@article {pmid42441689,
year = {2026},
author = {de Vienne, D and de Vienne, DM},
title = {Age-based risk estimates for C9orf72RE-related diseases: Theoretical developments and added value for genetic counseling.},
journal = {PLoS genetics},
volume = {22},
number = {7},
pages = {e1012230},
doi = {10.1371/journal.pgen.1012230},
pmid = {42441689},
issn = {1553-7404},
abstract = {The C9orf72 hexanucleotide repeat expansion is the most common genetic cause of amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD). In genetic counseling, children of mutation carriers are often told that they have a 50% risk of carrying the mutation, but this figure does not take into account the fact that penetrance is age-related, with a unimodal distribution of disease onset around 58 years of age. Using a Bayesian approach, we developed a theory to calculate the probability of carrying the mutation for asymptomatic relatives (children/siblings and grandchildren/niblings) as well as the probability of developing ALS/FDT within a given time frame, based on their age. Using published data on age-related penetrance, we then calculated these probabilities and developed an online simulator that makes it easy to calculate them on a case-by-case basis. The conditional probabilities obtained can be very different from Mendelian values. For example, a 70-year-old asymptomatic child born to a carrier has approximately a 6% risk of being a carrier, which is far from 50%. For grandchildren, taking into account both their age and that of their parents also leads to figures that are much lower than those obtained if only their age were considered. For consultands, the decision to undergo testing is based in part on risk estimates. In this regard, the refined estimates and simulator we propose may prove to be valuable tools for genetic counseling for families affected by ALS/FTD linked to the C9orf72RE mutation. In addition, the formulas used in this study could also be used to calculate risk estimates for other diseases caused by autosomal dominant mutations with age-dependent penetrance.},
}

@article {pmid42441693,
year = {2026},
author = {Fisher, K and Ligay, A and Stratford, M and Hirani, R and Ober, DT and Al-Seykal, I and Frishman, WH and Etienne, M},
title = {Cardiac Autonomic Dysfunction and Sudden Cardiac Death in Amyotrophic Lateral Sclerosis: Clinical Implications and Considerations for Care.},
journal = {Cardiology in review},
volume = {},
number = {},
pages = {},
doi = {10.1097/CRD.0000000000001392},
pmid = {42441693},
issn = {1538-4683},
abstract = {Amyotrophic lateral sclerosis (ALS) is traditionally viewed as a motor neuron disease that progresses from muscular weakness to respiratory failure and death. Increasing evidence, however, demonstrates clinically meaningful involvement of the autonomic nervous system, particularly in cardiovascular regulation. This narrative review synthesizes current evidence on the mechanisms, clinical implications, and palliative considerations of cardiac autonomic dysfunction in ALS, with particular emphasis on its relationship to sudden cardiac death (SCD). Cardiac autonomic dysfunction is increasingly recognized as a significant contributor to disease burden in ALS, manifesting as abnormalities in heart rate variability, sympathetic overactivity, and corrected QT prolongation. These derangements may contribute to malignant arrhythmias, increasing susceptibility to SCD in combination with respiratory decline. Epidemiologic data suggest that SCD accounts for a meaningful proportion of ALS-related mortality, although it is likely underrecognized due to misclassification and lack of routine cardiac monitoring. Clinical implications include the need for improved risk stratification and earlier detection of autonomic dysfunction using accessible markers, such as electrocardiographic indices, orthostatic vital signs, and ambulatory monitoring. Emerging technologies, including wearable biosensors, may further enhance longitudinal assessment. These considerations also have direct relevance for advanced care planning, as ALS may involve unpredictable and abrupt cardiac death in addition to progressive respiratory decline. Recognizing ALS as a multisystem disorder with significant cardiac involvement supports the integration of structured cardiovascular monitoring into multidisciplinary care models and highlights the need for prospective studies to guide standardized management strategies.},
}

@article {pmid42442024,
year = {2026},
author = {Andreeva, T and Tuparev, N and Taneva, SG},
title = {Multimodal biophysical markers of neurodegeneration: Morphology, mechanics, and thermodynamics.},
journal = {Current opinion in structural biology},
volume = {100},
number = {},
pages = {103330},
doi = {10.1016/j.sbi.2026.103330},
pmid = {42442024},
issn = {1879-033X},
abstract = {The identification of novel noninvasive biomarkers remains a major challenge in the diagnosis of neurodegenerative diseases. Significant efforts focus on fluid biomarkers, including proteins, peptides, and miRNAs, detectable in blood plasma and peripheral blood cells. Here, we review recent findings on blood plasma and peripheral blood cells physical parameters in Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis emphasizing atomic force microscopy and calorimetry assay. Alterations in morphology, nanostructure, and stiffness of red blood cells and platelets, together with thermodynamic signatures of red blood cells and plasma, provide sensitive indicators of disease-related changes. These integrated biophysical parameters not only distinguish neurodegeneration from healthy states but also enable discrimination among different neurodegenerative disorders, highlighting their potential as minimally invasive diagnostic markers.},
}

@article {pmid42442469,
year = {2026},
author = {Kerner, D and Carey, L and Hughes, J},
title = {Using CoI to Address Emerging Problems in Academic Pharmacy.},
journal = {American journal of pharmaceutical education},
volume = {},
number = {},
pages = {102051},
doi = {10.1016/j.ajpe.2026.102051},
pmid = {42442469},
issn = {1553-6467},
abstract = {Pharmacy education is currently facing numerous challenges, such as concerning first-time pass rates on licensure examinations, decreasing applicant pools, new accreditation standards, progression concerns, and changing financial and regulatory landscapes. These complex and shared issues require collaborative and innovative approaches across the academy. One potential strategy is the development of Communities of Inquiry (CoI), a collaborative model grounded in Garrison et al.'s theoretical framework of social, cognitive, and teaching presence. CoI emphasize active engagement, shared problem-solving, reflective discourse, and collective responsibility for learning and innovation. This manuscript describes the theoretical foundation of the CoI model and its application within pharmacy academia. Existing applications of CoI principles in pharmacy education literature, including faculty development initiatives and webinar-based learning experiences, are also reviewed. Additionally, a real-world example of a successful CoI is presented through the development of a NAPLEX Preparation CoI. Communities of Inquiry represent an effective framework for addressing new challenges in pharmacy education. Faculty, administrators, and professional organizations are encouraged to establish and participate in CoIs. As pharmacy education continues to evolve, the CoI approach presents a promising strategy for fostering innovation, meeting accreditation standards, and enhancing student outcomes through community-driven solutions.},
}

@article {pmid42442754,
year = {2026},
author = {Sonnenberg, A and Bakis, LK and Kohen, R},
title = {Gastrointestinal Diagnoses and Symptoms in Medicare Patients With Neuropsychiatric Diseases.},
journal = {Journal of clinical gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1097/MCG.0000000000002422},
pmid = {42442754},
issn = {1539-2031},
abstract = {BACKGROUND AND AIMS: Many patients with psychiatric and neurological diseases suffer from gastrointestinal symptoms. Our study aimed to analyze the frequency of gastrointestinal disease in patients with underlying neuropsychiatric diagnoses.

METHODS: The study utilized the 2018 Inpatient Standard Analytic File of the Centers for Medicare and Medicaid Services (CMS), which contains the electronic health records of 6,462,321 unique patients. The concurrence of 2 diagnoses was assessed by calculating odds ratios (OR) with their 95% CIs, adjusted for the confounding influences of demographic characteristics (age, sex, ethnicity).

RESULTS: Dementia was most strongly associated with dysphagia (2.85, 2.83 to 2.88). Schizophrenia was associated with functional GI disorders (1.62, 1.60 to 1.64), constipation (1.67, 1.65 to 1.69), and dyspepsia (2.02, 1.88 to 2.17). Bipolar disorder was most significantly associated with irritable bowel syndrome (1.83, 1.79 to 1.87) and dyspepsia (1.88, 1.77 to 2.01). Depression was significantly associated with all types of upper and lower GI symptoms with significant ORs ranging from 1.33 to 2.14. Amyotrophic lateral sclerosis was strongly associated with complaints of functional GI disorder (2.32, 2.18 to 2.46), constipation (2.37, 2.23 to 2.51), dysphagia (11.77, 11.19 to 12.39), flatulence and bloating (2.75, 2.14 to 3.54). Parkinson disease was mostly associated with constipation (1.79, 1.77 to 1.82) and dysphagia (2.96, 2.92 to 3.00). In Alzheimer disease, only symptoms of dysphagia (2.15, 2.12 to 2.17) stood out. Multiple sclerosis was associated with most GI diagnoses (OR ranging from 1.32 to 2.06), except for abdominal pain and reflux symptoms.

CONCLUSIONS: Concurrence of gastrointestinal and neuropsychiatric diagnoses is common. Caring for patients with neuropsychiatric diseases, physicians need to be aware of and proactively search for the presence of concurrent gastrointestinal disease.},
}

@article {pmid42442908,
year = {2026},
author = {Dongre, S and Soni, N and Bissa, B},
title = {Role of ESCRT pathway and autophagy in neurodegenerative diseases.},
journal = {International review of neurobiology},
volume = {187},
number = {},
pages = {1-16},
doi = {10.1016/bs.irn.2026.05.022},
pmid = {42442908},
issn = {2162-5514},
mesh = {Humans ; *Endosomal Sorting Complexes Required for Transport/metabolism ; *Autophagy/physiology ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; },
abstract = {Neurodegenerative diseases are characterized by progressive neuronal dysfunction and loss resulting from impaired proteostasis and vesicular trafficking. Neurons are particularly vulnerable to these processes due to their post-mitotic nature and complex architecture. Autophagy and the endolysosomal system constitute the primary degradative pathways responsible for maintaining neuronal homeostasis. However, increasing evidence indicates that their effective function critically depends on coordination with the endosomal sorting complexes required for transport (ESCRT). Beyond their canonical role in multivesicular body biogenesis and membrane scission, ESCRT components are now recognized as essential regulators of autophagosome closure, amphisome formation, autophagosome-lysosome fusion, and endolysosomal membrane repair. Disruption of this ESCRT-autophagy interface has emerged as a common pathological feature across major neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis/frontotemporal dementia. This review synthesizes evidence from genetic, biochemical, and neuropathological studies to highlight shared molecular nodes, such as ESCRT-III components, the VPS4 ATPase, the adaptor protein ALIX, and late endosomal regulators, including Rab7, that couple membrane remodeling to autophagic flux. Failure of these regulatory checkpoints destabilizes endolysosomal integrity, arrests autophagic maturation, and promotes the accumulation of toxic protein species, thereby driving progressive neuronal degeneration. By framing neurodegeneration through the lens of ESCRT-autophagy coupling failure, this review provides a unified mechanistic perspective that links diverse pathogenic proteins to shared cellular vulnerabilities and identifies ESCRT-mediated membrane dynamics as a critical determinant of neuronal survival.},
}

Humans
*Endosomal Sorting Complexes Required for Transport/metabolism
*Autophagy/physiology
*Neurodegenerative Diseases/metabolism/pathology
Animals

@article {pmid42443201,
year = {2026},
author = {Wang, Y and Hu, W and Huang, R and Wu, F and Su, H and Zang, J and Huang, X and Liu, Y and Ren, H and Li, J and Zhang, M and Zhang, Y and Wang, G and Hao, Z},
title = {Nuclear condensates formed by truncated mutant NEK1s impede ribosomal RNA biogenesis and drive motor dysfunction.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-75500-z},
pmid = {42443201},
issn = {2041-1723},
support = {32000676//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {NIMA-related kinase 1 (NEK1), a serine/threonine kinase, is a risk variant for amyotrophic lateral sclerosis (ALS). While the full-length NEK1 is involved in diverse cellular processes, such as DNA damage response and microtubule stability, the pathogenic mechanism of NEK1 nonsense mutations in ALS remains elusive. Here, we demonstrate that three truncated forms of NEK1 derived from ALS-related NEK1 nonsense mutations translocate from the cytoplasm to the nucleus, exhibit nucleolar localization, and simultaneously form liquid-like nucleoplasmic foci. In contrast to the diffuse cytoplasmic distribution of wild-type NEK1, these nuclear-localized truncated mutants are prone to undergo liquid-liquid phase separation both in cells and in vitro. Mechanistically, the truncated NEK1s interact with the nucleolar protein FBL, thereby impairing ribosomal RNA biogenesis and translation. Transgenic flies expressing truncated mutant NEK1s display motor dysfunction and reduced survival length, and a knock-in transgenic mouse model expressing ALS-related NEK1 mutant similarly exhibits motor deficits accompanied by ribosomal RNA dysregulation. These findings suggest that ALS-related NEK1 mutants expressing truncated forms of NEK1 cause cell toxicity by interfering with ribosomal RNA metabolism and reveal a gain-of-function mechanism in ALS pathogenesis involving NEK1.},
}

@article {pmid42443387,
year = {2026},
author = {Kim, WS and Halliday, GM},
title = {Astrocytic lipid dysregulation as an early driver of neurodegeneration.},
journal = {Nature reviews. Neurology},
volume = {},
number = {},
pages = {},
pmid = {42443387},
issn = {1759-4766},
abstract = {Astrocytes have traditionally been cast as supportive glia, but they are increasingly recognized as metabolic hubs that regulate cholesterol synthesis, fatty acid detoxification, lipid droplet dynamics and redox homeostasis in the CNS. Neurons have a limited intrinsic capacity for lipid storage and detoxification and rely heavily on astrocytes to maintain a safe lipid environment. Emerging evidence indicates that dysregulation of astrocytic lipid homeostasis precedes overt neuronal degeneration in a range of neurodegenerative diseases, including Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, frontotemporal dementia and Huntington disease. Perturbations in astrocytic lipid handling can drive maladaptive reactive states, promote oxidative stress, impair lysosomal and mitochondrial function and disrupt neuron-glia lipid exchange, collectively creating an environment that leads to neurodegeneration. Therefore, lipid dysregulation within astrocytes could trigger or amplify neuronal vulnerability. In this Review, we assess evidence that astrocytic lipid metabolism is not solely protective or pathological but has instructive physiological roles and that astrocytic lipid dysregulation is an early driver of neurodegeneration. We critically evaluate disease-specific evidence, distinguishing correlative observations from causal mechanisms. We propose that targeting of astrocytic lipid homeostasis represents a promising strategy for preventing or minimizing neurodegeneration and opens new avenues for early detection and biomarker development.},
}

@article {pmid42444959,
year = {2026},
author = {Akpa, B},
title = {The role of radiologic assessment in evaluating and monitoring respiratory function in amyotrophic lateral sclerosis (ALS) patients: a narrative review.},
journal = {Journal of thoracic disease},
volume = {18},
number = {6},
pages = {672},
pmid = {42444959},
issn = {2072-1439},
abstract = {BACKGROUND AND OBJECTIVE: Respiratory failure is the primary cause of mortality in amyotrophic lateral sclerosis (ALS), usually caused by progressive neuromuscular respiratory weakness. Standard pulmonary function tests (PFTs) such as maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and both supine and upright forced vital capacity (FVC) are crucial for objective measurements of diaphragmatic weakness but have limitations, including dependence on the patient's performance and the inability to detect early, subclinical diaphragmatic impairment or be used effectively in patients with bulbar symptoms. Radiological assessments, particularly dynamic imaging, have emerged as potential objective tools for evaluating respiratory function. This review comprehensively summarizes findings on the use of diaphragmatic ultrasound (DUS), dynamic chest magnetic resonance imaging (MRI) and deep learning (DL)-based chest computed tomography (CT) for assessing lung function in ALS patients.

METHODS: Key radiological metrics include diaphragm thickness (DT), thickening fraction during inspiration, real-time diaphragmatic excursion, lung diameter changes and changes in pulmonary length and area. These measures have been compared with conventional PFTs in various studies to validate their use for diagnostic accuracy, particularly in early stages of disease.

KEY CONTENT AND FINDINGS: DUS is a non-invasive, widely available tool that strongly correlates with PFT measurements, especially FVC, MIP, and sniff nasal inspiratory pressure (SNIP). Dynamic measures, such as excursion and velocity, appear more sensitive to early dysfunction than thickness alone. Chest dynamic MRI has also shown significant correlations with spirometric parameters. Small cohort studies indicate that dynamic chest MRI is a superior, sensitive tool for detecting early respiratory impairment in asymptomatic patients with normal spirometry.

CONCLUSIONS: Radiological assessments, primarily DUS, DL-based chest CT and dynamic MRI, offer valuable, objective, and non-invasive methods for monitoring respiratory muscle strength in ALS. These techniques serve as complementary tools to traditional PFTs, particularly in selected clinical scenarios such ALS patients with early disease, bulbar involvement and unable to perform PFTs. Further longitudinal research with larger cohorts is needed to standardize protocols and validate their role as early parameters to guide the timely initiation of supportive interventions like non-invasive ventilation (NIV).},
}

@article {pmid42445484,
year = {2026},
author = {Ahmed, R and Kayande, A and Patil, R and Shelar, A and Zore, GB},
title = {Context-dependent reprogramming of ALS adhesin expression in Candida albicans: a multi-inducer analysis linking morphogenesis to virulence plasticity.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1848556},
pmid = {42445484},
issn = {1664-302X},
abstract = {Candida albicans employs the ALS (Agglutinin-Like Sequence) gene family to encode cell-surface adhesins that are central to host colonization, tissue invasion, and biofilm formation. Although individual ALS genes have been studied under specific conditions, no systematic, multi-inducer temporal analysis of the entire family has been reported to date. In this study, we present the first comprehensive temporal expression profiling of seven ALS genes (ALS1-ALS5, ALS7, and ALS9) under six host-relevant inducers, temperature (37 °C), neutral pH, serum, glucose, N-acetylglucosamine (NAG), and proline, across four time points (45 min, 90 min, 3 h, 6 h) in both yeast (30 °C) and hyphal (37 °C) growth phases. Morphological analysis confirmed that 37 °C and serum were the most potent hyphal inducers (94.13 ± 0.94% hyphae with serum at 37 °C). Quantitative PCR revealed a temporally stratified regulatory program: early-phase adhesins (ALS1, ALS2) showed transient induction during the first 90 min, whereas invasion-associated genes exhibited sustained late-phase activation. Notably, ALS3 displayed exceptional upregulation under glucose at 37 °C (25.17 ± 1.76-fold at 6 h; p < 0.001) and responded robustly to all inducers except serum. ALS7 reached 9.48-fold induction specifically under thermal stress, while ALS5 was preferentially expressed at 30 °C (6.70-fold under neutral pH), indicating niche-specific functional specialization. In silico promoter analysis linked these expression patterns to binding motifs for key transcription factors (Efg1, Cph1, Rim101, and Nrg1). Phylogenetic analysis revealed functional conservation of ALS2/ALS4 versus evolutionary divergence in ALS6/ALS7/ALS9. STRING-based protein interaction networks confirmed the central involvement of ALS proteins in adhesion and biofilm regulatory circuits. These findings establish a molecular framework for niche-specific virulence, identifying ALS3 as a prime therapeutic target for anti-adhesion strategies in invasive candidiasis. We hypothesize that C. albicans employs a temporally stratified and inducer-specific transcriptional program of the ALS family to adapt its surface architecture to diverse host microenvironments.},
}

@article {pmid42447123,
year = {2026},
author = {Wohnrade, C and Thau-Habermann, N and Gschwendtberger, T and Rückoldt, J and Huang, Z and Schreiber, S and Haastert-Talini, K and Petri, S},
title = {Neuromuscular ultrasound as a biomarker in the SOD1 mouse model of amyotrophic lateral sclerosis.},
journal = {PloS one},
volume = {21},
number = {7},
pages = {e0353397},
pmid = {42447123},
issn = {1932-6203},
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology/genetics/physiopathology ; Mice ; *Superoxide Dismutase/genetics ; Disease Models, Animal ; Superoxide Dismutase-1 ; Biomarkers/metabolism ; Ultrasonography ; Mice, Transgenic ; Humans ; Sciatic Nerve/diagnostic imaging/pathology ; Muscle, Skeletal/diagnostic imaging/pathology ; Motor Neurons/pathology ; Disease Progression ; },
abstract = {A progression marker that indicates early disease-related changes and treatment responses in the to date incurable neurodegenerative disease amyotrophic lateral sclerosis (ALS) is highly desirable. Translation of therapeutics that have been successful in in vivo models into trials in human patients has proven difficult in recent decades. This failure can be attributed, at least in part, to the lack of specific biomarkers for ALS diagnosis and progression in human ALS patients as well as in in vivo models. Neuromuscular ultrasound is an easily accessible, non-invasive tool to support diagnosis of ALS in humans. Our current study shows for the first time that the disease can be detected in an ALS mouse model with the help of neuromuscular ultrasound. We characterized disease progression regarding changes in the peripheral nerves and muscles of the hind limb in the SOD1G93A mouse model of ALS using different techniques (neuromuscular ultrasound, electroneurography, motor function tests, phenotypic assessments and histology). By neuromuscular ultrasound, we measured the cross-sectional area and diameter of the sciatic nerve and analyzed hind limb muscle texture and thickness. Our results show that motor neuron loss and muscle atrophy - analogous to ALS in humans - can be measured by ultrasound in the SOD1G93A mouse model. Changes in nerve and muscle morphology appear at the same time or even before changes in the established tests (including electroneurographic measurements) performed in vivo in this model. Correlations with histologic features of disease progression make neuromuscular ultrasound a sensitive, non-invasive outcome marker for preclinical studies.},
}

Animals
*Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology/genetics/physiopathology
Mice
*Superoxide Dismutase/genetics
Disease Models, Animal
Superoxide Dismutase-1
Biomarkers/metabolism
Ultrasonography
Mice, Transgenic
Humans
Sciatic Nerve/diagnostic imaging/pathology
Muscle, Skeletal/diagnostic imaging/pathology
Motor Neurons/pathology
Disease Progression

@article {pmid42447443,
year = {2026},
author = {Hicks-Courant, K},
title = {Taking Responsibility.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2502100},
doi = {10.1200/JCO-25-02100},
pmid = {42447443},
issn = {1527-7755},
abstract = {This essay is about how caring for my complicated father with amyotrophic lateral sclerosis (ALS) unexpectedly shaped how I approached my work as a gynecologic oncologist.},
}

@article {pmid42447895,
year = {2026},
author = {Arnolds, KB and Peinemann, F},
title = {[Infant-driven versus Practitioner-driven Feeding of Preterm Infants: A Systematic Review of Randomized Controlled Trials].},
journal = {Zeitschrift fur Geburtshilfe und Neonatologie},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2894-2931},
pmid = {42447895},
issn = {1439-1651},
abstract = {HINTERGRUND: Voraussetzung für eine erfolgreiche orale Ernährung ist die Berücksichtigung des individuellen Entwicklungsstands der Frühgeborenen. Pflegekräfte und Eltern sollten geschult sein, wie sie Verhaltenssignale des Säuglings während des Fütterns erkennen und darauf angemessen reagieren können. Diese Art der Ernährung wird in dieser Arbeit als "signalorientiertes und co-reguliertes" Füttern von Frühgeborenen bezeichnet. Im Unterschied zeichnet sich das "herkömmliche" Füttern dadurch aus, dass eine vorab festgelegte Flüssigkeitsmenge zu einer festgelegten Zeit verabreicht wird.

ZIELSETZUNG: Es soll untersucht werden, ob das "signalorientierte und co-regulierte" Füttern im Vergleich zum "herkömmlichen" Füttern zu einer früheren vollständigen oralen Ernährung führen kann.

METHODEN: Wir haben am 26. Juni 2024 in den elektronischen Datenbanken MEDLINE und Cochrane Library nach thematisch relevanten randomisierten Studien gesucht. Als primärer Endpunkt wurde die Anzahl der Tage bis zur vollständigen oralen Ernährung und als Effektmaß die mittlere Differenz gewählt. Die Metaanalyse wurde unter Verwendung der inversen Varianzmethode und des Random-Effects-Modells durchgeführt, und wir verwendeten den GRADE-Ansatz (Grading of Recommendations Assessment, Development, and Evaluation) für die Bewertung der Evidenz.

ERGEBNISSE: In der Studienauswahl fanden sich 12 randomisierte Studien, die den Einschlusskriterien entsprachen. Von diesen wurden 5 Studien in eine Metaanalyse einbezogen. Die geschätzte mittlere Differenz favorisierte die Gruppen mit signalorientiertem und co-reguliertem Füttern im Vergleich zu den Gruppen mit herkömmlicher Fütterung: -4,93 (95%-Konfidenzintervall -6,60 bis -3,26, p<0,00001, I[2] =66%). Die Qualität der Evidenz wurde als moderat eingestuft.

