@article {pmid42033202,
year = {2026},
author = {Yusuf, S and Allen, MD and Kang, H and Phillips, DE and Genge, A},
title = {Opportunities and challenges related to participant stratification and cohort enrichment in ALS clinical trials.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/21678421.2026.2659128},
pmid = {42033202},
issn = {2167-9223},
abstract = {Amyotrophic lateral sclerosis (ALS) is marked by substantial clinical heterogeneity. This heterogeneity has impacted clinical trials by obscuring treatment effects and causing inefficiency. In this review, we summarize potential approaches for addressing heterogeneity in ALS via patient stratification and cohort enrichment methods and highlight potential challenges and limitations. These categories include stratification based on genetics, clinical characteristics (e.g. pattern of weakness, ALS Functional Rating Scale rates of progression), wet biomarkers (e.g. neurofilament light chain), neuroimaging, and novel methods employing statistical modeling or machine learning. These stratification methods have yet to be fully leveraged in clinical trial design. But these strategies must be employed thoughtfully and judiciously due to potential issues stratification can introduce. Future clinical trials should explore how participant stratification and cohort enrichment strategies may improve our ability to identify treatment effects, which may ultimately aid in the quest to establish more personalized medicine for persons with ALS.},
}

@article {pmid42033225,
year = {2026},
author = {Barber, HM and Parasrampuria, MA and Jurado-Arjona, J and Gamir-Morralla, A and Berninger, B and González, C and Gagnon, KT and Damha, MJ and Garavís, M},
title = {Direct targeting of C9ORF72 repeat RNA with fluorinated antisense oligonucleotides.},
journal = {Nucleic acids research},
volume = {54},
number = {8},
pages = {},
doi = {10.1093/nar/gkag343},
pmid = {42033225},
issn = {1362-4962},
support = {MSCA-IF-799693//European Union Marie Skłodowska-Curie Actions/ ; MSCA-IF-841260//European Union Marie Skłodowska-Curie Actions/ ; MSCA-IF-750624//European Union Marie Skłodowska-Curie Actions/ ; RYC2023-043599-I//CSIC/ ; 1R01GM135646-01/NH/NIH HHS/United States ; #2022-03372//Natural Sciences and Engineering Research Council of Canada/ ; PID2023-146366NB-I00//Ministerio de Ciencia e Innovación/ ; P2024-02-015//ERA-NET Neuron/ ; //Fonds de Recherche du Québec/ ; },
mesh = {*C9orf72 Protein/genetics/antagonists & inhibitors ; *Oligonucleotides, Antisense/chemistry/genetics/pharmacology ; Humans ; *DNA Repeat Expansion ; Amyotrophic Lateral Sclerosis/genetics/therapy ; Frontotemporal Dementia/genetics ; Nucleic Acid Conformation ; Halogenation ; Fluorine/chemistry ; Protein Biosynthesis ; RNA/genetics/chemistry ; },
abstract = {Hexanucleotide repeat expansions in the C9ORF72 gene are the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. These expansions give rise to pathogenic sense and antisense repeat RNAs that form nuclear foci and undergo repeat-associated non-AUG translation, producing dipeptide repeat proteins with cellular toxicity. Directly targeting the causative repeat RNAs with antisense oligonucleotides represents a promising therapeutic strategy. One barrier to further development is the propensity of this G-rich repeat-containing RNA target to form stable secondary structures, which may hinder efficient hybridization. In this study, we designed a panel of fluorine-modified ASOs that target the sense repeat expansions. We identified C-rich F-ASO gapmers that reduced translation from sense repeat RNAs in a cell-based reporter assay and lowered the RNA foci burden in patient-derived cells. Structural analyses in vitro revealed that the 2'F-RNA gapmer formed a stable hairpin structure. Our results demonstrate that structural properties of fluorine modifications can be leveraged for effective binding of repeat RNA and highlight the potential for F-ASOs to serve as therapeutic tools when targeting toxic repeat RNAs in C9ORF72-mediated FTD/ALS and other repeat expansion diseases.},
}

*C9orf72 Protein/genetics/antagonists & inhibitors
*Oligonucleotides, Antisense/chemistry/genetics/pharmacology
Humans
*DNA Repeat Expansion
Amyotrophic Lateral Sclerosis/genetics/therapy
Frontotemporal Dementia/genetics
Nucleic Acid Conformation
Halogenation
Fluorine/chemistry
Protein Biosynthesis
RNA/genetics/chemistry

@article {pmid42033865,
year = {2026},
author = {Wang, F},
title = {Polyphenols and physical activity stimulate gut microbiota mediated Nrf2 signaling to combat neurodegeneration.},
journal = {Pathology, research and practice},
volume = {283},
number = {},
pages = {156478},
doi = {10.1016/j.prp.2026.156478},
pmid = {42033865},
issn = {1618-0631},
abstract = {Polyphenols and regular physical activity are increasingly recognized as complementary lifestyle interventions that influence the gut-brain axis and contribute to neuroprotection. Emerging evidence highlights the central role of the gut microbiota in mediating these effects by transforming dietary and host-derived substrates into bioactive metabolites. These metabolites can activate the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, a key regulator of cellular antioxidant defenses, mitochondrial function, and anti-inflammatory responses processes that are critically impaired in neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This review synthesizes current mechanistic insights into how polyphenol-derived metabolites and exercise-induced alterations in gut microbial composition converge to modulate Nrf2 signaling. We discuss the roles of key microbiota-derived metabolites, including short-chain fatty acids, urolithins, and indole derivatives, in regulating oxidative stress, neuroinflammation, and synaptic function. Furthermore, we examine evidence from preclinical models supporting the synergistic effects of dietary polyphenols and physical activity on gut microbiota-mediated neuroprotection. Finally, we address translational challenges and highlight the potential of integrating dietary and exercise-based strategies to harness microbiota-dependent Nrf2 activation. This integrative framework provides a basis for developing personalized, microbiome-informed interventions aimed at delaying or mitigating neurodegeneration.},
}

@article {pmid42034127,
year = {2026},
author = {Ghaderi, S and Mohammadi, S and Kalra, S and Batouli, SAH},
title = {Functional Adaptive Longitudinal Reorganization of Superior Parietal Lobule Networks in Amyotrophic Lateral Sclerosis: Evidence Suggesting Compensatory Mechanisms.},
journal = {Brain research bulletin},
volume = {},
number = {},
pages = {111900},
doi = {10.1016/j.brainresbull.2026.111900},
pmid = {42034127},
issn = {1873-2747},
abstract = {PURPOSE: To investigate longitudinal changes in resting-state functional connectivity (rs-FC) of the superior parietal lobule (SPL) in limb-onset amyotrophic lateral sclerosis (ALS).

METHODS: Resting-state fMRI was used to compare SPL connectivity between 14 ALS patients and 14 healthy controls (HCs) at baseline and during a 5-month follow-up (n=10 ALS patients). Imaging sequences were acquired using a 3-Tesla scanner equipped with a 64-channel head coil. The data were preprocessed and analyzed using CONN and SPM12, employing FDR correction (p<0.05) to identify significant resting-state functional connectivity (rs-FC) alterations.

RESULTS: ALS patients showed significant FC alterations in both right and left SPL compared to HCs. At baseline, the right SPL exhibited increased FC with the right Lateral Visual Network, Medial Visual Network (MVN), right Occipital Fusiform Gyrus (OFG), and left Lingual Gyrus (LG). At follow-up, these increases persisted and expanded, notably to the Occipital Visual Network and left LVN. For several connections, including the right OFG and MVN, the corresponding beta values were descriptively larger at follow-up than at baseline. Conversely, at follow-up, the right SPL showed decreased FC with the left Salience Network (SN). The left SPL showed no baseline changes but, at follow-up, exhibited increased FC with visual networks and the Default Mode Network, alongside decreased FC with the SN.

CONCLUSION: These findings may be suggestive of adaptive reorganization of SPL-related brain networks in response to neurodegeneration in ALS.},
}

@article {pmid42035155,
year = {2026},
author = {Pedde, M and Adar, SD and Jang, DG and Feldman, EL and Goutman, SA},
title = {Air pollution and mortality in a University of Michigan amyotrophic lateral sclerosis cohort: a survival analysis.},
journal = {Environmental health : a global access science source},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12940-026-01295-7},
pmid = {42035155},
issn = {1476-069X},
support = {R01TS000327/TS/ATSDR CDC HHS/United States ; R01TS000327/TS/ATSDR CDC HHS/United States ; },
}

@article {pmid42035914,
year = {2026},
author = {Li, F and Tao, S and Wang, S and Ren, T and Qiu, M and Xu, X},
title = {New Perspectives on oligodendrocytes: Guardians of iron homeostasis and defenders against ferroptosis.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2026.04.052},
pmid = {42035914},
issn = {2090-1224},
abstract = {BACKGROUND: Oligodendrocytes (OLs) play a pivotal role in preserving iron homeostasis within the central nervous system (CNS), as they harbor the largest cellular iron reservoir essential for myelination. However, this indispensable function places OLs at heightened risk of ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxidation. The susceptibility of OLs to ferroptosis has significant implications for CNS health, particularly in the context of neurodegenerative diseases where OL dysfunction exacerbates demyelination and accelerates disease progression.

AIM OF REVIEW: This review aims to systematically elucidate the mechanisms by which mature OLs balance their dual roles as guardians of iron homeostasis and defenders against ferroptosis. Furthermore, it aims to underscore the ramifications of impaired OL iron regulation in prominent neurodegenerative conditions and to investigate potential therapeutic interventions aimed at bolstering OL resilience.

Mature OLs employ a sophisticated, multi-layered defense system to maintain iron homeostasis and prevent ferroptosis, encompassing precise metabolic regulation of iron uptake and storage, alongside a specialized antioxidant network centered on selenoprotein synthesis. Disruption of this delicate balance renders OLs vulnerable in diseases such as multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD), leading to a vicious cycle of OL death, iron dysregulation, and demyelination. Targeting OL iron homeostasis and anti-ferroptotic pathways through iron modulation, antioxidant reinforcement, or direct ferroptosis inhibition represents a promising strategy to promote remyelination and mitigating neurodegeneration.},
}

@article {pmid42035928,
year = {2026},
author = {Codron, P and Desquiret, V and Prunier, D and Amati-Bonneau, P and Nguefackngoune, V and Rapenne, C and Legoff, L and Cassereau, J and Procaccio, V},
title = {Analysis of mitochondrial DNA heteroplasmy in sporadic ALS suggests technical limitations rather than disease association.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107412},
doi = {10.1016/j.nbd.2026.107412},
pmid = {42035928},
issn = {1095-953X},
abstract = {Mitochondrial DNA (mtDNA) has received increasing attention in amyotrophic lateral sclerosis (ALS) following the recent report of recurrent low-heteroplasmy mtDNA variants in patients. Here, we performed mtDNA analysis on an independent cohort of 20 sporadic ALS patients using an in-house next-generation sequencing pipeline designed for diagnostics. Using standard filters, none of the previously reported low-heteroplasmy mtDNA variants were detected. These variants only appeared in the low-quality data and were present at similar rates in a large reference population without ALS, localizing to homopolymeric regions that are prone to sequencing errors. Our findings suggest that these low-level mtDNA variants are a result of the technical limitations of short-read next-generation sequencing rather than being associated with the disease.},
}

@article {pmid42036021,
year = {2026},
author = {Kim, YH and Jing, FZ and Brewer, JD and Demer, AM},
title = {Response to O'Neill et al.'s "Disparities in melanoma survival in Asian American and Pacific Islander patients: A Surveillance, Epidemiology, and End Results (SEER) program-based analysis".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.03.112},
pmid = {42036021},
issn = {1097-6787},
}

@article {pmid42036022,
year = {2026},
author = {Chen, B and Yang, L and Wang, J and Hu, T},
title = {Response to Bar et al.'s "Cancer progression, recurrence, and infection outcomes in psoriasis patients with active or recent malignancy treated with biologic therapy: A cohort study showing comparable safety to conventional agents".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.02.133},
pmid = {42036022},
issn = {1097-6787},
}

@article {pmid42036024,
year = {2026},
author = {Xiao, Y and Li, S and Cao, X},
title = {Comments on Chiu et al.'s " Comparative risk of reactivation of hepatitis B and C after treatment with biologics and targeted synthetic DMARDs in psoriasis and psoriatic arthritis: A 15-year multicenter cohort study".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.03.113},
pmid = {42036024},
issn = {1097-6787},
}

@article {pmid42031611,
year = {2026},
author = {Etik, DÖ and Dişibeyaz, S and Özmert, EH},
title = {Pancreatitis due to afferent loop syndrome: A case report and a brief review of the literature.},
journal = {Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajg.2026.02.003},
pmid = {42031611},
issn = {2090-2387},
abstract = {Afferent loop syndrome (ALS) should be a part of the differential diagnosis in a patient with acute pancreatitis with a history of gastric surgery. Although it is a rare clinical entity, association of ALS with acute pancreatitis can lead to poor clinical outcomes. Herein, we report the case of a 41-year-old man with a history of subtotal gastrectomy and Roux-en-Y gastric bypass who presented with abdominal pain and tenderness. Treatment of choice in this case was purely medical. A brief review of similar cases in the literature highlights the wide array of etiologies of acute pancreatitis due to ALS and reveals a broad spectrum of treatment options from medical to surgical.},
}

@article {pmid42032949,
year = {2026},
author = {Sipilä, J and Solje, E and Ahola, S and Surakka, L and Jokela, M},
title = {Death certificate data of patients with amyotrophic lateral sclerosis in easternmost Finland.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/21678421.2026.2662015},
pmid = {42032949},
issn = {2167-9223},
abstract = {Objective: Topical data on causes of death and death certificate (DC) accuracy in patients with amyotrophic lateral sclerosis (ALS) are constantly needed. Methods: Data on a previously published ALS cohort from North Karelia in easternmost Finland was updated by extracting DC information from the electronic health records. Results: Death certificate data were available for 91% of the deceased. In all cases, ALS had been coded as a cause of death. In four cases, it had been inserted as a contributory cause of death. In three cases, ALS was indicated but incorrect coding was used. Three of the four cases in which ALS had not been deemed the underlying or immediate cause of death were cardiovascular deaths. One or more contributory causes of death had been recorded in 28% of DCs (54% of these were cardiovascular disorders), although comorbidities had not always been coded in the DC. In individual cases, the death had been sudden and unexpected, resembling a cardiovascular death, but this had not been coded. Conclusion: Finnish DC data remain a very reliable data source for ALS epidemiology, albeit with the caveat that data need to be obtained rigorously. Comorbidities are incompletely recorded as may be some immediate causes of death.},
}

@article {pmid42026720,
year = {2026},
author = {Kamal, S and Kennel, N and Li, AM and Gale, S and Hennessey, EL and Rodriguez, BN and Feany, MB and Stern, AM and Ganesh, VS and Schildkrout, B and Daffner, K and Silbersweig, DA and Singhal, T and Kletenik, I and Miller, MB},
title = {Case Study 11: A 67-Year-Old Man With Behavioral Disturbances and Frequent Falls.},
journal = {The Journal of neuropsychiatry and clinical neurosciences},
volume = {},
number = {},
pages = {appineuropsych20250213},
doi = {10.1176/appi.neuropsych.20250213},
pmid = {42026720},
issn = {1545-7222},
}

@article {pmid42027094,
year = {2026},
author = {McElvaney, R and Starrs, B},
title = {Adolescents' Positive Experiences of Psychotherapy Following Sexual Abuse: A Systematic Review.},
journal = {Trauma, violence & abuse},
volume = {},
number = {},
pages = {15248380261437090},
doi = {10.1177/15248380261437090},
pmid = {42027094},
issn = {1552-8324},
abstract = {While a small body of work focuses directly on young people's experiences of psychotherapy following sexual abuse, to our knowledge, there are no existing reviews of this literature. This systematic review was conducted using Siddaway et al.'s guidelines. Inclusion criteria were: published between 2000 and 2022; used qualitative methodologies; and captured adolescents' perspectives. Eleven studies were identified, representing an aggregated sample size of 72 young people aged 12 to 18. Methodologies used included thematic analysis, content analysis, conversation analysis, and narrative analysis. A total of 9 of the 11 studies addressed experiences of individual therapy using semi-structured interviews; 2 studies explored experiences of group therapy through focus groups. The review identified three key processes that reflect adolescents' experiences: engagement, ambivalence to trust; painful processing: exercising agency; and integrating: taking responsibility. Young people struggled to engage in therapy, and it took time to build trust; they experienced improvements in mood and general well-being, facilitated by psychoeducation, talking about the abuse, experiencing difficult emotions, and learning coping skills. They described integrating their abuse experience into their life story, discovering their inner strength and resilience. The therapeutic experience was underpinned by two key support processes: the therapeutic relationship and a supportive environment outside of therapy. This review supports the components of trauma-focused therapy alongside personalizing psychotherapy to the needs of adolescents for agency and autonomy.},
}

@article {pmid42027125,
year = {2026},
author = {Aiello, EN and De Luca, G and Curti, B and Torre, S and Gendarini, C and Cocuzza, A and Colombo, E and De Sandi, A and Mellace, D and Ferrucci, R and Barbieri, S and Maranzano, A and Verde, F and Messina, S and Doretti, A and Morelli, C and Silani, V and Ticozzi, N and Poletti, B},
title = {Prevalence and determinants of anxiety in amyotrophic lateral sclerosis.},
journal = {BJPsych open},
volume = {12},
number = {3},
pages = {e114},
doi = {10.1192/bjo.2026.11025},
pmid = {42027125},
issn = {2056-4724},
abstract = {BACKGROUND: Clinically relevant anxiety can be detected in patients with amyotrophic lateral sclerosis (ALS), but its prevalence and determinants have not yet been fully assessed.

AIMS: This study aimed at assessing the prevalence and clinical underpinnings of anxiety in ALS.

METHOD: Non-demented ALS patients (N = 433) and healthy controls (N = 313) were administered the State- and Trait-Anxiety Inventory - Form Y (STAI-Y1 for state-anxiety and STAI-Y2 for trait-anxiety) and the Beck Depression Inventory (BDI). Patients were further assessed for cognition (Edinburgh Cognitive and Behavioural ALS Screen), behaviour (Frontal Behavioural Inventory) and motor status (disease duration, ALS Functional Rating Scale-Revised and progression rate). The prevalence of clinically significant state- and trait-anxiety were estimated by applying age-stratified cut-offs to STAI-Y1/-Y2 t-scores. Linear and logistic regressions were run to test the determinants of STAI-Y1/-Y2 scores.

RESULTS: STAI-Y1 and -Y2 scores above cut-off were detected in 18.2 and 13.9% of patients, respectively - with proportions being higher in cases versus controls (ps < 0.001). BDI, but neither cognitive/behavioural nor motor variables, was identified as a significant predictor of STAI-Y1/-Y2 scores (ps < 0.003). The cognitive-affective subscale of BDI was the sole predictor of scores above cut-off on both STAI-Y1 and STAI-Y2 (ps < 0.001).

CONCLUSIONS: Clinically significant levels of state- and trait-anxiety occur in ∼18 and ∼14% of non-demented ALS patients, respectively, mostly driven by cognitive and affective facets of depression, and are independent of motor and cognitive/behavioural features.},
}

@article {pmid42029573,
year = {2026},
author = {Kuroiwa, N and Sakaue, F and Miura, M and Go, A and Iwase, R and Iwata Hara, R and Sanjo, N and Ui-Tei, K and Yokota, T},
title = {Rational Design of a Multivalent RNA Combining Structural Motifs Tailored to Multiple Domains of Fused in Sarcoma for Potent Inhibition of Aggregation.},
journal = {Chembiochem : a European journal of chemical biology},
volume = {27},
number = {8},
pages = {e202500568},
doi = {10.1002/cbic.202500568},
pmid = {42029573},
issn = {1439-7633},
support = {KKCS20220502009//Kyowa Hakko Kirin/ ; },
mesh = {*RNA-Binding Protein FUS/metabolism/chemistry/antagonists & inhibitors ; Humans ; *RNA/chemistry/pharmacology/metabolism ; G-Quadruplexes ; Protein Aggregates/drug effects ; Drug Design ; Protein Domains ; },
abstract = {Fused in sarcoma (FUS) is an RNA-binding protein whose pathological aggregation, driven by aberrant phase separation, is implicated in amyotrophic lateral sclerosis (ALS). Although RNA molecules can modulate the FUS phase behavior, identifying highly effective sequences remains challenging because of FUS's multiple low-specificity RNA-binding domains. In this study, we rationally designed a 65-mer RNA, U1'+TERRA, by combining a stem-loop-GGU motif and a G-quadruplex (G4) structure, each known to interact with distinct FUS domains. U1'+TERRA exhibited strong binding affinity and effectively inhibited FUS aggregation in vitro. We introduced 2'-O-methyl modifications, generating (U1'+TERRA)-2'-OMe, which retained structural integrity and demonstrated resistance to nuclease degradation to enhance biological stability. Notably, (U1'+TERRA)-2'-OMe suppressed FUS aggregation even at a low concentration. These findings suggested that multivalent RNA constructs with rationally arranged motifs can serve as potent inhibitors of FUS aggregation. Our approach highlights the potential of structure-guided RNA engineering for the development of nucleic acid therapeutics targeting RNA-binding proteins involved in neurodegenerative diseases, such as ALS.},
}

*RNA-Binding Protein FUS/metabolism/chemistry/antagonists & inhibitors
Humans
*RNA/chemistry/pharmacology/metabolism
G-Quadruplexes
Protein Aggregates/drug effects
Drug Design
Protein Domains

@article {pmid42029829,
year = {2026},
author = {Bordoni, M and Scarian, E and Messa, L and Garofalo, M and Jacchetti, E and Raimondi, MT and Diamanti, L and Gagliardi, S and Carelli, S and Cereda, C and Pansarasa, O},
title = {Development and characterization of 3D spinal cord organoids to advance the study of amyotrophic lateral sclerosis.},
journal = {Molecular biomedicine},
volume = {7},
number = {1},
pages = {},
pmid = {42029829},
issn = {2662-8651},
support = {Starting Grant//BraYn Association/ ; RC2025-2027//Ministero della Salute/ ; },
}

@article {pmid42029890,
year = {2026},
author = {Aktan, R and Yakıt Yeşilyurt, S and Özalevli, S and Sonbahar, AE},
title = {Response to Letter to the Editor: "Concerns Regarding Baseline Balance, Blinding Validity, and Clinical Relevance in Aktan et al.'s Study on Home-Based Inspiratory Muscle Training for Stress Urinary Incontinence".},
journal = {International urogynecology journal},
volume = {},
number = {},
pages = {},
pmid = {42029890},
issn = {1433-3023},
}

@article {pmid42030003,
year = {2026},
author = {Arslan, HN and Bozkul, G and Çelik, SŞ},
title = {Emotional, Ethical and Cultural Challenges in Percutaneous Endoscopic Gastrostomy (PEG) Decision-Making: A Systematic Review and Meta-Synthesis.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {29},
number = {2},
pages = {e70294},
doi = {10.1111/hex.70294},
pmid = {42030003},
issn = {1369-7625},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Humans ; *Gastrostomy/ethics/psychology/methods ; *Decision Making/ethics ; *Emotions ; Qualitative Research ; Caregivers/psychology ; },
abstract = {BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a critical intervention for patients with neurological and gastrointestinal conditions affecting oral intake. While clinical guidelines emphasise medical indications, they often overlook the intricate emotional, ethical and cultural concerns that shape decision-making. This gap in understanding leads to variability in clinical recommendations and uncertainty among patients and their families. A deeper exploration of these factors is necessary to support informed, patient-centred decision-making.

