@article {pmid41546073,
year = {2026},
author = {Dewan, MF and Rayani, AM and Hannan, J},
title = {Improving nursing students' clinical experience with genetics: the influence of prior knowledge and leadership support through the Donabedian Model.},
journal = {BMC nursing},
volume = {25},
number = {1},
pages = {},
pmid = {41546073},
issn = {1472-6955},
abstract = {BACKGROUND: As advancements in genetics and genomics continue to evolve, nursing students need to be equipped with prior knowledge and academic leadership support (ALS) to interpret genetic information, educate patients, and participate in clinical decision-making. ALS is actions or behaviors by leaders to support, guide, and empower their students. The incorporation of genetics/genomics into the nursing curriculum has been recognized on a global scale.

AIM: To evaluate the impact of nursing students’ prior knowledge of genetics/Genomics and genomics and academic leadership support on their clinical experience.

METHOD AND DESIGN: A cross-sectional study was conducted among nursing students at xxxxx University College of Nursing, Saudi Arabia, between December 2024 and February 2025 (IRB# KSU-HE-24-1055). A total of 169 participants completed an online survey.

RESULTS: Most participants were in their fourth year, internship year, or enrolled in postgraduate programs (BSN = 118; Master’s = 46; PhD = 3). The average age was 26.6 years (SD = 5.8), and more participants were female (58.5%) than male (41.5%). Male participants reported receiving higher levels of leadership support than their female counterparts did. ALS on clinical experience (p < 0.01); and prior knowledge (p < 0.008); R[2] = 0.440 with large effect size = 0.78.

CONCLUSIONS: Integrating genetics and genomics education into the nursing curriculum is needed to meet today’s healthcare standards. Academic nursing leaders in educational settings play a key role in advancing nursing students’ curriculum thereby increasing their knowledge and preparedness for clinical practice.

Educational settings that integrate nursing genetics and genomics courses into curricula and provide leadership support to students will improve their clinical experience and enhance patients’ care.

IMPACT: What problem did the study address? ALS is a key driver of improving students’ clinical experience. What were the main findings? Male nursing students reported higher levels of leadership support than female nursing students highlighting the need for strategies that support equity and prevent disparities in educational settings on the basis of gender. Who will benefit? Nurse educators and nurse leaders could utilize these findings to improve educational environments. Nurses with up-to-date knowledge will benefit their patients’ outcomes by being better informed.

REPORTING METHOD: We adhered to the STROBE guidelines for cross-sectional research.},
}

@article {pmid41912662,
year = {2026},
author = {Liu, Y and Huang, Z and Hsu, YW and Deme, P and Frankenfield, AM and Wu, S and Zhao, X and Liu, H and Zhang, T and Alexander, EJ and Liu, M and Zhang, Y and Wang, H and Zhou, Y and Monteiro, MJ and Hao, L and Haughey, NJ and Wang, J},
title = {UBQLN2 links proteotoxicity with lipid metabolism in neurodegeneration.},
journal = {Nature neuroscience},
volume = {},
number = {},
pages = {},
pmid = {41912662},
issn = {1546-1726},
support = {NS089616//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; NS110098//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; NS074324//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; NS128494//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; NS098243//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; FS-2023-SBF-S6//Target ALS (Target ALS Foundation)/ ; },
abstract = {Protein homeostasis and lipid metabolism are essential processes frequently disrupted in neurodegenerative diseases. However, their mechanistic intersection in disorders such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) remains unclear. Ubiquilin 2 (UBQLN2) is a protein quality control factor linked to ALS/FTD. Through multi-omic analyses of induced pluripotent stem cell (iPSC)-derived neurons harboring disease-associated UBQLN2 mutations, we uncovered UBQLN2 as a molecular hub linking lipid dysregulation and proteostasis, the perturbation of which contributes to neurodegeneration. UBQLN2 mediated the degradation of ILVBL (acetolactate synthase-like protein) and ALDH3A2 (aldehyde dehydrogenase 3 family member A2), two enzymes essential for mitochondrial lipid catabolism associated with lipid droplets and neuronal viability. ALS/FTD-linked UBQLN2 mutations and TAR DNA-binding protein 43 (TDP-43) pathology impair the degradation of ILVBL and ALDH3A2, leading to metabolic dysfunction and neurodegeneration. Restoring the UBQLN2-ILVBL/ALDH3A2 axis attenuates neurodegenerative phenotypes in neurons, organoids and mice, establishing UBQLN2 as a critical regulator of metabolic homeostasis in ALS/FTD and other related neurodegenerative diseases.},
}

@article {pmid41912988,
year = {2026},
author = {Zheng, H and Yu, S and Zhou, T and Fu, S and Zhang, J and Zhang, N and Liu, Y and Huang, Y and He, Z and Zhang, J and Liu, P and Gong, M and Zhou, C},
title = {Distinct amino acid metabolic subtypes predict prognosis and stratify treatment response in acute-on-chronic liver failure: a multicenter prospective study.},
journal = {Hepatology international},
volume = {},
number = {},
pages = {},
pmid = {41912988},
issn = {1936-0541},
support = {82305067//National Natural Science Foundation of China/ ; 2018ZX10725506-002//National Science and Technology Major Project of China during the 13th Five-Year Plan Period/ ; },
abstract = {BACKGROUND: Acute-on-chronic liver failure (ACLF) exhibits high mortality and heterogeneity, demanding precise risk stratification. We aimed to identify metabolic subtypes and explore their association with prognosis and real-world artificial liver support (ALS) responsiveness.

METHODS: This prospective, multicenter, observational cohort study enrolled 142 ACLF patients. Serum was collected at baseline, prior to ALS initiation. Patients were subtyped via metabolomics clustering. ALS exposure was analyzed using inverse probability of treatment weighting (IPTW) and Cox models to test for heterogeneity of treatment effect.

RESULTS: Two subtypes were identified (Cluster 1/2). Cluster 2 showed significantly higher 90 day mortality (p = 0.032) and severe amino acid metabolic reprogramming, particularly in branched-chain amino acid and glutamine pathways. Exploratory analysis suggested a differential association between ALS and survival across subtypes (interaction p = 0.12). ALS showed a weaker survival association in Cluster 2 after IPTW adjustment.

CONCLUSION: ACLF patients possess distinct amino acid-based metabolic subtypes that are potent prognostic indicators. Baseline metabolic profiling can serve as a stratification tool to identify patients who may derive the greatest clinical benefit from ALS therapy, guiding personalized treatment strategies.},
}

@article {pmid41913878,
year = {2026},
author = {Elfadil, U and Al-Majmuei, A and Alatoom, M and Juma, S and Shukralla, A},
title = {The Impact of Preoperative Nutritional Status on the Incidence of Anastomotic Leaks in Colorectal Surgery.},
journal = {Cureus},
volume = {18},
number = {2},
pages = {e104329},
pmid = {41913878},
issn = {2168-8184},
abstract = {Anastomotic leaks (ALs) are among the most serious complications following colorectal surgery, contributing to significant morbidity, reoperation, and prolonged hospitalisation. Poor preoperative nutritional status has been proposed as a modifiable risk factor; however, evidence from studies remains inconsistent. This systematic review, conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD420251034523), synthesised findings from 32 eligible studies, including randomised controlled trials, cohort studies, and case-control designs, published between 2005 and 2025. Across 474 initially identified articles, nutritional status was assessed using serum albumin, body mass index (BMI), Subjective Global Assessment (SGA), Nutritional Risk Index (NRI), or Prognostic Nutritional Index (PNI). AL incidence ranged from 2.8% to 11.3%, with hypoalbuminaemia and low nutritional indices consistently associated with increased risk. Several studies have suggested that nutritional optimisation, particularly immunonutrition and enteral support initiated 7-14 days preoperatively, improves secondary outcomes, such as wound infection rates, hospital stay, and overall morbidity. However, reductions in leak incidence are less consistent. The certainty of evidence linking poor nutritional status to leak risk was rated as moderate, while the evidence for nutritional interventions was rated as low due to heterogeneity and small sample sizes. Perioperative factors, including operative time, intraoperative blood loss, transfusion, and steroid use, were also significant contributors to leak risk. Overall, nutritional status is a key, modifiable predictor of AL; however, integration with surgical and perioperative optimisation is essential. High-quality multicentre trials are needed to define optimal nutritional strategies and establish standardised risk assessment tools for clinical practice.},
}

@article {pmid41914380,
year = {2026},
author = {Chen, L and Chen, EW and Chen, BW and Wang, D},
title = {Retinol Taking a Detour Promotes Neural Stem Cell Self-Renewal In Vivo Accompanied by Down-Regulation of Some Retinoic Acid Receptors.},
journal = {Stem cells and development},
volume = {},
number = {},
pages = {15473287261436286},
doi = {10.1177/15473287261436286},
pmid = {41914380},
issn = {1557-8534},
abstract = {Since our previous studies have indicated retinol promotes self-renewal of embryonic stem cells in vitro culture, we speculate that retinol may be directly involved in regulating adult stem cell self-renewal or developmental function in vivo. Vitamin A or retinoic acid (RA) solution was first injected into the abdominal cavities of mice, and then self-renewal and development marker gene expressions were investigated. The in vivo effects of retinol and RA on RA receptor expressions were further examined. The results showed that retinol not only significantly promotes self-renewal of neural stem cells in vivo but also induces orientational development of neural stem cells in vivo and significantly downregulates the expression of some RA receptor gene expression in the brain. This study provides experimental and theoretical bases for elucidating the regulation mechanism of retinol-mediated cell development in vivo, especially in brain, and the development of therapeutic drugs for neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Multiple sclerosis, and Huntington's disease.},
}

@article {pmid41915953,
year = {2026},
author = {Zhang, Y},
title = {Letter to the editor: "Evolution of triglyceride and total cholesterol levels after critical illness: Preliminary insights into post-ICU metabolic sequelae".},
journal = {Journal of critical care},
volume = {94},
number = {},
pages = {155557},
doi = {10.1016/j.jcrc.2026.155557},
pmid = {41915953},
issn = {1557-8615},
abstract = {This letter evaluates Rousseau et al.'s recent study on post-intensive care unit dyslipidemia. While commending their focus on metabolic sequelae, we propose three clinical refinements. First, defining "de novo" hypertriglyceridemia using acute-phase ICU lipid troughs risks overestimating its true incidence, as these values represent pathological stress rather than physiological baselines. Second, profound post-discharge lifestyle transitions, particularly severe physical inactivity and ad libitum diets, must be considered alongside systemic inflammation as primary drivers. Finally, stratifying the cohort's diverse admission etiologies is essential to avoid diluting distinct metabolic phenotypes and improve targeted post-ICU care.},
}

@article {pmid41916013,
year = {2026},
author = {Phan, PQ and Nagata, JM and Le, TP},
title = {Queer Asian American men's self-objectification: A test of racially relevant factors.},
journal = {Body image},
volume = {57},
number = {},
pages = {102079},
doi = {10.1016/j.bodyim.2026.102079},
pmid = {41916013},
issn = {1873-6807},
abstract = {Queer Asian American men face pervasive experiences of racial discrimination within the queer community and the broader society, which may critically impact their body image outcomes. While some studies have documented how racially relevant factors may shape body image attitudes among queer Asian American men, no studies have investigated the racialized experience of self-objectification among this under-researched subgroup. Hence, the present study adopts Cheng et al.'s (2017) racially expanded model of objectification theory among Asian American college women and applies a strengths-based approach to examine the associations between resistance and empowerment against racism (REAR), internalized racism, pride in Asian features, and self-objectification. Thus, among a sample of 265 queer Asian American men, analyses of indirect effects revealed that REAR was indirectly associated with lower self-objectification via greater pride in Asian features, whereas internalized racism was not indirectly associated with self-objectification via pride in Asian features. Furthermore, internalized racism was directly associated with greater self-objectification and lower pride in Asian features. Our findings contribute to the limited yet growing literature on the racialized experience of body image among queer Asian American men, underscoring the nuanced ways in which resistance against racism and internalization of racial oppression are associated with self-objectification. Social justice-informed implications are discussed, including efforts to deconstruct the internalization of White supremacist ideologies and empower queer Asian American men to engage in resistance through future research, clinical interventions, and prevention programs.},
}

@article {pmid41916622,
year = {2026},
author = {Addington, C and Davies, N and Howell, P and Cruickshank, S and Hainsworth, E},
title = {Lived experiences of cancer care for people living with HIV who are treated for anal cancer: a scoping review.},
journal = {BMJ open},
volume = {16},
number = {3},
pages = {e114180},
doi = {10.1136/bmjopen-2025-114180},
pmid = {41916622},
issn = {2044-6055},
mesh = {Humans ; *Anus Neoplasms/therapy/psychology/complications ; *HIV Infections/complications/psychology ; *Quality of Life ; },
abstract = {OBJECTIVE: This scoping review aims to identify existing evidence on the lived experiences of people living with HIV and treated for anal cancer, and to identify what aspects of health and well-being are addressed in clinical guidance.

DESIGN: A preregistered protocol (Open Science Framework, 2025) guided the review. We followed the Arksey and O'Malley framework, incorporating Levac et al's refinements around stakeholder consultation. Joanna Briggs Institute (JBI) guidance informed eligibility and data for charting, and reporting adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.

DATA SOURCES: Systematic searches were performed across multiple databases, including CINAHL, MEDLINE, PsycINFO and Embase, using EBSCOhost and Ovid, supplemented handsearching reference lists. Two search strategies were used: one for research studies and one for clinical guidelines.

ELIGIBILITY CRITERIA: Sources included people living with HIV treated for anal cancer, capturing lived experiences directly through qualitative studies or indirectly via quantitative patient-reported outcomes and/or health-related quality of life. Guidelines addressing HIV or anal cancer were also included.

DATA CHARTING AND SUMMARIES: Data were charted to capture patient experiences and outcomes on living with and beyond cancer, and how these are addressed in clinical management and guidance, including biomedical, psychosocial, sexual and functional aspects, and patient-reported outcomes.

RESULTS: Of 945 records, three studies and four guidelines met criteria. No study focused exclusively on people living with HIV; findings reflect broader anal cancer populations with HIV-positive subsets. Studies addressed aspects of health-related quality of life which we mapped into physical, psychosocial and sexual domains. Clinical guidance prioritised treatment dosage and survival, with limited attention to broader effects. Stakeholders highlighted that existing research and guidance miss important nuances of lived experience and care needs.

CONCLUSIONS: No identified research solely explored the lived experiences of people living with HIV treated for anal cancer, leaving guidance non-specific and biomedical. The identified domains offer a starting point for future research; however, to inform patient-centred care, stakeholders emphasised the need to understand how living with HIV and anal cancer shapes health needs.},
}

Humans
*Anus Neoplasms/therapy/psychology/complications
*HIV Infections/complications/psychology
*Quality of Life

@article {pmid41916881,
year = {2026},
author = {Calma, AD and Pavey, N and Silva, CS and Tsuji, Y and Ghapar, AA and Morris, K and Kiernan, MC and Farrar, MA and Menon, P and Vucic, S},
title = {Utility of Far-Field Potentials as a Biomarker of Neurodegeneration in Spinal Muscular Atrophy.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70231},
pmid = {41916881},
issn = {1097-4598},
abstract = {INTRODUCTION/AIMS: Far field potentials (FFP) have been proposed as a reliable neurophysiological prognostic biomarker in amyotrophic lateral sclerosis (ALS). This study evaluated the utility of ulnar nerve FFP as a robust research biomarker of lower motor neuron degeneration in spinal muscular atrophy (SMA).

METHODS: Peripheral neurophysiological assessments were performed in 13 participants with SMA, 19 with amyotrophic lateral sclerosis (ALS), and 19 healthy controls. The ulnar nerve was stimulated at the wrist, and motor responses were recorded over the abductor digiti minimi (ADM) muscle. Recorded measures included compound muscle action potential (CMAP), FFP and near-field potential (NFP) amplitudes, and motor unit number index (MUNIX).

RESULTS: The FFP amplitude was significantly lower in SMA participants compared to healthy volunteers (p < 0.001), but comparable to ALS (p = 0.11). The FFP amplitude showed strong correlations with the Revised Upper Limb Module (RULM) (ρ = 0.92), ALS Functional Rating Score-Revised (ρ = 0.85), upper limb MRC score (ρ = 0.89), CMAP amplitude (ρ = 0.97), NFP amplitude (ρ = 0.88), and MUNIX values (ρ = 0.84), all of which were highly statistically significant. Multiple linear regression indicated that FFP amplitude was an independent predictor of RULM (p < 0.001).

DISCUSSION: FFP amplitude appears to be a promising neurophysiological biomarker for SMA, with potential utility for monitoring disease progression, particularly in a clinical trial setting.},
}

@article {pmid41917183,
year = {2026},
author = {Eom, E and Kim, J and Kim, J and Kang, SJ},
title = {STING is the scaffold protein for stress granule pre-condensation at the ER.},
journal = {Cell death and differentiation},
volume = {},
number = {},
pages = {},
pmid = {41917183},
issn = {1476-5403},
support = {RS-2024-00339685//National Research Foundation of Korea (NRF)/ ; RS-2024-00339685//National Research Foundation of Korea (NRF)/ ; },
abstract = {Stress granules (SGs) are dynamic, membraneless ribonucleoprotein condensates that assemble in response to cellular stress and coordinate diverse cellular stress responses and diseases. Although SG have been reported to associate with the endoplasmic reticulum (ER), how ER-localized stress granule assembly is organized and regulated remains unclear. STING (stimulator of interferon genes) is a central innate immune adaptor that has recently been implicated in diverse non-canonical cellular functions, yet its potential link to SG regulation has not been established. Independent of its canonical functions in innate immune signaling, we identified a novel role of STING as a regulator of SG formation. We found that prior to stress stimulation, STING interacts with key SG core components G3BP1 and UBAP2L via its C-terminal domain (CTD) at the ER, forming a pre-condensation complex that facilitates SG maturation in response to stress. Loss of STING reduces SG formation and increases stress-induced cell death, whereas ER-anchored STING CTD is sufficient to reverse them. Mechanistically, STING enhances basal interactions between G3BP1 and UBAP2L, lowering the threshold for SG maturation upon stress. In addition, STING promotes the pathologic effects of TDP-43 mutations associated with amyotrophic lateral sclerosis. Our findings implicate STING as an ER-resident regulator of SG dynamics that contributes to neurodegenerative pathology, highlighting it as a potential therapeutic target in diseases associated with aberrant SG assembly.},
}

@article {pmid41906032,
year = {2026},
author = {Abdelaal, Z and Boya, BR and Lee, JH and Lee, J},
title = {Targeting Als3 adhesin of clinically relevant Candida species using natural carotenoids: an in-silico study.},
journal = {Molecular diversity},
volume = {},
number = {},
pages = {},
pmid = {41906032},
issn = {1573-501X},
support = {RS-2025-00513239//the National Research Foundation of Korea (NRF)/ ; },
abstract = {Candidemia, caused by the opportunistic Candida spp., poses a severe global health threat, characterized by mortality rates reaching 75% and the increasing prevalence of multidrug-resistant biofilms. In this study, we targeted the Agglutinin-Like Sequence 3 (Als3) adhesin protein, the primary mediator of Candida species attachment, as a non-lethal strategy to inhibit biofilm formation. Using molecular docking, we screened a library of 1570 natural carotenoids against the conserved N-terminal domain of Als3 of Candida albicans and compared to five positive controls. Our virtual screening identified five compounds (mangicrocin, MODU, α-zeacarotene-3,17'-diol, BTTB, and (15Z)-zeaxanthin-3'-rhamnoside), with the best binding pose and the least binding energy. Among them, mangicrocin showed best binding affinity (docking score - 7.18 kcal/mol, ΔGbind - 35.23 kcal/mol) against C. albicans Als3, compared to the in vitro and in silico positive control, rutin (docking score - 5.772 kcal/mol, ΔGbind - 30.59). It consistently achieved the best docking scores across C. albicans Als family proteins (Als1 and Als5) and Als3 proteins of other species in the Candida genus like C. auris, C. tropicalis, C. parapsilosis, and C. dubliniensis. Molecular electrostatic potential (MESP) mapping analysis further clarified that the hydrophobic polyene backbone and the negative electrostatic potential of the OH groups on the aromatic rings aid in anchorage to the key cadherin-binding residues-Lys59 and Ser170 in the Als3 binding pocket. Density Functional Theory (DFT) analysis shows high electrophilicity and a narrow energy gap contributes to mangicrocin's interactions and chemical reactivity. Molecular dynamics simulations suggested stable retention of mangicrocin within the Als3 binding pocket, supported by stable structural parameters and favorable interaction energy profiles. In silico ADMET profiling concludes these top five hits had limited toxicity and are druggable. As this study is entirely computational, these findings are predictive and require future in vitro validation to confirm biological efficacy.},
}

@article {pmid41906147,
year = {2026},
author = {Zhou, X and Yu, P and Shen, X},
title = {m6A RNA methylation in neural plasticity, brain aging, and neurodegenerative vulnerability.},
journal = {Molecular brain},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13041-026-01297-z},
pmid = {41906147},
issn = {1756-6606},
support = {82471208 and 82171184//National Natural Science Foundation of China/ ; },
abstract = {m6A is a pervasive post-transcriptional RNA modification that regulates RNA splicing, stability, localization, and translation in the brain. In this review, we outline the core m6A regulatory machinery and summarize its spatial organization across neurons and glial cells, highlighting established roles in brain development, synapse formation, and axon growth. We then focus on experience-dependent plasticity, synthesizing evidence that neuronal activity and environmental inputs dynamically reshape m6A to regulate immediate-early transcription and local translation at synapses across sensory, cognitive, emotional, and motor domains. With aging, m6A programs are reconfigured in a cell-type-specific manner, a shift associated with reduced plasticity and increased vulnerability. We further survey disease-associated alterations in m6A across Alzheimer's disease, Parkinson's disease, Huntington's disease, stroke-related cognitive impairment, ALS and FTD, as well as metal or toxin exposure, emphasizing convergent effects on dopaminergic and glutamatergic signaling, synaptic integrity, inflammation, and cellular stress responses. Finally, we discuss emerging opportunities and conceptual challenges in targeting m6A enzymes or reader proteins, and outline priorities for future work, including cell-type- and subcellular-resolved mapping, causal perturbation in defined circuits and life stages, and the development of biomarkers and selective modulators. Together, these observations position m6A as a molecular interface linking experience-dependent plasticity, brain aging, and neurodegenerative vulnerability.},
}

@article {pmid41906403,
year = {2026},
author = {Correale, J},
title = {Glial Plasticity and Dysfunction: Mechanistic Insights and Therapeutic Opportunities in Neurodegeneration.},
journal = {Journal of neurochemistry},
volume = {170},
number = {4},
pages = {e70414},
doi = {10.1111/jnc.70414},
pmid = {41906403},
issn = {1471-4159},
mesh = {Humans ; *Neuroglia/metabolism/pathology/physiology ; Animals ; *Neurodegenerative Diseases/therapy/metabolism/pathology/physiopathology ; *Neuronal Plasticity/physiology ; *Cell Plasticity/physiology ; },
abstract = {Recent advances, including single-cell transcriptomics, lineage tracing, and in vivo imaging, have unveiled the heterogeneity, plasticity, and functional versatility of astrocytes, microglia, oligodendrocytes, and Schwann cells. These cells respond to metabolic and immune cues, participate in synaptic regulation, and provide metabolic and trophic support to neurons. Their dual roles in neuroprotection and neurodegeneration underscore the complexity of their contributions across CNS disorders. This review examines the diverse physiological and pathological roles of glia, emphasizing their involvement in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Mechanisms including metabolic dysfunction, inflammatory polarization, glial-immune crosstalk, and extracellular vesicle-mediated signaling are critically discussed. Emerging therapeutic strategies, ranging from glial reprogramming and senolytic therapies to the use of engineered extracellular vesicles and metabolic modulators, are evaluated for their potential to harness glial plasticity and mitigate disease progression. The review also outlines current challenges in translating glial biology into clinical interventions, including cellular heterogeneity, delivery barriers, and the need for specific biomarkers. A glia-centered therapeutic paradigm offers promising avenues to restore CNS homeostasis and promote regeneration in neurodegenerative diseases.},
}

Humans
*Neuroglia/metabolism/pathology/physiology
Animals
*Neurodegenerative Diseases/therapy/metabolism/pathology/physiopathology
*Neuronal Plasticity/physiology
*Cell Plasticity/physiology

@article {pmid41906714,
year = {2026},
author = {Schellenberg, KL and Nataraj, R},
title = {Reviewer Comment on Li et al. "Nocturnal Hypoxia and Sleep-Disordered Breathing as Potential Early Biomarkers of Respiratory Progression in Mild ALS".},
journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques},
volume = {},
number = {},
pages = {1},
doi = {10.1017/cjn.2026.10558},
pmid = {41906714},
issn = {0317-1671},
}

@article {pmid41907197,
year = {2026},
author = {Elshony, H and Almuhanna, R and Albazli, KO and Muddassir, R},
title = {Hereditary transthyretin amyloidosis mimicking ALS: First genetically proven case report from Saudi Arabia.},
journal = {eNeurologicalSci},
volume = {43},
number = {},
pages = {100607},
pmid = {41907197},
issn = {2405-6502},
abstract = {BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv) is a systemic disorder that may mimic motor neuron disease (MND), leading to misdiagnosis and delayed access to disease-modifying therapies.