SCHLUSSFOLGERUNGEN: Die Daten der Studienteilnehmer sind mit einem leicht vorteilhaften Effekt für die signalorientierte und co-regulierte Ernährung von Frühgeborenen im Vergleich zur herkömmlichen Ernährung von Frühgeborenen vereinbar. Zukünftige Studien könnten weitere Daten zu unerwünschten Ereignissen während der Ernährung und Informationen zur häuslichen Nachsorge ergänzen.},
}

@article {pmid42448407,
year = {2026},
author = {Rangappa, N and Upadhyay, R and Lakshman, N and Ramasamy, S and Sevanan, M and Justin, A and Chinnathambi, S},
title = {Small molecular therapeutic targets for neurodegenerative diseases.},
journal = {Advances in protein chemistry and structural biology},
volume = {153},
number = {},
pages = {135-167},
doi = {10.1016/bs.apcsb.2025.10.012},
pmid = {42448407},
issn = {1876-1631},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology/genetics ; Animals ; *Molecular Targeted Therapy ; },
abstract = {Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis disease are characterized by progressive neuronal loss, protein aggregation, and synaptic dysfunction. These diseases share common pathological mechanisms including oxidative stress, mitochondrial impairment, chronic neuroinflammation, protein misfolding, and epigenetic dysregulation. Current therapies offer only symptomatic relief and fail to halt disease progression. Recent advances in transcriptomics and proteomics have enabled the identification of shared molecular pathways and druggable targets across multiple neurodegenerative diseases. The key targets, such as BDNF-TrkB, TREM2, SIRT1, PINK1-Parkin, GSK-3β, NLRP3, and mTOR have shown promise in preclinical models, offering opportunities for broad-spectrum therapeutic development. Importantly, blood-brain barrier disruption and neuroinflammatory crosstalk exacerbate disease pathology and hinder drug delivery. Innovative strategies involving nanocarriers, gene therapy, and epigenetic modulation are emerging to overcome these barriers. This review highlights the convergence of disease mechanisms, discusses common molecular signatures and therapeutic vulnerabilities, and explores novel small molecular interventions targeting shared pathways mainly in AD and PD. A deeper understanding of aging-associated molecular dysfunction is essential to design sustainable, disease-modifying therapeutics with cross-disease relevance.},
}

Humans
*Neurodegenerative Diseases/drug therapy/metabolism/pathology/genetics
Animals
*Molecular Targeted Therapy

@article {pmid42449472,
year = {2026},
author = {de Albuquerque Bueno, MG and Dos Santos, DF and Rossor, AM and Laura, M and Horga, A and Frezatti, RSS and de Sousa Ferreira, EV and Blake, JC and Morrow, JM and Reilly, MM and Marques Júnior, W and Tomaselli, PJ},
title = {VRK1-Related Motor Neuropathy With Upper Motor Neuron Signs and Selective Muscle Involvement.},
journal = {Journal of the peripheral nervous system : JPNS},
volume = {31},
number = {3},
pages = {e70145},
doi = {10.1111/jns.70145},
pmid = {42449472},
issn = {1529-8027},
support = {MR/S005021/1//International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD)/ ; 25000.160.096/2014-07//Programa Nacional de Apoio à Atenção da Saúde da Pessoa com Deficiência (PRONAS)/ ; 465 458/20114-9//National Institute of Sciences and Technology (INCT)-Translational Medicine/ ; 310378/2021-4//Conselho Nacional de Pesquisa (CNPq)/ ; FE-CLI-24-0005-05//Biogen/ ; },
mesh = {Humans ; Female ; Male ; *Motor Neuron Disease/genetics/physiopathology/diagnostic imaging/pathology ; *Protein Serine-Threonine Kinases/genetics ; Adult ; Middle Aged ; Magnetic Resonance Imaging ; *Intracellular Signaling Peptides and Proteins/genetics ; *Muscle, Skeletal/physiopathology/diagnostic imaging/pathology ; Nerve Conduction Studies ; Young Adult ; Electromyography ; Neural Conduction/physiology ; Adolescent ; Child ; },
abstract = {INTRODUCTION: Hereditary motor neuropathies (HMN) represent a heterogeneous group of disorders with wide clinical and genetic variability. Despite advances in molecular diagnostics, approximately 50% of cases remain genetically unresolved, particularly those where distinguishing length-dependent motor neuropathy from motor neuron disorder with disproportionate segmental involvement is a challenge. Variants in the VRK1 gene, originally described in association with pontocerebellar hypoplasia, are now known to produce a broad clinical spectrum, including amyotrophic lateral sclerosis, dHMN, and less frequently, spastic paraplegia.

OBJECTIVES: This study's aim was to characterize the clinical presentation, electrophysiological findings, and muscle MRI patterns associated with VRK1-related motor neuron disease in a cohort of nine patients from five unrelated families.

METHODS: Five unrelated families with inherited motor neuropathy were investigated using next-generation sequencing techniques, including targeted gene panels or whole-exome sequencing, with subsequent confirmation by Sanger sequencing. A total of nine affected individuals underwent detailed clinical evaluation, nerve conduction studies (NCS), electromyography (EMG), and whole-body muscle MRI (wbMRI).

RESULTS: Nine affected individuals carrying biallelic VRK1 variants were evaluated. In most cases (66%), symptom onset occurred during the first decade of life. All patients presented with gradually progressive distal muscle weakness. Mean Medical Research Council (MRC) scores were 2.8 for ankle dorsiflexion and 1.9 for plantar flexion. Sensory nerve conduction studies were normal in all individuals evaluated (8/9), although mild sensory complaints were reported in four patients. Muscle cramps were observed in two-thirds of the cohort, while fasciculations were uncommon (11%). EMG findings consistently demonstrated a neurogenic pattern with predominant distal involvement, and evidence of both acute and chronic denervation was present in four patients. Whole-body muscle MRI, available for all patients, revealed a consistent pattern of fatty infiltration predominantly affecting posterior muscle compartments, with minimal STIR signal changes. Brain and spinal imaging, performed in all individuals, showed no abnormalities.

INTERPRETATIONS: Biallelic mutations in VRK1 are associated with a recognizable form of motor neuron disease characterized by features of dHMN combined with upper motor neuron involvement, along with a distinctive posterior-predominant pattern on muscle MRI. Identifying this phenotype, a known presentation of VRK1-related disorders, highlights the importance of targeted genetic testing in unresolved cases of hereditary motor neuropathy.},
}

Humans
Female
Male
*Motor Neuron Disease/genetics/physiopathology/diagnostic imaging/pathology
*Protein Serine-Threonine Kinases/genetics
Adult
Middle Aged
Magnetic Resonance Imaging
*Intracellular Signaling Peptides and Proteins/genetics
*Muscle, Skeletal/physiopathology/diagnostic imaging/pathology
Nerve Conduction Studies
Young Adult
Electromyography
Neural Conduction/physiology
Adolescent
Child

@article {pmid42450002,
year = {2026},
author = {Kim, Y and Jung, YK},
title = {Proteasome Dysfunction and Aggregation-Prone Proteins in Neurodegenerative Diseases: From Mechanisms to Therapeutic Opportunities.},
journal = {International journal of molecular sciences},
volume = {27},
number = {13},
pages = {},
doi = {10.3390/ijms27135730},
pmid = {42450002},
issn = {1422-0067},
support = {RS-2025-00519823//National Research Foundation of Korea/ ; RS-2024-00439842//National Research Foundation of Korea/ ; },
mesh = {Humans ; *Proteasome Endopeptidase Complex/metabolism ; *Neurodegenerative Diseases/metabolism/therapy/pathology/drug therapy ; Animals ; Proteostasis ; *Protein Aggregation, Pathological/metabolism ; *Protein Aggregates ; Proteotoxic Stress ; Ubiquitin/metabolism ; Proteolysis ; Oxidative Stress ; },
abstract = {Neurodegenerative diseases are characterized by the accumulation of misfolded and aggregation-prone proteins, reflecting a failure of proteostasis. The ubiquitin-proteasome system (UPS), a major pathway for selective intracellular protein degradation, is essential for maintaining neuronal protein homeostasis. Proteasome dysfunction has been implicated in several major neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), although its extent and mechanisms vary across disease contexts. In this review, we examine current evidence for proteasome dysfunction in neurodegeneration and discuss how disease-associated proteins impair proteasome function through direct inhibition, defective substrate processing, and sequestration into protein aggregates. We also address the contribution of oxidative stress, neuroinflammation, and aging to proteasome dysregulation. Finally, we highlight emerging therapeutic strategies aimed at restoring proteasome function, including pharmacological activation, modulation of proteasome assembly and stability, and targeted protein degradation approaches. Understanding the context-dependent nature of proteasome dysfunction will be important for developing effective proteostasis-based therapies.},
}

Humans
*Proteasome Endopeptidase Complex/metabolism
*Neurodegenerative Diseases/metabolism/therapy/pathology/drug therapy
Animals
Proteostasis
*Protein Aggregation, Pathological/metabolism
*Protein Aggregates
Proteotoxic Stress
Ubiquitin/metabolism
Proteolysis
Oxidative Stress

@article {pmid42450899,
year = {2026},
author = {Gerymski, R},
title = {Does Life Lose Its Meaning When the Heart Fails? Illness Perception, Perceived Stress and Meaning in Life in Polish Patients with Heart Failure.},
journal = {Healthcare (Basel, Switzerland)},
volume = {14},
number = {13},
pages = {},
doi = {10.3390/healthcare14131889},
pmid = {42450899},
issn = {2227-9032},
support = {Fifty percent of the study was conducted free of charge by the author (R.G.). The other half of the study was financed by the Institute of Psychology at the Opole University (no grant number provided)//University of Opole/ ; },
abstract = {Background/Objectives: Heart failure (HF) is a highly unpredictable disease that significantly impacts patients' well-being. One of the fundamental problems faced by cardiac patients is trying to answer the question of how to lead a meaningful life. Meaning in life is a crucial predictor of well-being, ill-being and quality of life for everyone, not just cardiac patients. Therefore, identifying its predictors is crucial. Based on Leventhal et al.'s common-sense model of self-regulation of health and illness, and Lipowski's disease perception concept, this study verified the role of illness perception and perceived stress in existential meaning in Polish HF patients. Methods: This manuscript presents the results of a cross-sectional study. Overall, 336 HF patients from Poland were examined. Four questionnaires were used: the Meaning in Life Questionnaire (MLQ), the Multidimensional Existential Meaning Scale (MEMS), the Perceived Stress Scale (PSS-10) and the Disease-Related Appraisals Scale (DRAS). Results: Negative illness perception and positive cognitive assessment of the illness were shown to be significant predictors of meaning in life in patients with HF. Furthermore, this relationship was mediated by perceived stress. Additionally, the positive correlation between negative illness assessment and positive illness perception was found. Conclusions: This study demonstrates that cognitive assessment of the disease can be associated with the existential resources of heart failure patients. It also highlights the importance of working on the existential sphere of cardiac patients and accurately verified theoretical assumptions regarding the relationship between illness perception and meaning in life, providing a basis for future longitudinal studies and meaning-oriented psychological help focused on individuals with HF.},
}

@article {pmid42451086,
year = {2026},
author = {Soni, N and Debnath, N and Rekapally, E and Jabbar, A and Tyagi, SC and Bissa, B and Tyagi, N},
title = {Vitamin D Signaling in Neurodegenerative Disorders: Mechanisms, Therapeutic Potential, and Clinical Implications.},
journal = {Nutrients},
volume = {18},
number = {13},
pages = {},
doi = {10.3390/nu18132082},
pmid = {42451086},
issn = {2072-6643},
support = {971566; 24 TPA1304527 and 25 TPA1481771 to Neetu Tyagi.//American Heart Association/ ; },
mesh = {Humans ; *Vitamin D/metabolism/therapeutic use ; *Neurodegenerative Diseases/metabolism/drug therapy/etiology ; *Signal Transduction ; Vitamin D Deficiency/complications ; Animals ; Oxidative Stress/drug effects ; Receptors, Calcitriol/metabolism ; Blood-Brain Barrier/metabolism ; Neuroprotective Agents ; },
abstract = {Vitamin D has long been recognized for its role in calcium homeostasis and bone metabolism; however, it is now emerging as an important regulator of central nervous system (CNS) function. Recent evidence suggests that vitamin D signaling contributes to the pathogenesis and progression of several neurodegenerative disorders. Vitamin D exerts neuroprotective effects through multiple mechanisms, including regulation of calcium homeostasis, modulation of immune responses, reduction in oxidative stress, stimulation of neurotrophic factors, and maintenance of blood-brain barrier (BBB) integrity. Vitamin D receptors and metabolizing enzymes are widely distributed across several brain regions, highlighting their direct involvement in neuronal function. This review summarizes the biosynthesis, metabolism, and signaling pathways of vitamin D. It explores its role in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), stroke, and traumatic brain injury (TBI). Evidence from experimental and clinical studies indicates that vitamin D deficiency is associated with an increased risk and severity of these conditions, while supplementation may provide therapeutic benefits.},
}

Humans
*Vitamin D/metabolism/therapeutic use
*Neurodegenerative Diseases/metabolism/drug therapy/etiology
*Signal Transduction
Vitamin D Deficiency/complications
Animals
Oxidative Stress/drug effects
Receptors, Calcitriol/metabolism
Blood-Brain Barrier/metabolism
Neuroprotective Agents

@article {pmid42451691,
year = {2026},
author = {Singh, AA and Arukha, AP and Song, M},
title = {Indole-Derived Compounds as Redox-Modulators: Antioxidant Mechanisms in Neuronal Protection.},
journal = {Molecules (Basel, Switzerland)},
volume = {31},
number = {13},
pages = {},
doi = {10.3390/molecules31132323},
pmid = {42451691},
issn = {1420-3049},
mesh = {Humans ; *Antioxidants/pharmacology/chemistry ; *Indoles/chemistry/pharmacology ; Animals ; *Neuroprotective Agents/pharmacology/chemistry ; Oxidation-Reduction/drug effects ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neurons/drug effects/metabolism ; Oxidative Stress/drug effects ; Signal Transduction/drug effects ; Reactive Oxygen Species/metabolism ; },
abstract = {Neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Amyotrophic lateral sclerosis, are distinguished by progressive neuronal dysfunction caused primarily by oxidative stress, mitochondrial impairment, neuroinflammation, and redox imbalance. Growing evidence suggests that indole-derived compounds have significant neuroprotective potential due to their antioxidant, anti-inflammatory, and redox-modulating properties. This review summarizes the structural and biological significance of indole scaffolds, focusing on the mechanisms by which natural, endogenous, microbiota-derived, and synthetic indole compounds protect neuronal networks. Indole-3-carbinol, 3,3'-diindolylmethane, indole-3-propionic acid, and melatonin are major indole derivatives that control important neuroprotective pathways like Nrf2/ARE signaling, mitochondrial bioenergetics, neurotrophic factor expression, apoptotic regulation, and suppression of proinflammatory mediators. These compounds also maintain synaptic plasticity, reduce reactive oxygen species production, and improve neuronal survival in neurodegenerative disease models. Additionally, updated information from translational and clinical research indicates that indole-based compounds may have promising therapeutic applications; however, obstacles like low bioavailability, metabolic instability, and blood-brain barrier penetration continue to be major obstacles to clinical application. Development in nanoparticle delivery systems, microbiome-targeted interventions, and rational structural optimization may improve therapeutic efficacy and translational potential. Overall, indole-derived compounds are a versatile class of redox modulators with potential applications in the prevention and treatment of neurodegenerative diseases via integrated antioxidant and neuroprotective mechanisms.},
}

Humans
*Antioxidants/pharmacology/chemistry
*Indoles/chemistry/pharmacology
Animals
*Neuroprotective Agents/pharmacology/chemistry
Oxidation-Reduction/drug effects
*Neurodegenerative Diseases/drug therapy/metabolism
*Neurons/drug effects/metabolism
Oxidative Stress/drug effects
Signal Transduction/drug effects
Reactive Oxygen Species/metabolism

@article {pmid42453524,
year = {2026},
author = {Yang, HI and Hsueh, KW and Ding, DC and Harn, HJ and Lin, YC and Chang, CY and Tsai, ST and Lin, SZ},
title = {Therapeutic potential of adipose-derived stem cell transplantation in amyotrophic lateral sclerosis: A combined clinical case and preclinical study.},
journal = {Tzu chi medical journal},
volume = {38},
number = {3},
pages = {332-339},
pmid = {42453524},
issn = {2223-8956},
abstract = {OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is an inevitably fatal neurodegenerative disease with no adequate treatment. Transplantation of adipose-derived stem cells (ADSCs) may be an effective therapeutic strategy for delaying progression or restoring neurological function in ALS.

MATERIALS AND METHODS: We evaluated the safety and therapeutic efficacy of intravenous (i.v.) and intracerebral (i.c.) ADSC injection in a late-stage ALS patient and in a SOD1 transgenic (Tg) mouse model. Magnetic resonance imaging (MRI) and computed tomography (CT) were conducted to examine potential cerebral hemorrhage and tumor generation in the treated patient. In addition, maximal inspiratory pressure, maximal expiratory pressure, tidal volume, and respiratory rate were measured as indices of respiratory function.

RESULTS: ADSC transplantation was safe, with MRI and CT showing no hemorrhage or tumorigenesis up to 12 months. The patient's Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score improved from 7 to 9 at 3 months and remained above baseline for 6 months. Respiratory function was preserved during this period. In SOD1 Tg mice, i.c. and i.v. ADSC infusion significantly prolonged survival (165.0 ± 10.4 and 147.3 ± 4.5 days vs. 129.7 ± 3.9 days) and improved motor scores (P < 0.01).

CONCLUSION: This preliminary finding suggests potential therapeutic feasibility, but further studies with larger cohorts are needed to confirm its safety and efficacy.},
}

@article {pmid42436608,
year = {2026},
author = {Teng, Z and Bushman, BJ},
title = {Rethinking Longitudinal Studies of Media Violence and Aggression: A Rejoinder to Lacko et al.'s (2026) Comment.},
journal = {Aggressive behavior},
volume = {52},
number = {4},
pages = {e70078},
pmid = {42436608},
issn = {1098-2337},
mesh = {*Aggression/psychology ; Humans ; *Violence/psychology ; Longitudinal Studies ; Media Exposure ; },
abstract = {Lacko et al. responded to the concerns raised in our commentary, providing an opportunity to reflect on broader methodological and theoretical issues in longitudinal research on media violence and aggression. This exchange highlights five lessons for future research: (1) longitudinal studies should place greater emphasis on developmental processes; (2) analytical approaches and the interpretation of findings are important; (3) examining the longitudinal effects of media violence on aggression requires high-quality longitudinal data; (4) greater transparency and openness in both data and analytical methods strengthen the field; and (5) future research should place greater emphasis on understanding when, how, and for whom media violence influences aggression. We hope these lessons will contribute to more rigorous longitudinal research and a deeper understanding of the developmental processes linking media violence and aggression.},
}

*Aggression/psychology
Humans
*Violence/psychology
Longitudinal Studies
Media Exposure

@article {pmid42436960,
year = {2026},
author = {Gromprasit, A and Thremthakanpon, W and Siripocaratana, K and Wanitcharoenporn, W and Jitprapaikulsarn, S and Sutthapakti, B and Laoruengthana, A},
title = {Accuracy and Reliability of Magnetic Resonance Imaging Measurement of Medial Femoral Condyle for Femoral Component Sizing in Oxford Unicompartmental Knee Arthroplasty.},
journal = {Arthroplasty today},
volume = {40},
number = {},
pages = {102088},
pmid = {42436960},
issn = {2352-3441},
abstract = {BACKGROUND: Accurate femoral component sizing is critical for Oxford unicompartmental knee arthroplasty (UKA) because inappropriate sizing can lead to early implant failure. Therefore, we developed a magnetic resonance imaging (MRI) measurement of medial femoral condyle (MRMFC) technique and compare its accuracy to existing methods.

METHODS: This study included 54 Oxford UKAs. Five sizing methods were assessed: radiographic templating, intraoperative sizing spoon, anthropometric estimation (based on patient height and gender), Yang et al.'s MRI method, and the MRMFC. The MRMFC determined 3 reference points of medial femoral condyle on the sagittal plane of MRI. The primary outcome was an overhang or underhang of femoral component over posterior femoral condyle as determined on postoperative lateral radiographs which ±2 mm are considered as ideal size.

RESULTS: The MRMFC method yielded the highest accuracy (50/54; 92.6%; 95% CI: 82.1-97.9), followed by the intraoperative sizing spoon (38/54; 70.4%, 56.4-82.0), Yang et al. MRI method (32/54; 59.3%, 45.0-72.4), anthropometric estimation (30/54; 55.6%, 41.4-69.1), and radiographic templating (25/54; 46.3%, 32.6-60.4). Pairwise testing demonstrated that MRMFC was better than the sizing spoon (P = .008), radiographic templating (P < .001), Yang et al. MRI method (P < .001), and anthropometric estimation (P < .001). The sizing spoon was superior to radiographic templating (P = .029). No significant differences were observed among radiographic templating, Yang et al. MRI method, and anthropometric estimation.

CONCLUSIONS: The MRMFC demonstrated the highest accuracy and reproducibility in preoperative planning for Oxford UKA. Intraoperative spoon sizing, however, remains a simple and practical method and performed moderately well with significantly better than radiographic templating.},
}

@article {pmid42437951,
year = {2026},
author = {Williams, KJ},
title = {Anti-inflammatory agents in atherosclerosis-and a need for reform: Extraordinary claims require extraordinary evidence.},
journal = {Journal of internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.1111/joim.70128},
pmid = {42437951},
issn = {1365-2796},
support = {//Ruth and Yonatan Ben-Avraham Fund/ ; },
abstract = {Since 1858, human atherosclerotic plaques have been shown to contain immune cells. But are these cells suitable therapeutic targets? Dozens of clinical trials of anti-inflammatory agents other than colchicine have been performed in patients with clinically evident atherosclerosis. None of these trials led any regulatory body in any jurisdiction to allow a cardiovascular indication for any of these agents. This discouraging work provides a background to evaluate new data on colchicine. In 2024-2025, new clinical trials of colchicine in patients with atherosclerosis showed benefit, no benefit, or harm. In 2025-2026, over a dozen meta-analyses so far have appeared, drawing on ∼34 trials, but do not agree with each other. One of these meta-analyses, Xie et al.'s in the Journal of Internal Medicine, provides a compelling graphical display of the pre-specified primary outcomes of six long-term clinical trials as they were published over time. The pattern of early positive trials, then newer negative (null) trials, suggests regression to the truth. Jeon and Cho et al.'s population-wide study in the Journal of Internal Medicine of patients with Type 2 diabetes and gout found no benefit from colchicine over nonsteroidal anti-inflammatory drugs on major adverse cardiovascular events. This information suggests several areas for reform of research on inflammation in atherosclerosis. Fully informed consent should require that clinical trials of anti-inflammatory agents in atherosclerotic arterial disease must disclose to trial participants the failures of this approach in over 50 clinical trials to date, spanning decades. Additionally, the field might reconsider its commitment to the Big Idea that inflammation must be a definitive therapeutic target in atherosclerosis. The track record so far for inflammation inhibition in atherosclerosis is extensive and disappointing-a fact that merits wider discussion. Therapeutic successes from targeting cholesterol-rich, apolipoprotein-B-containing lipoproteins-the proven causative agents of this disease-provide extraordinary evidence. Current data for colchicine and other anti-inflammatory therapies do not.},
}

@article {pmid42438447,
year = {2026},
author = {Jewett, G and Chan, E and Jagt, K and Petrillo Ballantyne, J and Wesolosky, J and Perera, T and Karnik, V and Hahn, C and Luk, C and Mobach, T},
title = {An intrathecal therapeutics clinic for administration of tofersen in amyotrophic lateral sclerosis: A Canadian nurse practitioner and neurologist collaborative model.},
journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques},
volume = {},
number = {},
pages = {1-10},
doi = {10.1017/cjn.2026.10647},
pmid = {42438447},
issn = {0317-1671},
}

@article {pmid42439979,
year = {2026},
author = {Langreen, S and Uecker, M and Juhl, S and Dingemann, J and Kiblawi, R},
title = {Is hypoalbuminemia a risk factor for small bowel anastomotic leaks in infants? A multivariate analysis.},
journal = {Pediatric surgery international},
volume = {42},
number = {1},
pages = {},
pmid = {42439979},
issn = {1437-9813},
mesh = {Humans ; *Hypoalbuminemia/complications ; Retrospective Studies ; *Anastomotic Leak/etiology/epidemiology ; Risk Factors ; Female ; *Intestine, Small/surgery ; Male ; Infant ; Multivariate Analysis ; Anastomosis, Surgical ; Infant, Newborn ; Incidence ; Serum Albumin ; },
abstract = {PURPOSE: Anastomotic leaks (AL) are critical complications following bowel anastomosis with an incidence of up to 10.5% in infants. Previous studies in animal models and adults have suggested a link between postoperative fluid overload and hypoalbuminemia with anastomotic leaks. In infants, the role of hypoalbuminemia on anastomotic integrity after small bowel anastomosis remains unclear.