AIM: This systematic review and meta-synthesis aimed to explore the emotional, ethical and cultural challenges influencing PEG decision-making, while also considering the broader context of shared decision-making.

DESIGN: A systematic review and meta-synthesis of qualitative studies.

METHODS: The review was conducted by systematically searching six databases, including CINAHL, Scopus, Web of Science, MEDLINE, PubMed and TRDizin. Only qualitative studies published between 2004 and 2024 were included to capture subjective experiences related to PEG decision-making. Studies focusing only on clinical outcomes or utilising quantitative methodologies were excluded. The review considered perspectives from adult patients, family members, caregivers and healthcare professionals while paediatric studies were excluded due to differences in decision-making dynamics. Data were synthesised using thematic analysis to organise findings into main themes and sub-themes.

RESULTS: A total of 15 studies representing a variety of clinical settings and patient conditions, such as amyotrophic lateral sclerosis, advanced dementia and stroke, were included. These studies involved 141 patients (41.1%), 62 caregivers (18.1%) and 140 healthcare professionals (40.8%), ensuring a comprehensive analysis of perspectives on PEG decision-making. Seven major themes were identified: (1) emotional and psychological impact of decision-making, (2) ethical and moral considerations both patients and caregivers, (3) communication challenges and information gaps, (4) impact of healthcare professionals on decision-making, (5) ethical and emotional challenges in decision-making, (6) communication barriers and conflicting advice and (7) professional responsibility and advocacy. Family members and caregivers reported feelings of anxiety, guilt and regret, often due to uncertainty and inadequate communication. Healthcare professionals also faced challenges, including conflicting messages and a lack of comprehensive information.

CONCLUSION: Emotional, ethical and cultural factors significantly impact the PEG decision-making process involving patients, caregivers and healthcare professionals. Improving healthcare professionals' communication skills, developing decision aids and encouraging interdisciplinary collaboration are crucial for supporting informed and shared decision-making.

IMPLICATIONS FOR NURSING: Nurses play a central role in the PEG decision-making process, as they are the healthcare professionals with the most frequent and direct contact with patients and their family support networks. Addressing the gaps in communication and emotional support can help improve the quality of care provided to patients undergoing PEG. Implementing structured emotional support programmes, integrating psychological counselling into routine care and training healthcare professionals in empathetic communication strategies can significantly reduce patient and caregiver distress. Beyond providing clinical care, nurses act as essential advocates, educators and emotional support providers, ensuring that patients and families receive clear, consistent and compassionate guidance throughout the decision-making process. Their involvement in interdisciplinary collaboration and shared decision-making frameworks is crucial for aligning PEG decisions with patient values and preferences.

This review synthesised findings from studies capturing the experiences of patients, families, caregivers and healthcare professionals involved in PEG decision-making, ensuring their perspectives were represented.},
}

Humans
*Gastrostomy/ethics/psychology/methods
*Decision Making/ethics
*Emotions
Qualitative Research
Caregivers/psychology

@article {pmid42030149,
year = {2026},
author = {Varela, V and Garcimartín, S and Trias, E and Zeida, A and Richter, M and de León, A and Miquel, E and King, PH and Vulliez-Le Normand, B and Martinez, M and Alzari, PM and Bartesaghi, S and Radi, R and Barbeito, L},
title = {Monoclonal antibodies against nitrated nerve growth factor reveal an oxidation-dependent pathogenic hallmark in ALS.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {17},
pages = {e2536562123},
doi = {10.1073/pnas.2536562123},
pmid = {42030149},
issn = {1091-6490},
support = {EI_2020//Universidad de la República Uruguay (UdelaR)/ ; CSIC I + D _ 2022//UdelaR | Comisión Sectorial de Investigación Científica (CSIC)/ ; CSIC I _ 2023//UdelaR | Comisión Sectorial de Investigación Científica (CSIC)/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/immunology/pathology ; *Antibodies, Monoclonal/immunology ; Humans ; *Nerve Growth Factor/immunology/metabolism/chemistry ; Animals ; Oxidation-Reduction ; Mice ; Rats ; Motor Neurons/metabolism/pathology ; Tyrosine/metabolism ; Epitope Mapping ; Female ; *Nitrates/metabolism ; Male ; },
abstract = {Nerve growth factor (NGF) is a member of the neurotrophin family, essential for neuronal survival and phenotypic maintenance. However, in vitro, its function can be disrupted by oxidative posttranslational modifications such as tyrosine nitration. Nitrated NGF (NO2NGF) has been shown to have a gain-of-toxic, pro-apoptotic, activity in motoneuron cultures. Herein, we report the generation and characterization of monoclonal antibodies (mAbs) that specifically recognize NO2NGF to unravel its formation in vivo. Using hybridoma technology, we produced mAbs with high affinity and selectivity for NO2NGF, as demonstrated immunochemically and by surface plasmon resonance. The antibodies elicit neutralizing capacity to NO2NGF in neuronal cells. Nitrated Tyr52 within the NGF48-58 sequence was identified as the primary antigenic determinant by crystallographic analysis of antibody:peptide complexes at atomic resolution, peptide-based epitope mapping and molecular dynamics simulations, whereas local sequence NGF motifs around the nitrated tyrosine are important for protein specificity. The antibodies revealed NO2NGF accumulation in amyotrophic lateral sclerosis (ALS) rodent models and human subjects. Indeed, immunofluorescence showed selective accumulation of NO2NGF in spinal cord regions undergoing motor neuron degeneration, as well as in sciatic nerves and neuromuscular junctions. Our findings establish NGF nitration as an oxidative hallmark in ALS and demonstrate that monoclonal antibodies targeting this chemical modification are powerful tools for both mechanistic studies and biomarkers development. This work proposes a link between neurotrophin nitration and neurodegenerative disease progression and opens avenues for therapeutic exploration along the peroxynitrite-tyrosine nitration pathway.},
}

*Amyotrophic Lateral Sclerosis/metabolism/immunology/pathology
*Antibodies, Monoclonal/immunology
Humans
*Nerve Growth Factor/immunology/metabolism/chemistry
Animals
Oxidation-Reduction
Mice
Rats
Motor Neurons/metabolism/pathology
Tyrosine/metabolism
Epitope Mapping
Female
*Nitrates/metabolism
Male

@article {pmid42031063,
year = {2026},
author = {Shi, C and Jia, K and Guo, Y and Qian, S and Wang, B and Qiu, Y and Dan, L and Dang, Z and Xue, K and Gao, F and Zhao, L},
title = {Disulfidptosis in Neurodegenerative Diseases: From Redox Imbalance to Neuronal Dysfunction.},
journal = {Behavioural brain research},
volume = {},
number = {},
pages = {116242},
doi = {10.1016/j.bbr.2026.116242},
pmid = {42031063},
issn = {1872-7549},
abstract = {Disulfidptosis is a recently identified form of regulated cell death driven by disulfide stress and cytoskeletal collapse under conditions of impaired reducing capacity. Neurodegenerative diseases (NDs), including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis, are characterized by oxidative stress, mitochondrial dysfunction, metabolic impairment, protein aggregation, and cytoskeletal instability-features that may provide a permissive intracellular context for disulfidptosis. However, its occurrence and pathological relevance in these disorders remain incompletely understood. In this review, we examine the potential involvement of disulfidptosis in neurodegenerative diseases from a disease-centered perspective. We emphasize that current evidence is largely indirect and based on mechanistic overlap rather than direct experimental validation in neural systems. Accordingly, we distinguish between direct evidence, indirect mechanistic support, and pathophysiological plausibility. We further discuss cell-type-specific susceptibility across neurons and glial cells, analyze its relationship with other cell death pathways, and consider potential therapeutic implications. Overall, disulfidptosis is best regarded as a context-dependent and emerging mechanism that may contribute to neuronal vulnerability under specific metabolic and redox constraints. Clarifying its disease relevance will be essential for determining its significance in neurodegeneration and its potential as a therapeutic target.},
}

@article {pmid42021292,
year = {2026},
author = {Yang, T and Wang, Y and Dong, N and Ding, J and Yan, X and Luo, J and Chen, P and Qiu, Y and Lin, T and Tong, J and Mao, J and Dai, Y and Shentu, H and Tang, S and Sheng, L and Zhao, M and Yang, G},
title = {Predicting amyotrophic lateral sclerosis stage based on multi-parameter ultrasound: development and validation of an interpretable machine learning model.},
journal = {BMC medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12916-026-04871-3},
pmid = {42021292},
issn = {1741-7015},
support = {2025HZZD09//The Construction Fund of Key Medical Disciplines of Hangzhou - Rare Disease (Motor Neuron Disease)/ ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) lacks sensitive, objective staging tools to guide clinical management and trials. Existing methods have limited granularity and rely on subjective assessment, while biomarker and imaging approaches can be invasive or impractical for serial use. Ultrasound is a safe, portable imaging modality that can detect neuromuscular changes, but it has not yet been applied to ALS staging. We developed and validated an interpretable ultrasound model for clinical staging and risk stratification in ALS.

METHODS: We enrolled 300 ALS patients, classified as early-stage (King's stages 1-2; n = 148) or late-stage (3-4; n = 152). Each patient underwent ultrasound of key muscle groups, including the diaphragm (excursion and thickening), geniohyoid (shear-wave velocity), and peripheral skeletal muscles (thickness and cross-sectional area). Six machine learning models were trained to predict early vs late stage from these ultrasound metrics combined with clinical factors. Performance was evaluated on a test set using area under the curve (AUC), F1 score and Brier score. Feature importance was analyzed with SHapley Additive exPlanation (SHAP) values.

RESULTS: In the test set, the random forest achieved an AUC of 0.843, an F1 score of 0.727, and a Brier score of 0.177, with sensitivity 0.80 and specificity 0.68. SHAP analysis identified diaphragm excursion during deep breathing (DEDB) as the top predictor, followed by masseter muscle thickness (MMT) and geniohyoid shear-wave velocity (GHSWVmean). Higher DEDB, MMT and GHSWVmean values predicted earlier stage, whereas lower peripheral muscle thickness and older age indicated late-stage disease.

CONCLUSIONS: Multiparameter ultrasound combined with machine learning offers a non-invasive, bedside tool for ALS staging. The model's accuracy and interpretability enable objective tracking of disease progression and may support timely interventions and patient stratification in clinical practice and trials. Leveraging widely accessible ultrasound technology, this approach is feasible for routine ALS care and research.},
}

@article {pmid42021677,
year = {2026},
author = {Mukhija, S and Lehner, F and Jung, HH},
title = {[Amyotrophic lateral sclerosis (ALS): current perspectives and the Swiss ALS Registry].},
journal = {Praxis},
volume = {115},
number = {4},
pages = {100-106},
doi = {10.23785/PRAXIS.2026.04.003},
pmid = {42021677},
issn = {1661-8157},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/therapy/epidemiology ; *Registries ; Switzerland ; Disease Progression ; Risk Factors ; Riluzole/therapeutic use ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease leading to muscle weakness, atrophy, and ultimately death. In addition to mutations in ALS-related genes, environmental and lifestyle factors may increase disease risk. Diagnosis is based on clinical evaluation, supplemented by electroneuromyography, imaging, and molecular genetic testing. No curative therapy exists, but Riluzole and Edaravone can slow progression, and genetic therapies offer promising perspectives in certain genetically determined forms. In practice, diagnosis is often delayed. The Swiss ALS Registry collects comprehensive data on environmental, lifestyle, clinical, genetic, and biomarker factors, aiming to improve understanding of risk, disease progression, and therapeutic approaches.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/genetics/therapy/epidemiology
*Registries
Switzerland
Disease Progression
Risk Factors
Riluzole/therapeutic use

@article {pmid42021792,
year = {2025},
author = {Iztleuov, M and Abugaliyeva, N and Ryzhkin, S and Iztleuov, Y and Saparbaev, S and Smagulova, G},
title = {Current Insights into Plausible Mechanisms of Chromium (VI) Neurotoxicity in the Brain and Future Perspectives.},
journal = {Medical journal of the Islamic Republic of Iran},
volume = {39},
number = {},
pages = {157},
pmid = {42021792},
issn = {1016-1430},
abstract = {BACKGROUND: Hexavalent chromium (Cr (VI)) is a known neurotoxin and environmental contaminant. Despite its recognition, the underlying mechanisms by which Cr (VI) induces neurological damage remain insufficiently explored. The complexities of the Central Nervous System (CNS), including the Blood Brain Barrier (BBB) and supporting brain cells, contribute to regions-specific susceptibility within the brain. Understanding Cr (VI) neurotoxicity is crucial for its potential role in neurodegenerative diseases.

METHODS: A Systematic Review was conducted using international databases (PubMed, Medline, Scopus, and Web of Science) and Google Scholar. Only open-access, free full-text articles published in English between 2010 and 2025 were included. Following PRISMA 2020 guidelines, a total of 19 relevant studies were selected, comprising 12 animal-based and 7 human cohort studies.

RESULTS: Animal studies investigated the effects of Cr (VI) via various administration methods and doses, revealed evidence of oxidative stress, inflammatory markers, and apoptotic changes in the brain. Interventional studies showed delayed toxicity when antioxidant agents were used prior to Cr (VI) exposure, including PDC (Potassium Dichromate), SA (Sodium Alginate), and TNG (Tangeretin). Human studies, including autopsies and cell culture analyses, demonstrated neurotoxic effects in conditions such as ALS (Amyotrophic Lateral Sclerosis), nAMD (Neovascular Age-Related Macular Degeneration).

CONCLUSION: Animal studies have clarified the role of oxidative stress in Cr (VI)-induced neurotoxicity. Human cohort studies have identified Cr (VI) as an environmental risk factor for both neurodegenerative and neurobehavioral disorders. Future research should focus on defining harmful levels of Cr (VI) and exploring potential antioxidant therapies.},
}

@article {pmid42022335,
year = {2026},
author = {Cutti, L and Turra, GM and Machado, FM and Sulzbach, E and Angonese, PS and Markus, C and Gaines, TA and Merotto, A},
title = {Subgenomic Distribution and Herbicide Cross-Resistance of ALS Gene Mutations in Allohexaploid Echinochloa crus-galli.},
journal = {Plant direct},
volume = {10},
number = {},
pages = {e70168},
pmid = {42022335},
issn = {2475-4455},
abstract = {Herbicide target site resistance in polyploid species is more complex than in diploids due to potential subgenome interactions. This study characterized mutations in the ALS gene across distinct subgenomes of hexaploid Echinochloa crus-galli and evaluated the cross-resistance patterns conferred by each mutation to various ALS-inhibiting herbicides. E. crus-galli populations were screened, and dose-response curves were performed with ALS inhibitors from different chemical groups. The ALS gene copies of each subgenome (A, B, and C) were sequenced. Copy number variation, global relative expression, and the specific relative expression of ALS gene from each subgenome were performed. The mutations Ala122Thr, Ala205Asn, and Ser653Asn conferred resistance only to imazethapyr, whereas Trp574Leu to imazethapyr, penoxsulam, bispyribac-sodium, and nicosulfuron, when considered the label rate. ALS mutations were more frequent in subgenome A, but ALS from subgenome C had the highest expression. Biotypes with the same mutation showed different resistance level to herbicides. The biotype SAOJER-01 had Trp574Leu mutation in subgenome C and was 22 times more resistant to imazethapyr and penoxsulam than CAMAQ-01, which had the same Trp574Leu mutation in subgenome A. Both SAOJER-01 and CAMAQ-01 biotypes showed CYP450 metabolism mediating penoxsulam resistance in addition to the target site mutation. In conclusion, the mutations Ala122Thr, Ala205Asn, Trp574Leu, and Ser653Asn confer resistance to imazethapyr, but only Trp574Leu confers resistance to the other chemical groups. The herbicides penoxsulam, bispyribac-sodium, and nicosulfuron are effective in controlling three out of four mutations. CYP450-mediated metabolism coexists in biotypes carrying the Trp574Leu mutation. The subgenome location of the ALS mutation may result in variable levels of resistance.},
}

@article {pmid42023099,
year = {2026},
author = {Galluzzi, G and Ruocco, G and Fornetti, E and Genovese, I},
title = {Modeling ALS in a dish: how organoids are transforming research.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1792336},
pmid = {42023099},
issn = {2296-858X},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive neurodegenerative disease characterized by the selective loss of upper and lower motor neurons, leading to muscle weakness, paralysis, and ultimately respiratory failure. The multifactorial etiology of ALS, encompassing genetic mutations, protein aggregation, oxidative stress, excitotoxicity, and dysregulated RNA metabolism, has hindered the development of effective therapies. Traditional animal and 2D cell models have provided important mechanistic insights but often fail to fully capture the human-specific and multicellular aspects of disease pathophysiology. Recent advances in induced pluripotent stem cell (iPSC)-derived organoids offer a promising human-based platform for ALS research, enabling the generation of disease-relevant neural and neuromuscular subtypes in three-dimensional architectures. These models recapitulate key pathological features, including protein mis-localization, neuromuscular junction defects, synaptic impairments, and glial contributions to motor neuron degeneration, while also serving as platforms for drug screening and mechanistic studies. Importantly, spinal and neuromuscular organoids bridge the gap between simplified in vitro systems and the complex human nervous system, providing a unique framework to study ALS pathogenesis. This review provides a comprehensive overview of the various differentiation protocols, experimental strategies and key results obtained to date, with a primary focus on validating and benchmarking organoid models, while also highlighting their limitations, emerging clinical applications, translational potential, and opportunities for personalized therapeutic discovery.},
}

@article {pmid42024796,
year = {2026},
author = {Mei, J and Xia, M and Peng, L and Li, X},
title = {Alcohol and neurodegenerative diseases: a review of mechanistic insights and disease specific effects.},
journal = {The American journal of drug and alcohol abuse},
volume = {},
number = {},
pages = {1-16},
doi = {10.1080/00952990.2026.2645215},
pmid = {42024796},
issn = {1097-9891},
abstract = {Background: Neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD) represent a significant global public health problem. Alcohol consumption is a common lifestyle factor that has been implicated as both a risk factor and potential modifier of disease progression.Objectives: This review integrates evidence from human and experimental studies to characterize the effects of alcohol consumption on the onset and progression of major neurodegenerative diseases.Methods: A narrative review was undertaken examining the pathophysiological effects of alcohol on the brain and its disease-specific effects on neurodegenerative disorders, integrating findings from human cohort studies and mechanistic investigations in preclinical models.Results: Experimental evidence indicates that chronic alcohol consumption exacerbates neurodegeneration through multiple converging mechanisms, including oxidative stress, mitochondrial dysfunction, lipid peroxidation, inflammatory signaling, disruption of neurotrophic pathways, impairment of dopaminergic neurotransmission, and alcohol-induced gut microbiota dysbiosis with blood-brain barrier compromise. Epidemiological data suggest dose-dependent and disease-specific associations, with heavy and sustained consumption more consistently linked to increased risk or accelerated progression of AD and PD, while evidence in ALS and HD remains inconsistent.Conclusion: Alcohol exerts a multifaceted and context-dependent influence on neurodegenerative diseases. Accumulating evidence supports that long-term heavy alcohol consumption is associated with enhanced neurodegeneration. Minimizing alcohol consumption may present a pragmatic opportunity to reduce neurodegenerative risk.},
}

@article {pmid42025804,
year = {2026},
author = {Woodard, GE},
title = {C3 and C5 Complement Cascade Activation in Brain Injury and Disease: Molecular Mechanisms, Pathological Roles, and Therapeutic Implications.},
journal = {Neurochemistry international},
volume = {},
number = {},
pages = {106161},
doi = {10.1016/j.neuint.2026.106161},
pmid = {42025804},
issn = {1872-9754},
abstract = {The complement system represents a crucial component of innate immunity with increasingly recognized roles in central nervous system pathology and homeostasis. Complement components C3 and C5 serve as central molecular hubs in the complement cascade, orchestrating inflammatory responses, synaptic pruning, and neuronal injury across diverse neurological conditions. This comprehensive review examines the molecular mechanisms underlying C3 and C5 activation in the brain, their pathological contributions to acute brain injuries including traumatic brain injury and ischemic stroke, and their complex involvement in chronic neurodegenerative diseases such as Alzheimer disease, multiple sclerosis, Parkinson disease, Huntington disease, and amyotrophic lateral sclerosis. Emerging evidence demonstrates that complement activation in the central nervous system extends beyond traditional immune functions to encompass critical roles in neurodevelopment, synaptic plasticity, and neural circuit refinement. The dual nature of complement function in the brain, exhibiting both neuroprotective and neurodegenerative properties depending on context and activation levels, presents unique therapeutic challenges and opportunities. This review synthesizes current understanding of complement-mediated neuroinflammation, discusses validated and emerging therapeutic strategies targeting C3 and C5, evaluates complement biomarkers for disease diagnosis and monitoring, and identifies critical knowledge gaps requiring future investigation. Understanding the nuanced roles of C3 and C5 in neurological disease provides essential foundations for developing targeted immunomodulatory therapies that preserve beneficial complement functions while mitigating pathological activation.},
}

@article {pmid42025938,
year = {2026},
author = {McColgan, L and Evans, TV and Marku, RN and Perim, RR and Xu, G and Amorim, IP and Urdaneta, M and Mitchell, GS},
title = {Physiological Predictors of Respiratory Motor Plasticity: A Machine-Learning Reappraisal of Phrenic Motor Facilitation.},
journal = {Respiratory physiology & neurobiology},
volume = {},
number = {},
pages = {104574},
doi = {10.1016/j.resp.2026.104574},
pmid = {42025938},
issn = {1878-1519},
abstract = {Acute intermittent hypoxia (AIH)-induced phrenic long-term facilitation (pLTF) is a well-established form of respiratory motor plasticity and a subtype of phrenic motor facilitation (pMF), which also includes pharmacologically induced plasticity. Understanding the mechanisms of pLTF and pMF represents opportunities for therapeutic targets for spinal cord injury, amyotrophic lateral sclerosis and other neurological disorders. Here, we performed a secondary analysis of previously generated experimental datasets to reassess physiological predictors of pLTF and pMF. Given the limitations of expressing pMF as a percent, and to systematically evaluate complex and potentially nonlinear relationships among physiological variables, we employed a supervised machine learning approach using Gradient Boosted Decision Trees and Shapley Additive Explanations (SHAP) analysis to identify and rank both established and novel determinants of respiratory plasticity via percent-based (%) and absolute (Δ) changes in pLTF and pMF. Gradient Boosted Decision Trees models were trained to predict Δ and % outcomes using baseline physiological variables and AIH- or drug-evoked responses as input features, and model interpretability was achieved using SHAP to quantify the contribution of each predictor. The pooled datasets included experiments in which pLTF was induced via AIH (n=75) and pMF via pharmacologic intervention (n=39) using established experimental protocols. All animals underwent standardized measurement of phrenic nerve activity, respiratory frequency, arterial blood pressure, and evoked hypoxic responses, which were incorporated into the predictive models. Hypoxia-induced phrenic nerve response (ΔHypoxicPNA) was the primary predictor of ΔpLTF, while ΔMaximalPNA exerted a lesser influence in our analysis. Similarly, %pLTF was most strongly influenced by %HypoxicPNA but was also influenced by baseline phrenic nerve activity (BL PNA) and the hypoxia-evoked blood pressure response (ΔHypoxicBP). Notably, calculating percent change in pLTF versus absolute change in pLTF presents certain limitations. Each animal has a unique level of baseline phrenic nerve activity, so calculation via percent change can conceal or misrepresent the overall magnitude of respiratory motor plasticity. For ΔpMF, BL PNA was the strongest positive correlate, while body mass, which strongly correlates with age in laboratory rats, was inversely correlated to ΔpMF. Rat body mass was strongly inversely correlated with %pMF, while BL PNA and BL respiratory frequency (RF) exerted some influence. Similarities in determinant variables for pMF and pLTF indicate the two phenomena exhibit overlapping mechanisms of action, while the differing variables in each measure of respiratory motor plasticity demonstrate the unique sensitivities of pLTF and pMF. This study provides a comprehensive evaluation of respiratory motor plasticity, discovering new determinants while validating previous research regarding pLTF. Better understanding its mechanism could further research into new therapies for increasing respiratory drive.},
}

