@article {pmid42548030,
year = {2026},
author = {Matsuki, Y and Bokuda, K and Morishima, R and Kawazoe, T and Kimura, H and Takahashi, K and Nakayama, Y and Shimizu, T},
title = {Sensory Cortical Hyperexcitability in Amyotrophic Lateral Sclerosis Involves a Broad Hand Representation Within the Primary Somatosensory Cortex.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70371},
pmid = {42548030},
issn = {1097-4598},
support = {22H03398//JSPS KAKENHI/ ; },
abstract = {INTRODUCTION/AIMS: Sensory cortical hyperexcitability, reflected by enlarged median nerve somatosensory evoked potentials (SEPs), has been reported in amyotrophic lateral sclerosis (ALS) and is associated with shorter survival. This study investigated whether similar changes involve the ulnar nerve representation within the hand area of the primary somatosensory cortex and examined their relationship with survival.

METHODS: Ninety-nine patients with sporadic ALS and 42 healthy controls were retrospectively studied. Sensory nerve action potentials (SNAPs) and SEPs were recorded following median and ulnar nerve stimulation. SNAP amplitudes and the peak-to-peak amplitudes between N20 and P25 (N20p-P25p) were compared between groups. Patients were followed until death or tracheostomy, and associations between SEP amplitudes and survival were analyzed using Kaplan-Meier and Cox proportional hazards analyses.

RESULTS: SNAP amplitudes did not differ between patients and controls. In contrast, patients with ALS showed larger N20p-P25p amplitudes for both median and ulnar nerve SEPs. N20p-P25p amplitudes were positively correlated between the two nerves, and the ulnar-to-median amplitude ratio did not differ from controls. Patients with ulnar N20p-P25p ≥ 4.89 μV had significantly shorter survival than those with lower amplitude (log-rank test, p = 0.035). Multivariate Cox analysis identified increased N20p-P25p amplitude as an independent predictor of shorter survival for both nerves.

DISCUSSION: Sensory cortical hyperexcitability in ALS extends beyond the median nerve to the ulnar nerve hand area of the somatosensory cortex. Its association with survival supports the notion that sensory cortical dysfunction represents a fundamental pathophysiological feature of ALS and a potential electrophysiological prognostic marker.},
}

@article {pmid42548241,
year = {2026},
author = {Konarbayeva, Z},
title = {Rheological and Technological Design of Texture-Modified Food Systems for Dysphagia Management in Amyotrophic Lateral Sclerosis.},
journal = {Journal of texture studies},
volume = {57},
number = {4},
pages = {e70105},
pmid = {42548241},
issn = {1745-4603},
mesh = {*Deglutition Disorders/etiology/diet therapy ; *Amyotrophic Lateral Sclerosis/complications ; *Rheology ; Humans ; Viscosity ; *Food Technology ; Animals ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is frequently accompanied by progressive dysphagia, weight loss, and hypermetabolism, which complicate the maintenance of adequate nutritional status. For these patients, food systems must not only provide sufficient energy and protein within a limited volume but also exhibit textural and rheological properties that support safe swallowing. This review analyzes technological and rheological approaches to the design of texture-modified food systems for nutritional support in ALS. Particular attention is given to apparent viscosity, shear-thinning behavior, yield stress, structural homogeneity, and storage stability as parameters affecting bolus formation, swallowing safety, and product performance. The relevance of the International Dysphagia Diet Standardization Initiative framework for classifying food textures and liquid consistencies is also considered. The review further examines the functional and technological roles of animal- and plant-based raw materials, including regional raw materials, in the formulation of energy-dense and structurally stable foods. Proteins, lipids, hydrocolloids, starch gels, and polysaccharide networks are discussed as key components for controlling texture, viscosity, gelation, emulsion stability, and nutritional density. Technological strategies such as homogenization, emulsification, protein-based structuring, hydrocolloid thickening, high-pressure homogenization, and 3D food printing are considered in relation to their potential for developing safe, acceptable, and locally adaptable products for patients with ALS-related dysphagia. The findings highlight the need to integrate food texture science, rheological control, nutritional adequacy, sensory acceptability, and regional availability in the development of clinically relevant texture-modified foods.},
}

*Deglutition Disorders/etiology/diet therapy
*Amyotrophic Lateral Sclerosis/complications
*Rheology
Humans
Viscosity
*Food Technology
Animals

@article {pmid42548317,
year = {2026},
author = {Hwang, JJ and Donnelly, TT and Davidson, S and Raffin Bouchal, S},
title = {Between Denial and Delay: Barriers to Accessing Nonpharmacological Interventions for Seniors With Mild-to-Moderate Dementia in Canada.},
journal = {Qualitative health research},
volume = {},
number = {},
pages = {10497323261468186},
doi = {10.1177/10497323261468186},
pmid = {42548317},
issn = {1552-7557},
abstract = {Dementia is a growing public health concern in Canada, yet timely access to nonpharmacological interventions (NPIs) for persons with dementia (PWDs) remains poorly understood. This critical ethnographic study explored factors influencing access to NPIs among private-dwelling seniors with mild-to-moderate dementia and their family/friend care partners (CPs) in Alberta, Canada. Guided by McLeroy et al.'s Ecological Perspective and Habermas' Critical Social Theory, we conducted 53 semi-structured interviews with eight PWDs and 21 CPs across 20 families. Reconstructive, thematic analysis revealed 10 interrelated factors across socioecological domains: intrapersonal (denial, acceptance, and perceived benefits), interpersonal (support from CPs, physicians, and case managers), organizational (program acceptability and accessibility), community (stigma), and policy (funding constraints). Findings illuminate how systemic conditions such as market-driven care models and fragmented care pathways intersect with lifeworld dynamics, including stigma and relational coping, to shape families' navigation of NPIs. While PWDs relied on their CPs for information and coordination of NPIs, CPs encountered significant informational and navigational barriers. Program invisibility, lengthy referrals, and limited capacity compounded inequities, often leaving families to cope in isolation or seek privatized alternatives. Stigma operated subtly yet systematically, reinforcing therapeutic nihilism, evidence-practice gaps, and policy stagnation. These findings highlight the need to reconceptualize two widely used and valued services, adult day programs and companion care, within a rehabilitative, nonpharmacological framework, strengthen anticipatory guidance, and invest in early, equitable care pathways. Addressing system-lifeworld tensions is essential for dementia care that promotes dignity, connection, and quality of life.},
}