METHODS: Retrospective study of infants < 1 year, undergoing elective small-bowel anastomosis between 2015 and 2024 (Ethics No.-11362-_BO_K_202). Data on demographics, weight gain, serum albumin levels and use of diuretic medication during the first five postoperative days were collected. Univariate and multivariate analysis were performed to detect risk factors for ALs in infants.

RESULTS: 13 of 219 patients (5.9%) developed ALs. Demographics were similar comparing patients with and without leaks. In univariate analysis, serum albumin levels were significantly lower (20.3 g/l vs. 26,3 g/l, p < 0.0001) in patients with AL compared to patients without AL and multivariate analysis confirmed a significant association between low serum albumin levels and AL occurrence, CONCLUSION: In infants, small bowel anastomotic leaks are associated with low postoperative serum albumin. Whether hypoalbuminemia should be regarded as an early warning sign of an undiagnosed, developing anastomotic leak or represents a causal risk factor can only be determined with further studies.},
}

Humans
*Hypoalbuminemia/complications
Retrospective Studies
*Anastomotic Leak/etiology/epidemiology
Risk Factors
Female
*Intestine, Small/surgery
Male
Infant
Multivariate Analysis
Anastomosis, Surgical
Infant, Newborn
Incidence
Serum Albumin

@article {pmid42432671,
year = {2026},
author = {Chen, F and Wang, L and Liu, H and Khan, Q and Tang, B and Bao, N},
title = {The role of AI-assisted drug repurposing in neurological disorders: a systematic review of validation strategies, challenges and opportunities.},
journal = {Journal of nanobiotechnology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12951-026-04551-7},
pmid = {42432671},
issn = {1477-3155},
abstract = {Neurological disorders refer to a diverse group of conditions that affect the brain, peripheral nerves, and spinal cord and impair socioemotional, cognitive, motor, and sensory functions. Alzheimer's disease (AD), Multiple Sclerosis (MS), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS) are some of the well-known neurodegenerative diseases that affect millions of people worldwide. Despite the advanced technologies and nano-drug delivery systems, the success rate of developing drugs for neurological disorders is significantly low. Among several constraints, including gastrointestinal irritation, rapid metabolism, and low stability, the blood-brain barrier (BBB) emerges as one of the key challenges in the development and application of drugs against neurological disorders. These challenges necessitate innovative approaches to develop cost-effective therapeutic strategies. Drug repurposing, the discovery of new therapeutic benefits of existing drugs, is a promising drug discovery approach for discovering potential treatment options for complex neurological disorders. This review aims to explore the advanced and significant progress in drug repurposing for major neurological disorders, including MS, AD, PD, ALS, HD, stroke, and neuropsychiatric conditions. It places an explicit emphasis on discussing the potential role of artificial intelligence (AI)-assisted drug repurposing and understanding of the biological mechanisms in discovering new drugs for these neurological conditions. This also examines current challenges in drug repurposing and provides a critical review of the available opportunities and limitations in AI-assisted drug repurposing.},
}

@article {pmid42432783,
year = {2026},
author = {Choi, Y and Lee, S and Ashim, J and Yu, W and Cho, E and Lee, HW and Park, JS and Yoon, JH and Kim, HJ and Cheon, M},
title = {Cross-disease LC-MS/MS plasma proteomics identifies reproducible shared and disease-enriched biomarker signatures in neurodegenerative disorders.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-026-02377-w},
pmid = {42432783},
issn = {2051-5960},
support = {RS-2024-00454715//the National Research Foundation of Korea (NRF) grant funded by the Korean government/ ; RS-2024-00343239//the National Research Foundation of Korea (NRF) grant funded by the Korean government/ ; RS-2023-00230402//the Ministry of Environment of Korea/ ; 26-BR-04-01//the KBRI basic research program through the Korea Brain Research Institute funded by the Ministry of Science and ICT/ ; 26-BR-02-03, 26-BR-02-05, 26-BR-04-01//the KBRI basic research program through the Korea Brain Research Institute funded by the Ministry of Science and ICT/ ; 26-BR-02-03, 26-BR-02-05, 26-BR-04-01, 26-BR-06-02//the KBRI basic research program through the Korea Brain Research Institute funded by the Ministry of Science and ICT/ ; RS-2024-00512888//the Korea Technology and Information Promotion Agency for SMEs (TIPA) funded by the Ministry of SMEs and Startups/ ; },
abstract = {Neurodegenerative diseases (NDDs) exhibit considerable molecular heterogeneity, making it difficult to pinpoint robust, disease-specific biomarkers. Although proteomic studies have deepened our understanding of individual disorders, systematic cross-disease comparisons with cross-platform validation remain scarce, especially for rare conditions like spinal and bulbar muscular atrophy (SBMA). To address this gap, we conducted a comparative plasma proteomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 264 participants across major neurodegenerative and related diagnostic groups, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), SBMA, and cognitively healthy controls. This unified framework allowed us to capture both disease-specific and shared protein signatures across neurodegenerative conditions. Candidate proteins were then validated in the UK Biobank (Olink Explore) and the Global Neurodegeneration Proteomics Consortium (SomaScan). Of 23 proteins assessed in the UK Biobank, four unique proteins (yielding six disease-protein associations) showed nominally significant and directionally concordant changes; of 20 proteins represented by 27 probes tested in the Global Neurodegeneration Proteomics Consortium, seven proteins reached nominal significance, all with full directional concordance across both cohorts. Notably, IGFBP2 was consistently elevated in AD and PD across independent datasets, pointing to shared metabolic dysregulation, while ADIPOQ showed parallel increases in the same conditions, reinforcing convergent shifts in energy metabolism. By contrast, CRTAC1 and COMP were selectively reduced in motor neuron diseases, suggesting disease-enriched alterations in extracellular matrix composition. Taken together, our findings provide a cross-disease, cross-platform framework for uncovering reproducible proteomic biomarkers and shed light on both overlapping and distinct molecular pathways in neurodegeneration.},
}

@article {pmid42432887,
year = {2026},
author = {Ye, H and Wang, JL and Xu, QH and Gao, YL},
title = {Refining the link between REM sleep behavior disorder and neurodegeneration: Genetic correlation, Mendelian randomization, and colocalization evidence.},
journal = {Medicine},
volume = {105},
number = {28},
pages = {e48922},
doi = {10.1097/MD.0000000000048922},
pmid = {42432887},
issn = {1536-5964},
mesh = {Humans ; *REM Sleep Behavior Disorder/genetics/complications ; Mendelian Randomization Analysis ; *Neurodegenerative Diseases/genetics ; Linkage Disequilibrium ; Genome-Wide Association Study ; Alzheimer Disease/genetics ; Parkinson Disease/genetics ; },
abstract = {Observational studies have proposed a link between isolated rapid eye movement sleep behavior disorder (iRBD) and several neurodegenerative diseases. We employed genome-wide linkage disequilibrium score regression (LDSC), standard two-sample Mendelian randomization (MR), and colocalization analysis to assess the causal links between iRBD and these neurodegenerative conditions. iRBD demonstrated a positive causal association with Alzheimer disease (odds ratio [OR] = 1.02, 95% confidence interval [CI]: 1.00-1.03, P = 1.10E-02), Parkinson disease (OR = 1.10, 95% CI: 1.03-1.16, P = 2.96E-03), and multiple sclerosis (OR = 1.09, 95% CI: 1.02-1.17, P = 1.61E-02). A strong positive genetic correlation with dementia with Lewy bodies was observed (rg = 1.6313, P = .0002), along with a causal association (OR = 1.45, 95% CI: 1.03-2.06, P = 3.53E-02), further supported by colocalization analysis. No significant causal relationship was identified between iRBD and amyotrophic lateral sclerosis (all P > .05). Additionally, reverse Mendelian randomization analyses did not reveal any causal relationships between the neurodegenerative diseases studied and iRBD. Our findings provide robust genetic evidence supporting a causal relationship between iRBD and the risk of multiple neurodegenerative diseases, highlighting the potential for shared pathophysiological mechanisms.},
}

Humans
*REM Sleep Behavior Disorder/genetics/complications
Mendelian Randomization Analysis
*Neurodegenerative Diseases/genetics
Linkage Disequilibrium
Genome-Wide Association Study
Alzheimer Disease/genetics
Parkinson Disease/genetics

@article {pmid42432946,
year = {2026},
author = {Jeong, J and Song, KJ and Lee, JC and Shin, SD and Kim, YJ},
title = {A simulation study on optimizing stationary camera locations for physician-directed telemedical supervision of prehospital advanced life support: Single-versus dual-camera setups.},
journal = {Medicine},
volume = {105},
number = {28},
pages = {e49685},
doi = {10.1097/MD.0000000000049685},
pmid = {42432946},
issn = {1536-5964},
support = {2020R1F1A1076561//National Research Foundation of Korea/ ; },
mesh = {Humans ; *Telemedicine ; *Emergency Medical Services/methods ; Prospective Studies ; *Emergency Medical Technicians/education ; Smartphone ; *Video Recording/instrumentation/methods ; },
abstract = {Prehospital telemedicine, particularly real-time video conferencing, offers significant benefits in prehospital and disaster settings by enabling rapid data transmission. Using a smartphone mounted on a tripod as a stationary camera provides stable footage, comprehensive scene evaluation, and reduced technical complexity, thus complementing smart glasses and built-in cameras. However, the optimal camera location for visualizing key procedures remains unexplored. This study aims to compare the optimal stationary camera location and the effectiveness of single-camera versus dual-camera setups in visualizing key procedures for physician-directed telemedical supervision of prehospital advanced life support (ALS). This prospective, non-randomized simulation study involved 9 advanced emergency medical technicians performing ALS procedures in 20 simulations. Each simulation was recorded simultaneously from 4 stationary camera locations: right head, left head, right leg, and left leg. Reviewers evaluated the visibility of 6 key procedures (airway management, breathing support, chest compressions, intravenous access, electrocardiogram rhythm monitoring, and teamwork) using a 1 to 5 scale. Mixed models and generalized linear mixed models were applied to analyze the visibility scores and compare the effect sizes of the different camera setups. The median visibility scores and proportion of optimal visibility (scores of 4-5) varied significantly across the 4 camera locations for most procedures. However, the mixed model and generalized linear model analyses for overall visibility did not reveal significant differences in effect sizes between individual camera locations. Dual-camera setups showed significant improvement over single-camera setups, with an adjusted odds ratio of 4.89 (95% confidence interval: 1.92-12.4) for the right head + left head combination and 3.74 (95% confidence interval: 1.50-9.32) for the right head + left leg combination. Although no single-camera location provided optimal visualization for all procedures, dual-camera setups were more effective than single cameras in capturing field activity. These findings support the use of dual-camera setups to enhance physician-directed telemedical supervision of prehospital ALS, with potential applicability to disaster settings, and may inform the development of future protocols for prehospital telemedicine.},
}

Humans
*Telemedicine
*Emergency Medical Services/methods
Prospective Studies
*Emergency Medical Technicians/education
Smartphone
*Video Recording/instrumentation/methods

@article {pmid42434198,
year = {2026},
author = {Sleutjes, BTHM and Jacobsen, AB and Tankisi, H and Sirin, NG and Oge, AE and Henderson, RD and van Doorn, PA and van den Berg, LH and van Eijk, RPA},
title = {Quantifying motor unit loss prior to functional impairment in muscles affected by amyotrophic lateral sclerosis.},
journal = {Clinical neurophysiology practice},
volume = {11},
number = {},
pages = {538-542},
pmid = {42434198},
issn = {2467-981X},
abstract = {OBJECTIVES: The compound muscle action potential (CMAP) scan is a non-invasive method for deriving motor unit number estimates (MUNE) to track disease progression in muscles affected by amyotrophic lateral sclerosis (ALS). It remains to be established whether and how long motor unit loss precedes functional impairment.

METHODS: In 56 patients with ALS, we compared the longitudinal trajectories of MUNE derived from thenar CMAP scans, and fine motor function (FMF) using a functional rating scale. Linear and sigmoidal disease trajectories were modelled from which time differences were estimated between these measures to reach their half-maximum scores.

RESULTS: The normalized linear decline per month was 0.02 (95% CI 0.01 to 0.03) for FMF and 0.03 (95% CI 0.03 to 0.04) for MUNE. Half-maximum of FMF was reached after 26.3 months (95% CI 18.9 to 35.1) for the linear model, while MUNE had a shorter time required to reach 50% of its maximum with 13.0 months (95% CI 10.3 to 16.4). The head-to-head comparison between FMF and MUNE showed that MUNE values reached 50% of its maximum 13.1 months (95% CI 7.0-20.8) earlier. Results were similar for sigmoidal disease trajectories.

CONCLUSIONS: Simulated disease trajectories of MUNE values derived from CMAP scans in muscles affected by ALS indicated that MUNE may reach 50% of its maximum in approximately 60% of the time compared to functional impairment.

SIGNIFICANCE: These explorative findings underscore how neurophysiological measures may be of use for early disease monitoring, with relevance for both care and research settings.},
}

@article {pmid42434808,
year = {2026},
author = {Baker, B and Emerson, S and Tran, T and Mohapatra, N and Wang, D and Zaw, T and Doshi, A and Lopez, JM and Hassan, D and Kumar, P and Farmer, D and Wang, A},
title = {Brain targeting and trafficking of extracellular vesicles in central nervous system diseases: a therapeutic roadmap.},
journal = {Nanomedicine (London, England)},
volume = {},
number = {},
pages = {1-19},
doi = {10.1080/17435889.2026.2698782},
pmid = {42434808},
issn = {1748-6963},
abstract = {Extracellular vesicles (EVs) mediate intercellular signaling in the central nervous system (CNS) by transferring lipids, proteins, and nucleic acids among neurons, glia, endothelium, and immune cells. Brain targeting depends on a linked sequence: EV ligands and adsorbed protein coronas engage receptor modules, select endocytic routes, determine intracellular fate, and define the therapeutic readouts. These fates include lysosomal degradation, recycling, rare cytosolic delivery, or transport across the blood-brain barrier (BBB). In disease, the same pathways can disseminate proteopathic seeds and amplify neuroinflammation. Heparan sulfate proteoglycans (HSPGs) and LDL receptor family members, including low-density lipoprotein receptor-related protein 1 (LRP1), regulate tau, α-synuclein, and amyloid-β handling. Phosphatidylserine readers and complement shape myeloid sink capture and inflammatory output. Integrin, tetraspanin, and ICAM-1 nanoclusters influence avidity, organotropism, and immune suppression. At the BBB, endothelial HSPGs, LRP1, and transferrin receptor (TfR) support receptor-mediated uptake, motivating engineered ligands such as rabies virus glycoprotein-derived peptides, Angiopep-2, and TfR binders. However, endosomal escape remains a major kinetic barrier to nucleic acid delivery. We synthesize these principles across Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, glioblastoma, and demyelinating disease, and outline design and assay standards needed to translate EV biology into safe, manufacturable CNS therapeutics.},
}

@article {pmid42435104,
year = {2026},
author = {Qiao, Y and Ma, ZS},
title = {Deterministic selection and compositional turnover in Parkinson's disease-associated gut dysbiosis.},
journal = {Antonie van Leeuwenhoek},
volume = {119},
number = {8},
pages = {},
pmid = {42435104},
issn = {1572-9699},
support = {NSFC Grant# 72274192//National Natural Science Foundation of China/ ; },
mesh = {*Parkinson Disease/microbiology/complications ; *Dysbiosis/microbiology ; Humans ; *Gastrointestinal Microbiome ; *Bacteria/classification/genetics/isolation & purification ; },
abstract = {The scientific understanding of links between Parkinson's disease (PD) and gut microbiome dysbiosis has advanced significantly, yet the ecological mechanisms driving these microbial changes remain poorly understood. To address this gap, we postulated that PD-associated gut dysbiosis arises as harmful microbes outcompete beneficial bacteria, and consequently any therapeutic strategies must both suppress opportunistic pathogens and restore protective, fiber-degrading microbes to effectively rebalance the gut microbiome in PD. To evaluate ecological patterns consistent with this hypothesis, we apply Sloan's near-neutral model (SNM), Ning et al.'s stochasticity framework, and ecological network analysis to reanalyze six published gut microbiome datasets (1957 samples total: 804 healthy controls, 1153 PD cases). We first applied SNM to categorize bacterial species as neutral, positively selected, or negatively selected. While the overall proportions of these categories were similar between groups (neutral: ~ 40%, positively selected: ~ 47%, negatively selected: ~ 13%), stochasticity framework analysis revealed significantly stronger deterministic selection in PD microbiomes. Shared species analysis (SSA) resolved this apparent paradox by demonstrating substantial compositional shifts within each species category, indicating that while classification frequencies remained stable, the specific microbes occupying these ecological niches changed significantly in PD. This divergence between SNM category proportions and NSR values highlights a subtle yet critical aspect of community assembly dynamics. Ecological network analysis further revealed that neutral species had fewer antagonistic co-occurrence links, consistent with their ecological equivalence, while negatively selected species maintained higher relative abundances in both groups. Together, these findings indicate that PD-associated gut microbiomes are characterized by stronger deterministic assembly signatures and substantial compositional turnover within near-neutral ecological categories. These patterns are consistent with altered ecological assembly signatures in PD-associated dysbiosis.},
}

*Parkinson Disease/microbiology/complications
*Dysbiosis/microbiology
Humans
*Gastrointestinal Microbiome
*Bacteria/classification/genetics/isolation & purification

@article {pmid42435587,
year = {2026},
author = {Domínguez-García, A and Delgado-Uriarte, JC and Cervantes-Arriaga, A},
title = {Precision therapeutics and innovative clinical trial design in neurodegenerative diseases.},
journal = {Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion},
volume = {78},
number = {4},
pages = {100050},
doi = {10.1016/j.ric.2026.100050},
pmid = {42435587},
issn = {2564-8896},
abstract = {Neurodegenerative diseases are biologically heterogeneous disorders characterized by progressive neuronal dysfunction, overlapping molecular pathologies, and limited disease-modifying therapies. Advances in biomarker development, molecular staging, and precision medicine are reshaping therapeutic strategies and clinical trial design across Parkinson's disease, Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, Huntington's disease, and related disorders. This review summarizes emerging therapeutic approaches, including monoclonal antibodies targeting protein aggregation, immune-modulating and metabolic interventions, antisense oligonucleotides, gene replacement and genome-editing strategies, stem cell-based therapies, and neurosurgical delivery platforms and neuromodulation technologies. It also examines evolving clinical trial methodologies such as biomarker-enriched recruitment, adaptive and delayed-start designs, platform trials, decentralized models, and master protocols. Additional emphasis is placed on diagnostic biomarkers, multimodal artificial-intelligence pipelines, systems-biology perspectives, network-based therapeutic strategies, and the reproducibility and interpretability requirements for computational tools. Despite recent progress, major challenges remain, including biological heterogeneity, limited translatability of preclinical models, delivery barriers, long-term safety concerns, and inequities in access to biomarker-based care and trial participation. Future directions will require combination therapies, integrated biomarker pipelines, preventive strategies, and pragmatic trial systems capable of translating biological advances into durable and equitable clinical benefit.},
}

@article {pmid42436372,
year = {2026},
author = {Roy, T and Ramesh, M and Nizam, NAA and Tandiono, S and Al-Jamal, KT and Al-Chalabi, A and Iacoangeli, A and Al Khleifat, A},
title = {Plasma exosomal HERV-K transcripts are increased in amyotrophic lateral sclerosis.},
journal = {BMC neuroscience},
volume = {27},
number = {1},
pages = {},
pmid = {42436372},
issn = {1471-2202},
support = {303476//National Institute for Health and Care Research/ ; MRC (MR/Z505705/1)//South London and Maudsley NHS Foundation Trust/ ; LS Association Milton Safenowitz Research Fellowship (RE19765)//NIHR Maudsley Biomedical Research Centre/ ; RE23378//LifeArc/ ; 1819242//Dementia Consortium/ ; 1122462/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/Z505705/1/MRC_/Medical Research Council/United Kingdom ; },
abstract = {Human endogenous retrovirus-K (HERV-K) reactivation is increasingly implicated in amyotrophic lateral sclerosis (ALS), with ongoing clinical trials investigating antiretroviral therapies. However, there is limited understanding of how HERV-K is trafficked in peripheral biofluids, and the role of exosomes, nano-sized extracellular vesicles, in this process remains largely unexplored. Exosomes offer a stable and cell-specific cargo reservoir that may reflect central pathogenic processes and serve as a minimally invasive biomarker source. In this study, we isolated plasma-derived exosomes from ALS patients (n = 21) and healthy controls (n = 16), and quantified exosomal HERV-K gag, env, and pol transcript levels using SYBR Green qPCR with RNase treatment and normalization to both traditional and exosome-enriched reference genes. HERV-K pol expression was significantly elevated in ALS, with fold-changes ranging from 1.59 to 1.85 (P = 0.037-0.051). env and gag also showed increased expression, though with greater variability. Normalization to the exosome-specific gene SOD2 provided the most consistent signal. These findings suggest that exosomal HERV-K transcripts, particularly pol, could serve as accessible biomarkers for patient stratification and treatment monitoring in HERV-K-targeted ALS trials. This work establishes proof-of-concept for using exosomal cargo to track endogenous retroviral activity in neurodegeneration and supports further investigation of liquid biopsy approaches in ALS precision medicine.},
}

@article {pmid42436431,
year = {2026},
author = {Parks, ASE and Conn, LG and Abrahao, A and Zinman, L and Sale, JEM},
title = {"Straddling two worlds": complexities of spousal caregiving in amyotrophic lateral sclerosis during younger middle age.},
journal = {BMC palliative care},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12904-026-02230-w},
pmid = {42436431},
issn = {1472-684X},
abstract = {BACKGROUND: Family support is central to amyotrophic lateral sclerosis (ALS) care. Spouses often assume the role of primary caregiver, facing daily challenges as their partner's needs progressively increase. Younger ALS caregivers appear to have distinct experiences and needs, yet age- or life-stage variations and processes of caregiving are seldom considered in studies of ALS family caregiver experience.

METHODS: We undertook a qualitative study, guided by constructivist grounded theory methodology, to explore the dynamics of family caregiving following an ALS diagnosis in a younger middle-aged family member (≤55 years). Data were coded to identify psychosocial processes, including how family caregivers engage in caregiving.

RESULTS: In-depth interviews were conducted with ten spousal caregivers between August 2023 and August 2025. Overall, our theoretical understanding of spousal caregiving for younger middle-aged adults with ALS (YMAs) was captured by the core category 'straddling two worlds,' reflecting how caregivers navigated multiple interconnected dichotomies: present and future, familiar and new norms, current and anticipated losses, and the worlds of the living and the dying. To contend with an uncertain future, caregivers anchored themselves in the present as they navigated a shifting sense of normalcy. Middle age expectations and social norms shaped how caregivers engaged in caregiving and experienced losses that were often unending and ambiguous.