@article {pmid42026110,
year = {2026},
author = {Trad, G and Lenglet, T and Ledoux, I and Querin, G and Blancho, S and Marchand-Pauvert, V and Pradat, PF and Hogrel, JY},
title = {Exploring the interplay between quantitative muscle strength, functional performance, and patient-reported outcomes in amyotrophic lateral sclerosis: a cross-sectional pilot study.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-45898-z},
pmid = {42026110},
issn = {2045-2322},
support = {ANR-23-BIOC-0003//Agence Nationale de la Recherche/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) shows marked clinical heterogeneity, while standard clinical assessments may fail to capture its multidimensional burden. Integrating quantitative muscle strength, functional tests and patient-reported outcomes (PROs) may improve disease characterization. Ten ambulant adults with ALS were enrolled in a cross-sectional pilot study. Functional performance was assessed with the Revised ALS Functional Rating Scale (ALSFRS-R), Six-Minute Walk Test (6MWT), Ten-Meter Walk Test, Timed Up and Go, Berg Balance Scale and a fatigability index, lower-limb strength with dynamometry, and PROs with ALS Assessment Questionnaire-40 (ALSAQ-40), Hospital Anxiety and Depression Scale, Fatigue Severity Scale and Modified Fatigue Impact Scale (MFIS). Despite relatively preserved ALSFRS-R scores (40.6 ± 2.8), participants showed reduced 6MWT (61.3 ± 21.7% predicted), marked fatigability (- 47.3 ± 112.3%) and a lower-limb strength index of 58.2 ± 13.8% predicted. The ALSAQ-40 score averaged 183.1 ± 59.5. Fatigue was prominent, while anxiety and depression remained mild. Muscle strength correlated positively with ALSFRS-R gross motor score and inversely with anxiety. ALSAQ-40 and MFIS components showed significant associations with both functional and walking performance. Even at ambulant stages, measurable muscle weakness and fatigability co-occur with functional and PROs changes in ALS, supporting the use of multidomain, sensitive clinical assessment. The trial was registered at ClinicalTrials.gov (NCT06199284) on 29/12/2023.},
}

@article {pmid42026661,
year = {2026},
author = {Kuppens, A and Rogister, B and Neirinckx, V},
title = {Pharmacological modulation of CXCL12/CXCR4/ACKR3 for brain disorders - an overview.},
journal = {Cell communication and signaling : CCS},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12964-026-02877-1},
pmid = {42026661},
issn = {1478-811X},
support = {7.6518.24//Fonds De La Recherche Scientifique - FNRS/ ; },
}

@article {pmid42015728,
year = {2026},
author = {Wang, H and Li, G and Liang, F and Xia, X and Zhang, W and Fan, Z},
title = {A nomogram for estimating baseline respiratory insufficiency in patients with amyotrophic lateral sclerosis.},
journal = {Annals of medicine},
volume = {58},
number = {1},
pages = {2654938},
doi = {10.1080/07853890.2026.2654938},
pmid = {42015728},
issn = {1365-2060},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/physiopathology ; Male ; Female ; *Nomograms ; Middle Aged ; Retrospective Studies ; *Respiratory Insufficiency/etiology/diagnosis/physiopathology/epidemiology ; Aged ; Respiratory Function Tests/methods ; Muscle Strength/physiology ; Vital Capacity ; Adult ; ROC Curve ; },
abstract = {OBJECTIVES: To develop and validate a nomogram for estimating the risk of baseline respiratory insufficiency in patients with amyotrophic lateral sclerosis (ALS). This also aims to analyze the association between readily available clinical predictors and pulmonary function.

MATERIALS AND METHODS: This retrospective study assessed 142 ALS patients treated at the First Hospital of Shanxi Medical University from August 2020 to June 2023. ALS was diagnosed based on revised El Escorial criteria with Awaji modifications. Clinical data and pulmonary function tests (PFTs) were performed during a single hospital stay. Respiratory insufficiency was marked as forced vital capacity (FVC) < 80% of predicted. Muscle strength of neck and limbs was measured with the Medical Research Council (MRC) scale. Multivariable logistic regression evaluated independent predictors of respiratory insufficiency. A nomogram was created and internally validated using bootstrap resampling (1,000 iterations). Model performance was assessed with ROC curve analysis, calibration curve analysis, and decision curve analysis (DCA).

RESULTS: Of the 142 patients, 30 (21.1%) presented with baseline respiratory insufficiency. In the multivariable analysis, neck flexor muscle strength (OR = 0.497, 95% CI: 0.321-0.769; p = 0.002) and bulbar onset (OR = 4.392, 95% CI: 1.674-11.521; p = 0.003) were independent predictors in the multivariable analysis. The nomogram showed good discrimination and calibration (AUC = 0.823, 95% CI: 0.739-0.907).

CONCLUSIONS: Weakness of neck flexors and bulbar onset are independently associated with baseline respiratory insufficiency in ALS patients. The proposed nomogram may serve as a useful tool for baseline screening and risk stratification. External validation in larger multicenter cohorts is warranted before clinical application.},
}

Humans
*Amyotrophic Lateral Sclerosis/complications/physiopathology
Male
Female
*Nomograms
Middle Aged
Retrospective Studies
*Respiratory Insufficiency/etiology/diagnosis/physiopathology/epidemiology
Aged
Respiratory Function Tests/methods
Muscle Strength/physiology
Vital Capacity
Adult
ROC Curve

@article {pmid42016758,
year = {2026},
author = {Liu, Y and Xia, X and Chen, Y and Yang, H and Chen, X and Cai, L and Shi, B},
title = {When Rare Is Not Small: Amyotrophic Lateral Sclerosis Initiatives and Therapy.},
journal = {Exploration (Beijing, China)},
volume = {6},
number = {2},
pages = {70114},
pmid = {42016758},
issn = {2766-2098},
abstract = {In the precision-medicine era, rare diseases must not be sidelined in translational infrastructure. The Mr. Cai Lei-led "Ice-Breaking Team" turns an amyotrophic lateral sclerosis patient community into a sustainable ecosystem, realigning philanthropy, data, and research and development to reshape rare-disease pipelines and guide precision therapies, offering a replicable blueprint for rare-disease strategies.},
}

@article {pmid42016770,
year = {2026},
author = {Cao, L and Chen, G and Zhou, J and Huang, H and Xu, A and Zhan, T and Zhao, Y and Liu, H},
title = {Subtype-specific associations between serum lipid profiles and disease severity in patients with amyotrophic lateral sclerosis.},
journal = {Biomedical reports},
volume = {24},
number = {6},
pages = {68},
pmid = {42016770},
issn = {2049-9442},
abstract = {Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative disorder. Notably, the differences in lipid metabolism between bulbar- and limb-onset subtypes of ALS remain unclear, particularly in non-Western populations. The present study investigated serum lipid profiles in a Chinese cohort of patients with ALS to explore their associations with disease severity and clinical subtypes. A retrospective, cross-sectional study was conducted, involving 158 patients with ALS and 62 matched healthy controls. Serum lipid parameters, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), small dense LDL cholesterol (sdLDL-c), apolipoprotein A-1 (ApoA1), apolipoprotein B (ApoB) and the TG/HDL ratio, were compared between the groups. Correlation analyses and multivariable linear regression models incorporating phenotype x lipid interaction terms were conducted after adjusting for age, sex, body mass index and disease duration. Patients with ALS exhibited significantly higher TC, TG, LDL, sdLDL-c, ApoA1, ApoB and TG/HDL ratios than controls. Subtype-specific analyses revealed different associations; in bulbar-onset ALS, higher sdLDL-c and TG/HDL ratios were associated with better functional status, whereas higher HDL and ApoA1 levels were negatively correlated with functional status. By contrast, in limb-onset ALS, higher sdLDL-c and ApoB levels were associated with worse function. Interaction analyses confirmed significant phenotype modification for sdLDL-c, TG/HDL ratio, HDL and ApoA1. These results suggest that lipid-severity relationships in ALS vary by subtype, indicating metabolic heterogeneity across phenotypes and supporting the potential of specific lipid parameters as exploratory markers for disease monitoring.},
}

@article {pmid42018749,
year = {2026},
author = {Niu, RZ and Zhang, MY and Yang, HH and Zeng, XF and Liu, J and Bao, TH},
title = {Single-cell multiregion dissection of central nervous system aging.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {},
number = {},
pages = {},
doi = {10.1093/gerona/glag103},
pmid = {42018749},
issn = {1758-535X},
abstract = {Central nervous system (CNS) aging is a major risk factor for many disorders, including cerebrovascular disease, neurodegeneration and amyotrophic lateral sclerosis, yet the cellular pathways driving its progression across CNS regions remain poorly defined. Here we present a single-nucleus transcriptomic atlas spanning seven human CNS regions, comprising ∼1.0 million nuclei from 235 post-mortem samples derived from 200 neurologically and psychiatrically normal donors aged 19-101 years. Across regions, we delineate both shared and region-specific features of CNS aging, integrating analyses of transcriptional noise, programmed cell-death signatures, disease associations, metabolic reprogramming and transcriptomic remodeling. We identify cross-regional vulnerability of astroglia, oligodendrocytes, and excitatory and inhibitory neurons, and show that microglial and astrocytic activation represents a broadly conserved aging response across the CNS, highlighting potential targets for intervention. Finally, we present within-dataset proof-of-concept predictive modeling use cases based on aging-associated gene signatures, providing a resource for within-atlas prioritization and hypothesis generation of candidate biomarkers of CNS aging. Together, this work offers a region-by-region map of the aging human CNS and informs the selection of specific cell types and/or regions for future anti-aging strategies.},
}

@article {pmid42020605,
year = {2026},
author = {},
title = {Somatic mutations link focal onset to widespread neurodegeneration in ALS and FTD.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {42020605},
issn = {1546-1718},
}

@article {pmid42020791,
year = {2026},
author = {Tsagkas, C and Donadieu, M and Sun, R and Bujak, B and Hu, K and Rood, C and Cameron, K and Dodd, S and Reich, DS and Nair, G},
title = {A pipeline to characterize spinal cord pathology in neurological disorders combining magnetic resonance microscopy and histopathology.},
journal = {Communications medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s43856-026-01577-8},
pmid = {42020791},
issn = {2730-664X},
abstract = {BACKGROUND: The length, shape, and size of the spinal cord (SC) present unique challenges for MRI, including the need for high resolution to distinguish anatomical and pathological features along its span. Postmortem MRI offers an opportunity to map SC tissue abnormalities and investigate their histological correlates.

METHODS: We developed a pipeline combining postmortem microscopic resolution MRI (MR microscopy; MRM) of whole formalin-fixed SC specimens with targeted histopathological analysis. A gadolinium-based tissue preparation protocol was optimized using SC tissue from common marmosets with experimental autoimmune encephalomyelitis. A custom tissue holder and container were designed to enable postmortem MRI of the entire human SC. Human SC samples from individuals with multiple sclerosis, amyotrophic lateral sclerosis, and intracranial hemorrhage were scanned at 75 μm isotropic resolution on a 9.4 T Bruker system after gadolinium preparation.

RESULTS: MRM after gadolinium-based tissue preparation yields images with high signal- and contrast-to-noise ratio while minimizing acquisition times. MRI demonstrates fine anatomical detail and pathological features, including demyelination and neurodegeneration throughout the SC. A complementary custom-made cutting rack enables targeted histological sectioning of MRI-identified regions. This approach provides precise spatial correspondence between imaging and histological findings, demonstrating strong agreement across modalities.

CONCLUSIONS: In summary, this pipeline facilitates comprehensive SC assessment by integrating MRM with histology. It enables accurate localization of both subtle and widespread SC pathology and enhances interpretation of MRI signals in the context of neurodegenerative and inflammatory diseases.},
}

@article {pmid41313264,
year = {2026},
author = {Chancel, A and Fort, P and Maciel, RM and Duval, B and Malcey, J and Bellini, S and Schmidt, MH and Luppi, PH},
title = {Comparative distribution of the hypothalamic neurons activated during wakefulness and paradoxical (REM) sleep using male TRAP2-red mice: contribution of orexin, MCH, Lhx6, and a new marker Meis2.},
journal = {Sleep},
volume = {49},
number = {4},
pages = {},
doi = {10.1093/sleep/zsaf368},
pmid = {41313264},
issn = {1550-9109},
mesh = {Animals ; Male ; Orexins/metabolism ; *Neurons/physiology/metabolism ; Mice ; *Hypothalamus/physiology/cytology/metabolism ; *Hypothalamic Hormones/metabolism/physiology ; *Melanins/metabolism/physiology ; *Wakefulness/physiology ; *Pituitary Hormones/metabolism/physiology ; *Sleep, REM/physiology ; *Transcription Factors/metabolism/physiology ; *Nerve Tissue Proteins/metabolism/physiology ; *Homeodomain Proteins/metabolism/physiology ; LIM-Homeodomain Proteins/metabolism ; Proto-Oncogene Proteins c-fos/metabolism ; Mice, Transgenic ; Neuropeptides/physiology ; },
abstract = {STUDY OBJECTIVES: Paradoxical sleep (PS) is a state involving numerous hypothalamic neuronal subpopulations, many remaining neurochemically uncharacterized. Our goal was to compare hypothalamic neurons active during wakefulness or PS rebound (PSR) and explore their potential overlap, with a focus on melanin-concentrating hormone (MCH), Orexin (Orx), Lhx6, and a new contingent of Meis2-expressing neurons.

METHODS: In the same male TRAP2-red mouse, neurons activated during wakefulness (4 h) and PSR (2 h) express TdTomato and c-Fos, respectively. Double-labeling and triple immunofluorescence with neurochemical markers were performed to characterize and quantify cell populations in hypothalamic structures.

RESULTS: Twelve hypothalamic structures showed distinct activation patterns. The anterior hypothalamic area (AHA), zona incerta (ZI), and tuberal nucleus contained more activated neurons during PSR than wakefulness, whereas the paraventricular hypothalamic, supraoptic, parasubthalamic nuclei, and retrochiasmatic area were predominantly activated during wakefulness. MCH and Lhx6 neurons were mainly recruited during PSR, whereas Orx neurons were more activated during wakefulness. The ventral subpopulation of MCH neurons showed higher activation during PSR than the dorsal subpopulation. Additionally, ~30 per cent of the c-Fos+ neurons in ZI and ~20 per cent in LHA expressed Meis2. Overall, ~20 per cent of all hypothalamic neurons activated during PSR are now neurochemically identified.

CONCLUSIONS: Our study identifies new neuronal populations activated during PSR in AHA, ZI, and tuberal nucleus. We further provide evidence that Meis2 is expressed in novel populations of neurons activated during PSR. In summary, our results using male TRAP2-red mice characterize the cell populations activated during wakefulness and PSR, opening experimental paths for determining their function regarding vigilance states. Statement of Significance Wakefulness and paradoxical sleep are very similar at the electroencephalographic level. It remains relevant to determine the potential overlap of the neurons active during each vigilance state. We here took advantage of the powerful transgenic male TRAP2-red mice to directly compare in the same animal the brain cell activation during both states, with a focus on the hypothalamus. A deeper knowledge of each individual subpopulation of hypothalamic neurons within complex brain circuits underlying the sleep-waking cycle will help the understanding and validation of treatments of sleep disorders, at least those directly linked to demonstrated hypothalamic dysfunction such as narcolepsy (Orx neurons), amyotrophic lateral sclerosis (MCH and Orx signaling) or neurodegenerative diseases (Parkinson's and Alzheimer diseases).},
}

Animals
Male
Orexins/metabolism
*Neurons/physiology/metabolism
Mice
*Hypothalamus/physiology/cytology/metabolism
*Hypothalamic Hormones/metabolism/physiology
*Melanins/metabolism/physiology
*Wakefulness/physiology
*Pituitary Hormones/metabolism/physiology
*Sleep, REM/physiology
*Transcription Factors/metabolism/physiology
*Nerve Tissue Proteins/metabolism/physiology
*Homeodomain Proteins/metabolism/physiology
LIM-Homeodomain Proteins/metabolism
Proto-Oncogene Proteins c-fos/metabolism
Mice, Transgenic
Neuropeptides/physiology

@article {pmid42008451,
year = {2026},
author = {Pena, C and Sinar, MK and Koza, LA and Boehler, N and Buechler, E and Smith, AC and McGarr, A and Baybayon-Grandgeorge, AN and Herda, MS and Jaques, S and Linseman, DA},
title = {Preclinical study of red dragon fruit (Hylocereus polyrhizus) betacyanins in the G93A mutant hSOD1 mouse model of amyotrophic lateral sclerosis.},
journal = {Nutritional neuroscience},
volume = {},
number = {},
pages = {1-20},
doi = {10.1080/1028415X.2026.2661760},
pmid = {42008451},
issn = {1476-8305},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by loss of cortical and spinal motor neurons, oxidative stress, neuroinflammation, and mitochondrial dysfunction. Betacyanins, betalain pigments found in red dragon fruit and beetroot, display powerful anti-inflammatory and free-radical scavenging properties which may help ameliorate ALS pathology and slow disease progression. The present study characterized the therapeutic effects of a betacyanin-rich red dragon fruit extract (DFE) in the G93A mutant hSOD1 transgenic mouse model of ALS. Mice were treated orally with 5% (v/v) DFE in drinking water ad libitum, from disease onset until end-stage. DFE treatment had a statistically significant effect on survival, with an approximate 13-day extension of median lifespan in the treated G93A mutant hSOD1 group. Treatment with DFE also significantly preserved muscle strength and endurance, as assessed by grip strength and rotarod behavioral testing. This was associated with a modest but statistically significant preservation of gastrocnemius muscle weight in the DFE-treated group. Histopathological analyses demonstrated improvements in NMJ size and complexity, an increase in surviving spinal cord motor neurons, and a reduction in spinal cord astrogliosis in G93A mutant hSOD1 mice treated with DFE, when compared to their untreated mutant littermates. Overall, these findings indicate that DFE, or purified betacyanin compounds, should be investigated further as potential therapeutic agents for patients with SOD1-related ALS. Additional preclinical studies in non-SOD1 models of ALS will need to be completed to determine the potential benefit of betacyanin compounds in sporadic ALS.},
}

@article {pmid42008552,
year = {2026},
author = {Sidibe, DK and Smith, EM and Spivey, ML and Vogel, MC and Maday, S},
title = {Differential regulation of p62-ubiquitin conjugates in neurons versus astrocytes during cellular stress.},
journal = {PloS one},
volume = {21},
number = {4},
pages = {e0345890},
doi = {10.1371/journal.pone.0345890},
pmid = {42008552},
issn = {1932-6203},
mesh = {*Astrocytes/metabolism/cytology ; *Neurons/metabolism/cytology ; *Sequestosome-1 Protein/metabolism ; *Ubiquitin/metabolism ; Animals ; *Stress, Physiological ; Lysosomes/metabolism ; Humans ; Mice ; Autophagy ; Cells, Cultured ; },
abstract = {Sequestosome 1/p62 (hereafter referred to as p62) is a multifunctional protein that orchestrates various cellular stress response pathways including autophagy, proteasome-mediated degradation, antioxidant defense, nutrient sensing, and inflammatory signaling. Mutations in distinct functional domains of p62 are linked with the neurodegenerative disease amyotrophic lateral sclerosis (ALS), underscoring its importance in neural cells. Neurons and astrocytes, two key cell types in the brain, perform distinct roles in brain physiology and thus encounter a unique landscape of cellular stress. However, how p62 is regulated in these cell types in response to various stress modalities remains largely unexplored. Several functions for p62 depend on its engagement with ubiquitinated substrates. Thus, we investigated how the regulation of p62-ubiquitin conjugates differs between neurons and astrocytes exposed to two stress modalities: lysosomal membrane damage and metabolic stress. Lysosomal damage triggered ubiquitin-dependent assembly of p62 puncta in both neurons and astrocytes. In contrast, nutrient deprivation elicited different responses between neurons and astrocytes. Neurons formed p62-ubiquitin structures more prominently and displayed a greater dependence on ubiquitin for p62 clustering. Together, these findings reveal cell-type-specific and stress-specific regulation of p62-ubiquitin conjugates, indicating that neurons and astrocytes can deploy distinct quality control strategies.},
}

*Astrocytes/metabolism/cytology
*Neurons/metabolism/cytology
*Sequestosome-1 Protein/metabolism
*Ubiquitin/metabolism
Animals
*Stress, Physiological
Lysosomes/metabolism
Humans
Mice
Autophagy
Cells, Cultured

@article {pmid42008764,
year = {2026},
author = {Stone, AK and Veinot, TC},
title = {Access to Technology-Mediated Community Mental Health Care Among Low-Socioeconomic Status Consumers With Serious Mental Illness: Qualitative Study.},
journal = {JMIR formative research},
volume = {10},
number = {},
pages = {e79608},
doi = {10.2196/79608},
pmid = {42008764},
issn = {2561-326X},
mesh = {Humans ; *Mental Disorders/therapy/psychology ; *Health Services Accessibility/statistics & numerical data ; Qualitative Research ; Female ; Male ; Adult ; Middle Aged ; *Community Mental Health Services/statistics & numerical data/methods ; Telemedicine ; Social Class ; Poverty ; },
abstract = {BACKGROUND: Access to mental health care is critical for the effective management of serious mental illness (SMI), but consumers with low socioeconomic status (SES) have lower rates of service usage and worse retention in care. Digital technologies are often lauded as a way to bridge access gaps; however, little is known about how technology-mediated care may influence care access among low-SES consumers and how consumers use technology in care access.

OBJECTIVE: This study aimed to examine the applicability of Levesque et al's access framework to technology-mediated care for SMI and analyze how low-SES consumers use technology to facilitate care access. Furthermore, the study assesses whether and how technologies are involved in care access at multiple points within the process of accessing care.

METHODS: This study used 2 qualitative methods: ethnographic observations at a mental health treatment court and interviews with low-SES consumers with SMI using community mental health care (n=14) and key informant interviews with health and service providers working with this population (n=14). Observations occurred from July 2022 through September 2023, and interviews occurred between January 2022 and May 2024. Data analysis involved both inductive and deductive coding approaches. Data from both the interviews and observations were analyzed in NVivo and further triangulated through analytic memos.

RESULTS: Levesque et al's framework required several extensions to accommodate technology-mediated care related to SMI for low-SES consumers: (1) a cyclical rather than linear trajectory; (2) simultaneous care acquisition from multiple health and service providers; (3) staying in care long-term; (4) identification of both one-time and ongoing health needs; and (5) an emergency pathway for entering care. Consumers often faced challenges related to the varied digital requirements of each provider and a dearth of integrative, patient-facing tools like portals. Within this context, some consumers use mobile apps, communication, and telehealth technologies across various care access stages. Consumers used technology by figuring out how to navigate technology-mediated care, especially by leaning on others, such as case managers, for support. These others provided consumers with temporary technologies, showed them how to use technologies, and accompanied them through the process of using technology for accessing care.

