better prognosis for the flail limb syndromes.},
}

@article {pmid42248993,
year = {2026},
author = {Gad, AG and Kelani, KM and Mahmoud, AM and Arafa, RM and Abbas, AEF},
title = {Fedorov algorithm-optimized chemometric spectrophotometry for cefepime-tazobactam microanalysis in plasma and pharmaceuticals with integrated MA and NQS sustainability assessment.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {42248993},
issn = {2045-2322},
abstract = {A green, sustainability-oriented chemometric-assisted UV spectrophotometric platform was developed for the simultaneous determination of Cefepime (CFPM) and Tazobactam (TAZO) in pharmaceutical formulations and human plasma. Water served as the sole diluent, eliminating hazardous organic solvents and substantially reducing the environmental impact of the analytical procedure. Calibration and validation sets were efficiently constructed using the Fedorov exchange algorithm within Brereton's multilevel design framework, yielding 25 calibration and 13 validation mixtures and reducing experimental workload by approximately 70% compared with conventional designs. Three complementary chemometric models were evaluated: Principal Component Regression (PCR), Firefly Algorithm-assisted Partial Least Squares (FA-PLS), and Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS). Among them, MCR-ALS demonstrated superior predictive performance, with correlation coefficients exceeding 0.9998 for both analytes, minimal systematic bias confirmed by Elliptical Joint Confidence Region analysis, and high robustness across pharmaceutical and plasma matrices. Limits of detection were 0.0487 and 0.0396 µg mL[-1], while limits of quantification were 0.1476 and 0.1200 µg mL[-1] for CFPM and TAZO, respectively. The method was validated in accordance with ICH guidelines and successfully applied to CEFE-MAX™ powder for injection and fortified human plasma. Matrix effect evaluation showed negligible signal suppression (- 2.35% to - 1.27%), indicating strong matrix tolerance and calibration transferability. Comparative benchmarking against reported HPLC-UV, LC-MS/MS, capillary zone electrophoresis, and UV spectrophotometric methods demonstrated that the proposed approach achieves an optimal balance of sensitivity, simplicity, and environmental sustainability. Sustainability assessment using the Multi-Color Assessment (MA), carbon footprint analysis, and the Need-Quality-Sustainability (NQS) index yielded a Whiteness Score of 83.6%, an NQS score of 90, and a low carbon footprint of 0.032 kg CO2-eq per analysis. Overall, the developed platform provides a rapid, cost-effective, and environmentally responsible alternative for routine quality control and preliminary therapeutic monitoring of the CFPM-TAZO combination.},
}

@article {pmid42250142,
year = {2026},
author = {Jalaiei, A and Kiani Darabi, AH and Sakkaki, E and Rezazadeh, M and Ghafouri-Fard, S},
title = {Molecular interplay between Non-coding RNAs and BDNF in Neurodegenerative Disorders: a systematic review.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {},
pmid = {42250142},
issn = {1573-4978},
abstract = {Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays essential roles in nervous system development, neuronal maintenance, and neurogenesis. Aberrant BDNF concentrations, observed both peripherally and within the central nervous system (CNS), have been consistently implicated in the pathogenesis of a spectrum of neurodegenerative disorders (NDDs), including Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Huntington's disease, and Multiple sclerosis. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), regulate gene expression and are critical factors in cellular processes relevant to neurodegenerative disease pathobiology. Consequently, ncRNAs are posited as promising biomarkers and potential therapeutic modalities for CNS-related pathologies. However, robust empirical evidence substantiating ncRNA-mediated, post-transcriptional regulation of BDNF expression in the context of neurodegeneration remains relatively scarce. The objective of this systematic review is to provide a critical synthesis of the current literature on the diagnostic and prognostic utility of ncRNAs that modulate BDNF expression, specifically within the scope of neurodegenerative disorders. Furthermore, we will explore innovative therapeutic strategies centered on targeting BDNF-associated miRNAs for the treatment of these disorders.},
}