CONCLUSIONS: Caregiving for a spouse with ALS in younger middle age involves temporal, practical, emotional, and existential processes. Caregivers of YMAs may benefit from interventions that help them tolerate uncertainty, stay grounded in the present, maintain normalcy, and grieve losses throughout the caregiving trajectory.},
}

@article {pmid42436563,
year = {2026},
author = {Gregory, JM},
title = {Context of use matters: interpreting extracellular vesicle TDP-43 as a biomarker in ALS.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-026-02376-x},
pmid = {42436563},
issn = {2051-5960},
}

@article {pmid42432003,
year = {2026},
author = {Chen, J and Xu, P and Chen, M and Lu, Z and Li, X and Stampas, A and Zong, Y and Zhou, P},
title = {Compound muscle action potential scan dataset in adults with spinal cord injury and healthy controls.},
journal = {Scientific data},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41597-026-07864-2},
pmid = {42432003},
issn = {2052-4463},
support = {ZR2024QH582//Natural Science Foundation of Shandong Province/ ; ZR2024YQ077//Natural Science Foundation of Shandong Province/ ; tsqn202211226//Taishan Scholar of Shandong Province/ ; tstp20221144//Taishan Scholar of Shandong Province/ ; 25S11907200//Science and Technology Commission of Shanghai Municipality/ ; KFKT-2024-KF-013//Chinese Association of Rehabilitation Medicine/ ; 82572355//National Natural Science Foundation of China/ ; },
abstract = {Certain neurological conditions, such as amyotrophic lateral sclerosis (ALS) and spinal cord injury (SCI), result in motor unit loss in muscles. The stimulus-evoked compound muscle action potential (CMAP) scan captures comprehensive information on motor unit recruitment that enables rapid and non-invasive assessment of motor unit status. However, few publicly available CMAP scan datasets exist to support research on motor unit number estimation (MUNE). To address this gap, we collected CMAP scan data from the first dorsal interosseous (FDI) muscle of 13 individuals with SCI and 13 healthy participants, and established a dedicated CMAP scan dataset. The dataset includes CMAP waveforms evoked by each nerve stimulus from which CMAP scan curve and typical parameters were extracted for direct use. All SCI participants underwent multiple clinical assessments and exhibited a spectrum of impairment severity from mild to severe, resulting in diverse CMAP features. We anticipate that this dataset will facilitate the development of advanced CMAP scan-based assessment techniques and aid in the investigation of neuromuscular impairment.},
}

@article {pmid42432423,
year = {2026},
author = {Sugisawa, R and Sekiguchi, K and Noda, Y and Matoba, S and Suehiro, H and Kozuki, J and Tanaka, T and Chihara, N},
title = {Quantitative Spatiotemporal Analysis of Ultrasound Images of Fasciculations in ALS.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70338},
pmid = {42432423},
issn = {1097-4598},
support = {JP256f0137011//Japan Agency for Medical Research and Development/ ; 25K14534//Japan Society for the Promotion of Science/ ; 24K14297//Japan Society for the Promotion of Science/ ; },
abstract = {INTRODUCTION/AIMS: Fasciculations are a hallmark of amyotrophic lateral sclerosis (ALS), yet quantitative description of individual events on muscle ultrasound (MUS) is limited. We characterized the spatiotemporal kinematics of individual fasciculations to determine whether they differ between ALS and other neurogenic conditions.

METHODS: We retrospectively analyzed biceps brachii MUS recordings from 680 examinations (January 2020-June 2025), identifying 74 ALS and 40 non-ALS neurogenic recordings with fasciculations (167 and 62 segments). After propensity score matching for age and muscle strength, 62 matched pairs were analyzed. The Lucas-Kanade optical flow algorithm, which estimates frame-to-frame displacement vectors from local intensity gradients, was applied at 1-pixel intervals (57,600 points per 240 × 240 region; ≈60 μm) to quantify twitch durations, peak displacement velocity, and directional anisotropy as a measure of spatial movement coherence.

RESULTS: ALS fasciculations showed prolonged total duration (582.8 ± 112.8 ms vs. 489.2 ± 128.7 ms, p < 0.001), reduced directional anisotropy (0.534 ± 0.245 vs. 0.627 ± 0.215, p = 0.028), and lower peak displacement velocity (6.55 ± 6.56 vs. 9.53 ± 9.07 μm/ms, p = 0.039). MANOVA showed significant multivariate differences (Pillai's trace = 0.317 ± 0.030, p < 0.001) with moderate group separation (Mahalanobis distance = 1.10 ± 0.05).

DISCUSSION: ALS fasciculations showed spatially heterogeneous and temporally prolonged contraction patterns, suggesting motor units in a transitional state of incomplete reinnervation, distinct from the more stable architecture of chronic neurogenic disorders. This framework may complement existing ultrasound assessment and aid the study of motor unit pathology in ALS.},
}

@article {pmid42432439,
year = {2026},
author = {Kavale-Henderson, LA and Buckberry, J and Buckley, H and Cameron, C and King, C and Koon, H and Petchey, P and Snoddy, AME and Loch, C},
title = {"An Injurious and Utterly Unfit Environment": A Case Study Comparing Dental Evidence of Childhood Stress in Nineteenth Century Working-Class Peoples From British and Colonial New Zealand Contexts.},
journal = {American journal of biological anthropology},
volume = {190},
number = {3},
pages = {e70315},
pmid = {42432439},
issn = {2692-7691},
support = {21-UOO-01//Ministry of Business, Innovation and Employment/ ; //University of Otago/ ; },
mesh = {Humans ; New Zealand ; History, 19th Century ; United Kingdom ; Child ; Adult ; Male ; *Tooth/pathology ; *Stress, Psychological/pathology/history ; Female ; Child, Preschool ; Young Adult ; Infant ; Adolescent ; Transients and Migrants/history ; },
abstract = {OBJECTIVES: During the nineteenth century, the health and living conditions of many working-class European peoples declined in association with growing industrialization and urbanization. Emigration to British colonies grew as people sought to escape such hardships. This research presents the first direct comparison of dental markers of stress in a case study of migrants to a British colony (Otago, New Zealand) alongside a contemporaneous assemblage representing an origin population (London, United Kingdom).

MATERIALS AND METHODS: Dental markers of childhood stress, accentuated lines, were observed in thin-sections of archeological teeth from adults (n = 9) and children (n = 16) interred in London, United Kingdom (UK), and adult European migrants interred in Otago, New Zealand (NZ) (n = 24) using standard histological techniques.

RESULTS: All individuals interred in London, and 92% (22/24) of those in New Zealand exhibited evidence of accentuated line formation within the first 2.5 years of life. There was no difference in median accentuated line occurrence between adults and children interred in the UK. However, NZ adults had a lower median occurrence of accentuated lines over the first 2.5 years since birth (5 ALs/individual) than UK adults (13 ALs/individual). Accentuated lines most frequently occurred in infancy for all three groups examined. However, temporal trends in accentuated line occurrence differed between groups in association with age.

DISCUSSION: These results highlight the impact of childhood stresses on working-class people growing up during the nineteenth century, underlining potential differences in the childhood experiences of hardship in individuals that remained in Britain and those that departed for foreign soils.},
}

Humans
New Zealand
History, 19th Century
United Kingdom
Child
Adult
Male
*Tooth/pathology
*Stress, Psychological/pathology/history
Female
Child, Preschool
Young Adult
Infant
Adolescent
Transients and Migrants/history

@article {pmid42427320,
year = {2026},
author = {Uchino, A and Kanemaru, K and Tarutani, A and Hasegawa, M and Naruse, H and Ishiura, H and Murayama, S and Saito, Y},
title = {Frontotemporal Lobar Degeneration-TDP Type C With Striatal Glial Cytoplasmic Inclusions and Motor Neuron Degeneration.},
journal = {Neuropathology and applied neurobiology},
volume = {52},
number = {4},
pages = {e70090},
pmid = {42427320},
issn = {1365-2990},
support = {JP21wm0425019//Japan Agency for Medical Research and Development/ ; JP25wm0625126//Japan Agency for Medical Research and Development/ ; JP24dk0207074h0001//Japan Agency for Medical Research and Development/ ; JP22H04923//MEXT/JSPS KAKENHI/ ; JPMH23FC1008//Research on rare and intractable diseases Program/ ; },
mesh = {Humans ; *Inclusion Bodies/pathology ; *Frontotemporal Lobar Degeneration/pathology ; *Neuroglia/pathology ; *DNA-Binding Proteins/metabolism ; *Motor Neurons/pathology ; *Corpus Striatum/pathology ; Male ; *Motor Neuron Disease/pathology ; Female ; Aged ; },
abstract = {We report an autopsy case of frontotemporal lobar degeneration (FTLD)-TDP type C with severe striatal involvement and annexin A11- and phosphorylated TDP-43-positive glial cytoplasmic inclusions. The patient developed progressive asymmetric rigidity accompanied by marked striatal atrophy and showed both upper and lower motor neuron involvement. These findings expand the clinicopathological spectrum of FTLD-TDP type C and may support the concept of an annexin A11-associated pathogenic continuum linking FTLD and amyotrophic lateral sclerosis.},
}

Humans
*Inclusion Bodies/pathology
*Frontotemporal Lobar Degeneration/pathology
*Neuroglia/pathology
*DNA-Binding Proteins/metabolism
*Motor Neurons/pathology
*Corpus Striatum/pathology
Male
*Motor Neuron Disease/pathology
Female
Aged

@article {pmid42427517,
year = {2026},
author = {Chen, Y and Zhang, S},
title = {AART enables fast and accurate cross-platform proteomic translation.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.06.29.735313},
pmid = {42427517},
issn = {2692-8205},
abstract = {Plasma proteomic profiling has been widely used for biomarker discovery, disease prediction and diagnosis, and patient stratification. However, technical differences across assay platforms often result in low-to-moderate agreement, limiting study reproducibility, data integration, and model transferability. Here we present AART, a cross-platform proteomic translation framework that integrates matched-protein ridge regression with proteome-wide residual learning. We benchmarked AART spanning three independent cohorts profiled using three major platforms, including Olink, SomaScan, and mass spectrometry. Across all six translation directions, AART achieved the best performance compared with baseline methods for both overlapping and non-overlapping protein translations, with a relative improvement of 92.0% on average over direct mapping and by up to 31.6% over cpiVAE, the strongest baseline. Proteins that were accurately translated and improved by AART were enriched for extracellular, vesicle-associated, and tissue-restricted plasma biology. In downstream applications, AART improved the reproducibility of proteomic association analyses relative to direct cross-platform comparison by 75.5% for type 2 diabetes and 370.6% for Alzheimer's disease. AART-enabled cohort integration enhanced diagnostic accuracy for amyotrophic lateral sclerosis by 92.6% compared with non-integration analysis. AART was overall one to three orders of magnitude faster than cpiVAE, facilitating biobank-scale applications. Together, these results establish AART as a fast, accurate, and scalable framework for cross-platform proteomic translation, enabling more reproducible, transferable, and integrated proteomic research.},
}

@article {pmid42427576,
year = {2026},
author = {Wang, H and Sun, S and Mathé, EA and Zhu, Q},
title = {RD-OMICS: An Integrative Multi-Omics Data Inventory in Rare Diseases.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.06.29.735296},
pmid = {42427576},
issn = {2692-8205},
abstract = {Rare diseases (RD) impact over 30 million individuals in the United States, yet fewer than 5% of the identified conditions have FDA-approved treatments. Progress in RD research is hindered by small patient cohorts, biological heterogeneity, and the fragmented, inconsistently annotated publicly available omics data, which limits integrative analysis and translational discovery. Here, we present RD-OMICS, a data inventory with integrated and structured RD omics data from Gene Expression Omnibus (GEO), in the form of a knowledge graph. We developed a metadata harmonization pipeline that combines rule-based mapping and large language model (LLM)-assisted semantic categorization. The graph-based data model was defined to integrate different types of data including disease conditions, experiments, samples, platforms, projects, and publications into a centralized inventory graph. In this preliminary study, 11,049 GEO series for 126 rare diseases were processed and integrated into RD-OMICS, which includes 375,930 individual biospecimen samples, 1,578 sequencing and array platforms, 10,938 biological projects. Case studies demonstrate the use of RD-OMICS in supporting rare disease research, omics cohort construction, and transcriptome-based drug repurposing for amyotrophic lateral sclerosis (ALS). RD-OMICS provides a scalable foundation for transforming fragmented omics data into a structured, harmonized and interoperable resource, facilitating therapeutic development and other translational discoveries in rare diseases.},
}

@article {pmid42427672,
year = {2026},
author = {Dixon, E and Azimian, F and Joby Chacko, A and Tatum, R and Boykin, C and Chen, YH and Lu, Q},
title = {Small molecules targeting ARF1 interaction with C9orf72:SMCR8:WDR41 complexes suppress its overactivation implicated in ALS/FTD.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.01.24.701325},
pmid = {42427672},
issn = {2692-8205},
abstract = {The hexanucleotide repeat expansion in C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). The C9orf72 protein forms a complex with SMCR8 and WDR41 (CSW), which functions as a GTPase-activating protein (GAP) regulating ARF1 and RAB small GTPases. While these findings implicated ARF1-GAP dysregulation in ALS/FTD and supported ARF1 suppression as potential intervention, small molecules that modulate ARF1-CSW interactions are lacking. In this study, we demonstrated upregulation of tyrosine-phosphorylated (Tyr-782) ASAP1 (also known as AMAP1, DDEF1, or Centaurin β4), an ARF-GAP, in human motor cortex of both sporadic ALS and ALS with C9orf72 mutations. Ectopic C9orf72 expression partially mimicked the effects of a known ARF1 inhibitor brefeldin A to disperse Golgi apparatus. Computer-aided rational drug design with high-throughput in-silico screening identified MCULE-5095997944 (Named as SCC944) as a ARF1-CSW modulator. SCC944 binds directly to ARF1 and reduced GTP-bound ARF1 levels upon ARF1 activation. SCC944 demonstrated brefeldin A-like ARF1-dependent alteration of organelle organization including Golgi, microtubules, and mitochondria, but also a protein trafficking pattern that is distinct from brefeldin A mechanism. These studies identified the first small molecule targeting ARF1-CSW interaction and further support ARF1 modulation as a potential therapeutic approach for ALS/FTD.},
}

@article {pmid42428129,
year = {2026},
author = {Raemaekers, M and Geukes, SH and Aarnoutse, EJ and Branco, MP and Freudenburg, ZV and Schippers, A and Crone, NE and Leinders, S and Berezutskaya, J and Ramsey, NF and Vansteensel, MJ},
title = {Association between motor cortex grey matter loss and inability to control an ECoG-based implanted Brain-Computer Interface in ALS.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.06.23.26355654},
pmid = {42428129},
abstract = {BACKGROUND: The field of implantable Brain-Computer Interfaces (iBCIs) is rapidly advancing, with individuals with amyotrophic lateral sclerosis (ALS) as key beneficiaries. However, ALS-related cortical degeneration may impair iBCI effectiveness. This study investigated whether structural magnetic resonance imaging (MRI) and functional MRI (fMRI) metrics are associated with the quality of electrocorticography (ECoG) signals critical for iBCI use.

METHODS: Six late-stage ALS participants and 76 controls underwent T1-weighted structural MRI and task-based fMRI during right-hand movement or attempts thereof. ECoG data of ALS participants was benchmarked using ECoG data acquired in epilepsy patients. Grey matter thickness in the sensorimotor cortex and fMRI activation in the motor-hand area were measured.

RESULTS: Four ALS participants showed >0.4 mm thinning in the precentral gyrus, while the postcentral gyrus was spared. ECoG signal quality was significantly associated with precentral grey matter thickness, but not with fMRI activity.

CONCLUSIONS: These findings suggest that presurgical assessment of precentral grey matter thickness could potentially prove useful for iBCI candidate selection in advanced ALS.

PLAIN LANGUAGE SUMMARY: People with amyotrophic lateral sclerosis (ALS) can lose the ability to move and speak, but their thinking often remains intact. Implantable brain-computer interfaces (iBCIs) can help by translating brain signals into commands for communication devices. However, ALS damages the motor cortex, which may reduce the quality of these signals. In this study, we examined brain scans and electrical recordings from six people with advanced ALS. We found that thinning of the motor cortex was linked to weaker brain signals needed for iBCI control, while functional MRI activity was less predictive. This suggests that measuring motor cortex thickness before surgery could help identify who will benefit most from an iBCI, improving treatment decisions and future clinical trials.

TWO SENTENCE SUMMARY: We examine presurgical MRI/fMRI and ECoG recordings from people with advanced ALS receiving implanted brain-computer interfaces. Motor cortex thinning is associated with poorer ECoG signal quality, suggesting cortical thickness may help identify candidates likely to benefit.},
}

@article {pmid42428455,
year = {2026},
author = {Cheng, P and Liu, S and Shen, Q},
title = {Laparoscopic temporary uterine artery occlusion combined with en bloc lesion resection for type III cesarean scar pregnancy: surgical technique.},
journal = {Gynecology and pelvic medicine},
volume = {9},
number = {},
pages = {16},
pmid = {42428455},
issn = {2617-4499},
abstract = {This article presents a refined laparoscopic surgical technique for the management of type IIIb cesarean scar pregnancy (CSP), as classified by Ban et al.'s 2023 criteria [residual myometrial thickness <3 mm, maximum sac diameter (MSD) ≥3 cm, bladder protrusion], in a 35-year-old female with vaginal bleeding and a history of two cesarean sections. The core protocol integrates temporary bilateral uterine artery occlusion (simple ligation of the main trunk with No. 1 absorbable Vicryl suture at 2 cm from the uterine wall) immediately before resection, adhesiolysis, en bloc excision of the ectopic mass with a 0.3 cm safe margin, and multilayer anatomical uterine repair. This technique addresses the key clinical challenge of massive intraoperative bleeding in highly vascular type IIIb CSP, with innovations in precise timing of occlusion and reversible minimally invasive ligation. Perioperative outcomes demonstrated excellent hemostasis (total blood loss 100 mL), complete lesion removal confirmed by frozen section, and intact uterine anatomy post-surgery. The study emphasizes the technique's value in hemorrhage control, anatomical restoration, and fertility preservation for patients with large type IIIb CSP (66 mm in this case). We provide a detailed step-by-step surgical guide, clarify patient selection criteria and contraindications, and discuss the technique's advantages, limitations, and potential to revise the standard of care for type III CSP. Postoperative 18-month follow-up showed successful natural conception and uncomplicated second-trimester pregnancy, validating its long-term fertility benefits.},
}

@article {pmid42428795,
year = {2026},
author = {Craig, EJ and Ryan, VH},
title = {Dysregulated neuronal mRNA transport and translation in FTD/ALS.},
journal = {NPJ dementia},
volume = {2},
number = {1},
pages = {56},
pmid = {42428795},
issn = {3005-1940},
abstract = {Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are fatal, co-occurring neurodegenerative disorders. Dysregulation of mRNA metabolism, transport, and local translation is a significant mechanism contributing to FTD/ALS. Here, we review the processes of neuronal RNA transport and translation, their disruption in FTD/ALS, and mechanistic interplay between the two. Finally, we discuss current progress targeting transport and translation defects and identify potential future directions for therapeutic development.},
}

@article {pmid42428879,
year = {2026},
author = {Hermosillo-Abundis, C and Arias-Carrion, O and Contreras-Ibáñez, C and Mendez-Rojas, MA},
title = {From Air to Brain: Environmental Nanoparticles as Modifiable Risk Factors for Neurodevelopmental, Neurodegenerative, and Mental Disorders.},
journal = {ACS omega},
volume = {11},
number = {26},
pages = {38267-38287},
pmid = {42428879},
issn = {2470-1343},
abstract = {Ultrafine particles (≤100 nm) and other environmental nanoparticles have emerged as biologically active pollutants that can cross biological barriers, including the blood-brain barrier and the placenta. Growing evidence implicates ultrafine particles in a wide range of neuropsychiatric conditions, yet their effects remain poorly integrated into clinical and public health frameworks. In this review, we distinguish between size-defined ultrafine particles (UFPs, ≤100 nm), composition-defined environmental nanoparticles originating from combustion and secondary formation processes, and engineered nanomaterials (ENPs), which differ in physicochemical properties, exposure scenarios, and regulatory status. This narrative systematic review synthesizes findings from human and experimental studies on the neuropsychiatric and neurodevelopmental effects of environmental nanopollutants. A structured search was conducted in PubMed, Web of Science, Scopus, and Google Scholar up to November 2025, following explicit inclusion and exclusion criteria. Eligible studies included peer-reviewed human and animal research assessing mental health or neurological outcomes of nanopollutant exposure. Epidemiological studies(?)primarily involving traffic-related air pollution and mixed combustion-derived ultrafine particle exposures(?)suggest associations with increased risk of cognitive impairment, autism spectrum disorder, depression, schizophrenia, and neurodegenerative diseases, including Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. Prenatal and early life exposures were linked to cortical thinning, altered neurodevelopmental trajectories, and early proteinopathies. Underlying mechanisms include neuroinflammation, oxidative stress, and protein aggregation. Despite methodological heterogeneity, the evidence supports the urgent need for regulation and prevention. Environmental nanopollutants constitute an under-recognized, modifiable risk factor for neuropsychiatric and neurodegenerative conditions. A paradigm shift is needed to incorporate environmental exposure history into mental health research, risk assessment, and prevention strategies. Regulatory action targeting nanopollutant emission and exposure, particularly in vulnerable populations, is critical to mitigating long-term neurological consequences.},
}

@article {pmid42429266,
year = {2026},
author = {Macpherson, CE and Muccini, J and Blacutt, ME and Bjalme-Evans, M and Lough, ME and Quinn, L},
title = {Gait speed and future ambulatory status in amyotrophic lateral sclerosis: a retrospective observational study with implications for power wheelchair referral.},
journal = {Physiotherapy theory and practice},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/09593985.2026.2700400},
pmid = {42429266},
issn = {1532-5040},
abstract = {BACKGROUND OR INTRODUCTION: Amyotrophic lateral sclerosis (ALS) causes rapid and progressive loss of ambulation resulting in immobility. A power wheelchair (PWC) increases safety, independence, and quality of life, however, the PWC referral process is lengthy and complex. When the PWC is delayed, immobility complications can occur. One barrier is the lack of a universal predictive "gait speed threshold" to help clinicians determine when to initiate the PWC referral process.

OBJECTIVE OR PURPOSE: Identify a clinically relevant gait speed threshold associated with future loss of ambulation in people with ALS.

METHODS: This was a retrospective chart review of a single multidisciplinary ALS Center of Excellence from July 1, 2016 - July 1, 2019 (36-months). Participants were included in this study if they were adults (age >18 years) with clinically definite ALS who were ambulatory at baseline. The primary outcome was gait speed on the 10-meter walk test. Secondary outcomes included the ALS Functional Rating Scale-Revised, forced vital capacity, falls, and ambulation status.

RESULTS: Of N = 180 people with ALS identified during the study period, n = 72 met inclusion for analysis with a mean age 66.1 ± 11.9 years, 64% male, 76% with an ALS phenotype of spinal onset, and 24% bulbar onset. A gait speed threshold of 0.79 m/s maximized the combined sensitivity and specificity for classifying ambulatory status at the subsequent 6-month visit. Faster gait speeds (>1.2-1.4 m/s) were associated with greater odds of remaining ambulatory at 6-months based on Bayesian logistic regression.