CASE REPORT: We report the first genetically confirmed case of ATTRv mimicking amyotrophic lateral sclerosis (ALS) in Saudi Arabia. A 47-year-old male presented with progressive right-sided limb weakness (proximal > distal) and dysarthria over 18 months. Neurological examination revealed fasciculations, distal atrophy, and brisk reflexes with normal muscle tone and no spasticity. Electrophysiological studies demonstrated a length-dependent sensorimotor axonal neuropathy with widespread denervation changes involving bulbar, cervical, and lumbosacral regions. Brain and spine MRI, along with whole-body CT, excluded structural or paraneoplastic causes. Genetic testing identified a pathogenic heterozygous variant in the TTR gene: NM_000371.4:c.424G > A (p.Val142Ile). Transthoracic echocardiography revealed mild concentric left ventricular hypertrophy. There was no clinical evidence of autonomic, renal, or ocular involvement.

DISCUSSION: This case underscores the importance of considering ATTRv in patients presenting with atypical MND, particularly when clinically significant sensory symptoms, absent upper motor neuron signs, or unexplained cardiac abnormalities are present. Early diagnosis enables access to targeted therapies such as TTR stabilizers and gene-silencing agents, which can alter disease trajectory.},
}

@article {pmid41907482,
year = {2026},
author = {Pham, N and Nguyen, CTH and Van, TT},
title = {Response to Brenaut et al., "Response to Pham et al's 'Sensory symptoms of scalp psoriasis are not sensitive scalp syndrome'".},
journal = {JAAD international},
volume = {25},
number = {},
pages = {139},
pmid = {41907482},
issn = {2666-3287},
}

@article {pmid41907560,
year = {2026},
author = {Ozgor, B and Goktas, OF and Baygin, M and Dogan, S and Tuncer, T},
title = {Differential quadruple pattern: A new EEG signal classification framework.},
journal = {IBRO neuroscience reports},
volume = {20},
number = {},
pages = {492-505},
pmid = {41907560},
issn = {2667-2421},
abstract = {EEG signals are the letters of the brain and reflect neural activity. Abnormal EEG patterns indicate brain disorders such as epilepsy. Recently, machine learning has enabled automated EEG interpretation with high accuracy. This study introduces an explainable EEG classification model based on feature engineering. A novel feature extractor, Differential Quadruple Pattern (DiffQuadPat), is proposed. DiffQuadPat computes relations between four channel values using difference-based transformations and combinational transition tables. Feature selection is performed by Cumulative Weight Neighborhood Component Analysis (CWNCA), and classification is achieved with t-algorithm-based k-Nearest Neighbors (tkNN). For interpretability, Directed Lobish (DLOB) is used to produce symbolic explanations. The proposed DiffQuadPat-centric XFE framework was validated on two EEG datasets: Amyotrophic Lateral Sclerosis (ALS) and neonatal epilepsy detection. The model achieved over 98% accuracy under 10-fold cross-validation. Furthermore, cortical and hemispheric connectome diagrams were generated, enabling transparent visualization of brain-level interactions.},
}

@article {pmid41908423,
year = {2026},
author = {Girdthep, S and Yodsin, N and Phonprasert, J and Suwanchawalit, C and Swanglap, P},
title = {Sustainable Natural Lake Pigments from Caesalpinia sappan: Improving Stability through Inorganic Support Morphologies for Colored PLA Packaging Films.},
journal = {ACS omega},
volume = {11},
number = {11},
pages = {17948-17966},
pmid = {41908423},
issn = {2470-1343},
abstract = {Red-pink natural lake pigments were prepared from Caesalpinia sappan L. extract colorant powder (S-Alum, without inorganic supports) and as colorant-adsorbed inorganic supports: silica (S-Si) and kaolinite (S-Kaol). Among these, S-Kaol demonstrated the highest stability and color strength (K/S), supported by its superior initial thermal degradation at 450 °C, high pH and UV stability, and consistent hue (H° = 19-22). X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) analyses confirmed the formation of a stable structure in S-Kaol, involving strong electrostatic interactions between brazilein and the kaolinite surface through Al[3+] chelation. The DFT results further revealed an Al adsorption energy of -0.97 eV and a strong orbital hybridization between the Al (s) and the O (p) orbitals. The resulting pigments were incorporated into PLA to produce pinkish-red composite films. PLA/S-Kaol demonstrated superior pigment dispersity, thermal stability, and photostability, showing only a minor hue shift (H° shifting from 33.12° to 32.21°) after 168 h of UV exposure, attributed to the UV-shielding effect of kaolinite layers. In contrast, spherical S-Si particles introduced film defects, while amorphous S-Alum yielded moderate improvements. Overall, the inorganic supports acted as nucleating agents, enhancing PLA crystallization and thermal performance. These findings highlight S-Kaol as a renewable, nontoxic with heavy metal-free alternative to synthetic dyes for biodegradable polymer applications.},
}

@article {pmid41908699,
year = {2025},
author = {Barai, P and Leroy, G and Ahmed, A},
title = {Comparative Evaluation of Text and Audio Simplification: A Methodological Replication Study.},
journal = {Communications of the Association for Information Systems},
volume = {57},
number = {},
pages = {1059-1084},
pmid = {41908699},
issn = {1529-3181},
abstract = {This study serves as a methodological replication of Leroy et al.'s (2022) research, which investigated the impact of text simplification on healthcare information comprehension in the evolving multimedia landscape. Building upon the original study's insights, our replication study evaluates audio content, recognizing its increasing importance in disseminating healthcare information in the digital age. Specifically, we explored the influence of text simplification on perceived and actual difficulty when users engage with audio content automatically generated from that text. Our replication involved 44 participants for whom we assessed their comprehension of healthcare information presented as audio created using Leroy et al.'s (2022) original and simplified texts. The findings from our study highlight the effectiveness of text simplification in enhancing perceived understandability and actual comprehension, aligning with the original study's results. Additionally, we examined the role of education level and language proficiency, shedding light on their potential impact on healthcare information access and understanding. This research underscores the practical value of text simplification tools in promoting health literacy. It suggests the need for tailored communication strategies to reach diverse audiences effectively in the healthcare domain.},
}

@article {pmid41909467,
year = {2026},
author = {Nagamatsu, Y and Umezu, T and Hong, T and Niijima, T and Ohno, SI and Harada, Y and Kanekura, K and Ochiya, T and Kuroda, M},
title = {Exosome-like nanovesicles from acerola for CRISPR-Cas9 ribonucleoprotein delivery to the central nervous system.},
journal = {Molecular therapy. Nucleic acids},
volume = {37},
number = {2},
pages = {102896},
pmid = {41909467},
issn = {2162-2531},
abstract = {An aberrant six-base repeat in intron 1 of C9orf72 is the most frequent cause of solitary and familial amyotrophic lateral sclerosis and frontotemporal dementia. This mutation is a potential target for CRISPR/Cas9-based genome editing. However, the blood-brain barrier and limitations of current viral or nanoparticle-based delivery systems to neurons significantly restrict the clinical application of CRISPR-Cas9 in the brain. To address these challenges, we developed a drug delivery system using acerola-derived exosome-like nanoparticles (AELNs), which may overcome several limitations associated with human exosomes. AELNs stably form complexes with ribonucleoproteins (RNPs) comprised of Cas9 proteins and guide RNAs (gRNAs). We improved the delivery efficiency and selectivity of AELN/RNP complexes in GLP2-receptor-expressing neurons by incorporating GLP2 peptides into the AELN/RNP complexes. Intranasal administration of peptide-tagged AELN/RNP complexes in vivo confirmed the successful genome editing of C9orf72, demonstrating the potential of this system for treating neurodegenerative diseases. This study presents a potentially innovative approach for in vivo genome editing using a noninvasive delivery system.},
}

@article {pmid41909487,
year = {2026},
author = {Gowdy, J and Ahn, J and Miller, RH and Islam, Y},
title = {Neurovascular dysfunction in the development and progression of neuroinflammatory diseases.},
journal = {Frontiers in cellular neuroscience},
volume = {20},
number = {},
pages = {1741928},
pmid = {41909487},
issn = {1662-5102},
abstract = {The neurovascular unit (NVU) is critical for brain homeostasis through its roles in maintenance of an effective blood brain barrier (BBB) and regulation of cerebral blood flow. Perturbation of the NVU is a hallmark of the pathology of multiple neurodegenerative diseases resulting in loss of BBB integrity, neuroinflammation and neuronal dysfunction. The NVU is a complex structure composed of endothelial cells, pericytes, as well as central nervous system (CNS) glial and neuronal components. While the importance of the CNS vasculature in health and disease is well established, the mechanisms underlying vascular pathology and its contributions to neurodegenerative diseases are less well defined. Neuroinflammation and reactive gliosis occurs in the majority of neurodegenerative diseases and recent studies suggest that immune mediated disruption of the BBB contributes to the induction of reactive gliosis and neuronal dysfunction. Potential consequences of NVU disruption include immune-driven vascular inflammation and leukocyte infiltration in Multiple Sclerosis (MS), protease-mediated tight junction degradation in ischemic stroke (IS), α-synuclein-associated endothelial dysfunction in Parkinson's Disease (PD), amyloid-β- and tau-induced pericyte injury in Alzheimer's Disease (AD), and complement-mediated vascular damage in Amyotrophic Lateral Sclerosis (ALS). Here we review the nature of NVU perturbations in these common neurodegenerative diseases, with an emphasis on the contribution of immune modulation of BBB disruption in neuropathology and disease progression.},
}

@article {pmid41909553,
year = {2026},
author = {J, MA and C, A},
title = {Gender euphoria reimagined: toward an Extended Theory of Trans-Identity.},
journal = {Frontiers in psychology},
volume = {17},
number = {},
pages = {1738195},
pmid = {41909553},
issn = {1664-1078},
abstract = {INTRODUCTION: The paper focuses on developing an Extended Theory of Trans-Identity integrating Nagoshi et al.'s trans-identity theory with the creative expression of the self to explore gender-euphoric experiences.

METHOD: Having explored Austin et al.'s research on the artistic expression of trans people, the article attempts to explore the creative manifestation of identity as an important aspect of trans-identity formation, alongside Nagoshi et al.'s trans-identity theory. The synthesis of four aspects, including physical embodiment, self-construction, social construction, and the creative manifestation of the identified gender leading to the attainment of gender-euphoric factors identified by Austin et al. and Leitch et al., culminates in an Extended Theory of Trans-Identity. The theoretical framework is applied to I Am Vidya: A Transgender's Journey (2013), the autobiography of Living Smile Vidya, who is an eminent trans theatre artist and activist from Tamil Nadu, India. Furthermore, the use of a literary text to validate the Extended Theory draws on Schilling's concept of theory extrapolation from literature. The exemplifying textual analysis of the dynamic role of the four aspects of trans-identity in asserting transness and achieving gender euphoria attempts to substantiate the proposed theoretical extension.

RESULTS: The results indicate that identity construction through the creative aspect, in combination with the biopsychosocial aspects, contributes to the utmost attainment of gender euphoria.

DISCUSSION: Therefore, the article formulates an extended version of the trans-identity framework, emphasising the inclusion of creativity in the gender-affirmative journeys of trans people.},
}

@article {pmid41910574,
year = {2026},
author = {Zhang, W},
title = {The evolving portrait of psychologists: A commentary on Xu et al. (2026).},
journal = {The American psychologist},
volume = {81},
number = {3},
pages = {423-425},
doi = {10.1037/amp0001694},
pmid = {41910574},
issn = {1935-990X},
mesh = {Humans ; *Psychology/trends ; Psychologists ; },
abstract = {Xu et al.'s (2026) portrayal of the evolving portrait of psychologists is valuable, yet several points merit further discussion or refinement. When interpreting the "decline of conscientiousness and rise of openness," additional factors should be considered-such as psychology's growing applied attribute, the public impact of psychoanalysis, transformations in book publishing, and the increasing number of female psychologists. The analysis could also benefit from: A stronger account of psychology's own disciplinary self-positioning, cross-cultural extensions and comparative findings, and comparisons with personality assessments of actual psychologists. (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}

Humans
*Psychology/trends
Psychologists

@article {pmid41910654,
year = {2026},
author = {Yu, Z and Li, H and Wang, Y and Li, Y and Shen, F and Wang, Y},
title = {The Microglial Lactate-Lactylation Axis as a Metabolic-Epigenetic Driver of Alzheimer's Disease.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2025.1487},
pmid = {41910654},
issn = {2152-5250},
abstract = {The idea of amyloid-β (Aβ) plaques and tau neurofibrillary tangles has long been central to framing an understanding of Alzheimer disease (AD), but emerging and growing evidence now points to bioenergetic failure and metabolic-epigenetic crosstalk as central to AD progression. Hai et al. summarize animal and human biofluid and neuroimaging data to carve out the pathophysiology of AD in relation to the role of disrupted glucose metabolism, lactate build-up and protein lactylation in glucose metabolism, in their comprehensive review "Lactate, Lactylation and Alzheimer Disease". Building on Hai et al.'s key contributions, we offer a complementary perspective. The microglial lactate-lactylation axis may be remodeled across disease stages during chronic neuroinflammation, potentially serving compensatory functions early but shifting toward maladaptive, pro-inflammatory amplification at later stages. In light of emerging evidence for tau lactylation in human AD brain tissue, we propose a testable hypothesis of intercellular metabolic crosstalk: lactate exported from highly glycolytic microglia may alter local lactate availability and provide an additional substrate for neuronal tau lactylation. Although the causal contribution of lactate from distinct cellular sources remains to be established, this framework provides a useful lens for interpreting coupled metabolic and epigenetic mechanisms in AD. Our future efforts should focus particularly on glycolytic flux, lactate, epigenetic writers/erasers, therapeutic approaches, and non-pharmacological approaches to stage- and cell-specific lactylation profiling, biomarker development, and the incorporation of metabolic and epigenetic endpoints into interventional studies.},
}

@article {pmid41910849,
year = {2026},
author = {Akram, SW and K, C},
title = {Enhancing Parkinson's Disease Staging: An Integrative Deep Learning Framework for Multimodal Feature Selection.},
journal = {Journal of molecular neuroscience : MN},
volume = {76},
number = {2},
pages = {},
pmid = {41910849},
issn = {1559-1166},
mesh = {Humans ; *Parkinson Disease/diagnostic imaging/genetics/pathology/diagnosis ; *Deep Learning ; Neuroimaging/methods ; Magnetic Resonance Imaging ; Male ; Female ; },
abstract = {Parkinson's disease (PD) affects 10 million globally, with accurate staging essential for personalized treatment planning. Current UPDRS assessments achieve < 93% accuracy due to subjective clinical judgment and unimodal data limitations, failing to capture complex genetic-neuroimaging-clinical interactions driving disease heterogeneity. This study introduces MAFNet, a novel deep learning framework pioneering Iterative Adaptive Vold-Kalman Filter (IAVKF) temporal denoising, Accelerated Binary Particle Swarm Optimization (ABPSO) swarm feature selection, Multilayer Perceptron-Lagrangian Support Vector Machine (MLP-LSVM) classification, and Graph-Attention Based Multimodal Fusion Network (GAMF). Applied to PPMI cohort (200 patients) with genetic SNPs (50), neuroimaging voxels (1,024), and UPDRS-III scores, the end-to-end pipeline delivers 97.6% accuracy, 98.2% precision, 96.8% recall, and 97.3% F1-score-outperforming CNN (92.4%), Autoencoder (90.8%), InceptoFormer (96.6%), and HCT (97.0%). IAVKF boosts SNR + 15.2dB (+ 2.9% accuracy vs. PCA/t-SNE); ABPSO reduces 1,276→340 features (73% reduction); regularization cuts overfitting gap to 0.9% (vs. 4.2% baseline). SHAP interpretability validates clinical plausibility (top predictors: LRRK2 SNPs, UPDRS-III tremor, hippocampal volume). Five-fold CV confirms stability with the Indian cohort external validation. Real-time inference (0.2s/patient, RTX 3090) enables clinical deployment. Future scope includes longitudinal temporal modelling, modality-agnostic fusion, edge deployment, federated learning, and extension to Alzheimer's/ALS. MAFNet transforms PD staging from subjective assessments to objective precision medicine, enabling biomarker discovery, progression forecasting, and personalized therapies across diverse global populations.},
}

Humans
*Parkinson Disease/diagnostic imaging/genetics/pathology/diagnosis
*Deep Learning
Neuroimaging/methods
Magnetic Resonance Imaging
Male
Female

@article {pmid41910875,
year = {2026},
author = {Rajagopalan, V and Pioro, EP},
title = {Diffusion network model analysis of multimodal neuroimaging reveals differential patterns of brain disease propagation in four subgroups of ALS patients.},
journal = {Brain imaging and behavior},
volume = {20},
number = {2},
pages = {},
pmid = {41910875},
issn = {1931-7565},
}

@article {pmid41911331,
year = {2026},
author = {Kwan, JY and Lantz, CI and Korobeynikov, VA and Snyder, A and Huang, X and Haselhuhn, T and Dore, KN and Madruga, A and Danielian, LE and Schindler, AB and Chia, R and Rasheed, M and Crook, J and Szabo, M and Portley, M and Sherer, CM and King, MC and Huang, TH and Kosa, P and Bielekova, B and Ward, ME and Grunseich, C and Shneider, NA and Traynor, BJ and Narendra, DP},
title = {Clinical and biochemical characterization of amyotrophic lateral sclerosis in a CHCHD10 R15L family.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag115},
pmid = {41911331},
issn = {1460-2156},
abstract = {Familial forms of ALS are potential candidates for gene-directed therapies, but many recently identified genes remain poorly characterized. Here, we provide a comprehensive clinical, neuropathological, and biochemical description of fALS caused by the heterozygous p.R15L missense mutation in the gene CHCHD10. Using a cross-sectional study design, we evaluated five affected and nine unaffected individuals from a large seven-generation pedigree with at least 68 affected members. The pedigree suggests a high (68 - 81%) but incomplete disease penetrance. Through cloning of the disease-allele from distant members of the family, we establish the disease haplotype in the family. Notably, the haplotype was distinct from that of a previously reported p.R15L mutation carrier with ALS, demonstrating that the variant is in a mutational hotspot. The clinical presentation was notable for being highly stereotyped; all affected individuals presented with the rare ALS variant Flail Arm Syndrome (FAS; also known as, brachial amyotrophic diplegia or Vulpian-Bernhardt Syndrome), suggesting greater involvement of the cervical spinal cord. Consistently, neuropathology from one family member demonstrated substantially increased CHCHD10 protein aggregation and neuronal loss (though absent TDP-43 pathology) in the cervical vs. lumbar spinal cord. This FAS phenotype could be captured by a simple timed finger tapping task, suggesting potential utility for this task as a clinical biomarker. Additionally, through analysis of fibroblast lines from 12 mutation carriers, isogenic iPSC cells, and a knockin mouse model, we determined that CHCHD10 with the R15L variant is stably expressed and retains substantial function both in cultured cells and in vivo, in contrast to prior reports. Conversely, we find loss of function (LoF) variants are more common in the population but are not associated with a highly penetrant form of ALS in the UK Biobank (31 in controls; 0 in cases). Together, this argues against LoF and in favor of toxic gain-of-function as the mechanism of disease pathogenesis, similar to the myopathy-causing variants in CHCHD10 (p.G58R and p.S59L). Finally, through proteomic analysis of CSF of variant carriers, we identify that CHCHD10 protein levels are elevated approximately 4-fold in mutation carriers, and that affected and unaffected individuals are differentiated by elevation of two neurofilaments: neurofilament light chain (NfL) and Peripherin (PRPH). Collectively, our findings help set the stage for gene-directed therapy for a devasting form of fALS, by establishing the likely disease mechanism and identifying clinical and fluid biomarkers for target engagement and treatment response.},
}

@article {pmid41911483,
year = {2026},
author = {Nusir, A and Anthony, SM and Zhou, W and Kabbani, N},
title = {Microglial Adaptations to Chronic Nicotine in the Cerebellum: Proteomic Evidence for Neuroimmune Vulnerability.},
journal = {Journal of proteome research},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jproteome.5c01027},
pmid = {41911483},
issn = {1535-3907},
abstract = {Smoking is a major public health concern with widespread effects on multiple organ systems, including the immune system. Chronic nicotine exposure can alter immune cell function through nicotinic receptors expressed on peripheral macrophages and microglia in the brain. Recent evidence indicates that the cerebellum is impacted by nicotine, contributing to motor and nonmotor outcomes, during drug use. In this study, we investigated the effect of chronic nicotine on microglia proteomes in the adult mouse cerebellum. Microglia were isolated by fluorescence-activated cell sorting (FACS) based on CD11b[high] CD45[low/intermediate] expression from male and female mice (n = 9 per group) exposed to 200 μg/mL nicotine (dissolved in 2% saccharin drinking water) for 30 days. Proteomic analysis was performed using liquid chromatography electrospray ionization (LC-ESI) mass spectrometry (MS) comparing the effect of nicotine relative to vehicle control. Our results reveal a sex-dependent effect of nicotine on microglial proteomes. While both males and females exhibited histone-related genomic responsiveness to nicotine, males demonstrated enrichment in cytoskeletal and metabolic proteins, and females showed complement-protein adaptations. The microglial proteome in male mice displayed nicotine-related adaptations in proteins that can contribute to neurodisorders including Huntington's disease and amyotrophic lateral sclerosis (ALS), of which smoking is a known risk factor. Together, these results highlight an effect of nicotine on the proteome of microglia providing insight into immune pathways that can contribute to smoking-related behavior and disease.},
}

