@article {pmid42374626,
year = {2026},
author = {Walton, EI and Sun, J},
title = {Microbiome and metabolites impact enteric and central nervous systems in ALS.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2692737},
doi = {10.1080/19490976.2026.2692737},
pmid = {42374626},
issn = {1949-0984},
mesh = {*Amyotrophic Lateral Sclerosis/microbiology/metabolism/physiopathology ; Humans ; *Central Nervous System/metabolism/microbiology/physiopathology ; *Enteric Nervous System/metabolism/physiopathology/microbiology ; *Gastrointestinal Microbiome/physiology ; Animals ; Dysbiosis/microbiology ; },
abstract = {Amyotrophic lateral sclerosis (ALS) has been linked to gastrointestinal symptoms and alterations in the gut microbiota. The enteric nervous system (ENS) coordinates intestinal function and sits at the host-microbe interface. The mechanisms by which luminal changes relay to the central nervous system (CNS), where motor neurons reside, have yet to be completely defined. In this narrative review, we first present evidence from ALS patient cohorts and preclinical models alongside mechanistic studies of infection, dysbiosis, and related neurodegenerative diseases to discuss how the microbiota and its metabolites may affect the ENS and CNS in ALS. Next, we propose a plausible mechanism of ALS pathogenesis through the gut-microbiome-brain axis. We further offer a summary of clinical trials that have studied the impacts of the microbiota on human ALS. Finally, we discuss future directions for studies of microbiota-ENS-CNS interactions in ALS. Better understanding of the dynamic interactions among the microbiota, microbial metabolites, neuroactive metabolites, and inflammation through the ENS/CNS in ALS will provide innovative insights into ALS prevention and treatment.},
}

*Amyotrophic Lateral Sclerosis/microbiology/metabolism/physiopathology
Humans
*Central Nervous System/metabolism/microbiology/physiopathology
*Enteric Nervous System/metabolism/physiopathology/microbiology
*Gastrointestinal Microbiome/physiology
Animals
Dysbiosis/microbiology

@article {pmid42375068,
year = {2026},
author = {Siddik, SH and Miah, MBA and Alam, SKM and Sumaiya, TS and Debnath, D and Haque, SMA},
title = {Distal Motor Latency in Amyotrophic Lateral Sclerosis: A Robust and Reliable Prognostic Marker.},
journal = {Mymensingh medical journal : MMJ},
volume = {35},
number = {3},
pages = {924-931},
pmid = {42375068},
issn = {2408-8757},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Prognosis ; Female ; Male ; Longitudinal Studies ; Middle Aged ; Adult ; },
abstract = {An electrophysiological test is routinely done to confirm Amyotrophic Lateral Sclerosis (ALS) and rule out differentials. Distal Motor Latency (DML) is a simple electrophysiological measure that is always done in a primary setting. It can be used as an excellent prognostic marker for ALS so that we can know ALS better and formulate precise management plans. This longitudinal study was conducted in the Neurology Department of Bangladesh Medical University (BMU), Dhaka, Bangladesh from April 2022 to October 2023. In this study a total of 34 subjects, 17 ALS patients with normal DML and 17 ALS patients with prolonged DML, were enrolled. Severity was assessed by the ALS functional rating scale-revised (ALSFRS-R). The study's endpoints were determined as death during this 6-month follow-up or reaching an advanced stage (ALSFRS-R <20). Then, an electrophysiological test was used to measure DML in all four commonly tested nerves. ALSFRS-R was significantly reduced (p<0.025) at 6 months in ALS patients with prolonged DML than normal DML. It was found that having a higher odd (p<0.012, OR=20.718), prolonged DML had a significant impact on the outcome of ALS patients than that of normal DML. In multivariate analysis, lower ALSFRS-R at diagnosis (B= -0.124, p<0.001, HR=0.883) and prolonged DML (B=1.412, p<0.031, HR=4.104) were associated with poor outcomes. ALS patients with prolonged DML also had a poorer prognosis than patients with normal DML (log-rank test, p<0.045). In this study, patients with prolonged DML had a significant functional decline, rapid disease progression and poor prognosis than patients with normal DML. So, prolonged DML can be used as a robust prognostic marker for patients with ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/diagnosis
Prognosis
Female
Male
Longitudinal Studies
Middle Aged
Adult

@article {pmid42375130,
year = {2026},
author = {Bozkurt, H and Reid, KR and Newton, J and Gill, J and Chau, I and Parker, C and Kurucu King, H and Tam, J and Ng, D and Stavrou, M and Baxter, P and Marland, O and Burr, K and Heslegrave, A and Veleva, E and Swann, OJ and Zetterberg, H and Hunt, DPJ and Thangaraj Selvaraj, B and Chandran, S and Pal, S},
title = {Blood-based biomarker discovery in motor neuron disease using nucleic acid-linked immuno-sandwich assay.},
journal = {Brain communications},
volume = {8},
number = {3},
pages = {fcag180},
pmid = {42375130},
issn = {2632-1297},
abstract = {Motor neuron disease (MND) presents with phenotypic heterogeneity, is diagnostically challenging, and has poor prognosis. The absence of accessible blood-based biomarkers has hampered progress towards precision medicine. Highly sensitive immunoassays offer considerable promise for identifying blood-based biomarkers informing underlying pathophysiology and enabling accurate diagnosis and monitoring. We report findings on parallel use of the ultra-sensitive multiplexed NUcleic Acid-Linked Immuno-Sandwich Assay (NULISA) and single molecule array (Simoa), to interrogate serum from people with MND. Sera (48 MND, 38 controls) were analysed using a NULISAseq targeted neurodegenerative panel and a Simoa neurofilament light chain (NfL) and glial fibrillary acid protein (GFAP) duplex assay. Neurofilament light and heavy chain, total tau (t-tau), phosphorylated tau (pTau)-181, pTau-217, pTau-231, fatty acid binding protein 3, amyloid beta (Aβ) 38 and Aβ40 levels were significantly elevated in MND (P < 0.05). Simoa and NULISAseq assays demonstrated strong correlations for NfL and GFAP (r > 0.90). Use of the multiplexed NULISAseq panel confirmed a well-established NfL elevation in MND, and replicated findings for other proteins from recent studies. Results add confidence in the validity and reproducibility of biomarkers identified using NULISAseq, while offering insights into the underlying pathophysiology and heterogeneity of MND.},
}

@article {pmid42375131,
year = {2026},
author = {Thomas, EV and Pant, DC},
title = {Beyond neurofilaments: a multidimensional blood signature for amyotrophic lateral sclerosis.},
journal = {Brain communications},
volume = {8},
number = {3},
pages = {fcag231},
pmid = {42375131},
issn = {2632-1297},
abstract = {This scientific commentary refers to 'Blood-based biomarker discovery in motor neuron disease using nucleic acid-linked immuno-sandwich assay', by Bozkurt et al. (https://doi.org/10.1093/braincomms/fcag180).},
}

@article {pmid42375239,
year = {2026},
author = {Koçer, AM and Acar, A},
title = {Letter to the Editor: Comment on Gümüş et al.'s "Toluene-Related Toxic Optic Neuropathy: A Case Report".},
journal = {Neuro-ophthalmology (Aeolus Press)},
volume = {50},
number = {4},
pages = {397-398},
pmid = {42375239},
issn = {0165-8107},
abstract = {We highlight key diagnostic gaps in a reported case of toluene-related toxic optic neuropathy, including the absence of anion gap calculation, lack of explicit methanol exclusion, and incomplete temporal characterization of visual symptoms. A comprehensive toxicological workup - including serum methanol levels, osmolar gap, and metabolic profiling - is essential to distinguish toluene from methanol or mixed solvent toxicity in cases of acute bilateral visual loss.},
}

@article {pmid42376391,
year = {2026},
author = {Ali, MA and Al-Ezzy, AIA},
title = {Investigating the human-animal interface: Clinical and molecular features of oral Candida spp. in cat owners.},
journal = {Open veterinary journal},
volume = {16},
number = {2},
pages = {1012-1026},
pmid = {42376391},
issn = {2218-6050},
mesh = {Animals ; Cats ; Humans ; *Cat Diseases/microbiology/epidemiology ; Male ; Female ; *Mouth/microbiology ; *Candida/isolation & purification/genetics ; *Candidiasis, Oral/veterinary/microbiology/epidemiology ; Candida albicans/isolation & purification/genetics ; Risk Factors ; },
abstract = {BACKGROUND: Candida albicans is a ubiquitous commensal fungus and is capable of transitioning from commensalism to infection.

AIM: To isolate and identify Candida spp. from oral swabs of domestic cats. Detection of virulence factors, agglutinin-like sequence agglutinin-like sequence 1 (ALS), and Candidalysin (ECE1) genes exploration of the possible relationship between Candida and potential risk factors in cat owners.

METHODS: A total of 119 oral swabs were collected from cat owners and streaked directly on Sabouraud's dextrose and chrome agars. Confirmation was performed by testing the isolates using the Vitek 2 compact system and conventional polymerase chain reaction (PCR) using primers specific to the ITS4 and ITS5 regions. ALS and ECE1 genes were detected using conventional PCR.

RESULTS: The total number of Candida spp. isolated from the oral cavity of cat owners was 10/119 (8.40%). Correlations were reported between the isolation of Candida from the oral cavity and age group; use of oral antibiotic drops; diabetes mellitus; oral lesions; and vitamin D3 deficiency (p value < 0.001). No significant correlation was reported between sex, season, smoking habit, denture wearing, steroid inhalation, immune suppression, and Candida isolation from the oral cavity of cat owners. ASL1 and ECE1 were detected in 100% of C. albicans isolated from the oral cavity of cat owners.

CONCLUSION: This study reveals a low prevalence but high pathogenic potential of oral C. albicans in domestic cat owners, as evidenced by the universal presence of major virulence genes (ALS1, ECE1). Older age, antibiotic drops, Diabetes miletus, oral lesions, and vitamin D3 deficiency were associated with the risk of colonization. The commonly suspected risk factors showed no association. The universal presence of ALS1 and ECE1 highlights the pathogenic threat posed by these yeasts.},
}

Animals
Cats
Humans
*Cat Diseases/microbiology/epidemiology
Male
Female
*Mouth/microbiology
*Candida/isolation & purification/genetics
*Candidiasis, Oral/veterinary/microbiology/epidemiology
Candida albicans/isolation & purification/genetics
Risk Factors

@article {pmid42376656,
year = {2026},
author = {Baik, J and Hughes, N and Ferrer, V},
title = {Afferent loop syndrome secondary to recurrent pancreatic adenocarcinoma post-Whipple procedure: case report.},
journal = {Frontiers in oncology},
volume = {16},
number = {},
pages = {1838218},
pmid = {42376656},
issn = {2234-943X},
abstract = {BACKGROUND: Afferent loop syndrome (ALS) is a rare but serious complication following pancreaticoduodenectomy, most often due to recurrent malignancy.

CASE PRESENTATION: A 62-year-old male patient with stage IIb pancreatic ductal adenocarcinoma status post-Whipple procedure presented with acute abdominal pain, bowel obstruction, and sepsis after months of persistent watery diarrhea. Imaging demonstrated recurrent pancreatic malignancy causing obstruction of the pancreaticobiliary limb consistent with ALS. Blood cultures grew Klebsiella pneumoniae, confirming sepsis secondary to obstruction. Endoscopy revealed a severe non-traversable afferent limb stricture, and palliative decompression with uncovered metal stent placement resulted in rapid clinical improvement.

DISCUSSION/CONCLUSION: This case highlights the need for a high degree of suspicion for ALS in post-Whipple patients with nonspecific gastrointestinal symptoms, particularly in the setting of recurrent malignancy. The prolonged refractory diarrhea preceding acute obstruction illustrates an atypical presentation that may delay diagnosis. Early imaging and minimally invasive endoscopic intervention can provide effective palliation and prevent severe complications.},
}

@article {pmid42377311,
year = {2026},
author = {Price, TR and Chang, CY and Skinner, K and Dinneny, M and Nafezi, P and Kuramoto, L and De Vera, MA and Cashman, NR and Cragg, JJ},
title = {Could anticholinergics accelerate ALS progression? A critical perspective on drug safety and disease vulnerability.},
journal = {Expert opinion on drug safety},
volume = {},
number = {},
pages = {1-16},
doi = {10.1080/14740338.2026.2687628},
pmid = {42377311},
issn = {1744-764X},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with limited treatment options and diverse symptoms necessitating active management. Anticholinergic medications are frequently used in ALS care, particularly for sialorrhea and mood disturbances. Their cumulative effects, termed anticholinergic burden, may pose underrecognized risks in this neurologically vulnerable population. This review highlights a plausible safety signal and outlines priorities for future research.

AREAS COVERED: This narrative review synthesizes evidence from non-ALS populations reporting associations between higher anticholinergic burden and cognitive decline, respiratory complications, functional deterioration, and mortality. Evidence was identified through targeted PubMed/MEDLINE and Embase searches with reference chaining, emphasizing recent and seminal studies. Mechanistic overlap with ALS pathophysiology, including neuromuscular junction disruption, impaired cholinergic signaling, and neuroinflammation, supports biological plausibility for harm. Current ALS guidelines do not address cumulative anticholinergic exposure, leaving clinicians without a framework for evaluating risk or deprescribing.

EXPERT OPINION: This article proposes a testable hypothesis that anticholinergic burden may represent a clinically relevant yet unmeasured risk factor in ALS. Emerging pharmacoepidemiologic methods and validated burden tools offer approaches to quantify exposure and evaluate relationships with ALS outcomes, supporting safer symptomatic management. Prioritizing longitudinal studies and integrating burden assessment into multidisciplinary care may help clarify risk.},
}

@article {pmid42377323,
year = {2026},
author = {Wei, LC},
title = {Clinical Confidence in Personality Disorder Care Requires Team-Based Formulation.},
journal = {Personality and mental health},
volume = {20},
number = {3},
pages = {e70092},
doi = {10.1002/pmh.70092},
pmid = {42377323},
issn = {1932-863X},
mesh = {Humans ; *Personality Disorders/therapy ; *Patient Care Team ; *Clinical Competence ; Surveys and Questionnaires ; *Psychotherapy, Psychodynamic ; },
abstract = {This letter responds to Pingani et al.'s validation of a questionnaire on clinical confidence and psychodynamic skills in personality disorder care. It argues that confidence should be interpreted at the team level, where formulation, boundaries, risk communication, and emotional containment shape the patient's experience of care.},
}

Humans
*Personality Disorders/therapy
*Patient Care Team
*Clinical Competence
Surveys and Questionnaires
*Psychotherapy, Psychodynamic

@article {pmid42378369,
year = {2026},
author = {Kim, J and Lee, H and Lim, J and Oh, J and Shin, SS and Yoon, M},
title = {RETRACTED: Kim et al. The Angiogenesis Inhibitor ALS-L1023 from Lemon-Balm Leaves Attenuates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease Through Regulating the Visceral Adipose-Tissue Function. Int. J. Mol. Sci. 2017, 18, 846.},
journal = {International journal of molecular sciences},
volume = {27},
number = {13},
pages = {},
pmid = {42378369},
issn = {1422-0067},
abstract = {The journal retracts the article titled "The Angiogenesis Inhibitor ALS-L1023 from Lemon-Balm Leaves Attenuates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease through Regulating the Visceral Adipose-Tissue Function" [...].},
}

@article {pmid42379746,
year = {2026},
author = {Farsang, Z and Pánczél, Z and Jaskó, R and Kiss, E and Altorjay, ÁG and Szigeti, M and Rüll, M and Szilágyi, A and Altorjay, Á and Vereczkei, A},
title = {Navigating Unanticipated Non-recurrent Laryngeal Nerves in Thyroid Surgery: Strategies for Preservation and Anticipation.},
journal = {In vivo (Athens, Greece)},
volume = {40},
number = {4},
pages = {2150-2156},
doi = {10.21873/invivo.14368},
pmid = {42379746},
issn = {1791-7549},
mesh = {Humans ; Female ; Male ; *Thyroid Gland/surgery ; *Thyroidectomy/adverse effects/methods ; *Recurrent Laryngeal Nerve/surgery ; Middle Aged ; Adult ; *Laryngeal Nerves/surgery ; Aged ; Ultrasonography ; Adolescent ; },
abstract = {BACKGROUND/AIM: This study aimed to investigate the incidence, anatomical characteristics, and clinical implications of non-recurrent laryngeal nerves (NRLNs) discovered during thyroid surgeries and autopsies.

PATIENTS AND METHODS: A total of 2,215 thyroid surgeries and 194 autopsies were reviewed, identifying 17 and 1 case of NRLN, respectively. Data regarding nerve anatomy, associated vascular anomalies, and patient medical history were collected and analyzed. Neck ultrasound examinations were subsequently performed on the 17 living patients, 5 months to 19 years post-surgery, by three radiologists specializing in head and neck soft-tissue imaging. Two radiologists were blinded to the specific nerve anatomy, while one was unblinded.

RESULTS: Vascular anomalies of the aortic arch were described only by the unblinded radiologist. Among the 17 NRLN cases, three (16.7%) exhibited normal vascular anatomy. According to Toniato et al.'s classification, one case each was categorized as 2a, 2b, and one case involved a coexisting right NRLN and right RLN. No definitive recurrent paresis was observed, with only one patient experiencing transient palsy lasting 5 weeks. Histological evaluation revealed no structural differences between NRLN and RLN variants, although their epineurium and adventitia were notably thinner than those of the vagal nerve.

CONCLUSION: Achieving blood-free conditions for meticulous dissection and preserving sympathetic nerve branches are essential for optimal functional outcomes in thyroid surgeries involving NRLNs.},
}

Humans
Female
Male
*Thyroid Gland/surgery
*Thyroidectomy/adverse effects/methods
*Recurrent Laryngeal Nerve/surgery
Middle Aged
Adult
*Laryngeal Nerves/surgery
Aged
Ultrasonography
Adolescent

@article {pmid42381214,
year = {2026},
author = {Suer, IE and Tursun, N},
title = {Effects of elevated CO2 and temperature on cocklebur (Xanthium strumarium L.) and its herbicide response.},
journal = {Pest management science},
volume = {},
number = {},
pages = {},
doi = {10.1002/ps.71064},
pmid = {42381214},
issn = {1526-4998},
support = {//Tarimsal Araştirmalar ve Politikalar Genel Müdürlüğü, Türkiye Cumhuriyeti Tarim Ve Orman Bakanliği/ ; },
abstract = {BACKGROUND: Climate change, characterized by rising atmospheric CO2 and temperature fluctuations, significantly alters crop-weed interactions and weed management efficacy. This study evaluated the interactive effects of elevated CO2 (400, 600, 800, and 1000 ppm) and temperature regimes (26/16°C and 29/19°C) on the biomass accumulation of Xanthium strumarium and the efficacy of two herbicides with distinct modes of action: trifloxysulfuron-sodium (systemic, ALS inhibitor) and fluometuron (soil-active, PSII inhibitor).

RESULTS: Elevated CO2 concentration up to 1000 ppm at the optimal temperature (26/16°C) significantly stimulated the vegetative growth and dry biomass of X. strumarium. Crucially, dose-response analyses revealed that this climate-driven accelerated growth did not induce herbicide resistance; rather, it increased the weed's susceptibility to the systemic herbicide. Elevated CO2 facilitated the translocation of trifloxysulfuron-sodium due to increased plant metabolism, thereby significantly lowering ED50 values. In contrast, the efficacy of the soil-applied fluometuron remained highly stable and unaffected by variations in either CO2 or temperature.

CONCLUSION: The interaction between climate change variables and chemical weed control is fundamentally driven by the herbicide's mode of action. While elevated CO2 acts as a fertilizer for X. strumarium, the resulting rapid growth paradoxically increases the efficacy of systemic herbicides by accelerating the movement of active ingredients. Meanwhile, soil-active herbicides like fluometuron offer a climate-resilient weed management strategy. Future studies should incorporate molecular approaches to fully elucidate these mode-of-action-specific physiological responses under changing climatic conditions. © 2026 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.},
}

@article {pmid42381488,
year = {2026},
author = {Eigenhuis, KN and Ferrer, RM and Pasterkamp, RJ},
title = {Neural Organoid Models as a Platform for Studying Disease Mechanisms in Amyotrophic Lateral Sclerosis.},
journal = {Journal of neurochemistry},
volume = {170},
number = {7},
pages = {e70513},
doi = {10.1111/jnc.70513},
pmid = {42381488},
issn = {1471-4159},
support = {//Stichting ALS Nederland/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/metabolism ; *Organoids/pathology/metabolism ; *Induced Pluripotent Stem Cells/pathology/metabolism ; Animals ; *Neurons/pathology/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting upper and lower motor neurons leading to muscle wasting. However, structural and molecular abnormalities, including cortical thinning and TDP-43 pathology, extend into frontal, parietal, and temporal areas, pointing to defects across broader cortical regions. The advent of human induced pluripotent stem cell (hiPSC) technology has enabled the generation of human-specific brain cell types in vitro. Here, we provide an overview of the three-dimensional (3D) hiPSC-derived neural organoid platforms used to model cortical structures and to study cortical ALS-associated phenotypes. We review which pathological hallmarks have been recapitulated in these organoids and discuss disease phenotypes reported to date. Further, we comprehensively cover different neural organoid models and experimental strategies, including patient-derived hiPSC models and exogenous pathology induction, while addressing current technical challenges. Together, these advances position neural organoids as an emerging tool to study cell-type-specific and circuit-level mechanisms related to cortical changes in ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/pathology/metabolism
*Organoids/pathology/metabolism
*Induced Pluripotent Stem Cells/pathology/metabolism
Animals
*Neurons/pathology/metabolism

@article {pmid42381982,
year = {2026},
author = {Deng, Z and Zhang, R and Zhu, Y and Xu, C and Yang, M and Li, L and Cheng, Y and Shi, H and Dou, C and Zhang, M and Xia, Y and Fan, K},
title = {Antioxidant Nanozymes: From Rational Design to Biomedical Applications.},
journal = {Research (Washington, D.C.)},
volume = {9},
number = {},
pages = {1318},
pmid = {42381982},
issn = {2639-5274},
abstract = {Antioxidant nanozymes regulate reactive oxygen species homeostasis by mimicking the core catalytic functions of natural antioxidant enzymes, including superoxide dismutase-, catalase-, and glutathione peroxidase-like activities. The clinical translation of natural antioxidant enzymes has long been hampered by inherent limitations: short in vivo half-life, susceptibility to inactivation under physiological conditions, cumbersome purification processes, high production costs, non-negligible immunogenicity, and limited targeting capacity. In contrast, antioxidant nanozymes can overcome these bottlenecks with superior structural stability, tunable catalytic activity, low preparation cost, and flexible multifunctional modification. Guided by the catalytic mechanisms of natural enzymes, researchers have established rational design strategies for antioxidant nanozymes. To date, a diverse array of antioxidant nanozymes have been developed, with promising applications in multiple biomedical fields, including inflammatory diseases, ischemia-reperfusion injury, neurodegenerative disorders, and cancer adjuvant therapy. Notably, landmark clinical progress has been achieved: The catalytic nanocrystal suspension CNM-Au8, a therapeutic candidate for amyotrophic lateral sclerosis, has advanced to phase II clinical trials. This review systematically summarizes the core catalytic mechanisms of antioxidant nanozymes, clarifies the structure-activity relationships between rational material design and catalytic performance, reviews the latest advances in their biomedical applications, and dissects the key bottlenecks restricting preclinical research and clinical translation. It aims to provide rational design principles for researchers in this field, reduce empirical trial and error in material development, and provide guidance for the further optimization and clinical translation of antioxidant nanozymes.},
}

@article {pmid42382427,
year = {2026},
author = {Sugimoto, T and Tachiyama, K and Hironaka, A and Naito, H and Nakamori, M and Aoki, S and Yamazaki, Y and Maruyama, H},
title = {Simultaneous ultrasound and needle electromyography recording of fasciculations in amyotrophic lateral sclerosis.},
journal = {Clinical neurophysiology practice},
volume = {11},
number = {},
pages = {448-452},
pmid = {42382427},
issn = {2467-981X},
abstract = {OBJECTIVE: Fasciculations can be detected using both muscle ultrasonography and needle electromyography, yet the correspondence between ultrasonographically observed fasciculations (U-fas) and needle electromyography-detected fasciculation potentials (N-fas) has not been clarified. This study investigated their correspondence using fully synchronized recordings.