CONCLUSIONS: This study highlights that accessing care is iterative and ongoing, involving multiple forms of co-occurring service provision. A theoretical contribution of this work is its extension of Levesque et al's care access framework to better reflect technology-mediated care for SMI among low-SES consumers. This work also underscores ongoing challenges for accessing technology-mediated care and the importance of human support in addressing access difficulties. Clinical implications include incorporating digital readiness assessments and providing comprehensive guidance on how consumers can effectively use technologies for care. Future work should investigate how technology-mediated care can make care access easier rather than harder.},
}

Humans
*Mental Disorders/therapy/psychology
*Health Services Accessibility/statistics & numerical data
Qualitative Research
Female
Male
Adult
Middle Aged
*Community Mental Health Services/statistics & numerical data/methods
Telemedicine
Social Class
Poverty

@article {pmid42009215,
year = {2026},
author = {Nassar, JE and Knebel, A and Ammar, LA and Singh, M and Kuris, EO and Diebo, BG and Daniels, AH},
title = {Differentiating Neurologic Disorders from Spinal Conditions: Evidenced-Based History and Physical Examination Clues for the Orthopedic Clinic.},
journal = {The American journal of medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.amjmed.2026.04.017},
pmid = {42009215},
issn = {1555-7162},
abstract = {This narrative review highlights neurologic disorders that mimic or worsen degenerative spine disease and provides key clinical clues for recognition in spine surgery practice. A focused review examined amyotrophic lateral sclerosis, normal pressure hydrocephalus, multiple sclerosis, Parkinson's disease, Guillain-Barré syndrome, peripheral neuropathies, and transverse myelitis. These conditions frequently overlap with structural spinal pathology through motor, sensory, and gait disturbances. Amyotrophic lateral sclerosis presents with combined upper and lower motor neuron signs. Normal pressure hydrocephalus is characterized by gait impairment, urinary incontinence, and cognitive decline. Multiple sclerosis often causes relapsing multifocal deficits that do not localize to a single spinal level. Parkinson's disease is identified by bradykinesia, rigidity, tremor, and progressive postural deformity. Other mimics including Guillain-Barré syndrome, small and large fiber neuropathies, and transverse myelitis further complicate evaluation. Careful history and neurologic examination remain central, while disease-specific tools such as the 2017 McDonald criteria and the Dubousset Functional Test improve recognition. Early identification is essential to avoid unnecessary surgery, guide multidisciplinary referral, improve risk stratification, and optimize patient outcomes.},
}

@article {pmid42011674,
year = {2026},
author = {Doyle, L and Galvin, M and Tague, AM and Meldrum, D and Murphy, D and Hardiman, O and Murray, D},
title = {Speech and swallow outcome measures for ALS and perspectives on remote monitoring: an international survey of speech & language therapists.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/21678421.2026.2655735},
pmid = {42011674},
issn = {2167-9223},
abstract = {OBJECTIVE: Dysarthria and dysphagia occur frequently in Amyotrophic Lateral Sclerosis (ALS). To manage these symptoms, speech & language therapists (SLTs) must identify relevant speech and swallow outcomes and select suitable outcome measurement instruments. Remote monitoring is an evolving mode of health status tracking. This survey aimed to establish SLT perspectives on ALS assessment regarding 1) the clinical meaningfulness of existing outcome measurement instruments 2) remote monitoring 3) usefulness of assessment devices for patient care and 4) bulbar function outcomes and measurement instruments useful for research studies.

METHODS: An online English-language survey was distributed internationally through gatekeepers and social media.

RESULTS: Sixty-six SLTs responded from 13 countries. Current outcome measurement instruments were regarded as clinically meaningful in ALS by 35% for speech and 41% for swallow. Only 12% had access to remote monitoring, but 77% would like to avail of it, with 58% perceiving its potential to enhance care. Eighty-two percent deemed remote monitoring using digital patient-reported outcome measures (PROMs) useful. Speech intelligibility measurement was selected as the most useful communication outcome for remote monitoring (92%) and research (94%). SLTs agreed that speech intelligibility test software (72%), smart device apps (70%) and tongue pressure measurement devices (54%) are useful assessment equipment.

CONCLUSIONS: SLTs want better measurement instruments for speech and swallow in ALS. They regarded technologies including remote monitoring incorporating digital PROMs as useful. Outcomes reflecting communication and swallow functional success level were deemed most useful. These survey findings can inform the selection of digital speech and swallow outcomes for ALS.},
}

@article {pmid42011986,
year = {2026},
author = {Palma, A and Stefanelli, R and Trenta, F and Projetti, C and Massa, G and Canterini, S and Fiorenza, MT},
title = {A Cross-Disease Microglial Transcriptional Program Characterizes Neurodegeneration and Highlights SPP1 as a Biomarker.},
journal = {Glia},
volume = {74},
number = {6},
pages = {e70163},
doi = {10.1002/glia.70163},
pmid = {42011986},
issn = {1098-1136},
support = {RM123188F700A7B2//Sapienza Università di Roma/ ; RG1221816B9646F5//Sapienza Università di Roma/ ; GSP20006_Covid050//Fondazione Telethon/ ; },
mesh = {*Microglia/metabolism/pathology ; Animals ; Humans ; Mice ; *Neurodegenerative Diseases/metabolism/genetics/pathology ; *Osteopontin/genetics/metabolism ; Biomarkers/metabolism ; Transcriptome ; Cells, Cultured ; },
abstract = {Microglial cells are key players in maintaining brain homeostasis and responding to pathological conditions. Their multifaceted roles in health and disease have garnered significant attention in the context of neurodegeneration. In recent years, single-cell transcriptomic techniques have provided unprecedented insights into microglial heterogeneity, revealing distinct subpopulations and gene expression patterns associated with neuroprotection or neurotoxicity. Here, we dissect the transcriptomic landscape of microglia by leveraging human single-nuclei RNA sequencing datasets from multiple neurodegenerative conditions, including Amyotrophic Lateral Sclerosis, frontotemporal dementia, Alzheimer's disease, aging, and Parkinson's disease. This integrative analysis identifies distinct microglial subpopulations, reflecting functional heterogeneity across diseases and reveals a shared cross-disease microglial transcriptional program associated with inflammatory and neurodegenerative processes. Using a machine learning framework, we further demonstrate that this transcriptional program enables robust discrimination between neurodegenerative and control samples. Experimental validation in primary microglia isolated from a mouse model of Niemann-Pick disease type C, also known as juvenile Alzheimer's disease, supports the conservation of key components of this program and highlights Spp1 as a biomarker of disease-associated microglia states. Overall, this study provides an improved portrait of microglia transcriptional remodeling across neurodegenerative disorders and offers a framework for identifying conserved molecular features that may inform therapeutic strategies aimed at modulating microglial activity to mitigate disease progression and foster neuroprotection.},
}

*Microglia/metabolism/pathology
Animals
Humans
Mice
*Neurodegenerative Diseases/metabolism/genetics/pathology
*Osteopontin/genetics/metabolism
Biomarkers/metabolism
Transcriptome
Cells, Cultured

@article {pmid42012311,
year = {2026},
author = {Erol, ZY and Quintanilla, C and Ozdinler, PH},
title = {Bringing cellular clarity to the cortical component of ALS with a high-density multi-electrode array system.},
journal = {The FEBS journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/febs.70552},
pmid = {42012311},
issn = {1742-4658},
support = {R01AG061708//NIH-NIA/ ; },
abstract = {There is selective vulnerability in diseases, requiring the understanding of cell-type specific aspects of neurodegeneration with cellular resolution. Single-cell electrophysiology enables direct investigation of neuronal excitability, ion-channel dynamics, and synaptic transmission with high temporal precision, which is crucial in understanding neuronal circuitries and how they are affected in diseases. Microelectrode arrays (MEAs) have emerged as powerful platforms enabling long-term, parallel, and non-invasive extracellular measurements. The advent of complementary-metal-oxide-semiconductor (CMOS)-based and high-density microelectrode arrays (HD-MEAs) has expanded the spatial and temporal resolution attainable both in vitro and ex vivo. Combined with acute slices, novel cell-culture approaches and three-dimensional (3D) brain organoids, these tools now expedite translational research in disease modeling, neurotoxicity, and pharmacology. Here, we summarise the significance of single-cell electrophysiology, the advantages of the MEA systems, and the latest biomedical and technological advances in this area of research.},
}

@article {pmid42013251,
year = {2026},
author = {Wu, ZC and Deng, LJ and Huang, TZ and Dou, HX and Vivone, G and Liu, Y},
title = {Tensor Wheel Decomposition: Theory and Application to Tensor Completion.},
journal = {IEEE transactions on image processing : a publication of the IEEE Signal Processing Society},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/TIP.2026.3684420},
pmid = {42013251},
issn = {1941-0042},
abstract = {Recently, tensor network (TN) decompositions have gained prominence in computer vision and contributed promising results to tensor recovery for their capability of compactly and efficiently representing high-order tensors. However, current TN topologies are rather being developed towards more intricate structures to pursue incremental improvements, resulting in a drastically increased number of TN ranks, which requires laborious hyper-parameter selection, especially for higher-order cases. In this paper, we propose a novel TN decomposition, dubbed tensor wheel (TW) decomposition, in which a high-order tensor is represented by a set of latent factors mapped into a specific wheel topology. Such a decomposition is constructed starting from analyzing the graph structure, aiming to more accurately characterize the complex interactions inside objectives while maintaining a lower hyper-parameter scale, theoretically alleviating the above deficiencies. The comprehensive analysis of the mathematical properties fully demonstrates that TW decomposition can be more potential in representation capabilities and more flexible in controlling both parameter storage and computational costs. To compute the TW-format decomposition, the sequential singular value decomposition (SVD)-based and the alternating least squares (ALS)-based learning algorithms are developed. Furthermore, to investigate the validity of TW decomposition, we provide its one numerical application, i.e., tensor completion (TC), yet develop an efficient proximal alternating minimization-based solving algorithm with guaranteed convergence. Experimental results on both synthetic and real-world data reveal that TW decomposition significantly outperforms other state-of-the-art tensor decompositions for incomplete-tensor inference, especially under solely few observations, thus substantiating the superiority and reliability of TW decomposition.},
}

@article {pmid42013353,
year = {2026},
author = {Szabo, A},
title = {When treatment becomes the problem: A qualitative analysis of addiction components in rhinitis medicamentosa.},
journal = {Journal of behavioral addictions},
volume = {},
number = {},
pages = {},
doi = {10.1556/2006.2025.00461},
pmid = {42013353},
issn = {2063-5303},
abstract = {Prolonged use of topical nasal decongestants such as xylometazoline or oxymetazoline can lead to rhinitis medicamentosa (RM). This medication-induced condition is characterized by rebound congestion and compulsive reuse. A debated question is whether RM signifies physiological dependence, addiction, or simply a habit. This commentary aimed to evaluate Lakatos et al.'s (2025) work, which investigated this issue through qualitative interviews with 20 affected individuals. Using directed content analysis based on Griffiths' (2005) components model of addiction, Lakatos et al., identified all six elements (salience, mood modification, tolerance, withdrawal, conflict, and relapse) in patient histories. Lakatos et al. (2025) performed a timely and conceptually sophisticated study that connects addiction theory to a common otorhinolaryngological condition. Their qualitative approach captures the everyday lived experience of patients with RM with robust ecological validity and clinical relevance. However, the theory-driven analysis risks confirmation bias by fitting data to Griffiths' addiction model, and the small, convenience-based sample limits generalizability. Despite these constraints, the paper offers valuable insight into how negative reinforcement and conditioned anxiety sustain compulsive nasal spray use. Overall, it successfully bridges clinical observation and theoretical debate, advancing understanding of iatrogenic dependence within everyday medical practice.},
}

@article {pmid42013406,
year = {2026},
author = {Weemering, DN and van Unnik, JWJ and Genge, A and van den Berg, LH and van Eijk, RPA},
title = {Heterogeneity in the Analysis of the ALSFRS-R in ALS Clinical Trials and its Effect on the Validity and Precision of Trial Conclusions.},
journal = {Neurology},
volume = {106},
number = {9},
pages = {e214937},
doi = {10.1212/WNL.0000000000214937},
pmid = {42013406},
issn = {1526-632X},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/drug therapy/therapy ; *Randomized Controlled Trials as Topic/standards ; Reproducibility of Results ; *Disability Evaluation ; Severity of Illness Index ; },
abstract = {BACKGROUND AND OBJECTIVES: Disability rating scales play a pivotal role in clinical trials, but there is a notable lack of guidance on how to analyze these scales. Using amyotrophic lateral sclerosis as a case study, our aim was to explore how disability rating scales have been analyzed in completed clinical trials and to assess how these different approaches influence both the risk of false-positive findings and the statistical power to detect true treatment effects.

METHODS: We searched PubMed and Embase to systematically identify randomized, placebo-controlled clinical trials using the revised ALS functional rating scale (ALSFRS-R) as primary end point, with ≥20 randomly assigned patients and ≥12-weeks of follow-up. Data were extracted on the statistical analysis approaches and strategies for handling missing data. Variability in statistical methods was mapped to the various research questions that the trials aimed to address. A simulation study assessed how each statistical method influenced validity (false-positive rate) and precision (statistical power), using the Ceftriaxone trial data set to model a realistic trial scenario.

RESULTS: Our analysis included 45 randomized clinical trials, comprising a total sample size of 7,338 patients, and identified 39 distinct statistical methods using a mixture of longitudinal and cross-sectional techniques. Most trials (55.6%) did not use all available (longitudinal) ALSFRS-R measurements, resulting in suboptimal utilization of patient data and reduced statistical precision. Applying the different statistical methods to the same trial data set resulted in large differences in the estimated treatment effect size, ranging from a negative 1.33 to a positive 2.33 SD difference. Among the methods used, 38.9% (95% CI 24.8%-55.1%) were at risk of increasing false-positive rates, potentially contributing to the erroneous advancement of ineffective treatments. Statistical power of valid strategies varied widely, ranging from 17.9% to 78.2%.

DISCUSSION: Our results demonstrate considerable variability in statistical methods, with the choice of method able to influence the estimated treatment effects, potentially resulting in misleading conclusions and uncertainty about treatment effects. This limits the interpretability and comparability of clinical trials and influences clinical decision-making and drug development. Establishing statistical consensus recommendations could improve the utility of disability scales in clinical trials and accelerate progress toward effective therapies for neurodegenerative diseases.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/drug therapy/therapy
*Randomized Controlled Trials as Topic/standards
Reproducibility of Results
*Disability Evaluation
Severity of Illness Index

@article {pmid42013408,
year = {2026},
author = {de Carvalho, M},
title = {The Cat is Out of the Bag: Confronting False-Positive Risks in Amyotrophic Lateral Sclerosis Clinical Trials.},
journal = {Neurology},
volume = {106},
number = {9},
pages = {e218029},
doi = {10.1212/WNL.0000000000218029},
pmid = {42013408},
issn = {1526-632X},
}

@article {pmid42013466,
year = {2026},
author = {Darke, A and Orsulak, C},
title = {How effective does a new drug for Amyotrophic Lateral Sclerosis need to be - the patient perspective: a letter in response to "Estimating the minimum important difference in the ALSFRS-R-instrument in people living with MND" published in vol. 26, pp. 249-258.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {27},
number = {3-4},
pages = {485-486},
doi = {10.1080/21678421.2025.2589781},
pmid = {42013466},
issn = {2167-9223},
}

@article {pmid42013476,
year = {2026},
author = {El-Agamy, SE and Mattedi, F and Fratta, P},
title = {Cryptic Splicing in ALS: From Driving Disease Progression to Unlocking Novel Therapeutics.},
journal = {Annual review of genomics and human genetics},
volume = {},
number = {},
pages = {},
doi = {10.1146/annurev-genom-022024-011307},
pmid = {42013476},
issn = {1545-293X},
abstract = {TDP-43 is an RNA-binding protein that regulates multiple aspects of RNA processing, and its mislocalization from the nucleus to the cytoplasm is a defining feature of amyotrophic lateral sclerosis (ALS). While both loss- and gain-of-function mechanisms contribute to disease, the discovery of cryptic splicing has shed light on the downstream consequences of TDP-43 nuclear clearance for neuronal health. Here, we highlight how loss of nuclear TDP-43 can drive a cascade of events that lead to the impairment of cellular proteostasis and result in a positive feedback loop that perpetuates neuronal dysfunction. This sustains the appearance of cryptic splicing events in genes that are involved in key pathways for the maintenance of axonal homeostasis and synaptic transmission. In contrast to their detrimental effects on neuronal health, cryptic splicing mechanisms may be harnessed to develop novel therapeutic strategies, unprecedentedly expanding the availability of therapeutic avenues for TDP-43 proteinopathies.},
}

@article {pmid42013513,
year = {2026},
author = {Saldanha-Castro, P and Vyas, MV and Jain, D and Santos-Neto, D and Mirian, A and , and Zinman, L and Abrahao, A},
title = {Association between statin use and survival in patients with ALS: A propensity score-matched analysis.},
journal = {Journal of the neurological sciences},
volume = {486},
number = {},
pages = {125916},
doi = {10.1016/j.jns.2026.125916},
pmid = {42013513},
issn = {1878-5883},
abstract = {OBJECTIVE: To evaluate the association between statin use, disease progression, and survival in patients with amyotrophic lateral sclerosis (ALS) using data from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database.

METHODS: We conducted a retrospective cohort study of adults (≥18 years) diagnosed with ALS and included in the PRO-ACT database. Statin exposure was defined as any statin use at cohort entry. Statin users were matched 1:1 to non-users using propensity score matching based on age, baseline ALS Functional Rating Scale (ALSFRS), disease duration, ethnicity, bulbar onset, riluzole use, and cardiovascular or metabolic comorbidities. Participants were followed from cohort entry or statin initiation until death, end of follow-up (36 months), or loss to follow-up. The primary outcome was all-cause mortality at three years. The secondary outcome was disease progression, defined as time to a four-point decline in ALSFRS score. Cox proportional hazards models were used to estimate hazard ratios (HRs).

RESULTS: Among 3439 eligible participants, 131 statin users (mean age 63.1 years; 34% female) were identified and matched to 131 non-users. Statin use was not associated with all-cause mortality at three years (HR 0.97; 95% CI 0.66-1.44; P = 0.89). Disease progression was also similar between statin users and non-users (HR 1.02; 95% CI 0.80-1.31; P = 0.90).

CONCLUSIONS: In this large observational cohort, statin use was not associated with survival or disease progression in ALS. These findings do not support statin initiation or discontinuation based solely on ALS diagnosis or disease course.},
}

@article {pmid42013739,
year = {2026},
author = {Mirveis, Z and Patil, N and Byrne, HJ},
title = {Evaluating data-mining strategies for label-free Raman microspectroscopic analysis of cellular processes in vitro: dynamic dimensionality reduction.},
journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy},
volume = {359},
number = {},
pages = {127923},
doi = {10.1016/j.saa.2026.127923},
pmid = {42013739},
issn = {1873-3557},
abstract = {Understanding dynamic intracellular metabolism is essential for elucidating cellular function and disease mechanisms. However, analysing time-resolved spectral data is challenging due to overlapping signals, high dimensionality, and biological variability. This study evaluates the applicability of Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) for resolving complex cellular spectral data and introduces a framework that integrates Principal Component Analysis (PCA) of sequential time points as a preprocessing step. PCA was used to extract dominant spectral variance associated with biological kinetics (PC1), and MCR-ALS was subsequently applied to the sequential PC1 loadings to enhance the recovery of kinetic trends. To validate the approach, simulated Raman datasets were generated by combining predefined component spectra with known kinetic profiles, representing sequential (glycolysis-like) and parallel (glycolysis + glutaminolysis) models. These signals were superimposed onto real cellular spectra ("Sim-Cell" data) to include intercellular variability and background interference. Standard MCR-ALS was first assessed to determine the optimal number of components and, when applied to cell-free datasets, resolved up to three components. It was then applied to Sim-Cell datasets to evaluate performance under simulated biological conditions. MCR-ALS resolved the sequential model up to a cellular background weight of 2 but failed for the parallel model, highlighting limitations in complex, overlapping systems. In contrast, PCA-MCR-ALS substantially improved performance under strong cellular background, maintaining accurate resolution up to weight = 5 for sequential and weight = 8 for parallel models. Overall, this study benchmarks chemometric performance in label-free Raman microspectroscopy and highlights PCA-assisted MCR-ALS for analysing time-resolved intracellular spectral data.},
}

@article {pmid42013766,
year = {2026},
author = {Kravitz, D and Saker, TS and Odess, N and Drory, VE and Abraham, A},
title = {Quantitative sonographic assessment of relaxed and contracted muscle thickness predicts survival in ALS.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {187},
number = {},
pages = {2111845},
doi = {10.1016/j.clinph.2026.2111845},
pmid = {42013766},
issn = {1872-8952},
abstract = {OBJECTIVES: To explore the ability of quantitative sonographic assessment of muscle thickness to predict mortality in amyotrophic lateral sclerosis (ALS) patients compared with manual muscle testing (MMT) and the ALS functional rating scale-revised (ALSFRS-R).

METHODS: 86 prospectively recruited ALS patients underwent clinical assessment and quantitative sonographic assessment of muscle thickness in 8 relaxed and 4 contracted limb muscles. Average monthly decline rates of MMT and ALSFRS-R scores and measured relaxed and contracted muscle thickness were calculated at study entry. The area under the curve (AUC), optimal cutoff points, and hazard ratio (HR) for 1 to 3-year mortality were calculated and adjusted for covariates.

RESULTS: Significant increased 1-year mortality was associated only with lower contracted muscle thickness (HR-8.1), while increased 3-year mortality was in greater correlation with a reduced contracted muscle thickness (HR-4.85) than with a decline in MMT (HR-3.31) and ALSFRS-R (HR-2.12) or a reduced relaxed muscle thickness (HR-2.65).

CONCLUSION: Reduced limb muscle thickness, especially in a contracted state, is associated with significantly increased mortality in ALS.