@article {pmid41911992,
year = {2026},
author = {Di Napoli, G and Alfurno, L and Fissore, A and Raccuia, E and Olivieri, P and Marengo, M and Oliaro-Bosso, S and Piaz, FD and Catucci, G and Gilardi, G and Velazquez-Campoy, A and Prischi, F and De Simone, A and Spyrakis, F and Di Palma, F and Adinolfi, S},
title = {Calcium as a molecular switch that regulates Annexin A11 N- and C-terminal domains interaction and its role in ALS.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {151719},
doi = {10.1016/j.ijbiomac.2026.151719},
pmid = {41911992},
issn = {1879-0003},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease marked by progressive motor neuron loss, leading to muscle paralysis and respiratory failure. Genetic mutations, notably in the ANXA11 gene, have been implicated in both familial and sporadic ALS forms. ANXA11 functions as a cellular "tether," orchestrating the transport of RNA-protein complexes and lysosomes through its N-terminal (Nt) and C-terminal (Ct) domains, respectively. This study uncovers a novel calcium-dependent regulatory mechanism governing the intramolecular interaction between these domains. Using biochemical, biophysical, and computational approaches, we suggest that in the absence of calcium, ANXA11 adopts a closed conformation with stable Nt-Ct interactions. Elevated calcium levels induce a conformational shift, disrupting this interaction and exposing binding sites for RNA and membranes. Crucially, we show that the ALS-associated D40G mutation in the Nt domain impairs this calcium-regulated interaction, favoring a persistent open conformation that predisposes to toxic protein aggregation. These findings reveal that calcium acts as a molecular switch modulating ANXA11 conformation and function, providing new insights into its role in ALS pathogenesis and potential therapeutic targets.},
}

@article {pmid41912102,
year = {2026},
author = {Li, A and Xiao, X and Liu, G and Li, K and Ling, Y and Deng, S and Xu, C and Cao, SQ and Wen, J and Lu, G and Yang, G and Fang, EF and Qin, D and Su, H},
title = {Isoginkgetin protects against degeneration of ALS motor neurons via regulating the GSK-3β-TFEB signaling axis.},
journal = {Pharmacological research},
volume = {},
number = {},
pages = {108172},
doi = {10.1016/j.phrs.2026.108172},
pmid = {41912102},
issn = {1096-1186},
abstract = {Lysosomal dysfunction is a core pathological driver of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Transcription factor EB (TFEB) serves as a master regulator of lysosomal biogenesis, and its pharmacological activation represents a strategy to restore lysosomal function in disease and aging. Here, using a series of artificial intelligence-powered computational virtual screening workflows, we have identified isoginkgetin (ISO), a small-molecule compound, as a potent TFEB activator that promotes mechanistic target of rapamycin complex 1 (mTORC1)-independent TFEB nuclear translocation to enhance lysosomal biogenesis and function. Mechanistically, ISO functions as an ATP-competitive inhibitor that binds to the key Lys85 residue within the ATP-binding pocket of glycogen synthase kinase 3β (GSK-3β), thereby regulating the GSK-3β-TFEB signaling axis to activate TFEB nuclear translocation. Functionally, ISO improves lysosomal function and protects motor neurons differentiated from induced pluripotent stem cells derived from patients with ALS from degeneration. Collectively, these results support the hypothesis that lysosomal dysfunction is a druggable target for ALS.},
}

@article {pmid41912266,
year = {2026},
author = {Pennington, CR and Shaw, DJ and Skubera, M and Rose, AK and Jones, A},
title = {Declining trends in adolescent alcohol consumption and related harms: No room for complacency (an empirical reply to Vieira et al. 2025).},
journal = {Addiction (Abingdon, England)},
volume = {},
number = {},
pages = {},
doi = {10.1111/add.70413},
pmid = {41912266},
issn = {1360-0443},
support = {ES/Y001877/1//Economic & Social Research Council (ESRC)/ ; SBF0010\1109/AMS_/Academy of Medical Sciences/United Kingdom ; },
abstract = {Vieira et al. report that alcohol-related harms among adolescents have generally declined in high-income countries where youth drinking has decreased, but several methodological choices complicate this conclusion. By performing reproducibility analyses on Vieira et al.'s raw data, we show that their findings are more nuanced and complex. Secondary data analyses reveal that 19-24-year-olds have elevated vulnerability to alcohol-related harms. Any discussion of declining trends in adolescent alcohol consumption and related harms should acknowledge that current prevalence rates and harms remain unacceptably high and require continued public health attention.},
}

@article {pmid41912367,
year = {2026},
author = {Garbey, M and Lesport, Q and Öztosun, G and Ghodasara, V and Kaminski, HJ and Bayat, E},
title = {Authors' Response to "Comment on 'Improving Care for Amyotrophic Lateral Sclerosis with Artificial Intelligence and Affective Computing'".},
journal = {Journal of the neurological sciences},
volume = {},
number = {},
pages = {125885},
doi = {10.1016/j.jns.2026.125885},
pmid = {41912367},
issn = {1878-5883},
}

@article {pmid41856244,
year = {2026},
author = {Behling, E and Bloch, MH},
title = {Editorial: Should Weight Gain Be a Factor in Choosing an Antidepressant?.},
journal = {Journal of the American Academy of Child and Adolescent Psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaac.2026.03.008},
pmid = {41856244},
issn = {1527-5418},
abstract = {There is limited evidence to guide clinicians regarding the side effect profiles of antidepressants in youth. Weight gain is a frequent concern raised by patients and their families when starting psychiatric medications. In the current issue of JAACAP, Rifas-Shiman et al.[1] present a retrospective cohort study using electronic health record (EHR) data from 67,039 patients 5 to 19 years of age to investigate the impact of antidepressants on body mass index (BMI) in children and adolescents over the longer term (up to 1 year). The authors found a small, albeit statistically significant, increase in BMI with the most commonly used selective serotonin reuptake inhibitors (SSRIs) (citalopram, escitalopram, fluoxetine, sertraline), but not with bupropion.[1] Rifas-Shiman et al.'s findings of slight weight gain associated with SSRIs in youth align with observational studies in adults.[2] Previous smaller prospective cohort studies in youth have suggested possible differences in effect of SSRIs on weight gain, with (es)citalopram being associated with more weight gain than sertraline (fluoxetine was intermediate).[3] The weight changes seen with escitalopram and citalopram are highly variable across patients and potentially associated with slow CYP2C19 metabolizer status.[4] Rifas-Shiman et al. did not replicate these differences in weight change between SSRI agents at 1-year follow-up despite the much larger sample size.},
}

@article {pmid41901170,
year = {2026},
author = {Kwaśniewska, K and Fic, W and Polak-Szczybyło, E},
title = {Vitamins as Modulators of Neurodegenerative Disease Pathways: Mechanisms and Therapeutic Perspectives.},
journal = {Nutrients},
volume = {18},
number = {6},
pages = {},
pmid = {41901170},
issn = {2072-6643},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Vitamins/therapeutic use/pharmacology/administration & dosage ; *Neuroprotective Agents/pharmacology ; *Dietary Supplements ; Antioxidants ; Oxidative Stress/drug effects ; Ubiquinone/analogs & derivatives ; Animals ; },
abstract = {Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, currently represent one of the major challenges in contemporary medicine and geriatrics. Progressive degeneration of the nervous system affects not only patients' physical functioning but also their psychosocial well-being, often leading to social isolation and disruption of interpersonal relationships. These processes are most strongly associated with individuals over 65 years of age, in whom metabolic syndrome is frequently diagnosed and constitutes a significant factor predisposing them to the exacerbation of neuropathological changes. This review analyzes the role of selected vitamins in modulating the course of neurodegenerative disorders, with particular emphasis on their neuroprotective potential. Specific attention is given to their involvement in antioxidant defense mechanisms, regulation of inflammatory pathways, prevention of abnormal protein aggregation, participation in neurotransmitter synthesis, and support of mitochondrial function and cellular energy metabolism. The review also considers key interactions between vitamins and coenzyme Q10, which synergistically enhance neuroprotective mechanisms. Deficiencies in certain vitamins may exacerbate oxidative stress, impair synaptic transmission, and intensify neuroinflammatory responses, thereby contributing to disease progression. The study analyzes the available data on therapeutic doses of vitamins and compares them with the recommended dietary intake and the upper tolerable intake levels (UL). The available evidence suggests that personalized vitamin supplementation, when integrated with a well-balanced and nutrient-dense diet, may constitute a valuable adjunctive therapeutic strategy. Such an approach may help attenuate disease progression, support neuronal integrity, and improve functional outcomes. Ultimately, targeted nutritional interventions may enhance overall well-being and quality of life in patients affected by neurodegenerative diseases.},
}

Humans
*Neurodegenerative Diseases/drug therapy/metabolism
*Vitamins/therapeutic use/pharmacology/administration & dosage
*Neuroprotective Agents/pharmacology
*Dietary Supplements
Antioxidants
Oxidative Stress/drug effects
Ubiquinone/analogs & derivatives
Animals

@article {pmid41902308,
year = {2026},
author = {Datoo, M and Kadir, S},
title = {Voices from the minority: Understanding the acculturative experiences of British Shia Muslims.},
journal = {Psychology and psychotherapy},
volume = {},
number = {},
pages = {},
doi = {10.1111/papt.70058},
pmid = {41902308},
issn = {2044-8341},
support = {//University of Leicester/ ; },
abstract = {OBJECTIVES: The aim of this research was to understand the acculturative experiences of British Shia Muslims, with hopes for practitioners to better understand how to support this population.

DESIGN: Qualitative methodology was used, utilising semi-structured interviews. Braun and Clarke's (Thematic analysis: A practical guide, Sage Publications Limited, 2022) reflexive thematic analysis was chosen to analyse the data and identify themes within 15 interview transcripts.

METHODS: Recruitment took place through mosques, with inclusion criteria involving British Shia Muslim participants over 18 years, who had lived in England for a minimum of 5 years. First-, second- and third-generation participants were recruited.

RESULTS: Five themes were identified, sitting under the main overarching theme, 'navigating through multiple worlds', which depicted acculturation as a fluid, complex journey, consistent with Schwartz et al.'s (American Psychologist, 2010, 65, 37) multidimensionality model of acculturation. These themes included: do I belong here, with subthemes of conflicting cultural values and who am I, the emotional toll of acculturation, with subthemes of negotiating authenticity and Muslim therapeutic support, negotiating faith in a secular society, living with layered discrimination, with a subtheme of Shia-specific discrimination and, finally, holding each other up: sources of strength.

CONCLUSIONS: This research demonstrates the multidimensional and complex journey of acculturation for British Shia Muslims. Through this, there is an emphasis on understanding more about the experiences of minoritised communities to improve their mental health support. The clinical implications to support this are diversifying the workforce, enhancing cultural competence and humility, adopting an intersectional approach and addressing discrimination.},
}

@article {pmid41903716,
year = {2026},
author = {Alam, Z and Nguyen, KT and Lauck, KC and Malick, H and Tolkachjov, SN},
title = {Response to Newell et al.'s commentary on DPP4 inhibitor use and skin cancer risk in type 2 diabetes.},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.03.073},
pmid = {41903716},
issn = {1097-6787},
}

@article {pmid41903799,
year = {2026},
author = {Chamorro-Muñoz, MI and Afkir-Ortega, MN and Aguilar-Monge, A},
title = {Impact of care by a multidisciplinary team on the assessment of cognitive aspects and decision-making at the end of life in a Spanish population with amyotrophic lateral sclerosis.},
journal = {Neurologia},
volume = {},
number = {},
pages = {501950},
doi = {10.1016/j.nrleng.2026.501950},
pmid = {41903799},
issn = {2173-5808},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a disease with a fatal course, often associated with unassessed cognitive-behavioural disturbances, and very relevant end-of-life care decisions. The aim of this study is to verify whether multidisciplinary team care for ALS patients in our setting has modified the cognitive assessment and the end-of-life decision making, compared to a model of uncoordinated specialist care.

METHODS: An observational, longitudinal, retrospective study was conducted on a cohort of patients with probable or definite ALS, in a referral hospital, between 01-01-2000 and 31-12-2022, differentiating whether they were treated before or after the implementation of a multidisciplinary model. We analysed the performance of cognitive assessment, the use of riluzole, gastrostomy, non-invasive ventilation and invasive ventilation, and the recording of patients' decisions regarding the care they wished to receive. Comparisons between variables were performed using the chi-square test or Fisher's exact test.

RESULTS: We evaluated 47 patients seen by uncoordinated specialists and 146 with a multidisciplinary model. Patients cared for using the multidisciplinary model were more frequently cognitively assessed (55.48% vs 12.8%, p < 0.001), diagnosed with dementia (11.6% vs 2.3%, p < 0.048) and their advance directives were recorded (56.8% vs 23.4%, p < 0.001). We found no differences in the use of advanced interventions, except for invasive ventilation, which was only performed in the context of multidisciplinary care.

CONCLUSIONS: The multidisciplinary model of care for ALS patients in our setting has improved cognitive assessment, promoted the registration of their advance directives, and thus helped to improve respect for their autonomous decisions and dignity.},
}

@article {pmid41903869,
year = {2026},
author = {Yang, Y and Yang, Y and Zhang, X and Ma, H and Ji, S and Zou, F and Yu, X and Du, G and Zhu, X and Tian, J},
title = {Targeting ME1 rescues redox-metabolic coordination in ALS: A core effector of NRF2-directed therapy.},
journal = {Neuropharmacology},
volume = {},
number = {},
pages = {110940},
doi = {10.1016/j.neuropharm.2026.110940},
pmid = {41903869},
issn = {1873-7064},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss, muscle weakness, and respiratory failure, with dysregulated energy metabolism and oxidative stress representing core pathological features. Epidemiological studies indicate geographical variations in incidence, and recent multi-omics evidence identifies a hypermetabolic state and mitochondrial dysfunction as key drivers of disease progression. The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2), which regulates antioxidant response and metabolism, represents a promising therapeutic target; however, the exploration of specific activators remains insufficient. This study evaluated the efficacy and mechanism of a novel KEAP1-NRF2 activator, MKL01351, in SOD1 G93A transgenic mice and NSC-34 motor neuron-like ALS models. Behavioral analyses demonstrated that MKL01351 significantly delayed disease onset, improved motor coordination in the rotarod and hanging tests, and extended survival. The compound alleviated oxidative stress by reducing malondialdehyde (MDA) levels and restoring the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, while also ameliorating the energy deficit by modulating glycolytic and mitochondrial functions, as confirmed by Seahorse analysis. Mechanistic investigations revealed that MKL01351 activated the NRF2 pathway, upregulating downstream targets such as NQO1 and HO-1, and specifically enhanced the expression of malic enzyme 1 (ME1). Loss-of-function experiments confirmed that ME1 knockdown abolished the protective effects, indicating that the NRF2-ME1 axis is a central hub for the synergistic regulation of metabolic and oxidative homeostasis. In conclusion, MKL01351 concurrently ameliorates oxidative stress and metabolic dysregulation via the NRF2-ME1 signaling pathway, offering a novel neuroprotective strategy for ALS treatment.},
}

@article {pmid41904003,
year = {2026},
author = {Kinger, S and Choudhary, A and Kumar, P and Jagtap, YA and Sharma, V and Dhiman, R and Prasad, A and Verma, R and Chinnathambi, S and Mishra, A},
title = {Molecular chaperones mediated proteostasis depletion: A cause of neurodegeneration?.},
journal = {Advances in protein chemistry and structural biology},
volume = {150},
number = {},
pages = {181-219},
doi = {10.1016/bs.apcsb.2025.10.033},
pmid = {41904003},
issn = {1876-1631},
mesh = {Humans ; *Proteostasis ; *Neurodegenerative Diseases/metabolism/pathology ; *Molecular Chaperones/metabolism ; Animals ; },
abstract = {Protein homeostasis is a critical aspect of cellular homeostasis as proteins are one of the most diverse biomolecules, responsible for multiple molecular and cellular functions. Protein quality control machinery is essential for maintaining integrity of cellular proteome via regulating its synthesis, structure, function, and degradation. Molecular chaperones are central to the protein quality control apparatus of cells and assist in folding nascent polypeptides, maturation, sequestration, solubilisation, and degradation of proteins. The coordination and cooperation between multiple cellular chaperones and other quality control elements, such as ubiquitin-proteasome system and autophagy, form a network, critical for proteostasis. Disturbed proteostasis and protein aggregation are hallmark features of neurodegenerative diseases. Re-establishing cellular proteostasis and enhancing chaperones' levels and functions can alleviate protein aggregation and associated cytotoxicity. Here, we have explored the potential of abundant cellular chaperone Hsp90, large chaperone Hsp110, small chaperone Hsp27, and anti-oxidant and mitoprotective chaperone DJ-1 in the regulation of proteostasis, with implications for neurodegenerative diseases, Alzheimer's, Parkinson's, Huntington's, and Amyotrophic lateral sclerosis. We have focused on roles and mechanisms of function of these chaperones in countering disturbed proteostasis in neurodegenerative disorders.},
}

Humans
*Proteostasis
*Neurodegenerative Diseases/metabolism/pathology
*Molecular Chaperones/metabolism
Animals

@article {pmid41904009,
year = {2026},
author = {Chinnathambi, S and Malik, S},
title = {Cytoskeltal intermediate filaments in Tau pathology and neurodegeneration.},
journal = {Advances in protein chemistry and structural biology},
volume = {150},
number = {},
pages = {351-376},
doi = {10.1016/bs.apcsb.2025.10.028},
pmid = {41904009},
issn = {1876-1631},
mesh = {Humans ; *Intermediate Filaments/metabolism/pathology ; *tau Proteins/metabolism ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; *Cytoskeleton/metabolism/pathology ; Alzheimer Disease/metabolism/pathology ; Intermediate Filament Proteins/metabolism ; },
abstract = {Intermediate filaments are cytoskeletal proteins that are vital for proper cell structure formation and functioning. There are six types of these proteins. Type I includes acidic keratins, Type II includes basic and neutral keratins, both of which are present in epithelial cells. Type III includes vimentin, desmin, glial fibrillary acidic protein and peripherin, among which the last two are highly involved in neurodegenerative diseases. Type IV includes three types of neurofilament proteins, NF-L, NF-M and NF-H, where L signifies light, M signifies medium and H signifies heavy. The fourth protein in this category is α-internexin. All of these proteins are highly involved in neurodegenerative diseases, especially the neurofilament proteins. The type V intermediate filament proteins are lamins. The type VI intermediate filaments are nestins. Their involvement in a variety of neurodegenerative diseases has been observed, including Alzheimer's disease, Cerebral Ischemia, Multiple Sclerosis, Alexander Disease, Neuronal IF inclusion disease (NIFID) and Amyotrophic Lateral Sclerosis (ALS). Alzheimer's disease is a neurodegenerative disease in which two proteins are mainly involved, the Tau protein and the Amyloid-β protein. This review discusses the crosstalk of the intermediate filament proteins with the pathological proteins involved in the neurodegenerative diseases. For the case of the Alzheimer's disease, many of the intermediate filament proteins are involved in the disease pathology and are vital markers for the disease. One of the category of proteins involved is neurofilaments, among which NF-L is a marker for the disease. Keratin 9 and the glial fibrillary acidic protein (GFAP) are other intermediate filament proteins that are being explored as markers for the Alzheimer's disease.},
}

Humans
*Intermediate Filaments/metabolism/pathology
*tau Proteins/metabolism
*Neurodegenerative Diseases/metabolism/pathology
Animals
*Cytoskeleton/metabolism/pathology
Alzheimer Disease/metabolism/pathology
Intermediate Filament Proteins/metabolism

@article {pmid41904011,
year = {2026},
author = {Selvaraj, C and Desai, D and Sumitha, E},
title = {The quest to restore neuronal structure: Targeting cytoskeletal proteins in neurodegenerative diseases.},
journal = {Advances in protein chemistry and structural biology},
volume = {150},
number = {},
pages = {397-422},
doi = {10.1016/bs.apcsb.2025.10.026},
pmid = {41904011},
issn = {1876-1631},
mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology/therapy ; *Cytoskeletal Proteins/metabolism/genetics/antagonists & inhibitors ; Animals ; *Neurons/metabolism/pathology ; Cytoskeleton/metabolism ; },
abstract = {Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and Huntington's disease are characterized by progressive neuronal dysfunction and loss. A growing body of evidence implicates cytoskeletal disruption as a central pathological mechanism in these conditions. Cytoskeletal proteins, including microtubules, actin filaments, tau, neurofilaments, and alpha-synuclein, not only provide structural integrity but also regulate axonal transport, synaptic connectivity, and neuroplasticity. Its dysfunction will lead to impaired intracellular trafficking, protein aggregation, and neuronal degeneration. This chapter explores clearly about the specific cytoskeletal abnormalities that are evident in major neurodegenerative disorders, highlighting the biological mechanisms such as tauopathy-induced microtubule instability in Alzheimer's, actin cytoskeleton dysregulation in Parkinson's, and neurofilament aggregation in ALS. Current therapeutic strategies aimed at the stabilizing cytoskeletal components, enhancing protein clearance, and restoring transport dynamics are examined, alongside the cutting-edge approaches including the gene therapy, CRISPR/Cas9 editing, and nanotechnology-based delivery systems. Challenges such as limited blood-brain barrier penetration, off-target toxicity, and patient heterogeneity are also discussed with the focus on need for precision medicine. Additionally, we have also explored the future directions that specifically focused on the biomarker development, combination therapies, and strategies to promote neuroregeneration and structural plasticity. Targeting cytoskeletal pathways holds significant promise not only for suppressing the disease progression but also for rebuilding the structural foundation of the nervous system, potentially reversing the neurodegenerative decline.},
}

Humans
*Neurodegenerative Diseases/metabolism/pathology/therapy
*Cytoskeletal Proteins/metabolism/genetics/antagonists & inhibitors
Animals
*Neurons/metabolism/pathology
Cytoskeleton/metabolism

@article {pmid41904090,
year = {2026},
author = {Haidar, M and Viden, A and Daniel, C and Cuic, B and Wang, T and Rosier, M and Tomas, D and Mills, SA and Govier-Cole, A and Djouma, E and Perera, ND and Luikinga, S and Rytova, V and Barton, SK and Gonsalvez, DG and Palmer, LM and McLean, C and Kiernan, MC and Vucic, S and Turner, BJ},
title = {Corrigendum to "Cortical hyperexcitability drives dying forward amyotrophic lateral sclerosis symptoms and pathology in mice"[Prog. Neurobiol. 252 (2025) 102809].},
journal = {Progress in neurobiology},
volume = {},
number = {},
pages = {102910},
doi = {10.1016/j.pneurobio.2026.102910},
pmid = {41904090},
issn = {1873-5118},
}

@article {pmid41904598,
year = {2026},
author = {Amholt, TT and Kurtzhals, M and Melby, P and Bølling, M and Møller, OM and Lise, MK and Stage, A and O'Brien, W and Belton, S and Elsborg, P and Nielsen, G and Bentsen, P},
title = {Feasibility of the Promoting Pupils' Physical Literacy (3PL) intervention: Does it work? Will it work?.},
journal = {Pilot and feasibility studies},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40814-026-01806-w},
pmid = {41904598},
issn = {2055-5784},
support = {153181//TrygFonden/ ; },
abstract = {BACKGROUND: The rise in physical inactivity among children poses serious health risks impacting physical, mental, and social well-being. Physical literacy (PL) has been identified as an effective approach to encourage long-term physical engagement. Schools and communities, particularly through physical education (PE) programs, play a critical role in promoting PL. However, while there are several PL-focused PE interventions worldwide, no such programs have been specifically tailored to Nordic contexts, making feasibility testing essential for effective implementation. This study investigated the feasibility of a Danish adaptation of an Irish PL program, Y-PATH.