CONCLUSION: A gait speed threshold of 0.79 m/s was associated with increased likelihood of subsequent loss of ambulation, though modest predictive accuracy limits its use as a stand-alone indicator. Gait speed may serve as one component of clinical decision-making regarding PWC planning and referral in people with ALS. Larger multicenter studies are needed to confirm and generalize results across ALS phenotypes.},
}

@article {pmid42429841,
year = {2026},
author = {Li, D and Ye, Q},
title = {Re: Effects of resistance training with/without photobiomodulation on muscle and respiratory function in difficult-to-control asthma: a randomized trial.},
journal = {Lasers in medical science},
volume = {41},
number = {1},
pages = {},
pmid = {42429841},
issn = {1435-604X},
support = {2022KY1159, 2025KY1423, 2025KY1417 and 2025HY1019//Zhejiang Provincial Medical and Health Plan/ ; 2022020405//Ningbo High-Level Medical and Health Team Major Tackling Project and the Talent Development Program/ ; 2026-A36//Ningbo Municipal Key Modern Medical Discipline Development Project/ ; No.2024Z222//Key Technology Breakthrough Program of 'Ningbo Sci-Tech Innovation Yongjiang 2035'/ ; Yongweifa 2024-102-77//Ningbo Municipal Specialized Training Program for Young Technical Backbone Talents in Health/ ; },
mesh = {Humans ; *Resistance Training ; *Asthma/therapy/physiopathology/radiotherapy ; *Low-Level Light Therapy/methods ; Muscle Strength/radiation effects ; },
abstract = {This letter discusses Costa et al.'s randomized trial of resistance training (RT) combined with photobiomodulation therapy (PBMT) for difficult-to-control asthma (DTCA). The triple-blind study shows RT+PBMT safely improves peripheral muscle strength and exercise capacity better than RT alone. PBMT has dose-dependent effects, but optimal parameters for chronic respiratory patients remain unclear. Some clinicians have proposed standalone PBMT for DTCA patients unable to complete resistance training, but this approach has not been validated in clinical trials. The absence of a PBMT-only group limits assessment for patients unable to tolerate RT. The intervention did not improve lung function or asthma control, acting only peripherally. RT+PBMT is a useful adjuvant therapy; future studies should optimize PBMT dosing, test standalone PBMT, and examine long-term outcomes, and compare different PBMT wavelengths, energy settings and irradiation sites to refine real-world treatment protocols.},
}

Humans
*Resistance Training
*Asthma/therapy/physiopathology/radiotherapy
*Low-Level Light Therapy/methods
Muscle Strength/radiation effects

@article {pmid42429860,
year = {2026},
author = {D'Andrea, T and Benedetti, MC and Mochi, M and De Turris, V and Rosa, A and Fucile, S},
title = {Human iPSC-Derived Spinal Neurons Carrying the ALS FUS (P525L) Mutation Exhibit Lower Response to Inhibitory Neurotransmitters.},
journal = {Cellular and molecular neurobiology},
volume = {},
number = {},
pages = {},
doi = {10.1007/s10571-026-01773-z},
pmid = {42429860},
issn = {1573-6830},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disorder characterized by motoneurons degeneration. Functional studies have linked ALS to hyperexcitability and excitotoxicity, but the cause of the disease is unknown, though familial ALS cases are linked to pathogenic variants in several genes, including SOD1, TARDBP and FUS. Here we focused on the effect of the severe FUS (P525L) mutation on the functional properties of human spinal neurons derived from induced pluripotent stem cells (hiPSCs). This mutation delayed functional maturation, as revealed by the observation that mutated neurons showed alterations of membrane potential, reduced spontaneous synaptic activity, and altered action potentials at early differentiation stages. FUS (P525L) mutation was associated with a significant alteration of inhibitory signalling transmission: mutated neurons showed a significantly lower current response to GABA and glycine compared to control isogenic WT neurons of the same age. Also, glutamatergic currents exhibited a different temporal evolution in control and mutated neurons, but at a lower extent in comparison to inhibitory neurotransmitters. The decrease in the glycine-evoked currents was confirmed by the reduction of the expression of the α1 subunit of glycine receptor, measured by immunofluorescence assay. Similar functional alterations were measured in spinal neurons differentiated form a second hiPSC line, confirming the causative role of the FUS (P525L) mutation. Our data indicate that the FUS (P525L) mutation reduces the maturation rates and the function of hiPSC-derived spinal neurons, with a strong decrease of inhibitory transmission, which may affect the excitatory/inhibitory balance, possibly predisposing to excitotoxicity and neurodegeneration.},
}

@article {pmid42430091,
year = {2026},
author = {You, Y and Duan, D and Xiang, Q},
title = {The Role of PGC-1α in Neurodegenerative Diseases: Molecular Mechanisms, Translational Challenges, and Therapeutic Potential.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42430091},
issn = {1559-1182},
mesh = {Humans ; *Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism ; *Neurodegenerative Diseases/metabolism/therapy ; Animals ; Mitochondria/metabolism ; *Translational Research, Biomedical ; *Translational Science, Biomedical ; },
abstract = {Neurodegenerative diseases (NDDs) are progressive disorders in which mitochondrial dysfunction, oxidative stress, proteostasis failure, neuroinflammation, and synaptic damage progressively interact to drive neuronal vulnerability. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) links metabolic adaptation to stress-response pathways that are repeatedly disrupted in Alzheimer's disease, Parkinson's disease, Huntington's disease, polyglutamine (PolyQ) disorders, and amyotrophic lateral sclerosis. Rather than providing only an updated catalogue of studies, this review organizes the evidence into a cross-disease rheostat framework that explains why PGC-1α modulation is protective in some settings but incomplete or maladaptive in others. Current findings indicate that PGC-1α supports mitochondrial biogenesis, oxidative phosphorylation, antioxidant defense, mitophagy, autophagy, protein quality control, and inflammatory balance. However, its effects are highly context dependent. In several models, restoration of PGC-1α-related signaling improves mitochondrial function and reduces neuronal injury, whereas broad, sustained, or cell-inappropriate activation may produce limited benefit or undesirable outcomes. These observations suggest that PGC-1α is not a simple neuroprotective switch, but a flexible regulatory hub whose therapeutic value depends on cell type, isoform profile, disease stage, and activation level. Emerging strategies, including small-molecule modulators, gene delivery, antisense-based approaches, nanoparticle systems, and exercise-related interventions, remain largely preclinical and face major barriers related to CNS delivery, pathway selectivity, dose and cell-type control, peripheral safety, and validated target-engagement biomarkers. Nevertheless, clinical translation requires stronger causal validation, reliable target-engagement biomarkers, selective delivery methods, and long-term safety assessment. Future research should focus on precision-based modulation of PGC-1α to determine when and how this pathway can be safely used for disease modification. Such a careful approach may help transform PGC-1α from a broad experimental target into a clinically relevant strategy for well-defined neurodegenerative phenotypes.},
}

Humans
*Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism
*Neurodegenerative Diseases/metabolism/therapy
Animals
Mitochondria/metabolism
*Translational Research, Biomedical
*Translational Science, Biomedical

@article {pmid42430317,
year = {2026},
author = {Buczak, MK and Brignone, J and Caden Hamrick, W and Cole, KM and Bromberg, MB and Zhang, H and George, JA},
title = {Preliminary Investigation of Myoelectric Control of an Assistive Neck Exoskeleton by Individuals with Amyotrophic Lateral Sclerosis.},
journal = {IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/TNSRE.2026.3712219},
pmid = {42430317},
issn = {1558-0210},
abstract = {Neck weakness limits head control and quality of life for individuals with Amyotrophic Lateral Sclerosis (ALS). The Utah Neck Exoskeleton can restore neck motion, but current control methods-joystick and gaze tracking-have limited accessibility and reliability. These preliminary offline analyses investigate neck electromyography (EMG) as an alternative control modality from ALS patients. EMG signals were recorded from four male participants with ALS while performing neck flexion/extension, axial rotation, and lateral deviation. The resulting dataset was used to train convolutional neural networks (CNNs) per patient to classify either head position or movement direction from EMG features offline. Position classification significantly outperformed direction classification, with a mean accuracy of 82.5% ± 0.010 across participants. Performance was consistent when controlling one, two, or all three neck degrees of freedom. A subset of participants with sufficient residual motor function also completed neck movements while talking or chewing. Classification accuracy decreased during talking and chewing, although these effects were not statistically significant. Importantly however, training CNNs with diverse data that included periods of talking and chewing improved algorithm robustness across all conditions. These findings suggest that neck EMG signals can reliably predict intended head movements in ALS, even in the presence of weak and often confounding muscle activity. Offline accuracy and real-time computational speed suggest the approach is feasible for future online user-in-the-loop studies. Altogether, this pilot work advances EMG-based assistive technology for individuals with severe motor impairments, laying the groundwork for clinically viable, intuitive control systems.},
}

@article {pmid42430680,
year = {2026},
author = {Chang, CY and Price, TR and Jia, A and Cragg, JJ},
title = {Neurology® Journal Club: Duration of Current Statin Use and Amyotrophic Lateral Sclerosis Risk.},
journal = {Neurology},
volume = {107},
number = {3},
pages = {e218358},
doi = {10.1212/WNL.0000000000218358},
pmid = {42430680},
issn = {1526-632X},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/chemically induced ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects/therapeutic use ; Time Factors ; Cohort Studies ; Risk Factors ; Norway/epidemiology ; },
abstract = {This article critically appraises the study by Nakken et al., "Duration of Current Statin Use and Amyotrophic Lateral Sclerosis (ALS) Risk." Previous observational studies and Mendelian randomization studies examining statin use and ALS risk have reported mixed results. Millions of adults receive statins for cardiovascular prevention and may be concerned when neuromuscular symptoms suggestive of ALS appear. Using linked nationwide health survey and prescription data, this Norwegian population-based cohort study applied time-dependent models to evaluate statin use and subsequent ALS risk. Short-term statin use was associated with increased ALS risk, whereas long-term use was associated with lower risk. The authors interpreted this as evidence of reverse causation rather than a causal or protective effect of statins. Key strengths of the study include its large population-based design, the use of a negative control, and time-dependent Cox modeling. However, limitations inherent to observational study designs and potential residual confounding should be considered. In this article, we summarize the findings, highlight key statistical concepts, and discuss the study's major strengths and limitations.},
}

Humans
*Amyotrophic Lateral Sclerosis/epidemiology/chemically induced
*Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects/therapeutic use
Time Factors
Cohort Studies
Risk Factors
Norway/epidemiology

@article {pmid42431020,
year = {2026},
author = {Romano, C and Johar, L and Hundhausen, K and Kimonis, V},
title = {Clinical studies in 82 individuals with valosin-containing protein (VCP) associated multisystem proteinopathy and literature review.},
journal = {Neuromuscular disorders : NMD},
volume = {65},
number = {},
pages = {106469},
doi = {10.1016/j.nmd.2026.106469},
pmid = {42431020},
issn = {1873-2364},
abstract = {Valosin-containing protein (VCP) pathogenic variants cause a multisystem proteinopathy characterized by myopathy, Paget disease of bone, frontotemporal dementia, and amyotrophic lateral sclerosis (ALS). We evaluated 82 affected individuals, 14 presymptomatic carriers, and 36 unaffected first-degree relatives from 48 families to identify sensitive measures for disease monitoring. Mean age of onset was ∼42 years for myopathy, Paget disease, or ALS, and 53 years for dementia. Functional assessments included the Inclusion Body Myositis Functional Rating Scale (IBMFRS), ALSFRS-R, Fatigue Severity Scale (FSS), and six-minute walk test (6MWT). Affected individuals demonstrated progressive functional decline, with IBMFRS decreasing 1.9% annually, FSS increasing 4.4%, and 6MWT decreasing 6% annually when modeled against disease duration. Women declined more rapidly on IBMFRS but showed slower ambulatory and fatigue progression. Potential genotype-specific effects were observed, with earlier onset and shorter survival in p.Arg155Cys compared to later onset in p.Arg155His. Strong correlations among IBMFRS, FSS, and 6MWT indicate these as accessible endpoints for longitudinal monitoring and clinical trials. Rapid decline with ALS and dementia necessitates multidisciplinary support, while longer survival after myopathy or Paget onset offers a window for preventive and supportive interventions.},
}

@article {pmid42431556,
year = {2026},
author = {Singh, N and Gomes, J},
title = {Fisetin prevents deterioration of cellular functions in amyotrophic lateral sclerosis variants G262R and P438L of SQSTM1 in SH-SY5Y cells.},
journal = {Toxicology and applied pharmacology},
volume = {},
number = {},
pages = {117943},
doi = {10.1016/j.taap.2026.117943},
pmid = {42431556},
issn = {1096-0333},
abstract = {Oxidative stress is widely accepted as one of the important factors contributing to neurodegeneration, leading to fatal neurodegenerative diseases (NDD) such as Amyotrophic Lateral Sclerosis. Since flavonoids possess antioxidant properties, we investigated whether Fisetin (FS) and Quercetin (QR) protected cells from oxidative stress arising from pathogenic mutations G262R (G > A) and P438L (C > T) of SQSTM1 found in Indian ALS patients. SQSTM1 codes for p62 protein and is involved in multiple signaling pathways through its various domains. We studied changes in cell viability and cellular functions using immunoblotting, confocal microscopy, immunoprecipitation and FACS analysis in the presence and absence of FS and QR. Supplementation with FS and QR in SH-SY5Y cells expressing SQS-wild type and mutants increased cell viability and decreased ROS formation. Also, Nrf2 protein levels increased to offset oxidative stress response. In addition, we studied the effect of FS on the nuclear-cytoplasmic distribution of TDP-43 protein, which serves as a hallmark for ALS. FS corrected the nuclear-cytoplasm translocation of TDP-43 protein and decreased late apoptosis in mutants. Our study illustrates that both FS and QR shield cells from oxidative stress, and that FS imparted better protection against the pathogenic effect of SQSTM1 mutants in SH-SY5Y neuronal cells.},
}

@article {pmid42236288,
year = {2026},
author = {Chinoy, A and Soo, A},
title = {Effectiveness of Surgical Sealants in Reducing Prolonged Air Leaks After Pulmonary Resection: A Systematic Review.},
journal = {Interdisciplinary cardiovascular and thoracic surgery},
volume = {41},
number = {7},
pages = {},
doi = {10.1093/icvts/ivag164},
pmid = {42236288},
issn = {2753-670X},
mesh = {Humans ; *Pneumonectomy/adverse effects ; *Tissue Adhesives/therapeutic use/adverse effects ; *Surgical Stapling/adverse effects ; Treatment Outcome ; *Fibrin Tissue Adhesive/therapeutic use ; *Anastomotic Leak/prevention & control/etiology ; Time Factors ; Female ; },
abstract = {OBJECTIVES: Prolonged air leak (PAL) is the most common complication following pulmonary resection, leading to increased morbidity, hospital stay, and healthcare costs. Although staplers are currently the standard for lung parenchymal closure, ALs remain frequent. Surgical sealants have been introduced as adjuncts to staplers to reduce PAL, but evidence remains inconsistent. Prior systematic reviews frequently pooled together stapled and sutured resections, limiting applicability to contemporary practice. This review specifically evaluates whether surgical sealants reduce the incidence and duration of PAL when used with staplers in adult patients.

METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (CRD420251064592). A literature search was conducted in PubMed, Ovid MEDLINE, and Cochrane Library for studies published between 2005 and June 2025. Eligible studies included adult patients undergoing stapler-based pulmonary resection comparing sealants plus staplers versus staplers alone. Risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials (RoB2) and risk of bias in non-randomized studies of interventions (ROBINS-I) tools.

RESULTS: Eight studies were included. Surgical sealants studied included fibrin-based (autologous fibrin sealant (FS), FS patch, human FS) and synthetic polymers (polyethylene glycol hydrogel sealant, cyanoacrylate-based sealant). Most studies reported a statistically significant reduction in PAL incidence and/or duration with sealant use. Some also showed reduced chest tube duration and hospital stay, though not always statistically significant. One study showed worse outcomes in the sealant group. No study reported increased complications. Subgroup analyses were limited.

CONCLUSIONS: Sealants used with staplers may reduce PAL incidence and duration, particularly in high-risk patients, without increased complications. However, variability in study design and limited subgroup data weaken current evidence. Larger, standardized randomized controlled trials are needed to confirm clinical benefit and inform routine use.},
}

Humans
*Pneumonectomy/adverse effects
*Tissue Adhesives/therapeutic use/adverse effects
*Surgical Stapling/adverse effects
Treatment Outcome
*Fibrin Tissue Adhesive/therapeutic use
*Anastomotic Leak/prevention & control/etiology
Time Factors
Female

@article {pmid42421808,
year = {2026},
author = {Ang, NKJ and Lim, JQ and Lye, TJY and Tan, DMY and Lim, CH},
title = {Endoscopic salvage for afferent loop syndrome: the antegrade lumen-apposing metal stent technique.},
journal = {VideoGIE : an official video journal of the American Society for Gastrointestinal Endoscopy},
volume = {11},
number = {7},
pages = {298-303},
pmid = {42421808},
issn = {2468-4481},
abstract = {BACKGROUND AND AIMS: Afferent loop syndrome (ALS) is a rare postgastrectomy condition with biliopancreatic limb obstruction. Revision surgery carries high morbidity in patients with hostile anatomy. We aimed to demonstrate the feasibility of a double-scope, antegrade EUS-guided lumen-apposing metal stent (LAMS) enteroenterostomy as an endoscopic alternative in the management of complex ALS.

METHODS: A patient with extensive prior gastric surgery presented with ALS. With a double-scope antegrade technique, a pediatric gastroscope (GIF-XP190 N; Olympus, Tokyo, Japan) was used to cannulate the afferent limb to place a guidewire, and a linear echoendoscope (GF-UCT180; Fujifilm, Tokyo, Japan) was advanced into the blind loop. The pediatric gastroscope was reintroduced into the efferent limb, which was water-distended to approximately 3 cm in diameter to achieve sonographic apposition. Under combined EUS and fluoroscopic guidance, a 15- × 15-mm electrocautery-enhanced LAMS (Boston Scientific, Marlborough, Mass, USA) was deployed to create an enteroenterostomy.

RESULTS: Postdeployment contrast confirmed optimal position and immediate patency without leak. Symptoms resolved rapidly; the patient resumed a diet within days and gained weight. Abdominal radiography showed progressive LAMS expansion without adverse events.

CONCLUSIONS: Double-scope antegrade EUS-guided LAMS placement safely decompressed the afferent limb in our patient, restoring enteral flow and avoiding high-morbidity reoperation. This technique merits consideration within multidisciplinary care and warrants larger comparative studies to define long-term outcomes.},
}

@article {pmid42422319,
year = {2026},
author = {Nie, J and Peters, S and Ge, CB and Portengen, L and Rothman, N and Hu, W and Ou, R and Wei, Q and Zhang, L and Hou, Y and Lan, Q and Shang, HF and Vermeulen, R},
title = {Smoking and the risk of neurodegenerative diseases in a Chinese case-control study.},
journal = {BMJ neurology open},
volume = {8},
number = {2},
pages = {e001728},
pmid = {42422319},
issn = {2632-6140},
abstract = {BACKGROUND: While smoking is inversely associated with Parkinson's disease (PD) risk, its relationship with amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA) remains unclear, particularly in Asian populations. We investigated these associations in a Chinese case-control study.

METHODS: We recruited newly diagnosed ALS (n=430), MSA (n=271), PD (n=523) cases and hospital-based controls (n=1033) in Sichuan, China. Logistic regression models were used to evaluate associations between smoking and disease risks, adjusting for demographic, lifestyle and occupational factors.

RESULTS: Compared with never-smokers, the adjusted ORs and 95% CIs of ALS for current and former smokers were 1.00 (0.61 to 1.65) and 1.79 (1.01 to 3.17), respectively. For MSA, ORs were 1.27 (0.73 to 2.23) for current smokers and 2.54 (1.41 to 4.60) for former smokers. Individuals who quit within 4 years before diagnosis showed the highest risk of ALS (OR=1.93, 95% CI 0.96 to 3.88) and MSA (OR=2.09, 95% CI 1.11 to 3.93). For both ALS and MSA, no consistent trend was found with increasing smoking duration or pack-years. In contrast, ever-smokers had a significantly lower PD risk (OR=0.49, 95% CI 0.33 to 0.71), particularly current smokers (OR=0.30, 95% CI 0.19 to 0.48). Longer smoking duration and higher cumulative smoking were also linked to PD risk with clear negative exposure-response patterns (P trend=0.039 and 0.029, respectively).

CONCLUSIONS: Consistent with findings in non-Asian populations, smoking was inversely associated with PD risks in the Chinese population. For ALS and MSA, we found evidence suggestive of positive relationships with cigarette smoking, but no clear exposure-response relationships were observed.},
}

@article {pmid42422504,
year = {2026},
author = {Tomikawa, E and Takahashi, K and Hattori, H and Arai, T and Kawai, M and Nishimura, K and Goto, Y and Yagi, R and Miyamoto, Y and Miyoshi, T},
title = {Multinucleation and cytotoxicity induced by multikinase inhibition in highly proliferative cells.},
journal = {Journal of toxicologic pathology},
volume = {39},
number = {3},
pages = {93-101},
pmid = {42422504},
issn = {0914-9198},
abstract = {Phenotypic screening using motor neurons derived from the induced pluripotent stem (iPS) cell of a patient with amyotrophic lateral sclerosis led to the identification of Compound X, a novel agent with potent neuroprotective activity that is hypothesized to act by inhibiting hematopoietic progenitor kinase/germinal center kinase-like kinase (HGK). Unlike known HGK inhibitors, including Prostetin and GNE-495, Compound X and related Compounds Y and Z exhibited broader multi-kinase-inhibition profiles, including the strong inhibition of Aurora B kinase and strong-to-moderate inhibition of Src-family kinases in kinase panel screening. Owing to their roles in cytokinesis, we performed in vitro micronucleus tests to assess their genotoxicity. Compounds X, Y, and Z induced the multinucleation of cells at rates of 88.8, 71.5, and 91.8%, respectively, whereas Prostetin and GNE-495 resulted in rates of 0.5 and 1.3%, respectively, which were comparable to the control. A 5-day repeated-dose oral toxicity study of Compound X using mice, at doses of 125, 250, and 500 mg/kg/day, revealed decreased locomotor activity, hypothermia, and mortality at 500 mg/kg/day. Histopathology showed necrosis/hemorrhage in bone marrow cells; single-cell necrosis in the thymus, spleen, and mesenteric lymph nodes; nuclear pleomorphism and single-cell necrosis/necrosis in the gastrointestinal mucosa; and karyomegaly and a reduction in testicular germ cells. These toxicopathological findings suggest that Compound X induces nuclear pleomorphism and necrosis in highly proliferative cells. Although Compound X strongly suppressed HGK, its toxicity may be associated with broader multikinase inhibition, which is consistent with the finding that Prostetin and GNE-495 do not induce multinucleation in vitro.},
}

@article {pmid42422879,
year = {2026},
author = {Grassmann, G and Amadei, M and Lardieri, A and Montemiglio, LC and Passeri, AA and Mattarelli, M and Di Rienzo, L and Miotto, M and Ruocco, G and Milanetti, E},
title = {Investigating the effect of progressive truncations at the ALS-linked protein TDP-43 RRM2 on its aggregation mechanism.},
journal = {Frontiers in molecular biosciences},
volume = {13},
number = {},
pages = {1849627},
pmid = {42422879},
issn = {2296-889X},
abstract = {Amyotrophic lateral sclerosis is a neurodegenerative disease characterized by inclusions of TDP-43 protein. C-terminal fragments (CTFs) of TDP-43, generated by cleavage within its second RNA recognition motif (RRM2), have been found forming aggregates in patients. Aggregation has often been attributed to the C-terminal domain, but increasing evidence indicates that RRM2 fragments contribute to pathological inclusions. We performed extensive molecular dynamics simulations to investigate the changes resulting from the truncation that could lead to aggregation. We analyzed the full RRM2 domain (fRRM2, residues 192-261) and two fragments commonly observed in CTFs (tRRM2A, residues 220-261, and tRRM2B, residues 209-261). We found that truncation results in distinct aggregation-prone states. tRRM2B appears to rely on β -sheet elements associated with amyloid-like aggregation, whereas tRRM2A exhibits higher structural variability and a reduced β -content, suggesting a phase separation-like aggregation mechanism. We further simulated an extended fragment of tRRM2A, tRRM2A-l (residues 220-269). Although its predicted aggregation propensity remains largely unchanged, tRRM2A-l exhibits increased structural flexibility, and a stronger exposure of Nuclear Export Signal residues. Our results indicate that subtle differences in RRM2 fragment length influence potential misfolding pathways. Future studies and therapeutic strategies to prevent TDP-43 aggregation should carefully consider the specific domain adopted.},
}

@article {pmid42422903,
year = {2026},
author = {Singh, T and Khare, SK and Siddhanta, S},
title = {Spectroscopic discrimination of bacterial species of variable pathogenicity through explainable machine learning.},
journal = {Nanoscale},
volume = {},
number = {},
pages = {},
doi = {10.1039/d6nr00689b},
pmid = {42422903},
issn = {2040-3372},
abstract = {Rapid and accurate identification of bacterial pathogens and their degree of pathogenicity is essential for guiding antimicrobial therapy. Current culture-based methods require a timeframe of at least 24-48 h for species-level identification alone, which often leads to substantial disease progression and increases the propensity of antimicrobial resistance (AMR). Surface-Enhanced Raman Spectroscopy (SERS) shows promise in mitigating these drawbacks by providing a fast, non-invasive, label-free method to capture the biochemical fingerprints of bacteria achievable under clinical settings. However, the molecular complexity of SERS spectra, which has been an impediment for conventional data analysis, demands robust computational frameworks for reliable species-level identification. Here, we employ a comprehensive SERS analysis scheme with supervised machine learning and explainable artificial intelligence (XAI) to discriminate five clinically relevant pathogens, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and Enterococcus faecalis, and to probe their degree of pathogenicity from a biomarker perspective. Among the tested models - Support Vector Machine (SVM), k-Nearest Neighbour (kNN), Random Forest (RF), and a 1D Convolutional Neural Network (CNN) - CNN achieved near-perfect classification accuracy, capturing subtle and spectrally relevant variations often inaccessible to traditional algorithms. Notably, the 1D-CNN also achieved 100% discrimination between MRSA and methicillin-sensitive S. aureus - two strains of the same species differing only in resistance phenotype. To ensure transparent decision-making and eliminate the black-box nature of machine learning models, SHapley Additive exPlanations (SHAP) analysis was applied to both RF and CNN models, which facilitated the convergence of both frameworks on the same discriminatory Raman regions, revealing conserved biochemical determinants of species identity. Complementary MCR-ALS decomposition further resolved the spectra into interpretable biochemical components and provided the rubric for biochemical differentiation. Together, this study aims to demonstrate an end-to-end explainable workflow that couples SERS with interpretable AI, offering a rapid, transparent approach for pathogenic disease diagnosis.},
}