@article {pmid42250707,
year = {2026},
author = {Hosseinpoor, Z and Seyedalipour, B and Behjou, NK and Hosseinkhani, S and Baziyar, P},
title = {Inhibitory effect of silymarin on amyloid formation in ALS-associated hSOD1 P66R mutant.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {152922},
doi = {10.1016/j.ijbiomac.2026.152922},
pmid = {42250707},
issn = {1879-0003},
abstract = {The aberrant aggregation of human superoxide dismutase 1 (hSOD1) into β-sheet-rich amyloid fibrils is a crucial process in the pathogenesis of amyotrophic lateral sclerosis (ALS), enhancing motor neuron degeneration and disease progression. The P66R mutation in SOD1 destabilizes local structure and promotes β-sheet-driven fibrillation, which makes it a suitable model for exploring approaches for reducing pathogenic aggregation. Here, we evaluate silymarin, a polyphenolic compound with known antioxidant and neuroprotective properties, for its potential to inhibit P66R-hSOD1 aggregation. ThT fluorescence and transmission electron microscopy analyses demonstrate a significant decrease in amyloid fibril formation in the presence of silymarin; in addition, FTIR spectroscopy confirms the suppression of β-sheet formation. Fluorescence quenching and ANS binding assays indicate a moderate-affinity binding between silymarin and the mutant protein, along with a reduction in surface hydrophobicity. Hemolysis assays confirm its protective effect against membrane damage induced by aggregates, while molecular docking and dynamic simulations indicate that silymarin stabilizes aggregation-prone areas with hydrogen bonding and hydrophobic interactions, thereby promoting compact conformations and reducing solvent-exposed surfaces. The findings identified silymarin as an effective anti-amyloidogenic agent that reduces β-sheet accumulation and fibril formation while also decreasing cytotoxicity, highlighting its potential as a therapeutic candidate for ALS.},
}

@article {pmid42251349,
year = {2026},
author = {Masrori, P and Amado, DA},
title = {RAN translation as a dominant pathogenic axis in C9ORF72-associated ALS and FTD models.},
journal = {Molecular neurodegeneration},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13024-026-00959-9},
pmid = {42251349},
issn = {1750-1326},
}

@article {pmid42251967,
year = {2026},
author = {Manchinu, MF and Congiu, M and Massidda, M and Borghero, G and Marongiu, J and Marzi, I and Maschio, A and Rallo, V and Serra, M and Porcedda, C and Etzi, M and Palmas, MF and Angius, A and Sogos, V and Pateri, MI and Steri, M and Coroneo, V and de Simone, A and Cossu, G and Chiti, F and Carta, AR},
title = {PBMC DEG/miRNA biomarkers of TDP-43 pathology in ALS.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107473},
doi = {10.1016/j.nbd.2026.107473},
pmid = {42251967},
issn = {1095-953X},
abstract = {Amyotrophic lateral sclerosis (ALS) lacks reliable, disease-specific, and minimally invasive biomarkers, representing a major barrier to early diagnosis and patient stratification. The primary aim of this translational pilot study was to identify a disease-specific, TDP-43-related, gene-microRNA (miRNA) signature in peripheral blood mononuclear cells (PBMCs) of ALS patients with potential diagnostic value. To this end, we first identified differentially expressed disease-specific genes (dsDEGs) using a TDP-43-based rat model of ALS, generated by stereotaxic infusion of full-length (FL) TAR DNA-binding protein 43 (TDP-43) into the motor cortex. Transcriptomic profiling of the motor cortex revealed candidate dsDEGs, which were subsequently validated by RT-qPCR in motor cortex, spinal cord, and PBMCs from the same animals. To assess translational relevance, expression levels of these dsDEGs were analyzed in PBMCs from early- to mid-stage ALS patients and matched healthy controls, while disease specificity was evaluated using Parkinson's disease (PD) samples. In parallel, conserved miRNAs predicted to target the identified dsDEGs were examined in both rat and human PBMCs. Five dsDEGs, Mctp1, Penk, Mt2A, Drd1, and Rasgrp2, were consistently dysregulated across central and peripheral tissues in the TDP-43 rat model. RT-qPCR analysis of human PBMCs confirmed significant and selective dysregulation of these genes in ALS, but not in PD, supporting disease specificity. Moreover, exposure of human neuroblastoma cells and healthy PBMCs to TDP-43 recapitulated the ALS-like expression changes. Computational and experimental analyses identified seven conserved miRNAs targeting these dsDEGs, of which four were significantly downregulated in ALS PBMCs, supporting a coordinated regulatory network. Receiver operating characteristic (ROC) analyses demonstrated strong discriminative performance for both the gene signature (AUC 0.87-1.00) and the associated miRNAs (AUC 0.95-1.00). Together, these findings define a novel PBMC-based gene-miRNA signature that mirrors central ALS pathology and shows high diagnostic accuracy and disease specificity, highlighting its potential as a minimally invasive biomarker for ALS.},
}