METHODS: The adapted program, the Promoting Pupils' Physical Literacy (3PL) intervention, provided PE teachers with resources, courses, and a website to enhance motivational climates in PE and promote PL among 4th and 5th grade pupils. The study was conducted in accordance with Medical Research Council guidelines and Bowen et al.'s (2009) framework. Feasibility indicators including acceptability, demand, implementation, practicality, adaptation, and integration were investigated using a weekly questionnaire for PE teachers, interviews (n = four teachers and 20 pupils), observations, and field notes. The quantitative data were analyzed descriptively, while the qualitative data were analyzed using thematic analyses.

RESULTS: 3PL was found to be feasible and acceptable among pupils and teachers (e.g., materials were used in 71% of lessons). While the materials supported implementation for teachers, workload adjustments are needed. Teachers adapted lessons effectively, balancing an inclusive and motivating learning environment. Despite minor challenges, 3PL fostered engagement among pupils and teachers with potential for expansion.

CONCLUSION: 3PL represents a feasible and promising approach to promote PL in a Danish school setting. Feasibility testing demonstrated the potential for scaling 3PL, while recognizing that large-scale trials are needed to validate its broader impact.

TRIAL REGISTRATION: A protocol for adaptation of 3PL was published in Open Science Framework, registered in December 2022 (1). The 3PL study was preregistered at ClinicalTrials.gov (ID NCT05822024), April 2023, version 1 (https://classic.

CLINICALTRIALS: gov/ct2/show/NCT05822024), before enrolment. A study protocol was written before intervention start (August 2023) and hereafter officially published in January 2024 (2).},
}

@article {pmid41905172,
year = {2026},
author = {Balaji, R and Joshi, H and Patel, BK},
title = {Elucidating the conformational dynamics of the mitochondrial localization signal, M3, of TDP-43 and accessing potential binders using molecular docking and simulation.},
journal = {Computational biology and chemistry},
volume = {123},
number = {},
pages = {109029},
doi = {10.1016/j.compbiolchem.2026.109029},
pmid = {41905172},
issn = {1476-928X},
abstract = {Aberrant mitochondrial localization of RNA/DNA-binding protein TDP-43 is implicated in amyotrophic lateral sclerosis (ALS), which may affect mitochondrial dynamics and contribute to neuronal toxicity. Inhibitors of the cytoplasmic aggregation of TDP-43 were reported previously, but their effect on the mitochondrial mislocalization of TDP-43 remains to be investigated. Three internal peptide sequences from TDP-43, M1, M3, and M5, were found to enable TDP-43's mitochondrial localization. The peptides carrying these sequences thwarted mitochondrial import of TDP-43 and rescued TDP-43-induced cytotoxicity to neurons. In the current study, we aimed to assess the repurposing potential of 2115 FDA-approved small molecules for binding to the M3 region of TDP-43 (aa: 146-150) through virtual screening. The M3 region is present in the RNA-recognition motif-1 (RRM-1); hence, multiple all-atom molecular dynamics (MD) simulations, with two different starting conformations, of the tandem RRM1-2 domains of TDP-43 in explicit solvent water were performed to understand the dynamics of the target M3 region. The analysis of the simulation trajectories suggests that the M3 region is relatively non-flexible and buried relative to the other regions of the tandem RRM1-2 domains. Cholecalciferol (Vitamin D3), as identified through virtual screening, consistently docked with the M3 region across various docking strategies, despite the region's poor accessibility in most conformations. Vitamin D3 also remained stably bound to the M3 region in most frames of four replica MD simulations, each of one microsecond. Taken together, our study proposes vitamin D3 as a potential binder to the M3 region, which may inhibit the pathogenic mitochondrial mislocalization of TDP-43.},
}

@article {pmid41905471,
year = {2026},
author = {Kuiper, MM and Cuppers, L and Sewell-Green, A and Kruithof, WJ and Visser-Meily, JMA and Beelen, A},
title = {Criterion validity of equations as alternatives to reference standards for assessing body composition and energy expenditure in amyotrophic lateral sclerosis - a systematic literature review.},
journal = {Clinical nutrition ESPEN},
volume = {},
number = {},
pages = {103262},
doi = {10.1016/j.clnesp.2026.103262},
pmid = {41905471},
issn = {2405-4577},
abstract = {BACKGROUND & AIM: People living with amyotrophic lateral sclerosis (ALS) are at high risk of malnutrition, making it essential to monitor their nutritional status through measurements of body composition and energy expenditure. However, validity of equations, as alternatives to reference standards for assessing these parameters in ALS, is unclear. This systematic review evaluates criterion validity of equations to estimate body composition and energy expenditure in ALS.

METHODS: Four electronic databases (EMBASE, MEDLINE, CINAHL and Cochrane) were systematically searched from inception until July 7[th], 2025. Studies were included if criterion validity of an instrument or method for estimating body composition or energy expenditure was examined in people diagnosed with ALS. Methodological quality was assessed using the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) risk of bias checklist. Criterion validity was rated as sufficient (+), indeterminate (?) or insufficient (-) based on COSMIN criteria for good measurement properties. Results were qualitatively summarised.

RESULTS: Twelve studies were included: five evaluated the criterion validity of equations to estimate body composition using Bioelectrical Impedance Analysis (BIA) or anthropometry, and seven to estimate resting or total daily energy expenditure. No equation was rated as sufficient for criterion validity across studies.

CONCLUSION: Equations to estimate body composition and energy expenditure should be applied with caution, as no equation exhibited high criterion validity in ALS. ALS-specific equations require further validation, and ideally, new equations tailored to the unique physiological characteristics of ALS should be developed.

PROSPERO REGISTRATION NUMBER: CRD42024573509.},
}

@article {pmid41905645,
year = {2026},
author = {Martín-Sánchez, FJ and Marcos Sastre, MC and Muñoz de Maya, E and Sánchez-Pinto Pinto, B and Trueba Vicente, Á and Artero Ortiz, J and Arribas Guerrero, J and Soto Vargas, N and García Sánchez, IM and Marco Martínez, J and , },
title = {Six months of experience at a specialized daytime care center for people with amyotrophic lateral sclerosis (ALS) in the Community of Madrid.},
journal = {Neurologia},
volume = {},
number = {},
pages = {502006},
doi = {10.1016/j.nrleng.2026.502006},
pmid = {41905645},
issn = {2173-5808},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, leading to motor deterioration and a reduced quality of life. In the Community of Madrid, the ALS Network was established to improve patient care. In April 2024, the Specialized Day Care Centre for ALS (CEADELA) was inaugurated, complementing the care provided by the ALS Network. The aim of this study was to describe the experience of CEADELA during its first six months.

MATERIALS AND METHODS: A retrospective descriptive study was conducted on a cohort of CEADELA patients between April and October 2024. Clinical, functional, and therapeutic data were analyzed, along with overall satisfaction levels.

RESULTS: A total of 91 patients were included, with a mean age of 65.2 years (SD 11); of these, 59 (64.8%) were men. Most had spinal-onset ALS and were receiving treatment with riluzole. A significant increase was observed in the use of physiotherapy, speech therapy, and occupational therapy after referral to the centre. Functionality significantly declined over six months. The mortality rate was 12.1% (18.2% opted for assisted dying). Overall, 76 patients (83.5%) responded to the survey, with 100% reporting satisfaction or high satisfaction with the centre (80.2% very satisfied and 18.4% satisfied).

CONCLUSIONS: CEADELA has improved access to specialized therapies with a high level of satisfaction, although disease progression remains a challenge. The need to continue developing integrated, evidence-based care models to optimize ALS management is highlighted.},
}

@article {pmid41895273,
year = {2026},
author = {Kim, D and Kondo, T and Inoue, H},
title = {Dissecting microglial contributions to neurodegenerative disease pathophysiology using human pluripotent stem cells.},
journal = {Stem cell reports},
volume = {},
number = {},
pages = {102866},
doi = {10.1016/j.stemcr.2026.102866},
pmid = {41895273},
issn = {2213-6711},
abstract = {Neurodegenerative diseases are characterized by progressive neuronal dysfunction and loss. Microglia, the brain's resident macrophages, are key contributors to disease pathogenesis, with many genetic risk variants enriched in microglia-specific genes. While rodent models have provided valuable insights, human induced pluripotent stem cell (iPSC) and embryonic stem cell (ESC) technologies now enable the generation of human microglia-like cells, offering a physiologically relevant platform to study human microglial biology. This review discusses the developmental origins and functions of microglia, current differentiation approaches, and how these models help elucidate disease-relevant phenotypes and molecular mechanisms in neurodegeneration.},
}

@article {pmid41895675,
year = {2026},
author = {Barthes, R and Niérat, MC and Rivals, I and Gatignol, P and Raux, M and Faure, M and Bruneteau, G and Serresse, L and Morélot-Panzini, C and Similowski, T},
title = {Association between dyspnea and cognitive task performance in amyotrophic lateral sclerosis: an exploratory study.},
journal = {Respiratory physiology & neurobiology},
volume = {},
number = {},
pages = {104566},
doi = {10.1016/j.resp.2026.104566},
pmid = {41895675},
issn = {1878-1519},
abstract = {Dyspnea is a major sensory and emotional burden in patients with chronic respiratory insufficiency. While experimentally induced acute dyspnea has been shown to interfere with cognition in healthy participants, interferences between cognition and chronic clinical dyspnea have not been studied. We conducted an exploratory study to examine the association between dyspnea severity and cognitive performance in patients with amyotrophic lateral sclerosis (ALS) and chronic respiratory failure. Twenty patients were studied during unassisted breathing and during non-invasive ventilation (NIV). Dyspnea was assessed using the Multidimensional Dyspnea Profile, and cognitive performance was evaluated using the Paced Auditory Serial Addition Test (PASAT) and the Corsi block-tapping test. Respiratory-related cortical activity was assessed using electroencephalography. Linear mixed-effects models were used to examine associations between dyspnea descriptors and cognitive outcomes, adjusting for age, educational level, and disease severity. NIV markedly relieved dyspnea, anxiety, and respiratory-related cortical activity but was not associated with changes in cognitive performance. Dyspnea unpleasantness was independently associated with longer PASAT response time, whereas no associations were observed with PASAT accuracy measures or Corsi test outcomes. Neither ventilation condition nor respiratory-related cortical activity was associated with cognitive performance. These findings suggest that, in patients with ALS, dyspnea unpleasantness may be associated with slower PASAT response time without detectable relationships with other cognitive measures assessed in this study. Given the exploratory and focal nature of the study, further investigations are warranted to better characterize dyspnea-cognition interactions in this population.},
}

@article {pmid41896845,
year = {2026},
author = {Chang, J and Lipscombe, H and Lv, J and McCombe, PA and Henderson, RD and Ngo, ST and Steyn, FJ and Shaw, TB},
title = {White matter changes in reward circuits of amyotrophic lateral sclerosis: a fixel-based study of appetite loss.},
journal = {BMC medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12916-026-04763-6},
pmid = {41896845},
issn = {1741-7015},
support = {UQ Graduate School Scholarship (RTP)//University of Queensland/ ; Scott Sullivan MND Research Fellowship//University of Queensland/ ; Faculty of Medicine//University of Queensland/ ; TU2201//Motor Neurone Disease Research Australia/ ; PDF2112//Motor Neurone Disease Research Australia/ ; Scott Sullivan MND Research Fellowship//Royal Brisbane and Women's Hospital Foundation/ ; Scott Sullivan MND Research Fellowship//MND and Me Foundation/ ; Scott Sullivan MND Research Fellowship//FightMND/ ; Collaborative Initiative Grant//FightMND/ ; 2017-07//Wesley Medical Research/ ; APP2029871//National Health and Medical Research Council/ ; },
abstract = {BACKGROUND: Non-motor symptoms such as appetite loss contribute to weight and fat mass reduction in people living with Amyotrophic Lateral Sclerosis (plwALS), both of which are strong prognostic factors in the disease. Consequently, understanding the neural mechanisms underlying appetite and other non-motor disturbances in ALS is of significant clinical concern. Previous studies highlight widespread grey and white matter involvement beyond the motor system, including hypothalamic volume loss and functional changes in reward-related regions. However, it remains unclear whether structural alterations in white matter tracts implicated in reward processing and behaviour contribute to the multisystem pathology of ALS.

METHODS: In this case-control study, we employ fixel-based analysis to examine changes in fibre characteristics of non-motor and motor tracts and their associations with clinical, anthropometric, and appetite-related measures within plwALS. Thirty-two plwALS and 24 non-neurodegenerative disease (NND) controls underwent multiband diffusion and structural imaging. Fixel-based analysis was conducted using MRtrix3 to model fibre pathways. For group-level statistical contrasts, fixels were generated in a common template space. We considered case-control differences, appetite, metabolism, body composition, and clinical measures.

RESULTS: Results reveal reductions in fibre density and cross-section in the corticospinal/corticobulbar and cerebellothalamic tracts. Exploratory analyses identified fibre density cross-section reductions throughout the temporo-ponto-cerebellar tract, the medial forebrain bundle, and the uncinate fasciculus. Though no direct associations were observed between fibre characteristics and measures of appetite or metabolism, we found significant correlation between fibre cross-section of the corticospinal/corticobulbar tracts and fat-free mass in NND controls, but not in plwALS. Furthermore, disease severity was associated with reduced fibre cross-section in the corticospinal/corticobulbar tract, medial forebrain bundle, uncinate fasciculus, and the temporopontine tract.

CONCLUSIONS: These findings highlight white matter fibre alterations in both motor and non-motor circuits in ALS. Although direct associations with appetite and metabolism were not observed, the results provide evidence of structural degeneration within reward- and behaviour-related pathways. Taken together, these findings reinforce that ALS is not confined to motor pathways but represents a multisystem neurodegenerative disease with both motor and extra-motor network involvement, offering important insights for future research into disease mechanisms and therapeutic targets.},
}

@article {pmid41897327,
year = {2026},
author = {Romano, R and Ruotolo, G and Perrone, F and Tomaselli, S and Mazzoni, M and Spataro, R and Conforti, FL and Rosati, J and Bucci, C},
title = {Selective Silencing of TDP-43 P. G376D Mutation Reverses Key Amyotrophic Lateral Sclerosis-Related Cellular Deficits.},
journal = {Biomolecules},
volume = {16},
number = {3},
pages = {},
doi = {10.3390/biom16030393},
pmid = {41897327},
issn = {2218-273X},
support = {PRIN2022 N. 2022XTM2S3//Ministero dell'università e della ricerca/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; Humans ; *DNA-Binding Proteins/genetics/metabolism ; Motor Neurons/metabolism/pathology ; RNA, Small Interfering/genetics ; Induced Pluripotent Stem Cells/metabolism ; *Mutation ; Oxidative Stress ; Cell Survival ; Lysosomes/metabolism ; Gene Silencing ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease for which there is currently no cure. Dominant mutations in the TARDBP gene are causative of ALS. In particular, the p. G376D substitution in TDP-43 causes familial ALS and it is associated with TDP-43 mislocalization in the cytosol, increased presence of cytoplasmic aggregates, and lysosomal and mitochondrial dysfunction. We previously designed a small interfering RNA (siRNA) that specifically targets and silences the mutant allele and we demonstrated that, in patient-derived fibroblasts, it can reduce TDP-43 aggregation, decrease oxidative stress, and improve cell viability. Here, we investigated the ability of this siRNA to revert some ALS-associated pathological phenotypes in motor neurons derived from induced pluripotent stem cells (iPSCs), as motor neurons are the primary cells affected in ALS. siRNA treatment reduced TDP-43 mislocalization, enhanced lysosomal function and cell viability, and decreased oxidative stress. These findings indicate that this allele-specific siRNA effectively reverses key ALS-related cellular deficits in motor neurons, representing a promising candidate for targeted therapy in patients carrying the TDP-43 G376D mutation.},
}

*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism
Humans
*DNA-Binding Proteins/genetics/metabolism
Motor Neurons/metabolism/pathology
RNA, Small Interfering/genetics
Induced Pluripotent Stem Cells/metabolism
*Mutation
Oxidative Stress
Cell Survival
Lysosomes/metabolism
Gene Silencing

@article {pmid41898328,
year = {2026},
author = {Nesci, S},
title = {Mitochondrial Dysfunction in the Inflammatory Process of Neurodegenerative Diseases.},
journal = {Biomedicines},
volume = {14},
number = {3},
pages = {},
doi = {10.3390/biomedicines14030682},
pmid = {41898328},
issn = {2227-9059},
abstract = {Neurodegenerative diseases share a mitochondrial-immune axis in which impaired oxidative phosphorylation reshapes neuronal metabolism and drives chronic inflammation. Complex I play a redox gatekeeper role at the coenzyme Q (CoQ) junction: catalytic defects, misassembly, or reverse electron transport over-reduce the CoQ pool, increase electron leak, and elevate ROS. How respiratory supercomplex plasticity (CI-CIII2, CIII2-CIVn, or CI-CIII2-CIVn) modulates carrier channelling, flux control, and ROS propensity through dynamic reorganization of the electron transport chain is highlighted. Excess ROS damages lipids and mitochondrial DNA, promoting the release of mitochondrial damage-associated molecular patterns s that activate NLRP3 inflammasome signalling, cGAS-STING-dependent interferon programs, and endosomal TLR9 pathways, establishing feed-forward loops between mitochondrial injury and neuroinflammation. Disease-focused sections integrate evidence from Parkinson's, Alzheimer's, amyotrophic lateral sclerosis, and Huntington's models, and map these mechanisms onto therapeutic opportunities spanning electron transport chain support, supercomplex stabilization, and consider mtDNA-sensing inflammatory nodes.},
}

@article {pmid41898412,
year = {2026},
author = {Rakovskaya, A and Volkova, E and Pchitskaya, E},
title = {Neuronal Calcium Signaling and Cytoskeletal Dynamics in Neurodegeneration.},
journal = {International journal of molecular sciences},
volume = {27},
number = {6},
pages = {},
doi = {10.3390/ijms27062550},
pmid = {41898412},
issn = {1422-0067},
support = {25-74-10019//Russian Science Foundation/ ; },
mesh = {Humans ; *Calcium Signaling ; *Cytoskeleton/metabolism ; Animals ; *Neurodegenerative Diseases/metabolism/pathology ; *Neurons/metabolism/pathology ; Calcium/metabolism ; },
abstract = {Neuronal function relies on the precise coordination between intracellular calcium (Ca[2+]) signaling and the cytoskeletal architecture that underpins synaptic transmission, plasticity, and structural stability. Disruption of this calcium-cytoskeleton interplay has been noted in numerous neurodegenerative diseases. We discuss how Ca[2+]-dependent cytoskeletal remodeling governs long-term potentiation and depression, dendritic spine morphology, and presynaptic function, highlighting the functions of end-binding proteins, STIM (Stromal Interaction Molecule)/Orai-mediated store-operated calcium entry, and the spine apparatus. Disease-specific manifestations of cytoskeletal-calcium dysregulation are reviewed across Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, tauopathies, and prion disorders. Finally, we evaluate emerging therapeutic strategies targeting calcium homeostasis, cytoskeletal dynamics, and their downstream effectors, including multi-target approaches.},
}

Humans
*Calcium Signaling
*Cytoskeleton/metabolism
Animals
*Neurodegenerative Diseases/metabolism/pathology
*Neurons/metabolism/pathology
Calcium/metabolism

@article {pmid41898662,
year = {2026},
author = {Katz, M and Robertson, T and Ngo, ST and Yarlagadda, S and Henderson, RD and McCombe, PA and Noakes, PG},
title = {Review of the Pathology of Muscle in Amyotrophic Lateral Sclerosis.},
journal = {International journal of molecular sciences},
volume = {27},
number = {6},
pages = {},
doi = {10.3390/ijms27062802},
pmid = {41898662},
issn = {1422-0067},
support = {DIS-202403-01216//Fight MND/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/pathology/metabolism ; Humans ; Animals ; *Muscle, Skeletal/pathology/metabolism ; Neuromuscular Junction/pathology/metabolism ; Motor Neurons/pathology/metabolism ; Disease Models, Animal ; Biomarkers/metabolism ; },
abstract = {In amyotrophic lateral sclerosis (ALS), a central event is the withdrawal of the motor nerve terminal from its target muscle. Whether this defect is driven by faults in the motor neuron or faults that originate within the muscle remains an area of investigation. In this review, we focus on the pathological abnormalities that are found in skeletal muscle, focusing, when possible, on human ALS, with support from ALS animal models. We begin with an overview of skeletal muscle, including a review of muscle fiber type, motor units and the neuromuscular synapse. Next, we provide a description of the clinical and biomarker changes that occur in the muscles of patients with ALS. We provide an extensive account of the histopathological changes that are evident in ALS muscle, such as fiber type grouping, muscle inflammation, protein misfolding, mitochondrial dysfunction, and alterations in neuromuscular junctions and muscle satellite cells. Our review then concludes with an update of metabolic and molecular-genetic changes that are found in ALS muscle. The evidence shows that muscle can be an additional target for therapy in ALS, in combination with therapies targeting neurons and glia within the central nervous system (CNS).},
}

*Amyotrophic Lateral Sclerosis/pathology/metabolism
Humans
Animals
*Muscle, Skeletal/pathology/metabolism
Neuromuscular Junction/pathology/metabolism
Motor Neurons/pathology/metabolism
Disease Models, Animal
Biomarkers/metabolism