@article {pmid42423631,
year = {2026},
author = {Chu, HS and Oh, J},
title = {Identifying Gastrostomy Care and Home Gastrostomy Tube Feeding-Related Educational Content for Patients With Amyotrophic Lateral Sclerosis and Their Family Caregivers: A Delphi Panel With Professional Stakeholders.},
journal = {Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates},
volume = {},
number = {},
pages = {},
pmid = {42423631},
issn = {1538-9766},
abstract = {Enteral nutrition is delivered through a gastrostomy tube to provide nutritional support to patients with amyotrophic lateral sclerosis (ALS) who have developed severe dysphagia at home. Complications may arise from gastrostomy and enteral nutrition when family caregivers do not provide adequate care. This study identifies key areas of educational content that can improve the care of patients with ALS requiring gastrostomy and home enteral nutrition. We conducted a modified three-round e-Delphi survey with health care experts to clarify their perspectives on the educational content regarding gastrostomy and home enteral nutrition disseminated among patients with ALS and their family caregivers. The experts provided their opinions on specific educational content areas, and their responses were analyzed to identify areas of consensus and divergence. Accordingly, in Rounds 1-3 of the survey, 16 experts, including registered nurses (n = 6), advanced practice registered nurses (n = 3), clinical neurologists (n = 3), and dieticians (n = 4), participated. In Round 3, four categories and 39 educational components reached consensus. The results provide a framework for developing educational nursing interventions for family caregivers of patients with ALS receiving home enteral nutrition through gastrostomy tubes and for defining the essential elements of the educational content of such interventions.},
}

@article {pmid42423712,
year = {2026},
author = {Lu, J and Wang, XTX},
title = {Tackling challenges in large language model-based data extraction via context engineering: A commentary on Jansen et al. (2025).},
journal = {Psychological bulletin},
volume = {152},
number = {4},
pages = {404-419},
doi = {10.1037/bul0000520},
pmid = {42423712},
issn = {1939-1455},
support = {//National Natural Science Foundation of China/ ; },
mesh = {*Large Language Models ; Humans ; },
abstract = {Systematic reviews, particularly meta-analyses, involve crucial yet labor-intensive and error-prone stages of data extraction. Recent advances in large language models (LLMs) have unlocked new avenues for automating this process, potentially enhancing both efficiency and reliability. Recently, Jansen et al. (2025) systematically evaluated the accuracy and error patterns of LLM-assisted data extraction across 22 reviews published in Psychological Bulletin. Their findings indicated that while achieving acceptable-to-good accuracy for some variables describing study characteristics, LLMs struggled with numerical variables, especially those related to effect sizes. In this commentary, we discuss the current challenges of automated data extraction and potential pathways to improve the work reported in Jansen et al.'s study. We situate our discussion within the framework of context engineering, aiming to refine the information provided to LLMs through dynamic optimization strategies tailored to specific tasks. We identify five key challenges that reflect either LLMs' unique patterns or standard practices in research synthesis: parsing semistructured data, understanding long contexts, performing arithmetic induction, engaging in complex reasoning, and ensuring the reproducibility of coding protocols. We then outline potential solutions inspired by context engineering implementations such as retrieval-augmented generation and tool-integrated reasoning. For illustration, we present four examples: extracting semistructured data via optical character recognition, reliably computing effect sizes through function calls, performing adaptive retrieval with LLM-based agents, and iteratively improving outputs through self-refinement. We conclude by calling for future research in automated data extraction to advance beyond simple instruction-following paradigms toward more reliable forms of context engineering. (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}

*Large Language Models
Humans

@article {pmid42423935,
year = {2026},
author = {Elvish, TM and Trowell, D and Bonacci, J and Turner, KJ and Kremer, P and Millett, EL and Pickering, C and Saunders, N},
title = {Biological and Race Strategy Characteristics Investigated in Elite Endurance Track Running: A Systematic Review.},
journal = {Sports medicine (Auckland, N.Z.)},
volume = {},
number = {},
pages = {},
pmid = {42423935},
issn = {1179-2035},
abstract = {BACKGROUND: Understanding biological and race strategy characteristics of endurance track runners competing at benchmark events provides high-performance athletics programmes and coaches with valuable insight into what is required to succeed.

OBJECTIVES: The aim of this systematic review was to identify biological and race strategy characteristics investigated in elite able-bodied endurance track runners (Aim 1) and, where examined, highlight whether these characteristics could differentiate performance success within this elite cohort (Aim 2).

METHODS: For this systematic review, searches across EBSCOhost (Academic Search Complete, CINAHL Complete, MEDLINE Complete and SPORTDiscus), Scopus, PubMed and Web of Science were completed until May 2023. Searches also involved World Athletics Research Centre, New Studies in Athletics, handsearching and scanning of reference lists of included studies. Eligible studies were required to be published in English and have investigated performance-related biological or race strategy characteristics among senior able-bodied endurance track runners (800-10,000 m) capable of competing at benchmark events. Risk of bias of included studies was evaluated based on Sarmento et al.'s 16-item checklist. The review separated middle-distance runners (MDR) and long-distance runners (LDR), to account for the differing performance demands of these event groups. Studies were considered to address Aim 2 if they assessed for statistical associations between athlete characteristics and overall performance (e.g. race time) or compared characteristics between athletes with different competitive results (e.g. medallists and non-medallists).

RESULTS: Thirty-nine articles were included in this review, with 23 and 21 of these articles relevant to MDR and LDR, respectively. The most commonly reported characteristics were related to anthropometry (7 studies for MDR and LDR), biomechanics (7 studies for LDR), pacing (9 and 10 studies for MDR and LDR, respectively), qualification pattern (6 studies for MDR) and benchmark performance relative to athlete history (9 and 7 studies for MDR and LDR, respectively). However, the diversity of biological characteristics investigated and the generally small sample sizes makes it difficult to define an optimal biological profile for elite endurance runners. In contrast, race strategy characteristics investigated often included larger sample sizes providing a better understanding, especially in relation to pacing and for middle-distance events qualification patterns. Further, studies investigating whether characteristics differentiate performance among elite endurance track runners indicate that the most successful runners consistently demonstrate superior finishing ability. This is reflected in faster speeds during at least one 100-m segment of the final 400 m of the race and the ability to complete the final segments of the race at a pace close to, or faster than, their season best or 32-month best performance. In long distance events, better performance was associated with faster personal best times across the previous 32 months, indicating that having a high-ranking recent best time may be a prerequisite for succeeding at benchmark events. Faster 10,000-m runners had lower body mass and smaller arm and calf circumferences, suggesting a potential advantage of having lower non-functional mass. In middle distance events, success was associated with achieving superior qualification positions in the heats and semi-final, highlighting the importance of tactical positioning and efficient progression through qualification rounds. Faster male 800-m runners had a technique characterised by longer contact times and more compliant spring mechanics which may allow athletes to maintain or elevate speed during the sprint finish.

CONCLUSION: Biological and race strategy characteristics that profile elite endurance track runners and that, in several studies, showed association with performance success were discussed. These findings may assist high-performance athletics programmes and coaches in informing athlete development and investment. However, further research is required to establish a more holistic understanding of the biological profile of elite endurance track athletes and to determine which biological and race strategy characteristics may differentiate performance reliably among these elite runners.},
}

@article {pmid42424231,
year = {2026},
author = {Szyłak, E and Czarnowska, A and Kulczyńska-Przybik, A and Kopitelow, J and Mroczko, B and Kochanowicz, J and Kułakowska, A},
title = {Neurofilament Light Chain as a Biomarker in Neurology.},
journal = {European neurology},
volume = {},
number = {},
pages = {1-18},
doi = {10.1159/000552933},
pmid = {42424231},
issn = {1421-9913},
abstract = {Neurofilament light chain (NfL) has emerged as a highly sensitive biomarker of neuroaxonal injury across diverse neurological disorders. This review synthesizes current evidence regarding its diagnostic, prognostic, and therapeutic-monitoring utility, while outlining major clinical limitations and emphasizing the complementary role of glial fibrillary acidic protein (GFAP). NfL concentrations increase following axonal damage and correlate with inflammatory activity, lesion burden, and long-term disability progression in multiple sclerosis. Elevated levels also reflect neurodegeneration in Alzheimer's disease, predict disease severity and survival in amyotrophic lateral sclerosis, and are associated with motor and cognitive decline in Parkinson's disease and multiple system atrophy. In acute neurological conditions, including traumatic brain injury and stroke, NfL serves as a robust indicator of the extent of neuronal injury. Interpretation is constrained, however, by substantial physiological variability related to age, renal function, body mass index, and comorbidities, limiting the utility of absolute cut-off values. GFAP provides complementary information by capturing astrocytic damage, and the GFAP/NfL ratio may aid in differentiating multiple sclerosis from neuromyelitis optica spectrum disorder. Integration of NfL with multimodal biomarkers- such as GFAP, tau proteins, proteomic and metabolomic signatures, and advanced neuroimaging-may enhance diagnostic specificity and prognostic accuracy. Future research priorities include establishing age-adjusted reference intervals, validating longitudinal thresholds, and incorporating NfL into therapeutic monitoring frameworks. Advances in these areas are expected to improve diagnostic precision and support broader clinical implementation of NfL.},
}

@article {pmid42425084,
year = {2026},
author = {Hosokawa, M and Kawakami, R and Imami, K and Kurosawa, R and Yoshizawa, T and Ishihama, Y and Imamura, T and Hagiwara, M and Takeuchi, A},
title = {RNA-dependent SFPQ condensates coordinate multidimensional regulation of extra-long neuronal genes.},
journal = {Cell chemical biology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.chembiol.2026.06.004},
pmid = {42425084},
issn = {2451-9448},
abstract = {The mammalian brain uniquely expresses a large repertoire of extra-long genes critical for neuronal development and function, yet these transcripts are particularly vulnerable to dysregulation linked to neurological disorders, such as autism spectrum disorder and amyotrophic lateral sclerosis. The molecular mechanisms that ensure their stable expression remain poorly understood. Here, we show that the RNA-binding protein SFPQ forms meshwork-like biomolecular condensates that scaffold a multidimensional gene regulatory complex essential for long-gene expression. Super-resolution microscopy and functional perturbation assays demonstrate that disruption of SFPQ condensates impairs both extra-long gene expression and splicing. Proximity-dependent biotin labeling combined with mass spectrometry (BioID-MS) reveals that SFPQ condensates recruit transcriptional elongation factors, splicing regulators, and chromatin remodelers. Notably, many of these interactors overlap with autism-associated genes, suggesting direct disease relevance. These findings define a higher-order nuclear architecture organized by SFPQ and provide mechanistic insight into long-gene transcriptopathies underlying neurological disorders.},
}

@article {pmid42425146,
year = {2026},
author = {Hoppe, JM and Deniz, S and Czihal, M and Lottspeich, C},
title = {Contrast-Enhanced Ultrasound versus Contrast-Enhanced Computed Tomography in the Detection of Renal and Splenic Infarctions.},
journal = {Ultraschall in der Medizin (Stuttgart, Germany : 1980)},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2908-8526},
pmid = {42425146},
issn = {1438-8782},
abstract = {PURPOSE: Intra-abdominal organ infarctions require prompt imaging for diagnosis. Contrast-enhanced computed tomography (CECT) is considered the gold standard but involves radiation, iodinated contrast, and logistical challenges in critically ill patients. Contrast-enhanced ultrasound (CEUS) enables real-time assessment of microvascular perfusion without ionizing radiation. The aim of this study was to evaluate the diagnostic performance of CEUS compared to CECT for detecting intra-abdominal organ infarctions.

MATERIALS AND METHODS: This retrospective observational study included patients treated at a tertiary care center (2010-2024) who underwent both CEUS and CECT for suspected intra-abdominal organ infarction. With CECT as reference standard, diagnostic performance parameters and agreement (Cohen's kappa) were calculated.

RESULTS: 24 patients (median age 60 years; 12 female) were included. CECT confirmed organ infarction in 16/24 patients (66.7%). CEUS correctly identified 15 of these cases (Sensitivity 93.8%; 95% confidence interval [CI]: 71.7-98.9%). Specificity was 75.0% (95% CI: 40.9-92.9%), with two false-positive CEUS findings. Positive and negative predictive values were 88.2% (95% CI: 65.7- 96.7%) and 85.7% (95% CI: 48.7-97.4%), respectively. Agreement of CECT and CEUS was substantial (Cohen's κ = 0.71). Wedge-shaped perfusion defects were identified in 93.8% of CT-confirmed infarctions on both modalities.

CONCLUSION: CEUS demonstrates high sensitivity and good agreement with CECT for the detection of intra-abdominal organ infarctions. CEUS represents a valuable imaging modality, particularly when CECT is contraindicated or not available. Prospective studies are warranted to further define its role in clinical practice. Zielsetzung: Intraabdominelle Organinfarkte erfordern eine rasche bildgebende Diagnostik. Die kontrastmittelverstärkte Computertomographie (CECT) gilt als Goldstandard, ist jedoch mit Strahlenexposition, jodhaltigen Kontrastmitteln sowie logistischen Herausforderungen bei kritisch kranken Patienten verbunden. Der kontrastmittelverstärkte Ultraschall (CEUS) ermöglicht eine Echtzeitbeurteilung der Perfusion ohne ionisierende Strahlung. Ziel dieser Studie war die Evaluation der diagnostischen Leistungsfähigkeit der CEUS zur Detektion intraabdomineller Organinfarkte im Vergleich zur CECT.

MATERIAL UND METHODEN: In diese retrospektive Beobachtungsstudie (2010-2024) wurden Patientinnen und Patienten an einem tertiären Versorgungszentrum eingeschlossen, bei denen sowohl eine CEUS- als auch eine CECT-Untersuchung bei Verdacht auf intraabdominelle Organinfarkte durchgeführt wurde. Mit der CECT als Referenzstandard wurden die diagnostischen Testparameter und Übereinstimmung (Cohen's kappa) berechnet. Ergebnisse: 24 Patientinnen und Patienten wurden eingeschlossen (Medianalter 60 Jahre; 12 weiblich). Die CECT bestätigte in 16/24 Fällen (66,7%) einen Organinfarkt. Der CEUS identifizierte 15 Fälle korrekt (Sensitivität 93,8%, 95% Konfidenzintervall [KI]: 71,7-98,9%). Die Spezifität betrug 75,0% (95% KI: 40,9-92,9%) bei zwei falsch-positiven CEUS-Befunden. Der positive und negative prädiktive Wert betrugen 88,2% (95% KI: 65,7- 96,7%) respektive 85,7% (95% CI: 48,7-97,4%). Die Übereinstimmung zwischen CECT und CEUS war substantiell (Cohen's κ = 0,71). Keilförmige Perfusionsdefekte wurden in 93,8% der bestätigten Infarkte in beiden Modalitäten identifiziert. Schlussfolgerung: Der CEUS zeigt eine hohe Sensitivität und eine gute Übereinstimmung mit der CECT bei der Detektion intraabdomineller Organinfarkte. Der CEUS stellt für diese Fragestellung eine wertvolle Bildgebungsmodalität dar, insbesondere wenn CECT kontraindiziert oder nicht verfügbar ist. Prospektive Studien sind erforderlich, um seine Rolle in der klinischen Praxis weiter zu definieren.},
}

@article {pmid42425169,
year = {2026},
author = {Yu, W and Zhao, B and Ma, M and Gao, N and Yun, Y and Sun, X and Shao, K and Lin, P and Li, W and Zhao, Y and Yu, D and Zhao, C and Liu, F and Yan, C and Liu, S},
title = {Sex-associated neuroinflammatory and astrocytic responses in amyotrophic lateral sclerosis: evidence from clinical cohorts and a TDP-43 N390D mouse model.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {106884},
doi = {10.1016/j.bbi.2026.106884},
pmid = {42425169},
issn = {1090-2139},
abstract = {BACKGROUND: Sex differences are increasingly recognized as important modifiers of neuroimmune processes in neurodegenerative disorders. However, the sex-associated clinical phenotypes and underlying neuroinflammatory mechanisms in amyotrophic lateral sclerosis (ALS) remain poorly understood. This study integrated multimodal clinical assessments, cerebrospinal fluid (CSF) neuroimmune biomarkers, neuroimaging-based glymphatic metrics, and complementary animal analyses to characterize shared and sex-associated alterations in male and female ALS patients.

METHODS: Two independent cohorts including 158 newly diagnosed ALS patients and 112 healthy controls (HCs) underwent evaluations of motor function, cognition, sleep disturbances, and emotional symptoms. Glymphatic function was assessed using choroid plexus volume (CPV), diffusion-derived analysis along the perivascular space (ALPS) index, and white-matter free-water (FW) fraction. In the original cohort, 12 CSF biomarkers spanning astrocytic activation, neuroinflammation, TDP-43 pathology, synaptic dysfunction, and axonal injury were quantified, and glial fibrillary acidic protein (GFAP), interleukin-6 (IL-6), and interleukin-18 (IL-18) were further examined in an independent verification cohort. Complementary neuroimmune alterations were further examined in TDP-43 N390D knock-in mice using ELISA and immunofluorescence.

RESULTS: Male ALS patients showed markedly elevated CSF GFAP, IL-6, and IL-18 compared with female ALS patients and HCs after false discovery rate correction (q < 0.05). Female ALS patients exhibited increased CSF IL-6 versus HCs, whereas GFAP and IL-18 levels were unchanged. Female ALS patients also demonstrated more severe depressive symptoms and post-traumatic stress disorder than male ALS patients and HCs (p < 0.05). Both sexes displayed glymphatic impairment characterized by increased CPV and FW and reduced ALPS index, as well as pronounced sleep disturbances relative to HCs (all p < 0.05), with no clear sex-related differences. Complementary animal data showed that, at a fixed chronological age, male TDP-43 N390D mice exhibited more severe motor impairment accompanied by higher brain levels of GFAP, IL-6, and IL-18 and more prominent astrocyte-associated IL-6 and IL-18 signals than female mutant mice. Although microglial activation was also observed in TDP-43 N390D mice, no clear sex-related difference was detected at the sampled age.

CONCLUSIONS: This multimodal clinical-translational study reveals sex-associated neuroinflammatory heterogeneity in ALS. Male patients exhibit a more pronounced GFAP-, IL-6-, and IL-18-related inflammatory profile, whereas female patients display more prominent affective disturbances. Glymphatic dysfunction and sleep impairment emerge as common pathological pathways across sexes. These findings highlight sex as a crucial biological variable shaping ALS heterogeneity and underscore the importance of incorporating sex-stratified analyses in future ALS neuroimmune research and clinical trials.},
}

@article {pmid42425598,
year = {2026},
author = {Pucciarelli, DM and Patel, R and Sawicki, S and Jain, S and Saulino, P},
title = {Unusual presentation of amyotrophic lateral sclerosis years after a motor-vehicle collision.},
journal = {BMJ case reports},
volume = {19},
number = {7},
pages = {},
doi = {10.1136/bcr-2026-272139},
pmid = {42425598},
issn = {1757-790X},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology/complications ; Female ; Middle Aged ; *Accidents, Traffic ; Diagnosis, Differential ; *Muscle Weakness/etiology ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a rare disease caused by the destruction of motor neurons, typically presenting with unilateral lower motor neuron and upper motor neuron symptoms. Here, we report the case of a female in her mid-60s with a complex history of lower extremity weakness following a motor-vehicle collision 3 years before her current presentation with a subacute complaint of right-sided leg weakness. With an atypical symptom course consisting of resolved and recurrent weakness of her left leg, the patient had multi-level chronic, evolving spinal-column damage, severe weight loss, newly discovered rectal neoplasm and longstanding psychiatric pathology. With symptoms concerning for both medical and psychosomatic explanations, several potentially compounded aetiologies were considered. Here, we discuss important considerations for fluctuating chronic and subacute neurological complaints with a broad differential diagnostic spectrum and how a macro-perspective of symptoms over years can aid in the diagnosis of a challenging ALS presentation.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology/complications
Female
Middle Aged
*Accidents, Traffic
Diagnosis, Differential
*Muscle Weakness/etiology

@article {pmid42426573,
year = {2026},
author = {Zhan, Y and Luo, Y and Lu, H and Lu, Y and Zhao, S and Pan, L and Liu, M},
title = {TSR and peroxidase genes confer resistance to fenoxaprop-P-ethyl and mesosulfuron-methyl in Alopecurus aequalis.},
journal = {Pest management science},
volume = {},
number = {},
pages = {},
doi = {10.1002/ps.71103},
pmid = {42426573},
issn = {1526-4998},
support = {//Modern Agricultural Industrial Technology System of Hunan Province (grants numbers 2022-31)/ ; //the National Key R&D Program of China (No. 2023YFD1401100)/ ; //China Agriculture Research System (CARS-01)/ ; },
abstract = {BACKGROUND: Alopecurus aequalis poses severe threat to global wheat production due to evolving resistance to acetyl-CoA carboxylase (ACCase)- and acetolactate synthase (ALS)-inhibiting herbicides. In this study, the resistance mechanisms of a field-evolved resistant population (R) were systematically investigated using dose-response bioassays, target-site gene sequencing, inhibitor assays, antioxidant enzyme activity measurements, RNA sequencing (RNA-seq), quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), and yeast functional validation.

RESULTS: Dose-response results revealed that the R population exhibited moderate resistance to fenoxaprop-P-ethyl (RI = 9.58) and low-level resistance to mesosulfuron-methyl (RI = 3.07). Cross-resistance testing indicated that the R population was resistant to other ACCase-inhibiting herbicides (haloxyfop-P-methyl, clodinafop-propargyl, clethodim, and pinoxaden) and the ALS-inhibiting herbicide rimsulfuron. Target-site sequence analysis identified two mutations in the R population: Ile-1781-Leu (ACCase) and Pro-197-Ser (ALS1). Pretreatment with the cytochrome P450 and GST inhibitor did not reverse resistance to fenoxaprop-P-ethyl or mesosulfuron-methyl. Compared to the susceptible (S) population, the R population had significantly lower H2O2 content and higher activities of peroxidase (POD) and catalase (CAT), indicating an enhanced reactive oxygen species (ROS) scavenging capacity. RNA-seq and qRT-PCR analyses identified three POD-annotated contigs (PODSPC4, POD12-1, POD12-2) that were upregulated in the R population. Yeast heterologous expression validated that AaPOD12-1 and AaPOD12-2 significantly increased yeast resistance to fenoxaprop-P-ethyl and mesosulfuron-methyl.

CONCLUSION: These results demonstrate that resistance in the R population is co-mediated by target-site mutations and non-target-site resistance involving enhanced ROS scavenging, with AaPOD12-1 and AaPOD12-2 representing the first functionally characterized antioxidant enzyme genes associated with herbicide resistance in A. aequalis. © 2026 Society of Chemical Industry.},
}

@article {pmid42426879,
year = {2026},
author = {Marynen, F and van Bijsterveld, MG and Van Loon, K and Kempenaers, S and Buelens, S and Roosen, J and Fieuws, S and van der Horst, ICC and van Mook, WN and Dewolf, P},
title = {Evaluating the impact of implementing an ECPR protocol on prehospital resuscitation quality: a randomized controlled simulation study.},
journal = {Advances in simulation (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1186/s41077-026-00458-3},
pmid = {42426879},
issn = {2059-0628},
support = {R-aiders Grant (2023)//Belgian Society of Emergency and Disaster Medicine (BESEDIM)/ ; },
abstract = {BACKGROUND: Extracorporeal Cardiopulmonary Resuscitation (ECPR) is increasingly considered for prehospital cardiac arrest management; however, its impact on resuscitation performance remains unclear. This study aimed to determine whether integrating an ECPR protocol into prehospital cardiac arrest care affects the quality of resuscitation compared to application of the standard Advanced Life Support (ALS) protocol.

METHODS: A randomized controlled simulation study was conducted at the University Hospital Leuven in Belgium using standardized pre-hospital cardiac arrest scenarios. Participants, who were physicians functioning as part of resuscitation teams, were randomized into intervention and control groups. The study included a pre- and post-intervention phase. In the pre-phase, all participants followed the standard ALS protocol. Only the intervention group received training in the additional ECPR protocol between the phases. In the post-phase, the intervention group combined this protocol with standard ALS, whereas the control group continued with ALS alone. The primary outcome was overall resuscitation quality, which was assessed using the modified Peltonen score. The secondary outcomes included occurrence and timing of critical resuscitation actions.