METHODS: Adult patients showing fasciculation-like contractions on muscle ultrasonography were enrolled; all were subsequently diagnosed with amyotrophic lateral sclerosis. Ultrasound and needle electromyography were recorded simultaneously in up to three muscles per patient, with a recording duration of 3 min per muscle. For each ultrasonographically observed fasciculation, the presence of a corresponding electromyographic event and contraction duration assessed by M-mode imaging were evaluated.

RESULTS: Ten patients with amyotrophic lateral sclerosis were included. A total of 472 focused U-fas events were analyzed. Corresponding N-fas were detected in 437 events, yielding an overall concordance rate of 92.6% (95% confidence interval, 90.2-95.0%). U-fas contraction duration ranged from 343 to 971 ms, whereas N-fas duration ranged from 10.9 to 76.4 ms. The number of phases of N-fas observed during U-fas events ranged from 1 to 10.

CONCLUSIONS: Most ultrasonographically observed fasciculations corresponded to electromyography-detected events on simultaneous recording.

SIGNIFICANCE: Ultrasonographically detected fasciculations may serve as a supplementary indicator of lower motor neuron involvement in amyotrophic lateral sclerosis.},
}

@article {pmid42383056,
year = {2026},
author = {Liu, DZ and Cheng, GL and Hu, CF and Li, RY and Yang, CC and Chen, NC and Li, X and Jiang, DY and Chang, JY},
title = {Alternative splicing-based therapeutics for neurodegenerative diseases: a dual-database bibliometric and NLP-driven analysis (2000-2025).},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1849726},
pmid = {42383056},
issn = {2296-858X},
abstract = {BACKGROUND: Neurodegenerative diseases (NDDs) are driven by complex molecular dysregulation, among which aberrant alternative splicing (AS) has emerged as a critical pathogenic mechanism. Despite the rapid development of splicing-targeted therapeutics, including antisense oligonucleotides (ASOs) and small molecules, comprehensive big-data syntheses mapping this translational landscape remain scarce. This study systematically analyzes the global research trends, conceptual frameworks, and clinical evolution of AS-based therapeutics for NDDs using an integrated bibliometric and natural language processing (NLP) approach.

METHODS: A dual-database retrieval strategy utilized the Web of Science Core Collection (WoSCC) and PubMed. The analysis targeted literature published between January 1, 2000, and December 31, 2025. A primary dataset of 620 records was extracted from WoSCC for comprehensive bibliometric mapping and Latent Dirichlet Allocation (LDA) topic modeling. A parallel analysis incorporated 10 targeted clinical trials and randomized controlled trials (RCTs) from PubMed using CLARA clustering to characterize high-evidence research. Bibliometric analyses, encompassing network topologies, citation bursts, and keyword evolution, were visualized using VOSviewer, CiteSpace, SCImago, and R.

RESULTS: Publication output exhibited sustained linear growth from 2000 to 2025. The United States and Western Europe emerged as the dominant collaborative hubs, while China exhibited high productivity but limited international integration. LDA topic modeling identified three core conceptual axes: molecular mechanisms, disease-specific pathological models (e.g., ALS, Alzheimer's, and SMA), and translational methodological frameworks. Keyword trajectories delineated a transition from fundamental in vitro exploration to in vivo models, culminating in clinical "drug discovery" and "RNA" therapeutics. CLARA clustering of clinical trials demonstrated a stark concentration of splicing-modifying interventions in pediatric spinal muscular atrophy (SMA), revealing a dual-track paradigm of supportive care and molecular interventions.

CONCLUSION: This multi-database bibliometric and NLP-driven study delineates the structural landscape of AS-based therapeutics for NDDs. It identifies a definitive paradigm shift from descriptive molecular biology to clinically actionable splicing interventions. These insights highlight the necessity to expand targeted RNA platforms beyond SMA into adult neurodegenerative populations, providing a strategic roadmap for future translational research.},
}

@article {pmid42369228,
year = {2026},
author = {Wojtowicz, E and Yous, ML and Baxter, P and Kaasalainen, S},
title = {Talking about the hypothetical future: Serious illness communication for residents living with dementia in long-term care homes - An integrative review.},
journal = {Palliative care and social practice},
volume = {20},
number = {},
pages = {26323524261462628},
pmid = {42369228},
issn = {2632-3524},
abstract = {BACKGROUND: In long-term care (LTC) homes, residents living with dementia frequently experience serious illness communication that is crisis-initiated and oriented to institutional documentation (e.g., transfer and resuscitation orders), rather than iterative, values-based discussions aligned with a palliative approach and substitute decision-making frameworks. Unpaid care partners often make high-stakes decisions with limited preparation, and residents are inconsistently included.

OBJECTIVES: To explore how serious illness communication occurs with residents living with dementia, unpaid care partners, and healthcare providers in LTC, and to identify practice-relevant communication strategies and contextual factors applicable to clinical practice.

METHODS: An integrative review following Toronto and Remington's six-stage methodology included 31 high-relevance studies (qualitative, quantitative, mixed methods, reviews, theoretical) published from 2015 to 2025 on serious illness, goals-of-care, or end-of-life communication in LTC dementia care. Directed content analysis was guided by Tarbi et al.'s basic science of communication in serious illness (lexical, non-lexical, contextual elements, and outcomes).

RESULTS: Serious illness communication was predominantly biomedical and documentation-focused, often occurring at admission or during crises and directed mainly to unpaid care partners, with limited resident involvement. Lexical practices such as clear, jargon-free information, explicit invitations to discuss "what matters most," and early conversations about hypothetical future scenarios enhanced trust, preparedness, and alignment of care with resident values. Non-lexical elements (tone, eye contact, pacing, use of silence) shaped perceived empathy but were seldom explicitly addressed by interventions.

CONCLUSIONS: For LTC healthcare providers, embedding earlier, iterative serious illness communication, explicitly involving residents where possible, and cultivating both lexical and non-lexical skills are key to achieving relationship-centred, legally compliant, and goal-concordant palliative approaches to care.​.},
}

@article {pmid42369360,
year = {2026},
author = {Keihani, A and Hassani, M and Sajadi, SS and Modarresi, SA and Khoshkholgh, M and Haresabadi, M and Amani, K and Jourahmad, Z and Ferrarelli, F},
title = {Assessing upper motor neuron dysfunction in ALS: from TMS-EEG and EMG neurophysiology to a combined tFUS-TMS translational framework.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1798525},
pmid = {42369360},
issn = {1664-2295},
abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the progressive loss of upper motor neurons (UMNs) and lower motor neurons (LMNs). Despite significant advances in molecular and neuroimaging biomarkers, the initial site of pathology and the causal contribution of UMN dysfunction to disease progression remain undetermined. Accumulating neurophysiological evidence points to cortical hyperexcitability as an early and potentially upstream mechanism, raising the possibility that UMN pathology drives LMN degeneration through an anterograde dying-forward process. In this review, we synthesize findings from noninvasive brain stimulation (NIBS) studies, with particular emphasis on transcranial magnetic stimulation (TMS)-based neurophysiological markers of UMN dysfunction. We review evidence from TMS-electromyography (TMS-EMG) and TMS-electroencephalography (TMS-EEG) paradigms demonstrating cortical disinhibition and excitatory-inhibitory imbalance in ALS, consistent with impaired GABAergic interneuronal dysfunction and supportive of a cortical onset hypothesis. Finally, we propose integrating transcranial focused ultrasound (tFUS) with TMS as a novel experimental and translational framework to directly examine and modulate cortical hyperexcitability and test the causal role of UMN dysfunction in ALS. The combination of targeted neuromodulation with sensitive neurophysiological readouts in controlled experimental designs offers a promising avenue to advance mechanistic insight, refine biomarkers, and inform mechanism-based therapeutic strategies. Together, these approaches position noninvasive neurophysiology as a powerful tool for elucidating UMN dysfunction in ALS.},
}

@article {pmid42369427,
year = {2025},
author = {Liu, H and Tang, M and Che, L and Lu, J and Zhang, L},
title = {Investigating the potential mechanism of bisphenols on neurodegeneration through network toxicology and molecular docking.},
journal = {NAM journal},
volume = {1},
number = {},
pages = {100044},
pmid = {42369427},
issn = {3050-6204},
abstract = {This study aims to elucidate the mechanisms underlying bisphenols (BPs)-induced neurodegeneration and their contribution to neurodegenerative diseases. Focusing on four major disorders-Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis, and Huntington's Disease-we systematically examined key molecular pathways potentially perturbed by BPs during disease progression. Preliminary toxicological profiling of four representative BPs was conducted using ProTox-3.0, ADMETlab 3.0, and the Xundrug database. Subsequent target identification involved integrated analyses of multiple bioinformatics resources, including CHEMBL and STITCH. Protein-protein interaction networks constructed with STRING and Cytoscape identified core targets such as HSP90AA1, ESR1, BCL2, and PTGS2. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses further revealed critical biological processes, including enzyme binding and heme binding, as well as key pathways associated with BPs neurotoxicity, such as chemical carcinogenesis-receptor activation, chemical carcinogenesis-DNA adducts, and arachidonic acid metabolism. Molecular docking studies demonstrated strong binding affinities between BPs and core targets, supported by low free energy values. Molecular dynamics simulations further validated stable binding conformations and dynamic interactions. Additionally, we analyzed regulatory networks of mRNA-miRNA-lncRNA interactions for core targets. In summary, our findings establish a novel multi-target and multi-pathway framework for BPs-induced neurodegeneration, revealing synergistic effects of pathways including carcinogenic signaling activation and metabolic dysregulation. This study advances understanding of environmental neurotoxicity and provides a foundation for developing preventive strategies against neurodegenerative diseases.},
}

@article {pmid42370031,
year = {2026},
author = {Head, A and Birkett, M and Fleming, K and Kypridemos, C and O'Flaherty, M},
title = {Exploring theoretical policy options for reducing socioeconomic inequalities in multimorbidity: A microsimulation study in England from 2019-2049.},
journal = {Journal of multimorbidity and comorbidity},
volume = {16},
number = {},
pages = {26335565261441403},
pmid = {42370031},
issn = {2633-5565},
abstract = {BACKGROUND: Projections suggest that the number of adults living with multimorbidity will continue growing in the coming decades. Little is known, however, about the potential impact of prevention policies on multimorbidity.

METHODS & FINDINGS: We applied a validated microsimulation model of multimorbidity accumulation to simulate theoretical scenarios of health improvement and inequality reduction in England over 30 years (2019-2049), compared to a baseline scenario of continuing patterns in accumulation. Four theoretical scenarios were based on Benach et al.'s typology of health policies: 1) targeted intervention on the worst-off; 2) universal policy + additional focus on the gap; 3) redistributive policy; 4) proportionate universalism; plus an idealistic fifth scenario completely removing socioeconomic inequality in transition times between states. We selected a target of 3% reduction in mortality for scenarios 1-4, based on reductions seen from tobacco control policies. Outputs compared were: difference in 2049 projected prevalence and numbers compared to baseline, total cases prevented/postponed compared to baseline, and expected years lived without multimorbidity at age 30. Our results suggest that gains in levelling socioeconomic inequalities in health would prevent/postpone multimorbidity cases and reduce relative health inequalities among those aged <65. However, this would also likely lead to increased absolute numbers living with multimorbidity overall.

CONCLUSIONS: Our theoretical modelling suggests effective and equitable policies have potential to reduce the population-level burden of multimorbidity, postponing a substantial number of multimorbidity cases, particularly before age 65. This is, however, likely to lead to greater absolute numbers of multimorbidity cases as individuals live for longer.},
}

@article {pmid42370313,
year = {2026},
author = {Alkorom, S and Chong, MC and Che Seman, NH and Aqtam, I},
title = {Resilience-Building Interventions and Advanced Life Support Competency for Emergency Nurses in Palestinian Hospitals: A Scoping Review.},
journal = {SAGE open nursing},
volume = {12},
number = {},
pages = {23779608261464872},
pmid = {42370313},
issn = {2377-9608},
abstract = {BACKGROUND: Emergency nurses in Palestinian hospitals operate under chronic stress related to political instability, resource constraints, and high trauma exposure. These conditions may affect both psychological resilience and Advanced Life Support (ALS) competency, yet the evidence base remains unclear. This scoping review sought to map the available body of literature about psychological resilience and ALS competency among emergency nurses in Palestine, identify gaps in research, and determine the relationship between psychological resilience and ALS competency, which is the core focus of this review.

METHODS: Following PRISMA-ScR guidelines and JBI scoping review methodology, a comprehensive search of seven electronic databases and grey literature was conducted for studies published between January 2000 and January 2026. Two reviewers independently screened studies and extracted data using a standardized, pilot-tested charting form. Findings were synthesized descriptively using narrative synthesis organized around the review objectives.

RESULTS: From 1,292 records identified, 18 studies met inclusion criteria. Most studies were descriptive or correlational (94.4%). Burnout prevalence among emergency nurses ranged from 64% to 72.9%, and substantial gaps in ALS/BLS knowledge were reported, including low accuracy in resuscitation sequence identification (26.6%). Only one intervention study was identified, evaluating simulation-based BLS training. No studies were found that assessed resilience-based or comprehensive programs which address psychological wellbeing and clinical competency issues. There were no studies that specifically analyzed the connection between psychological resilience and competency in ALS.

CONCLUSION: The existing literature on Palestinian emergency nurses is dominated by descriptive studies, with a marked absence of intervention research. Despite documented psychological distress and clinical competency gaps, no studies have evaluated psychological resilience-focused or integrated interventions. This review highlights critical evidence gaps and provides a foundation for future intervention-oriented research.},
}

@article {pmid42371053,
year = {2026},
author = {Stipa, G and Colosimo, C and Vanacore, N},
title = {Neurodegenerative diseases and environmental risk factors: an overview of the available scientific evidence.},
journal = {Journal of neural transmission (Vienna, Austria : 1996)},
volume = {},
number = {},
pages = {},
pmid = {42371053},
issn = {1435-1463},
abstract = {Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are among the most well-known and prevalent neurodegenerative disorders. These diseases result from an interaction between the environment and genetically predisposed individuals. This review examines the evidence available in the literature underlying this multifaceted interaction, focusing on various chemical substances such as metals, fertilizers, and herbicides, as well as toxic agents of microbiological origin, including cyanobacteria and their neurotoxins. In addition, the pathways through which toxic substances can enter the human body are discussed, such as air and water, which may lead to absorption through the lungs, the gastrointestinal tract, the skin, and mucosae. The routes by which neurotoxic substances gain access to the human body may help explain the increased risk of developing neurodegenerative diseases observed in sports played on soil and grass surfaces, such as soccer, American football, and golf.},
}

@article {pmid42371122,
year = {2026},
author = {Gremmler, PA and von der Gablentz, J and Meyer, J and Ilse, B and Farahi Ghasraboonasr, B and Dalbert, S and Buchholz, IJ and Grosskreutz, J and Steinbach, R},
title = {Quantification of amyotrophic lateral sclerosis (ALS) disease accumulation with T1-weighted high-resolution magnetic resonance imaging: validation in an independent cohort.},
journal = {Journal of neurology},
volume = {273},
number = {7},
pages = {},
pmid = {42371122},
issn = {1432-1459},
support = {EXC 2167//Deutsche Forschungsgemeinschaft/ ; 413668513//Deutsche Forschungsgemeinschaft/ ; 583362031//Deutsche Forschungsgemeinschaft/ ; ACSP 14//Interdisciplinary Centre of Clinical Research of the Medical Faculty Jena/ ; PROMO-2025-01//Interdisciplinary Centre of Clinical Research of the Medical Faculty Jena/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; *Magnetic Resonance Imaging/methods ; Female ; Male ; Cohort Studies ; Middle Aged ; Aged ; Disease Progression ; *Gray Matter/diagnostic imaging/pathology ; *White Matter/diagnostic imaging/pathology ; Image Processing, Computer-Assisted ; Adult ; Case-Control Studies ; },
abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a progressive neuromuscular disease with multifaceted phenotypic presentation thus obstructing objective disease staging. The D50 disease progression model is a framework to comprehensively dissect biomarker-signals towards their relevance regarding disease accumulation/phase (rD50), or disease aggressiveness (D50). Based on previous findings using 1.5-Tesla Magnetic-Resonance-Imaging (MRI), this study hypothesized that high-resolution MRI markers of Grey-Matter (GM) structural integrity would enable quantification of disease accumulation, independent of aggressiveness.

METHODS: A separate cohort of 75 patients with ALS and 73 Healthy Controls (HC) underwent T1-weighted 3-Tesla MRI. Voxel-Based-Morphometry measured GM and White-Matter (WM) density and Surface-Based-Morphometry assessed Cortical Thickness (CT). Non-parametric Threshold-Free-Cluster-Enhancement with 5000 permutations was applied for inter-group and regression contrasts, whilst correcting for possibly interfering co-variates and applying Family-Wise-Error-adjustment.

RESULTS: Compared with HC, the ALS cohort showed widespread decreases of CT and GM/WM density (p < 0.001). These case-control effects were driven by patients scanned during rD50-defined disease Phase 2 (p < 0.001). Within the ALS-cohort, direct Phase 2 versus Phase 1 contrasts revealed spatially-distributed decreases, reflecting higher disease accumulation (p < 0.05). These were independent of disease aggressiveness (and onset-region), as corrected for in the models. Accordingly, all contrasts assessing aggressiveness did not yield significant results.

CONCLUSIONS: These semi-automated analyses of T1-weighted-images captured disease accumulation related GM structural integrity-loss in this cohort scanned with 3-Tesla MRI, independent of the underlying disease aggressiveness. This principle was validated across different scanners and field strengths, supporting its application for objective and non-invasive staging of patients with ALS, whereby true longitudinal studies are necessary.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology
*Magnetic Resonance Imaging/methods
Female
Male
Cohort Studies
Middle Aged
Aged
Disease Progression
*Gray Matter/diagnostic imaging/pathology
*White Matter/diagnostic imaging/pathology
Image Processing, Computer-Assisted
Adult
Case-Control Studies

@article {pmid42372734,
year = {2026},
author = {Pena, C and Barker, C and Grossberg, AN and Mian, I and Williams, S and MacAllister, T and Vu, T and Linseman, DA},
title = {An open-label Phase 2a study of fasudil in amyotrophic lateral sclerosis: safety and exploratory endpoints.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/21678421.2026.2694507},
pmid = {42372734},
issn = {2167-9223},
abstract = {OBJECTIVES: The primary objective was to assess the safety of oral fasudil in amyotrophic lateral sclerosis (ALS) patients. Changes in serum neurofilament light (NfL) levels and the ratio of phosphorylated to total AKT (pAKT/tAKT) were exploratory endpoints.

METHODS: This was a multicenter, open-label study. Two 31-patient cohorts were sequentially enrolled and treated with either 180 mg or 300 mg per day of oral fasudil for 24 weeks. The primary endpoint was safety. Secondary endpoints evaluated changes in the ALS functional rating scale-revised (ALSFRS-R), slow vital capacity, and muscle strength. We also assessed changes in serum NfL and pAKT/tAKT ratios in plasma (neuron-derived) and CSF (total) extracellular vesicles (EVs).

RESULTS: Eighty-one percent (25/31) and 71% (22/31) of patients completed 24 weeks of treatment in the 180 and 300 mg cohort, respectively. Fasudil was safe and well tolerated, with predominantly mild drug-related adverse events. Secondary endpoints, though not statistically significant, were directionally consistent with a treatment effect. Exploratory analyses showed a 15.4% reduction in serum NfL at 24 weeks (p = 0.001) in the 180 mg cohort, with no change in the 300 mg cohort (-0.4%, p = 0.990). The NfL reduction was inversely correlated with ALSFRS-R decline (Spearman = -0.45, p = 0.028). Ratios of pAKT/tAKT, a pharmacodynamic marker of rho kinase (ROCK) inhibition, were significantly increased at 24 weeks in plasma (neuron-derived) and CSF EVs.