SIGNIFICANCE: Sonographic muscle measurement is a novel estimator of ALS mortality and has the potential to serve as an additional biomarker in future multi-variable prognostication models, clinical decision making and research.},
}

@article {pmid42013845,
year = {2026},
author = {Xu, Y and He, J and Wang, S and Ge, Y and Jia, Y and Guo, W and Lv, C and Yao, X and Mao, Y and Mei, F and Fan, D and Yuan, P and Lu, B},
title = {BDNF insufficiency exacerbates ALS progression.},
journal = {Cell reports. Medicine},
volume = {},
number = {},
pages = {102758},
doi = {10.1016/j.xcrm.2026.102758},
pmid = {42013845},
issn = {2666-3791},
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with progressive loss of motor neurons. Insufficiency of neurotrophic factors is suspected to underlie the disease, but direct evidence remains scarce. In this study, we discover that brain-derived neurotrophic factor (BDNF) val/met mutation, which results in a decrease in BDNF secretion, reduces survival time of ALS patients in two separate cohorts. Using a knockin mouse model of the ALS causal gene FUS[R521C], we demonstrate that BDNF haploinsufficiency leads to shortened lifespan, accelerated motor dysfunctions, and exacerbated motor neuron death. Importantly, activation of the BDNF receptor TrkB by an agonistic antibody effectively rescues these ALS-associated phenotypes. In additional ALS mouse models, TrkB activation antibody also shows superior therapeutic effects compared to current ALS medication riluzole. Our data indicate that insufficient BDNF could be a crucial contributing factor for ALS progression, and activation of BDNF-TrkB pathway may represent a promising therapeutic strategy against ALS.},
}

@article {pmid42014727,
year = {2026},
author = {Guo, X and Hu, J and Kanwal, S and Yuan, J and Tariq, M and Zheng, J and Sun, M and Lu, Y and Wang, J and Jiang, M and Wang, A and Castells-Garcia, A and Zheng, X and Peng, B and Wang, D and Wei, X and Yang, T and Volpe, G and Wu, L and Mazid, MA and Li, W and Lai, Y and Qin, D and Aguilo, F and Zhou, Y and Liu, C and Cosma, MP and Xu, X and Lundberg, E and Mulder, J and Hutchins, AP and Maxwell, PH and Di Croce, L and Zhang, X and Esteban, MA and Lv, Y},
title = {A framework for the exploration of subcellular compartmentalization of RNA-binding proteins.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-71511-y},
pmid = {42014727},
issn = {2041-1723},
abstract = {The ability of RNA-binding proteins to form complexes with other biomolecules underpins a broad range of structural properties and functions. Understanding the subcellular distribution of RNA-binding proteins and their interacting partners in the steady state and upon perturbation can therefore shed light on these aspects. Here, we present the compartmentalized RNA-Binding Protein (or coRBP) map, an experimental resource and analytical pipeline to study subcellular RNA-binding proteins through multimodal dataset integration and machine learning. Using this approach, we generate a dataset of 1,768 known and putative RNA-binding proteins distributed in a broad panel of subcellular compartments and delineate their intermolecular and intercompartmental relationships. We also establish a hierarchy of RNA-binding protein-containing complexes at multiple scales across the cell, which suggests additional functions for multiple RNA-binding proteins. Furthermore, we investigate changes in RNA-binding protein complex composition and subcellular distribution in response to C9ORF72-associated amyotrophic lateral sclerosis/frontotemporal dementia dipeptide repeats and DNA damage stress. The coRBP map provides a resource to study the roles of RNA-binding proteins in homeostasis and disease.},
}

@article {pmid42014913,
year = {2026},
author = {Cai, F and Xu, D and Yang, D and Huang, F and Song, X and Jiang, Q and Wan, S and Zhao, Y and Zhou, J},
title = {Correction: Multidimensional predictors of fatigue in amyotrophic lateral sclerosis: a cross-sectional study in China.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
doi = {10.1038/s41598-026-49397-z},
pmid = {42014913},
issn = {2045-2322},
}

@article {pmid42002556,
year = {2026},
author = {Selvam, AK and Loganathan, A},
title = {An intelligent EEG-based ensemble framework for communication assistance in Locked-In Syndrome patients.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-47041-4},
pmid = {42002556},
issn = {2045-2322},
}

@article {pmid42003855,
year = {2026},
author = {Casey, M and Coghlan, D and Carroll, Á and Buckley, T and Stokes, D},
title = {Assessing Quality of Action Research Using the Quality Assessment Action Research Checklist (QuARC): A Hybrid Systematic Narrative Review.},
journal = {Journal of advanced nursing},
volume = {},
number = {},
pages = {},
doi = {10.1111/jan.70607},
pmid = {42003855},
issn = {1365-2648},
abstract = {AIM: To evaluate the quality of action research studies using the Quality Assessment Action Research Checklist (QuARC) and to assess its utility as a tool for quality appraisal.

DESIGN: A hybrid systematic narrative review following Turnbull et al.'s six-stage methodology and reported in accordance with PRISMA 2020 guidance.

DATA SOURCES: Scopus was searched for author self-identified action research studies published between January 2020 and March 2024.

REVIEW METHODS: Two reviewers independently selected studies meeting inclusion criteria: health science action research papers addressing any or all of QuARC's four quality factors. A scoring system was used to capture each of QuARC's 17 quality items, which was scored as 0 (absent), 0.5 (partial) or 1 (comprehensive). Narrative synthesis was undertaken across the four QuARC domains.

RESULTS: Thirty-two studies met the inclusion criteria. Reporting frequencies across QuARC were: Context (92.5%, mean = 3.7/4), Quality of Relationships (55% mean = 2.2/4), Quality of Action Research Process (62.5% mean = 2.5/4), and Quality of Outcomes (62.5% mean = 3.1/5). Reporting gaps were most evident in reflexive co-analysis, relational evaluation and explicit theoretical contribution.

CONCLUSION: Global reporting of rigour and quality in action research remains inconsistent. QuARC functioned both as an appraisal instrument and as an analytic lens, revealing systematic patterns in how action research privileges practical change over theoretical articulation and reflexive relational work. Further refinement and validation are recommended to strengthen its reliability as an appraisal tool.

IMPLICATIONS: Findings highlighted a critical need to establish a standardised, validated approach to assess quality in action research. Adoption of QuARC can enhance consistency, clarity and comparability across studies, strengthening the evidence base for action research methodologies.

IMPACT: This first systematic synthesis of QuARC's application provides an evidence base for its further development. This lays foundations for international standards in quality appraisal, strengthening the credibility, reproducibility and influence of action research.},
}

@article {pmid42004396,
year = {2026},
author = {Kallavus, K and Laisaar, T and Laisaar, KT},
title = {Lung cancer screening knowledge, opinions and attitudes among healthcare professionals in Estonia prior to national program initiation.},
journal = {Journal of public health research},
volume = {15},
number = {2},
pages = {22799036261439973},
pmid = {42004396},
issn = {2279-9028},
abstract = {BACKGROUND: This study aimed to gain insight into the opinions and attitudes about, and potential barriers and facilitators to lung cancer screening (LCS) among healthcare professionals in Estonia. It also aimed to determine knowledge gaps that could be addressed when planning next steps toward a national LCS program.

METHODS: A cross-sectional, web-based survey was conducted in June to August 2023 among primary care providers (PCPs), pulmonologists, radiologists, oncologists, and thoracic surgeons in Estonia. Differences between PCPs and other specialists were analyzed with regard to their knowledge, beliefs and attitudes toward LCS.

RESULTS: About 146 healthcare professionals responded, 57% were family physicians. Less than half of all respondents considered existing evidence or international recommendations sufficient to support national LCS implementation, with uncertainty higher among PCPs. Adjusted analyses revealed that the PCPs had substantially higher odds of responding "Do not know" concerning international recommendations (aOR 5.06; 95% CI 1.97-13.85), and were far less likely to agree to assigning main responsibility for LCS participation to family physicians (aOR 0.10; 95% CI 0.02-0.40). PCPs also demonstrated greater uncertainty about the costs and labor intensity in LCS.

CONCLUSION: This study reveals substantial variation in LCS knowledge, attitudes, and certainty across healthcare profession(al)s, highlighting the need for targeted training. Although for most professionals the benefits of LCS outweigh potential harms, structural constraints and uncertainty should still be carefully considered. Despite limited generalizability, study findings support evidence-informed planning and have already been considered in the Estonian LCS pilot study, the first step toward a national LCS program.},
}

@article {pmid42006515,
year = {2026},
author = {Cheung, N},
title = {Synaptic Plasticity Fragility Underlies a Microglial Pruning Continuum in Major Depressive Disorder and Amyotrophic Lateral Sclerosis.},
journal = {Cureus},
volume = {18},
number = {4},
pages = {e107259},
pmid = {42006515},
issn = {2168-8184},
abstract = {Background Major depressive disorder (MDD) and amyotrophic lateral sclerosis (ALS) are clinically distinct yet show intriguing comorbidity, often early in the disease course. We hypothesized a shared microglia-mediated synaptic pruning vulnerability, amplified differently by disorder-specific pathways, autophagy collapse in ALS versus RNA processing and immune dysregulation in MDD, thereby creating a biological continuum. Methods Using large-scale genome-wide association study (GWAS) from the Psychiatric Genomics Consortium (PGC) (MDD, N=829,249) and Project MinE (ALS, effective N=87,381), we applied Multi-marker Analysis of GenoMic Annotation (MAGMA) for gene- and set-level associations, Gene Set Enrichment Analysis (GSEA)/Differential Gene Set Enrichment Analysis (DGSEA) for pathway enrichment and differential enrichment, S-PrediXcan transcriptome-wide association study (TWAS) across 14 GTEx tissues, and linkage disequilibrium score regression (LDSC) for partitioned heritability and cross-trait genetic correlation. Eight gene sets (housekeeping controls, monoaminergic, neurosteroid, glutamatergic, synaptic pruning, autophagy/protein quality, RNA processing, and immune/neuroinflammation) were tested for convergence and divergence. Results Synaptic pruning emerged as the sole consistent cross-disorder signal, with robust enrichment in MDD (LDSC 1.32×, GSEA NES=1.415, p=0.0001) and nominal but consistent signals in ALS (GSEA NES=1.40, p=0.011; TWAS HLA-B). Autophagy dominated ALS (LDSC 2.20×, TWAS C9orf72 Z=13.43, GSEA NES=1.94) but was depleted in MDD. RNA processing and immune pathways were prominent in MDD (LDSC 1.48× and 1.89×, respectively), with only nominal signals in ALS. Overall genetic correlation was near zero (rg=-0.044, p=0.196). Conclusions These findings support a microglial pruning continuum model: shared pruning liability as the foundation, with autophagy failure driving ALS neurodegeneration and RNA/immune dysregulation shaping MDD stress sensitivity. The low rg explains the modest overlap, while pathway specificity accounts for comorbidity and divergent progression. This framework offers testable predictions for polygenic risk score (PRS) stratification, complement modulators in ALS mood subsets, and microglial therapies in treatment-resistant MDD.},
}

@article {pmid42006781,
year = {2026},
author = {Raikes, AC and Garza, M and Murrell, AN and Brinton, RD},
title = {Meta analysis of glucose metabolism across Alzheimer's, Parkinson's and ALS Reveals emergence of adaptive brain glucometabolic responses and associated neurological functional profiles.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.04.07.26350339},
pmid = {42006781},
abstract = {IMPORTANCE: Glucose metabolic dysregulation in brain is a common feature of late-onset age-associated neurodegenerative disease (A [2] ND). Prior meta-analyses have identified disease-specific effects compared to healthy, unimpaired individuals. Yet, a unifying A [2] ND glucose dysregulation spatial signature remains undescribed.

OBJECTIVE: To determine the common signature of dysregulated glucose metabolism on FDG-PET using activation likelihood estimation (ALE) meta-analyses across A [2] ND.

DATA SOURCES: Searches were conducted using MEDLINE, Embase, PsycINFO, Scopus, and Cochrane from inception through July 2025. The search terms included controlled vocabulary and keywords for four neurodegenerative diseases Parkinson Disease, Amyotrophic Lateral Sclerosis, Alzheimer Disease, and Multiple Sclerosis, Fluorodeoxyglucose F18, glucose, and positron-emission tomography (PET).

STUDY SELECTION: Studies comparing adults with late-onset neurodegenerative diseases to non-diseased controls using FDG-PET to quantify brain glucose uptake and reporting whole-brain coordinate findings in either Talairach or Montreal Neurological Institute space were included.

DATA EXTRACTION AND SYNTHESIS: Three researchers, assisted by an AI screening tool, screened 7275 potential titles and abstracts for inclusion. Full texts were then retrieved for potentially relevant articles and were evaluated by three researchers using prespecified inclusion/exclusion criteria.

MAIN OUTCOMES AND MEASURES: Cluster peak and subpeak coordinates, cluster-wise t-or Z-values, and annotations indicating the disease of interest, whether the outcome was for hyper-(disease group > control) or hypometabolism (disease group < control), were extracted from included texts and analyzed using ALE.

RESULTS: A total of 130 FDG-PET studies were included in the meta-analysis, with a combined sample of 5298 individuals with A [2] ND and 3499 controls. Meta-analyses revealed dysregulated glucose metabolism as a unifying feature across A [2] ND which included both hypo-and hypermetabolic patterns. Neuroanatomical metabolic pattern was unique and disease specific. Each A [2] ND metabolic phenotype was associated with unique and complex patterns of neurological functionalities.

CONCLUSIONS AND RELEVANCE: These data demonstrate dysregulated glucose metabolism as a common A [2] ND feature, suggesting responsive remodeling of neural bioenergetics. While hypometabolism is a common research focus, due to functional relevance, hypermetabolism may reflect a compensatory, maladaptive, or neuroinflammatory signal, that requires focused investigation. A [2] ND prevention and treatment efficacy may depend on addressing bidirectional metabolic dysregulation in addition to disease-specific drivers of pathology.},
}

@article {pmid42007068,
year = {2026},
author = {Li, Z and Catelli, E and Stergar, J and Milanič, M and Sáez-Hernández, R and Prati, S and Oliveri, P and Sciutto, G},
title = {Expanding the Capabilities of Portable Mapping in Macroscopic External Reflection FT-IR through a Targeted Data-Driven Spectral Enhancement and Denoising Strategy.},
journal = {ACS measurement science au},
volume = {6},
number = {2},
pages = {361-373},
pmid = {42007068},
issn = {2694-250X},
abstract = {Reliable spectral quality is essential for extracting meaningful information from infrared reflectance data, particularly when using portable systems with limited scan numbers. This study presents a data-driven spectral enhancement workflow designed to improve the interpretability of portable macroscopic external reflection Fourier Transform Infrared (MA-rFT-IR) mapping systems developed by the Authors, operating in the near- and mid-infrared (NIR-MIR) ranges. Despite the growing use of reflectance imaging spectroscopy, limited attention has been devoted to the development of robust denoising strategies capable of minimizing noise and unwanted variability while preserving spectral quality and enabling more reliable and accurate data analysis. This study proposes a broadly applicable processing framework aimed at enhancing the efficiency and performance of reflectance-based spectral analysis. Denoising methods including Savitzky-Golay filtering and wavelet- and PCA-based denoising were tested and evaluated individually and in combination. Quantitative performance was assessed using arccosine similarity (ACOS) and derivative-based root-mean-square error (dRMSE) metrics across selected spectral regions of interest, with a derivative ACOS (dACOS) index applied to monitor band-shape variations. The evaluation results were integrated through Pareto analysis to identify the optimal trade-off between noise reduction and spectral-feature preservation. Application of the proposed approach to a multilayered painting mock-up demonstrated that the enhancing spectral data workflow preserves key diagnostic features revealing subtle spectral bands. Furthermore, applying multivariate curve resolution-alternating least-squares (MCR-ALS) to the denoised data enabled chemically meaningful separation of complex overlapping signals, improving the interpretability of compositional information compared with traditional denoising methods and data processing. The workflow strengthens the analytical reliability of low-scan reflection-mode data and provides a transferable framework for optimizing denoising strategies in portable infrared applications.},
}

@article {pmid41513843,
year = {2026},
author = {Keritam, O and Kleinveld, VE and Klotz, S and Caliskan, H and Mayerhofer, M and Sener, M and Jäger, F and Weng, R and Bormann, D and Pugna, I and Gebert, J and Fedak, I and Renner, A and Antoniewicz, L and Rath, J and Zulehner, G and Krenn, M and Zimprich, F and Löscher, WN and Cetin, H},
title = {Demographic, clinical and genetic characteristics of patients with amyotrophic lateral sclerosis from two specialised centres in Austria.},
journal = {Journal of neurology},
volume = {273},
number = {1},
pages = {74},
pmid = {41513843},
issn = {1432-1459},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/epidemiology/physiopathology/diagnosis ; Austria/epidemiology ; Female ; Male ; Middle Aged ; Retrospective Studies ; Aged ; Adult ; Registries ; C9orf72 Protein/genetics ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterised by progressive muscle weakness and ultimately death from respiratory failure. Heterogeneity in disease trajectories and outcomes among patients with ALS (pwALS) is influenced by healthcare access, rehabilitation, and palliative care, but real-world data on demographic and clinical characteristics remain scarce in many countries, including Austria.

OBJECTIVES: To characterise the demographic, clinical, and genetic landscape of pwALS in Austria.

METHODS: In this retrospective cohort study, we included pwALS diagnosed according to the Gold Coast criteria and treated at two large tertiary referral centres. Demographic, clinical, and genetic data were extracted from the local ALS registries, and survival was determined via linkage with Statistik Austria, censored in December 2023.

RESULTS: A total of 341 patients with motor neuron disease were included (44.9% female), of whom 5% were diagnosed with primary lateral sclerosis and 2.9% with progressive muscular atrophy. Among pwALS (n = 314), spinal onset was most common (67.2%), followed by bulbar onset (29.6%) and respiratory onset (2.5%). Median survival from symptom onset was 36.0 months (IQR 20.0-74.0), with age at onset (HR 1.04, 95% CI 1.02-1.05; p < 0.0001), diagnostic delay (HR 0.97, 95% CI 0.96-0.98; p < 0.0001), and PEG tube placement (HR 0.72, 95% CI 0.50-1.00; p = 0.0478) as the only independent predictors of survival. (Likely) pathogenic variants were identified in 5.5% of patients, including two in SOD1 and one each in C9orf72, OPTN, TARDBP, and FUS.

CONCLUSIONS: This study provides the first comprehensive description of the demographic, clinical, and genetic characteristics of pwALS in Austria, offering valuable real-world insight into disease presentation and genetic diversity.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/epidemiology/physiopathology/diagnosis
Austria/epidemiology
Female
Male
Middle Aged
Retrospective Studies
Aged
Adult
Registries
C9orf72 Protein/genetics

@article {pmid41513898,
year = {2026},
author = {Roos, AK and Forsberg, S and Stenvall, E and Andersen, PM and Zetterström, P and Nordin, A and Forsberg, KME},
title = {Heterogeneous phenotype and cardiovascular comorbidities in Swedish patients with spinobulbar muscular atrophy.},
journal = {Journal of neurology},
volume = {273},
number = {1},
pages = {75},
pmid = {41513898},
issn = {1432-1459},
support = {FO 2022-0309//Hjärnfonden/ ; FO2023-0088//Hjärnfonden/ ; 2012-3167//Vetenskapsrådet/ ; 2017-03100//Vetenskapsrådet/ ; . JLL-980693//Region Jämtland Härjedalen/ ; 2012.0091//Knut och Alice Wallenbergs Stiftelse/ ; 2014.0305//Knut och Alice Wallenbergs Stiftelse/ ; 2020.0232//Knut och Alice Wallenbergs Stiftelse/ ; F2021-0044//Neuroförbundet/ ; 2023.10//Ulla-Carin Lindquists stiftelse för ALS-forskning/ ; 2023.16//Ulla-Carin Lindquists stiftelse för ALS-forskning/ ; RV-993493//Västerbotten Läns Landsting/ ; RV-996140//Västerbotten Läns Landsting/ ; RV-939329//Västerbotten Läns Landsting/ ; RV56103-7002829//Västerbotten Läns Landsting/ ; RV-1014212//Västerbotten Läns Landsting/ ; RV-996234//Västerbotten Läns Landsting/ ; RV-941598//Västerbotten Läns Landsting/ ; },
mesh = {Humans ; Male ; Sweden/epidemiology ; Middle Aged ; Female ; Aged ; Comorbidity ; *Cardiovascular Diseases/epidemiology/genetics ; Adult ; Phenotype ; Cohort Studies ; Receptors, Androgen/genetics ; Bulbo-Spinal Atrophy, X-Linked/epidemiology ; },
abstract = {BACKGROUND: Spinobulbar muscular atrophy (SBMA) is an X-linked neuromuscular disorder characterized by adult-onset progressive muscle atrophy, flaccid paresis, and bulbar palsy. In addition, increasing evidence indicates that SBMA is a multisystem disorder with prominent non-motor symptoms, such as sensory neuropathy, androgen insensitivity, and glucose intolerance. This study aimed to further characterize the clinical manifestations and biomarker profile in a large Swedish SBMA cohort.

METHODS: 49 genetically confirmed SBMA patients were identified from a motor neuron disease database at Umeå University Hospital, Sweden. CAG repeat length in the androgen receptor (AR) gene was assessed by RP-PCR. Blood samples were analyzed for cardiovascular and muscle biomarkers. Clinical data were collected from medical records and interviews, with autopsy findings reviewed in two cases.

RESULTS: The mean CAG repeat length was 43.1, with a mean age at motor symptom onset of 58.6 years. Notably, 19% of patients initially presented with sensory symptoms. High prevalence of hypertonia (70%), diabetes mellitus (39%), and cardiac disease (38%) was observed. Elevated troponin levels were common, and pNfL (neurofilament light chain in plasma) was elevated in seven patients, likely reflecting combined cerebrovascular and cardiovascular comorbidity. Importantly, two of these seven patients exhibited rapid disease progression, and a concomitant diagnosis of ALS was confirmed histopathologically.