RESULTS: A total of 40 physicians participated in the study. Resuscitation quality was not affected by the ECPR protocol; the modified Peltonen score showed no difference in the pre-post change between the groups (0.02, CI: -0.15; 0.19, p = 0.83). However, secondary outcomes showed delayed actions related to the identification and management of the presumed cause of cardiac arrest in the intervention group, such as significantly later verbal suggestions to initiate causal treatments including PCI or thrombolysis.

CONCLUSIONS: In this simulation study, combining a prehospital ECPR protocol with standard ALS resulted in resuscitation performance comparable to ALS alone. Nonetheless, the protocol was associated with delayed diagnostic and therapeutic actions concerning the reversible causes of cardiac arrest, highlighting the need for ECPR training that integrates diagnostic and therapeutic vigilance with procedural execution.

TRIAL REGISTRATION: Clinical Trial Center UZ Leuven, S65846 - September 2021.},
}

@article {pmid42427030,
year = {2026},
author = {Tan, X and Sun, S and Yan, Y and Li, W and Ding, N and Xu, L and He, L and Zhang, Y and Chen, W and Zheng, Y and Li, L},
title = {C9orf72-associated poly-GR in skeletal muscle leads to neuromuscular junction deficits and muscle atrophy.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2026.07.002},
pmid = {42427030},
issn = {1525-0024},
abstract = {Hexanucleotide repeat expansions in C9orf72 produce dipeptide repeat (DPR) proteins that are widely expressed, including the nervous system and skeletal muscle. Among these DPRs, arginine-containing proteins, poly-GR and poly-PR are toxic in the nervous system, but whether DPRs in skeletal muscle contribute to ALS pathogenesis is unclear. Here, we show that muscle-restricted expression of poly-GR drives motor deficits in mice, including muscle atrophy and neuromuscular junction (NMJ) deficits. Poly-GR in muscle interacted with the NMJ key organizer MuSK and promoted MuSK degradation, disrupting postsynaptic structure and impairing neuromuscular transmission. Importantly, a MuSK agonist antibody (X-17) stabilized NMJs and rescued neuromuscular transmission. Moreover, poly-GR in muscle activated the integrated stress response (ISR), elevating eIF2α phosphorylation and broadly suppressing protein translation. ISR inhibition with ISRIB restored translation and MuSK protein levels, and ameliorated both muscle atrophy and NMJ deficits. These findings demonstrate that skeletal muscle actively contributes to C9orf72-ALS pathology. Targeting muscle with ISRIB offers a therapeutic strategy to preserve motor function in C9orf72-ALS.},
}

@article {pmid42414791,
year = {2026},
author = {Gray, C and Hou, CG and Brayton, CE and Shepardson, RL and Leung, LB},
title = {Optimization of Virtual and In-Person Care Coordination Between VA Primary Care and Mental Health Teams: A Qualitative Study.},
journal = {Journal of general internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.1007/s11606-026-10617-x},
pmid = {42414791},
issn = {1525-1497},
support = {I01 HX003635/HX/HSRD VA/United States ; I21 HX003593/HX/HSRD VA/United States ; IK2 HX002867/HX/HSRD VA/United States ; },
abstract = {BACKGROUND: In the Veterans Health Administration (VA), primary care teams include embedded specialists to facilitate timely access to effective mental health treatments, including same-day warm handoffs from primary care clinicians/staff to integrated mental health specialists.

OBJECTIVE: Understand the impact of the post-COVID-19 shift to virtual care on depression assessment and treatment and explore clinician-identified ways to optimize hybrid (virtual/in-person) integrated care for primary care patients with depression.

DESIGN: Semi-structured interviews across three geographically diverse VA healthcare systems.

PARTICIPANTS: Forty-seven primary care clinicians/staff and integrated mental health specialists.

APPROACH: Interview questions were based on Fortney et al.'s Reconceptualized (Digital) Access Framework. Transcripts were coded using a qualitative descriptive approach with constant comparison.

KEY RESULTS: Participants indicated that post-pandemic use of virtual care helped increase access to depression treatment. Particularly, they cited a model where integrated mental health clinicians/staff cover clinics across a healthcare system by offering telephone or video visits to patients at multiple sites. Primary care and mental health coordination appeared to work well; nevertheless, some primary care clinicians/staff preferred in-person warm handoffs. When asked about the optimal mix of in-person and virtual depression care, primary care clinicians/staff thought the initial assessment should be done in person, especially for patients presenting complicated cases. Ongoing care, namely cognitive behavioral therapy and medication management, was thought to be ideal for virtual delivery. Participants emphasized the need for offering Veteran-centric care, or care that "meets the Veterans where they are" and encourages them to continue engagement in mental healthcare.

CONCLUSIONS: Clinicians generally deferred to patients on their preferred care modality, but some indicated certain situations (e.g., initial assessment, complicated cases) may be better suited for in-person over virtual care. Further research should examine quality of virtual and in-person primary care-based mental healthcare, and patient satisfaction and experiences with these care modalities.},
}

@article {pmid42414949,
year = {2026},
author = {Njohjam, MN and Ngoule, MO and Niakam, TF},
title = {Biological sex differences in neurodegenerative diseases in Africa: a scoping review of evidence and research gaps.},
journal = {BMC neurology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12883-026-05123-w},
pmid = {42414949},
issn = {1471-2377},
abstract = {BACKGROUND: Biological sex is a well-established determinant of risk, progression, and therapeutic response in neurodegenerative diseases (NDs). However, current evidence on sex differences in NDs is from high-income Western populations. This review aims to map and synthesize evidence on biological sex differences in NDs in Africa, and to identify key research gaps.

METHODS: This scoping review was conducted in accordance with the Joanna Briggs Institute methodology and reported in accordance with the PRISMA-ScR guidelines. A literature search was conducted on PubMed, African Journals Online, Sabinet Journals, ScienceDirect, and Google Scholar. We included studies conducted in African countries that reported sex disaggregated data or examined biological sex differences in at least one ND. Data were synthesized descriptively.

RESULTS: All included studies reported sex distribution, but most (about 84%) did so only descriptively. Approximately 17% conducted sex-stratified analyses beyond prevalence. Similar to global epidemiological trends, several studies suggested a higher prevalence or odds of dementia and multiple sclerosis among females, while male predominance was observed in Parkinson's disease and Amyotrophic lateral sclerosis studies. An earlier onset and a higher mutation frequency in LRRK2-G2019S were reported in females with Parkinson's disease in some studies, while another study reported a higher mortality rate in females with dementia. No study evaluated sex specific biomarker profiles, disease progression, or treatment response.

CONCLUSIONS: Evidence on biological sex differences in NDs in Africa remains limited and is largely descriptive. Mechanistic, longitudinal, and biomarker-based investigations are largely absent.},
}

@article {pmid42417277,
year = {2026},
author = {Wamkpah, NS and Pepper, JP},
title = {Invited Commentary on: Lu et al.'s "Functional and Aesthetic Considerations for Selective Facial Neurectomy with Simultaneous Deep Plane Facelift and Structural Neck Contouring for Facial Paralysis with Synkinesis".},
journal = {Facial plastic surgery & aesthetic medicine},
volume = {},
number = {},
pages = {26893614261465163},
doi = {10.1177/26893614261465163},
pmid = {42417277},
issn = {2689-3622},
}

@article {pmid42417282,
year = {2026},
author = {Yver, CM and Hadlock, TA},
title = {Invited Commentary on: Lu et al.'s "Functional and Aesthetic Considerations for Selective Facial Neurectomy with Simultaneous Deep Plane Facelift and Structural Neck Contouring for Facial Paralysis with Synkinesis".},
journal = {Facial plastic surgery & aesthetic medicine},
volume = {},
number = {},
pages = {26893614261465165},
doi = {10.1177/26893614261465165},
pmid = {42417282},
issn = {2689-3622},
}

@article {pmid42417572,
year = {2026},
author = {Cooper, BR and Cena, S and Rasul, T and Blalock, TW and Chavez, AE},
title = {Response to Cooper et al.'s "Reflected Surgical Lighting Exposure at the Mohs Surgeon's Eye Level: Quantifying Effects of Working Distance, Drape Color, and Lamp Positioning".},
journal = {Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]},
volume = {},
number = {},
pages = {},
pmid = {42417572},
issn = {1524-4725},
}

@article {pmid42418280,
year = {2026},
author = {Zhang, C and Chen, S and Zhao, H and Wang, Y and Zhou, L and Fan, H and Sun, Y},
title = {Phase Separation Drives Pathological Aggregation in Neurodegenerative Diseases: A 15-Year Bibliometric Landscape (2009-2024).},
journal = {Annals of the New York Academy of Sciences},
volume = {1561},
number = {1},
pages = {e70311},
pmid = {42418280},
issn = {1749-6632},
support = {#82371153//National Natural Science Foundation of China/ ; #82571317//National Natural Science Foundation of China/ ; #ZR2022QH073//Natural Science Foundation of Shandong Province/ ; #ZR2025MS1188//Natural Science Foundation of Shandong Province/ ; #ZR2025LZ044//Natural Science Foundation of Yantai/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology ; Phase Separation ; *Protein Aggregation, Pathological/metabolism/pathology ; *Bibliometrics ; Animals ; DNA-Binding Proteins/metabolism ; },
abstract = {Liquid-liquid phase separation (LLPS), a biophysical driver of membraneless organelle assembly, is central to pathological aggregation in neurodegenerative diseases. Initially linked to amyotrophic lateral sclerosis (ALS), LLPS dysregulation has now been implicated in Alzheimer's, Parkinson's, and frontotemporal dementia, where aberrant transitions convert dynamic condensates into insoluble fibrils. To systematically map this landscape, we employed CiteSpace-based bibliometrics to analyze 784 Web of Science articles from 2009 to 2024. Our analyses reveal dominant contributions from the United States, China, and Germany, with collaborative networks focusing on protein dynamics. Key hotspots include LLPS-driven aggregation of TARDBP (TDP-43), FUS, and α-synuclein, alongside stress granule dysfunction and nucleocytoplasmic transport defects. Emerging frontiers highlight therapeutic strategies targeting pathological condensates utilizing small-molecule chaperones and posttranslational modification modulators to restore cellular homeostasis. Our findings underscore LLPS as a critical axis bridging molecular pathology and translational innovation. The field is rapidly shifting from mechanistic exploration to therapeutic applications, emphasizing interventions to halt or reverse aggregation. By delineating global trends and changing priorities, our study highlights the transformative potential of phase-targeted interventions and provides a roadmap of groundbreaking interdisciplinary research into neurodegenerative disorders.},
}

Humans
*Neurodegenerative Diseases/metabolism/pathology
Phase Separation
*Protein Aggregation, Pathological/metabolism/pathology
*Bibliometrics
Animals
DNA-Binding Proteins/metabolism

@article {pmid42418533,
year = {2026},
author = {Hsu, YW and Lu, YN and Liu, M and Wang, J},
title = {Multi-regional transcriptomic profiling reveals divergent molecular mechanisms in ALS-related neurodegeneration.},
journal = {PLoS genetics},
volume = {22},
number = {7},
pages = {e1012225},
doi = {10.1371/journal.pgen.1012225},
pmid = {42418533},
issn = {1553-7404},
abstract = {Neurodegenerative disorders including amyotrophic lateral sclerosis (ALS) remain largely unsolved, with complex etiology yet to be fully elucidated. The most common genetic cause of ALS in both familial and sporadic cases is the expansion of a hexanucleotide repeat in the C9orf72 gene. To systemically dissect the molecular landscape of ALS, we performed integrative transcriptomic analyses across multiple central nervous system regions from ALS patients carrying pathological C9orf72 repeat expansions (ALS-C9) and those without the mutation (ALS-non-C9). In parallel, we performed transcriptome-wide cell-type deconvolution to assess the cellular composition of neuronal and non-neuronal populations. We identified a set of dysregulated molecular pathways that were consistently altered in both ALS-C9 and ALS-non-C9 patients, suggesting shared pathogenic mechanisms. Distinct gene-specific alterations also pointed to divergent subtype-dependent molecular trajectories. Gene-specific alterations were also associated with short clinical duration in ALS-non-C9, highlighting a sex-dependent immunological contribution to disease outcome. Our cross-regional integrative transcriptomic analyses reveal both convergent and divergent molecular and cellular features between ALS-C9 and ALS-non-C9 subgroups, underscoring the clinical heterogeneity of ALS and providing a framework for subtype- and sex-specific therapeutic stratifications.},
}

@article {pmid42418847,
year = {2026},
author = {de La Seiglière, H and Letourneur, Æ and Ichas, F and De Giorgi, F},
title = {Phase separation and protein aggregation in neurodegenerative diseases.},
journal = {Biophysical chemistry},
volume = {338},
number = {},
pages = {107678},
doi = {10.1016/j.bpc.2026.107678},
pmid = {42418847},
issn = {1873-4200},
abstract = {Neurodegenerative diseases such as Alzheimer's, Parkinson's, frontotemporal dementia, and ALS are characterized by amyloid protein aggregation involving intrinsically disordered proteins that are also capable of liquid-liquid phase separation (LLPS). LLPS, known to drive the formation of dynamic membraneless organelles essential for cellular functions, can play a role in limiting fibrillation process or aberrantly transition into solid aggregates under pathological conditions. Here we review how mutations, post-translational modifications, and environmental factors can modulate LLPS of proteins like Tau, TDP-43, FUS, and α-synuclein, potentially regulating amyloid aggregation. We also examine the interplay of these proteins exploring how LLPS and condensate maturation could impinge on the emergence of co-pathologies contributing to disease progression. Finally we discuss emerging therapeutic strategies, aimed at modulating phase separation dynamics.},
}

@article {pmid42419281,
year = {2026},
author = {Kournoutis, A and Stenmark, H},
title = {Sealing and healing: A two-step model for plasma membrane repair.},
journal = {Developmental cell},
volume = {61},
number = {7},
pages = {1345-1346},
doi = {10.1016/j.devcel.2026.06.011},
pmid = {42419281},
issn = {1878-1551},
mesh = {*Cell Membrane/metabolism ; Animals ; Humans ; Models, Biological ; *Annexins/metabolism ; Endosomal Sorting Complexes Required for Transport/metabolism ; Mutation ; },
abstract = {Plasma membrane damage can cause cell death and is associated with neurodegeneration. In this issue of Developmental Cell, Heffner et al. show that annexin A11 (ANXA11) first plugs membrane lesions, before ESCRT-III is recruited to extrude the damaged patch-a two-step repair mechanism compromised by ALS- and FTD-linked mutations.},
}

*Cell Membrane/metabolism
Animals
Humans
Models, Biological
*Annexins/metabolism
Endosomal Sorting Complexes Required for Transport/metabolism
Mutation

@article {pmid42419491,
year = {2026},
author = {Ellappan, S and Kujur, PP and Mondal, AC},
title = {The Autophagy-Senescence-Inflammasome Axis: A Novel Triad in Neurodegenerative Diseases?.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {103248},
doi = {10.1016/j.arr.2026.103248},
pmid = {42419491},
issn = {1872-9649},
abstract = {Chronic neuroinflammation is a defining feature of brain ageing and neurodegenerative disorders, yet the molecular mechanisms responsible for its persistence remain incompletely understood. Although autophagy dysfunction, glial senescence, and inflammasome activation are well-established contributors to progressive neurodegeneration, these processes are often analysed independently or through pairwise interactions, leaving their collective contribution to persistent neuroinflammation and disease progression insufficiently defined. Here, we synthesise emerging evidence supporting an integrated 'Autophagy-Senescence-Inflammasome (ASI) axis', in which reciprocal interactions among impaired autophagy, senescent glia, and inflammasome signalling establish a self-sustaining cycle of neuroinflammation. We discuss how defective autophagy promotes mitochondrial dysfunction, oxidative stress, and danger signalling, while senescent astrocytes and microglia amplify inflammatory responses through the senescence-associated secretory phenotype (SASP). These intertwined processes converge on chronic inflammasome activation, with mitochondrial dysfunction emerging as a central mechanistic hub. Evidence across Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, stroke, and chronic neuropathic pain highlight the broad relevance of this pathological network. We further analyse current therapeutic strategies targeting autophagy, senescence, and inflammasome pathways, emphasising the limitations of single-target approaches and the potential of multi-target interventions. By integrating these processes into a unified framework, this review provides new insights into the possible molecular mechanisms underlying neuroinflammaging and identifies the 'ASI axis' as a promising target for neurodegenerative disease-modifying therapies.},
}

@article {pmid42419740,
year = {2026},
author = {Varga, D and Ráduly, Z and Boros-Oláh, B and Nagy, É and Karányi, Z and Halász, L and Bálint, BL and Vámosi, G and Tóth, E and Bai, P and Santangelo, S and Bossolasco, P and Ratti, A and Géli, V and Pommier, Y and Székvölgyi, L},
title = {TOP1MT rs2293925 is an enhancer-active regulatory SNP that shapes mitochondrial R-loop dynamics.},
journal = {The FEBS journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/febs.70649},
pmid = {42419740},
issn = {1742-4658},
support = {//Thematic Excellence Programme/ ; 142137//NKFIH/ ; 130913//NKFIH/ ; 135107//NKFIH/ ; K146028//NKFIH/ ; K124141//NKFIH/ ; K152259//NKFIH/ ; TKP2021-EGA-19//NKFIH/ ; TKP2021-EGA-20//NKFIH/ ; //HUN-REN Hungarian Research Network/ ; //National Research, Development and Innovation Fund of Hungary/ ; },
abstract = {Mitochondrial topoisomerase 1 (TOP1MT) regulates mitochondrial DNA (mtDNA) topology during transcription and replication. Perturbed mtDNA maintenance and RNA metabolism have been implicated in neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). Here we show that the common TOP1MT variant rs2293925 (R525W) has enhancer-like activity and is associated with increased mitochondrial R-loops (RNA : DNA hybrids). Tissue-dependent expression, quantitative trait locus analysis, chromatin-state annotation, reporter assays, and allele-specific DNA-protein binding assays support a transcriptional regulatory role for rs2293925. In isogenic cell models, rs2293925 increased TOP1MT mRNA and protein abundance, and this was accompanied by increased mitochondrial R-loop signal. TOP1MT trapping with lamellarin D supported increased TOP1MT-R525W occupancy at mitochondrial control region sites together with enhanced R-loops, consistent with altered TOP1MT-mtDNA interaction and/or increased TOP1MT abundance. Elevated mitochondrial R-loop signal was also detected in a pilot cohort of sporadic ALS samples carrying rs2293925 and in neural stem cells derived from C9orf72-positive ALS patients. These data support a dual-effect model in which rs2293925 increases TOP1MT expression and is associated with altered mitochondrial R-loop dynamics, linking common genetic variation to mitochondrial nucleic acid stress in disease-relevant contexts.},
}

@article {pmid42420066,
year = {2026},
author = {Tien-Smith, AZ and Absar, S and Rogowski, CB and Phillips, V and Andersen, ZJ and Bredell, C and Fung, KW and Hong, L and Szybka, M and Woodcock, J and Brayne, C and Khreis, H and Navaratnam, AMD},
title = {Association of long-term outdoor air pollution exposure with incidence of Parkinson's disease, multiple sclerosis and motor neuron diseases: a systematic review and meta-analysis.},
journal = {Environment international},
volume = {},
number = {},
pages = {110377},
doi = {10.1016/j.envint.2026.110377},
pmid = {42420066},
issn = {1873-6750},
abstract = {BACKGROUND: Parkinson's disease (PD), multiple sclerosis (MS) and motor neurone disease (MND) are progressive and debilitating diseases that are increasing in prevalence globally. Some primary studies show an increased risk from long-term outdoor air pollution exposure, while others contradict this association.

METHODS: A systematic review and meta-analysis were undertaken to assess the associations of long-term (≥1 year) outdoor air pollution exposure with PD, MS and MND incidence. We searched eight databases for publications up to July 2025. Primary case-control, cohort, cross-sectional or ecological studies investigating the association between long-term air pollution exposure and adult (>18 years old) PD, MS, or MND incidence were included. Meta-analyses were carried out using random-effects models with assessment of heterogeneity, meta-bias and shape of the exposure-response functions. PROSPERO (CRD42023417961).

RESULTS: Of 42 papers included, 26, 3 and 3 were meta-analysed for PD, MS, and MND outcomes, respectively. 19 studies from North America, 12 from Europe and 10 from Asia were meta-analysed. For every 5 μg/m[3] and 15 μg/m[3] increase of Particulate Matter 2.5 (PM2.5) and PM10 concentration, estimated (95% Confidence Interval) PD risk was 10% (1.10; 1.03-1.19) and 18% (1.18; 1.01-1.38), respectively but effects varied across settings (Prediction Interval: 0.80-1.52 for PM2.5 and 0.41-3.36 for PM10), with the largest estimated risk for PM2.5 in Asia (1.19; 1.01-1.41). There was no clear evidence that PM2.5 (1.01; 0.77-1.32) or nitrogen dioxide (NO2, 0.98, 95% CI: 0.95-1.01) were associated with MS risk or PM2.5 with MND risk (1.07, 95% CI: 0.86-1.33).

CONCLUSION: This systematic review reports increased PD risk from long-term PM2.5 and PM10 exposure. No association was observed for MS and MND from a very limited evidence base. The neurodegenerative diseases investigated here are rare and therefore alternatives to insufficiently powered cohort studies are needed to strengthen the evidence on risk.},
}

@article {pmid42420185,
year = {2026},
author = {Shan, D and Wang, H and Liu, F and Yan, C and Zhao, Y and Sun, X},
title = {Neuronal Intranuclear Inclusion Disease Mimicking Familial ALS: A Multigenerational Case Series With Diagnostic Pitfalls.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70336},
pmid = {42420185},
issn = {1097-4598},
support = {20201125//Qilu Young Scholar Program of Shandong University/ ; ZR2023MH180//the Natural Science Foundation of Shandong Province/ ; ZR2022QH325//the Natural Science Foundation of Shandong Province/ ; },
}

@article {pmid42420559,
year = {2026},
author = {Compagnion, AC and Ivanov, A and Rana, A and Espinoza, F and Sandmann, T and Martineau, FS and Monsorno, K and Facchinetti, R and Matera, A and Rougé, L and González Ibáñez, F and Catale, C and Bizzotto, M and Garel, S and Matteoli, M and Kashiwagi, Y and Koyama, R and Haass, C and Tremblay, ME and Beule, D and Jelescu, I and Zerbi, V and Di Paolo, G and Paolicelli, RC},
title = {Microglial TDP-43 mediates myelin refinement and represses Tyrobp cryptic exon inclusion in mice.},
journal = {Nature neuroscience},
volume = {},
number = {},
pages = {},
pmid = {42420559},
issn = {1546-1726},
abstract = {TDP-43 proteinopathy is a hallmark of neurodegenerative disorders such as amyotrophic lateral sclerosis and frontotemporal dementia where mislocalization of TDP-43 has been observed in neurons and glial cells. However, the role of TDP-43 in microglia and the consequences of its loss of function remain unexplored. Combining magnetic resonance imaging, and confocal, and electron microscopy, we uncovered structural changes and myelin abnormalities in the early postnatal brain of mice lacking microglial TDP-43. Spatial transcriptomics further revealed an enriched interferon-responsive signature associated with oligodendrocyte dysfunction. Early depletion of microglial TDP-43 led to motor deficits in adult mice. Mechanistically, knocking out TDP-43 impaired microglial ability to engulf and degrade myelin. It also led to cryptic exon inclusion in the Tyrobp mRNA, resulting in truncated DAP12 protein, thus causing defective TREM2 signaling. Our findings reveal a role for TDP-43 in regulating the TREM2-DAP12 axis in mice, highlighting a previously unrecognized mechanism through which TDP-43 controls microglial function.},
}

@article {pmid42421532,
year = {2026},
author = {Jiang, Z and Zhang, R and Jiang, Z and Zeng, S and Wang, L and Zhao, S and Zhang, X and Yu, H},
title = {Accelerating reaction kinetics of AlCl3/acetamide electrolyte by co-solvation for Al-S batteries.},
journal = {Materials horizons},
volume = {},
number = {},
pages = {},
doi = {10.1039/d6mh00252h},
pmid = {42421532},
issn = {2051-6355},
abstract = {Deep eutectic solvents such as AlCl3/acetamide (AcA) have demonstrated great potential as room-temperature electrolytes for Al-S batteries, but their high viscosities and low ionic conductivities severely impede the electrochemical reaction kinetics. Herein, we report an effective strategy to optimize AlCl3/AcA by screening fluorobenzene co-solvents. The optimal 1,2,3-trifluorobenzene (tFBn) effectively dilutes AlCl3/AcA and has a crowding effect that creates a local high-concentration zone for efficient transport of electro-active ions. Rather than merely functioning as a diluent, tFBn induces the localized aggregation of neutral molecules and ion clusters, which reduces the bulk viscosity by 50% and doubles the ionic conductivity. This localized high concentration, coupled with the rapid migration of ion clusters, accelerates the reaction kinetics and improves the long-cycling stability of Al stripping/plating. tFBn also promotes the transportation of Al-Cl species onto Al to regulate the interphase structures and reduce the resistance. Due to the accelerated reaction kinetics, the tFBn-modified AlCl3/AcA further improves the S utilization, reduces the polarization, and enhances the capacity retention of Al-S batteries. This study provides important insights into the design of high-performance electrolytes toward practical Al-S batteries.},
}

@article {pmid42407404,
year = {2026},
author = {Gündüz, A and Şirin, NG and Boran, E and Baslo, SA and Baslo, MB and Kuruoğlu, HR and Kocasoy Orhan, E and Öge, AE and Yıldız, FG and Tümer, O and Tütüncü, M and Tan, E and Temuçin, ÇM and Uysal, H and Uzun, N and Cengiz, B},
title = {The contribution of trapezius and sternocleidomastoideus motor evoked potentials in the diagnosis of Amyotrophic lateral sclerosis.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {190},
number = {},
pages = {2112331},
doi = {10.1016/j.clinph.2026.2112331},
pmid = {42407404},
issn = {1872-8952},
abstract = {OBJECTIVE: We aimed to evaluate the role of corticobulbar motor evoked potentials (MEPs) as an objective electrophysiological measure to support clinical assessment of upper motor neurons in amyotrophic lateral sclerosis (ALS).