@article {pmid42252093,
year = {2026},
author = {Arlt, FA and Miske, R and Appeltshauser, L and Zinnow, V and Borowski, K and Stenzel, W and Radbruch, H and Meisel, A and Ruprecht, K and Endres, M and Blau, I and Kirchner, M and Mertins, P and Sanchez-Sendin, E and Wernick, S and Pressler, H and Stascheit, F and Linke, J and Hümmert, S and Werner, HB and Wibisono, EA and Doppler, K and Komorowski, L and Spiliotis, ET and Dubey, D and Zeckeridou, A and Pittock, SJ and Mills, JR and McKeon, A and Scharf, M and Prüss, H},
title = {Septin multimer autoantibodies in severe motor neuropathy mimicking lower motor neuron disease.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag183},
pmid = {42252093},
issn = {1460-2156},
abstract = {Severe neuropathies with predominant involvement of motor fibers can resemble lower motor neuron disease (LMND) phenotypes. Given the fatal prognosis of LMND, identifying underlying autoimmune syndromes is crucial to provide treatment options to patients. We investigated a novel autoantibody binding pattern observed on murine teased sciatic nerve fibers. Target antigens were identified using immunoprecipitation combined with mass spectrometry. Target specificity of these autoantibodies was validated in cell-based assays, neutralization assays, and knock-out models. A retrospective study cohort consisting of different neuropathies (chronic inflammatory demyelinating polyradiculopathy n=86, Guillain-Barré syndrome n=37, multifocal motor neuropathy n=18, diabetic neuropathy n=30, other inflammatory neuropathies n=10), amyotrophic lateral sclerosis (n=50), multiple sclerosis (n=50), and healthy controls (n=50) was negative for septin multimer autoantibodies. Histopathological analysis of skin and sural nerve including electron microscopy was performed in one seropositive patient, and autoantibody binding was characterized in vitro. Extensive immunotherapy was initiated in one patient, with clinical and serological follow-up over four years. Among 3,543 total samples tested, three patients (two male, one female) - diagnosed with the LMND variant of amyotrophic lateral sclerosis (ages 65, 72, and 79, respectively) - showed a novel and distinct autoantibody binding pattern of indirect immunofluorescence staining on peripheral nerves, targeting Schmidt-Lanterman incisures (SLIs), paranodes, and the abaxonal myelin. Target identification and validation revealed septin multimers as autoantibody epitopes. Despite the primarily intracellular location of septins, autoantibody binding was evident in living myelinated dorsal root ganglia, primarily at SLIs ("incisuropathy"). Septin multimer autoantibodies further initiated complement deposition on fixed and permeabilized cell-based assays. Sural nerve and skin biopsies showed inflammation, myelin and axonal pathology. Extensive immunotherapy in one patient was followed by disease stabilization over three years. The other two patients died of rapid disease progression: One of them received no immunotherapy while the other had ineffective treatments with single administrations of IVIG and rituximab. Our data suggest that septin multimer autoimmunity occurs in severe motor predominant neuropathies which can clinically resemble a neurodegenerative LMND. Screening for septin multimer autoantibodies should be considered in patients presenting with this phenotype. Follow-up studies need to determine the direct pathogenicity of septin multimer autoantibodies, their potential as a biomarker of an autoimmune syndrome, and responses to immunotherapy in larger cohorts.},
}