DISCUSSION: This cohort was characterized by a relatively low number of AR gene CAG repeats and a late onset of motor symptoms. Sensory symptoms frequently occurred before motor decline. Cardiovascular disease and diabetes were common comorbidities and, in some cases, preceded neurological symptoms. These findings underscore the need for improved clinical awareness of the heterogeneous presentation of SBMA and support routine cardiovascular monitoring to reduce diagnostic delays and prevent early mortality.},
}

Humans
Male
Sweden/epidemiology
Middle Aged
Female
Aged
Comorbidity
*Cardiovascular Diseases/epidemiology/genetics
Adult
Phenotype
Cohort Studies
Receptors, Androgen/genetics
Bulbo-Spinal Atrophy, X-Linked/epidemiology

@article {pmid41515048,
year = {2025},
author = {Ramírez-May, AG and Rivera-Cruz, MDC and Mendoza-López, MR and Acosta-Pech, RG and Trujillo-Narcía, A and Bautista-Muñoz, C},
title = {The Use of Rhizospheric Microorganisms of Crotalaria for the Determination of Toxicity and Phytoremediation to Certain Petroleum Compounds.},
journal = {Plants (Basel, Switzerland)},
volume = {15},
number = {1},
pages = {},
pmid = {41515048},
issn = {2223-7747},
abstract = {Microbial toxicity tests in the rhizosphere play an important role in the risk assessment and phytoremediation of chemical compounds in the environment. Tests for the inhibition of nodule number (NN), Rhizobia in the rhizosphere (RhR), Rhizobium in nodules (RhN) and arbuscular mycorrhizal fungi (AMFs) are important to evaluate the toxicity as well as the removal of total petroleum hydrocarbons (TPHs), 15 linear alkanes (LAs), and total linear alkanes (TLAs). The inhibition and removal was evaluated at 60 (vegetative stage, VS) and 154 days (reproductive stage, RS) of the life cycle of Crotalaria incana and Crotalaria pallida in soil with four doses of CRO (3, 15, 30, and 45 g/kg) plus a control (16 treatments). Results indicated that RhN and five structures of the AMFs present an index of toxicity (IT < 1), and the microbiological variable is inhibited by the CRO. RhR exhibits a hormesis index (IT > 1) that is stimulated by the CRO in the VS and RS for C. incana and C. pallida. The highest removal of TPHs (77%) was in the rhizosphere of C. incana in the RS with 45 g/kg of CRO. C. pallida removed the greatest amount of TLA (91%). There was a positive correlation between the RhR and the removal of TPHs, TLA, and LAs (higher molecular weight). It could be argued that symbiotic microorganisms are significant for use in toxicity testing, and the rhizosphere of C. incana and C. pallida can be used for the phytoremediation of HTPs and ALs in loamy-clay soil contaminated with CRO.},
}

@article {pmid41516158,
year = {2025},
author = {Lee, BC and Wang, CC and Chen, SP and Tsai, HJ},
title = {Multilevel Screening Platform Utilizing Cellular and Zebrafish Models to Identify Short Peptides with High Improvement of Motor Neuron Growth.},
journal = {International journal of molecular sciences},
volume = {27},
number = {1},
pages = {},
pmid = {41516158},
issn = {1422-0067},
support = {NSTC-114-2313-B-030-001//National Science and Technology Council, Taiwan/ ; 9991F02-1120232 and A0113210//Fu Jen Catholic University, Taiwan/ ; CPL-202508003//Collaborative Research Project between Fu Jen Catholic University Hospital and Fu Jen Catholic University, Taiwan/ ; },
mesh = {Animals ; Zebrafish ; *Motor Neurons/drug effects/metabolism/cytology ; Disease Models, Animal ; Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology/genetics ; *Peptides/pharmacology ; Humans ; Drug Evaluation, Preclinical/methods ; Zebrafish Proteins/genetics/metabolism ; Neuronal Outgrowth/drug effects ; },
abstract = {Zebrafish is emerging as a model animal for phenotype-based drug screening. Drugs screened from the zebrafish platform have advanced into clinical trials, underscoring their translational potential. Amyotrophic lateral sclerosis is a progressive motor neurons (MN) degenerative disease with few approved drugs. Previously, supplementation with exogenous recombinant phosphoglycerate kinase 1 (Pgk1) was found to improve MN growth through its interaction with receptor Eno2. To bypass the high complexity and cost of full-length Pgk1 production, a short segment within Pgk1 (M08) was predicted as the key motif interacting with Eno2, and a zebrafish phenotypic screening platform was established to find the most neurotrophic compound(s) among M08 and its mutants. We first found that M08-injected zebrafish embryos significantly increased branched caudal primary MNs (CaPMNs). However, compared to M08 (59.20 ± 1.80%), M039, among 17 mutants further screened, showed even more improvement of branched CaPMNs, up to 74.54 ± 3.73%. Next, when we administered the M039 peptide to C9ORF72-knockdown ALS-like zebrafish embryos, it improved axonal growth and swimming ability. Then, we employed a cellular model as a secondary screen, and M039 exhibited improved neurite outgrowth of MN (NOMN) and reduced p-Cofilin in NSC34 neural cells grown in ALS-like condition. Therefore, by using a zebrafish MN phenotype as a primary screening platform, we identified a mutated short peptide M039 having the most pronounced positive effect on improving neurite growth among all 17 mutants in comparison to parental M08, demonstrating the feasibility of zebrafish screening as a cost-effective strategy for finding promising neuroprotective short peptides that serve as neurotherapeutic potentials.},
}

Animals
Zebrafish
*Motor Neurons/drug effects/metabolism/cytology
Disease Models, Animal
Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology/genetics
*Peptides/pharmacology
Humans
Drug Evaluation, Preclinical/methods
Zebrafish Proteins/genetics/metabolism
Neuronal Outgrowth/drug effects

@article {pmid41517507,
year = {2025},
author = {Koska, V and Teufel, S and Aytulun, A and Weise, M and Ringelstein, M and Guthoff, R and Meuth, SG and Albrecht, P},
title = {Evolution of Retinal Morphology Changes in Amyotrophic Lateral Sclerosis.},
journal = {Journal of clinical medicine},
volume = {15},
number = {1},
pages = {},
pmid = {41517507},
issn = {2077-0383},
abstract = {Background/Objectives: To compare changes in the thickness of retinal layers between patients with amyotrophic lateral sclerosis (ALS) and healthy controls using optical coherence tomography. Amyotrophic lateral sclerosis is a degenerative disease of the upper and lower motoneurons with a rapidly progressive course, but non-motor symptoms such as decreased ocular motility and reduced visual acuity have also been reported. Specific biomarkers or surrogate parameters assessing neurodegeneration in ALS are of interest. Methods: In a retrospective, longitudinal study using optic coherence tomography of the retinal layers, we compared changes in the thickness of the layers between patients with ALS and healthy controls. Correlations to clinical scores, such as the modified ranking scale, were analyzed. Results: In our cohort of patients with early ALS (disease duration 5.15 ± 21.4 months at baseline), we neither observed differences in retinal layer thickness at baseline nor did the thickness changes in any retinal layer differ in comparison to healthy controls at baseline. Moreover, we observed no significant thickness changes over the course of the observational period in our patients with ALS. However, a correlation analysis revealed a negative association of the thickness change rates in the complex of ganglion cell and inner plexiform layer and the inner nuclear layer with a higher modified Rankin scale at follow-up. Conclusions: This study adds to the notion that OCT may not be a suitable tool to monitor atrophy and disease progression in ALS. However, further longitudinal studies with longer follow-up times and larger cohorts are warranted.},
}

@article {pmid41517538,
year = {2025},
author = {Dziadkowiak, E and Marschollek, K and Kwaśniak-Nowakowska, A and Zimny, A and Rałowska-Gmoch, W and Boroń, M and Koszewicz, M},
title = {Establishing Diagnostic and Differential Diagnostic Criteria for Amyotrophic Lateral Sclerosis.},
journal = {Journal of clinical medicine},
volume = {15},
number = {1},
pages = {},
pmid = {41517538},
issn = {2077-0383},
abstract = {Motor neuron disease (MND) represents a broad and heterogeneous group of disorders involving the upper or lower motor neurons, represented mainly by amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), progressive muscular atrophy (PMA) and progressive bulbar palsy (PBP). Primary motor neuronopathies are characterized by progressive degenerative loss of anterior horn cell motoneurons (lower motor neurons) or loss of giant pyramidal Betz cells (upper motor neurons). Rare atypical variants of MND-ALS include flail arm syndrome (FA), flail leg syndrome (FL), facial-onset sensory and motor neuronopathy (FOSMN), finger extension weakness and downbeat nystagmus motor neuron disease (FEWDON-MND) and long-standing and juvenile MND-ALS. In this article, we present a review of diagnostic criteria and the differential diagnosis for MND, focusing on ALS.},
}

@article {pmid41517697,
year = {2026},
author = {Wang, Z and Yao, L and Tu, M},
title = {Evaluating the causal connections between sleep duration and disease prevalence: A comprehensive systematic review and meta-analysis of Mendelian randomization studies.},
journal = {Medicine},
volume = {105},
number = {2},
pages = {e45225},
pmid = {41517697},
issn = {1536-5964},
mesh = {Humans ; Mendelian Randomization Analysis ; *Sleep/genetics/physiology ; Prevalence ; Genetic Predisposition to Disease ; Sleep Duration ; },
abstract = {BACKGROUND: The causal link between sleep duration and diverse health conditions remains unconfirmed. This meta-analysis aimed to clarify these relationships by synthesizing Mendelian randomization (MR) study evidence.

METHODS: PubMed was systematically searched up to February 15, 2024, for MR studies exploring genetic predispositions to sleep duration/insomnia (short/long/overall sleep duration, insomnia) and associations with circulatory, digestive, neurodegenerative, metabolic diseases, and cancers. Eligible effect estimates were meta-analyzed.

RESULTS: Fifty-one MR studies were included. Genetic variations in sleep traits were strongly linked to elevated risk of 12 cardiovascular diseases, obesity-related metrics (Type 2 diabetes, fasting glucose/insulin, HbA1c), neurological disorders (Alzheimer, amyotrophic lateral sclerosis, Parkinson disease), mental health conditions (attention-deficit/hyperactivity disorder, autism, bipolar disorder, major depressive disorder, schizophrenia), inflammatory bowel disease, and lung cancer.

CONCLUSION: Genetic evidence confirms causal associations between sleep characteristics and multiple diseases, emphasizing sleep's key role in health promotion and supporting personalized sleep management to reduce disease risk.},
}

Humans
Mendelian Randomization Analysis
*Sleep/genetics/physiology
Prevalence
Genetic Predisposition to Disease
Sleep Duration

@article {pmid41517814,
year = {2026},
author = {Jacob, SM and Son, B and Bagheri, S and Lee, S and Leckie, J and Chohan, B and Belway, C and Mascarenhas, J and Mobach, T and Korngut, LW and Sharkey, KA and Park, J and Nguyen, MD and Kim, SH and Pfeffer, G},
title = {The Oral Microbiome in Amyotrophic Lateral Sclerosis Shows Differentially Abundant Organisms in Limb Versus Bulbar Onset Disease: A Binational Study.},
journal = {Journal of clinical neurology (Seoul, Korea)},
volume = {22},
number = {1},
pages = {66-75},
pmid = {41517814},
issn = {1738-6586},
support = {//ALS Canada Discovery Grant/Canada ; //Barry Barrett Foundation/Canada ; /CAPMC/CIHR/Canada ; //International Development Research Council/Canada ; //Rose Family Foundation/Canada ; //Fondation Brain Canada/Canada ; /MOHW/Ministry of Health and Welfare/Korea ; RS-2024-00348451/MSIT/Ministry of Science and ICT, South Korea/Korea ; },
abstract = {BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of upper and lower motor neurons leading to progressive disability and death. Approximately 10% of cases are caused by single-gene disorders with the remaining 90% of cases presumed to be caused by a combination of environmental and genetic factors. The microbiome (the ensemble of microorganisms that colonize body surfaces and organs) was recently identified for its importance in the pathogenesis of ALS.

METHODS: In this study, we recruited 100 participants from two ethnically and geographically distinct sites (71 from Calgary, Canada, and 29 from Seoul, Republic of Korea) which included 59 ALS participants and 41 controls. All participants provided saliva samples for oral microbial analysis using 16S rRNA sequencing. Basic demographic information was collected from all participants, and ALS participants provided additional clinical information including site of disease onset, disease duration, and ALS Functional Rating Scale - Revised score.

RESULTS: Significant differences in beta diversity of the oral microbiomes were seen between limb- and bulbar-onset ALS participants. Two bacterial genera were differentially abundant between these groups, Bifidobacteriaceae Bifidobacterium was enriched in bulbar-onset cases, while Pasteurellaceae Haemophilus was enriched in limb-onset cases. No significant differences were found between ALS participants and controls, but there were significant differences when comparing participants from different sites of recruitment. Amongst household pairs (n=35 pairs), ALS participants differed from control participants at the Seoul site.

CONCLUSIONS: Despite the cohort and household effects, our study identified differentially abundant organisms that may be important to the phenotypic variability of ALS and should be considered for future study. Our study provides novel insights into design for future multi-site microbiome research in ALS.},
}

@article {pmid41517820,
year = {2026},
author = {Choi, SJ and Park, H and Sung, JJ},
title = {First Korean Case of C9orf72-Related Amyotrophic Lateral Sclerosis With Progressive Supranuclear Palsy-Like Features.},
journal = {Journal of clinical neurology (Seoul, Korea)},
volume = {22},
number = {1},
pages = {125-127},
pmid = {41517820},
issn = {1738-6586},
}

@article {pmid41517981,
year = {2026},
author = {Xu, X and Xu, J and Zhao, B and Guo, B and Wei, S and Li, B and Qi, Z and Chen, S and Wang, G and Liu, X},
title = {Target-site mutations and non-target-site detoxification confer ALS-inhibitor resistance in Bromus japonicus populations in China.},
journal = {Pest management science},
volume = {82},
number = {4},
pages = {3874-3883},
doi = {10.1002/ps.70510},
pmid = {41517981},
issn = {1526-4998},
support = {//the HAAFS Science and Technology Innovation Special Project (2022KJCXZX-LYS-13)/ ; //the Basic Research Funds of Hebei Academy of Agriculture and Forestry Sciences (2024060203)/ ; //the HAAFS Youth Innovation Fund Project (2023LYS03)/ ; },
mesh = {*Herbicide Resistance/genetics ; *Acetolactate Synthase/genetics/antagonists & inhibitors/metabolism ; *Herbicides/pharmacology ; China ; Mutation ; *Plant Proteins/genetics/metabolism/antagonists & inhibitors ; Inactivation, Metabolic ; },
abstract = {BACKGROUND: The emergence of herbicide-resistant Japanese brome (Bromus japonicus) populations has been increasingly documented throughout China. Two such populations, DZ-R and XL-R, exhibit resistance to acetolactate synthase (ALS)-inhibiting herbicides, yet their resistance level and mechanism remain undetermined. This study sought to: (i) quantify resistance levels to flucarbazone-sodium, mesosulfuron-methyl, and pyroxsulam; (ii) screen for ALS mutations conferring target-site resistance (TSR); and (iii) characterize non-target-site resistance (NTSR) mechanisms using a multi-omics approach.

RESULTS: Whole-plant bioassay results indicated that the resistance indices of DZ-R and XL-R populations were 111.3 and 90.5 to flucarbazone-sodium, 36 and 206.4 to mesosulfuron-methyl, and 109.8 and 429.5 to pyroxsulam. The TSR mechanism was mediated by distinct ALS gene mutations: a Pro197-Ser substitution in DZ-R and a Pro197-Thr substitution in XL-R. Integrated transcriptomic, metabolomics and malathion-inhibited bioassay analyses revealed the NTSR mechanism, identifying two ABCB4, ABCG48, ABCB11 genes, two unnamed ABC, POD 35, POD P7-like, GST1, GSTU17, 2 GSTU6, IN2-1-like isoform X3 genes, three unnamed GST, GT 73C6-like, ZWY2020_001091, cis-zeatin O-GT, CYP74A15, noroxomaritidine synthase 2-like, indole-2-monooxygenase-like genes and four unnamed CYP450 genes as candidate genes. These genes participated in ATP-binding cassette transporters, phenylpropanoid biosynthesis, glutathione metabolism and zeatin biosynthesis metabolic pathways that synergistically mediate herbicide detoxification. Notably, two putative flucarbazone-sodium degradation pathways were deduced in the resistant populations.

CONCLUSION: Collectively, these findings demonstrated that both TSR and NTSR mechanisms contributed to herbicide resistance in the DZ-R and XL-R populations. Future research should prioritize functional validation of the identified candidate genes to elucidate their specific roles in herbicide metabolism. © 2026 Society of Chemical Industry.},
}

*Herbicide Resistance/genetics
*Acetolactate Synthase/genetics/antagonists & inhibitors/metabolism
*Herbicides/pharmacology
China
Mutation
*Plant Proteins/genetics/metabolism/antagonists & inhibitors
Inactivation, Metabolic

@article {pmid41518572,
year = {2026},
author = {Zhang, Z and Zhang, M and Cao, Z and Zhao, H and Li, X and Luo, P},
title = {Fibrillarin: bridging ribosome biogenesis and apoptosis in cellular stress and disease.},
journal = {Apoptosis : an international journal on programmed cell death},
volume = {31},
number = {1},
pages = {11},
pmid = {41518572},
issn = {1573-675X},
support = {82171363//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Apoptosis/genetics ; *Ribosomes/metabolism/genetics ; *Neoplasms/genetics/metabolism/pathology ; *Stress, Physiological ; Animals ; Tumor Suppressor Protein p53/metabolism/genetics ; *Neurodegenerative Diseases/genetics/metabolism/pathology ; Cell Nucleolus/metabolism ; Signal Transduction ; Chromosomal Proteins, Non-Histone ; },
abstract = {Nucleolar stress has emerged as a critical regulatory mechanism linking ribosome biogenesis defects to apoptotic cell death in various pathological conditions. Fibrillarin (FBL), the catalytic component of box C/D small nucleolar ribonucleoproteins, participates in multiple forms of programmed cell death through both p53-dependent and p53-independent pathways across diverse disease contexts including cancer and neurodegeneration. In malignancies including breast cancer, colorectal cancer, and hepatocellular carcinoma, FBL overexpression promotes apoptosis resistance, whereas in Alzheimer's disease and ALS/FTD, FBL dysfunction contributes to pathological neuronal death. Dysregulation of FBL can lead to excessive apoptosis or apoptosis resistance depending on cellular context and disease state. Various cellular stressors trigger aberrant FBL function, disrupting rRNA processing and ribosome assembly, which then activates nucleolar stress responses that culminate in cell death through ribosomal protein-MDM2-p53 axis activation or selective translational control of survival factors in a context-dependent manner. Therefore, targeting FBL-mediated apoptotic pathways is considered an important avenue for the treatment of various cancers and neurodegenerative diseases. In this review, we summarize the major and recent findings focusing on the mechanisms of FBL-regulated apoptosis in disease pathogenesis and provide a systematic overview of current therapeutic strategies targeting nucleolar stress pathways, including RNA polymerase I inhibitors and precision medicine approaches based on p53 status, which may provide important therapeutic targets that merit further investigation.},
}

Humans
*Apoptosis/genetics
*Ribosomes/metabolism/genetics
*Neoplasms/genetics/metabolism/pathology
*Stress, Physiological
Animals
Tumor Suppressor Protein p53/metabolism/genetics
*Neurodegenerative Diseases/genetics/metabolism/pathology
Cell Nucleolus/metabolism
Signal Transduction
Chromosomal Proteins, Non-Histone

@article {pmid41518628,
year = {2026},
author = {Chevet, ML and Garnier, M and Fadel, M and Scherer, C and Cassereau, J and Levaillant, M and Codron, P},
title = {Epidemiology of Amyotrophic Lateral Sclerosis in the Pays de la Loire, France: A 20-Year Study from a Centralized Diagnostic Center.},
journal = {Neuroepidemiology},
volume = {},
number = {},
pages = {1-8},
pmid = {41518628},
issn = {1423-0208},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal motor neurons disease with multifactorial etiology. The epidemiology of ALS in France is mainly documented through the Limousin regional registry (FRALim). We aimed to determine the incidence and clinical characteristics of ALS cases over a 20-year period in another French region, the Pays de la Loire, served by a single centralized diagnostic center.

METHODS: All patients diagnosed with ALS at the Angers University Hospital reference center between 2003 and 2023 were retrospectively included. Demographic and clinical data were extracted from medical records, and incidence rates were calculated using annual population estimates from the National Institute of Statistics and Economic Studies. Spatial analyses were performed to identify over-incidence areas and potential environmental or occupational determinants.

RESULTS: A total of 1,316 patients were diagnosed with ALS during the study period, corresponding to a crude incidence rate of 1.88 cases per 100,000 person-years (95% CI: 1.78-1.98), with no significant variation over time. The standardized incidence rate was 1.73 (95% CI: 1.63-1.83). The mean age at symptom onset was 63.6 ± 11.2 years, 58.7% of patients were male. The mean disease duration was 3.7 ± 3.5 years. ALS onset was spinal in 70.3%, bulbar in 27.9%, and respiratory in 1.7% of cases. Familial or genetic forms accounted for 6% of patients. Four geographical over-incidence areas were identified, with no correlation found with pesticide use, air pollution, or other environmental indicators. One occupational cluster was observed among farmers in a specific commune, prompting a dedicated investigation.

CONCLUSION: This 20-year retrospective study provides the first epidemiological data on ALS in western France. The incidence and clinical features are consistent with national and European data. The identification of spatial and occupational clusters underlines the importance of continued regional surveillance and of prospective, registry-based studies to clarify environmental and occupational risk factors for ALS.},
}

@article {pmid41518742,
year = {2026},
author = {Milella, G and Carlone, S and Luisi, F and Velucci, V and Defazio, G},
title = {Facial-onset SOD1 amyotrophic lateral sclerosis: A case report and systematic review.},
journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia},
volume = {145},
number = {},
pages = {111856},
doi = {10.1016/j.jocn.2026.111856},
pmid = {41518742},
issn = {1532-2653},
mesh = {Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/genetics/complications ; *Facial Paralysis/genetics/etiology ; *Superoxide Dismutase-1/genetics ; },
abstract = {BACKGROUND: Facial-onset weakness is an exceptionally rare presentation of SOD1-associated amyotrophic lateral sclerosis (ALS), and its natural history, anatomical spread, and prognostic implications remain unclear.

METHODS: We report a woman carrying a heterozygous SOD1 A5T variant who presented with isolated, rapidly progressive bilateral facial palsy, and we performed a PRISMA-compliant systematic review of MEDLINE, Scopus, and Web of Science to identify genetically confirmed SOD1-positive ALS with facial-onset weakness. Case-level demographic, genetic, clinical, neurophysiological, and outcome data were extracted and synthesised descriptively.

RESULTS: Eleven patients were included (7 men, 4 women; mean age at onset 52.3 years). Seven SOD1 variants were represented, predominantly associated with short survival (e.g. A5V, C7G, A5T). Facial weakness was initially confined to the lower face in 5/11 patients, while 6/11 had combined upper and lower facial involvement. Disease spread followed a stereotyped pattern: early contralateral facial recruitment (mean 3.6 months), rapid bulbar involvement (4.2 months), and later extension to the upper limbs (9.2 months), frequently with side-concordance between facial and arm involvement. Lower motor neuron (LMN) signs predominated in the early phases of the disease. Survival was short (median 16 months), lower than reported for unselected SOD1-ALS cohorts with the same genotypes. Three patients received tofersen, with heterogeneous outcomes.

CONCLUSIONS: Facial-onset SOD1 ALS defines a distinctive phenotype characterised by LMN-predominant facial palsy in early phases, near-neighbour spread, and an aggressive course exceeding genotype-based expectations. Prompt recognition and genetic testing in progressive facial palsy unresponsive to immunotherapy are essential to ensure access to gene-targeted treatments.},
}

Female
Humans
Male
Middle Aged
*Amyotrophic Lateral Sclerosis/genetics/complications
*Facial Paralysis/genetics/etiology
*Superoxide Dismutase-1/genetics

@article {pmid41519115,
year = {2026},
author = {Chen, MH and Bai, YM and Tsai, SJ},
title = {Depression, cognition, and GLP-1 receptors: Heterogeneity and therapeutic prospects.},
journal = {Med (New York, N.Y.)},
volume = {7},
number = {1},
pages = {100954},
doi = {10.1016/j.medj.2025.100954},
pmid = {41519115},
issn = {2666-6340},
mesh = {Humans ; *Glucagon-Like Peptide-1 Receptor Agonists ; *Depression/drug therapy ; Glucagon-Like Peptide-1 Receptor ; Glucagon-Like Peptides/therapeutic use/pharmacology ; *Cognition/drug effects ; Quality of Life ; *Cognitive Dysfunction/drug therapy ; Glucagon-Like Peptide 1 ; Semaglutide ; },
abstract = {Cognitive impairments in depression, driven by both the illness per se and low-grade systemic inflammation, markedly reduce functional capacity and quality of life among patients who suffer. Findings from Badulescu et al.'s placebo-controlled trial reported that semaglutide, a GLP-1 receptor agonist, may improve attention and memory, although there was no significant improvement in overall depressive symptoms.},
}

Humans
*Glucagon-Like Peptide-1 Receptor Agonists
*Depression/drug therapy
Glucagon-Like Peptide-1 Receptor
Glucagon-Like Peptides/therapeutic use/pharmacology
*Cognition/drug effects
Quality of Life
*Cognitive Dysfunction/drug therapy
Glucagon-Like Peptide 1
Semaglutide

@article {pmid41520601,
year = {2026},
author = {Squintani, G and Muzio, MD and Rasera, A and Paio, F and Borin, GU and Humaidan, K and Orlando, D and Refatti, N and Romito, S and Tinazzi, M and Bonetti, B and Ermani, M},
title = {Sensory and motor cortical hyperexcitability in patients with amyotrophic lateral sclerosis: are they related? a prospective pilot study.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {183},
number = {},
pages = {2111485},
doi = {10.1016/j.clinph.2025.2111485},
pmid = {41520601},
issn = {1872-8952},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Male ; Female ; Middle Aged ; *Motor Cortex/physiopathology ; Pilot Projects ; *Evoked Potentials, Somatosensory/physiology ; Aged ; *Somatosensory Cortex/physiopathology ; *Evoked Potentials, Motor/physiology ; Transcranial Magnetic Stimulation/methods ; Prospective Studies ; Adult ; },
abstract = {OBJECTIVE: Our study evaluates sensory and motor cortical hyperexcitability as diagnostic biomarkers in ALS patients and investigates their relationship, identifying distinct or interconnected pathophysiological mechanisms in different sub-groups.