@article {pmid41899342,
year = {2026},
author = {Hermann, M and Stoiber, A and Schmid, A and Hamp, T and Santos, AA and Grassmann, D and Krammel, M and Lintschinger, JM and Ulbing, S and Stria, A and Hafner, C},
title = {Relevance of Reversible Causes of Out-of-Hospital Cardiac Arrest: The "REBECCA" Interactive Checklist.},
journal = {Journal of clinical medicine},
volume = {15},
number = {6},
pages = {},
doi = {10.3390/jcm15062422},
pmid = {41899342},
issn = {2077-0383},
abstract = {Background/Objectives: Adequate cardiopulmonary resuscitation (CPR), defibrillation, and treatment of reversible causes are essential for improving the survival of patients suffering from out-of-hospital cardiac arrests (OHCAs). The Advanced Life Support (ALS) algorithm includes reversible causes for cardiac arrest. This study aimed to develop an interactive mobile checklist to identify reversible causes of OHCA (REBECCA) and evaluate their usability and usefulness among emergency physicians. Methods: This mixed-methods study was conducted at the Emergency Medical Service Vienna, Austria. All participants were emergency physicians from the Medical University of Vienna. An interactive mobile checklist was developed using a participatory design approach involving a focus group of 10 emergency physicians. Usability and applicability were assessed using structured questionnaires. Descriptive statistics were used to summarize participant characteristics and evaluation outcomes. Results: Among the included participants, 70% were specialists with a median prehospital experience of 2.0 (1.0-4.3) years. Although most participants were confident about their level of professional experience with OHCA, 85% still found the checklist to be helpful. The majority of the participants preferred the digital checklist over the paper-based checklist and appreciated its integration with the point-of-care ultrasound (POCUS) application. Although the participants did not communicate a significant need for further details on most causes, a small majority favored more information on intoxication and electrolyte disorders. Conclusions: The majority of the included emergency physicians found the REBECCA checklist helpful regardless of training level, whereas almost no physician needed further detailed information on the reversible causes. Our findings underscore the potential importance of future investigations aiming to reduce the cognitive load of emergency physicians during OHCA scenarios.},
}

@article {pmid41900026,
year = {2026},
author = {Jamerlan, A and Hulme, J},
title = {Chemical and Molecular Strategies in Restoring Autophagic Flux in TDP-43 Proteinopathy.},
journal = {Molecules (Basel, Switzerland)},
volume = {31},
number = {6},
pages = {},
doi = {10.3390/molecules31060924},
pmid = {41900026},
issn = {1420-3049},
support = {RS-2025-02292973//Korea Institute of Marine Science and Technology Promotion/ ; RS-2021-NR060117//National Research Foundation of Korea/ ; },
mesh = {Humans ; *Autophagy/drug effects ; *TDP-43 Proteinopathies/metabolism/drug therapy/pathology ; Lysosomes/metabolism ; Animals ; *DNA-Binding Proteins/metabolism/genetics ; Oligonucleotides, Antisense/pharmacology ; Proteolysis ; },
abstract = {The cytoplasmic accumulation of TDP-43 aggregates remains a persistent pathological hallmark of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and limbic-predominant age-related TDP-43 encephalopathy (LATE). The cell's natural clearance mechanisms, the Ubiquitin-Proteasome System (UPS) and the autophagy-lysosome pathway (ALP), are hypothesized to fail, at least in part, due to the sequestration of key components of these pathways by pathological TDP-43 species, thereby impairing autophagosome-lysosome fusion and lysosomal competence. Classical autophagic activators (e.g., rapamycin) can initiate upstream steps in the pathway but cannot address downstream flux bottlenecks, limiting their ability to restore effective TDP-43 clearance. This review revisits classical strategies and discusses newer approaches to modulate TDP-43 clearance, including transcription factor EB (TFEB) activators, proteolysis-targeting chimeras (PROTACs), and antisense oligonucleotides (ASOs). We propose that adopting multi-targeting strategies and developing better biomarkers are vital for clinical success.},
}

Humans
*Autophagy/drug effects
*TDP-43 Proteinopathies/metabolism/drug therapy/pathology
Lysosomes/metabolism
Animals
*DNA-Binding Proteins/metabolism/genetics
Oligonucleotides, Antisense/pharmacology
Proteolysis

@article {pmid41900140,
year = {2026},
author = {Krzymiński, K and Zadykowicz, B and Czechowska, J and Rudnicki-Velasquez, P and Serdiuk, I and Sieradzan, AK and Holec-Gąsior, L},
title = {Acridinium Chemiluminogenic Labels-Synthesis, Analytical Performance, and Mechanism of Light Generation-A Comparison in View of Biomedical Diagnostics.},
journal = {Molecules (Basel, Switzerland)},
volume = {31},
number = {6},
pages = {},
doi = {10.3390/molecules31061041},
pmid = {41900140},
issn = {1420-3049},
support = {2011/03/D/ST4/02419//National Science Centre/ ; },
mesh = {*Acridines/chemistry/chemical synthesis ; Humans ; *Luminescent Measurements/methods ; Immunoassay/methods ; Luminescence ; Immunoglobulin G/chemistry ; },
abstract = {This paper presents the synthesis, physicochemical characterisation, and analytical applications of chemiluminescent (CL) labels based on acridinium salts (ALs) for biomedical diagnostics. These compounds emit light as a result of oxidative reactions and represent an established class of reagents widely employed in chemiluminescence immunochemical assays (CLIAs) today. A series of structurally differentiated acridinium labels (AL1-AL5) was synthesised applying mostly original synthetic routes and purified to chromatographic purity (>90%, RP-HPLC). The compounds, including a commercial product treated as a reference, were successfully conjugated to anti-human IgG, yielding stable immunochemical reagents suitable for immunoassays with CL detection. The chemiluminescence properties of the obtained labels and their protein conjugates were investigated in aqueous buffers and in the presence of surfactants. The emission profiles exhibited characteristic flash-type kinetics with emission maxima occurring within 0.15-0.25 s after reaction initiation. The presence of surfactants more or less significantly enhanced the emission intensity, with signal increases of up to approx. 2-fold compared to surfactant-free systems. Analytical calibration demonstrated a linear response of signal derived from native labels over at least one order of magnitude of concentration, with detection limits falling in the range of 10[-9]-10[-10] M, confirming the high sensitivity of the developed compounds. The experimental results were supported by theoretical studies using density functional theory (DFT), which confirmed the energetic feasibility of the CL reaction pathway and identified structural factors influencing activation barriers. Additional semiempirical calculations (PM7) indicated that the dielectric environment and proximity of ionic species can influence the reaction energetics, providing mechanistic support for the experimentally observed effects of surfactants. The results demonstrate that both molecular structure and microenvironment influence CL efficiency and kinetics of the investigated systems. The developed acridinium labels exhibit analytical performance better or comparable to commercial reagents and are fully compatible with standard immunodiagnostic conjugation protocols, confirming their suitability for use in modern chemiluminescent immunoassays.},
}

*Acridines/chemistry/chemical synthesis
Humans
*Luminescent Measurements/methods
Immunoassay/methods
Luminescence
Immunoglobulin G/chemistry

@article {pmid41900340,
year = {2026},
author = {Iungin, O and Potters, G and Kalinichenko, O and Prekrasna-Kviatkovska, Y and Moshynets, O and Kazakov-Kravchenko, O and Sidorenko, M and Okhmat, O and Mickevičius, S},
title = {Temperature-Dependent Biofilm Development in Antarctic Endophytic Microbial Communities.},
journal = {Microorganisms},
volume = {14},
number = {3},
pages = {},
doi = {10.3390/microorganisms14030580},
pmid = {41900340},
issn = {2076-2607},
support = {0124U003829//National Antarctic Scientific Center of Ukraine/ ; 0125U003135//National Antarctic Scientific Center of Ukraine/ ; 984834//NATO SPS/ ; },
abstract = {Climate change is reshaping Antarctic ecosystems, where the resilience of Deschampsia antarctica and Colobanthus quitensis is mediated by endophytic microbial communities assembled under strong abiotic drivers. This study explores the temperature-dependent biofilm development in two Antarctic endophytic microbial communities (ALS and LS). Multivariate analysis revealed a fundamental trade-off between planktonic expansion and biofilm matrix investment as a function of thermal cues. While moderate warming (15-25 °C) optimized cell viability and turbidity, extreme thermal stress at 37-42 °C in nutrient-rich conditions triggered a significant shift toward a matrix-rich signature, characterized by a synergistic increase in total DNA and cellulose. Crucially, at the thermal extreme of 42 °C, we observed a decoupling of optical density from culturable biomass, where high turbidity did not translate into viable cells, signaling a state of severe environmental stress. These results identify 25 °C as the quantitative threshold for optimal growth, while temperatures of 37-42 °C act as a specific trigger for protective matrix production. Such thermal plasticity suggests that Antarctic endophytes are evolutionarily primed for persistence not only in cold native niches but also during bird-mediated dispersal at endothermic host temperatures.},
}

@article {pmid41900568,
year = {2026},
author = {Kostadinova-Slaveva, A and Savov, V and Antov, P and Malcheva, B and Todorova, E and Yusein, J and Dudeva, V and Ivanov, G},
title = {Aesthetic Profiling and Exploratory Composting Screening of Wood-Fiber Biocomposites Bonded with Spent Coffee Grounds and Ammonium Lignosulfonate.},
journal = {Materials (Basel, Switzerland)},
volume = {19},
number = {6},
pages = {},
doi = {10.3390/ma19061077},
pmid = {41900568},
issn = {1996-1944},
support = {BG16RFPR002-1.014-0015//European Regional Development Fund through Bulgarian Programme "Research, Innovation and Digitalisation for Smart Transformation"/ ; },
abstract = {Spent coffee grounds (SCGs) and lignin-derived binders, such as ammonium lignosulfonate (ALS), are increasingly being explored as renewable resources to reduce reliance on conventional formaldehyde-based resins in wood-fiber biocomposites. Although prior work has shown that SCG-ALS adhesive systems can achieve promising mechanical performance, two practical aspects essential for industrial applications and circular design remain insufficiently explored: a predictable and reproducible visual appearance and credible end-of-life options. In this study, sustainable wood-fiber biocomposites bonded with SCG and ALS were assessed from an aesthetic performance and end-of-life perspective. Color was quantified in the CIE L*a*b* (CIELAB) space and expressed as total color difference (ΔE*) relative to a reference panel. Increasing total SCG + ALS content from 40 to 75 wt.% based on oven-dry fibers produced pronounced darkening, with lightness decreasing from L* = 47.1 to 34.3 and ΔE* increasing from 18.38 to 32.51. Short-term composting behavior was explored by embedding fragments from formulations with 40-60 wt.% total SCG + ALS (based on oven-dry fibers; equal SCG/ALS shares) into a mixed organic substrate adjusted to an initial C/N ≈ 30 and monitored for 30 days in pots and trays. The process remained predominantly mesophilic (≈14-22 °C); nevertheless, visible microbial colonization and progressive surface degradation were observed, indicating susceptibility to biological activity under moist, nutrient-rich conditions. Overall, the results show that SCG-ALS content strongly governs the visual identity of the biocomposites and suggest composting-oriented routes as a potential end-of-life direction at an exploratory level, while highlighting the need for standardized compostability assessment and longer-term monitoring to substantiate circularity claims.},
}

@article {pmid41900684,
year = {2026},
author = {Pigato, M and Agresti, F and Benato, A and Bucci, C and Calliari, I and Cortis, D and D'Eramo, S and Fu, S and Giancarli, C and Pezzato, L and Zambon, A and D'Addabbo, A},
title = {Microstructural and Mechanical Characterization of Ultra-Pure Aluminum for Low-Amplitude-Vibration Cryogenic Applications.},
journal = {Materials (Basel, Switzerland)},
volume = {19},
number = {6},
pages = {},
doi = {10.3390/ma19061195},
pmid = {41900684},
issn = {1996-1944},
support = {2022KRKM2X//Programma Nazionale di Ricerca e Progetti di Rilevante Interesse Nazionale/ ; },
abstract = {In fundamental physics, sensors operating below liquid helium temperatures are highly vulnerable to vibrations, which can affect the sensitivity, for example, of high-performance particle detectors. Pulse-tube refrigerators, while generating vibrations lower than those of conventional systems, may still introduce several disturbances. Hence, flexible thermal connections are a commonly used mechanical solution to mitigate these undesirable effects. Among the materials that can be used, ultra-high-purity aluminum (UHP-Al) has attracted the attention for low-amplitude-vibration cryogenic applications, including gravitational wave interferometry, quantum information systems, precision space instrumentation, and cryogenic resonators. Thus, the aim of the paper is the characterization of the mechanical and microstructure properties of three UHP-Als (i.e., 5N-99.999 wt%, 5N5-99.9995 wt% and 6N-99.9999 wt%) intended for the production of thermal flexible connections with low stiffness, specifically designed to reduce vibration transmission in cryogenic environments. Mechanical properties were evaluated through standard tensile tests from room (+25 °C) to low temperature (i.e., -150 °C), providing insights into yield strength, ultimate tensile strength, elongation and elastic modulus. In addition, the dynamic elastic modulus of material loads, at cryogenic conditions (i.e., about -180 °C), was determined by measuring the natural resonance frequency, thereby assessing the material's response to vibrational. Moreover, an extensive microstructural analysis was conducted using electron backscatter diffraction and x-ray diffraction. The correlation between the observed microstructure and the elastic properties was systematically examined. The results underscore the pivotal role of microstructural characteristics in dictating the elastic behavior of UHP Als. Eventually, the analysis provides valuable guidelines for the materials employment inside cryogenic systems, where severe vibration control is critical to maintain high operational performance.},
}

@article {pmid41885638,
year = {2026},
author = {Sadhukhan, A and Chauhan, A and Kumar, M and Singh, TG and Mujwar, S and Awasthi, A},
title = {Cryptoxanthin as a multitarget neuroprotective agent: mechanistic and in silico perspectives.},
journal = {The Journal of pharmacy and pharmacology},
volume = {78},
number = {3},
pages = {},
doi = {10.1093/jpp/rgag029},
pmid = {41885638},
issn = {2042-7158},
mesh = {*Neuroprotective Agents/pharmacology/therapeutic use ; Humans ; Molecular Docking Simulation ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Xanthophylls/pharmacology/therapeutic use ; Animals ; Oxidative Stress/drug effects ; Anti-Inflammatory Agents/pharmacology ; Antioxidants/pharmacology ; Computer Simulation ; },
abstract = {OBJECTIVES: Neurodegenerative diseases such as Parkinson's disease (PD), Huntington's disease (HD), Alzheimer's disease (AD), and Amyotrophic lateral sclerosis (ALS) are complex disorders driven by multiple pathological processes, including oxidative stress, mitochondrial dysfunction, protein misfolding, and neuroinflammation. Due to this multifactorial nature, there is a growing interest in identifying natural compounds with multi-targeted neuroprotective properties. This review aims to evaluate the therapeutic potential of β-cryptoxanthin, a naturally occurring xanthophyll carotenoid, as a candidate molecule for mitigating neurodegenerative diseases.

METHODS: A comprehensive literature review was conducted to examine the neuroprotective mechanisms of β-cryptoxanthin, focusing on its antioxidant, anti-inflammatory, and immunomodulatory properties. In addition, in silico molecular docking studies were performed using AutoDock Vina to investigate the binding interactions of β-cryptoxanthin with key molecular targets associated with inflammation and neurodegenerative pathways.

KEY FINDINGS: β-Cryptoxanthin demonstrated strong neuroprotective potential due to its ability to scavenge reactive oxygen species (ROS) and modulate key molecular pathways involved in neuroinflammation and oxidative damage. Structurally characterized by a hydroxylated β-carotene backbone with 11 conjugated double bonds, β-cryptoxanthin showed favorable binding affinities with several inflammation- and neurodegeneration-related targets, including COX-2 (-11.6 kcal/mol), PI3K (-9.6 kcal/mol), mTOR1 (-9.2 kcal/mol), and GSK-3β (-8.7 kcal/mol). Additionally, interactions with JAK2, MAPK1, NF-κB, NRF2, and TLR4 suggest its involvement in regulating neuroimmune signalling pathways and inflammatory mediators.

CONCLUSIONS: The findings of this review highlight β-cryptoxanthin as a promising candidate for future neurotherapeutic investigation due to its multi-targeted mechanisms of action against key pathways implicated in neurodegeneration. Molecular docking results support its potential mechanistic role in modulating inflammation- and oxidative stress-related targets. However, these findings represent mechanistic plausibility rather than confirmed clinical efficacy, and further validation through preclinical and clinical studies is required.},
}

*Neuroprotective Agents/pharmacology/therapeutic use
Humans
Molecular Docking Simulation
*Neurodegenerative Diseases/drug therapy/metabolism
*Xanthophylls/pharmacology/therapeutic use
Animals
Oxidative Stress/drug effects
Anti-Inflammatory Agents/pharmacology
Antioxidants/pharmacology
Computer Simulation

@article {pmid41885937,
year = {2026},
author = {Akiyama, T and Zeng, Y and Guo, C and Gautier, O and Koepke, L and Lyons, H and Molotsky, E and Bombosch, JS and Sianto, O and Ross, JP and Hoang, P and Zhao, L and Spencer, C and Sumner, CJ and Monje, M and Day, JW and Gitler, AD},
title = {KIF5A downregulation in spinal muscular atrophy links axonal regeneration defects with ALS.},
journal = {JCI insight},
volume = {},
number = {},
pages = {},
doi = {10.1172/jci.insight.197941},
pmid = {41885937},
issn = {2379-3708},
abstract = {Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder caused by mutations in the survival motor neuron 1 (SMN1) gene leading to decreased SMN protein levels and motor neuron dysfunction. SMN-restoring therapies offer clinical benefit, but the downstream molecular consequences of SMN reduction remain incompletely understood. SMN deficiency resulted in downregulation of kinesin heavy chain isoform 5A (KIF5A) in human neurons and in a mouse model of SMA. SMN associated with KIF5A mRNA and contributed to its stability. Reduced SMN levels impaired axon regeneration, which was rescued by KIF5A overexpression. Because KIF5A has also been connected to ALS, these findings provide evidence of a molecular link between SMA and ALS pathophysiology, highlighting KIF5A as an SMN regulated factor. Our findings suggest SMN-independent interventions targeting KIF5A could represent a complementary therapeutic approach for SMA and other motor neuron diseases.},
}

@article {pmid41888300,
year = {2026},
author = {Sanchez-Mico, MV and Calvo-Rodriguez, M and Bacskai, BJ},
title = {Role of dysregulated calcium homeostasis in astrocytes in neurodegenerative disorders.},
journal = {Nature reviews. Neuroscience},
volume = {},
number = {},
pages = {},
pmid = {41888300},
issn = {1471-0048},
abstract = {Calcium signalling in astrocytes is a fundamental mechanism for maintaining brain homeostasis, shaping neuronal activity, and coordinating vascular and immune responses. Once considered secondary to neuronal signalling, astrocytic Ca[2+] dynamics are now recognized as highly versatile, spatially compartmentalized and essential for regulating neurotransmitter uptake, ion buffering, metabolic support and mitochondrial function. Accumulating evidence shows that these Ca[2+] signalling pathways are progressively remodelled during ageing and become profoundly dysregulated in neurodegenerative diseases, including Alzheimer disease, Parkinson disease, Huntington disease and amyotrophic lateral sclerosis. Importantly, astrocyte Ca[2+] alterations are heterogeneous and context-dependent, ranging from aberrant spontaneous activity to loss of signalling in specific subcellular domains, reflecting the disease stage, brain region and molecular pathology. Disruption of astrocyte Ca[2+] homeostasis compromises core homeostatic functions and contributes to neuronal vulnerability, circuit dysfunction and impaired neurovascular regulation. By integrating current evidence across physiological, ageing and disease contexts, this Review highlights astrocytic Ca[2+] signalling as a central node in neurodegenerative pathophysiology and underscores its potential as a target for therapeutic intervention.},
}

@article {pmid41888437,
year = {2026},
author = {McLellan, C and Campos-Melo, D and Hammond, R and Strong, MJ},
title = {Preservation of miR-9-5p and miR-124-3p in ALS-resistant oculomotor neurons contrasts with their downregulation in vulnerable spinal motor neurons, irrespective of TDP-43 pathology.},
journal = {Acta neuropathologica},
volume = {151},
number = {1},
pages = {},
pmid = {41888437},
issn = {1432-0533},
support = {201806SOP-411481/CAPMC/CIHR/Canada ; },
mesh = {*MicroRNAs/metabolism/genetics ; *Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics ; *Motor Neurons/metabolism/pathology ; Humans ; Male ; Middle Aged ; Female ; Down-Regulation ; *DNA-Binding Proteins/metabolism ; Aged ; *Spinal Cord/pathology/metabolism ; Adult ; },
abstract = {Selective vulnerability of motor neurons is a defining feature of amyotrophic lateral sclerosis (ALS) and provides a valuable framework for uncovering mechanisms that distinguish resilient from vulnerable neuronal populations. We investigated whether dysregulation of neuroprotective microRNAs (miRNAs), miR-9-5p and miR-124-3p, contributes to the differential susceptibility of motor neuron subtypes. We focused on cervical spinal motor neurons (SMNs), which undergo drastic degeneration in ALS, and oculomotor neurons (OMNs), which remain functionally intact and rarely degenerate, allowing preservation of eye movement in ALS patients. Using a modified multiplexed fluorescent in situ hybridization protocol combined with immunofluorescence, we quantified the expression of miR-9-5p and miR-124-3p in cervical SMNs and OMNs from ALS and control cases. We observed significant downregulation of both miRNAs in ALS SMNs, while their expression was maintained in ALS OMNs. Stratification of ALS SMNs by TDP-43 pathological status revealed similarly reduced miRNA expression in neurons with and without cytoplasmic inclusions, suggesting that miRNA downregulation occurs independently of visible TDP-43 pathology. We assessed the localization of the Dicer cofactor TRBP and found that it colocalized with TDP-43 inclusions in ALS SMNs, suggesting that TRBP sequestration could prevent proper miRNA processing. However, TRBP remained normally localized in neurons without cytoplasmic inclusions, indicating that sequestration cannot fully account for miRNA reduction across all ALS motor neurons. These findings support a model in which early or subtle disruptions, preceding visible pathology, may also contribute to miRNA downregulation in ALS. By identifying preserved miRNA networks as correlates of oculomotor neuron resilience in ALS, this work also exposes new therapeutic targets potentially capable of reinstating miRNA expression and reprogramming vulnerable SMNs.},
}

*MicroRNAs/metabolism/genetics
*Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics
*Motor Neurons/metabolism/pathology
Humans
Male
Middle Aged
Female
Down-Regulation
*DNA-Binding Proteins/metabolism
Aged
*Spinal Cord/pathology/metabolism
Adult

@article {pmid41888964,
year = {2026},
author = {Haddouali, K and Simma, K and Bellakhdar, S and El Otmani, H and El Moutawakil, B and Rafai, MA},
title = {Multifocal motor neuropathy secondary to gluten intolerance: a case report.},
journal = {Journal of medical case reports},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13256-026-05968-2},
pmid = {41888964},
issn = {1752-1947},
abstract = {BACKGROUND: Peripheral nervous system manifestations of gluten sensitivity usually present as distal symmetric axonal polyneuropathy, small fiber neuropathy, or sensory neuropathy, often accompanied by ataxia or painful symptoms. By contrast, motor neuropathies are extremely rare, with only a few cases of multifocal motor neuropathy reported. Notably, the most recent guidelines of the European Society for the Study of Coeliac Disease do not recognize multifocal motor neuropathy as a classical neurological manifestation of gluten-related disorders. The main differential diagnoses include amyotrophic lateral sclerosis and chronic inflammatory demyelinating polyneuropathy. Currently, strict adherence to a gluten-free diet remains the only therapeutic option. Although clinical improvement is not universal, when observed, it strongly supports the causal role of gluten-related neurotoxicity.