CONCLUSIONS: Oral fasudil is safe and well-tolerated in ALS patients. The reduction in NfL and demonstration of CNS target engagement, supports studying the 180 mg dose in a double-blind placebo-controlled study.},
}

@article {pmid42373582,
year = {2026},
author = {Granger, SM and Staniforth, RA and Snorradottir, AO and Cooper-Knock, J and De Vos, KJ and Highley, JR},
title = {Unravelling the Significance of Cystatin C and Bunina Bodies in Amyotrophic Lateral Sclerosis Pathogenesis.},
journal = {Neuropathology and applied neurobiology},
volume = {52},
number = {4},
pages = {e70083},
pmid = {42373582},
issn = {1365-2990},
support = {/MNDA_/Motor Neurone Disease Association/United Kingdom ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/metabolism ; *Cystatin C/metabolism ; Animals ; *Inclusion Bodies/pathology/metabolism ; *Motor Neurons/pathology/metabolism ; DNA-Binding Proteins/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a fatal neurodegenerative disease primarily affecting motor neurons. Two key protein inclusions found in lower motor neurons serve as neuropathological hallmarks of the disease in human tissue: the TDP43-positive inclusion and the cystatin C-positive Bunina body. Despite their diagnostic specificity and presence in most sporadic and familial ALS cases, Bunina bodies remain poorly understood, and their true prevalence is likely underestimated. The co-occurrence of the Bunina body and the TDP43 inclusion may provide valuable insights into the development of TDP43 pathology in ALS. Thorough characterisation of the Bunina body is needed to understand this interplay and the broader pathomechanisms of disease. This review examines our current knowledge of Bunina bodies and the biochemical properties of cystatin C that may promote its aggregation. Sequestration and aggregation of cystatin C into Bunina bodies may diminish its neuroprotective functions, including cysteine protease inhibition, autophagy induction and anti-amyloidogenic activity, thereby contributing to ALS pathogenesis. This review also evaluates findings from human post-mortem tissue and ALS disease models, discussing the value and limitations of these models in the context of Bunina bodies and TDP43 pathology. Finally, we discuss cystatin C's use as a biomarker and its therapeutic potential. A deeper understanding of cystatin C biology, its relationship with TDP43 pathology and improved ALS models will be essential for determining whether targeting cystatin C could provide a viable avenue for future ALS therapies.},
}

Humans
*Amyotrophic Lateral Sclerosis/pathology/metabolism
*Cystatin C/metabolism
Animals
*Inclusion Bodies/pathology/metabolism
*Motor Neurons/pathology/metabolism
DNA-Binding Proteins/metabolism

@article {pmid42373784,
year = {2026},
author = {Li, Y and Ulrich, JD and Holtzman, DM},
title = {Adaptive immunity in the pathogenesis of neurodegeneration.},
journal = {Nature immunology},
volume = {27},
number = {7},
pages = {1375-1389},
pmid = {42373784},
issn = {1529-2916},
support = {AG085374//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; AG069701//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; AG078106//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; AG083977//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; NS090934//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; },
mesh = {Humans ; *Adaptive Immunity/immunology ; *Neurodegenerative Diseases/immunology/pathology/therapy ; Animals ; Microglia/immunology ; *Central Nervous System/immunology/pathology ; Astrocytes/immunology ; Immunity, Innate ; },
abstract = {Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and others, are a group of neurological disorders characterized by progressive neuronal loss in the central nervous system (CNS) and the deterioration of CNS function. Multiple lines of evidence have highlighted activation of innate immune cells in the CNS, namely microglia and astrocytes, as hallmark pathological features in neurodegeneration and key drivers of disease progression. Advances in genetic, neuropathological and experimental studies also underscore the potential role of the adaptive immune system in disease pathogenesis. Here we summarize the current understanding of how adaptive immunity can shape the progression of neurodegenerative diseases and highlight cross-disease parallels and potentially shared mechanisms. We also examine cellular events leading to the recruitment of peripheral immune cells to the CNS, as well as candidate antigens driving the adaptive immune response. Last, we discuss potential therapeutic strategies to treat neurodegeneration via the manipulation of adaptive immune cells.},
}

Humans
*Adaptive Immunity/immunology
*Neurodegenerative Diseases/immunology/pathology/therapy
Animals
Microglia/immunology
*Central Nervous System/immunology/pathology
Astrocytes/immunology
Immunity, Innate

@article {pmid42373786,
year = {2026},
author = {Guo, AX and Fisher, TM and Comandante-Lou, N and De Jager, PL and Liddelow, SA},
title = {Innate immune signaling and functions in astrocytes.},
journal = {Nature immunology},
volume = {27},
number = {7},
pages = {1364-1374},
pmid = {42373786},
issn = {1529-2916},
support = {AARF-24-1313800/ALZ/Alzheimer's Association/United States ; U01 AG061356/AG/NIA NIH HHS/United States ; },
mesh = {*Astrocytes/immunology/metabolism ; Humans ; *Immunity, Innate/immunology ; Animals ; *Signal Transduction/immunology ; Toll-Like Receptors/metabolism/immunology ; Innate Immunity Recognition ; Inflammasomes/metabolism/immunology ; },
abstract = {Astrocytes, long considered supportive cells of the central nervous system (CNS), have critical roles in innate immunity. This Review explores immune signaling pathways in astrocytes, including pattern recognition through Toll-like receptors, nucleic acid sensors and inflammasomes. These pathways enable the detection of danger signals and initiate protective responses and endogenous innate immune functions. Downstream signaling pathways, including the interferon, NF-κB and STAT3 pathways, mediate astrocyte reactivity and drive cytokine secretion, antiviral responses, phagocytosis and many other immune functions. While these responses are crucial for CNS health, their dysregulation can contribute to chronic inflammation and neurodegeneration in conditions such as Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis. Additionally, astrocytes exhibit regional heterogeneity in their immune behaviors, which may influence disease trajectories. We highlight unresolved questions regarding the immune functions of astrocytes, their interplay with professional immune cells and their dual protective and pathological roles.},
}

*Astrocytes/immunology/metabolism
Humans
*Immunity, Innate/immunology
Animals
*Signal Transduction/immunology
Toll-Like Receptors/metabolism/immunology
Innate Immunity Recognition
Inflammasomes/metabolism/immunology

@article {pmid42360563,
year = {2026},
author = {Ketabforoush, A and Arnold, WD and Ariaei, A and Faghihi, F and Azedi, F and Khalili, M and Gholami, F and Joghataei, MT and Ashtiani, BH},
title = {Characterization of sensory nerve conduction abnormalities at the time of ALS diagnosis.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {7},
pages = {},
pmid = {42360563},
issn = {1590-3478},
support = {1401-1-20-22913//Iran University of Medical Sciences/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Female ; Male ; Nerve Conduction Studies ; Middle Aged ; *Neural Conduction/physiology ; Cross-Sectional Studies ; Prospective Studies ; Aged ; Adult ; Sural Nerve/physiopathology ; Ulnar Nerve/physiopathology ; Motor Neurons/physiology ; Median Nerve/physiopathology ; },
abstract = {OBJECTIVES: Although sensory nerve abnormalities have been reported in amyotrophic lateral sclerosis (ALS), their distribution at diagnosis, relative to motor involvement and clinical onset phenotype remains incompletely characterized. We aimed to systematically compare sensory and motor nerve conduction abnormalities at ALS diagnosis and determine whether sensory involvement follows an onset-dependent pattern similar to motor dysfunction.

METHODS: In this prospective cross-sectional study, 40 newly diagnosed ALS patients enrolled in the Iran University ALS Registry (March 2022-March 2023) underwent standardized motor and sensory nerve conduction studies (NCS). For between-group comparisons, a matched ALS subgroup was compared with matched healthy controls, while the expanded ALS cohort was used for subgroup and correlation analyses.

RESULTS: SNAP amplitudes of the median, ulnar, and sural nerves were reduced by 45%, 34%, and 43%, respectively, compared with healthy controls, with similar reductions observed across upper- and lower-limb onset phenotypes and no significant onset-dependent differences. In contrast CMAP amplitudes were markedly reduced in ALS patients, most prominently in the peroneal (79%), median (47%), tibial (42%), and ulnar (37%) nerves. Motor abnormalities were most severe in the clinically affected limb but were also detectable in asymptomatic extremities, consistent with early subclinical spread.

CONCLUSION: At ALS diagnosis, sensory and motor nerve conduction abnormalities exhibited divergent spatial patterns, with asymmetric, onset-related motor involvement and relatively uniform sensory axonal dysfunction. These findings support the presence of measurable sensory nerve conduction abnormalities in a subset of ALS patients, while highlighting the need for cautious interpretation of sensory NCS changes in ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/diagnosis
Female
Male
Nerve Conduction Studies
Middle Aged
*Neural Conduction/physiology
Cross-Sectional Studies
Prospective Studies
Aged
Adult
Sural Nerve/physiopathology
Ulnar Nerve/physiopathology
Motor Neurons/physiology
Median Nerve/physiopathology

@article {pmid42361455,
year = {2026},
author = {Kim, JS and Yu, S and Mitchell, MB and Goss, D and Schumacher, DJ and Chen, JX},
title = {The Implementation of Competency-Based Medical Education in Surgical Training: A Scoping Review.},
journal = {Journal of surgical education},
volume = {83},
number = {9},
pages = {104056},
doi = {10.1016/j.jsurg.2026.104056},
pmid = {42361455},
issn = {1878-7452},
abstract = {BACKGROUND: The pace of implementation of competency-based medical education (CBME) in postgraduate surgical training has varied substantially across settings, due in part to inconsistent definitions of what constitutes CBME in practice. Employing the lens of Van Melle et al.'s 2019 codification of the core components of CBME, this scoping review aims to characterize how CBME has been implemented in surgical residency programs worldwide.

METHODS: Embase, PubMed, MedEdPortal, and ERIC were searched for English-language articles describing active CBME implementation in surgical residency programs. A scoping review was conducted using Covidence and reported using the PRISMA-ScR guidelines. Research abstracts, systematic/scoping reviews, and studies describing isolated workshops or training supplements were excluded. CBME implementations extracted from included studies were classified as systemic implementations, local innovations, or competency-based assessment instruments. Given substantial redundancy in the literature, not all studies describing the U.S. Accreditation Council for Graduate Medical Education Core Competencies or Milestones were included; 5 exemplary studies from this corpus were included as representative descriptions. All included studies were evaluated against the 5 CBME core components: outcome competencies, sequenced progression, tailored learning experiences, competency-focused instruction, and programmatic assessment.

RESULTS: Seventy studies published between 2001 and 2023 were included, predominantly from North America and Europe. Outcome competencies were clearly defined across all systemic implementations; however, sequenced progression, competency-focused instruction, and programmatic assessment were more variably incorporated, and were more often satisfied in Canadian and European frameworks. While local innovations and assessment instruments demonstrated novelty and the feasibility of CBME implementation, alignment with all 5 core components was uncommon.

CONCLUSIONS: CBME implementation in surgical residency remains heterogeneous, with many programs layering components of CBME onto existing curricular structures. These findings suggest that greater emphasis on future systemic educational reform efforts may support more impactful CBME implementation in surgical training programs.},
}

@article {pmid42361623,
year = {2026},
author = {Deptuła, P and Chmielewska-Deptuła, S and Spałek, J and Kaliniak, S and Okła, S and Bucki, R},
title = {Decoding the pathogenesis of Candida albicans infection and evaluating the efficacy of antifungal drugs using atomic force microscopy.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {201},
number = {},
pages = {119705},
doi = {10.1016/j.biopha.2026.119705},
pmid = {42361623},
issn = {1950-6007},
abstract = {Atomic force microscopy (AFM) has emerged as a pivotal method enabling multidimensional characterization of Candida albicans (C. albicans) by simultaneously providing topographical imaging, mechanical profiling, and quantitative measurements of adhesion forces under near-physiological conditions. AFM-derived data demonstrate that nanoscale surface alterations, including wrinkling, indentations, increased roughness, and perforations correlate closely with modulation of the Young's modulus and with the reorganization of mannoproteins and adhesins, particularly those of the Als family. The co-occurrence of structural, mechanical, and adhesive changes reflects the dynamic remodeling of the fungal cell wall that governs morphogenesis, virulence, and biofilm formation. AFM offers high resolution insight into the mechanisms of action of antifungal drugs, antimicrobial peptides, nanomaterials, and physical treatments that destabilize the cell wall, reduce its stiffness, or conversely induce compensatory stiffening and adhesin exposure. As a result, the technique enables the identification of critical steps in stress responses and hyperadhesive phenotypes that contribute to fungal invasion and treatment resistance. Integration of AFM with spectroscopic and microfluidic approaches further enhances its potential to reveal new therapeutic targets. Collectively, evidence from numerous studies underscores AFM as a foundational tool in the rational design of modern, multimodal antifungal strategies aimed at the cell wall and biofilm of C. albicans.},
}

@article {pmid42362190,
year = {2026},
author = {Lyu, R and Ruff, KM and Palmer, CS and Ramirez, AE and Ormsby, AR and Scott, DJ and Pappu, RV and Stojanovski, D and Stroud, DA and Hatters, DM},
title = {ASAP-ID: Proximity labelling with small tags.},
journal = {Molecular & cellular proteomics : MCP},
volume = {},
number = {},
pages = {101616},
doi = {10.1016/j.mcpro.2026.101616},
pmid = {42362190},
issn = {1535-9484},
abstract = {Biotinylation-based proximity labelling methods are valuable for discovering protein-protein interactions within cellular systems. However, one limitation of these approaches is that most require fusing the target protein with the enzyme that biotinylates nearby proteins (i.e., TurboID or APEX2), which risks sterically disrupting the protein's native function. Here, we present a method designed to reduce the steric impact of these fusions and offer greater flexibility in labelling modalities. The method, Antibody and Small-tag Assembly on Proteins for Interaction Detection (ASAP-ID), involves a bipartite system. Target proteins are fused to a small peptide antigen that recruits TurboID or APEX2 fused to an antibody directed to the antigen. Using two different antigen/antibody systems (SunTag and MoonTag), we show that ASAP-ID can specifically label human Lamin A in cells. The method works when the target protein and nanobody are co-expressed together in cis (ASAP-ID[IC]). We also demonstrate that the approach works when the antibody fusion is added in trans to fixed cells post-expression (ASAP-ID[IT]). ASAP-ID[IT] identified more than 448 known and previously undescribed potential interactors of lamin. We further used ASAP-ID[IT] to study how ALS-mutant profilin 1 affected its interactome. The method identified proteins involved in protein quality control that correlated with aggregation propensity. Moreover, the different mutants showed variation in the cellular location where aggregates formed. ASAP-ID[IT] revealed preferences for mitochondrial proteins for the two profilin mutants that tend to aggregate in the cytoplasm, C71G and M114T, and nuclear proteins for a mutant more prone to nuclear aggregation. These findings position ASAP-ID as a powerful addition to the proximity labelling toolkit, capable of probing subtle differences in interactomes in a less invasive manner.},
}

@article {pmid42362484,
year = {2026},
author = {Nakayama, Y and Kume, K and Baba, T and Ayaki, T and Hanada, K and Miyamoto, K and Inoue, N and Kawakami, H and Ito, H},
title = {Neuropathological and Molecular Features Associated With a Heterozygous DNAJC7 Mutation in Amyotrophic Lateral Sclerosis.},
journal = {Neuropathology and applied neurobiology},
volume = {52},
number = {4},
pages = {e70086},
doi = {10.1111/nan.70086},
pmid = {42362484},
issn = {1365-2990},
support = {18H02743//Japan Society for the Promotion of Science/ ; 25K10801//Japan Society for the Promotion of Science/ ; //Takeda Science Foundation/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; Female ; Male ; Middle Aged ; *Molecular Chaperones/genetics ; Mutation ; Aged ; Heterozygote ; Heat-Shock Proteins ; },
abstract = {AIMS: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with unclear molecular mechanisms. Heterozygous protein-truncating variants of DNAJC7, which encode a cochaperone involved in Hsp70/90-mediated protein quality control, are potential risk factors for ALS. However, the neuropathological consequences of heterozygous DNAJC7 mutations are unclear. We aimed to clarify the molecular and neuropathological features associated with a heterozygous DNAJC7 mutation in ALS.

METHODS: We genetically screened 39 Japanese patients with ALS and identified a novel heterozygous frameshift mutation in DNAJC7 (c.157_163del, p.Lys53Ter) in one patient that was neuropathologically diagnosed with Kii ALS. We performed biochemical and neuropathological analyses using postmortem tissues from this patient, from cases of ALS without the mutation and from control cases.

RESULTS: In the cases of ALS without DNAJC7 mutation, there was elevation of both DNAJC7 mRNA and protein levels compared with controls. The patient with DNAJC7 mutation showed relatively lower DNAJC7 mRNA and protein levels compared with the nonmutated cases of ALS, although mRNA expression remained relatively higher. DNAJC7 may be upregulated as a protective response against ALS pathogenesis, whereas a heterozygous mutation may attenuate this response. Immunohistochemistry and double immunofluorescence demonstrated partial colocalization of DNAJC7 with phospho-TDP-43-positive neuronal cytoplasmic inclusions, which supports a direct role for DNAJC7 in modulating pathological TDP-43 aggregation.

CONCLUSIONS: These findings provide neuropathological evidence linking heterozygous DNAJC7 mutation to ALS, demonstrating impaired protein expression and suggesting a loss-of-function mechanism that compromises protective responses to TDP-43 pathology. DNAJC7 may represent a key modulator of ALS pathogenesis and potential therapeutic target.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism
Female
Male
Middle Aged
*Molecular Chaperones/genetics
Mutation
Aged
Heterozygote
Heat-Shock Proteins

@article {pmid42363583,
year = {2026},
author = {Ludwig, TD and Rabelo-Araujo, JVDS and Munhoz Pedroso, R},
title = {Enhanced weed control in flooded rice through diversified pre-emergence programs integrating PROTOX-inhibiting herbicides.},
journal = {Journal of environmental science and health. Part. B, Pesticides, food contaminants, and agricultural wastes},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/03601234.2026.2694270},
pmid = {42363583},
issn = {1532-4109},
abstract = {Rice (Oryza sativa L.) productivity in Brazil is increasingly threatened by herbicide-resistant weeds. We evaluated diversified pre-emergence programs in flooded Clearfield rice (Puitá INTA CL) through two field experiments conducted in southern Brazil during the 2016/2017 season. Programs were based on acetolactate synthase (ALS) inhibitors alone or combined with alternative modes of action, including protoporphyrinogen oxidase (PROTOX) inhibitors (saflufenacil and flumioxazin). Weed control of Aeschynomene spp. and Echinochloa spp. was high (≥80%) at 14 days after application (DAA) and remained satisfactory up to 21 DAA in most programs. Crop injury was treatment-dependent, with higher early phytotoxicity observed in mixtures containing mesotrione, but visual symptoms declined over time and did not compromise grain yield. All herbicide programs significantly increased productivity compared to the untreated control. These findings indicate that integrating PROTOX inhibitors into Clearfield-based pre-emergence programs is a feasible strategy to diversify modes of action while maintaining effective weed control and yield stability under flooded conditions.},
}

@article {pmid42363684,
year = {2026},
author = {Majumder, P and Ahsan, A and Bubphachat, P and Akter, K and Huang, JK and Huang, CS},
title = {FMRP-Mediated Proteasome Regulation: A Novel Mechanism in ALS Pathology.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {40},
number = {13},
pages = {e72063},
doi = {10.1096/fj.202600563R},
pmid = {42363684},
issn = {1530-6860},
support = {NSTC 114-2320-B-038-055//National Science and Technology Council (NSTC)/ ; NSTC 110-2320-B-038-067-MY3//National Science and Technology Council (NSTC)/ ; NSTC 110-2320-B-038-090-MY3//National Science and Technology Council (NSTC)/ ; NSTC 113-2320-B-038-061//National Science and Technology Council/ ; },
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *Proteasome Endopeptidase Complex/metabolism ; DNA-Binding Proteins/metabolism/genetics ; Humans ; *Fragile X Messenger Ribonucleoprotein 1/metabolism/genetics ; Mice ; Mice, Transgenic ; Cytoplasm/metabolism ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a rare and fatal neurodegenerative disease characterized by the hallmark cytoplasmic accumulation and aggregation of TAR DNA binding protein 43 (TDP-43), which impairs proteasome activity through its interaction with Tankyrase (TNKS). Using molecular and imaging techniques, we have identified a novel role for the Fragile X Mental Retardation Protein (FMRP) in regulating the TNKS/PI31-mediated proteasome activation mechanism in co-operation with TDP-43. Our results demonstrate that depletion of FMRP causes nuclear translocation of TDP-43, reducing cytoplasmic TNKS/TDP-43 co-localization, thereby releasing TNKS in the cytoplasm. Free TNKS gets associated with proteasome inhibitor of 31 kDa (PI31), reversing PI31-mediated inhibition of proteasome assembly, trafficking, and activity. Thus, FMRP regulates proteasome activity by modulating the subcellular distribution of TDP-43. Interestingly, FMRP expression is elevated in specific brain regions and spinal cords of TDP-43[A315T] transgenic ALS mice that helps more TDP-43 to stay in cytoplasm to sequester more TNKS with it, resulting in proteasome dysfunction in ALS disease system. We have demonstrated for the first time that FMRP can act as a disease modifier for ALS. ALS patients with high FMRP expression in the brain and spinal cord may exhibit more severe protein aggregation due to proteasome dysfunction.},
}

Animals
*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics
*Proteasome Endopeptidase Complex/metabolism
DNA-Binding Proteins/metabolism/genetics
Humans
*Fragile X Messenger Ribonucleoprotein 1/metabolism/genetics
Mice
Mice, Transgenic
Cytoplasm/metabolism

@article {pmid42364760,
year = {2026},
author = {Baird, KT},
title = {The impedance mismatch theory: A non-equilibrium thermodynamic framework for a shared energetic stress pathway in neurodegeneration.},
journal = {Bio Systems},
volume = {},
number = {},
pages = {105862},
doi = {10.1016/j.biosystems.2026.105862},
pmid = {42364760},
issn = {1872-8324},
abstract = {Current neurobiological models of Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), and Huntington's Disease (HD) utilize multi-omic interactome analyses to map cascades of proteinopathy. While essential, these approaches often overlook the macroscopic thermodynamic limits of the neural substrate as an information processing system. We propose the Impedance Mismatch Theory, a theoretical biophysical model and quantitative framework for the thermodynamic limits of neural computation, positing that these distinct pathologies converge as a shared energetic stress pathway. We introduce the Neurophysiological Load Index (NLI)-a dimensionless parameter quantifying the mismatch between electrical computational drive, topological network impedance, and the local structural and microvascular dissipation capacity. Drawing on the Pennes Bioheat Transfer Equation and insights from multiplex network theory, we hypothesize that pathology initiates as localized thermal runaway, where resistive metabolic heat exceeds convective blood perfusion and thermal conduction, inducing acute decompensation. We outline cross-translational disease-network mechanisms, address the inverse cancer comorbidity paradox via speculative bioelectric attractor states, and propose falsifiable predictions involving high-resolution in vivo proton magnetic resonance spectroscopy thermometry ([1]H-MRS-t) and phosphorus-31 magnetic resonance spectroscopy ([31]P-MRS).},
}

@article {pmid42365206,
year = {2026},
author = {Hammond, RM and Salvalaggio, G and Nykiforuk, CIJ and Hyshka, E},
title = {Navigating the CBD: How Urban Risk Environment Shapes Daily Life for People Who Use Drugs in Edmonton's Central Business District.},
journal = {Journal of urban health : bulletin of the New York Academy of Medicine},
volume = {},
number = {},
pages = {},
pmid = {42365206},
issn = {1468-2869},
support = {Subcontract//Boyle Street Community Services/ ; },
abstract = {Public drug use in urban central business districts (CBDs) presents an urgent public health challenge in Canada. People who use drugs (PWUD) in CBDs navigate intersecting risks related to criminalization, stigma, hostile architecture, urban redevelopment, and limited access to essential services-factors that compound health disparities and increase morbidity and mortality. Yet CBDs also function as sites of informal social networks, mutual aid, and adaptive survival strategies that, while precarious, constitute critical resources for daily safety and belonging. This focused ethnographic study, conducted in Edmonton's CBD between July 2022 and September 2023, draws on 25 semi-structured interviews and over 170 h of embedded field immersion to investigate how intersecting environmental forces shape the daily lives of PWUD. Using Collins et al.'s (2019) intersectional risk environment framework and Duff's (2009) enabling environment concept, we analyzed how physical, social, economic, and policy environments-operating across micro and macro levels-produce differential harms and, simultaneously, generate precarious yet meaningful sites of connection, resourcefulness, and collective care. Findings reveal how displacement, over-policing, and gentrification-driven spatial change coexist with participants' place-based belonging, moral economies of reciprocity, and culturally grounded survival knowledge. We argue that effective interventions must account for this co-production of risk and enabling conditions and that urban governance must center the voices of those most structurally affected.},
}

@article {pmid42365390,
year = {2026},
author = {Zheng, H and Luo, H and Lu, Y and Yuan, Y and Zhang, N and Duan, S and Xia, Z and Xu, Y},
title = {Lysophagy protects against ANXA11 amyloid fibril toxicity and propagation in FTLD.},
journal = {Translational neurodegeneration},
volume = {15},
number = {1},
pages = {},
pmid = {42365390},
issn = {2047-9158},
support = {82301619//the National Natural Science Foundation of China/ ; 82571514//the National Natural Science Foundation of China/ ; 232102311229//the key scientific and technological breakthrough project in Henan province/ ; 2022M722875//the China Postdoctoral Science Foundation/ ; },
mesh = {Humans ; *Lysosomes/metabolism/pathology ; *Frontotemporal Lobar Degeneration/metabolism/pathology/genetics ; *Autophagy/physiology ; *Annexins/metabolism/genetics ; *Amyloid/metabolism ; Neurons/metabolism/pathology ; Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics ; },
abstract = {BACKGROUND: Accumulation of Annexin A11 (ANXA11) aggregates is a distinct pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). While genetic studies have linked ANXA11 mutations (e.g., D40G) to disease, the precise molecular events converting aggregation into neurotoxicity and intercellular propagation remain elusive. We hypothesize that lysosomal integrity serves as a critical checkpoint in ANXA11 proteinopathy and that its failure drives disease progression.