METHODS: We examined 26 ALS patients and 18 healthy controls. Motor cortex excitability was assessed using transcranial magnetic stimulation to measure the motor evoked potential (MEP) suppression ratio. Somatosensory cortex excitability was evaluated through upper-limb somatosensory evoked potentials (SEPs) with conventional and paired-pulse techniques. Statistical analyses included parametric/non-parametric tests, correlation analyses, and χ[2] tests. ROC analysis was used to assess diagnostic performance. Significance threshold was p < 0.05.

RESULTS: ALS patients showed a significantly reduced MEP suppression ratio (p < 0.001) with excellent discriminative power (100 % accuracy). SEP suppression ratio was significantly lower in ALS (p < 0.001), with sensitivity 76.3 %, specificity 91.7 %, and accuracy 84 %. In patients with giant SEPs, a strong inverse correlation was observed between MEP and SEP suppression ratios (r =  - 0.70, p < 0.001).

CONCLUSIONS: MEP and SEP suppression ratio are robust biomarkers of motor cortical dysfunction in ALS patients with a highlighting cortical heterogeneity between sub-groups, suggesting cortical interconnection.

SIGNIFICANCE: Alongside confirming motor and sensory cortical hyperexcitability as ALS hallmarks, this study reveals subgroup-specific patterns suggesting a compensatory interplay between sensory and motor cortex.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/diagnosis
Male
Female
Middle Aged
*Motor Cortex/physiopathology
Pilot Projects
*Evoked Potentials, Somatosensory/physiology
Aged
*Somatosensory Cortex/physiopathology
*Evoked Potentials, Motor/physiology
Transcranial Magnetic Stimulation/methods
Prospective Studies
Adult

@article {pmid41520654,
year = {2026},
author = {Mehdiyoun, NF and Wright, J and Robinson, RL and Brandt, AU and Hoyt, M and Guo, J and Ball, N and Iqbal, H and Ringland, C and Milligan, G and Curtis, SE},
title = {Evaluating ALSFRS-R as an indicator of disease milestones and functional independence: An observational study of US neurologists and their patients with amyotrophic lateral sclerosis.},
journal = {Journal of the neurological sciences},
volume = {481},
number = {},
pages = {125732},
doi = {10.1016/j.jns.2026.125732},
pmid = {41520654},
issn = {1878-5883},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; Male ; Female ; Middle Aged ; *Activities of Daily Living ; Cross-Sectional Studies ; Aged ; *Neurologists ; *Disease Progression ; United States/epidemiology ; Severity of Illness Index ; Adult ; },
abstract = {BACKGROUND: The Revised Amyotrophic Lateral Sclerosis (ALS) Functional Rating Scale (ALSFRS-R) is a clinician-reported outcome measure monitoring disease progression in people living with ALS (pALS). This study examined the relationship of ALSFRS-R scores with disease progression and independence levels for activities of daily living (ADLs) among pALS.

METHODS: Real-world data, including the ALSFRS-R, were drawn from a cross-sectional survey of US neurologists treating pALS (Adelphi ALS Disease Specific Programme™), conducted between July 2020 and March 2021. ALSFRS-R scores were modeled against 11 pre-defined disease milestones. The relationship between ALSFRS-R scores and levels of independence in 24 ADLs was examined using ordered logistic regression.

RESULTS: Fifty-nine neurologists provided data for 379 pALS (mean age: 59.5 years; mean disease duration: 16.1 months). Estimated mean ALSFRS-R total score decreased (worsened) from 46.1 at first consultation regarding ALS symptoms to 25.1 upon receipt of a feeding tube. In general, pALS were likely to be completely dependent in most ADLs when their ALSFRS-R total scores were ≤ 25. A 1-point decrease in ALSFRS-R total score was associated with increased risks of losing independence across all ADLs. For each ADL, a 1-point decrease in domain score was associated with varying risks of losing independence across different domains.

CONCLUSIONS: There is a correlation between ALSFRS-R scores and levels of independence in ADLs among pALS, facilitating score interpretation for monitoring disease and function status. Yet, the relevance of the ALSFRS-R total score diminishes in advanced stages of ALS, indicating a need for additional measures to provide comprehensive evaluation.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology
Male
Female
Middle Aged
*Activities of Daily Living
Cross-Sectional Studies
Aged
*Neurologists
*Disease Progression
United States/epidemiology
Severity of Illness Index
Adult

@article {pmid41521074,
year = {2026},
author = {Ham, HJ and Lee, JA},
title = {Stress granules as a central hub linking organelle stress, aging, and neurodegeneration.},
journal = {BMB reports},
volume = {59},
number = {2},
pages = {85-100},
pmid = {41521074},
issn = {1976-670X},
mesh = {Humans ; *Aging/metabolism/physiology ; *Neurodegenerative Diseases/metabolism/pathology ; *Stress Granules/metabolism/physiology ; Animals ; *Organelles/metabolism ; Mitochondria/metabolism ; Neurons/metabolism ; Cytoplasmic Granules/metabolism ; Autophagy ; Stress, Physiological ; },
abstract = {Stress granules (SGs) are dynamic cytoplasmic assemblies composed of RNAs and proteins that form in response to cellular stress, serving to halt translation and protect cellular integrity. In neurons, SGs mediate adaptive, pro-survival responses to acute stress; however, their dysregulation has been increasingly associated with both aging and neurodegenerative diseases. Aging neurons frequently exhibit changes in SG dynamics-with an increased propensity to form SGs while displaying reduced efficiency in their clearance-resulting in persistent granules that can facilitate the accumulation of pathological protein aggregates (e.g., TDP-43 or tau). Aberrant SG formation and defective clearance mechanisms are implicated in the pathogenesis of key neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease (AD), and Parkinson's disease (PD). Recent findings have shown that SGs interface with organelles such as lysosomes, mitochondria, and the endoplasmic reticulum, utilizing autophagic and other protein quality-control mechanisms for clearance. As these clearance pathways progressively decline with age, SGs can transition from promoting cellular adaptation to contributing to cellular dysfunction. In this mini-review, we examine how aging influences SG biology, detail the role of SGs in neurodegenerative diseases, and discuss emerging mechanistic insights and therapeutic strategies aimed at modulating SG dynamics in the context of brain aging. [BMB Reports 2026; 59(2): 85-100].},
}

Humans
*Aging/metabolism/physiology
*Neurodegenerative Diseases/metabolism/pathology
*Stress Granules/metabolism/physiology
Animals
*Organelles/metabolism
Mitochondria/metabolism
Neurons/metabolism
Cytoplasmic Granules/metabolism
Autophagy
Stress, Physiological

@article {pmid41521076,
year = {2025},
author = {Lee, SP and Choi, J and Park, JH and Lee, KN and Lee, HL and Sung, W},
title = {Predictors of Percutaneous Endoscopic Gastrostomy-Related Complications in Amyotrophic Lateral Sclerosis: A 19-Year Retrospective Study From a Tertiary Center.},
journal = {Journal of digestive diseases},
volume = {26},
number = {11-12},
pages = {492-508},
doi = {10.1111/1751-2980.70025},
pmid = {41521076},
issn = {1751-2980},
mesh = {Humans ; *Gastrostomy/adverse effects/methods ; Male ; Retrospective Studies ; Female ; *Amyotrophic Lateral Sclerosis/complications ; Middle Aged ; Aged ; Risk Factors ; Tertiary Care Centers ; *Postoperative Complications/etiology/epidemiology ; *Deglutition Disorders/etiology/therapy/surgery ; Adult ; *Gastroscopy/adverse effects ; Enteral Nutrition/adverse effects/methods ; Ileus/complications ; },
abstract = {OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that inevitably leads to swallowing difficulties as the disease progresses. Percutaneous endoscopic gastrostomy (PEG) is recommended for optimal supportive management of dysphagia among these patients. We aimed to investigate PEG-related complications and risk factors in patients with ALS.

METHODS: Medical records of the ALS patients who underwent PEG from March 2006 to February 2025 in a single tertiary care center were retrospectively reviewed. PEG-related complications and risk factors were assessed through chart review, endoscopic reports and images, radiological findings, and follow-up data.

RESULTS: Altogether 501 ALS patients (262 men) underwent PEG, of whom 60 developed early complications and 82 developed late complications, including 11 patients who developed both. Pneumoperitoneum was more common in underweight patients (p = 0.004), and wound infection was more common in patients with pre-PEG ileus (p = 0.044). Multivariate analysis revealed that low albumin level, long procedure time, and ileus were significantly associated with early complications. Obesity and ileus were independent risk factors for buried bumper syndrome. Those with an internal bolster at the upper body of the stomach and with an external bolster in the midline of the abdomen were at significant risk of inadvertent PEG removal.

CONCLUSIONS: Albumin and body mass index extremes are predictors of complications, and care is needed when PEG is performed on patients with pre-PEG ileus. To reduce such risks, the PEG tube should not be inserted into the upper body of the stomach or the midline of the abdomen.},
}

Humans
*Gastrostomy/adverse effects/methods
Male
Retrospective Studies
Female
*Amyotrophic Lateral Sclerosis/complications
Middle Aged
Aged
Risk Factors
Tertiary Care Centers
*Postoperative Complications/etiology/epidemiology
*Deglutition Disorders/etiology/therapy/surgery
Adult
*Gastroscopy/adverse effects
Enteral Nutrition/adverse effects/methods
Ileus/complications

@article {pmid41523053,
year = {2025},
author = {Nagmode, P and Deshmukh, V and Abraham, S and Lokhande, N and Diggikar, K and Chavhan, G},
title = {Comparative Evaluation of Effectiveness of 35% and 20% Concentration of Hydrogen Peroxide Alone and in Combination with Pomegranate Extract on Human Enamel Used for Tooth Bleaching - An Invitro Study.},
journal = {Journal of pharmacy & bioallied sciences},
volume = {17},
number = {Suppl 4},
pages = {S3322-S3324},
pmid = {41523053},
issn = {0976-4879},
abstract = {AIM: To evaluate the color change in human enamel bleached with two concentrations of hydrogen peroxide (35% and 20%) alone and in combination with pomegranate extract using a reflectance spectrophotometer.

MATERIALS AND METHODS: Forty extracted permanent maxillary incisors were randomly divided into four groups: Group 1a: 35% hydrogen peroxide alone, Group 1b: 35% hydrogen peroxide + pomegranate extract, Group 2a: 20% hydrogen peroxide alone, Group 2b: 20% hydrogen peroxide + pomegranate extract. Pomegranate extract was prepared from 1500 g of peeled white pomegranate blended with 25 ml distilled water and centrifuged at 2000 rpm for 2 minutes at 4°C. Teeth were artificially stained following Sulieman et al.'s protocol and immersed in respective bleaching agents for 20 minutes. Color change (ΔE) was measured using a reflectance spectrophotometer.

RESULTS: Groups using pomegranate extract with hydrogen peroxide exhibited significantly greater ΔE values, indicating enhanced bleaching efficacy compared to hydrogen peroxide alone.

CONCLUSION: Hydrogen peroxide combined with pomegranate extract significantly improves tooth color change compared to hydrogen peroxide alone.},
}

@article {pmid41523190,
year = {2026},
author = {Jiang, Y and Fu, Y and Song, X and Wang, X and Li, J and Cheng, L and Chen, Y and Zhang, Y and Wang, J and Yi, X and Palaniyappan, L},
title = {Microstructure and gene expression influence gyrification in amyotrophic lateral sclerosis.},
journal = {Brain communications},
volume = {8},
number = {1},
pages = {fcaf491},
pmid = {41523190},
issn = {2632-1297},
abstract = {Amyotrophic lateral sclerosis is a fatal neurodegenerative disease involving progressive degeneration of upper and lower motor neurons. Beyond well-established grey and white matter pathology, alterations in cortical gyrification have recently been observed, yet their clinical relevance and molecular underpinnings remain to be understood. Here, we investigated this premise by examining its microstructural and transcriptional basis in 60 patients with amyotrophic lateral sclerosis (median age = 55, range = 25-72 years) and 60 matched controls (median age = 56, range = 27-72 years) using structural and diffusion MRI. Patients exhibited a significant reduction in local gyrification index within bilateral precentral and postcentral gyri, left middle frontal gyrus and left superior parietal lobule. This was accompanied by reduced fractional anisotropy in the white matter tracts, primarily involving the corticospinal tract and corpus callosum. Higher local gyrification index and fractional anisotropy values were associated with better motor function as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised, and local gyrification index also showed positive associations with global cognitive status. A mediation analysis indicated that fractional anisotropy partially accounted for the relationship between local gyrification index and functional disability, suggesting that disrupted white matter pathways contribute to the clinical impact of gyrification changes. To explore underlying mechanisms, we integrated neuroimaging findings with transcriptomic data from the Allen Human Brain Atlas. Regions of reduced local gyrification index showed spatial convergence with cortical expression of amyotrophic lateral sclerosis-related genes such as TARDBP and C9orf72, enriched for biological processes related to protein aggregation, axon guidance and synaptic signalling. Together, these findings suggest that cortical gyrification abnormalities in amyotrophic lateral sclerosis are closely linked to white matter degeneration, functional impairment and genetic vulnerability, thereby offering an integrative window into the multiscale pathology of amyotrophic lateral sclerosis.},
}

@article {pmid41524979,
year = {2026},
author = {Sun, Y and Huang, C and Pan, Y and Zhang, H and He, X},
title = {Muscle Fibrosis in Amyotrophic Lateral Sclerosis: Molecular Mechanisms, Diagnostic Advances, and Therapeutic Strategies.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {357},
pmid = {41524979},
issn = {1559-1182},
support = {2021KY727//Health Commission of Zhejiang Province, Medical and health project/ ; A20210510//Hangzhou Municipal Health Commission, Medical and health science project/ ; },
mesh = {Animals ; Humans ; *Amyotrophic Lateral Sclerosis/therapy/pathology/diagnosis/metabolism/complications ; Fibrosis ; *Muscle, Skeletal/pathology/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder primarily characterized by the degeneration of motor neurons. However, the pathological process of ALS extends beyond the central nervous system, with dynamic changes in skeletal muscle playing a crucial role in the progression of the disease. Recent research has shown that muscle fibrosis, marked by the abnormal accumulation of extracellular matrix (ECM), leads to reduced muscle elasticity, compromised contractile function, and impaired regeneration of neuromuscular junctions (NMJs). This condition represents not only the final stage of muscle atrophy in ALS but also a significant factor accelerating disease progression through "neuromuscular interactions." We conducted a systematic review of the molecular mechanisms of muscle fibrosis in ALS. This included examining the dysregulation of transforming growth factor-β (TGF-β), connective tissue growth factor (CTGF/CCN2), and the Wnt/β-catenin signaling pathways. We also considered key cellular contributors, such as fibro-adipogenic precursor cells and macrophages. The review also covers the use of non-invasive imaging techniques, such as MRI and muscle ultrasound, for early detection and monitoring. We also evaluate potential therapeutic approaches, ranging from anti-fibrotic drugs and gene therapy to physical interventions. In summary, muscle fibrosis is a promising therapeutic target that could complement strategies focused on motor neurons, ultimately improving functional outcomes in patients with amyotrophic lateral sclerosis.},
}

Animals
Humans
*Amyotrophic Lateral Sclerosis/therapy/pathology/diagnosis/metabolism/complications
Fibrosis
*Muscle, Skeletal/pathology/metabolism

@article {pmid41525811,
year = {2026},
author = {Pradhan, LK and Das, SK},
title = {Zebrafish neural regeneration: mechanistic insights into human nervous system repair.},
journal = {Neuroscience},
volume = {596},
number = {},
pages = {1-15},
doi = {10.1016/j.neuroscience.2026.01.009},
pmid = {41525811},
issn = {1873-7544},
mesh = {Animals ; Zebrafish/physiology ; *Nerve Regeneration/physiology ; Humans ; Disease Models, Animal ; Neurogenesis/physiology ; },
abstract = {The zebrafish (Danio rerio) is a powerful vertebrate model for studying neurodegenerative diseases and regenerative medicine due to its genetic similarity to humans and its unique ability to regenerate the central nervous system (CNS). This review synthesizes key findings on zebrafish neural regeneration across the retina, spinal cord, and brain, emphasizing translational relevance. Zebrafish effectively model disorders such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, stroke, epilepsy, autism spectrum disorders, and CNS injuries. Unlike mammals, they restore damaged axons and recover function through a permissive extracellular matrix, transient inflammation, and glial plasticity. In the retina, Müller glia reprograms after injury to generate progenitors that replace lost neurons, regulated by Wnt/β-catenin, Shh, EGF, Hippo/YAP, and ROCK signaling. In the spinal cord, ependymo-radial glia forms a laminin- and fibronectin-rich "glial bridge," guided by FGF and CTGF signaling, supporting axon regrowth. In the brain, GFAP- and Olig2-positive radial glia drive neurogenesis within ventricular niches, integrating new neurons while maintaining circuit integrity. Regeneration involves transient Notch suppression, context-specific Wnt and FGF activation, and immune modulation without fibrosis. Advances in single-cell RNA sequencing, CRISPR-Cas9, lineage tracing, and multi-omics have identified injury-induced progenitor states, regulators (ascl1a, lin28, sox2, stat3), and epigenetic programs enabling regeneration. Emerging research on bioelectric signaling, microbiota-brain interactions, and lipid mediators further expands systemic understanding. Overall, zebrafish provide a unified model for decoding vertebrate CNS regeneration and guiding therapeutic strategies to restore neural repair in humans.},
}

Animals
Zebrafish/physiology
*Nerve Regeneration/physiology
Humans
Disease Models, Animal
Neurogenesis/physiology

@article {pmid41525886,
year = {2026},
author = {Zimyanin, V and Dash, BP and Simolka, T and Glaß, H and Pal, A and Haidle, F and Zarnack, K and Verma, R and Khatri, V and Deppmann, C and Zunder, E and Müller-McNicoll, M and Redemann, S and Hermann, A},
title = {Compartment-specific transcriptome of motor neurons reveals impaired extracellular matrix signaling and activated cell cycle kinases in FUS-ALS.},
journal = {Neurobiology of disease},
volume = {219},
number = {},
pages = {107268},
doi = {10.1016/j.nbd.2026.107268},
pmid = {41525886},
issn = {1095-953X},
mesh = {*Motor Neurons/metabolism/pathology ; *RNA-Binding Protein FUS/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Transcriptome ; *Extracellular Matrix/metabolism ; Humans ; *Cell Cycle Proteins/metabolism/genetics ; Animals ; Signal Transduction/physiology ; Axons/metabolism ; Induced Pluripotent Stem Cells/metabolism ; },
abstract = {Mutations in FUSED IN SARCOMA (FUS) cause juvenile-onset amyotrophic lateral sclerosis (ALS). Early pathogenesis of FUS-ALS involves impaired transcription and splicing, DNA damage response, and axonal degeneration. However, the molecular pathophysiology and the link between somatic and axonal phenotypes are still poorly understood. We evaluated whether compartment-specific transcriptome differences could distinguish and drive early axonal degeneration. We used iPSC-derived motor neurons (MNs) coupled with microfluidic approaches to generate RNA-sequencing profiles from axonal and somatodendritic compartments. We demonstrate that the axonal transcriptome is unique and distinct, with RNA metabolism, extracellular secretion, and matrix disassembly pathways particularly enriched in distal axonal compartments. FUS mutation leads to changes in distinct pathways that were clustered in only a few distinct protein-protein interaction (PPI) networks. Somatodendritic changes upon FUS mutation include WNT signaling, mitochondrial, extracellular matrix (ECM)-, and synapse-related functions. In contrast, analysis of the axonal transcriptome in mutant MNs centers on the PLK1 pathway, mitochondrial gene expression, and regulation of inflammation. Comparison to CLIP-seq data revealed a significant enrichment for PLK1 and DNA replication pathways in axons. PLK1 upregulation did not activate cell-cycle re-entry but contributed to mutant MNs survival, and its inhibition increased neuronal cell death. We propose that upregulation of PLK1 represents an early event in the pathogenesis of ALS and could act in response to DNA damage, mitochondrial damage, and immune response activation in the affected cells. Additionally, downregulation of ECM pathways in the somatodendritic compartment and axons could explain strongly compromised dynamics of axonal outgrowth. Overall, we provide a novel valuable resource of the potential targets and affected processes changed in the specific compartments of FUS-ALS motor neurons.},
}

*Motor Neurons/metabolism/pathology
*RNA-Binding Protein FUS/genetics/metabolism
*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology
*Transcriptome
*Extracellular Matrix/metabolism
Humans
*Cell Cycle Proteins/metabolism/genetics
Animals
Signal Transduction/physiology
Axons/metabolism
Induced Pluripotent Stem Cells/metabolism

@article {pmid41525888,
year = {2026},
author = {Tessitore, S and Torazza, C and Bonifacino, T and Bacchetti, F and Roselli, F and Raiteri, L and Milanese, M and Bonanno, G},
title = {Focus on the excitatory and inhibitory neurotransmission imbalance in amyotrophic lateral sclerosis: a harmful disease player or a potential therapeutic opportunity?.},
journal = {Neurobiology of disease},
volume = {219},
number = {},
pages = {107272},
doi = {10.1016/j.nbd.2026.107272},
pmid = {41525888},
issn = {1095-953X},
mesh = {*Amyotrophic Lateral Sclerosis/physiopathology/metabolism/drug therapy ; Humans ; *Synaptic Transmission/physiology ; Animals ; Motor Neurons/metabolism/physiology ; Glutamic Acid/metabolism ; *Neural Inhibition/physiology ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease affecting both upper and lower motor neurons. Evidence indicates that ALS is a "multifactorial" and "multicellular" disease; however, the causes of ALS remain elusive, as the mechanisms underlying the disease have not yet been completely clarified. One major proposed mechanism, first described in 1990, is the glutamate excitotoxicity theory. This theory suggests that excessive glutamatergic neurotransmission, combined with impaired glutamate clearance, significantly contributes to motor neuron degeneration. Aberrant glutamate neurotransmission may lead to precocious motor neuron hyperexcitability in the brain cortex and spinal cord, which can be later followed by hypoexcitability phases. Accumulating evidence suggests that impairment in inhibitory neurotransmission is relevant for excitation/inhibition imbalance, leading to excitotoxicity, a critical feature of ALS. Gamma-aminobutyric acid (GABA) and glycine are the primary inhibitory neurotransmitters that modulate neuronal excitability, including that of motor neurons. In ALS, dysfunction of inhibitory processes and loss of cortical and spinal inhibitory interneurons are observed. Renshaw cells, which mediate recurrent inhibition in the spinal cord, seem particularly vulnerable. The interactions among neurotransmitters, including glutamate, GABA, and glycine, play pivotal roles in regulating the excitation/inhibition balance. Auto- or hetero-receptor-mediated interactions are crucial, but auto- or hetero-transporter-mediated neurotransmission control, as well as other molecular mechanisms that regulate neuronal interplay, are also relevant, as they can be altered in pathological conditions such as ALS. To facilitate the search for new effective therapies for ALS, attention toward the impairment of inhibitory neurotransmission is essential to determine the role of excitation/inhibition imbalance on excitotoxicity. Different pharmacological agents are being used to treat other pathologies in which the excitation/inhibition ratio is impaired. Among these, we highlighted the potential of novel glycine and GABA receptor ligands and transporter inhibitors, as stand-alone interventions or in combination with other treatments. The present review aims to elucidate the complex interplay between excitatory and inhibitory neurotransmission in ALS, exploring the potential to target this imbalance for therapeutic purposes.},
}

*Amyotrophic Lateral Sclerosis/physiopathology/metabolism/drug therapy
Humans
*Synaptic Transmission/physiology
Animals
Motor Neurons/metabolism/physiology
Glutamic Acid/metabolism
*Neural Inhibition/physiology

@article {pmid41527739,
year = {2026},
author = {Le, J and Hu, X and Jiang, Y and Wang, Q and Ma, Q and Cui, W},
title = {Insights into phosphoproteomic studies and prospects of phosphoproteins as biomarkers for brain disorders.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {110},
number = {1},
pages = {5-25},
doi = {10.1177/13872877251411546},
pmid = {41527739},
issn = {1875-8908},
mesh = {Humans ; Biomarkers/metabolism ; *Phosphoproteins/metabolism ; *Proteomics/methods ; *Brain Diseases/metabolism/diagnosis ; Phosphorylation ; Animals ; },
abstract = {The dysregulation of phosphorylation networks plays a critical role in the pathogenesis of a wide spectrum of brain disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, ischemic stroke, drug abuse, major depressive disorder, and schizophrenia. Notably, phosphorylated isoforms of microtubule-associated protein tau and neurofilament heavy polypeptide are already utilized in clinical diagnostics, highlighting the promise of protein phosphorylation signatures as biomarkers for prediction, diagnosis, prognosis, and treatment monitoring. Recent advances in deep phosphoproteomic technologies now facilitate the comprehensive mapping of phosphorylation alterations across diverse biological samples and disease stages. This review summarizes current phosphoproteomic studies aimed at identifying biomarkers for brain disorders and elaborates on the promising application of phosphorylated proteins in this context.},
}

Humans
Biomarkers/metabolism
*Phosphoproteins/metabolism
*Proteomics/methods
*Brain Diseases/metabolism/diagnosis
Phosphorylation
Animals

@article {pmid41530082,
year = {2026},
author = {Cooper, P and Lu, M and Chan, M and Wilman, A and Kalra, S and Ghavanini, AA},
title = {Exploring the Value of Brain T2* Weighted and FLAIR Imaging for Diagnosing Amyotrophic Lateral Sclerosis.},
journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques},
volume = {},
number = {},
pages = {1-6},
doi = {10.1017/cjn.2026.10527},
pmid = {41530082},
issn = {0317-1671},
abstract = {OBJECTIVES: Early diagnosis of amyotrophic lateral sclerosis (ALS) is essential for treatment initiation and symptom management, yet it remains challenging due to nonspecific symptoms and the lack of reliable diagnostic biomarkers. Although conventional MRI sequences such as T2* weighted and fluid-attenuated inversion recovery (FLAIR) have shown potential in identifying upper motor neuron abnormalities, their diagnostic utility in ALS is not well established. This study aimed to evaluate the sensitivity and specificity of brain T2* weighted and FLAIR MRI sequences in diagnosing ALS using prospectively collected data and to assess associations with disease severity.