CASE PRESENTATION: We report the case of a 50-year-old North African man with a history of dermatitis herpetiformis and persistent chronic diarrhea. Over the past 5 years, he developed progressive asymmetric motor weakness. Clinical examination revealed an asymmetric, pure motor, peripheral neurogenic syndrome, confirmed by nerve conduction studies, without evidence of proximal conduction block. Cerebrospinal fluid analysis showed elevated protein levels (0.75 g/L), and serum anti-GD3 IgM antibodies were positive. Brachial plexus magnetic resonance imaging revealed bilateral hypertrophy on T1-weighted sequences, with hyperintensity on short tau inversion recovery sequences but no contrast enhancement. The motor deficit gradually improved after the introduction of a gluten-free diet. The patient also received intravenous immunoglobulin without significant clinical benefit. On the basis of clinical, paraclinical, and follow-up findings, a diagnosis of multifocal motor neuropathy secondary to gluten intolerance was established.

CONCLUSION: This case highlights the importance of considering gluten intolerance as a potential etiology, particularly given the reversible nature of this neuropathy, which can otherwise be misdiagnosed as a more severe condition such as amyotrophic lateral sclerosis. Further studies are needed to better elucidate the pathophysiology of this rare gluten-related neurological phenotype.},
}

@article {pmid41889878,
year = {2026},
author = {Hines, TJ and Funke, JR and Pratt, SL and Rice, AD and Twiss, JL and Burgess, RW},
title = {A mouse model of autosomal dominant spastic ataxia and myopathy caused by a mutation in Tuba4a.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.03.06.710113},
pmid = {41889878},
issn = {2692-8205},
abstract = {Hereditary ataxias are a heterogeneous group of neurodegenerative disorders characterized by impaired balance and coordination, often due to cerebellar dysfunction. Despite advances in identifying genetic causes, animal models remain essential for dissecting underlying mechanisms and testing therapeutic strategies. Here we describe a mouse model of spastic ataxia and myopathy caused by a missense mutation in Tuba4a (n.A626C, p.Gln176Pro). In an ENU mutagenesis screen, a male C57BL/6J mouse exhibiting muscle wasting and an intention tremor starting at approximately 4 weeks-of-age was identified. The male was bred by in vitro fertilization to BALB/cByJ oocyte donors. Genetic mapping determined dominant inheritance and localized the mutation to Chromosome 1. Genome sequencing revealed single nucleotide polymorphisms (SNPs) in serine threonine kinase 36 (Stk36 [Y1003N]) and alpha-tubulin 4A (Tuba4a [Q176P]) in the mapping interval. These SNPs were CRISPR-engineered into C57BL/6J mice, which confirmed the Tuba4a [Q176P] variant as the causative mutation. Mutant mice are normal at 3 weeks, except for decrement in muscle response following repetitive nerve stimulation. However, by 30 days these mice have ataxia, Purkinje neuron degeneration, and extensive skeletal muscle defects, which contribute to a decreased lifespan. Dominant TUBA4A mutations in humans are associated with spastic ataxia type 11 (SPAX11), congenital myopathy type 26 (CMYO26), and frontotemporal dementia/amyotrophic lateral sclerosis type 9 (FTDALS9). Our mice exhibit hallmark features of SPAX11 and CMYO26, but do not show motor neuron degeneration. This specificity makes this model a valuable tool for studying cell-type selective effects of TUBA4A mutations in neurodegeneration and myopathy.},
}

@article {pmid41890126,
year = {2026},
author = {Spence, H and Read, FL and Waldron, FM and Gregory, JM},
title = {Metabolic signatures of ferritin and TDP-43 co-pathology provide a mechanistic basis for stratified therapeutic approaches in ALS.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.03.13.711539},
pmid = {41890126},
issn = {2692-8205},
abstract = {BACKGROUND: ALS is increasingly recognized as a biologically heterogeneous disease in which several molecular and pathological mechanisms converge on a similar clinical phenotype. One of these molecular markers is ferritin accumulation which is observed in a subset of ALS cases and has been shown to directly correlate with TDP-43 pathology in some brain regions. Additionally, TDP-43 proteinopathy is observed outside of ALS which may complicate the interpretation of case vs control approaches to target discovery. Here, we propose a pathology-stratified approach to empower targeted theranostics. We hypothesised that biologically distinct ALS subtypes may be defined by specific metabolic dysfunction linked to brain-accumulated ferritin and TDP-43 pathology.

METHODS: Post-mortem primary motor cortex tissue from 15 ALS cases and 20 age- and sex-matched controls was stratified, using immunohistochemistry, by single- or co-occurrence of ferritin accumulation, and pathological TDP-43. Untargeted metabolomics (>1,000 metabolites) was performed, and samples were stratified into dual positive (ferritin and TDP-43), single positive (either), or negative. Group-discriminating metabolites were identified using partial least squares discriminant analysis.

RESULTS: Dual ferritin and TDP-43 pathology reflected a distinct metabolomic profile, separable from single-pathology states. This dual positive metabolic signature was characterised by disruption of lysophospholipid, lysoplasmalogen, and fatty acid metabolism, consistent with impaired membrane and energy homeostasis. In contrast, pathological TDP-43 presence without ferritin, was characterised metabolically by significant depletion of secondary bile acids and increase in glycosylation markers, whilst ferritin accumulation alone reflected significant increase in oxidative stress and depletion of lipid peroxidation inhibition markers. The dual positive state suggests failure of compensatory metabolic responses present in single-pathology conditions.

CONCLUSIONS: Ferritin accumulation and TDP-43 pathology define biologically distinct subtypes associated with ALS with divergent metabolic vulnerabilities. The metabolic signature associated with dual pathology provides a mechanistic correlate to MRI-visible ferritin accumulated iron, supporting paired non-invasive biomarker and target discovery for pathology-dependent patient stratification. These findings argue for pathway-targeted, subtype-specific therapeutic strategies and highlight the necessity of precision medicine approaches in ALS.

SHORT ABSTRACT: Amyotrophic lateral sclerosis (ALS) exhibits profound molecular heterogeneity that is not captured by current clinical classifications. Additionally, TDP-43 proteinopathy is observed outside of ALS which may complicate the interpretation of case vs control approaches to target discovery. Here, we propose a pathology-stratified approach to therapeutic target discovery, identifying convergent iron dysregulation and TDP-43 pathology with specific metabolic consequences. Post-mortem primary motor cortex tissue from 15 ALS cases and 20 controls was investigated for ferritin, and pathological TDP-43 using RNA aptamer-based immunostaining. Untargeted metabolomics (>1,000 metabolites) was performed with stratification into dual positive, single positive, or negative groups, followed by partial least squares discriminant analysis. Dual ferritin and TDP-43 pathology produced a distinct metabolic state characterised by disruption of lysophospholipid, lysoplasmalogen, and fatty acid metabolism, indicating impaired membrane integrity and energy homeostasis. In contrast, single positive states engaged divergent compensatory pathways involving bile acid metabolism, glycosylation, or oxidative stress regulation. Ferritin-TDP-43 convergence defines a metabolically decompensated ALS subtype corresponding to MRI signatures, providing a mechanistic basis for imaging-guided, pathology-dependent patient stratification and targeted intervention.

KEY FINDINGS: Metabolically distinct subtypes were defined by the presence or absence of ferritin-associated iron accumulation and TDP-43 pathology in the primary motor cortex.Concurrent ferritin and TDP-43 pathology produce a unique, metabolically decompensated state characterised by disrupted lipid, membrane, and energy metabolism, distinct from either pathology alone.Single positive states engage divergent compensatory metabolic pathways, which are lost when ferritin and TDP-43 co-occur.The metabolic signature of dual positivity provides a mechanistic correlate to the MRI-visible motor band sign.These findings support the use of pathology-based stratification of ALS patients and a foundation for pathway-targeted, precision therapeutic approaches.},
}

@article {pmid41890230,
year = {2026},
author = {Aguerd, A and Nouadi, B and Ezaouine, A and Fenjar, I and Bennis, F and Chegdani, F},
title = {An in silico protocol for predicting genetic biomarkers in rare diseases: a case study in sporadic amyotrophic lateral sclerosis.},
journal = {Frontiers in genetics},
volume = {17},
number = {},
pages = {1742595},
pmid = {41890230},
issn = {1664-8021},
abstract = {Studying the genetics of rare diseases is challenging because small sample sizes limit the statistical power of standard methods like Genome-wide association studies (GWAS). We created a new machine-learning approach to find candidate Single Nucleotide Polymorphisms (SNPs) when data is scarce. Our method trains a Random Forest model to spot similarities between SNPs. We used 189 known Sporadic Amyotrophic Lateral Sclerosis (sALS)-linked SNPs as positive examples and 938,544 unrelated SNPs as negatives. The model learns from genomic location, significance levels, nearby genes, and other features. When we tested it on sALS, it performed exceptionally well, with 93.8% accuracy and near-perfect AUC scores. The method uncovered 1,890 new SNP candidates for sALS. Among these, 209 reached genome-wide significance, and 50 appeared repeatedly in our analyses, making them strong candidates. Key genes like SARM1, OPHN1, and BPTF emerged from the results, all connected to neural health and survival pathways. Our examination revealed a notable excess of SNPs on chromosome 18 compared to expectations. This non-random distribution underscores the region's particular interest. Here, our approach demonstrates its ability to extract meaningful signals from a restricted sample. The results generated by this approach enable early diagnosis of the disease under study, explanation of its mechanism, and identification of therapeutic targets.},
}

@article {pmid41890274,
year = {2026},
author = {Silva-Hucha, S and Hernández, RG and Baena-López, D and Fernández de Sevilla, ME and Paradas, C and Morcuende, S},
title = {Excitotoxicity in amyotrophic lateral sclerosis: a key pathogenic mechanism.},
journal = {Brain communications},
volume = {8},
number = {2},
pages = {fcag098},
pmid = {41890274},
issn = {2632-1297},
abstract = {Amyotrophic lateral sclerosis is a complex neurodegenerative disease affecting motor neurons, characterized by the involvement of various factors, including oxidative stress, inflammatory processes, glutamate excitotoxicity, mitochondrial dysfunction, protein aggregation, axonal transport abnormalities, and apoptosis. The complexity of amyotrophic lateral sclerosis arises from its multifactorial aetiology involving diverse genetic, protein, metabolic, and cellular alterations. Mutations of different genes, such as SOD1, C9ORF72, TARDBP, and FUS, have been identified as critical contributors to disease pathophysiology through their facilitation of aberrant protein misfolding and aggregation. All these factors disrupt glutamate homeostasis, leading to calcium-mediated neurotoxicity. Under oxidative stress, motor neurons exhibit a diminished capacity to regulate calcium influx, along with impaired functioning of the mitochondria and endoplasmic reticulum, further compromising cellular integrity. Dysregulation of glutamate signalling also triggers astrocytic stress responses, leading to reduced glutamate clearance, thus worsening neuronal damage through excitotoxic mechanisms. These factors contribute to the excessive production of reactive oxygen species, which exacerbates glutamate imbalance and establishes a detrimental cycle of neuronal damage and glial dysfunction, ultimately intensifying excitotoxicity. This review aims to highlight the role of excitotoxicity in motor neuronal degeneration and to explore the molecular mechanisms underlying the pathogenesis of amyotrophic lateral sclerosis. It also examines current therapeutic approaches, including approved treatments and ongoing clinical trials to reduce excitotoxicity, while emphasizing the urgent need for novel, targeted strategies. Given the lack of definitive diagnostic tools and curative therapies, advancing our understanding of the molecular mechanisms driving excitotoxicity and neurodegeneration is, therefore, crucial for the development of more effective, disease-modifying treatments to slow amyotrophic lateral sclerosis progression.},
}

@article {pmid41890591,
year = {2026},
author = {Gabbay, U},
title = {Axonal transport impairment as an upstream mechanism in amyotrophic lateral sclerosis pathogenesis.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1802313},
pmid = {41890591},
issn = {1662-4548},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive loss of upper and lower motor neurons. Despite marked genetic and pathological heterogeneity, a unifying pathogenic framework remains lacking. We propose that axonal transport impairment represents an early and convergent but genotype-modulated upstream vulnerability in ALS, contributing to distal synaptic failure, bioenergetic stress, protein aggregation, neuroinflammation, and neuronal death. Across many ALS models, including SOD1, TARDBP (TDP-43), FUS, and C9orf72, transport deficits are frequently detectable in presymptomatic stages, often preceding overt motor neuron loss or clinical manifestation, although temporal ordering varies by molecular subtype. Human data from induced pluripotent stem cell-derived motor neurons and neuroimaging in mutation carriers further support early transport dysfunction in both familial and sporadic ALS. We synthesize genetic, cellular, and systems-level evidence demonstrating that diverse ALS-associated mutations converge on intracellular trafficking machinery through distinct but interacting mechanisms, disrupting long-range cargo delivery and clearance in motor neurons. This framework provides a mechanistic basis for selective motor neuron vulnerability, the dying-back pattern of neuromuscular junction degeneration, and the emergence of downstream pathological hallmarks including mitochondrial dysfunction, excitotoxicity, aggregation, and inflammation. This model generates testable predictions regarding presymptomatic transport biomarkers and the timing of therapeutic intervention. We discuss implications for biomarker development and therapeutic strategy, proposing restoration of axonal transport as a central component of rational multimodal disease modification in ALS.},
}

@article {pmid41892827,
year = {2026},
author = {Pérez-Bonilla, M and Mora-Ortiz, M and Díaz-Borrego, P and Muñoz-Alcaraz, MN and Mayordomo-Riera, FJ and Girela-López, E},
title = {Biomechanical Voice Parameters as Potential Biomarkers for Phenotype Differentiation in Amyotrophic Lateral Sclerosis: A Cross-Sectional Study.},
journal = {Medical sciences (Basel, Switzerland)},
volume = {14},
number = {1},
pages = {},
doi = {10.3390/medsci14010112},
pmid = {41892827},
issn = {2076-3271},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Aged ; Biomechanical Phenomena ; Phenotype ; Biomarkers ; *Voice/physiology ; *Voice Disorders/physiopathology/diagnosis/etiology ; Adult ; Phonation/physiology ; },
abstract = {Background/Objectives: Amyotrophic lateral sclerosis (ALS) is a clinically heterogeneous neurodegenerative disease in which bulbar involvement frequently affects speech and voice production. Although acoustic voice analysis can detect phonatory alterations in ALS, its ability to differentiate clinical phenotypes remains limited. This study investigated whether biomechanical voice parameters provide complementary information for characterizing bulbar involvement across bulbar-onset ALS (ALS-B) and spinal-onset ALS (ALS-S) and explored their association with clinical and functional measures. Methods: This cross-sectional observational study included 50 patients with ALS (20 ALS-B, 30 ALS-S) and 50 controls with non-neurological voice disorders. Sustained vowel phonation was analyzed using acoustic measures and biomechanical voice parameters derived from a standardized model of vocal fold vibration. Perceptual voice severity was assessed using the GRBAS scale, while functional status was evaluated with the ALS Functional Rating Scale-Revised (ALSFRS-R) and the Barthel Index. Associations with clinical measures were explored in secondary analyses. Results: Compared with controls, ALS patients showed significant differences in acoustic measures and several biomechanical parameters related to glottal closure and vibratory stability. Biomechanical analysis revealed significant differences between ALS-B and ALS-S, particularly in parameters reflecting vibratory asymmetry, glottal tension and cycle-to-cycle instability. Unexpectedly, ALS-B showed greater perceptual voice severity and higher Barthel Index scores than ALS-S, while no differences were observed in global ALSFRS-R total scores. Conclusions: Biomechanical voice analysis appears to capture physiologically meaningful alterations in vocal fold function in ALS and provides complementary information for characterizing bulbar motor involvement across clinical phenotypes, particularly ALS-B disease. When combined with acoustic and clinical assessments, this approach may enhance the evaluation of bulbar involvement and functional status in ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/diagnosis
Male
Female
Cross-Sectional Studies
Middle Aged
Aged
Biomechanical Phenomena
Phenotype
Biomarkers
*Voice/physiology
*Voice Disorders/physiopathology/diagnosis/etiology
Adult
Phonation/physiology

@article {pmid41893050,
year = {2026},
author = {Duranti, E and Villa, C},
title = {Misfolded Proteins and Cognitive Decline: Mechanistic Insights into Neurodegenerative Disorders.},
journal = {Neurology international},
volume = {18},
number = {3},
pages = {},
doi = {10.3390/neurolint18030048},
pmid = {41893050},
issn = {2035-8385},
abstract = {Cognitive decline represents one of the most common clinical manifestations of neurodegenerative diseases (NDs), substantially affecting the quality of life of both patients and their families. Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis are major NDs characterized by a progressive degeneration of the central nervous system, with functional impairments extending beyond motor symptoms to multiple cognitive domains, including memory, attention, language, and executive functions. Increasing evidence highlights misfolded protein accumulation as a key driver of neuronal dysfunction and cognitive deterioration. This narrative review examines the major cognitive deficits associated with these disorders, focusing on the underlying molecular mechanisms, particularly protein aggregation, as well as clinical manifestations and their effects on daily life. Furthermore, current diagnostic tools and emerging therapeutic options for mitigating cognitive decline will be further discussed.},
}

@article {pmid41894152,
year = {2026},
author = {Kutahyalioglu, NS and Onan, N},
title = {The Relationship Between Academic Literacy and Critical Thinking Disposition on Nursing Students.},
journal = {The Journal of nursing education},
volume = {},
number = {},
pages = {1-9},
doi = {10.3928/01484834-20260317-02},
pmid = {41894152},
issn = {1938-2421},
abstract = {BACKGROUND: Evidence-based nursing practice requires strong academic literacy (AL) and critical thinking (CT) skills, yet the link between these two competencies has not been adequately explored. This study aimed to assess nursing students' AL and CT levels and to examine the relationship between them.

METHOD: A descriptive and correlational design was used with 120 nursing students. Data was collected using a Socio-demographic Information Form, the Academic Literacy Scale (ALS), and the Critical Thinking Disposition Scale (CTDS), and analyzed through descriptive statistics and correlation analyses.

RESULTS: Students' mean ALS score was 86.54 (SD = 9.54), and the mean CTDS score was 3.85 (SD = 0.56). AL was strongly correlated with CT disposition (r = .641, p < .01). Regression analysis indicated that CT disposition explained 41% of the variance in AL (R[2] = .410).

CONCLUSION: Critical thinking significantly predicts academic literacy, underscoring the need for educational strategies that foster both skills.},
}

@article {pmid41894255,
year = {2026},
author = {Hirata, Y and Kobatake, Y and Koyama, H and Furuta, K and Takemori, H and Kamatari, YO},
title = {Destabilized Soluble SOD1 Species as Potential Determinants of Disease Severity in Familial Amyotrophic Lateral Sclerosis.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.5c00668},
pmid = {41894255},
issn = {1948-7193},
abstract = {Mutations in the Cu/Zn superoxide dismutase (SOD1) gene are linked to familial amyotrophic lateral sclerosis (ALS), yet the identity of the toxic molecular species remains unclear. We investigated the relationship between protein misfolding and pathogenicity by expressing GFP-tagged wild-type and mutant SOD1 (A4V, H46R, G93A) in mouse hippocampal HT22 cells. Western blotting under nonreducing conditions suggested that A4V, associated with rapid disease progression, was largely depleted of properly folded soluble SOD1 and instead produced highly destabilized soluble species. In contrast, H46R, associated with a milder phenotype, showed a moderate reduction in properly folded soluble SOD1 and generated partially folded/native-like conformers. G93A exhibited biochemical characteristics intermediate between those of A4V and H46R. A4V also showed a pronounced loss of GFP fluorescence, indicating severe structural destabilization; the extent of fluorescence loss in A4V, G93A, and H46R broadly correlated with clinical severity. Neither CuATSM nor ebselen─targeting metal binding and disulfide formation, respectively─rescued fluorescence, suggesting broader defects in SOD1 maturation. Nevertheless, both compounds inhibited ferroptosis, a nonapoptotic form of cell death characterized by iron-dependent lipid peroxidation, in HT22 cells, indicating alternative neuroprotective mechanisms. These findings identify destabilized soluble SOD1 species as a key toxic entity in ALS and highlight the utility of GFP-tagged constructs for evaluating folding status and screening therapeutic candidates.},
}

@article {pmid41895196,
year = {2026},
author = {Schmidlin, D and Thaysen, EM and Platikanov, S and Xu, J and Chesa, MJ and Tauler, R and Vázquez-Suñé, E and Teixidó, M},
title = {Impact of the superblock model on key components of the urban water cycle: Trace metals and dissolved organic matter dynamics across the built environment.},
journal = {Journal of hazardous materials},
volume = {508},
number = {},
pages = {141867},
doi = {10.1016/j.jhazmat.2026.141867},
pmid = {41895196},
issn = {1873-3336},
abstract = {Climate change, growing urban pollution, and increasing water scarcity are forcing cities to adopt strategies that enhance resilience to both climatic and anthropogenic pressures. The Barcelona Superblock model is a novel urban planning strategy that highly restricts vehicle traffic, converts streets into pedestrian-priority corridors, and promotes green spaces. Within this framework, green infrastructures, also called sustainable urban drainage systems (SUDS), are implemented as local, site-specific measures to capture (i.e., flood control), treat, and infiltrate treated stormwater (i.e., aquifer recharge). To evaluate the Superblock model impact on urban water quality, we conducted seven sampling campaigns across three Barcelona districts, targeting rainfall, stormwater "first-flush" from roads and pedestrianized streets, as well as SUDS influent and effluent within and in the vicinity to Superblocks, with a focus on dissolved trace metals and dissolved organic matter (DOM). Results showed that Superblocks reduced pollutant loads and mitigated ecotoxicological risks. Trace metal and DOM concentrations followed the trend: Rain < SUDS effluent < Pedestrian Street runoff < Road runoff, highlighting traffic-related impacts and SUDS treatment capacity (23-70% in best case scenario). Risk assessment indicated episodic ecotoxicological risk in stormwater, especially in road runoff due to elevated concentrations of Cu and Zn, while SUDS consistently remained below risk thresholds. SUDS also transform DOM into more stable, humic-like forms. Trace metals and DOM emerged as biogeochemical proxies for stormwater quality, enabling more effective and sustainable urban water management. These findings support the integration of Superblock-like strategies into urban planning to control and reduce contaminant urban discharges.},
}

@article {pmid41881396,
year = {2026},
author = {Zhou, R and Lin, X and Lin, J and Liao, Z and Ni, H and Lin, X and He, Q and Ning, W},
title = {Cellular senescence in neurodegenerative diseases: a bibliometric analysis and mechanistic synthesis linking translational pathways to therapeutic implications.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {103110},
doi = {10.1016/j.arr.2026.103110},
pmid = {41881396},
issn = {1872-9649},
abstract = {BACKGROUND: Cellular senescence is now recognized as a pivotal driver of neurodegenerative diseases (NDs). Despite advances in understanding senescence mechanisms, such as the p16[INK4A]/p53-p21[CIP1] pathways and the senescence-associated secretory phenotype (SASP), along with the development of therapeutic strategies like senotherapeutics, the research landscape remains fragmented.

OBJECTIVE: Systematically addresses the fragmentation characterizing current research on cellular senescence in NDs, integrating bibliometric analysis with a mechanistic synthesis of translational relevance and therapeutic implications.