METHODS: To model the human pathology of ANXA11, we generated pre-formed fibrils (PFFs) of wild-type and FTLD/ALS-linked D40G mutant ANXA11. Human iPSC-derived neurons, 3D cerebral organoids, and bulk RNA-sequencing were employed to investigate neurotoxicity. High-resolution imaging, lentiviral knockdown, and biochemical assays were performed to delineate the lysosomal damage response and the subsequent "prion-like" spreading of aggregates.

RESULTS: The internalized ANXA11 fibrils accumulated in lysosomes, triggering lysosomal membrane permeabilization (LMP). The D40G mutation exacerbated this toxicity, leading to severe LMP, mitochondrial depolarization, and specific transcriptional downregulation of the dynactin subunit ACTR10. Mechanistically, we identified a protective signaling axis involving p38 MAPK, MK2, and HSP27 that senses ANXA11-induced lysosomal damage and initiates lysophagy. Notably, in human cerebral organoids, failure of this lysophagic clearance facilitated the cytoplasmic escape of ANXA11, thereby accelerating its seeding activity and propagation to neighboring cells. Pharmacological or genetic modulation of this pathway significantly altered neuronal survival.

CONCLUSIONS: Our study established lysosomal rupture as a primary driver of ANXA11-associated neurodegeneration and validated the p38/MK2/HSP27 axis as a crucial defense mechanism in human neural tissue. These findings provide a novel mechanistic link between lysosomal quality control and ANXA11 propagation, highlighting that enhancing lysophagic flux represents a promising translational strategy to halt the progression of FTLD and ALS.},
}

Humans
*Lysosomes/metabolism/pathology
*Frontotemporal Lobar Degeneration/metabolism/pathology/genetics
*Autophagy/physiology
*Annexins/metabolism/genetics
*Amyloid/metabolism
Neurons/metabolism/pathology
Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics

@article {pmid42366580,
year = {2026},
author = {Macklin, EA and Berry, JD and Harkey, BA and Heyd, L and Chase, M and Yu, H and Sherman, AV and Dagostino, D and Kittle, G and Hall, M and Connolly, MR and Drake, K and Giacomelli, E and Scirocco, E and Sharma, S and Babu, S and Benatar, M and Simmons, Z and Young, E and Cudkowicz, ME and Shefner, J and Paganoni, S and , },
title = {At-Home Versus in-Clinic Vital Capacity Measurement: Insights From the HEALEY ALS Platform Trial.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70322},
pmid = {42366580},
issn = {1097-4598},
support = {MDA 1313867//Muscular Dystrophy Association/ ; //Tackle ALS/ ; //ALS Finding a Cure/ ; //ALS Association/ ; //ALS ONE/ ; //The Arthur M. Blank Family Foundation/ ; //The AMG Charitable Foundation/ ; },
abstract = {INTRODUCTION/AIMS: Respiratory weakness, typically monitored as vital capacity (VC), is a central feature of amyotrophic lateral sclerosis (ALS). VC is increasingly measured remotely in participants' homes, although in-clinic assessment remains the standard. We tested concordance between at-home and in-clinic VC to determine trial eligibility, track progression, and predict survival in a large ALS trial.

METHODS: At-home and in-clinic VC were assessed at baseline and approximately every 8 weeks for a year in the first four regimens of the HEALEY ALS Platform Trial. At-home assessments were coached via live videoconference and centrally reviewed. VC measurements, expressed as percent of predicted normal (%PN), were compared cross-sectionally, longitudinally, and for predicting survival time. Data from 233 participants with 3-8 paired at-home and in-clinic VC assessments completed < 14 days apart were analyzed.

RESULTS: At-home and in-clinic VC were well correlated (Lin's rc = 0.82) with no systematic bias. At-home VC ≥ 60%PN predicted in-clinic VC ≥ 60%PN with a positive predictive value of 91% and a negative predictive value of 65%. VC slopes were moderately correlated (rc = 0.68). At-home VC progressed 28% faster than in-clinic VC with proportionately less variance (at-home [SE] = -1.882 [0.153] %PN/month, in-clinic = -1.476 [0.131] %PN/month). Slopes of at-home and in-clinic VC explained 15% and 17% of variation in future survival time, respectively.

DISCUSSION: At-home and in-clinic VC were well correlated cross-sectionally. At-home VC performed well tracking longitudinal change and predicting survival. The reduced participant burden of assessment and concordance with in-clinic measurement support use of at-home monitoring of VC.},
}

@article {pmid42367369,
year = {2026},
author = {Morganroth, J and Yasek, J and Harms, M},
title = {Preparing Amyotrophic Lateral Sclerosis Clinics to Provide Longitudinal Care for Individuals Carrying ALS Risk Variants.},
journal = {Neurology. Genetics},
volume = {12},
number = {4},
pages = {e200406},
pmid = {42367369},
issn = {2376-7839},
abstract = {BACKGROUND AND OBJECTIVES: Emerging genetic therapies and the expansion of genetic testing are identifying individuals carrying amyotrophic lateral sclerosis (ALS) risk variants who would benefit from surveillance and early intervention. Anticipating the geographic distribution and clinical needs of this population is essential for optimizing care delivery and ensuring readiness as new therapies become available. We estimate the number of individuals in the United States carrying ALS risk variants and project the clinical engagement required to support this population. This is especially timely because ALS clinics are already grappling with rising numbers of patients with symptomatic ALS and deep funding cuts.

METHODS: We developed a population model to estimate the number of symptomatic individuals with gene-positive ALS and asymptomatic gene carriers across US states over the next decade (year 1: 2026). State-level ALS prevalence and incidence were calculated using 2 approaches: (1) race-adjusted ALS rates from the Atlanta metropolitan study applied to 2023 Census demographics and (2) observed state-level ALS case counts from the National ALS Registry (2011-2018). Gene-positive cases were estimated using published frequencies of SOD1, C9orf72, FUS, and TARDBP pathogenic variants. At-risk relatives were modeled assuming autosomal-dominant inheritance with ∼5 first-degree and ∼7 second-degree living relatives per proband, and broad uptake of cascade genetic testing. Surveillance needs were modeled as 1 annual visit per asymptomatic carrier, which was normalized by the number of ALS centers per state.

RESULTS: In year 1 (2026), the model estimated 2,704 symptomatic gene-positive ALS carriers. With an average of 4.25 carrier relatives per proband, 10,944 asymptomatic carriers were projected nationwide. Most states required <50 additional visits per clinic annually, with 12 states in the 50-99 range and none exceeding 100. By year 10 (2035), the model projected 7,474 symptomatic and 26,111 asymptomatic carriers. State-level demand shifted substantially: only 6 states remained below 50 visits per clinic annually; 22 reached 50-99; 18 reached 100-199; and 3 exceeded 200.

DISCUSSION: Gene-targeted testing is projected to substantially increase ALS clinic visits among asymptomatic gene carriers. While current infrastructure may accommodate the initial rise, within a decade, most states will require significant expansion. Anticipating and planning for this growth now is essential to ensure seamless integration of gene-positive individuals into ALS care.},
}

@article {pmid42367645,
year = {2025},
author = {Toussirot, E and Tatu, L and Bereau, M},
title = {Occurrence of amyotrophic lateral sclerosis during TNF inhibitor treatment in inflammatory rheumatic disease. What are the relationships?.},
journal = {EULAR rheumatology open},
volume = {1},
number = {4},
pages = {475-477},
pmid = {42367645},
issn = {3050-7081},
abstract = {Neurological adverse events have been reported in patients receiving tumor necrosis factor inhibitors (TNFi) for the treatment of inflammatory rheumatic diseases. The occurrence of amyotrophic lateral sclerosis (ALS) during TNFi therapy is rare but raises the question of a possible relationship. We report 2 cases of ALS diagnosed during TNFi treatment: the first in a patient with spondyloarthritis treated with adalimumab and the second in a patient with seronegative polyarthritis treated with infliximab. Tumor necrosis factor alpha (TNFα) has been implicated in ALS pathogenesis and is considered to exert both neuroprotective and neurotoxic effects, depending on the differential expression of its receptors in distinct regions of the central nervous system. We also review data from pharmacovigilance databases and discuss the potential influence of TNFα inhibition on ALS development.},
}

@article {pmid42367691,
year = {2026},
author = {Loser, V and Afanasiev, V and Vicino, A and Théaudin, M},
title = {Chronic Inflammatory Demyelinating Polyradiculoneuropathy-Like Neuropathy in Heterozygous C9orf72 Mutation: A Case Report.},
journal = {Case reports in neurology},
volume = {18},
number = {1},
pages = {260-266},
pmid = {42367691},
issn = {1662-680X},
abstract = {INTRODUCTION: C9orf72 repeat expansion is usually associated with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and ALS/FTD overlap. We report an atypical neuromuscular presentation of C9orf72 repeat expansion.

CASE PRESENTATION: A 68-year-old patient developed a sensorimotor polyneuropathy with slow continuous worsening over 3 years. Symptoms started in the left foot and slowly extended to all four limbs. Nerve conduction studies were consistent with a non-length-dependent predominantly axonal sensorimotor polyneuropathy, with some additional demyelinating features (proximal temporal dispersion and F-wave latency prolongation). Electro-clinical presentation fulfilled EAN/PNS 2021 criteria for CIDP, but the patient was not responsive to IVIg. RT-PCR revealed a heterozygous pathogenic expansion of the C9orf72 gene. The patient's father and brother died from ALS. At onset, his brother also had sensorimotor involvement and was misdiagnosed with CIDP.

CONCLUSION: This case may expand the phenotypic spectrum associated with C9orf72 repeat expansion. The initial phenotype could be a non-length-dependent sensorimotor polyneuropathy with demyelinating features that potentially mimics CIDP.},
}

@article {pmid42368190,
year = {2026},
author = {Meng, J and Deng, ZJ and Zhang, J and Yu, W and Wu, X and Lei, P},
title = {Atypical involvement of Alzheimer's tau proteins in diseases beyond tauopathies.},
journal = {Life medicine},
volume = {5},
number = {3},
pages = {lnag016},
pmid = {42368190},
issn = {2755-1733},
abstract = {Tau is a microtubule-associated protein traditionally involved in a collective group of disorders termed "tauopathy", including Alzheimer's disease. Tau protein self-aggregates and forms neurofibrillary tangles in neurons, which are considered a pathological hallmark of tauopathies. While the roles of neuronal tau in tauopathies have been extensively investigated, recent studies have shed light on its roles in other diseases without tau pathology and in other cells. In this review, we aim to discuss the "atypical" pathological involvement of tau in diseases other than tauopathies, including brain diseases (e.g., amyotrophic lateral sclerosis, multiple sclerosis, and spinal cord injury), vascular diseases (stroke and hypertension), diabetes, and cancers. We have discussed the expression and functions of tau in cell types other than neurons, and have summarized the evidence supporting a role of tau in these diseases. These cross-disease studies collectively suggest that tau protein is more broadly implicated in mechanisms such as axonal instability, dysregulated cell signaling, inflammatory activation, and cell death, independent of its aggregation, contributing to our knowledge of the functions of tau and the myriad ways in which it may be involved in pathological processes.},
}

@article {pmid42368206,
year = {2026},
author = {Zafarullah, M and Banerjee, R and Singh, A and Ghosh, A and Almeida, S},
title = {Editorial: Neuromuscular disorders: biomarkers, precision diagnosis, and targeted therapeutics.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1878340},
doi = {10.3389/fnins.2026.1878340},
pmid = {42368206},
issn = {1662-4548},
}

@article {pmid42369121,
year = {2026},
author = {Cao, G and Yang, X and Wang, X and Shi, X and Yang, L and Wang, P and Tan, H},
title = {Meniscal repair and partial meniscectomy demonstrated similar clinical outcomes with simultaneous combined anterior cruciate ligament and anterolateral structure reconstruction.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1847295},
pmid = {42369121},
issn = {2296-858X},
abstract = {PURPOSE: The clinical outcomes of patients after combined anterior cruciate ligament (ACL) and anterolateral structure (ALS) reconstruction with or without concomitant meniscal treatment were limited. The purpose of this study was to evaluate clinical outcomes and investigate the effect of concomitant treatment of meniscal injury on these outcomes following combined ACL and ALS reconstruction.

METHODS: A total of 86 patients with combined ACL and ALS reconstruction were eligible for inclusion, from August 2018 to November 2022, with at least 1-year follow-up. The patients were assigned to three groups based on meniscal status, including the no injury group (n = 26), the partial meniscectomy group (the meniscus was resected partially, n = 24), and the repair group (the meniscus was sutured, n = 36). Outcome measurements consisted of function, stability, and safety evaluation. Functional evaluation included Lysholm score, Tegner score, and International Knee Documentation Committee (IKDC) score.

RESULTS: At the last follow-up, the Lysholm, Tegner, and IKDC scores were significantly improved compared with preoperative status (p < 0.05). Functional scores in the no injury group were much higher than those in the partial meniscectomy and repair groups. In addition, the expense was significantly higher in the repair group (43840.9 ± 10804.9) than that in the no injury (37767.7 ± 4537.4, p = 0.003) and partial meniscectomy (37738.7 ± 3794.4, p = 0.004) groups. The stability and safety indices did not differ significantly among the three groups (p > 0.05).

CONCLUSION: Among patients following simultaneous ACL and ALS reconstruction with concomitant meniscal injury, meniscal repair and partial meniscectomy could demonstrate comparable functional outcomes.},
}

@article {pmid42359392,
year = {2026},
author = {Imamura, K and Nagahashi, A and Okusa, A and Yamamoto, T and Izumi, Y and Ueda, N and Kawahara, Y and Inoue, H},
title = {Nonlinear combinatorial analysis of blood transcriptomes identifies PRKAR1A as a regulator of TDP-43 pathophysiology in amyotrophic lateral sclerosis.},
journal = {Biology methods & protocols},
volume = {11},
number = {1},
pages = {bpag023},
pmid = {42359392},
issn = {2396-8923},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. Accurate and accessible blood-based diagnostics for neurodegenerative diseases, including ALS, are being progressively required. Although blood cell gene expression profiles have potential clinical utility for distinguishing ALS, robust transcriptomic biomarkers for supportive diagnosis have not yet been established. Here, we analyzed publicly available peripheral blood mononuclear cell (PBMC) transcriptomic data from ALS patients using Maximum Mean Discrepancy, a kernel-based method that captures nonlinear distributional differences in a reproducing kernel Hilbert space and enables the extraction of informative gene combinations while minimizing multicollinearity, a common issue in multiple regression models. Using this approach, we identified a nonlinear three-gene combination-PRKAR1A, QPCT, and TMEM71-that distinguished ALS from healthy controls with an area under the curve (AUC) of 0.83 in a public PBMC dataset. This achievement was confirmed in laboratory PBMC samples with an AUC of 0.85, supporting the robustness of the identified gene signature in independent samples. Furthermore, these genes also enabled ALS classification in induced pluripotent stem cell-derived motor neurons with an AUC of 0.79. Knockdown of PRKAR1A, QPCT, or TMEM71 in motor neurons increased the TDP-43 expression levels, and PRKAR1A knockdown induced the mislocalization of TDP-43, accompanied by phosphorylation, suggesting a potential link to ALS-related pathophysiology. These findings suggest that nonlinear gene combinations may provide a useful strategy for identifying blood-based biomarkers and offer insights into ALS pathogenesis. This nonlinear, data-driven analytical framework enabled the transition from unbiased gene discovery to the identification of pathophysiology-associated molecules by in vitro functional validation.},
}

@article {pmid42359947,
year = {2026},
author = {Rozman, SI and Hamzaid, NA and Lim, E and Hamzah, N},
title = {Noninvasive assessment of cardiovascular autonomic reflexes in amyotrophic lateral sclerosis: a systematic review.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-19},
doi = {10.1080/21678421.2026.2692135},
pmid = {42359947},
issn = {2167-9223},
abstract = {Dysautonomia is gradually recognized in amyotrophic lateral sclerosis (ALS), raising concerns of secondary complications from heightened autonomic burden. Autonomic disturbances, particularly cardiac dysautonomia, significantly impact patient outcomes, contributing to increased cardiovascular risks and mortality rate. While the ALS Functional Rating Score-Revised (ALSFRS-R) measures functional decline as disease progress, it overlooks autonomic criteria - a critical factor in ALS progression. This review aims to analyze noninvasive applications of cardiovascular signal variability for continuous real-time monitoring of autonomic dysfunction in ALS, while addressing gaps in current clinical assessments. A total of 584 literatures were gathered from four databases (WoS, PubMed, Science Direct and MEDLINE EBSCOhost) - published from inception till December 2023. 21 peer-reviewed studies were included in this review after screening and meeting the inclusion criteria. Various cardiovascular signal variability metrics and autonomic protocols were discussed. Key findings highlight cardiac autonomic dysfunction in ALS is marked by reduced heart rate variability, absent blood pressure regulation upon orthostatic stress and circadian changes, prolonged QTc interval and low baroreflex sensitivity. Moreover, increased autonomic burden is associated with a shift from sympathetic to parasympathetic dysregulation as the disease progresses. Evidence highlights the need to integrate noninvasive autonomic biomarkers into digital ALS monitoring frameworks, enabling earlier detection of autonomic involvement and more precise longitudinal monitoring beyond motor decline.},
}

@article {pmid42360043,
year = {2026},
author = {Sabetta, E and Rallmann, K and Taba, P and Pfaff, AL and Poudel, BH and Ferrari, D and Locatelli, M and Kõks, S and Bergquist, J},
title = {Comparison of Proteomic Analysis of Cerebrospinal Fluid From Neurological Patients With and Without Amyotrophic Lateral Sclerosis.},
journal = {Journal of neurochemistry},
volume = {170},
number = {6},
pages = {e70508},
doi = {10.1111/jnc.70508},
pmid = {42360043},
issn = {1471-4159},
support = {//Multiple Sclerosis Society of Western Australia/ ; SA EUS 100a Fund//Perron Institute for Neurological and Translational Science/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid/diagnosis ; *Proteomics/methods ; Female ; Male ; Biomarkers/cerebrospinal fluid ; Middle Aged ; Aged ; Adult ; Tandem Mass Spectrometry ; Cerebrospinal Fluid Proteins ; Chromatography, Liquid ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterised by progressive muscle weakness in both bulbar and extremity muscles, leading to a diverse clinical phenotype with motor and non-motor symptoms. Approximately 85% of ALS cases are sporadic (sALS), while the remaining 10%-15% are familial (fALS). Biological biomarkers of sporadic ALS remain poorly understood, hindering precise patient screening, delaying diagnosis and negatively affecting prognosis. This study aims to identify potential proteomic biomarkers by comparing the cerebrospinal fluid (CSF) of sALS patients with that of patients suffering from other neurological diseases. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for proteomic profiling of CSF samples from 24 sALS patients and 26 patients with other neurological diseases. The complete protein expression profiles were compared using a two-tailed Student's t-test, with a p < 0.05 considered statistically significant with additional FDR correction at the 0.1 level. Proteomic analysis of CSF samples identified significant quantitative changes in 96 proteins with threshold p < 0.05 and 74 proteins with FDR < 0.1 between sALS and non-ALS patients, including alterations in proteins associated with neurodegenerative processes, such as amyloid precursor proteins and inflammatory markers. CSF proteomic analysis reveals altered inflammatory and neurodegenerative metabolic pathways, providing valuable insights into the proteomic landscape of sALS. Several dysregulated proteins were consistent with the disease mechanisms highlighted in previous studies. These findings represent a step forward in developing personalised approaches for diagnosing and managing the disease.},
}

Humans
*Amyotrophic Lateral Sclerosis/cerebrospinal fluid/diagnosis
*Proteomics/methods
Female
Male
Biomarkers/cerebrospinal fluid
Middle Aged
Aged
Adult
Tandem Mass Spectrometry
Cerebrospinal Fluid Proteins
Chromatography, Liquid

@article {pmid42360520,
year = {2026},
author = {Jayaswal, RP and Thapliyal, S and Badyal, RK},
title = {Comments on: Predictors of pathologic complete response in early-stage triple-negative breast cancer treated with neoadjuvant chemo-immunotherapy.},
journal = {Breast cancer research and treatment},
volume = {217},
number = {3},
pages = {},
pmid = {42360520},
issn = {1573-7217},
mesh = {Humans ; Neoadjuvant Therapy/methods ; Pathologic Complete Response ; *Triple Negative Breast Neoplasms/pathology/drug therapy/therapy ; Female ; Neoplasm Staging ; *Immunotherapy/methods ; Treatment Outcome ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects ; },
abstract = {This correspondence comments on LeVee et al.'s real-world study of neoadjuvant chemo-immunotherapy in early-stage triple-negative breast cancer. We highlight diabetes as a potentially modifiable host-state factor influencing pathologic complete response and propose a metabolic immunotherapy-readiness framework integrating glycaemic control, treatment delivery, endocrine monitoring, and equity-focused implementation. This perspective aims to support globally applicable strategies for improving chemo-immunotherapy effectiveness and access.},
}

Humans
Neoadjuvant Therapy/methods
Pathologic Complete Response
*Triple Negative Breast Neoplasms/pathology/drug therapy/therapy
Female
Neoplasm Staging
*Immunotherapy/methods
Treatment Outcome
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects

@article {pmid42360551,
year = {2026},
author = {Pramanik, S and Debnath, B and Chakraborty, A and Islam, A and Mullick, S and Chaudhary, P and Nath, R and Chellappan, DK and Mondal, M and Ashique, S},
title = {Targeting mtDNA to Modulate Mitochondrial Dysfunction in Neurodegenerative Diseases.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42360551},
issn = {1559-1182},
mesh = {Humans ; *Neurodegenerative Diseases/genetics/therapy/pathology ; *DNA, Mitochondrial/genetics/metabolism ; Animals ; *Mitochondria/genetics/metabolism/pathology ; Gene Editing ; },
abstract = {Mitochondrial dysfunction is a common pathological feature of neurodegenerative diseases namely Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Although these disorders are primarily driven by disease-specific genetic and proteopathic mechanisms, increasing evidence suggests that secondary mitochondrial DNA (mtDNA) damage and heteroplasmy shifts may exacerbate bioenergetic failure and neuronal vulnerability. Distinguishing primary disease mechanisms from downstream mtDNA alterations is critical to accurately evaluate emerging therapeutic strategies. Recent advances in mtDNA-targeted genome editing have enabled the direct manipulation of mitochondrial genomes. Mitochondrially targeted zinc finger nucleases and TALENs can selectively alter mutant mtDNA to induce heteroplasmy shifts, whereas DddA-derived cytosine base editors allow precise base editing without double-strand breaks. However, each platform has distinct limitations related to the target scope, off-target risk, design complexity, and delivery efficiency. The application of CRISPR/Cas-based systems to mammalian mtDNA remains constrained by the unresolved challenges in guiding RNA import. This review critically examines mitochondrial dysfunction and mutant mtDNA accumulation in neurodegenerative diseases. It also evaluates current and emerging mtDNA-editing techniques, and highlights key translational barriers. We highlighted that mtDNA-targeted interventions can be a promising approach for disease-modifying or adjunctive strategies, rather than curative approaches.},
}