@article {pmid42252583,
year = {2026},
author = {Melone, M and Di Palma, M and Scimemi, A and Conti, F},
title = {Organization of Astrocytic GLT-1 at Cortical Inhibitory Synapses.},
journal = {Glia},
volume = {74},
number = {8},
pages = {e70180},
doi = {10.1002/glia.70180},
pmid = {42252583},
issn = {1098-1136},
support = {PRIN2022BZWEKA//Italian Ministry of University and Reearch/ ; R56NS12955601/NH/NIH HHS/United States ; },
mesh = {*Astrocytes/metabolism/ultrastructure ; Animals ; *Excitatory Amino Acid Transporter 2/metabolism ; *Synapses/metabolism/ultrastructure ; Humans ; *Cerebral Cortex/metabolism/ultrastructure/cytology ; Rats ; Male ; Female ; Rats, Sprague-Dawley ; Glutamic Acid/metabolism ; *Neural Inhibition/physiology ; },
abstract = {Glutamate spillover from excitatory synapses modulates neighboring inhibitory synapses, yet the ultrastructural organization of the major glutamate transporter GLT-1 at these sites remains poorly defined. Using quantitative pre-embedding electron microscopy in rat and human cortex, we found that GLT-1-positive astrocytic leaflets (ALs) were frequently juxtaposed to morphologically identified symmetric synapses, with similar prevalence across axo-somatic, proximal axo-dendritic, and distal axo-dendritic subtypes. Because inhibitory synapses are embedded in a dense excitatory neuropil, we applied distance-based phenotyping relative to the nearest asymmetric synapse to define symmetric-associated GLT-1+ ALs. Within this population, distal axo-dendritic symmetric synapses showed shorter AL-to-synaptic-edge distances and were embedded in a tighter local excitatory microenvironment. Post-embedding immunogold further showed that GLT-1 was enriched at the plasma membranes of ALs and localized extrasynaptically relative to symmetric synapses. Consistently, symmetric-associated membrane GLT-1 and closely spaced GLT-1/α2 couples (with an interdistance ≤ 50 nm) were preferentially localized within 1000 nm of distal symmetric synapses compared to proximal. Similar organizational features of membrane GLT-1/α2 couples were observed in human cortex. These findings identify a subtype-dependent extrasynaptic astrocytic GLT-1 organization at cortical inhibitory synapses and provide a morphological framework for glutamate-dependent modulation of inhibitory signaling.},
}

*Astrocytes/metabolism/ultrastructure
Animals
*Excitatory Amino Acid Transporter 2/metabolism
*Synapses/metabolism/ultrastructure
Humans
*Cerebral Cortex/metabolism/ultrastructure/cytology
Rats
Male
Female
Rats, Sprague-Dawley
Glutamic Acid/metabolism
*Neural Inhibition/physiology

@article {pmid42252587,
year = {2026},
author = {Jin, H},
title = {PET Molecular Probes for Neuroinflammation in Neurodegenerative Diseases: Progress and Prospects.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.6c00338},
pmid = {42252587},
issn = {1948-7193},
abstract = {Neuroinflammation is a central pathological process underlying neurodegenerative diseases, including Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis. Positron emission tomography (PET) molecular probes now enable the noninvasive, quantitative visualization of neuroinflammatory processes in the living brain. This review surveys recent advances in PET probes targeting microglial activation markers─including the 18 kDa translocator protein (TSPO), the purinergic P2X7 receptor (P2X7R), colony-stimulating factor 1 receptor (CSF1R), and sphingosine-1-phosphate receptor 1 (S1PR1)─as well as astrocyte reactivity markers such as monoamine oxidase B (MAO-B) and imidazoline-2 binding sites (I2BS). I discuss the evolution from first-generation TSPO ligands to polymorphism-insensitive third-generation tracers, highlight emerging targets beyond TSPO, and evaluate the translational value of these probes for early diagnosis, disease staging, treatment monitoring, and drug development. Current challenges-including limited cellular specificity, genetic polymorphism effects, quantification difficulties, and clinical accessibility barriers─are analyzed alongside promising solutions. Integrating neuroinflammation PET into multimodal biomarker frameworks will be essential for advancing precision medicine in neurodegenerative diseases.},
}