METHODS: A comprehensive bibliometric analysis was performed. Literature retrieval on cellular senescence and four NDs (AD, PD, ALS, HD) was executed in Web of Science Core Collection (WoSCC) on April 30, 2025. CiteSpace V.6.4 R1 and VOSviewer 1.6.20 reconstructed networks for temporal trends, burst detection, and co-occurrence visualization. In addition to bibliometric mapping, we provide a mechanistic synthesis of emerging translational pathways.

RESULTS: Analysis included 269 relevant articles (2002-April 2025). Annual publications and cumulative citations increased markedly since 2018. The US led in output/influence, followed by China and Italy. Key collaborative institutions included Chinese Academy of Sciences, University of Texas System, and University of California System. Leading authors were Lorenz Studer, Judith Campisi, and Julie K. Andersen. Tyler J. Bussian and Peisu Zhang were highly co-cited. Top-cited journals were Nature, PNAS, and PLOS One. Research hotspots focus on abnormal tau protein in senescence and senescent microglia mediating chronic neuroinflammation, development of multi-target senomorphics targeting SASP is emerging as a promising therapeutic direction.

CONCLUSION: Cellular senescence research in NDs (notably AD, PD) shows broad promise from mechanisms to therapy. Future priorities include elucidating tau dysregulation's core role in senescence, developing specific biomarkers and targeted interventions. Senescent microglia are new therapeutic targets. Multi-target senomorphics modulating SASP offer new mechanisms for delaying ND progression. Understanding senescence mechanisms and precise interventions may provide novel ND therapies.},
}

@article {pmid41882018,
year = {2026},
author = {Lin, J and Agote-Aran, A and Liao, Y and Cloarec, M and Andronov, L and Schoch, RL and Ronchi, P and Cochard, V and Zhu, R and Grandgirard, E and Liu, X and Lemée, MV and Kleiss, C and Golzio, C and Ruff, M and Chevreux, G and Schwab, Y and Klaholz, BP and Sumara, I},
title = {RanBP2-dependent annulate lamellae drive nuclear pore assembly and nuclear expansion.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-71101-y},
pmid = {41882018},
issn = {2041-1723},
support = {ANR-22-CE13-0025//Agence Nationale de la Recherche (French National Research Agency)/ ; },
abstract = {Nuclear pore complexes (NPCs) enable nucleocytoplasmic transport. While NPCs primarily localize to the nuclear envelope (NE), they also appear in cytoplasmic endoplasmic reticulum (ER) membranes called annulate lamellae (AL). Though discovered in the mid-20th century, AL's function and biogenesis remain unclear. Previously considered exclusive to embryonic and malignant cells, we find AL in somatic mammalian cells. Under normal conditions, AL store pre-assembled AL-NPCs that integrate into the NE, producing approximately one-third of newly formed nuclear pores and supporting nuclear expansion during G1. Upon pathological stimuli, AL transfer to the NE is impaired, leading to their cytoplasmic accumulation. RanBP2 (Nup358) is essential for AL biogenesis, with its phenylalanine-glycine repeats promoting AL-NPC scaffold oligomerization. ER-associated Climp63 (CKAP4) directs AL-NPCs to ER sheets and the NE. This AL-driven nuclear pore formation is complementary to the canonical routes, constituting a distinct NPC assembly pathway. Our work uncovers the biogenesis mechanism of AL and the nuclear function of this key cellular organelle.},
}

@article {pmid41883703,
year = {2026},
author = {Nassan, M and Ayala, I and Sloan, J and Bonfitto, A and Stark, B and Song, S and Naymik, M and Geula, C and Gefen, T and Barbieri, E and Piras, I and Mesulam, MM and Huentelman, M},
title = {The Genetics of TDP-43 Type C Neurodegeneration: A Whole-Genome Sequencing Study and Literature Review.},
journal = {Neurology. Genetics},
volume = {12},
number = {2},
pages = {e200369},
pmid = {41883703},
issn = {2376-7839},
abstract = {BACKGROUND AND OBJECTIVES: Frontotemporal lobar degeneration TDP43 type C (TDP-C) is a rare and unique neurodegenerative disease that attacks the anterior temporal lobe. Recently, it was shown that Annexin-A11 and TDP-43 coaggregate specifically in TDP-C. Current literature on the genetic associations with TDP-C, reviewed here, lacks a discernible corpus of robust or replicated findings. In this study, using blood tissue, we completed whole genome sequencing to investigate ANXA11 and TARDBP genetic variants for their association with TDP-C. Then, we completed genome-wide hypothesis-free analyses using artificial intelligence to identify rare pathogenic variants associated with TDP-C.

METHODS: (1) We tested common variants in ANXA11 and TARDBP for their association with 37 TDP-C cases vs 290 controls. We attempted to replicate our findings in a different cohort of 467 TDP-C cases vs 3,153 controls and contrasted them with cohorts of TDP-A and TDP-B. (2) AI-guided analyses were completed to prioritize pathogenic rare variants associated with TDP-C in our cohort.

RESULTS: (1) Four common variants in ANXA11 (rs113772135, rs2789686, rs1079242, rs61860017) were significantly associated with TDP-C in the discovery cohort and replicated in the other cohort of TDP-C but not in TDP-A or TDP-B, providing evidence for ANXA11 specific association with TDP-C. Rs1079242-A showed the most robust replication (p = 7.35 × 10[-05]) and correlates with higher ANXA11 level in CSF (p = 4 × 10[-11]). No associations were found between TARDBP and TDP-C (p > 0.05). Using AI-guided rare variant analyses, we identified a pathogenic variant in FIG4, a gene that has been implicated in amyotrophic lateral sclerosis (ALS). Because of the observed potential genetic overlap between some ALS genes and TDP-C, we leveraged mendelian randomization and found that ALS genetic load is associated with TDP-C risk (p = 0.0046).

DISCUSSION: This study provides replicated evidence for the association between common variants in ANXA11 with TDP-C. Knowing rs1079242-A affects ANXA11 level in CSF, future studies may aim to investigate ANXA11 level as potential CSF biomarker for TDP-C. Moreover, FIG4 and ANXA11 have been implicated in the inositol pathway. Our results provide novel insights into the genetic risk of TDP-C and offer new clues about its underpinning mechanisms.},
}

@article {pmid41884057,
year = {2026},
author = {Tannoury, C and Denwood, H and Khan, RR and Kyada, RJ and Zhou, OT and Atassi, S and Saade, A and Chahine, MN and Tannoury, T},
title = {Is the antepsoas oblique lumbosacral interbody fusion safe in patients with aortoiliac calcification?.},
journal = {North American Spine Society journal},
volume = {25},
number = {},
pages = {100867},
pmid = {41884057},
issn = {2666-5484},
abstract = {BACKGROUND: The anterior approaches to lumbar arthrodesis, including direct anterior (ALIF) and antepsoas (ATP)/oblique (OLIF) fusions, require careful manipulation of the abdominal prevertebral vessels for safe and adequate spinal access. Therefore, surgeons who perform anterior lumbar fusions in patients with aortoiliac calcifications are often cautious due to concerns for perioperative vascular complications, as well as the associated risks of concomitant medical comorbidities. This study sought to compare the incidence of perioperative vascular and medical complications in patients with and without abdominal aortoiliac calcification (AAC) undergoing the minimally invasive antepsoas (MIS-ATP) lumbosacral fusion.

METHODS: This was a retrospective matched cohort study including 482 adult patients undergoing MIS-ATP lumbosacral fusions at a single institution between 2014 and 2020 (227 with AAC and 255 without AAC), matched by sex and American Society of Anesthesiologists (ASA) scores. Through preoperative standing lateral lumbar radiographs, using Kaupilla et al.'s AAC grading system, we graded anterior and posterior aortic wall calcification from L1 to L4. Electronic medical records were reviewed to identify and collect the perioperative complications.

RESULTS: While there was no occurrence of intraoperative vascular injuries in either group, patients with AAC were more likely to develop medical complication (34.8% vs. 13.3%, p < .001), with anemia (18.9% vs. 9.2%), ileus (16.3% vs. 2.7%) and acute kidney injury (6.6% vs. 5.5%) being the most common. Overall, individuals with AAC had 2.62 times increased odds of developing a postoperative medical complication. Moreover, moderate AAC was found to be a significant risk factor (OR = 3.48).

CONCLUSIONS: Presence of AAC in patients undergoing MIS-ATP fusion was not associated with increased risk of direct surgical or exposure related vascular complications. However, patients with AAC were significantly more likely to experience medical complications following MIS-ATP fusion.},
}

@article {pmid41884172,
year = {2026},
author = {Seki, S and Enomoto, A and Tanaka, S},
title = {The mesencephalic trigeminal neuron: electrophysiological insights into function and dysfunction.},
journal = {Frontiers in cellular neuroscience},
volume = {20},
number = {},
pages = {1752701},
pmid = {41884172},
issn = {1662-5102},
abstract = {Mesencephalic trigeminal neurons (MTNs) are the sole primary afferent neurons with cell bodies located within the central nervous system. MTNs convey proprioceptive inputs from masticatory muscles and periodontal ligaments, thereby contributing to the precise regulation of jaw-oral motor functions. Through ionic mechanisms such as currents generated by the voltage-dependent sodium (Nav) channel isoform Nav1.6, hyperpolarization-activated currents, and persistent inward currents, MTNs generate sustained and burst firing that regulate masticatory rhythm and jaw-jerk reflex timing. Their activity is further modulated by neurotransmitters, including serotonin and norepinephrine, which provide flexibility in sensorimotor integration. Pathological conditions such as chronic stress and sodium channel dysfunction induce MTN hyperexcitability or irregular firing, contributing to bruxism, temporomandibular disorders, and feeding impairment in amyotrophic lateral sclerosis models. In addition, aging and tooth loss lead to Piezo2 downregulation and neuronal death, potentially resulting in masticatory dysfunction and cognitive decline. Recent findings suggest that interventions targeting vesicular glutamate transporter 1 projections, melanocortin 4 receptor signaling, and nitric oxide pathways represent novel therapeutic approaches. Taken together, MTNs have emerged as promising targets for treating conditions ranging from masticatory motor disorders to neurodegenerative diseases.},
}

@article {pmid41884597,
year = {2026},
author = {Milioto, C and Carcolé, M and Zanovello, M and Ahmed, M and Nirujogi, RS and Biggs, D and Roberts, MJ and Schweers, K and Cammack, AJ and Marchi, PM and Katona, E and Glaria, I and Santos, A and Devoy, A and Fratta, P and Alessi, DR and Davies, B and Greensmith, L and Fisher, EMC and Isaacs, AM},
title = {C9orf72 poly(glycine-alanine) knock-in mice exhibit mild rotarod and proteomic changes consistent with amyotrophic lateral sclerosis/frontotemporal dementia.},
journal = {Brain communications},
volume = {8},
number = {2},
pages = {fcag087},
pmid = {41884597},
issn = {2632-1297},
abstract = {A GGGGCC repeat expansion in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The repeat expansion is translated into five different dipeptide repeat proteins: poly(glycine-alanine) (polyGA), poly(glycine-proline) (polyGP), poly(glycine-arginine) (polyGR), poly(alanine-proline) (polyAP) and poly(proline-arginine) (polyPR). To investigate the effect of polyGA, which is the most abundant dipeptide repeat protein in patient brains, we used clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR associated nuclease 9 (Cas9) to insert 400 codon-optimized polyGA repeats immediately downstream of the mouse C9orf72 start codon. This generated (GA)400 knock-in mice driven by the endogenous mouse C9orf72 promoter, coupled with heterozygous C9orf72 reduction. PolyGA remains soluble up to 18 months of age and (GA)400 mice develop subtle dysfunction characterized by impaired rotarod performance, without overt neuropathological alterations. Quantitative proteomics revealed polyGA expression caused protein alterations in the spinal cord, including changes in previously identified polyGA interactors. Our findings show that (GA)400 mice are a complementary in vivo model to better understand C9orf72 ALS/FTD pathology and determine the specific role of individual DPRs in disease.},
}

@article {pmid41884646,
year = {2026},
author = {Sudwarts, A and Thinakaran, G},
title = {Female-specific Cx3cr1-driven regulation of ALS and Alzheimer's risk genes in tauopathy.},
journal = {Molecular neurodegeneration advances},
volume = {2},
number = {1},
pages = {16},
pmid = {41884646},
issn = {3059-4944},
abstract = {UNLABELLED: By introducing haploinsufficiency of Cx3cr1 in the P301S (PS19) transgenic model of tau pathology, we report remarkable transcriptional changes, including crucial amyotrophic lateral sclerosis and Alzheimer's disease risk genes, several of which showed co-expression, suggesting gene-gene interactions among these genetic risk factors.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s44477-026-00022-3.},
}

@article {pmid41884800,
year = {2026},
author = {Nette, S and Purvis, JK and Helpard, H},
title = {Identifying Student Learning Challenges and Potential Solutions in Nursing Education Delivery in Rural Nova Scotia Using Photovoice.},
journal = {SAGE open nursing},
volume = {12},
number = {},
pages = {23779608251413674},
pmid = {41884800},
issn = {2377-9608},
abstract = {INTRODUCTION: Rural nursing programs encounter obstacles in providing nursing education opportunities relevant to the escalating needs of rural healthcare. Rural nursing programs often experience limited clinical placements, a stressed and burned-out rural nursing workforce, and difficulty finding nursing preceptors. Moreover, students studying in rural nursing programs experience increased travel, financial and social burden, and have less access to resources and support from their university. There is limited research giving voice to rural nursing students' experience and their suggestions for solutions.

OBJECTIVE: The purpose of this study was to understand the learning challenges of and potential solutions for baccalaureate nursing students attending a rural university.

METHODS: This is a descriptive qualitative study using photovoice methodology. Participants captured two pictures of things in their school surroundings or personal life that created learning challenges in rural nursing education, and two pictures of potential solutions to these challenges. Participants titled each picture and, using guided questions provided by the researcher, wrote a short reflection of what the photos represented.

RESULTS: Guided by empowerment education for critical consciousness and using Braun and Clarke's thematic analysis and Oliffe et al.'s layered photograph analysis, two overarching themes emerged: access to resources and clinical learning. Findings highlight financial, academic, and accessibility barriers in rural nursing programs as well as participant-determined solutions that could enhance learning experiences, student well-being, and retention in the rural healthcare workforce.

CONCLUSIONS: This study identified targeted resources for nursing students attending a rural nursing baccalaureate program to support their learning, wellbeing, and growth into graduate nurses. This study also identified areas for future research to explore nursing student experiences across rural and urban institutions and develop effective learning support strategies for rural nursing education.},
}

@article {pmid41885096,
year = {2026},
author = {Wolfensberger, A and Faes Hesse, M and Sax, H and Clack, L},
title = {From plan to practice: a structured report on implementation strategies for preventing non-ventilator hospital-acquired pneumonia (nvHAP).},
journal = {Infection control and hospital epidemiology},
volume = {},
number = {},
pages = {1-9},
doi = {10.1017/ice.2026.10422},
pmid = {41885096},
issn = {1559-6834},
abstract = {BACKGROUND: There is increasing evidence on the effectiveness of prevention bundles against non-ventilator hospital-acquired pneumonia (nvHAP), but detailed reports on their implementation are lacking. This study aims to describe and structure the implementation activities undertaken in a single-center multimodal intervention that achieved a 31% reduction in nvHAP incidence.

DESIGN: Longitudinal descriptive qualitative study.

SETTING: Nine medical and surgical departments of a Swiss university hospital.

PARTICIPANTS: Healthcare professionals and implementation teams in study departments.

METHODS: We collected longitudinal data on implementation activities using (1) implementation activity logs, (2) drop-in interviews and observations, (3) "action plan meetings," (4) focus groups, and (5) unstructured recall sessions among the project team. Data were deductively coded using the "Expert Recommendations for Implementing Change" taxonomy, specified using Proctor et al.'s "Recommendations for specifying and reporting implementation strategies" and mapped to the "Exploration, Preparation, Implementation, Sustainment" framework phases.

RESULTS: A total of 174 activities were undertaken. Activities varied by implementation phase, most frequently involving "evaluative and iterative strategies," "develop stakeholder interrelationship strategies" and "training and education of stakeholders" during Exploration, Preparation, and Implementation, respectively. During Implementation, 54% of activities were initiated by department nurses, and 27% were initiated by the institutional implementation team. Activities included interdisciplinary kick-off events, education in various formats, posters, informational stickers for patients, provision of new equipment (e.g., toothbrushes), and electronic medical records order sets.

CONCLUSIONS: This report offers valuable insights for future implementation efforts by providing a structured overview of the concrete implementation activities performed in a successful one-hospital multimodal nvHAP prevention project.},
}

@article {pmid41885541,
year = {2026},
author = {Chen, RF and Liu, KF and Lee, CC and Li, YT and Chen, WY and Kuo, YR},
title = {Transcriptomic Analysis of Adipose-Derived Stem Cell Therapy Modulating B Cell Immune Tolerance in Vascularized Composite Allotransplantation.},
journal = {Plastic and reconstructive surgery},
volume = {},
number = {},
pages = {},
doi = {10.1097/PRS.0000000000013074},
pmid = {41885541},
issn = {1529-4242},
abstract = {BACKGROUND: Adipose-derived stem cells (ADSCs) have been shown to prolong vascularized composite allotransplantation (VCA) survival in rodent hindlimb transplantation. However, the mechanisms by which ADSCs modulate B cell responses and induce immune tolerance remain unclear. This study used next-generation sequencing (NGS) to investigate B cell gene expression after ADSC treatment.

METHODS: A rodent orthotopic hind-limb transplantation model was established using Brown-Norway to Lewis rats. The tolerance treatment group received a combination of ADSCs, short-term cyclosporine A (CsA) and anti-lymphocyte serum (ALS), while the control rejection group received no treatment. B cells were isolated from the spleens of rejection control group at 10-14 days post-transplantation when rejection was diagnosed, or tolerance group at least ≥100 days post-transplantation without rejection. RNA sequencing (RNA-Seq) was conducted to assess transcriptomic differences. Differentially expressed genes (DEGs) were analyzed using the EBSeq bioinformatics tool and pathway enrichment analyses, with validation by qPCR.

RESULTS: RNA-Seq identified 94 DEGs (out of 13,284 mRNAs) between the tolerance and rejection groups. Gene ontology and KEGG pathway analyses revealed significant enrichment in pathways associated with cytokine secretion, B cell receptor signaling, and humoral immunity. The tolerance group exhibited upregulation of key chemokines (e.g., Cxcl1, Cxcl2, Ccl4) and downregulation of pro-inflammatory genes (e.g., Tlr3, Siglec5, C3). qPCR validation confirmed the RNA-Seq findings. These results suggest that ADSCs modulate B cell-mediated immune responses and promote a shift toward an anti-inflammatory, tolerogenic profile.

CONCLUSIONS: ADSC-based therapy combined with short-term immunosuppression promotes immune tolerance in VCA by modulating B cell-related gene expression. These findings suggest that targeting B cell-mediated pathways may provide a novel approach may offer a novel therapeutic strategy for clinical application in VCA.},
}

@article {pmid41876403,
year = {2026},
author = {Yan, K and Jiang, Y and Yong, Y and Zhang, T and Zhang, N and Zeng, Q and Gong, X and Meng, L and Bi, F and Liu, Y},
title = {ALDOA Promotes Glycolysis and NLRP3/GSDMD Pyroptosis to Accelerate ALS Progression.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.70372},
pmid = {41876403},
issn = {2328-9503},
support = {81760238//National Natural Science Foundation of China/ ; 82171433//National Natural Science Foundation of China/ ; 2022JJ30918//Natural Science Foundation of Hunan Province/ ; 2023JJ30927//Natural Science Foundation of Hunan Province/ ; TSYC202401B119//Xinjiang Uygur Autonomous Region Health Commission "Tianshan Talent" High-Level Medical and Health Personnel Project/ ; 2025D01E38//Natural Science Foundation of Xinjiang Uygur Autonomous Region/ ; },
abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron degeneration. Glycolytic dysregulation is implicated in disease progression, yet the underlying mechanisms remain unclear. This study investigates how Aldolase A (ALDOA) drives ALS progression through glycolysis-mediated motor neuron pyroptosis.

METHODS: In vivo, tamoxifen-induced TDP-43 cKO mice were assessed for motor function (rotarod/suspension tests), motor cortex L-lactic acid, and ALDOA/NLRP3/GSDMD expression. The ALDOA inhibitor Aldometanib was administered. In vitro, TDP-43 KO NSC34 cells were used to measure viability, glucose uptake, and L-lactic acid.

RESULTS: ALS model mice exhibited significant motor deficits, progressive weight loss, and reduced survival. Their motor cortex showed elevated ALDOA expression, L-lactic acid accumulation, and NLRP3/GSDMD inflammasome activation. Aldometanib treatment suppressed glycolysis, prolonged survival, and slowed disease progression by inhibiting NLRP3/GSDMD-mediated pyroptosis. In vitro, TDP-43-deficient NSC34 cells displayed increased ALDOA levels, enhanced glycolytic flux, NLRP3/GSDMD pathway activation, and impaired proliferation.

CONCLUSION: We show that ALDOA-mediated glycolytic dysregulation activates the NLRP3/GSDMD inflammasome, leading to pyroptosis in motor neurons. Pharmacological inhibition of ALDOA alleviates glycolytic dysregulation and extends survival, identifying ALDOA as a potential therapeutic target.},
}

@article {pmid41877227,
year = {2026},
author = {Estiar, MA and Yu, E and Varghaei, P and Ross, JP and Ashtiani, S and Bayne, AN and Coarelli, G and Timmann, D and Klockgether, T and Beijer, D and Mengel, D and Coutelier, M and , and Dion, PA and Suchowersky, O and Ewenczyk, C and Goizet, C and Stevanin, G and Van Damme, P and Al-Chalabi, A and Zuchner, S and Synofzik, M and Veldink, JH and Trempe, JF and Durr, A and Rouleau, GA and Gan-Or, Z},
title = {Digenic inheritance of mutations in SPG7 and AFG3L2 causes motor neuron and cerebellar disorders.},
journal = {BMC medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12916-026-04805-z},
pmid = {41877227},
issn = {1741-7015},
abstract = {BACKGROUND: Biallelic SPG7 mutations cause one of the most common forms of hereditary spastic paraplegia (HSP). Several reports have suggested that heterozygous SPG7 variants may also play a role in HSP, but also in amyotrophic lateral sclerosis (ALS). However, it remains controversial whether heterozygous SPG7 mutations are pathogenic on their own, or if other mechanisms are at play. We recently provided evidence for non-Mendelian inheritance in spastic paraplegia 7 (SPG7), as heterozygous carriers of SPG7 mutations often also carried mutations in other disease-related genes, including AFG3L2, more frequently than expected by chance. Given that SPG7 and AFG3L2 encode interacting subunits of the mitochondrial m-AAA protease complex, we hypothesized that combined heterozygous mutations in these genes may act synergistically to disrupt mitochondrial function and contribute to disease. In this study, we aimed to examine whether digenic heterozygous mutations in SPG7 and AFG3L2 can lead to a spectrum of neurodegenerative disorders.

METHODS: We first analyzed genome and exome sequencing data of 6644 unrelated individuals including 4817 motor neuron disorder (MND) and ataxia patients and 1827 controls. We next analyzed an additional 18,748 exome data from rare disease cohorts to further examine the occurrence of variants in SPG7 and AFG3L2.