Humans
*Neurodegenerative Diseases/genetics/therapy/pathology
*DNA, Mitochondrial/genetics/metabolism
Animals
*Mitochondria/genetics/metabolism/pathology
Gene Editing

@article {pmid42347833,
year = {2026},
author = {Wesenberg, J and Matthies, P and Schwiecker, K and Bittner, V and Hamzic, S and Vielhaber, S and Radakovic, R},
title = {Validation of the German version of the Dimensional Apathy Scale (G-DAS): Application in amyotrophic lateral sclerosis.},
journal = {Journal of neuropsychology},
volume = {},
number = {},
pages = {},
doi = {10.1111/jnp.70061},
pmid = {42347833},
issn = {1748-6653},
support = {//Center for Behavioral Brain Sciences/ ; },
abstract = {Apathy is a common behavioural impairment in neurodegenerative conditions and is conceptualized within the Dimensional Apathy Framework as comprising Executive, Emotional and Initiation subtypes. The Dimensional Apathy Scale (DAS) is widely used to assess these domains, yet no validated German version has been available. This study aimed to translate and validate the German DAS (G-DAS) in control participants (HC) and to characterize apathy profiles in German-speaking people with amyotrophic lateral sclerosis (pwALS). Seventy-seven HC and 32 pwALS completed self-rated and caregiver-rated measures of apathy, depression, disinhibition and executive dysfunction. The G-DAS was translated using a multi-round back-translation procedure. Psychometric validation was undertaken in the HC cohort. A subsample of HC matched to pwALS on age and sex was used for between-group comparisons and for deriving exploratory reference thresholds. The G-DAS demonstrated good to high internal consistency across subscales (α = .76-.85) and total scores (self-rated: α = .88; caregiver-rated: α = .86). Convergent validity was supported by significant correlations with the Apathy Evaluation Scale and Frontal Systems Behavior subscales, particularly for the Initiation and Executive subscales. Divergent validity was evidenced by the absence of associations with anxiety and depression. PwALS showed significantly higher Executive and Initiation apathy compared with matched HC, whereas Emotional apathy did not differ. Exploratory threshold scores derived from matched HC indicated that up to 47% of pwALS exhibited clinically elevated Initiation apathy. The G-DAS is a reliable and valid German-language measure of multidimensional apathy. It effectively captures the characteristic Executive and Initiation apathy profile in ALS, supporting its clinical and research utility.},
}

@article {pmid42348198,
year = {2026},
author = {Walter, KL},
title = {Amyotrophic Lateral Sclerosis.},
journal = {JAMA},
volume = {},
number = {},
pages = {},
doi = {10.1001/jama.2026.9755},
pmid = {42348198},
issn = {1538-3598},
}

@article {pmid42349387,
year = {2026},
author = {Pusic, MV and Ten Cate, O},
title = {Artificial Intelligence, Cognitive Abundance, and the Multi-Layered Competence of Health Professionals.},
journal = {The Journal of continuing education in the health professions},
volume = {},
number = {},
pages = {},
doi = {10.1097/CEH.0000000000000656},
pmid = {42349387},
issn = {1554-558X},
abstract = {Artificial intelligence (AI) is transforming how health care professionals develop, maintain, and express competence across the span of their careers. Traditional continuing professional development has been shaped by a paradigm of what has been called cognitive scarcity (or informational resource scarcity) where clinicians had limited opportunity to find, read, synthesize, and interpret evidence, and learning systems evolved to deliver knowledge in periodic, curated updates. Emerging AI systems-large language models, multimodal analytic tools, predictive algorithms, and reflective agents-disrupt this scarcity by creating cognitive abundance (or informational resource abundance). These systems generate real-time evidence syntheses, contextual insights, adaptive learning trajectories, and continuous performance feedback. Using ten Cate et al.'s (2024, Medical competence as a multilayered construct. Med Educ, 58, 93) multilayered model of competence-canonical, contextual, and personalized-this paper analyzes how AI can both enhance existing educational processes and fundamentally reshape the developmental landscape. AI shifts clinicians from being knowledge stewards to orchestrators of distributed cognition, from experiential learners to data-informed practitioners, and from using opportunistic continuous personal development to continuous reshaping of professional identity. Continuing professional development must evolve to cultivate AI literacy, hybrid reasoning, interprofessional coherence, and ethical stewardship in work environments where cognition is abundant. The contents of long-term memory of clinicians will shift from a predominance of biomedical facts needed to steer daily clinical work, to new procedural inquiry skills needed to find, select, and evaluate the validity of information for clinical decision making.},
}

@article {pmid42349418,
year = {2026},
author = {Heffner, CM and Starling, GP and Straker, LC and Hawes, PC and Isaacs, AM and Carlton, JG},
title = {The ALS- and FTD-associated proteins annexin A11 and CHMP2B act sequentially in plasma membrane repair.},
journal = {Developmental cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.devcel.2026.05.014},
pmid = {42349418},
issn = {1878-1551},
abstract = {Maintenance of plasma membrane integrity is essential for compartmentalization of the cytosol and for cellular viability. Upon membrane damage, several factors including endosomal sorting complex required for transport-III (ESCRT-III) proteins, annexins, stress granules, lipids, and membrane fusion proteins are mobilized to orchestrate membrane repair. However, whether these factors operate independently or act together is unclear. Here, using human cell lines, we expose temporal differences and interdependencies in the recruitment of ESCRT-III and annexin proteins to sites of plasma membrane damage. We show that annexin proteins are recruited immediately and form a plug at the damage site, restricting membrane permeability. We find that ESCRT-III assembles later and acts to release plug-containing damaged membranes from the cell. Further, frontotemporal dementia (FTD)- and amyotrophic lateral sclerosis (ALS)-associated mutations in the ESCRT-III protein, CHMP2B, and the annexin protein, ANXA11, compromise plasma membrane repair, suggesting that defects in this process may contribute to these pathologies. These data present an integrated "sealing and healing" model of membrane repair.},
}

@article {pmid42349421,
year = {2026},
author = {Aubry, L and Korolchuk, VI and Sarkar, S},
title = {Rewiring ALS by modulating the autophagy receptor SQSTM1.},
journal = {Stem cell reports},
volume = {},
number = {},
pages = {102976},
doi = {10.1016/j.stemcr.2026.102976},
pmid = {42349421},
issn = {2213-6711},
abstract = {Drug screening for genetic disorders is limited by difficulty identifying disease-relevant phenotypes. In this issue, Roussange et al., show that reverse phenotypic mapping could uncover therapeutic gene expression signatures. Using this approach, they identified prazosin, which increases SQSTM1 expression and rescues disease phenotypes in iPSC-derived motor neurons and zebrafish model of amyotrophic lateral sclerosis with SQSTM1 haploinsufficiency.},
}

@article {pmid42349423,
year = {2026},
author = {Roussange, F and Gide, J and Tournois, J and Cailleret, M and Boland, A and Battail, C and Deleuze, JF and Polvèche, H and Auboeuf, D and Brockmann, K and Kabashi, E and Marian, A and El Kassar, L and Blondel, S and Salachas, F and Bruneteau, G and Peschanski, M and Martinat, C and Baghdoyan, S},
title = {Integrative analysis of drug-gene signatures in human pluripotent stem cells reveals prazosin as a novel SQSTM1 regulator for ALS therapeutics.},
journal = {Stem cell reports},
volume = {},
number = {},
pages = {102977},
doi = {10.1016/j.stemcr.2026.102977},
pmid = {42349423},
issn = {2213-6711},
abstract = {The classical paradigm of drug screening often faces significant limitations due to the challenges associated with identifying molecular or cellular read-outs that are relevant to specific genetic diseases. To remedy this, an alternative approach of reverse phenotypic mapping was tested: Compounds were evaluated for their effects on gene expression and alternative splicing in a healthy cell model, and the resulting data were matched to molecular signatures of diseases. A subset of 50 drugs was tested on mesenchymal stem cells derived from a human pluripotent stem cell line. Over half of the compounds altered gene expression, many affecting pathways linked to monogenic diseases. One hit, increased SQSTM1 expression induced by prazosin, was further validated in FTD/ALS type 3 models caused by SQSTM1 haploinsufficiency, including patient-derived fibroblasts, SQSTM1-depleted hiPSC-derived motor neurons, and a zebrafish model. Extending this paradigm could involve testing diverse cell types and larger drug libraries.},
}

@article {pmid42350166,
year = {2026},
author = {Tikkinen, KAO and Tondroanamag, F and Parpia, S and Guyatt, GH and Violette, PD and , },
title = {Reply to Vallée M, Stangl FP, Wagenlehner F et al's Letter to the Editor re: Tikkinen KAO, Najafabadi BT, Hajebrahimi S, et al. A Multicenter Randomized Controlled Trial of Antimicrobial Prophylaxis to Prevent Urinary Tract Infections After Shockwave Lithotripsy for Urolithiasis: The APPEAL Trial. Eur Urol 2025;88(6):543-51.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2026.06.008},
pmid = {42350166},
issn = {1873-7560},
}

@article {pmid42350373,
year = {2026},
author = {Casterton, R and Martinez-Cotrina, A and Barnard, J and Wycherley, E and Hu, Y and Anderson, R and Janel, S and Byun, J and Houghton, O and Solomon, DA and Alcalde, J and Lafont, F and Ruepp, MD and Hirth, F and Tummers, B and Cho, YY and De Nicola, G and Mizielinska, S and Fanto, M},
title = {Karyoptosis mediates cell death and neurodegeneration upon proteotoxic stress.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {},
pmid = {42350373},
issn = {2041-1723},
support = {ARUK-PG2019B-008//Alzheimer's Research UK (ARUK)/ ; },
mesh = {Proteotoxic Stress ; Animals ; Humans ; Cell Death ; Neurons/metabolism/pathology ; Lamin Type B/metabolism/genetics ; Phosphorylation ; Alzheimer Disease/pathology/metabolism ; *Neurodegenerative Diseases/metabolism/pathology ; Nuclear Lamina/metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism ; Mice ; Frontotemporal Dementia/pathology/metabolism ; Cell Nucleus/metabolism ; },
abstract = {Neurodegenerative diseases are frequently associated with proteotoxic stress linked to disease specific proteins. The autophagy-lysosome system provides essential control of proteotoxic stress and its failure can lead to initiation of apoptosis. However, in aging and neurodegenerative diseases apoptosis is insufficient to account for all neuronal death, and several different cell death types have been reported in these contexts. Here we show that karyoptosis, a distinct form of cell death, can be induced by proteotoxic stress and then develops through nuclear degeneration and cellular expulsion of nuclear material. We establish that karyoptosis is regulated by the p38 kinase signalling pathway, which controls stability of the nuclear lamina protein LaminB1 via direct phosphorylation. We demonstrate that karyoptosis affects neurons in models of amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) pathology. Finally, we identify karyoptotic features in post-mortem frontal cortex of FTD and Alzheimer's disease (AD) patients. Together these findings characterise a form of cell death directly linked to proteotoxic stress and nuclear lamina stability that is associated with neurodegeneration.},
}

Proteotoxic Stress
Animals
Humans
Cell Death
Neurons/metabolism/pathology
Lamin Type B/metabolism/genetics
Phosphorylation
Alzheimer Disease/pathology/metabolism
*Neurodegenerative Diseases/metabolism/pathology
Nuclear Lamina/metabolism
p38 Mitogen-Activated Protein Kinases/metabolism
Mice
Frontotemporal Dementia/pathology/metabolism
Cell Nucleus/metabolism

@article {pmid42350385,
year = {2026},
author = {Wan, F and He, J and Ma, H and PiresFerreira, D and Kumanan, V and Lee, JS and Chen, X and He, R and Su, Q and Gallagher, TL and Zhu, S and Cabrera, GT and Zhao, L and Shen, J and Gruntman, A and Brown, RH and Xu, Z and Gao, G and Xie, J},
title = {Intravenous administration of an engineered AAV9-gene-silencing vector suppresses human SOD1 and extends survival in an ALS mouse model.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {},
pmid = {42350385},
issn = {2041-1723},
support = {AL240123//United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP)/ ; },
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/therapy/genetics ; *Dependovirus/genetics ; *Superoxide Dismutase-1/genetics/metabolism ; Humans ; Disease Models, Animal ; *Genetic Vectors/administration & dosage/genetics ; Mice ; Motor Neurons/metabolism/pathology ; *Genetic Therapy/methods ; *Gene Silencing ; Mice, Transgenic ; Administration, Intravenous ; MicroRNAs/genetics ; Neuromuscular Junction/metabolism ; Female ; Gene Therapy Agents ; Male ; },
abstract = {Adeno-associated virus (AAV)-mediated gene silencing offers a promising strategy for achieving durable therapeutic effects with a single administration. Mutations in the human superoxide dismutase 1 (hSOD1) gene, inherited in an autosomal dominant manner, lead to motor neuron degeneration in amyotrophic lateral sclerosis (ALS)-a fatal neurodegenerative disease with no effective treatment. In this study, we employed AAV9 to deliver to the SOD1[G93A] ALS mouse model artificial microRNAs targeting SOD1, embedded in dual miR-33 scaffolds driven by the promoter of the human survival motor neuron 1 (hSMN1) gene. A single intravenous injection achieved widespread and sustained suppression of SOD1, preserved α-motor neurons, maintained neuromuscular junctions (NMJs), and improved muscle function. These benefits are translated into significantly improved respiratory function, motor performance, and survival. Therapeutic efficacy was observed both when the treatment was administered pre-symptomatically and during symptomatic stages. Compared with previous AAV-based interventions, the survival benefit achieved in this IV delivery approach is unprecedented, supporting its potential for clinical translation in SOD1-linked ALS and other central nervous system (CNS) diseases caused by gain-of-toxicity gene mutations.},
}

Animals
*Amyotrophic Lateral Sclerosis/therapy/genetics
*Dependovirus/genetics
*Superoxide Dismutase-1/genetics/metabolism
Humans
Disease Models, Animal
*Genetic Vectors/administration & dosage/genetics
Mice
Motor Neurons/metabolism/pathology
*Genetic Therapy/methods
*Gene Silencing
Mice, Transgenic
Administration, Intravenous
MicroRNAs/genetics
Neuromuscular Junction/metabolism
Female
Gene Therapy Agents
Male

@article {pmid42351201,
year = {2026},
author = {Dominguez, GTY and Alarcan, H and Peralta, V and Labroche, N and Corcia, P and Marcel, P and Blasco, H},
title = {Learning a distance for the clustering of patients with amyotrophic lateral sclerosis.},
journal = {BioData mining},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13040-026-00579-5},
pmid = {42351201},
issn = {1756-0381},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with median survival of 3-5 years. Patient responses to treatments vary widely, highlighting the need for personalized care. Clustering patients based on disease progression could improve prognosis, guide clinical decision-making, and optimize clinical trial design. This study aimed to identify robust ALS patient clusters using ALS Functional Rating Scale-Revised (ALSFRS-R) scores and to determine diagnostic parameters predictive of cluster membership, enabling earlier stratification and targeted management.

METHODS: Data from the Tours ALS center registry (April 1997-October 2023) were analyzed; after preprocessing, 353 patients monitored every three months between January 2004 and July 2023 with ALSFRS-R, clinical, biological, and demographic data were retained. After preprocessing to handle missing or aberrant data, a weakly supervised approach labeled patient pairs based on their ALSFRS-R sequences. These labels were used to train a classifier to learn a distance for off-the-shelf clustering algorithms. Multiple configurations were tested, varying clustering algorithms, dimensionality reduction method, and number of clusters. Random Forest (RF) model predicted cluster membership from diagnostic parameters. Optimal clustering was selected using silhouette score, validated with Kaplan-Meier survival analysis. Stability and robustness were assessed with the Adjusted Rand Index (ARI) and silhouette score respectively. Predictive performance was evaluated using specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV). Diagnostic parameters associated with clusters were identified using Kruskal-Wallis and chi-squared tests for continuous and categorical variables.

RESULTS: Three clusters (n = 139, 121, 93) were identified, demonstrating strong separation (silhouette ≈ 0.6) and high stability of results (ARI ≈ 0.7). Survival differed significantly among clusters: over 50% of patients in the third cluster survived beyond 50 months, compared to less than 25% in the other clusters. Thirteen diagnostic parameters-including ALSFRS-R subscores, IgG levels, albumin quotient, and time to diagnosis-were key predictors of cluster membership. Cluster prediction achieved specificity and NPV ≈ 0.75, with close sensitivity and PPV compared to state-of-the-art methods.

CONCLUSION: This framework successfully stratifies ALS patients into clinically meaningful clusters, revealing underlying disease heterogeneity and providing strong prognostic insight. Such classification can facilitate personalized care, guide therapeutic decisions, and inform the design of targeted interventions to improve outcomes.

CLINICAL TRIAL NUMBER: Not applicable.},
}

@article {pmid42351263,
year = {2026},
author = {Riggio, F and Fenili, G and Caporossi, D and Paronetto, MP},
title = {Dynamic integration of skeletal muscle signals via extracellular vesicles in motor neuron diseases.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-026-02356-1},
pmid = {42351263},
issn = {2051-5960},
support = {PNRR-MR1-2022-12376821//Ministero della Salute/ ; },
abstract = {Extracellular vesicles (EVs) are heterogenous lipid bilayer-enclosed particles secreted by virtually all cell types. They encapsulate a diverse array of bioactive molecules, including proteins, lipids, nucleic acids, and metabolites, which can be transferred to recipient cells, thereby modulating their function and phenotype. In recent years, skeletal muscle-derived EVs (SkM-EVs) have emerged as key players in the bidirectional communication between skeletal muscle and motor neurons, contributing to the establishment and maintenance of neuromuscular homeostasis. Disruptions in this intercellular signalling have been implicated in the pathophysiology of motor neuron diseases (MNDs) such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). In these contexts, SkM-EVs may contribute to disease progression by delivering pathogenic cargo, including misfolded proteins and aberrant RNAs, to motor neurons. A comprehensive understanding of SkM-EV biology, particularly their roles in neuromuscular communication, could offer critical insights into disease mechanisms and identify novel opportunities for biomarker discovery and therapeutic intervention. This review synthesizes current knowledge on the functional roles of SkM-EVs in motor neuron health and disease and evaluates their potential as diagnostic tools and therapeutic vectors in the context of MNDs.},
}

@article {pmid42351313,
year = {2026},
author = {Brenner, D and Ponomarenko, A and Petrut, I and Beyrle, S and Contardo, M and Loss, I and Radke, C and Frank, J and Zimmer, E and Schlesner, M and Achenbach, P and Scheveneels, W and Aly, A and Nazlican, H and Hesebeck-Brinkmann, J and Oeckl, P and Müller, K and Siebert, R and Böckers, T and van Eijk, K and Veldink, J and Kleger, A and Mulaw, M and Andersen, PM and Forsberg, K and Weishaupt, JH and Loghmani, SB and Grehl, T and van Damme, P and Weis, J and Catanese, A},
title = {A rare missense variant impacting NEK1 kinase function is associated with ALS.},
journal = {Acta neuropathologica communications},
volume = {14},
number = {1},
pages = {},
pmid = {42351313},
issn = {2051-5960},
mesh = {*NIMA-Related Kinase 1/genetics/metabolism ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; *Mutation, Missense/genetics ; Female ; Motor Neurons/pathology/metabolism ; Male ; Pedigree ; Animals ; },
abstract = {Heterozygous truncating loss-of-function (LoF) variants in NEK1 are a known cause of amyotrophic lateral sclerosis (ALS). NEK1 encodes the pleiotropic serine/threonine kinase NIMA-related kinase 1, and prior in vitro studies have implicated kinase dysfunction as the principal pathogenic mechanism underlying NEK1-associated ALS. However, bona fide pathogenic missense variants causally linked to ALS have not previously been reported, leaving this hypothesis unconfirmed. Here, we identify a rare NEK1 missense variant, p.N598S, that co-segregates with disease in a familial ALS pedigree and is enriched in European ALS cohorts. This variant exhibits normal protein expression levels, indicating a functional rather than quantitative defect. Using isogenic human motor neurons, we directly compared the effects of p.N598S with those of the ALS-associated truncating variant p.R812* to delineate disease mechanisms. The p.N598S variant induced pathological phenotypes consistent with NEK1 haploinsufficiency, including increased susceptibility to DNA damage, increased apoptosis, ciliary dysmorphia, and nucleocytoplasmic translocation of TDP-43. Importantly, p.N598S impaired NEK1 kinase activity, and pharmacological inhibition of NEK1 recapitulated the cellular phenotypes observed in both p.N598S- and p.R812*-mutant motor neurons. Collectively, these findings provide strong genetic and functional evidence for a disease-causing role of NEK1 kinase disruption in NEK1-ALS. Our findings provide immediate diagnostic and therapeutic implications, particularly for the functional interpretation of missense variants of uncertain significance and the development of targeted treatment strategies.},
}

*NIMA-Related Kinase 1/genetics/metabolism
Humans
*Amyotrophic Lateral Sclerosis/genetics/pathology
*Mutation, Missense/genetics
Female
Motor Neurons/pathology/metabolism
Male
Pedigree
Animals

@article {pmid42352309,
year = {2026},
author = {Morciano, G and Gorgoglione, R and Porcelli, V and Ahmed, A and Scarcia, P and Vozza, A and Lasorsa, FM and Fiermonte, G and Palmieri, L},
title = {Mitochondrial Dynamics and SLC25 Transporters in Neurodegeneration: From Mechanisms to Therapeutic Opportunities.},
journal = {Biomolecules},
volume = {16},
number = {6},
pages = {},
doi = {10.3390/biom16060842},
pmid = {42352309},
issn = {2218-273X},
support = {2020RRJP5L//Ministry of Universities and Research/ ; 2022ZY7ATN//Ministry of Universities and Research/ ; GR-2019-12369862//Italian Ministry of Health/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology/drug therapy ; *Mitochondrial Dynamics ; *Mitochondria/metabolism ; Animals ; *Mitochondrial Proteins/metabolism ; Energy Metabolism ; Mitochondrial Membrane Transport Proteins/metabolism ; },
abstract = {Neurodegenerative diseases are increasingly recognized as disorders of due to disrupted cellular homeostasis, with mitochondrial dysfunction playing a central and early role in disease progression. This review explores the intricate relationship between mitochondrial function and neuronal health, emphasizing the pivotal role of the solute carrier family 25 (SLC25) transporters in maintaining mitochondrial homeostasis. We provide a comprehensive overview of mitochondrial biology in the central nervous system, including energy metabolism, calcium signaling, redox regulation, organelle interactions and mitochondrial dynamics. We delve into the SLC25 transporter family, highlighting their transport mechanisms, substrates and roles in brain metabolism and neuroprotection. SLC25 on one hand and proteins involved in the regulation of mitochondrial morphology and calcium signaling on the other hand are two sides of the same coin influencing each other. A critical analysis follows, examining how mitochondrial dysfunction contributes to mitochondrial abnormalities in a spectrum of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, ALS and rare mitochondrial encephalopathies. Finally, we assess emerging therapeutic strategies targeting mitochondrial pathways and SLC25 function, including metabolic modulation, gene therapies, antioxidants and pharmacological agents. This review underscores mitochondria and the SLC25 transporters as promising targets for disease-modifying interventions in neurodegeneration and raises key questions about the causality between mitochondrial failure and neuronal death.},
}