@article {pmid42253115,
year = {2026},
author = {Orzechowski, K and Wasiluk, M and Milewska, W and Kowalska, N and Chuang, YT and Cao, JY and Wang, CT and Neumann, A and Strzeżysz, O and Kozanecka-Szmigiel, A and Konieczkowska, J and Schab-Balcerzak, E and Lewandowski, W and Woliński, TR},
title = {Synergistic Effects of Nanoparticles and Surface Anchoring on Fine-Tuning the Photonic Bandgap in Blue Phase Liquid Crystals.},
journal = {ACS nano},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsnano.6c01127},
pmid = {42253115},
issn = {1936-086X},
abstract = {Precise control over the photonic bandgap in Blue Phase Liquid Crystals (BPLCs) remains challenging due to the inherent limitations of existing tuning methods. Here, we present a 2-fold approach that synergistically combines internal and external effectors to enable controlled, fine modulation of the photonic bandgap across a wide spectral range of 200 nm. Internally, nanoparticles (NPs) embedded within the BPLC lattice enhance the thermal stability of the blue phase and reduce the cubic unit cell size, thereby shifting the reflection bandgap toward shorter wavelengths. Externally, the chemical structure of homogeneous alignment layers (ALs) affects the spectral position of the Bragg reflection. By systematically varying four ALs and three NP doping levels (0, 0.5, and 2 wt %), a cooperative influence of both effectors on spectral tuning is observed. These interactions are qualitatively explained by contact-angle measurements and chemical interactions at the LC-AL and LC-NP interfaces. Kossel diagram analysis, together with a factor based on the total tuning range and associated statistical descriptors, is used to confirm and quantify Bragg wavelength shifts. The results demonstrate that combined internal and external control provides an effective strategy for adjusting the optical response and thermal behavior of BPLCs, supporting their application in photonic devices.},
}

@article {pmid42253371,
year = {2026},
author = {Chen, X and Mo, Y and Jiang, H},
title = {NEK1 variants and reduced protein levels in Chinese ALS patients: a descriptive study.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1831861},
pmid = {42253371},
issn = {1663-4365},
abstract = {OBJECTIVE: NIMA-related kinase 1 (NEK1) have been implicated in amyotrophic lateral sclerosis (ALS). But genetic spectrum and clinical presentation have not been systematically defined.

METHODS: We screened 378 ALS patients and identified NEK1 variant carriers. Clinical records were reviewed retrospectively to characterise phenotypes. Leukocytes were isolated after routine testing and NEK1 protein abundance was quantified by western blot to assess the relationship between NEK1 protein levels and the rate of clinical progression. In parallel, we conducted a structured narrative review of published NEK1-ALS cases based on a systematic search of PubMed, Embase, and Web of Science. We extracted genetic and clinical information to summarise the variant spectrum, co-mutation profiles, and phenotype differences across populations.

RESULTS: NEK1 variants were identified in 8 of 378 patients (2.12%). Protein analysis showed lower peripheral NEK1 levels among carriers than among controls in this small exploratory sample. An exploratory analysis further suggested that lower systemic NEK1 protein levels may be associated with faster disease progression; however, because these measurements were obtained from peripheral leukocytes at highly heterogeneous sampling times and without adjustment for major clinical confounders, they should be interpreted strictly as descriptive observations and do not support biomarker claims. While phenotypic heterogeneity and population-specific variant distributions were observed, these findings remain descriptive due to the small sample size.

CONCLUSION: This regional case series provides a descriptive overview of NEK1 variants in a Chinese ALS cohort and offers preliminary exploratory evidence consistent with reduced peripheral NEK1 protein levels in variant carriers. The observed inverse relationship between lower measured protein levels and faster clinical decline should be regarded as hypothesis-generating only. Given the small sample size, highly heterogeneous sampling times, use of peripheral leukocytes, and lack of adjustment for major clinical confounders, these protein data do not support biomarker claims at this stage. Validation in larger, prospective multi-center cohorts with standardized longitudinal sampling is required.},
}