RESULTS: Among the first 4817 MND and ataxia patients, we identified a total of 6 patients, 4 of whom were unrelated, who carried potentially pathogenic variants in both SPG7 and AFG3L2, in contrast to none in 1827 unrelated controls. Further analysis of the 18,748 additional patients with rare disease, as well as a comprehensive literature review, identified 6 more patients, 5 of whom were unrelated, who had digenic mutations in SPG7 and AFG3L2. In the two families we identified, digenic mutations in SPG7 and AFG3L2 perfectly segregated with the disease. The 12 patients reported here exhibited predominant signs of motor neuron and cerebellar involvement.

CONCLUSIONS: Our findings demonstrate that digenic inheritance of concurrent heterozygous mutations in SPG7 and AFG3L2 may cause motor neuron and cerebellar disorders. Screening of the entire SPG7 and AFG3L2 genes in genetically undiagnosed cases of MND and spastic ataxia may help to increase the diagnostic yield.},
}

@article {pmid41877246,
year = {2026},
author = {Shen, R and Sung, K and Ding, J and Wu, C},
title = {Axonopathy: mechanisms and potential therapeutic targets for neurodegenerative diseases.},
journal = {Translational neurodegeneration},
volume = {15},
number = {1},
pages = {},
pmid = {41877246},
issn = {2047-9158},
mesh = {Humans ; *Neurodegenerative Diseases/pathology/therapy ; *Axons/pathology ; Animals ; },
abstract = {Axons are unique structural and functional features of nerve cells, which play a critical role in regulating neuronal homeostasis. Dysfunction and degeneration of axons (axonopathy) has been established as an early and prominent contributing mechanism to the pathogenesis of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. In this review, we briefly summarize the structure and function of axons, and highlight recent advances in the understanding of the role of axons in health and disease. We argue that axons are a potential target for developing novel therapies for neurodegenerative diseases.},
}

Humans
*Neurodegenerative Diseases/pathology/therapy
*Axons/pathology
Animals

@article {pmid41879495,
year = {2026},
author = {Singh, K and Sethi, P and Jain, D and Gupta, JK and Alsaidan, OA and Alzarea, SI and Kumar, A and Tabish, M and Sharma, MC},
title = {Emerging Roles of Small-molecule Derivatives in Modulating Neurodegenerative Pathways: From Molecular Targets to Therapeutic Applications.},
journal = {Mini reviews in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0113895575429412260112060311},
pmid = {41879495},
issn = {1875-5607},
abstract = {Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease involve progressive neuronal dysfunction driven by mechanisms including protein aggregation, oxidative stress, mitochondrial impairment, and neuroinflammation. Current treatments are largely symptomatic, with limited disease-modifying options. Advances in medicinal chemistry have led to the development of small-molecule derivatives targeting specific pathological pathways, offering new therapeutic opportunities. This review summarizes recent progress in designing and optimizing such molecules to modulate amyloid-β metabolism, tau acetylation, α-synuclein aggregation, RNA-binding protein interactions, and NLRP3 inflammasome activation. Compounds acting on key signaling cascades, including PI3K/Akt, MAPK/ERK, Nrf2/ARE, and Wnt/β-catenin, are discussed, alongside drug repurposing strategies and preclinical-to-clinical translation. Special focus is given to microglial modulation, challenges in crossing the blood-brain barrier, and integration of precision medicine, metabolomics, and artificial intelligence into drug discovery. The review also highlights novel therapeutic concepts such as multi- target ligands, metal-chelation approaches, and modulation of neuroinflammatory pathways. Despite promising leads, significant challenges remain in optimizing pharmacokinetics, target selectivity, and delivery. Future directions include the identification of robust biomarkers, advanced imaging techniques, and computational tools to accelerate candidate validation. Collectively, smallmolecule therapeutics hold considerable promise in addressing unmet needs in neurodegenerative disease management, but their successful translation will require multidisciplinary approaches bridging molecular insights and clinical application.},
}

@article {pmid41880105,
year = {2026},
author = {Ng, CA and Sousa, M and Patterson, T and Mulhern, B and Luckett, T},
title = {A qualitative study of cancer clinical trial network consumers' acceptability of the modular approach to patient-reported outcome measurement: how much of it is "common sense"?.},
journal = {Journal of patient-reported outcomes},
volume = {},
number = {},
pages = {},
doi = {10.1186/s41687-026-01045-w},
pmid = {41880105},
issn = {2509-8020},
abstract = {BACKGROUND: There is growing interest in customising patient-reported outcome measures (PROMs). This involves selecting specific domains (i.e., subscales) that focus on key health-related quality of life (HRQoL) issues most relevant to a particular study's context, referred to as the modular approach. Despite available recommendations from international stakeholders and PROM developers, the modular approach has not been widely adopted in cancer clinical trials. This qualitative study explored the acceptability of the modular approach to administering PROMs from the perspectives of cancer consumers.

METHODS: Consumers (patients, family members and/or caregivers) who have experience with cancer were recruited through cancer clinical trial networks in Australian and New Zealand. Data were collected through online focus groups. Interview probes and analysis were guided by Sekhon et al.'s Theoretical Framework of Acceptability.

RESULTS: Ten consumers, all with prior experience in clinical trial design, participated across four focus groups. The acceptability of the modular approach was discussed in reference to four themes: (1) minimising respondent burden is not simply about shortening PROMs; (2) competing priorities of reducing burden, preserving PROM measurement properties and assessing breadth versus depth of issues; (3) new strategies are needed to improve PROM relevance; and (4) who should select the domains, and how? Acceptable features of the modular approach included its potential to increase the relevance of questions, minimise duplication, and allow for more in-depth assessment of priority HRQoL issues. Participants also believed that involving consumer representatives in domain selection could alleviate the burden on researchers during trial design and were supportive of giving individual clinical trial patients the option to self-select domains that are personally meaningful.

CONCLUSIONS: Consumers were generally supportive of using the modular approach in administering PROMs in clinical trials, while also identifying ways to strengthen its acceptability. These included the need for clearer consensus and guidance on what constitutes a well-justified selection of domains and further personalisation of PROM domains (e.g., through branching questions). These insights can help inform regulatory agencies and other stakeholders about consumer needs and highlight the support needed if there is to be a paradigm shift in trial design towards tailored PROM administration.},
}

@article {pmid41871620,
year = {2026},
author = {Silva, DJD and Silveira, SCD and Souza, LC and Cruzeiro, MM and Vale, TC},
title = {Clinical and Sociodemographic Profile of Familial Amyotrophic Lateral Sclerosis Type 8 Compared to the Sporadic Form.},
journal = {Arquivos de neuro-psiquiatria},
volume = {84},
number = {3},
pages = {1-8},
doi = {10.1055/s-0046-1817037},
pmid = {41871620},
issn = {1678-4227},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/diagnosis/genetics/physiopathology/classification ; Female ; Male ; Middle Aged ; Adult ; Brazil/epidemiology ; Aged ; Age of Onset ; Socioeconomic Factors ; Retrospective Studies ; Sociodemographic Factors ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a rare degenerative disease of motor neurons, predominantly sporadic, with approximately 10% of the cases showing familial inheritance.To characterize the clinical and sociodemographic profile of patients with familial ALS type 8 (fALS8) and compare it with sporadic ALS (sALS).We reviewed the medical records (1997-2022) from a specialized Brazilian center. Patients with a confirmed diagnosis of ALSs were included, and sociodemographic and clinical data were collected.The sample was composed of 89 ALS patients, with a slight female predominance (53%) and a high frequency of fALS8 cases (45%). The fALS8 patients were diagnosed at a younger age, at approximately 50 years, compared to 53 years among the sALS patients (p = 0.043). Lower limb onset predominated in the fALS8 group (87%), while the sALS group showed more heterogeneous presentations, including bulbar onset (14%). The time until the diagnosis was significantly longer in the fALS8 group compared to the sALS group, both from symptom onset (approximately 51 versus 30 months respectively; p < 0.001) and after admission to a specialized center (7 versus 4 months respectively; p = 0.002). Dysphagia and gastrostomy were more frequent in the sALS group compared to the fALS8 group (p = 0.02 and p < 0.01 respectively), and older age at diagnosis was associated with worse functional scores.The fALS8 group presented with distinct clinical and demographic features compared to the sALS group, including younger age at diagnosis, more homogeneous symptom onset, and lower frequency of dysphagia and need for gastrostomy. The diagnosis was more delayed in the fALS8 group, and older age at diagnosis was associated with worse functional status. The current study contributes to the scarce data on fALS8 in South America.},
}

Humans
*Amyotrophic Lateral Sclerosis/epidemiology/diagnosis/genetics/physiopathology/classification
Female
Male
Middle Aged
Adult
Brazil/epidemiology
Aged
Age of Onset
Socioeconomic Factors
Retrospective Studies
Sociodemographic Factors

@article {pmid41872337,
year = {2026},
author = {Croteau, E and Rousseau, E and Tremblay, S and Rousseau, JF and Espinosa-Betancourt, E and Lavallée, E and Dubreuil, S and Ait-Mohand, S and Lareau-Trudel, É and Gosselin, S and Carrier, V and Côté-Bigras, S and Allard, C and Maier, M and Salzmann, M and Tétu, A and Houde, MP and Turcotte, É and Guérin, B},
title = {A phase I study to evaluate the dosimetry and safety of [[89]Zr]Zr-DFO-AP-101, a new antibody-based radiopharmaceutical to detect misfolded SOD1 in amyotrophic lateral sclerosis.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {},
number = {},
pages = {},
pmid = {41872337},
issn = {1619-7089},
support = {Fonds d'accélération des collaborations en santé (FACS)//Ministère de la Santé et des Services sociaux/ ; },
}

@article {pmid41872984,
year = {2026},
author = {Toomey, A and Kleinerova, J and Tan, EL and Siah, WF and Bede, P},
title = {Muscle MRI and Muscle Ultrasound Applications in MND/ALS: Academic Insights and Clinical Opportunities.},
journal = {European journal of neurology},
volume = {33},
number = {3},
pages = {e70582},
doi = {10.1111/ene.70582},
pmid = {41872984},
issn = {1468-1331},
support = {HRB JPND-Cofund-2025-3/HRBI_/Health Research Board/Ireland ; JPND-2025"Qual-Bulb-MND"//EU Joint Programme - Neurodegenerative Disease Research/ ; SFI-SP20/SP/8953/SFI_/Science Foundation Ireland/Ireland ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; *Magnetic Resonance Imaging/methods ; Ultrasonography/methods ; *Muscle, Skeletal/diagnostic imaging ; },
abstract = {BACKGROUND: There is an unmet need for the clinically relevant ALS biomarkers to facilitate an accurate diagnosis in suspected cases, monitor disease progression and evaluate response to therapy in clinical trials. While the MND/ALS literature is dominated by innovative brain studies, motor disability in ALS is primarily driven by neurogenic muscle change impacting mobility, dexterity, respiratory and bulbar function.

METHODS: With the intention of raising awareness of muscle-derived imaging markers in ALS, a systematic review has been conducted. Study designs, imaging methods, data interpretation frameworks, and cohort characteristics were systematically evaluated to identify innovative approaches and barriers to clinical implementation.

RESULTS: A total of 219 studies were screened and 73 original studies selected for systematic review; 37 muscle MRI studies and 36 studies using ultrasound, PET or CT. All of the selected studies successfully captured ALS-associated muscle degeneration and their methods included the evaluation of muscle dimensions (thickness/volumes n = 34), 'acute' denervation (water content, n = 15), fasciculation counts (n = 14), 'chronic' neurogenic change (fat content, n = 21), metabolic changes (n = 4), diffusion alterations (n = 8) and echo intensity changes (n = 13).

CONCLUSIONS: Despite the huge impact of lower motor neuron dysfunction on the patients' independence, survival and quality of life, muscle imaging is a glaringly overlooked frontier of MND/ALS research. This is a missed opportunity, as a variety of non-invasive quantitative muscle imaging techniques have been successfully used in other neurological conditions; these protocols are easy to implement on commercial MRI and ultrasound platforms and recent studies have demonstrated their ease of use and potential clinical utility.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnostic imaging
*Magnetic Resonance Imaging/methods
Ultrasonography/methods
*Muscle, Skeletal/diagnostic imaging

@article {pmid41873182,
year = {2026},
author = {Hinten, AE and Imuta, K},
title = {Executive Function Costs of Fantastical Interference in Narrative Comprehension: A Response to Lillard's (2026) Commentary.},
journal = {Developmental science},
volume = {29},
number = {3},
pages = {e70177},
doi = {10.1111/desc.70177},
pmid = {41873182},
issn = {1467-7687},
mesh = {Humans ; *Comprehension/physiology ; *Executive Function/physiology ; Child ; *Fantasy ; *Narration ; Child, Preschool ; Cognition ; },
abstract = {Through bringing together previous findings from 16 studies involving 121 effect sizes (based on 1,297 1.5- to 6-year-olds), Hinten et al.'s (2025) meta-analysis revealed that children who viewed fantastical media in an experimental setting performed worse on inhibitory control and cognitive flexibility tasks immediately post-viewing compared to those exposed to realistic media. Lillard's (2026) commentary provided one potential explanation for our findings, revolving around the idea that processing fantastical content is cognitively taxing because it conflicts with existing schemas. In this response, we extend Lillard's (2026) perspective by drawing on Loschky et al.'s (2020) Scene Perception and Event Comprehension Theory (SPECT) to provide an additional explanation: Fantasy overloads children's executive functions because it interferes with their narrative comprehension. SUMMARY: We present a novel perspective on why fantastical media may have adverse, short-term effects on children's executive functioning. Children's executive functions may become overloaded while watching fantastical media because fantastical elements can detract from and hamper narrative comprehension processes.},
}

Humans
*Comprehension/physiology
*Executive Function/physiology
Child
*Fantasy
*Narration
Child, Preschool
Cognition

@article {pmid41874673,
year = {2026},
author = {Li, J and Gao, C and Wang, Q and Liu, J and Xie, Z and Zhao, Y and Yu, M and Zheng, Y and Lv, H and Zhang, W and Yuan, Y and Meng, L and Deng, J and Wang, Z},
title = {Aberrant SOD1 aggregates in skeletal muscle target fibers in amyotrophic lateral sclerosis.},
journal = {Acta neuropathologica},
volume = {151},
number = {1},
pages = {},
pmid = {41874673},
issn = {1432-0533},
}

@article {pmid41875078,
year = {2026},
author = {Mamede, LD and Hu, M and Vaquer-Alicea, J and Titus, AR and Passos, PM and Lantelme, E and French, RL and Kirschner, PA and Diamond, MI and Miller, TM and Ayala, YM},
title = {A quantitative cell-based reporter links TDP-43 aggregation and dysfunction to define pathogenic mechanisms.},
journal = {PLoS biology},
volume = {24},
number = {3},
pages = {e3003662},
doi = {10.1371/journal.pbio.3003662},
pmid = {41875078},
issn = {1545-7885},
mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; *Protein Aggregation, Pathological/metabolism/genetics ; Neurons/metabolism/pathology ; Exons ; Protein Aggregates ; RNA Splicing ; Amyotrophic Lateral Sclerosis/metabolism ; TDP-43 Proteinopathies/metabolism/genetics ; Genes, Reporter ; },
abstract = {TDP-43 pathology is a hallmark of fatal neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and limbic-predominant age-related TDP-43-encephalopathy (LATE). In affected patients, cytoplasmic TDP-43 aggregates are accompanied by disruption of its normal nuclear localization and function. Because TDP-43 is an RNA binding protein that controls transcript processing, including repression of cryptic exon splicing, its loss leads to dysregulation of gene expression. Despite its central significance in disease, the connection between TDP-43 aggregation and dysfunction remains poorly understood, and models to study the underlying mechanisms are limited. Here, we characterize a robust and quantitative cell-based reporter that captures both aggregation and the resulting loss of function. Using this human biosensor cell line, we show that aggregation initiated by prion-like seeding drives progressive depletion of nuclear TDP-43 and induces signature features of diminished TDP-43 activity, such as increased DNA damage and activation of cryptic exon splicing. We find that aggregate seeding also induces cryptic exon splicing in human neurons implying that this pathological link extends to disease-relevant models. The seeding model provides a platform for dissecting mechanisms that underlie TDP-43 pathology and for identifying factors that modulate the aggregation-to-dysfunction transition. Our data shows that aggregate seeding impacts TDP-43 autoregulation, initiating a toxic feed-forward mechanism that disrupts TDP-43 homeostasis. Furthermore, reducing ataxin-2 levels decreases aggregation and restores TDP-43 activity. Together, these findings reveal a molecularly guided strategy to directly impact TDP-43 activity by decreasing its misfolding and aggregation, highlighting approaches to prevent TDP-43 dysfunction and mitigate toxicity under pathological conditions.},
}

Humans
*DNA-Binding Proteins/metabolism/genetics
*Protein Aggregation, Pathological/metabolism/genetics
Neurons/metabolism/pathology
Exons
Protein Aggregates
RNA Splicing
Amyotrophic Lateral Sclerosis/metabolism
TDP-43 Proteinopathies/metabolism/genetics
Genes, Reporter

@article {pmid41875115,
year = {2026},
author = {Uversky, VN},
title = {Why is it so difficult to discover drugs for amyotrophic lateral sclerosis? A protein intrinsic disorder perspective.},
journal = {Expert opinion on drug discovery},
volume = {},
number = {},
pages = {1-21},
doi = {10.1080/17460441.2026.2648612},
pmid = {41875115},
issn = {1746-045X},
abstract = {INTRODUCTION: Amyotrophic Lateral Sclerosis (ALS) is the most common adult motor neuron disease, now viewed as a spectrum disorder rather than a single entity. Because of the significant person-to-person variability in the disease's biology, driven by both genetic and environmental interactions, finding a single "magic bullet" drug is unlikely. Despite decades of research, only a few ALS drugs have being developed. Drug discovery has a 95% failure rate due to genetic complexity, lack of sensitive biomarkers, diagnostic delays, inadequate animal models, and poor clinical trial design.

AREAS COVERED: This article considers several aspects related to the prevalence of intrinsic disorder in ALS-related proteins and highlights how these features might hinder rational structure-based drug discovery.

EXPERT OPINION: There is a common oversight in current drug discovery methodologies, which is the neglect of intrinsically disordered proteins (IDPs) playing several crucial roles in the pathology of neurodegeneration in general and ALS in particular. Therefore, it seems that the 'one-size-fits-all' approach to ALS is hitting a wall because these 'shapeshifters' of the cellular world are ignored. Consequently, to be more successful in finding drugs treating ALS, gears should be shifted from rational structure-based models to intrinsic disorder-centric approaches.},
}

@article {pmid41866066,
year = {2026},
author = {Qian, J and Li, C and Wang, Y and Tong, J},
title = {Extracorporeal sliding knot technique for simplified hysteroscopic suture fixation of levonorgestrel-releasing intrauterine device.},
journal = {Journal of minimally invasive gynecology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jmig.2026.03.020},
pmid = {41866066},
issn = {1553-4669},
abstract = {OBJECTIVE: Approximately 20% of adenomyosis cases occur in women under 40 years of age [1]. While LNG-IUD is the first-line medical therapy, its treatment failure is closely associated with uterine volume [2], with expulsion rates reported as high as 37.5% in uteri exceeding 12 gestational weeks [3]. Tong et al's hysteroscopic suture fixation technique (HCSS) reduced expulsion to 2.6% [4][5]. Although clinical studies have confirmed the safety and efficacy of this technique [5], its technical complexity and the requirement for repeated instrument exchanges have limited widespread adoption. We therefore developed an optimized extracorporeal sliding knot method to overcome these barriers.

SETTING: University hospital.

PARTICIPANTS: A 45-year-old woman diagnosed with adenomyosis and prior LNG-IUD expulsion.

INTERVENTIONS: The key modification involves three critical steps: Step 1) Construction of a secure multi-loop sliding knot using 2-0 Ethibond suture attached to the "T junction" of the LNG-IUD; Step 2) Introduction of the pre-formed knot into the uterine cavity in a single maneuver using a knot-pusher; Step 3) Adjustment of the knot position under the hysteroscopic cold-knife surgery system (HCSS), achieving secure device fixation. The complete procedure obviates repeated instrument exchanges and intracavitary knot manipulation required by the original technique.

CONCLUSION: The extracorporeal sliding knot optimization preserves therapeutic efficacy while simplifying intrauterine manipulation, significantly enhancing surgical reproducibility and accessibility for widespread clinical adoption.},
}

@article {pmid41866414,
year = {2026},
author = {Li, X and Ding, W and Xu, E},
title = {Uncoupling of apnea-hypopnea index and oxygen desaturation in als: characterization and diagnostic implications of an "AHI-SpO2 dissociation" phenotype.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {4},
pages = {},
pmid = {41866414},
issn = {1590-3478},
support = {202610452//Health Commission of Jiangxi Province/ ; },
}

@article {pmid41866449,
year = {2026},
author = {Wang, Z and He, F and Li, L and Wang, W and Zhang, L and Tang, J and Le, W},
title = {Sleep Disorders in Neurodegenerative Diseases: Pathological Correlations and Underlying Mechanisms.},
journal = {Neuroscience bulletin},
volume = {},
number = {},
pages = {},
pmid = {41866449},
issn = {1995-8218},
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), multiple system atrophy (MSA), amyotrophic lateral sclerosis (ALS), and others, represent an escalating public health burden in aging populations. NDDs are characterized by progressive neuronal loss and misfolded protein aggregation. Despite distinct clinical heterogeneity, these diseases universally present with debilitating non-motor symptoms, among which sleep-wake disorders are highly prevalent. Once considered secondary to neuronal damage, growing evidence now highlights a bidirectional interplay: sleep disruption is not only a consequence of neurodegeneration but also exacerbates its progression. This review synthesizes this complex interplay, outlining sleep phenotypes across major NDDs, dissecting key underlying mechanisms (impaired protein homeostasis, glymphatic dysfunction, chronic neuroinflammation, sleep-regulatory nucleus vulnerability, and circadian dysregulation), and summarizing current pharmacotherapeutic and non-pharmacological interventions. Attenuating sleep disorders may therefore provide symptomatic relief and disease‑modifying effects for NDDs.},
}

@article {pmid41866924,
year = {2026},
author = {Seyam, M and Morelli, KH and Waheed, W and van den Berg, LH and Tandan, R},
title = {Predicting Disease Progression and Survival in Amyotrophic Lateral Sclerosis.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70198},
pmid = {41866924},
issn = {1097-4598},
abstract = {Amyotrophic lateral sclerosis (ALS) progresses relentlessly and is characterized by a median survival of 2-5 years from symptom onset with death from respiratory failure. ALS is a complex, multi-system neurodegenerative disorder with significant phenotypic heterogeneity and markedly variable disease progression. This variability presents challenges in determining the optimal timing for therapeutic interventions, complicates clinical trial design due to lack of effective stratification methods, and makes it difficult to reliably measure the longitudinal impact of specific interventions. Accurately capturing disease progression in ALS can be challenging. We propose that early respiratory phenotyping offers a promising approach to facilitate patient stratification, improve assessments of disease progression, and predict survival.},
}