Humans
*Neurodegenerative Diseases/metabolism/pathology/drug therapy
*Mitochondrial Dynamics
*Mitochondria/metabolism
Animals
*Mitochondrial Proteins/metabolism
Energy Metabolism
Mitochondrial Membrane Transport Proteins/metabolism

@article {pmid42352358,
year = {2026},
author = {Lee, BC and Hwang, JJ and Tsai, HJ},
title = {Extracellular Pgk1 or Its Derived Short Peptide Interacted with Membrane-Associated Enolase 2 Receptor: A Potential Therapy for ALS Motor Neuron Degeneration.},
journal = {Biomolecules},
volume = {16},
number = {6},
pages = {},
doi = {10.3390/biom16060893},
pmid = {42352358},
issn = {2218-273X},
support = {NSTC-114-2313-B-030-001//National Science and Technology Council/ ; F630410//USA FJCU Alumni Foundation/ ; CPL-202508003//Collaborative Research Project between FJUH and FJU/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology ; Humans ; *Phosphopyruvate Hydratase/metabolism ; Animals ; *Phosphoglycerate Kinase/metabolism ; *Motor Neurons/metabolism/pathology/drug effects ; *Peptides/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS) remains an intractable motor neuron (MN) disease with a growing patient population and few effective treatments. Here, we review how extracellular phosphoglycerate kinase 1 (ePgk1) improves neurite outgrowth of MNs (NOMN) and axonal growth, both in vitro and in vivo. Our group first elucidated a novel non-canonical function of ePgk1 as a cross-tissue mediator between nerve and muscle tissues. We then discovered that neural membranous Enolase 2 (Eno2) serves as a receptor of ligand ePgk1 and that ePgk1-Eno2 interaction suppresses the Rac1-GTP/p-Pak1-T423/p-P38-T180/pMK2-T334/p-Limk1-S323 axis, reducing p-Cofilin and promoting NOMN and axonal growth, finally suggesting that the 419th aspartic acid residue of Eno2 mediates this interaction. In a crucial preclinical step, we truncated two short 16-amino-acid derivatives from Pgk1, FD-1/-2, each mediating neuroprotection comparable to that of full-length 417-amino-acid Pgk1 in ALS animal models, in terms of improvements of innervated neuromuscular junction, MN cell bodies, motor performance, and endpoint prolongation. In this context, we also discuss the opposite function driven by Eno1-plasminogen interaction and by Eno2-ePgk1 interaction; the latter results in unfavorable for tumorigenesis. Unlike intracellular Pgk1 roles, ePgk1 is an extracellular factor with anti-angiogenic properties, further positioning ePgk1 and its FD-1/-2 as promising protein/peptide drugs for ALS treatment.},
}

*Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology
Humans
*Phosphopyruvate Hydratase/metabolism
Animals
*Phosphoglycerate Kinase/metabolism
*Motor Neurons/metabolism/pathology/drug effects
*Peptides/metabolism

@article {pmid42352620,
year = {2026},
author = {De Luca, E and Saba, A and Bertarini, L and Brusini, A and Artioli, G and Dellafiore, F},
title = {Spiritual Care Needs and Challenges Among Caregivers and Families of People with Neurodegenerative Diseases in Palliative and End-of-Life Care: A Scoping Review.},
journal = {Brain sciences},
volume = {16},
number = {6},
pages = {},
doi = {10.3390/brainsci16060611},
pmid = {42352620},
issn = {2076-3425},
abstract = {Background/Objectives: Spirituality is increasingly recognised as a core dimension of holistic and palliative care. Neurodegenerative diseases such as dementia, amyotrophic lateral sclerosis and Parkinson's disease involve prolonged trajectories of loss, uncertainty and relational change, which may heighten spiritual and existential needs for patients, particularly among those involved in caregiving, such as family caregivers and, to a lesser extent, healthcare professionals. However, evidence on how spirituality is understood, experienced and addressed within neurodegenerative palliative care remains fragmented and conceptually heterogeneous. This scoping review aimed to map the literature on caregivers' spiritual needs and challenges. Methods: A scoping review was conducted in accordance with the Joanna Briggs Institute (JBI) methodology for scoping reviews and the Preferred Reporting Items for Systematic Reviews and Meta Analyses extension for Scoping Reviews (PRISMA ScR). Searches were conducted across PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), APA PsycINFO, and Scopus, with no date or geographical restrictions. Grey literature was searched through Google Scholar and relevant organisational and policy sources in the field of palliative care and spirituality. Reference list screening of included studies and relevant reviews was also conducted. Quantitative, qualitative, and mixed methods studies published in English or Italian were included. Results: Twenty-four studies published between 2007 and 2025 were included. Findings were organised into three interconnected domains: spiritual needs, spiritual processes and spiritual care. Spirituality emerged as a dynamic, relational and context-dependent dimension of caregiving, encompassing meaning, identity, connection and coping with vulnerability and loss. Spiritual needs and processes were widely described, while spiritual care was inconsistently recognised within healthcare systems. Conceptual ambiguity, under-representation of end-of-life dementia and cultural imbalances were evident. The evidence predominantly focused on family caregivers, with limited representation of healthcare professionals. Conclusions: This scoping review highlights a persistent gap between caregivers' lived spiritual experiences and system-level responses in neurodegenerative palliative care in caregiving contexts globally. The findings support integrated, caregiver-inclusive and culturally responsive approaches to spiritual care.},
}

@article {pmid42352782,
year = {2026},
author = {Hümpfer-Gerhards, L and Schwager, S and Benecke, M and Fuhrmann, S and Kunert, J and Knigge, M},
title = {Reducing Barriers in Neurodiverse Schools-schAUT: A Program to Identify and Reduce Barriers for Autistic and All Students.},
journal = {Behavioral sciences (Basel, Switzerland)},
volume = {16},
number = {6},
pages = {},
doi = {10.3390/bs16060949},
pmid = {42352782},
issn = {2076-328X},
support = {01NV2104//Federal Ministry of Education and Research Germany/ ; },
abstract = {This paper presents results from the project schAUT, a participatory research project initiated by Humboldt University Berlin, Goethe University Frankfurt a.M. and White Unicorn e.V., funded by the German Federal Ministry of Education and Research (BMBF; FKZ: 01NV2104). It aimed to identify and reduce barriers to learning and participation in mainstream schools, with a particular focus on autistic students. This paper introduces a questionnaire and a program to support School Organizational Development (SOD), aiming to provide equitable and accessible learning environments grounded in international frameworks on inclusive education. This study combines qualitative and quantitative approaches to examine the subjective experiences of barriers. We present data obtained through a multi-phase development and validation phase. The results show that neurodivergent participants generally experienced higher subjective barriers, although we observed that barriers affect neurotypical students as well, highlighting a subjective nature. We argue that these findings support neurodiversity as a relevant concept, especially in educational contexts. This supports Larrauri et al.'s Big-Tent approach to neurodiversity, emphasizing individual variability while acknowledging structural biases towards neurotypical norms in educational environments. The study highlights the value of multiperspective approaches in (participatory) research and SOD, to develop strategies for an inclusive educational environment through neurodiversity-informed decision processes and enable equitable learning environments for all students.},
}

@article {pmid42352907,
year = {2026},
author = {Scrivo, A and Bernardino, L and Consiglio, A},
title = {The Dual Role of Glial Extracellular Vesicles in Neurodegeneration: Insights from iPSC-Based Models.},
journal = {International journal of molecular sciences},
volume = {27},
number = {12},
pages = {},
doi = {10.3390/ijms27125182},
pmid = {42352907},
issn = {1422-0067},
support = {2023 BP 00242//Agència de Gestió d'Ajuts Universitaris i de Recerca/ ; },
abstract = {Extracellular vesicles (EVs) have emerged as key mediators of intercellular communication in the brain, with glial cell-derived EVs increasingly recognized for their roles in maintaining brain homeostasis and contributing to the progression of neurodegenerative diseases. By transferring a diverse cargo of bioactive molecules, including proteins, RNAs, and organelles, EVs influence recipient cell behavior and overall brain function. In neurodegenerative conditions, glial EVs can either propagate pathogenic signals or deliver neuroprotective and regenerative cues, depending on their cellular origin and molecular composition. This context-dependent heterogeneity highlights the need for physiologically relevant human models to investigate EVs biology. Human induced pluripotent stem cell (iPSC)-derived glial models provide a disease-relevant platform, as they recapitulate key pathological features of Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). When further integrated with brain organoid platforms, these iPSC-based systems enable the generation of three-dimensional environments that closely resemble in vivo EVs dynamics. Importantly, glial EVs can modulate cellular pathways involved in neuronal survival and function. Indeed, their potential to interact with and, under specific experimental conditions, traverse the blood-brain barrier (BBB) has contributed to growing interest in their application for biomarker discovery and therapeutic development. Engineered and patient-specific EVs derived from iPSCs are emerging as promising tools for targeted, cell type-specific, therapeutic approaches, although their clinical applicability still requires further validation. This review discusses the emerging evidence supporting the dual role of iPSC-derived glial EVs in health and disease, underscores the translational potential of iPSC-based platforms for mechanistic studies, and outlines their promise as precision medicine tools for diagnostics and therapy.},
}

@article {pmid42353064,
year = {2026},
author = {Reedich, EJ and Chen, YT and Imhoff-Manuel, R and Li, D and Manuel, M},
title = {Chronic Diazepam Reveals Excessive Homeostatic Gain in SOD1[G93A] Mouse Spinal Motoneurons.},
journal = {International journal of molecular sciences},
volume = {27},
number = {12},
pages = {},
doi = {10.3390/ijms27125342},
pmid = {42353064},
issn = {1422-0067},
support = {1R01NS110953-05/NS/NINDS NIH HHS/United States ; },
mesh = {Animals ; *Motor Neurons/drug effects/metabolism/physiology ; *Diazepam/pharmacology ; Mice ; *Homeostasis/drug effects ; *Amyotrophic Lateral Sclerosis/genetics/drug therapy/metabolism/physiopathology/pathology ; *Spinal Cord/drug effects/metabolism ; *Superoxide Dismutase-1/genetics ; Mice, Transgenic ; Action Potentials/drug effects ; Disease Models, Animal ; Synaptic Transmission/drug effects ; },
abstract = {Motoneurons are under strong pressure to maintain stable motor output throughout an individual life, through homeostatic regulation of their electrical properties. Dysregulated spinal motoneuron excitability has long been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Recent work in SOD1[G93A] mice suggests that the homeostatic response of motoneurons becomes dysregulated as cellular processes are disrupted by the disease, causing fluctuations in motoneuron electrical properties. Yet, few studies directly test whether ALS motoneurons respond differently than wild-type motoneurons to a common chronic perturbation. Here, we used in vivo electrophysiology to test whether motoneurons from pre-symptomatic SOD1[G93A] mice modulate excitability differently than wild-type motoneurons in response to the same homeostatic perturbation: chronic inhibition exerted by the benzodiazepine diazepam. Using linear mixed-effects statistical models, we assessed whether diazepam treatment differentially modulated passive properties, firing behavior, spike properties, and/or synaptic inputs in SOD1[G93A] versus wild-type motoneurons. We identified a significant genotype × treatment interaction effect selectively for properties related to passive membrane integration and spike initiation, including membrane time constant, peak input resistance, and recruitment current. In contrast, firing gain, spike waveform characteristics, and synaptic inputs were largely unaffected. These findings indicate that sustained inhibitory perturbation selectively triggered overactive intrinsic compensatory mechanisms in SOD1[G93A] motoneurons rather than inducing widespread changes in firing or synaptic transmission. Together, our results provide direct evidence for over-active homeostatic control of motoneuron excitability and support a view of motoneuron dysfunction in ALS as a problem of altered feedback regulation rather than simply hyper- or hypo-excitability.},
}

Animals
*Motor Neurons/drug effects/metabolism/physiology
*Diazepam/pharmacology
Mice
*Homeostasis/drug effects
*Amyotrophic Lateral Sclerosis/genetics/drug therapy/metabolism/physiopathology/pathology
*Spinal Cord/drug effects/metabolism
*Superoxide Dismutase-1/genetics
Mice, Transgenic
Action Potentials/drug effects
Disease Models, Animal
Synaptic Transmission/drug effects

@article {pmid42353079,
year = {2026},
author = {Romano, G and Klima, R and Feiguin, F},
title = {Loss of TDP-43 Drives Innate Immune Activation Through Relish in Drosophila.},
journal = {International journal of molecular sciences},
volume = {27},
number = {12},
pages = {},
doi = {10.3390/ijms27125359},
pmid = {42353079},
issn = {1422-0067},
mesh = {Animals ; *Drosophila Proteins/genetics/metabolism/immunology ; *DNA-Binding Proteins/genetics/metabolism ; *Immunity, Innate/genetics ; *Transcription Factors/genetics/metabolism ; Signal Transduction ; *Drosophila melanogaster/immunology/genetics ; },
abstract = {Inflammatory and immune alterations are increasingly recognized as components of ALS pathology, yet whether they arise as a direct consequence of TDP-43 dysfunction or as a downstream response to neurodegeneration remains unresolved. To address this question, we profiled adult head transcriptomes of Drosophila lacking TBPH, the fly homolog of TDP-43, and identified marked overactivation of the conserved Toll/Imd/NF-κB (Relish) innate immune pathway, including increased expression of antimicrobial effector genes and inflammatory genes. We further found that TDP-43/TBPH regulates the NF-κB homolog Relish by associating with its mRNA and that its loss permits Relish-dependent immune overactivation. Genetic reduction in Relish in TDP-43-deficient flies suppressed inflammatory signaling and ameliorated neurological defects in vivo, indicating that immune dysregulation contributes to TDP-43 loss-associated phenotypes.},
}

Animals
*Drosophila Proteins/genetics/metabolism/immunology
*DNA-Binding Proteins/genetics/metabolism
*Immunity, Innate/genetics
*Transcription Factors/genetics/metabolism
Signal Transduction
*Drosophila melanogaster/immunology/genetics

@article {pmid42353250,
year = {2026},
author = {Sharma, N and An, SSA},
title = {Microglial Dysfunction Induced by C9ORF72 Dipeptide Repeat Proteins: Biomarker and Therapeutic Perspectives.},
journal = {International journal of molecular sciences},
volume = {27},
number = {12},
pages = {},
doi = {10.3390/ijms27125537},
pmid = {42353250},
issn = {1422-0067},
support = {RS-2021-NR060117//National Research Foundation of Korea/ ; RS-2025-02292973//Korea Institute of Marine Science and Technology Promotion/ ; },
mesh = {*C9orf72 Protein/genetics/metabolism ; Humans ; *Microglia/metabolism/pathology ; Biomarkers/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology/therapy ; *Frontotemporal Dementia/genetics/metabolism/pathology/therapy ; *Dipeptides/genetics/metabolism ; Animals ; DNA Repeat Expansion ; Autophagy ; },
abstract = {The GGGGCC hexanucleotide repeat expansion (HRE) in C9ORF72 was recognized as the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Repeat-associated non-AUG (RAN) translation of the expanded repeat generated dipeptide repeat proteins (DPRs), which disrupted multiple cellular processes and contributed to neurodegeneration. Emerging evidence indicated that disease pathogenesis involved both gain-of-function (GOF) and loss-of-function (LOF) mechanisms. DPR-mediated GOF toxicity induced ribosomal dysfunction, nucleolar stress, proteostatic impairment, and neuronal injury, whereas C9ORF72 LOF disrupted lysosomal and autophagic pathways in microglia, impairing the immune homeostasis. Neuronal injury further promoted the release of damage-associated signals that triggered secondary microglial activations and chronic neuroinflammations. This review summarized current knowledge of DPR biology, microglial dysfunction, and their contributions to disease progression in C9ORF72-associated ALS/FTD. Therapeutic strategies targeting repeated RNA, DPR productions, proteostasis, autophagy, and neuroinflammatory pathways were also discussed. In addition, the potentials of fluid biomarkers, including cerebrospinal fluid poly (GP) and blood neurofilament light chain (NfL), for diagnosis, disease monitoring, and therapeutic assessment were shown. Together, these findings provided important insights into disease mechanisms and potential avenues for improved clinical management.},
}

*C9orf72 Protein/genetics/metabolism
Humans
*Microglia/metabolism/pathology
Biomarkers/metabolism
*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology/therapy
*Frontotemporal Dementia/genetics/metabolism/pathology/therapy
*Dipeptides/genetics/metabolism
Animals
DNA Repeat Expansion
Autophagy

@article {pmid42355891,
year = {2026},
author = {Calabrese, L and Mion, M and Mandrini, A and Primi, R and Bendotti, S and Ulmanova, L and Currao, A and Morena, A and Dossi, F and Fogagnolo, L and Pizzi, F and Fava, C and Ghiraldin, D and Battioni, A and Genoni, P and Madonini, EMP and Maffeo, D and Dossena, C and Affinito, S and Bertazzoli, G and Pellegrino, M and Papi, G and Frattini, S and Della Torre, M and Fantoni, C and Praderio, A and Tarantino, L and Mongiovì, S and Politi, P and Savastano, S and Baldi, E and All The LombardiaCARe Researchers, },
title = {The Early Implementation of a Hub-and-Spoke Survivorship Pathway for Out-of-Hospital Cardiac Arrest Survivors: A 12-Month Formative Evaluation of the REVIVE Project.},
journal = {Journal of clinical medicine},
volume = {15},
number = {12},
pages = {},
doi = {10.3390/jcm15124722},
pmid = {42355891},
issn = {2077-0383},
support = {8049724//Italian Ministry of Health - Ricerca Corrente/ ; },
abstract = {Background/Objectives: A structured follow-up after out-of-hospital cardiac arrest (OHCA) is recommended, but implementation across regional networks remains challenging. REVIVE introduced a hub-and-spoke survivorship pathway in Lombardy. This 12-month formative implementation evaluation aimed to describe staged pathway progression, operational reach, attrition points, centre-level variation, and documented barriers to assessment completion. Methods: Adult OHCA survivors with Cerebral Performance Category (CPC) 1-2 or Modified Rankin Scale (mRS) ≤ 3 were considered eligible. The evaluation was structured using Proctor et al.'s implementation outcomes framework. Implementation outcomes were operationalised using prospectively collected pathway indicators: eligibility ascertainment, successful contact, T0 assessment completion, completion of planned assessment components, timeliness where available, and documented reasons for non-progression. Analyses were descriptive and used chi-square or Fisher's exact tests for unadjusted centre-level comparisons. Results: Of the 1663 patients hospitalised, 1458 (87.7%) were recorded as deceased or having an unfavourable neurological outcome and were therefore outside the intended REVIVE target population. Among the remaining 205 patients, eligibility could not be determined for 78 (4.7% of the total cohort), and 127 (7.6%) met eligibility criteria. Of eligible survivors, 96 (75.6%) were contacted and 64 completed the T0 assessment (66.7% of contacted; 50.4% of eligible). Pavia showed higher observed rates of eligibility ascertainment, contact, and assessment completion than spoke centres, but these differences were unadjusted and should be interpreted as centre-level implementation variation rather than evidence of causal superiority. Conclusions: REVIVE initiated a structured regional pathway for post-OHCA follow-up, but first-year implementation was partial rather than definitive. The 50.4% T0 completion rate among eligible survivors should be interpreted as an initial internal implementation indicator, not as evidence of established feasibility, effectiveness, or regional benchmarking. Priorities for further optimisation include eligibility ascertainment, transfer of contact information, patient engagement, and spoke-site support for assessment delivery.},
}

@article {pmid42356052,
year = {2026},
author = {Manay, B and Aygün, D and Şentürk, A and İbas, M and Güven, R and Belli, Ş},
title = {Association Between Clinical Dysphagia Assessment Tools and Videofluoroscopic Findings in Amyotrophic Lateral Sclerosis: A Retrospective Study.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {62},
number = {6},
pages = {},
doi = {10.3390/medicina62061039},
pmid = {42356052},
issn = {1648-9144},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/physiopathology ; Retrospective Studies ; *Deglutition Disorders/diagnosis/etiology/physiopathology ; Female ; Male ; Middle Aged ; Aged ; Fluoroscopy/methods ; ROC Curve ; Video Recording/methods ; },
abstract = {Background and Objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease frequently associated with dysphagia and aspiration risk. This study aimed to investigate the relationship between clinical dysphagia assessment tools (EAT-10, GUSS, RSST, and sialorrhea severity) and videofluoroscopic swallowing study (VFSS) findings in patients with ALS. Materials and Methods: This retrospective observational study included 60 patients with ALS classified as spinal-onset (n = 38) or bulbar-onset (n = 22). Relationships between clinical assessments and VFSS findings were analysed using Spearman correlation analysis. Exploratory multivariable regression and receiver operating characteristic (ROC) analyses were performed to evaluate associations and aspiration risk discrimination. Results: Strong negative correlations were observed between PAS-Liquid and RSST and GUSS scores, whereas EAT-10 showed a strong positive correlation (all p < 0.001). ROC analyses demonstrated good discriminative ability for aspiration risk for GUSS (AUC = 0.89), RSST (AUC = 0.88), and EAT-10 (AUC = 0.82). Patients with bulbar-onset ALS demonstrated higher penetration-aspiration severity and lower functional oral intake. Conclusions: Clinical dysphagia assessment tools showed significant associations with instrumental swallowing findings in ALS. GUSS and RSST demonstrated good discriminative ability for aspiration risk and may be clinically useful bedside screening tools. However, instrumental swallowing assessment remains essential whenever feasible.},
}

Humans
*Amyotrophic Lateral Sclerosis/complications/physiopathology
Retrospective Studies
*Deglutition Disorders/diagnosis/etiology/physiopathology
Female
Male
Middle Aged
Aged
Fluoroscopy/methods
ROC Curve
Video Recording/methods

@article {pmid42357346,
year = {2026},
author = {Costanzi, E and Fontana, L and Giroldo, F and Coco, S},
title = {Advancing MSC-EV Therapies: Harnessing Preconditioning and Mito-EVs to Tackle Neuroinflammation and Neurodegeneration.},
journal = {Pharmaceutics},
volume = {18},
number = {6},
pages = {},
doi = {10.3390/pharmaceutics18060730},
pmid = {42357346},
issn = {1999-4923},
support = {P2022LR49L//Ministry of Universities and Research/ ; 202229X8HW//Ministry of Universities and Research/ ; },
abstract = {Neuroinflammation plays a central role in the onset and progression of neurodegenerative disorders. Several disease-modifying therapies have been developed to target neuroinflammatory pathways in specific disorders. However, their ability to stop disease progression or restore neuronal and mitochondrial homeostasis remains limited. This is still a major unmet clinical need. In this context, mesenchymal stromal cell (MSC)-derived Extracellular Vesicles (EVs) have emerged as a promising cell-free therapeutic strategy due to their ability to modulate immune responses and promote neuroprotection through the delivery of bioactive cargo. Recent evidence has identified a distinct subset of EVs, known as mitochondrial EVs (mito-EVs), which carry mitochondrial DNA, proteins, and functional components. These vesicles may uniquely influence cellular bioenergetics, redox balance, and neuroinflammatory signaling, offering additional therapeutic potential compared to conventional MSC-EVs. This review summarizes the role of MSC-derived EVs in neuroinflammatory disorders, with a particular focus on mito-EVs. It also discusses preconditioning strategies to enhance EV efficacy, including hypoxic, inflammatory, pharmacological priming and genetic engineering approaches. Finally, we critically evaluate current preclinical evidence regarding the treatment of major neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, and Amyotrophic Lateral Sclerosis, as well as Traumatic Injury, highlighting the key challenges for clinical translation.},
}

@article {pmid42358489,
year = {2026},
author = {Lepski, G and Arévalo, A},
title = {Mesenchymal stromal/stem cells for neurological disorders in humans: an evidence-mapped clinical review.},
journal = {Frontiers in cellular neuroscience},
volume = {20},
number = {},
pages = {1844360},
pmid = {42358489},
issn = {1662-5102},
abstract = {Mesenchymal stromal/stem cells (MSCs) have been tested clinically across a wide spectrum of neurological disorders, motivated by their immunomodulatory and trophic ("bystander") mechanisms rather than durable neural replacement. Here, we synthesize human prospective clinical trials that administered MSC products for neurological indications, prioritizing study design/goals, disease stage/severity, cell source/manufacturing, dose/route, detailed clinical assessments, quantified score changes, and adverse events (AEs). Across indications, trials frequently demonstrate feasibility and short-term safety, while efficacy signals are heterogeneous and strongly dependent on disease stage and endpoint selection criteria. The most methodologically rigorous signals with quantified motor outcomes include stereotactic intracerebral implantation of SB623 for chronic motor deficits after traumatic brain injury (TBI). In amyotrophic lateral sclerosis (ALS), randomized evidence supports safety and early slope-based signals in selected subgroups after intrathecal MSC regimens, but durable clinical benefit remains unproven. In hypoxic-ischemic encephalopathy (HIE), controlled data suggest functional improvements in small cohorts, and neonatal studies support feasibility adjunctive to hypothermia. We highlight design features most likely to de-risk efficacy interpretation: adequately powered randomized controlled trials, disease-stage stratification, prespecified clinically meaningful change thresholds, standardized rehabilitation co-interventions, and transparent AE adjudication.},
}

@article {pmid42359101,
year = {2026},
author = {Carder, P and Smith, L and Bunker, JN and Hua, CL and Hsu, EC and Boun, I and Ainsworth, OM and Thomas, KS and Jutkowitz, E},
title = {How do US states define person-centered and family-involved care in assisted living regulations.},
journal = {Frontiers in dementia},
volume = {5},
number = {},
pages = {1824907},
pmid = {42359101},
issn = {2813-3919},
abstract = {INTRODUCTION: A large share of assisted living (AL) residents have a diagnosis of dementia or cognitive impairment, and these individuals can benefit from person-centered care and family-involved care. This study examines whether and how states' AL licenses address these topics.