METHODS: Seventy-three patients with ALS and 44 healthy individuals with similar age and sex underwent transcranial magnetic stimulation with MEP recordings from the sternocleidomastoideus (SCM), trapezius, and abductor pollicis brevis muscles. Corticobulbar involvement was defined by prolonged cortical MEP latency or central motor conduction time (CMCT) or absence of MEP responses. Awaji-Shima diagnostic categories were evaluated before and after the incorporation of corticobulbar MEP abnormalities.

RESULTS: Corticobulbar MEP abnormalities were significantly more frequent in patients with ALS than in controls. Prolonged SCM-MEP latency and CMCT were the most sensitive electrophysiological markers of corticobulbar involvement. When interpreted alongside clinical upper motor neuron signs, corticobulbar MEP abnormalities facilitated upward diagnostic reclassification within the Awaji-Shima framework. One-fifth of patients who were initially classified as possible or probable ALS were reclassified as probable ALS and definite ALS, respectively, following inclusion of SCM- and trapezius-MEP abnormalities.

CONCLUSIONS: Corticobulbar MEP assessment provides objective electrophysiological support for upper motor neuron dysfunction and enhances diagnostic sensitivity when used in conjunction with the Awaji-Shima diagnostic framework.

SIGNIFICANCE: This study demonstrates that electrophysiological assessment of the corticobulbar pathway using SCM- and trapezius-MEPs provides objective evidence of upper motor neuron dysfunction in ALS.},
}

@article {pmid42409373,
year = {2026},
author = {Kida, H and Kanai, T and Morita, M and Hasegawa, T},
title = {Bedside muscle ultrasonography to detect fasciculations and support diagnosis of amyotrophic lateral sclerosis in a mechanically ventilated intensive care unit patient.},
journal = {Acute and critical care},
volume = {},
number = {},
pages = {},
doi = {10.4266/acc.002080},
pmid = {42409373},
issn = {2586-6060},
}

@article {pmid42410102,
year = {2026},
author = {Binet, M and Jewett, G and Breiner, A and Chum, M and Genge, A and Schellenberg, K and Shoesmith, C and Pfeffer, G and Salmon, K},
title = {A changed landscape: five-year retrospective on the paradigm shift in genetic testing practices for ALS in Canada.},
journal = {European journal of human genetics : EJHG},
volume = {},
number = {},
pages = {},
pmid = {42410102},
issn = {1476-5438},
abstract = {Offering genetic testing is increasingly recommended for all individuals with amyotrophic lateral sclerosis (ALS), particularly following the development of gene-targeted therapies, such as tofersen for SOD1-ALS. Historically, testing was routinely offered to those with familial ALS (fALS), but inconsistently to those with sporadic ALS (sALS). We evaluated changes in genetic testing and counseling practices among Canadian ALS physicians over a five-year period spanning pivotal clinical trial results and regulatory approval of tofersen. Members of the Canadian ALS Research Network were surveyed in 2020, 2022, and 2025 about genetic testing practices for symptomatic and asymptomatic individuals, gene panel composition, access to genetic counseling, and perceived drivers of change. Clinics offering genetic testing for sALS increased from 33% of clinics in 2020 and 57% in 2022 to 100% of respondents in 2025. Genetic testing for patients with a family history (fALS) was near-universal across all timepoints. Broader use of multi-gene panel testing increased over time, coinciding with sponsored testing availability. 61% of respondents reported that Health Canada approval of tofersen directly influenced their practice. Predictive testing offerings increased from 37% in 2020 to 61% in 2025. Genetic testing practices in Canada shifted substantially during late-stage clinical development and following regulatory approval of a gene-targeted therapy (tofersen). Proactive planning during the clinical trial phase facilitated rapid, nationwide adoption. This study captures a key turning point in ALS care, illustrating how therapeutic breakthroughs can redefine national clinical standards.},
}

@article {pmid42410908,
year = {2026},
author = {Matsuo, T and Imamura, R},
title = {Nocturia Beyond the Bladder: Editorial Comment on Kira et al.'s Nationwide JaCS 2023 Analysis.},
journal = {International journal of urology : official journal of the Japanese Urological Association},
volume = {33},
number = {7},
pages = {e70564},
doi = {10.1111/iju.70564},
pmid = {42410908},
issn = {1442-2042},
}

@article {pmid42411077,
year = {2026},
author = {Singh, P and Bhardwaj, S and Nagarajan, K},
title = {A Review on the Mechanisms of Neurodegeneration and the Potential of Plant Bioactives in Managing Neurological Conditions.},
journal = {Current aging science},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118746098388719251206111338},
pmid = {42411077},
issn = {1874-6128},
abstract = {Neurodegenerative disorders encompass a wide range of debilitating neurological conditions characterized by the progressive loss of specific neuronal populations in the central and/or peripheral nervous systems. This disease often leads to a gradual decline in cognitive, motor, and sensory abilities. This review explores the role of various lifestyle factors, such as age, sex, poor diet, depression, etc., which contribute to the onset and progression of NDDs. Various diseases are included in the neurodegenerative disorder, like Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, and Lewy body disease, which are chronic conditions that significantly impact cognitive and motor functions. A literature search was conducted in the scientific database using the keywords "neurodegenerative disorders, phytoconstituents, and herbals". This review includes a collection of reports from ScienceDirect, Scholar Google, and PubMed, all searched up to 2024. The results were assessed, gathered, and reported in this paper. A total of 241 articles were included, with exponential growth in publication numbers from 1985 to 2024. Effective management and control of NDDs require addressing these risk factors, alongside exploring therapeutic interventions. Some plants and herbs used to treat neurodegenerative diseases, such as curcumin, ashwagandha, ginkgo biloba, epigallocatechin-3-gallate, quercetin, ginseng, and resveratrol, have shown potential to improve neuronal health and mitigate disease progression. This review highlights the dual role of natural compounds in promoting improvements and upregulating brain function while potentially reducing degradation. The phytopharmaceuticals show the potential for treating neurological conditions with better efficacy and safer profiles. The review suggested that future research should focus on integrating lifestyle modifications and natural therapies to enhance the quality of life for individuals at risk or suffering from neurodegenerative diseases.},
}

@article {pmid42411482,
year = {2026},
author = {Yang, EJ},
title = {Amyotrophic Lateral Sclerosis as a Systemic Disease: Why Integrative and Microbiome-Focused Approaches Deserve Re-Evaluation.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {31},
number = {6},
pages = {52497},
doi = {10.31083/FBL52497},
pmid = {42411482},
issn = {2768-6698},
support = {KSN2225011//KIOM/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/microbiology/physiopathology ; *Complementary Therapies/methods ; *Gastrointestinal Microbiome ; Animals ; Dysbiosis/microbiology ; },
abstract = {Despite decades of intensive research, therapeutic advances in amyotrophic lateral sclerosis (ALS) remain limited. Increasing evidence suggests that ALS is a multisystem disorder involving motor neuron degeneration, immune dysregulation, skeletal muscle pathology, and gastrointestinal dysfunction, thereby challenging the adequacy of current therapeutic strategies. Complementary and alternative medicine (CAM) approaches are widely used by patients with ALS. However, their efficacy remains controversial owing to limited clinical evidence and methodological limitations. The multicomponent herbal medicine and system-level characteristics of CAM conceptually align with the emerging view of ALS as a multisystemic disease. The involvement of gut microbiome dysbiosis in the pathophysiology of ALS has provided a unifying biological framework linking the peripheral, metabolic, and neuroinflammatory processes. These findings suggest that the combination of CAM and conventional therapy may serve as a potential integrative approach to target gut-brain-muscle interactions and systemic disease pathways. This article highlights critical gaps in the existing evidence and proposes that microbiome-focused, biomarker-driven clinical trials are essential to thoroughly evaluate CAM-based interventions in ALS. Embracing a system-oriented therapeutic framework may help address the complexity of ALS beyond traditional neuron-centered approaches.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/microbiology/physiopathology
*Complementary Therapies/methods
*Gastrointestinal Microbiome
Animals
Dysbiosis/microbiology

@article {pmid42411953,
year = {2026},
author = {Adachi, T and Nakano, T and Yoshida, K and Suzuki, Y and Sakuwa, M and Hasegawa, M and Jannah, AR and Hara, N and Miyashita, A and Ikeuchi, T and Hanajima, R},
title = {Reduced Soluble Ubiquilin2 in Amyotrophic Lateral Sclerosis Carrying Ubiquilin2 (P494L) Mutation: Clinicopathological and Biochemical Evidence From an Autopsy Case.},
journal = {Neuropathology and applied neurobiology},
volume = {52},
number = {4},
pages = {e70091},
doi = {10.1111/nan.70091},
pmid = {42411953},
issn = {1365-2990},
support = {24K10643//Japan Society for the Promotion of Science/ ; JP25dk0207060//Japan Agency for Medical Research and Development/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; Autophagy-Related Proteins ; Adaptor Proteins, Signal Transducing ; *Cell Cycle Proteins/genetics/metabolism ; Mutation ; DNA-Binding Proteins/metabolism ; Autopsy ; Male ; Female ; *Ubiquitins/genetics ; Brain/pathology/metabolism ; Middle Aged ; },
abstract = {We report the clinicopathological and biochemical findings of ALS associated with a UBQLN2 P494L mutation. Autopsy revealed widespread TDP-43 pathology and UBQLN2-positive inclusions. Immunoblot analysis demonstrated a marked reduction of soluble UBQLN2, supporting functional UBQLN2 insufficiency as a pathogenic mechanism underlying TDP-43 aggregation.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism
Autophagy-Related Proteins
Adaptor Proteins, Signal Transducing
*Cell Cycle Proteins/genetics/metabolism
Mutation
DNA-Binding Proteins/metabolism
Autopsy
Male
Female
*Ubiquitins/genetics
Brain/pathology/metabolism
Middle Aged

@article {pmid42412610,
year = {2026},
author = {Pasniceanu, IS and Atwal, MS and Santos Souza, CD and Moll, T and King, M and Treanor, C and Cabezas de la Fuente, D and West, RJH and Ferraiuolo, L and Livesey, MR},
title = {Striatal neuron dysfunction in C9ORF72-FTD/ALS is driven by AIS and potassium channel dysregulation.},
journal = {Cell reports},
volume = {45},
number = {7},
pages = {117672},
doi = {10.1016/j.celrep.2026.117672},
pmid = {42412610},
issn = {2211-1247},
abstract = {Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) form a neurodegenerative spectrum characterized by progressive cognitive, behavioral, and motor decline, yet the contribution of the striatum to disease pathophysiology remains poorly understood. Here, we generate inhibitory striatal medium spiny neurons (MSNs) from human induced pluripotent stem cells carrying the C9ORF72 repeat expansion, the most common genetic cause of FTD/ALS, and compare them with isogenic-corrected, control, and patient-derived motor neurons. Using whole-cell electrophysiology, pharmacological manipulation, and high-resolution imaging, we identify a vulnerability of C9ORF72 MSNs to develop intrinsic hypoexcitability with linked synaptic dysfunction. These abnormalities are associated with axon initial segment shortening and altered voltage-gated potassium channel function relative to control and isogenic-corrected neurons. Pharmacological modulation partially restores action potential waveform properties, indicating that key electrophysiological abnormalities are reversible. These findings identify the striatum as a critical site of dysfunction in FTD/ALS and highlight striatal excitability as a potential therapeutic target.},
}

@article {pmid42413223,
year = {2026},
author = {Mohammadi, S and Trojsi, F and Ghaderi, S},
title = {Are T1-weighted and T2-weighted volumetric pipelines interchangeable methodologies for investigating amyotrophic lateral sclerosis pathology in vivo?.},
journal = {Brain research bulletin},
volume = {243},
number = {},
pages = {112036},
doi = {10.1016/j.brainresbull.2026.112036},
pmid = {42413223},
issn = {1873-2747},
abstract = {PURPOSE: To test the hypothesis that T1-w and T2-w volumetric pipelines are not interchangeable, particularly regarding their differential sensitivity to physiological traits and disease effects in the red nucleus (RN) and substantia nigra (SN).

METHODS: Thirty-one patients with ALS (mean age: 59.39 ± 8.73 years; 23 males) and 21 non-neurodegenerative controls (mean age: 53.43 ± 10.01 years; 16 males). Bilateral RN and SN volumes were automatically extracted using deep learning pipelines optimized for T1-w (OpenMAP-T1) and T2-w (pBrain) images. Volumes were normalized to total intracranial volume. A 2 × 2 × 2 repeated-measures general linear model (GLM) assessed interactions between Method, Region, Side, and Group, controlling for age, sex, BMI, and handedness.

RESULTS: There was no significant main effect of the disease group (p = 0.829) or Method × Group interaction (p = 0.682), indicating both pipelines agreed on the absence of disease-specific macrostructural atrophy. However, a significant four-way Method × Region × Side × Age interaction (P = 0.031) was observed. In the RN, the T2-w pipeline detected robust age-related atrophy (Left: Slope = -1.84 × 10[-6]; Right: Slope = -1.70 ×10⁻⁶), whereas the T1-w pipeline did not (p > 0.05). Conversely, in the SN, T1-w consistently identified bilateral age-related loss, whereas T2-w yielded lateralized results (Right: p = 0.011; Left: P = 0.465).

CONCLUSIONS: T1-w and T2-w pipelines are not interchangeable. Though both confirm the absence of gross atrophy in this ALS cohort, their differing sensitivity to physiological aging highlights their distinct biological tissue properties, requiring method-specific interpretation.},
}

@article {pmid42414029,
year = {2026},
author = {Hata, T and Ogawa, N and Yabata, H and Kobashi, S and Nakayama, M and Ishigaki, H and Yamakawa, I and Itoh, Y and Nishino, I and Urushitani, M},
title = {Case of concurrent ALS and human T-cell leukaemia virus type 1-associated myositis.},
journal = {BMJ case reports},
volume = {19},
number = {7},
pages = {},
doi = {10.1136/bcr-2025-270944},
pmid = {42414029},
issn = {1757-790X},
mesh = {Humans ; Female ; *Amyotrophic Lateral Sclerosis/complications/diagnosis/pathology ; *Human T-lymphotropic virus 1 ; Aged ; Fatal Outcome ; *HTLV-I Infections/complications ; *Myositis/virology/complications/diagnosis ; Muscle, Skeletal/pathology ; Immunoglobulins, Intravenous/therapeutic use ; Magnetic Resonance Imaging ; },
abstract = {A woman in her late 70s presented with progressive limb weakness, muscle atrophy and hyper-reflexia. Laboratory findings revealed elevated creatine kinase and positive serum human T-cell leukaemia virus type 1 (HTLV-1) antibody. Clinical and electrophysiological findings met revised El Escorial criteria for amyotrophic lateral sclerosis (ALS), but muscle MRI showed inflammatory changes. Muscle biopsy revealed both neurogenic and inflammatory features. While methylprednisolone showed no benefit, intravenous immunoglobulin therapy produced transient improvement in weakness with normalisation of creatine kinase levels. The patient died from respiratory failure 3 years after symptom onset. Autopsy confirmed typical ALS-TDP pathology with phosphorylated TDP-43 inclusions in motor neurons. HTLV-1 Tax-positive lymphocytes infiltrated skeletal muscles but not the central nervous system, establishing dual pathology of ALS-TDP with HTLV-1-associated myositis. The improvement most likely reflected treatment of the HTLV-1-associated myositis rather than the underlying motor neuron disease. This case highlights the importance of evaluating treatable conditions in HTLV-1-seropositive ALS patients.},
}

Humans
Female
*Amyotrophic Lateral Sclerosis/complications/diagnosis/pathology
*Human T-lymphotropic virus 1
Aged
Fatal Outcome
*HTLV-I Infections/complications
*Myositis/virology/complications/diagnosis
Muscle, Skeletal/pathology
Immunoglobulins, Intravenous/therapeutic use
Magnetic Resonance Imaging

@article {pmid42414528,
year = {2026},
author = {Smith, CL and Robinson, JL and Lee, EB},
title = {Annexin A11 and TDP-43: core players in neurodegeneration.},
journal = {Acta neuropathologica},
volume = {152},
number = {1},
pages = {},
pmid = {42414528},
issn = {1432-0533},
support = {T32AG000255/NH/NIH HHS/United States ; P30AG072979/NH/NIH HHS/United States ; },
mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; *Annexins/metabolism/genetics ; *Neurodegenerative Diseases/pathology/metabolism/genetics ; Animals ; TDP-43 Proteinopathies/pathology/metabolism ; },
abstract = {Annexin A11 (ANXA11) is a Ca[2][+]-dependent phospholipid-binding protein that has recently emerged as a key player in neurodegeneration. Rare pathogenic ANXA11 variants were initially identified in cases of amyotrophic lateral sclerosis (ALS). Since then, ANXA11 has been linked to a broader spectrum of related neurodegenerative diseases. Two independent studies demonstrated that ANXA11 co-aggregates with TDP-43 in all cases of frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP) type C, with cryo-EM revealing heteromeric ANXA11-TDP-43 filaments. These discoveries support the direct pathological interaction between the two proteins as an important feature of FTLD-TDP type C. We also described secondary ANXA11 pathology in related neurodegenerative diseases, including limbic-predominant age-related TDP-43 encephalopathy (LATE), and more rarely in ALS and FTLD-TDP types A and B. ANXA11 and TDP-43 co-aggregates are also a feature of a FTLD-TDP associated with primary lateral sclerosis. These advances have renewed interest in ANXA11 as a major player in ALS/FTLD pathogenesis in both genetic and sporadic neurodegenerative diseases. In this review, we summarize ANXA11 pathology across genetic and sporadic cases, highlighting its heterogeneous overlap with TDP-43 pathology. We synthesize current knowledge of ANXA11's physiological roles in phase separation, membrane repair, and RNA granule dynamics, integrating emerging evidence on how disruption of these processes may promote pathological aggregation and toxicity. Finally, we outline priorities for future research, with particular emphasis on elucidating ANXA11's mechanistic connection to TDP-43.},
}

Humans
*DNA-Binding Proteins/metabolism/genetics
*Annexins/metabolism/genetics
*Neurodegenerative Diseases/pathology/metabolism/genetics
Animals
TDP-43 Proteinopathies/pathology/metabolism

@article {pmid42404161,
year = {2026},
author = {Riva, N and Finotto, E and Schito, P and Donzelli, G and Russo, T and Domi, T and Pozzi, L and Tettamanti, A and Riboldi, E and Lopez, ID and Quattrini, A and Cremona, G and Comola, M and Filippi, M},
title = {Perspective and quality of life in amyotrophic lateral sclerosis patients undergoing percutaneous endoscopic gastrostomy.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1756642},
pmid = {42404161},
issn = {2296-861X},
abstract = {INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) is commonly used to manage dysphagia and nutritional failure, which are among the most frequent and severe complications of amyotrophic lateral sclerosis (ALS). While several studies assessed PEG indications, outcomes, and prognostic factors, there is no evidence regarding ALS patients' perspectives and health-related quality of life (HRQoL) associated with PEG.

METHODS: This study included 48 consecutive ALS patients. At the 1-month follow-up after PEG, patients and their caregivers completed a PEG satisfaction questionnaire regarding their decision to proceed with the PEG-tube placement. HRQoL was assessed using the Gastrointestinal Quality of Life Index (GIQLI) and the Short Form-36 (SF-36).

RESULTS: In total, 77.1% of patients and 88.9% of caregivers confirmed that they would prefer to have a PEG tube placed again if required (p > 0.001); 93.8% of patients felt that PEG made feeding easier, exerting a positive effect on overall wellbeing (83.3%) and increasing survival rates (93.8%) (p > 0.001); 54.2% felt that PEG was cosmetically acceptable. Consistent positive rates were reported by caregivers. The GIQLI digestion subscale values significantly improved from baseline (28.3; SD = 6.6) to discharge (30.97, SD = 5.84) and were maintained at 1-month follow-up (30.21, SD = 6.7; p = 0.014). Conversely, in follow-up assessments, we observed a significant reduction in the SF-36 physical component summary (PCS) subscale (baseline = 33.3; 1-month follow-up = 28.61; p = 0.032), which was accompanied by a significant worsening in the GIQLI physical dimension subscale (baseline = 9.63; 1-month follow-up = 7.38; p = 0.044).

DISCUSSION: This study provides preliminary evidence that ALS patients have a positive perspective on PEG positioning, which may also have a beneficial effect on HRQoL related to gastrointestinal function.},
}

@article {pmid42404323,
year = {2026},
author = {Chigudu, D},
title = {Climate Variability, Communal Violence, and Population Health in Africa's Arc of Instability: A Scoping Review of Evidence and Gaps.},
journal = {Annals of global health},
volume = {92},
number = {1},
pages = {62},
pmid = {42404323},
issn = {2214-9996},
mesh = {Humans ; Evidence Gaps ; *Violence ; Africa/epidemiology ; *Population Health ; *Climate Change ; },
abstract = {Background: Africa's arc of instability - a band of countries stretching from Mauritania through the Sahel to the Horn of Africa - experiences a convergence of climate variability, communal violence, and fragile health systems. Evidence on their joint operation remains fragmented across disciplines, limiting policy-relevant synthesis. Objectives: This scoping review maps the published and grey literature on the joint operation of climate variability, communal violence, and population health in the arc of instability between January 2010 and March 2025; it identifies dominant pathways, populations, and methods, and articulates research gaps. Methods: Following Arksey and O'Malley's framework with Levac et al.'s refinements and reporting against the PRISMA-ScR checklist, five electronic databases (PubMed, Scopus, Web of Science, CINAHL, and Africa Wide Information) and grey literature from UN agencies, humanitarian organisations, and conflict and vulnerability databases were searched. Studies addressing at least two of the three domains in the arc, published in English or French, were included and synthesised narratively. Findings: Of 1623 records screened, 47 studies met the inclusion criteria. Four dominant pathways were identified: (i) resource scarcity, communal violence, displacement, and infectious disease; (ii) drought, food insecurity, and child malnutrition and mortality; (iii) heat extremes, weather events, mental health, and service disruption; and (iv) state fragility, health-system disruption, and maternal and child health deterioration. Pastoralist communities, internally displaced persons, women, and children were the most affected populations. Gaps include scarce longitudinal data, limited mental health surveillance in conflict zones, and under-representation of locally-led research among others. Conclusions: Evidence on the joint operation of climate variability, communal violence, and health in the arc of instability is accruing but remains thin, descriptive, and geographically uneven. A locally-led, transdisciplinary research agenda is needed to inform climate-resilient health systems and humanitarian responses, prioritising primary data collection, mental health surveillance, and longitudinal cohort studies.},
}

Humans
Evidence Gaps
*Violence
Africa/epidemiology
*Population Health
*Climate Change