METHODS: Data were analyzed from 20 patients with ALS and 20 healthy controls enrolled at the Edmonton site of the Canadian ALS Neuroimaging Consortium 1 (CALSNIC-1) study. Single-slice 2D axial susceptibility-weighted echo planar imaging (SWEPI) and FLAIR images were independently rated by a blinded neurologist and radiologist for signs of corticospinal tract and motor cortex abnormalities. Sensitivity and specificity were calculated, and linear regression was used to examine associations with ALS Functional Rating Scale-Revised (ALSFRS-R) scores.

RESULTS: T2* weighted and FLAIR MRI sequences showed high specificity (0.95 and 0.85, respectively) but low sensitivity (both 0.25) for ALS diagnosis. No significant correlation was found between imaging abnormalities and ALSFRS-R scores. Inter-rater reliability was poor (κ = 0.25 for SWEPI; κ = 0.14 for FLAIR).

CONCLUSION: While T2* weighted and FLAIR MRI sequences may have some specificity for ALS, our study suggests they are not sufficiently sensitive to be used as reliable diagnostic tools for ALS.},
}

@article {pmid41530593,
year = {2026},
author = {Muneer, MA and Tariq, I and Zulfiqar, E and Saaki, SS and Gupta, I and Bokhari, SMNA and Verma, A and Mehta, R and Sah, R and Ahmed, SI},
title = {Efficacy and safety of dextromethorphan/quinidine in treating pseudobulbar affect in neurological disorders: A systematic review and dose-classified network meta-analysis.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {1},
pages = {159},
pmid = {41530593},
issn = {1590-3478},
mesh = {Humans ; *Dextromethorphan/administration & dosage/adverse effects/pharmacology/therapeutic use ; Drug Combinations ; *Nervous System Diseases/drug therapy/complications ; *Pseudobulbar Palsy/drug therapy ; *Quinidine/administration & dosage/adverse effects/pharmacology/therapeutic use ; Randomized Controlled Trials as Topic ; },
abstract = {BACKGROUND: Pseudobulbar affect (PBA) is a disabling neuropsychiatric condition characterized by sudden, involuntary episodes of crying or laughing incongruent with mood. It occurs in several neurological disorders, including amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, and traumatic brain injury (TBI). Dextromethorphan/quinidine (DM/Q) is the only Food and Drug Administration (FDA)-approved therapy for PBA, but optimal dosing and safety profiles remain uncertain.

OBJECTIVE: To evaluate the efficacy and safety of different DM/Q dosing regimens for treating PBA through a systematic review and network meta-analysis.

METHODS: A comprehensive search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov was conducted through March 2025. Randomized controlled trials reporting outcomes on the Center for Neurologic Study-Lability Scale (CNS-LS), Visual Analog Scale-Quality of Life (VAS-QOL), Visual Analog Scale-Quality of Recovery (VAS-QOR), and adverse events were included. Analyses were performed using R (netmeta package), and bias was assessed with the Cochrane RoB 2.0 tool.

RESULTS: Five randomized controlled trials comprising 605 participants were analyzed. DM/Q 20/10 mg and 30/10 mg significantly improved CNS-LS scores (mean difference [MD] - 2.52 and - 2.45, respectively), while DM/Q 30/30 mg produced greater gains in VAS-QOL (MD 17.20) and VAS-QOR (MD 14.90). Dizziness was the only statistically significant, dose-related adverse event.

CONCLUSION: DM/Q combination therapy provides effective symptom control for PBA, with favorable tolerability. Both 20/10 mg and 30/10 mg doses improve emotional lability, while 30/30 mg yields additional quality-of-life benefits. Further studies should assess long-term safety and disorder-specific dosing optimization.},
}

Humans
*Dextromethorphan/administration & dosage/adverse effects/pharmacology/therapeutic use
Drug Combinations
*Nervous System Diseases/drug therapy/complications
*Pseudobulbar Palsy/drug therapy
*Quinidine/administration & dosage/adverse effects/pharmacology/therapeutic use
Randomized Controlled Trials as Topic

@article {pmid41531269,
year = {2026},
author = {Elmaleh, B and Faust, O and Rosenzweig, R},
title = {The ALS-associated E425K mutation uncouples DNAJC7 from the Hsp70 chaperone cycle.},
journal = {The FEBS journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/febs.70395},
pmid = {41531269},
issn = {1742-4658},
support = {1093/22//Israel Science Foundation/ ; //Minerva Foundation/ ; ERC-CoG-2024 101169856//H2020 European Research Council/ ; },
abstract = {DNAJC7, a member of the J-domain protein (JDP/Hsp40) family, plays a key role in protein homeostasis by regulating Hsp70 activity and preventing protein aggregation. Mutations in DNAJC7 have been linked to amyotrophic lateral sclerosis (ALS); yet, the molecular mechanisms by which these variants impair chaperone function remain poorly understood. DNAJC7 is a conserved chaperone featuring both a canonical J-domain, essential for Hsp70 activation, and three TPR domains, which serve as protein-protein binding interfaces. Here, we investigate the structural and functional consequences of the ALS-associated E425K mutation located within the conserved J-domain. Using NMR spectroscopy, we show that although the E425K mutation does not alter the structure of the protein, it significantly disrupts the conserved J-domain-Hsp70 interaction. We further identify a second Hsp70-binding interface within the TPR domains, which interacts with the C-terminal EEVD motif of Hsp70. This TPR-EEVD interaction is preserved in the E425K mutant but cannot compensate for the loss of J-domain binding or restore DNAJC7-dependent Hsp70 activation. Functionally, we show that the TPR domains of DNAJC7 directly bind TDP-43 and prevent its aggregation and that this holdase activity is retained in the E425K mutant. However, the mutant fails to support client transfer to Hsp70 and the subsequent Hsp70-mediated substrate refolding. Together, these findings demonstrate that DNAJC7 requires coordinated action of both J-domain and TPRs to regulate Hsp70 function and that disruption of J-domain-mediated activation uncouples DNAJC7 from the Hsp70 cycle, providing a mechanistic basis for its dysfunction in ALS.},
}

@article {pmid41531792,
year = {2026},
author = {Yang, X and Huang, S and Wang, Y and Yuan, J and Yao, X},
title = {Identification of Comprehensive Landscape of Peripheral Immunity and Chemokine-Related Genes in Amyotrophic Lateral Sclerosis.},
journal = {ImmunoTargets and therapy},
volume = {15},
number = {},
pages = {566733},
pmid = {41531792},
issn = {2253-1556},
abstract = {PURPOSE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Progressive loss of motor neuron function and disruption of the blood-brain barrier are key features of ALS. Under the influence of chemokines, peripheral immune cells migrate into the central nervous system, thereby affecting the neuronal microenvironment. The aim of this study is to classify ALS based on the immune characteristics of peripheral blood in patients with the disease, and to construct prognostic models.

PATIENTS AND METHODS: A total of 397 ALS patients and 645 healthy controls (GSE112676 and GSE112680) were included. ALS chemotactic subtypes were constructed based on differentially expressed genes of chemokine and chemokine receptors (CCRs). The Cibersort algorithm was used to investigate the abundance of immune cells in peripheral blood. Univariate Cox regression analysis was performed to screen for CCRs genes, clinical characteristics, and immune cells associated with prognosis. Prognostic models were constructed based on these variables. Finally, external validation was conducted using samples from ALS patients diagnosed at the First Affiliated Hospital of Sun Yat-sen University.

RESULTS: There were significant differences in the abundance of peripheral immune cells between ALS patients and healthy controls. 17 CCRs genes were identified as differentially expressed. CCL23, CCR8, CXCR4, site of onset, age of onset, and "CD4 naive T cells" were demonstrated to be significantly correlated with survival time. Two chemotactic subtypes were established. Eight prognostic models could distinguish between high-risk and low-risk ALS patients. At year five, the areas under the receiver operating characteristic curves for the PlsRcox, Coxboost, and Xgboost algorithms were 0.747, 0.733, and 0.728, respectively. External test sets successfully validated these results.

CONCLUSION: ALS patients exhibit peripheral immune abnormalities. Peripheral immune status could be used to distinguish ALS subtypes and construct prognostic models. Understanding peripheral immune changes in ALS patients may inform potential immunotherapies.},
}

@article {pmid41531877,
year = {2025},
author = {Finsterer, J},
title = {There is currently no evidence that long-COVID-19 leads to neurodegenerative diseases such as SDAT, amyotrophic lateral sclerosis, or Parkinson's disease.},
journal = {Brain circulation},
volume = {11},
number = {4},
pages = {354-355},
pmid = {41531877},
issn = {2455-4626},
}

@article {pmid41532955,
year = {2026},
author = {Bernal-Vicente, BN and Ponce, I and Ríos-Castro, E and Moreno-Castilla, P and Tovar-Y-Romo, LB},
title = {Unveiling the Proteomic Landscape of Extracellular Vesicles: Implications for Neurodegeneration and Neuroprotection.},
journal = {Journal of neurochemistry},
volume = {170},
number = {1},
pages = {e70350},
pmid = {41532955},
issn = {1471-4159},
support = {IN214723//Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México/ ; },
mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Proteomics/methods ; Animals ; *Neurodegenerative Diseases/metabolism/pathology ; *Neuroprotection/physiology ; Biomarkers/metabolism ; },
abstract = {Extracellular vesicles (EVs) are instrumental mediators of intercellular communication and molecular exchange in neurodegenerative and neurovascular diseases. This review integrates recent advances in EV proteomics to elucidate their roles in Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), traumatic brain injury (TBI), and ischemic stroke. Across these conditions, EVs carry disease-relevant proteins that reflect and influence key pathological processes such as synaptic dysfunction, neuroinflammation, blood-brain barrier (BBB) disruption, and cell death. Proteomic profiling of brain- and biofluid-derived EVs has uncovered specific biomarkers and signaling pathways, ranging from tau and α-synuclein in AD and PD to mutant SOD1 in ALS and complement activation in stroke and TBI. Moreover, cell-type-specific EVs (e.g., from neurons, astrocytes, microglia, and stem cells) have been shown to exert either protective or deleterious effects, modulating apoptosis, axonal regeneration, and immune responses. Recent evidence highlights the translational potential of EVs as non-invasive biomarkers and therapeutic vectors across multiple disorders. By mapping shared and divergent proteomic signatures in EVs, we review the mechanistic relevance and clinical utility of EVs in neurodegeneration and CNS injury.},
}

Humans
*Extracellular Vesicles/metabolism
*Proteomics/methods
Animals
*Neurodegenerative Diseases/metabolism/pathology
*Neuroprotection/physiology
Biomarkers/metabolism

@article {pmid41533211,
year = {2026},
author = {Shu, X and Zeng, J and Zhang, K},
title = {TREM2-mediated Crosstalk in ALS: Microglial Fate Transition, Protein Aggregate Clearance, and Peripheral Nerve Repair.},
journal = {Neuroscience bulletin},
volume = {},
number = {},
pages = {},
pmid = {41533211},
issn = {1995-8218},
}

@article {pmid41534282,
year = {2026},
author = {Hosseinpour Moghaddam, M and Karimian, N and Johnston, SG and Choppala, G and Rastegari, M and Burton, ED},
title = {Goethite as an antimony host-phase: Atomic-scale retention mechanisms and the selectivity of commonly-applied extraction schemes.},
journal = {Journal of hazardous materials},
volume = {503},
number = {},
pages = {141097},
doi = {10.1016/j.jhazmat.2026.141097},
pmid = {41534282},
issn = {1873-3336},
abstract = {Goethite (α-FeOOH) is one of the most important host-phases for Sb(V) in soils, sediments and geogenic wastes. This study examines, for the first time, how variability in the atomic-scale mechanisms of Sb(V) retention by goethite impacts the selectivity of commonly-applied Sb extraction schemes. EXAFS spectroscopy shows that Sb(V) retention via coprecipitation involves Sb(V) incorporation into goethite's structure through Sb(V)-for-Fe(III) substitution. In contrast, Sb(V) retention via sorption involves edge and double-corner sharing between SbO6 and FeO6 octahedra at the goethite surface. Incorporation of Sb(V) into goethite's structure causes Sb(V) to be largely inaccessible to 1 M HCl, steps 1, 2 and 3 of Wenzel et al.'s sequential extraction scheme and all 3 steps of the BCR extraction scheme. In contrast, Sb(V) sorption to goethite's surface facilitates more substantial Sb(V) extractability, which varies with the relative abundance of SbO6-FeO6 linkages. Importantly, Sb(V) sorption to the goethite surface is underestimated by both the Wenzel et al. and BCR schemes. In addition, the BCR scheme misidentifies a significant portion of goethite-sorbed Sb(V) as oxidisable phases (e.g. sulfides or organic matter). Hence, in soils, sediments or geogenic wastes where Sb(V) is sorbed to goethite, the BCR scheme is not appropriate for quantifying Sb(V) fractionation. Overall, our results demonstrate that variability in the atomic-scale mechanisms by which goethite retains Sb(V) translate to substantial complexity in Sb(V) extractability.},
}

@article {pmid41534442,
year = {2026},
author = {Nomura, E and Morihara, R and Osakada, Y and Yunoki, T and Takemoto, M and Yamashita, T and Ishiura, H},
title = {The utility of Gold Coast criteria for amyotrophic lateral sclerosis.},
journal = {Journal of the neurological sciences},
volume = {481},
number = {},
pages = {125733},
doi = {10.1016/j.jns.2026.125733},
pmid = {41534442},
issn = {1878-5883},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis ; Male ; Middle Aged ; Female ; Retrospective Studies ; Aged ; Sensitivity and Specificity ; Adult ; },
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease. Current diagnostic criteria, including the revised El Escorial (rEE) and Awaji (AW) criteria, have limitations in sensitivity. The Gold Coast (GC) criteria were proposed to simplify diagnosis and improve early detection, but their real-world performance remains unclear.

METHODS: We retrospectively analyzed 260 patients suspected of ALS who were admitted to our department between 2013 and 2022. The GC, AW, and rEE criteria were applied to data from initial hospitalization. Final diagnoses were based on follow-up data, and sensitivity/specificity were compared using McNemar's test.

RESULTS: The GC criteria showed equivalent sensitivity (91.6 %), but higher specificity (75.9 %) compared to all combined AW and rEE categories. GC sensitivity was significantly higher than that of AW/rEE definite/probable categories. False negatives of GC criteria were often due to insufficient LMN signs, particularly in bulbar-onset cases. Subgroup analysis showed consistent trends.

CONCLUSION: The GC criteria demonstrated high sensitivity and moderate specificity, supporting their clinical utility in early ALS diagnosis. However, variability in clinical presentation and retrospective limitations suggest the need for further prospective validation.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis
Male
Middle Aged
Female
Retrospective Studies
Aged
Sensitivity and Specificity
Adult

@article {pmid41534462,
year = {2026},
author = {Mortensen, CK and Jokinen, CLV and Sørensen, CLH and Løkkegaard, SS},
title = {Beyond the birthing body: Towards a relational and inclusive understanding of birth trauma. A commentary on Donegan et al. (2025).},
journal = {Midwifery},
volume = {154},
number = {},
pages = {104705},
doi = {10.1016/j.midw.2026.104705},
pmid = {41534462},
issn = {1532-3099},
mesh = {Humans ; Female ; Pregnancy ; Qualitative Research ; Adult ; *Parturition/psychology ; Denmark ; },
abstract = {In their recent scoping review, Donegan, Zhao, and Mansu (2025) provide a valuable synthesis of international best practice guidelines on birth trauma support for birthing women. While several reviews have explored fathers' experiences of traumatic or complicated births and proposed recommendations for improved care, systematic implementation and empirical evaluation remain limited. In this commentary, we broaden Donegan et al.'s focus on birthing women by extending the scope of trauma-informed perinatal care to also include non-birthing parents. Drawing on findings from a Danish qualitative study conducted in spring 2025, as well as existing research and theoretical perspectives, we explore how non-birthing parents can be profoundly affected by traumatic births - often without recognition or adequate support. We conclude by offering six recommendations for practice and future research aimed at broadening the scope of trauma-informed perinatal care to meaningfully include non-birthing parents and thereby reduce the triadic impact of birth trauma and support individual and family functioning.},
}

Humans
Female
Pregnancy
Qualitative Research
Adult
*Parturition/psychology
Denmark

@article {pmid41534629,
year = {2026},
author = {Ortega Douville, C},
title = {First evidence supporting the theory of the sensorimotor paradox on the origins of mind and language.},
journal = {Bio Systems},
volume = {262},
number = {},
pages = {105691},
doi = {10.1016/j.biosystems.2026.105691},
pmid = {41534629},
issn = {1872-8324},
mesh = {Humans ; *Language ; *Feedback, Sensory/physiology ; Electroencephalography ; *Biological Evolution ; Movement/physiology ; Brain/physiology ; },
abstract = {For now 15 years, I have been developing a hypothesis on the origins of mind and language during our evolution, called theory of the sensorimotor paradox. The core neuroimaging part of the hypothesis is that the switch in our relation to our hands, coming with bipedal stance, would have allowed us to disrupt the function of sensory prediction to resolve into motor action and sensory feedback: we can't take our hand as an object of interaction and have it grasp itself at the same time. This would later on be autonomised as mental representation. From there, non-resolution of prediction into motor action would prevent a system from liberating tension in order to be available again and collect feedback (meta-prediction). Using Schalk, G. et al.'s extensive dataset of EEG recordings on motor movement and imagery (2009), I am now able to support some of the theory's claims. Notably, meta-analysis of movement and imagery recordings tends to stress a higher variability of frequency activation amongst motor signals than imagery's. This would indicate a greater difficulty for a system to release tension in an effort to produce and maintain mental representation. Similar short oscillatory predictive change, but greater uncoupling of frontal and prefrontal regions suggests sensory suppression of efference-copy and greater instability toward the eventuality of collecting feedback when motor action is triggered, relying on somatosensory support. Event-related time-frequency analysis on proprioceptive areas shows delay of neural signal to mental representation compared to motor action, which could be a strong evidence of dissociation.},
}

Humans
*Language
*Feedback, Sensory/physiology
Electroencephalography
*Biological Evolution
Movement/physiology
Brain/physiology

@article {pmid41534661,
year = {2026},
author = {Costa, I and Barbosa, DJ and Remião, F and Sousa, ME and Silva, R},
title = {A dive into the untapped potential of marine compounds in counteracting neurodegeneration.},
journal = {Pharmacology & therapeutics},
volume = {279},
number = {},
pages = {108982},
doi = {10.1016/j.pharmthera.2026.108982},
pmid = {41534661},
issn = {1879-016X},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/physiopathology ; Animals ; *Aquatic Organisms/chemistry ; *Biological Products/pharmacology/therapeutic use/isolation & purification ; *Neuroprotective Agents/pharmacology/therapeutic use/isolation & purification ; },
abstract = {Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, are characterized by the progressive breakdown and eventual loss of synapses and neurons, primarily driven by the accumulation of pathologically altered proteins within the brain and spinal cord. These diseases have complex and multifactorial etiologies, involving a broad spectrum of pathophysiological mechanisms, many of which remain incompletely understood. Nonetheless, several key pathways are consistently implicated across these conditions, including oxidative stress, mitochondrial dysfunction, neuroinflammation, and apoptosis. Given their rising prevalence and the persistent lack of effective disease-modifying therapies, the development of novel therapeutic strategies capable of targeting multiple pathophysiological processes is of critical importance for delaying or halting disease progression. In this context, marine natural compounds have emerged as promising candidates for counteracting neurodegeneration, owing to their ability to modulate key pathophysiological hallmarks of distinct neurodegenerative diseases. Derived from a wide range of marine organisms - including algae, sponges, fungi, and cyanobacteria - these bioactive molecules possess unique chemical structures and exhibit a broad spectrum of neuroprotective effects. Many have demonstrated potent antioxidant, anti-apoptotic, and mitochondrial-stabilizing activities in preclinical models. This review highlights recent advances in the discovery and characterization of marine-derived compounds with therapeutic potential in neurodegenerative diseases, contextualizing their pathologic mechanisms.},
}

Humans
*Neurodegenerative Diseases/drug therapy/physiopathology
Animals
*Aquatic Organisms/chemistry
*Biological Products/pharmacology/therapeutic use/isolation & purification
*Neuroprotective Agents/pharmacology/therapeutic use/isolation & purification