METHODS: This research analyzed a national database of 249 unique licensing requirements that govern 35,602 ALs in all states and associated regulations, including those that govern memory care (MC) services. We reviewed each regulation for the presence of person-centered or family involved care and then used content analysis of license requirements with at least one relevant policy to identify key categories and regulatory specificity.

RESULTS: A larger share of AL with licenses that govern MC services are covered by person-centered care policies (44%) and family-involved policies (62%), compared to AL without MC-specific requirements (20 and 32% respectively). Key categories of person-centered care included staff training, care planning procedures, and social activities; and family-involved care included care planning, direct involvement in providing care, and support for families. Few states' licenses contained highly specific regulations.

DISCUSSION: This study reveals substantial variation in whether and how states define and regulate person-centered and family-involved care for people living with dementia in AL. MC-specific licenses are roughly twice as likely to require these policies, but fewer than two-thirds of MC-AL communities are covered. State licenses take different approaches to categorizing and specifying these policies. These findings suggest uneven application of core principles of AL associated with quality of life and satisfaction.},
}

@article {pmid42359165,
year = {2026},
author = {Morimoto, S and Kato, C and Takahashi, S and Okano, H},
title = {Therapeutic frontiers in ALS: iPSC-based drug discovery, cell therapy, and gene therapy-Advances through 2026.},
journal = {Regenerative therapy},
volume = {33},
number = {},
pages = {101150},
pmid = {42359165},
issn = {2352-3204},
abstract = {Three converging therapeutic paradigms-iPSC-based drug discovery, cell transplantation, and gene therapy-have substantially expanded the therapeutic pipeline for amyotrophic lateral sclerosis (ALS) between 2020 and 2026. The FDA's accelerated approval of tofersen (Qalsody) in April 2023 marked the first treatment targeting a genetic cause of ALS. iPSC-derived drug candidates, including ropinirole and bosutinib, have completed early-phase clinical trials led by Japanese institutions. Cell therapies targeting neuroinflammation through regulatory T cells are being actively explored as immunomodulatory strategies, although efficacy remains to be established in adequately powered trials. Next-generation gene-silencing approaches-including RNA interference (RNAi) therapeutics and AAV-delivered microRNA-entered first-in-human trials in 2024-2025. The identification of STMN2 as a downstream target of TDP-43 dysfunction has opened a potential TDP-43-downstream nucleic acid therapeutic avenue for sporadic ALS, which constitutes approximately 90% of all cases, with company-reported interim data suggesting target engagement in the ongoing Phase 1/2 ANQUR trial (QRL-201). This review synthesizes the latest evidence across all three therapeutic domains, with attention to the hierarchy of evidence, regulatory milestones, and the pioneering contributions of Japanese research groups.},
}

@article {pmid42359357,
year = {2026},
author = {Shu, X and Yu, X and Xu, P and Wang, A},
title = {Innate immune crosstalk in ALS/FTD pathogenesis.},
journal = {Cell insight},
volume = {5},
number = {4},
pages = {100340},
pmid = {42359357},
issn = {2772-8927},
abstract = {Marked by protein aggregation, impaired proteostasis, organelle stress, and chronic neuroinflammation, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) form a clinically, genetically, and pathologically overlapping disease spectrum. Increasing evidence indicates that innate immune activation is not merely a secondary response to neuronal injury, but an active driver of disease progression. In this review, we elaborate on how ALS/FTD-associated genetic lesions and pathogenic protein aggregates, including TDP-43, SOD1, FUS, and C9orf72-derived dipeptide repeat proteins, engage three interconnected innate immune pathways: cGAS-STING, NLRP3 inflammasomes, and TREM2-DAP12 signaling. We further highlight emerging crosstalk among these pathways, in which cGAS-STING and NLRP3 reinforce inflammatory signaling, while NLRP3-driven TREM2 shedding may impair microglial clearance and perpetuate proteostatic failure. Understanding this immune network may help define disease subtypes, identify biomarkers, and guide combinatorial therapeutic strategies that suppress harmful inflammation while preserving protective microglial functions.},
}

@article {pmid40506596,
year = {2025},
author = {Sajjad, MW and Muzamil, F and Naqvi, RZ and Amin, I},
title = {QBEmax redefines the precise base editing in crop plants.},
journal = {Functional & integrative genomics},
volume = {25},
number = {1},
pages = {127},
pmid = {40506596},
issn = {1438-7948},
abstract = {Hu et al.‘s new study, published in Nature Biotechnology, introduces QBEmax; a tiny, conformationally sound editing tool with a cytidine deaminase buried within a looping permuted Cas9 (cpCas9). Supported by molecular dynamics models and AlphaFold3 structural predictions, this unique internal fusion creates a structurally protected complex that improves editing accuracy and lowers typical artifacts such as indels and impure base conversions (Hu et al. Nature Biotechnology:1-7, 2025). High precision editing (up to 99.8% purity), lower indels, and lower off target impacts well suit imminent plant transformation events. Its tiny, stable architecture and wider editing window at PAM sites increase its ability for precise and adaptable trait change in complex plant genomes.},
}

@article {pmid40764894,
year = {2025},
author = {Sah, AK and Srinivasarao, D and Dey, P},
title = {Comment on "clinicopathological features of fatal mushroom poisoning: a 10-year retrospective autopsy-based study".},
journal = {Forensic science, medicine, and pathology},
volume = {},
number = {},
pages = {},
pmid = {40764894},
issn = {1556-2891},
abstract = {This commentary evaluates Dogan et al.‘s autopsy-based study on fatal mushroom poisoning in Türkiye, highlighting its forensic insights and public health implications. We address potential selection bias and lack of confounder adjustment, advocating for broader surveillance and early intervention. The study advances understanding of amatoxin toxicity and informs targeted prevention efforts.},
}

@article {pmid41088288,
year = {2025},
author = {Ikezoe, H and Horiuchi, S},
title = {A qualitative exploration of the mistreatment of women during childbirth in a rural Guatemalan hospital.},
journal = {Reproductive health},
volume = {22},
number = {1},
pages = {197},
pmid = {41088288},
issn = {1742-4755},
support = {Core-to-Core Program, Asia-Africa Science Platforms [(2021-2024) PI: Shigeko Horiuchi]//Japan Society for the Promotion of Science/ ; },
abstract = {BACKGROUND: In Guatemala, many women still give birth together with traditional birth attendants at home particularly in rural settings even though births attended by skilled birth attendants in healthcare facilities have been recommended. Mistreatment of women during childbirth is recognized as one of the obstacles to childbirth in healthcare facilities. However, little research has been conducted on childbirth care and the mistreatment of women during facility-based childbirth in Guatemala. Thus, this study aimed to explore women’s experiences of care during childbirth in a rural Guatemalan hospital. The women narrated their experiences from which themes were derived (whether mistreatment or not, and if mistreatment prevailed, the type). METHODS: This qualitative study involved interviews with 20 women of reproductive age who had given birth in a hospital in Quiché Department, Guatemala, within the past six months. Data were collected by semistructured interviews between December 2022 and February 2023. The contents of the semistructured interviews were past birth experiences, a recent birth experience in a hospital, and care received from healthcare providers. Thematic analysis was performed with deductive and inductive approaches using Bohren et al.’s typology of the mistreatment of women during childbirth. The study was approved by St. Luke’s International University Research Ethics Committee and the study hospital. RESULTS: Women reported experiencing various forms of mistreatment during childbirth in the rural Guatemalan hospital. These included six of the seven categories from Bohren et al.’s typology including physical abuse, verbal abuse, stigma and discrimination, failure to meet professional standards of care, poor rapport between women and providers, and health system conditions and constraints. Specifically, the participants reported experiences of reprimands and neglect by healthcare providers, as well as discrimination of those who do not speak Spanish. It became evident that mistreatment of women by healthcare providers had become normalized, and that culturally appropriate care was not adequately provided. CONCLUSIONS: Eliminating or reducing mistreatment requires a multilevel approach. Healthcare providers must acquire up-to-date knowledge and skills and develop appropriate professional attitudes. Both healthcare providers and women should have increased awareness of women’s rights and mistreatment.},
}

@article {pmid41697496,
year = {2026},
author = {Quinn, CJ and Velasco, ES and Wehrens, XHT},
title = {Mitochondria at the Heart of Ischemia-Reperfusion (I/R) Injury: the HOXB5-Sirt5 Axis.},
journal = {Cardiovascular drugs and therapy},
volume = {40},
number = {3},
pages = {805-808},
pmid = {41697496},
issn = {1573-7241},
support = {R01HL153350/NH/NIH HHS/United States ; R01HL153350/NH/NIH HHS/United States ; },
abstract = {Ischemic cardiomyopathy (ICM) arises from restricted myocardial blood flow, leading to ischemia/reperfusion (I/R) injury, mitochondrial dysfunction, and heart failure. This commentary highlights the role of mitochondrial homeostasis in cardiac health, emphasizing dysregulated dynamics, ROS production, and mitophagy in ICM and related conditions like diabetic cardiomyopathy. Li et al.‘s study identifies the HOXB5–Sirt5 signaling axis as a key regulator that protects against I/R injury by reducing apoptosis, oxidative stress, ferroptosis, and mitochondrial fragmentation in vitro and in vivo. Future research should explore cell-specific roles and human models to enhance translational potential.},
}

@article {pmid41961214,
year = {2026},
author = {King, H and Derrett, S and Wyeth, EH and Cunningham, R and Peterson, D},
title = {Integrated Care Within New Zealand's Specialist Mental Health and Addiction Services: Qualitative Research to Inform a New Model.},
journal = {Community mental health journal},
volume = {},
number = {},
pages = {},
pmid = {41961214},
issn = {1573-2789},
abstract = {Internationally, and within New Zealand (NZ), specialist mental health and addiction service-users (SMHAS-users) experience increased risks of comorbidities and premature mortality, and poorer health outcomes, compared to the general population. In particular, Indigenous Māori SMHAS-users face significant inequities compared to non-Māori. Integrated care has been found to improve outcomes by improving quality and coordination between services. This research aimed to develop a model of integrated care relevant to SMHAS-users in a NZ context, to inform the development of a questionnaire intended to assess SMHAS-users experiences of integrated care, support SMHAS to improve their services, and in turn, improve outcomes for SMHAS-users. Key informants working for, and/or with lived experience of, SMHAS were interviewed about existing integrated and people-centred care concepts. Barriers to integration were identified. The team met frequently to review and discuss coding, themes, and model development. Ten informants from across NZ were recruited, including five with lived experience of mental distress, and three who were Māori. Singer et al.,’s (Medical Care Research and Review, 68(1), 112–127, 2011) integrated patient care framework and the World Health Organization’s (2016) concept of people-centred care were found to be acceptable, although people-centred constructs were needed more clearly at a model’s core. SMHAS-user controlled funding and participation in multi-disciplinary team meetings were identified as key opportunities alongside other concepts such as cultural responsiveness, de-centralising services (to re-centralise people), and peer navigators. The resulting People-Centred Joined Up Care (PCJUC) model is proposed to convey a paradigm shift from a service-centric system, organised around the efficiencies and needs of services, to a people-centred system. Irrespective of the health workforce’s best intentions, the current service-centric orientation does not empower SMHAS-users. A people-centred model requires power structures to be inverted and the paramount authority of health professionals as the ‘decision-making experts’ to be challenged. Research is now underway exploring the use of a questionnaire developed to measure the concepts within the PCJUC model, to inform service improvements.},
}

@article {pmid41961447,
year = {2026},
author = {Tarzian, AJ},
title = {From Wise Counselors to Clinical Ethicists: Historical Milestones and Their Impact on Professional Identity Formation.},
journal = {HEC forum : an interdisciplinary journal on hospitals' ethical and legal issues},
volume = {},
number = {},
pages = {},
pmid = {41961447},
issn = {1572-8498},
abstract = {This paper explores how historical bioethics milestones have shaped the professional identity of clinical ethicists, discussing both the benefits and challenges of professionalizing the role of the clinical ethicist by comparing how a “wise counselor,” an ethics consultant, and a clinical ethicist provide healthcare ethics guidance. I examine the evolution of clinical ethics as a sub-category of bioethics, tracing its origins and key milestones in its development toward professionalization. These include the American Society for Bioethics and Humanities’ (ASBH) Core Competencies for Health Care Ethics Consultation reports, ASBH’s Code of Ethics and Professional Responsibilities for Healthcare Ethics Consultants, Fox et al.’s national surveys of healthcare ethics consultation in the United States, and the emergence of the Healthcare Ethics Consultant Certification (HEC-C) program. Practicing as a clinical ethicist requires mastery of a wide scope of knowledge, skills, and attitudes reflected in each stage of the field’s development. Reflecting on this history may yield clues for how clinical ethicists position themselves for the next phase of the field’s evolution.},
}

@article {pmid42339807,
year = {2026},
author = {Jewer, M and Snyder, J and Caulfield, T and Zenone, M},
title = {The connection between unproven stem cell-based interventions and complementary and alternative medicine in crowdfunding for Amyotrophic Lateral Sclerosis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/21678421.2026.2685157},
pmid = {42339807},
issn = {2167-9223},
abstract = {UNLABELLED: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disease associated with substantial medical and non‑medical costs. In the absence of effective treatments, patients and families may turn to crowdfunding to finance care, including unproven stem cell‑based interventions (SCBIs) that are frequently marketed directly to consumers.

OBJECTIVE: conduct content analysis of English‑language GoFundMe campaigns seeking funds for SCBIs for ALS to better understand the market for unproven direct‑to‑consumer SCBIs.

METHODS: 247 campaigns were identified, and their data were collected and analyzed to determine the characteristics of the campaigns, campaigners, and their desired treatments.

RESULTS: ALS crowdfunding campaigns that collectively requested over $16 million USD. In addition to SCBIs, campaigns frequently requested funding for international travel to access these treatments. Campaigners express relatively high confidence that stem cell treatments would slow disease progression, improve symptoms, or, in some cases, cure or reverse ALS; conclusions that exceed the scientific evidence. Confidence in SCBIs is linked to requests for other alternative therapies and unsupported causes of ALS, supporting an emerging link between proponents of alternative medicines and unproven stem cell therapies.

CONCLUSION: Crowdfunding for unproven stem cell interventions exposes ALS patients and donors to financial risk, misinformation, and medical exploitation. The frequent linkage between SCBIs, CAM, and exaggerated claims highlights gaps in regulation, patient protection, and access to credible treatment options. These findings underscore the need for stronger oversight of direct‑to‑consumer stem cell markets and greater support for patients facing catastrophic illness.},
}

@article {pmid42339846,
year = {2026},
author = {Burchert, HH and Stringer, WW and Dash, RK},
title = {Single-O2ligation of hemoglobin links aerobic and anaerobic metabolism.},
journal = {Journal of applied physiology (Bethesda, Md. : 1985)},
volume = {},
number = {},
pages = {},
doi = {10.1152/japplphysiol.00454.2026},
pmid = {42339846},
issn = {1522-1601},
abstract = {Oxygen (O2) binding and release by hemoglobin (Hb) are governed by cooperative interactions among its four subunits. During incremental workload exercise, femoral venous oxyhemoglobin (O2Hb) saturation exhibits a reproducible, momentary increase at the gas exchange threshold-coinciding with the inflection point of the in vivo O2 non-equilibrium curve (ONC). This suggests a transient shift in Hb's binding dynamics. We hypothesized that at this threshold, Hb tetramers carrying ≤1 bound O2 become predominant. In this state, the last bound O2 promotes further cooperative binding, but its release confers no cooperative advantage for unloading, biasing toward O2 rebinding. Using the O2 equilibrium curve models of Dash et al. (2016) and Adair, we computed the distribution of Hb's O2 ligation states across 12 pooled mean femoral venous blood samples from incremental workload cardiopulmonary exercise testing of five healthy male participants. At the gas exchange threshold-where the ONC inflects and flattens-tetramers with ≤1 O2 indeed dominated. This ligation-state distribution is consistent with Perrella et al.'s (1999) cryogenic resolution of native human Hb, which shows that carbon monoxide-ligated Hb tetramers peak at ~15-20% saturation, matching femoral venous ranges at the gas exchange threshold. Our results suggest that, at sufficiently low O2Hb saturation, Hb may favor O2 rebinding over cooperative unloading. We propose that glycolytic proton production and other Bohr effectors may counter this predicted binding bias supporting continued O2 unloading. If confirmed, this mechanism unifies long-standing controversies in O2 transport physiology, framing the Hb-Bohr system as a proportional-integral controller of tissue oxygenation.},
}

@article {pmid42341041,
year = {2026},
author = {Liu, D and Li, Y and Huang, S and Xu, Y and Sun, L and Li, W and O'Kane, CJ and Rubinsztein, DC and Lu, B and Li, S},
title = {IRE1 regulates the proteostasis of TDP-43/TARDBP in ALS/FTD through ribosome-associated quality control.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {26},
pages = {e2610001123},
doi = {10.1073/pnas.2610001123},
pmid = {42341041},
issn = {1091-6490},
support = {32270825//MOST | National Natural Science Foundation of China (NSFC)/ ; 2023HWYQ-013//| Natural Science Foundation of Shandong Province ()/ ; tsqn202306046//Taishan Scholar Project of Shandong Province/ ; R01AG089752 R01NS084412 and R37NS083417//HHS | National Institutes of Health (NIH)/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *DNA-Binding Proteins/metabolism/genetics ; Animals ; *Protein Serine-Threonine Kinases/metabolism/genetics ; Humans ; *Frontotemporal Dementia/metabolism/genetics/pathology ; Mice ; *Ribosomes/metabolism ; *Proteostasis ; *Endoribonucleases/metabolism/genetics ; Proteotoxic Stress ; },
abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive neurodegenerative disorders characterized by motor neuron degeneration, leading to muscle weakness, atrophy, and cognitive impairments. A defining pathological hallmark of ALS/FTD is the cytosolic mislocalization and accumulation of TAR DNA-binding protein 43 (TDP-43), highlighting its critical role in ALS pathogenesis. However, the molecular mechanisms underlying TDP-43 proteostasis remain poorly understood. Through a genetic screening approach, we identify inositol-requiring enzyme 1 (IRE1), an endoplasmic reticulum-resident transmembrane protein, as a potent suppressor of TDP-43 protein levels. Furthermore, we show that ribosome-associated quality control (RQC) factors play a crucial role in regulating TDP-43 proteostasis and cellular toxicity. Activation of the RQC pathway prevents excessive accumulation of TDP-43 and associated toxicity. Mechanistically, our findings suggest that IRE1 regulates TDP-43 protein level by promoting the degradation of aberrant TDP-43 translation product through the RQC pathway. IRE1 acts canonically to enhance the transcription of the RQC core component Clbn/NEMF and noncanonically to physically interact with Clbn/NEMF, thereby ameliorating TDP-43-induced proteotoxicity. Moreover, ectopic expression or pharmacological activation of IRE1 alleviates TDP-43 pathology and restores cognitive function in the TDP-43 A315T ALS mouse models. Collectively, our study identifies a role for IRE1 in the translational quality control of TDP-43 and establishes its potential as a therapeutic target for ALS/FTD.},
}

*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology
*DNA-Binding Proteins/metabolism/genetics
Animals
*Protein Serine-Threonine Kinases/metabolism/genetics
Humans
*Frontotemporal Dementia/metabolism/genetics/pathology
Mice
*Ribosomes/metabolism
*Proteostasis
*Endoribonucleases/metabolism/genetics
Proteotoxic Stress

@article {pmid42341118,
year = {2026},
author = {Copley, KE and Dykstra, MM and Miller, MR and Linsenmeier, M and Lai, L and Wang, Y and Chang, YW and Barmada, SJ and Shorter, J},
title = {Isoform-specific steric zippers drive aberrant assembly and mislocalization of shortened TDP-43.},
journal = {Science advances},
volume = {12},
number = {26},
pages = {eady0256},
pmid = {42341118},
issn = {2375-2548},
mesh = {*DNA-Binding Proteins/metabolism/chemistry/genetics ; Protein Isoforms/metabolism/chemistry/genetics ; Humans ; Animals ; Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; Protein Domains ; Protein Transport ; },
abstract = {Prion-like domain (PrLD)-mediated aggregation and concomitant dysfunction of the essential RNA-binding protein transactive response (TAR) DNA-binding protein of 43 kilodaltons (TDP-43) is a common feature of multiple debilitating neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). However, shortened TDP-43 (sTDP-43) splice isoforms where the PrLD is largely replaced by an 18-residue carboxyl-terminal tail also contribute to ALS pathophysiology and are enriched in motor neurons. Curiously, despite lacking most of the PrLD, sTDP-43 exhibits pronounced insolubility in cells and tissue of patients with ALS. Here, we establish that the short, isoform-specific carboxyl-terminal tail of sTDP-43 confers high aggregation propensity, which is encoded by two clusters of steric zippers, and can be mitigated by short RNA chaperones. Disrupting these zippers enhances sTDP-43 solubility at the pure protein level and in neurons. Notably, these steric zippers, rather than a predicted nuclear export signal in the carboxyl-terminal tail, drive cytoplasmic mislocalization and aggregation of sTDP-43 in neurons. Thus, we define the sequence-encoded determinants of aberrant sTDP-43 assembly and provide mechanistic insights into sTDP-43 disease pathology.},
}

*DNA-Binding Proteins/metabolism/chemistry/genetics
Protein Isoforms/metabolism/chemistry/genetics
Humans
Animals
Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology
Protein Domains
Protein Transport

@article {pmid42341897,
year = {2026},
author = {Hopkins, EL and Williams, PA},
title = {Programmed axon degeneration gene variants in human disease.},
journal = {Experimental neurology},
volume = {},
number = {},
pages = {115891},
doi = {10.1016/j.expneurol.2026.115891},
pmid = {42341897},
issn = {1090-2430},
abstract = {BACKGROUND: Programmed axon degeneration (PAD; also known as Wallerian degeneration) is a conserved pathway controlling axon breakdown following injury or metabolic stress. PAD is driven by the depletion of nicotinamide adenine dinucleotide (NAD) through loss of the pro-survival enzyme NMNAT2 and activation of the pro-degenerative NADase SARM1. Recent genetic studies have identified pathogenic variants in PAD pathway enzymes associated with severe neurodegenerative phenotypes.

MAIN BODY: Pathogenic variants in NAMPT, NMNAT1, NMNAT2, and SARM1 have been identified and will be discussed in this review. NAMPT variants cause sensory and motor neuropathy with neurodevelopmental symptoms. NMNAT1 variants are well-characterized causes of Leber Congenital Amaurosis type 9, while NMNAT2 variants result in peripheral neuropathies with childhood onset. SARM1 gain-of-function variants with constitutively active NADase activity are enriched in amyotrophic lateral sclerosis patients.

CONCLUSION: These findings demonstrate that maintaining proper NAD homeostasis is crucial for axon survival, and disruption through genetic variants leads to distinct neurodegenerative outcomes. Understanding these rare variants provides insight into PAD mechanisms and supports development of broad-spectrum neuroprotective therapies targeting this pathway. Current therapeutic approaches include SARM1 inhibitors in clinical trials, gene therapy, and NAD precursor supplementation, offering hope for treating multiple neurodegenerative diseases.},
}

@article {pmid42342533,
year = {2026},
author = {Brodribb, L and Camden, P and Dharmadasa, T and Blizzard, C},
title = {Amyotrophic lateral sclerosis: A rare but aggressive adult-onset disease.},
journal = {Trends in molecular medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.molmed.2026.06.001},
pmid = {42342533},
issn = {1471-499X},
}

@article {pmid42342547,
year = {2026},
author = {Messina, E and Borrelli, A and Panebianco, V},
title = {Reply to Andrew R. A. Godtman et al.'s Letter to the Editor re: The PROSA Trial: Some Prosaic Comments. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2026.03.036.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2026.06.010},
pmid = {42342547},
issn = {1873-7560},
}

@article {pmid42342625,
year = {2026},
author = {Forstmann, M and Weiss, A},
title = {Outsourcing moral cognition: Delegation, diffusion of responsibility, and coalitional exclusion.},
journal = {The Behavioral and brain sciences},
volume = {49},
number = {},
pages = {e141},
doi = {10.1017/S0140525X25101556},
pmid = {42342625},
issn = {1469-1825},
mesh = {Humans ; *Morals ; *Decision Making ; *Cognition ; *Outsourced Services ; Cooperative Behavior ; },
abstract = {Levine et al.'s resource-rational contractualism (RRC) models moral judgment as a cost-sensitive approximation to ideal bargaining among stakeholders. We identify three strategies agents use to reduce moral costs by outsourcing or bypassing virtual bargaining: strategic delegation, diffusion of responsibility, and coalitional boundary-setting. We propose extending RRC with parameters for agency transfer, responsibility tracking, and stakeholder inclusion to better capture real-world moral decision-making.},
}

Humans
*Morals
*Decision Making
*Cognition
*Outsourced Services
Cooperative Behavior

@article {pmid42342627,
year = {2026},
author = {Kuhlmeier, VA and Dunfield, KA},
title = {The third axis: partner choice.},
journal = {The Behavioral and brain sciences},
volume = {49},
number = {},
pages = {e146},
doi = {10.1017/S0140525X25101684},
pmid = {42342627},
issn = {1469-1825},
mesh = {Humans ; *Choice Behavior ; *Morals ; *Interpersonal Relations ; *Cooperative Behavior ; },
abstract = {Though we find the 'triple theory' of moral cognition, with its emphasis on resource-rational contractualism, to be well argued, we suggest that Levine et al.'s model starts too late in the process. That is, we agree that their proposed abstractions and heuristics can help to develop mutually beneficial arrangements, but effective contracts also require the identification of reliable actors.},
}

Humans
*Choice Behavior
*Morals
*Interpersonal Relations
*Cooperative Behavior

@article {pmid42342630,
year = {2026},
author = {Bystranowski, P},
title = {The veil and the deal: Bargaining between case-specific solutions and unknown rules.},
journal = {The Behavioral and brain sciences},
volume = {49},
number = {},
pages = {e136},
doi = {10.1017/S0140525X25101490},
pmid = {42342630},
issn = {1469-1825},
mesh = {Humans ; *Morals ; *Decision Making ; },
abstract = {Levine et al.'s resource-rational contractualism omits how people decide that a situation demands rule-, not case-based, guidance. I propose that moral cognition first tags contexts as rule-governed, then either uncovers an existing norm or forges a plausible one. Coordination stakes and the private-public divide likely trigger this tag. Distinguishing discovery from invention invites targeted experiments and refines the framework.},
}

Humans
*Morals
*Decision Making

@article {pmid42343420,
year = {2026},
author = {Morisaki, Y and Nomura, N and Ohshima, M and Matsuda, M and Komine, O and Okuda, T and Yamanaka, K and Misawa, H},
title = {Immune checkpoint LAG-3 governs stage-dependent and disease-associated microglial modules in ALS model mice.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-026-03919-8},
pmid = {42343420},
issn = {1742-2094},
support = {JP26K10309//Japan Society for the Promotion of Science/ ; JP22K06634//Japan Society for the Promotion of Science/ ; },
abstract = {Immune checkpoint molecules, inhibitory receptors originally characterized in T cell biology, have recently emerged as regulators of microglial function in neurodegeneration, yet their roles in amyotrophic lateral sclerosis (ALS) remain unexplored. Here, we investigated LAG-3, an inhibitory immune checkpoint receptor, in microglial regulation during ALS pathogenesis using SOD1[G93A] mice. LAG-3 expression was progressively upregulated in spinal cord microglia during disease progression, and LAG-3-high microglia exhibited a disease-associated microglia (DAM) transcriptional signature. Genetic deletion of LAG-3 produced a biphasic phenotype, with accelerated disease onset but significantly prolonged disease duration. LAG-3 deficiency enhanced inflammatory microglial responses at the early disease stage, whereas at the late stage it suppressed inflammatory signaling while selectively preserving phagocytic effector gene expression, demonstrating that LAG-3 dissociates the inflammatory and phagocytic modules within the DAM program in a stage-dependent manner. These transcriptional changes translated into enhanced phagocytic capacity in primary microglia and amelioration of the spinal cord environment through suppression of inflammatory pathways and restoration of oxidative phosphorylation. Our findings identify LAG-3 as a stage-dependent regulator of microglial functional states in ALS and support the concept that immune checkpoint molecules constitute a class of module-level regulators of microglial function in neurodegeneration.},
}

@article {pmid42343520,
year = {2026},
author = {Sun, L and Chen, J and Wu, Y and Bian, S and Wang, Q and Ha, L},
title = {[Effect of electroacupuncture at "Zusanli" (ST36) on TREM2-mediated microglial activation in amyotrophic lateral sclerosis mice].},
journal = {Zhongguo zhen jiu = Chinese acupuncture & moxibustion},
volume = {46},
number = {6},
pages = {948-955},
doi = {10.13703/j.0255-2930.20250113-k0001},
pmid = {42343520},
issn = {0255-2930},
mesh = {Animals ; *Electroacupuncture ; *Amyotrophic Lateral Sclerosis/therapy/genetics/metabolism/immunology ; Male ; Mice ; *Microglia/metabolism/immunology ; *Receptors, Immunologic/genetics/metabolism/immunology ; Humans ; *Membrane Glycoproteins/genetics/metabolism/immunology ; *Acupuncture Points ; Disease Models, Animal ; Mice, Transgenic ; Interleukin-4/genetics/metabolism ; Spinal Cord/metabolism ; Interleukin-1beta/genetics/metabolism ; },
abstract = {OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli" (ST36) on amyotrophic lateral sclerosis (ALS) in mouse models based on myeloid cell trigger receptor 2 (TREM2)-mediated microglial activation.

METHODS: Thirty-six SPF-grade male human mutant superoxide dismutase 1 (SOD1-G93A) transgenic mice were divided into a model group, an EA group, and a drug group, 12 mice in each group. Besides, 12 wide-type littermates were collected as a control group. In the EA group, EA was performed at the "Zusanli" (ST36), with an intermittent wave, at the frequency of 15 Hz, and for 10 min each intervention; once every other day, 3 interventions a week and for 4 continuous weeks. In the drug group, the intragastric administration of riluzole solution was given at 8 mg/kg, once daily, for 4 continuous weeks. After intervention completion, behavioral assessment of mice was conducted using rotarod test and wire hang test. With HE and Nissl staining adopted, morphology of motor neurons in the anterior horn of the spinal cord was observed. Immunofluorescence was used to detect the fluorescence intensity of TREM2 in the anterior horn of spinal cord. Western blot analysis was performed to measure the protein expression of interleukin (IL)-1β, γ interferon (IFN-γ), IL-4 and IL-10 in spinal cord tissue. Flow cytometry was used to analyze the proportion of CD86[+] and CD206[+] in spinal cord monocyte suspension.

RESULTS: Compared with the control group, in the model group, motor neurons in the anterior horn of the spinal cord exhibited disordered arrangement; accompanied by nuclear pyknosis and cytoplasmic shrinkage; the latency to fall in the rotarod test and the cut-off time in the wire hang test were shortened, fluorescence intensity of TREM2 in the spinal anterior horn, the protein expression of IL-1β, IFN-γ, IL-4, and IL-10, and the proportion of CD86[+] and CD206[+] in spinal cord tissue increased(P<0.01). When compared with the model group, in the EA and drug groups, motor neurons in the anterior horn of the spinal cord were arranged regularly; nuclear pyknosis and chromatolysis were attenuated, and the structural integrity of neurons was improved; the latency to fall and the the cut-off time were prolonged, fluorescence intensity of TREM2 in the spinal anterior horn was reduced, the protein expression of IL-1β and IFN-γ decreased, and that of IL-4, and IL-10 increased in the spinal cord tissue; the proportion of CD86[+] in spinal cord tissue was reduced and that of CD206[+] elevated(P<0.01, P<0.05). Compared with the drug group, the EA group showed the increase of protein expression of IL-1β,and the decrease of IL-4, IL-10 in the spinal cord tissue and the proportion of CD206[+] (P<0.05).

CONCLUSION: Electroacupuncture at "Zusanli" (ST36) exhibits a certain improvements in motor function of SOD1-G93A transgenic mice. The underlying mechanism may be related to attenuating neuroinflammation via the modulation of microglial activation mediated by TREM2.},
}

Animals
*Electroacupuncture
*Amyotrophic Lateral Sclerosis/therapy/genetics/metabolism/immunology
Male
Mice
*Microglia/metabolism/immunology
*Receptors, Immunologic/genetics/metabolism/immunology
Humans
*Membrane Glycoproteins/genetics/metabolism/immunology
*Acupuncture Points
Disease Models, Animal
Mice, Transgenic
Interleukin-4/genetics/metabolism
Spinal Cord/metabolism
Interleukin-1beta/genetics/metabolism

@article {pmid42343570,
year = {2026},
author = {Ellis, BCS and Avila, AS and Huang, WP and John, SJ and Bonsall, S and Hodgson, RE and Kumar, V and Nolan, M and West, RJH and Campbell, SG and De Vos, KJ and Lagier-Tourenne, C and Robin Highley, J and Cooper-Knock, J and Shelkovnikova, TA},
title = {STMN2 protein depletion via translation deficits and stress granules in amyotrophic lateral sclerosis.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag222},
pmid = {42343570},
issn = {1460-2156},
abstract = {STMN2 is an abundant neurospecific protein dysregulated in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). We previously reported that cellular stress can lead to STMN2 loss due to TDP-43 nuclear condensation. Here, using human and murine neuronal cell models, multiple pharmacological tools, in situ single-molecule analysis of translation and RNA localisation, and longitudinal analysis of neuronal fitness/survival, we establish TDP-43-independent mechanisms of STMN2 depletion under stress. We find that human STMN2 protein level is extremely labile under acute high-magnitude stress. Early in stress, STMN2 is suppressed via activated proteasomal degradation, phosphorylation and translation repression by stress granules, independently of TDP-43 loss of function in splicing. We further show that STMN2 protein level is highly sensitive to chronic translation deficits, such as those elicited by prolonged low-grade stress. We find that low pre-stress STMN2 sensitises neuronal cells to stress-induced apoptosis, whereas moderately increased STMN2 is protective under stress. Finally, we demonstrate that STMN2 mRNA is upregulated in non-TDP ALS (ALS-FUS) models, which may compensate for translation/stress granule defects in this disease subtype. Consistent with the compensation hypothesis, STMN2 mRNA is also upregulated in the relatively spared (cortex), but not severely affected (spinal cord), CNS regions in ALS-TDP. In conclusion, our study implicates two common denominators in neurodegeneration - dysregulation of translation and stress granules - in STMN2 depletion, independent of TDP-43 loss of function. It also describes an RNA-based compensatory mechanism in ALS underling the unique vulnerability of neurons with developing TDP-43 pathology.},
}

@article {pmid42344043,
year = {2026},
author = {Mantell, JE and Masvawure, TB and Thomas, NA and George, G and Howard, AA and Strauss, M and Ndagije, F and Lethoko, M and Low, A and Hirsch-Moverman, Y},
title = {Health system support and strengthening for cross-border HIV services: key informants' perspectives on testing and linkage for Lesotho-South Africa migrant workers.},
journal = {BMJ public health},
volume = {4},
number = {2},
pages = {e003284},
pmid = {42344043},
issn = {2753-4294},
abstract = {INTRODUCTION: Cross-border migrants, especially those in destination countries with high HIV burden and high population mobility, often face structural challenges in accessing HIV testing and linkage-to-care. There is limited research on the most effective HIV testing and linkage-to-care strategies tailored to cross-border migrants. We conducted a qualitative study to explore barriers and facilitators to HIV testing and linkage-to-care among Lesotho-South Africa cross-border migrant workers.

METHODS: We conducted in-depth interviews with 15 purposively selected stakeholders from Lesotho who interfaced with migrants, namely administrative and programme staff from the Ministry of Health, non-governmental organisations, community counsellors and testers and migrant advocates. We captured diverse perspectives on barriers and facilitators to HIV services among migrant workers. Template analysis, a rapid form of thematic analysis, was used to synthesise the data. We applied Chee et al's health systems framework differentiating health system support and health system strengthening to analyse our findings and guide actionable programme and policy strategies.

RESULTS: Participants recommended strategies that both support the health system by improving service provision and strengthen the health system by implementing structural and policy-level changes. Support strategies included expanding migrant-centred access to HIV testing and prevention services, reducing structural and economic barriers to service utilisation and strengthening community-based services. Strengthening strategies included cross-border collaboration and harmonised referral systems for continuity of care, expanding differentiated HIV care models for mobile populations, integrating HIV services into general healthcare, establishing workplace HIV policies for migrant workers and flexible cross-border funding for migrant health.

CONCLUSIONS: Chee et al's framework allows policymakers and programme implementers to more intentionally distinguish and plan for solutions that merely support versus actually strengthen health systems. Strengthening approaches, in contrast to supporting ones, have the potential to transform HIV services for migrants by ensuring continuity of services in both home and destination venues butrequire greater commitment and action from politicians, policymakers, funders and advocacy groups to implement.},
}

@article {pmid42345500,
year = {2026},
author = {Drążyk, M and Pyc, Z and Pietrzyk, SJ and Gajda-Janiak, A and Godziszewski, F and Pioterek, O and Tulski, M and Mazurek, M and Domagała, ZA},
title = {Formaldehyde neurotoxicity: Effects on the mammalian brain, cognitive function, and neurodegenerative risk. A scoping review.},
journal = {Advances in clinical and experimental medicine : official organ Wroclaw Medical University},
volume = {},
number = {},
pages = {},
doi = {10.17219/acem/209617},
pmid = {42345500},
issn = {1899-5276},
abstract = {Aqueous formaldehyde (FA) solution, known as formalin, is currently the primary agent used for preserving tissue samples and anatomical specimens. Formaldehyde is widely used in laboratories and the chemical industry; it also occurs as an air pollutant and endogenous cellular metabolite. The potential carcinogenic effects of formalin on the respiratory tract are well documented. A less recognized consequence of occupational exposure to FA is its detrimental effect on the central nervous system (CNS) and brain function. A literature review was conducted to investigate the effects of FA on the brain. Five databases were searched: PubMed, Web of Science (WoS), Embase, ScienceDirect, and Google Scholar. To describe the effects of FA exposure and endogenous FA generation, 35 relevant publications were collected and analyzed. The literature review demonstrated that inhalation is the most common route of FA exposure. Several studies have shown that FA may cause hippocampal damage, disrupt melatonin secretion, and induce a wide range of cognitive disorders with varying characteristics and severity. These disorders include memory impairment, disturbances in balance and spatial orientation, learning difficulties, sleep disturbances, impaired judgment, and prolonged reaction times to stimuli. Increased endogenous FA concentration has also been associated with a higher risk of neurodegenerative diseases, such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis. The literature analysis demonstrated the high neurotoxicity of FA, which may lead to numerous neuropsychiatric disorders. We aim to draw attention to the risks associated with the routine use of formalin, particularly among anatomists and pathologists, and to encourage consideration of less harmful alternative preservation agents.},
}

@article {pmid42345595,
year = {2026},
author = {de Sousa, SF and Marques, MDCMP and da Silva Amaral, GMM},
title = {Factors Influencing the Maintenance of Advanced Life Support Competencies Among Critical Care Professionals: A Scoping Review.},
journal = {Nursing in critical care},
volume = {31},
number = {4},
pages = {e70545},
doi = {10.1111/nicc.70545},
pmid = {42345595},
issn = {1478-5153},
support = {UID/06291/2025//Fundação para a Ciência e a Tecnologia/ ; },
mesh = {Humans ; *Clinical Competence/standards ; *Critical Care/standards ; *Advanced Cardiac Life Support/standards ; },
abstract = {BACKGROUND: Advanced life support (ALS) competence may deteriorate within months after certification, but what supports ongoing competence in critical care remains unclear.

AIM: To map factors influencing maintenance of ALS competence among critical care professionals working in critical care settings.

STUDY DESIGN: Scoping review conducted in accordance with Joanna Briggs Institute guidance and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. MEDLINE, CINAHL and the Cochrane Library were searched (from February to March 2025). We included peer-reviewed and grey sources from hospital-based critical care settings that assessed ALS competencies over time. Data were synthesised using inductive thematic analysis.

RESULTS: Twenty-five sources were included (19 peer-reviewed, 6 grey). Factors were mapped to three domains. Educational factors were most frequently reported and centred on simulation-based rehearsal, structured feedback and debriefing and spaced refreshers delivered in brief, frequent sessions. Institutional determinants related to protected training time, access to resources, standardised roles and content and monitoring through audit and feedback. Individual determinants included clinical exposure and experience, perceived preparedness and self-confidence, stress and cognitive load, engagement in ongoing learning and non-technical behaviours. Outcomes were largely simulation-based or self-reported, and longer-term durability was inconsistently assessed.

CONCLUSIONS: Maintenance of ALS competence appears to require coordinated educational and organisational supports; longitudinal evaluations with explicit definitions and validated outcomes are needed.

Critical care services may strengthen ALS competence maintenance by embedding recurrent, context-aligned rehearsal with feedback, supported by protected training time, accessible training infrastructure and ongoing performance monitoring.

REVIEW REGISTRATION: The review protocol was prospectively registered on the Open Science Framework https://doi.org/10.17605/OSF.IO/PEQJH.},
}

Humans
*Clinical Competence/standards
*Critical Care/standards
*Advanced Cardiac Life Support/standards

@article {pmid42346159,
year = {2026},
author = {Verde, EM and Secco, V and Ghezzi, A and Mandrioli, J and Carra, S},
title = {Correction: Verde et al. Molecular Mechanisms of Protein Aggregation in ALS-FTD: Focus on TDP-43 and Cellular Protective Responses. Cells 2025, 14, 680.},
journal = {Cells},
volume = {15},
number = {12},
pages = {},
doi = {10.3390/cells15121053},
pmid = {42346159},
issn = {2073-4409},
abstract = {In order to facilitate readers' better understanding, some language descriptions and grammar as well as the layout of some chapters have been modified [...].},
}

@article {pmid42347120,
year = {2026},
author = {Alves Ferreira, JM and Tukaiev, S and Giannouli, V},
title = {RNA-Binding Proteins in Ageing and Age-Related Disease.},
journal = {Neurology international},
volume = {18},
number = {6},
pages = {},
doi = {10.3390/neurolint18060112},
pmid = {42347120},
issn = {2035-8385},
abstract = {RNA-binding proteins (RBPs) are essential regulators of all aspects of RNA metabolism, including splicing, stability, localisation, translation, and degradation. Through their ability to recognise specific cis-elements in target transcripts, often via RNA-recognition motifs or other conserved domains, RBPs enable rapid cellular adaptation to stress and maintain proteostasis, particularly in post-mitotic tissues with limited transcriptional flexibility. Accumulating evidence positions RBPs as both modulators and drivers of the molecular hallmarks of ageing, including genomic instability, loss of proteostasis, mitochondrial dysfunction, cellular senescence, and chronic inflammation. This review synthesises peer-reviewed studies on the multifaceted roles of RNA-binding proteins in organismal ageing and age-related diseases. Key themes include the tissue- and age-dependent changes in expression of turnover and translation regulatory RBPs such as HuR (ELAVL1), AUF1 (HNRNPD), TIA-1, and tristetraprolin (ZFP36), which alter the stability of mRNAs encoding cell-cycle regulators, pro-inflammatory cytokines, and stress-response proteins. Systematic downregulation of core splicing factors, including PTBP1 and several heterogeneous nuclear ribonucleoproteins, drives widespread senescence-associated splicing alterations in pathways governing cell division, autophagy, DNA repair, and mitochondrial function, suggesting a causal contribution to the senescent phenotype. Prion-like RBPs such as TDP-43 and FUS exhibit age-dependent mislocalisation, nuclear depletion, and cytoplasmic aggregation, contributing to splicing defects, impaired RNA transport, and neurodegeneration in amyotrophic lateral sclerosis, frontotemporal dementia, and limbic-predominant age-related TDP-43 encephalopathy. Interactions between RBPs and non-coding RNAs, together with disrupted liquid-liquid phase separation dynamics, further exacerbate age-related decline. By integrating mechanistic studies from cellular and animal models with observations in human cohorts, this review underscores RBPs as central nodes linking multiple ageing hallmarks and highlights their potential as biomarkers and therapeutic targets to promote healthy ageing. Limitations of current models and priorities for future translational research are discussed.},
}