@article {pmid42548517,
year = {2024},
author = {Palm, A and Grote, L and Einarsson, J and Hansson, D and Ljunggren, M and Sundh, J and Ekström, M},
title = {Evolution of Home Mechanical Ventilation in Sweden Over 27 Years: Changing Trends in Incidence, Prevalence, and Patient Characteristics - The Population-Based the Course of Disease in Patients Reported to the Swedish CPAP Oxygen and Ventilator Registry (DISCOVERY) Study.},
journal = {CHEST pulmonary},
volume = {2},
number = {4},
pages = {100108},
pmid = {42548517},
issn = {2949-7892},
abstract = {BACKGROUND: Home mechanical ventilation (HMV), noninvasive ventilation and invasive ventilation outside a hospital setting, is a key treatment to improve outcomes in chronic hypoventilation.

RESEARCH QUESTION: What are the temporal trends observed over 27 years in Sweden regarding the incidence, prevalence, diagnostic spectrum, and patient characteristics associated with HMV?

STUDY DESIGN AND METHODS: This was a national population-based longitudinal analysis of the Course of Disease in Patients Reported to the Swedish CPAP Oxygen and Ventilator Registry (DISCOVERY) study of patients initiating HMV between 1996 and 2022. Time trends stratified by the underlying diagnosis group (lung disease, predominantly COPD, restrictive thoracal diseases, obesity hypoventilation syndrome [OHS], neuromuscular diseases, amyotrophic lateral sclerosis, and other neurologic disorders) were analyzed using linear regression models.

RESULTS: We included 10,555 patients aged ≥ 16 years (mean age 63 [SD, 15] years; 50% women). Between 1996 and 1998 and 2020 and 2022, the HMV incidence increased threefold to 7 per 100,000 people, and the prevalence increased sixfold to 33 per 100,000 people. The most common indication for incident HMV shifted from restrictive thoracal diseases (35% in 1996-1998 to 3% in 2020-2022) to lung disease (14% to 31%), OHS (23% to 33%), and amyotrophic lateral sclerosis (4% to 14%) by 2020 to 2022 (P < .001). The proportion of women increased from 47% to 54% (P < .013) and the age at initiation of HMV increased from 58 [SD, 15] to 66 [SD, 14] years (P < .001). Lung function measured as vital capacity at treatment start increased significantly in all diagnosis groups except for OHS, where both vital capacity and FEV1 decreased. In the registry's first and last 3-year periods, the proportion of patients ventilated invasively decreased from 10% to 2% (P < .001).

INTERPRETATION: In the 27 years until 2022, the incidence and prevalence of HMV in Sweden have increased markedly, patient demographics have changed, and use of invasive ventilation has decreased. The average age of patients initiated on HMV has increased, but treatment is started earlier in the disease trajectory.},
}

@article {pmid42548788,
year = {2026},
author = {Erazo, D and Hesters, A and Bruneteau, G and De La Cruz, E and Bernard, E and Grapperon, AM and Le Masson, G and Cintas, P and Soriani, MH and Guy, N and Cassereau, J and Camdessanché, JP and Genestet, S and Corcia, P and Pittion, S and Danel, V and Filliatre, M and Choumert, A and Jacquin-Piques, A and Salachas, F and Esselin, F and Bohic, A and Lautrette, G and Attarian, S and Catteau, J and Guissart, C and Vincent, MC and Mouzat, K and Temple, M and Vourc'h, P and Couratier, P},
title = {Tofersen Treatment in SOD1-ALS: Real-World Evidence from a Retrospective Multicenter Study in France (FORSLA Study).},
journal = {Mayo Clinic proceedings. Innovations, quality & outcomes},
volume = {10},
number = {5},
pages = {100739},
pmid = {42548788},
issn = {2542-4548},
abstract = {OBJECTIVE: To evaluate the effectiveness of Tofersen in patients with superoxide dismutase 1 gene (SOD1-ALS) patients in France in a real-world setting, using disease progression within patient comparisons and with a historical cohort.

PATIENTS AND METHODS: Patients with SOD1-ALS were included from across 19 French FILSLAN network centers. Baseline was defined as the treatment initiation date. Main endpoints were the ALSFRS-R progression rate and plasmatic neurofilament light chain (NfL) levels at baseline and 12 months after baseline.

RESULTS: In the Tofersen Cohort (N=46), within-group comparisons showed that the mean ALS functional rating scale revised (ALSFRS-R) progression rate slowed from 0.53 ± 0.5 at baseline to 0.22 ± 0.3 point/month at 12 months (P=.006). NfL levels significantly decreased from 89.0 ± 9.0 pg/ml at baseline to 29.2 ± 19.5.5 at 12 months (P=.004). Exploratory comparisons with a propensity score (PS) matched historical cohort (39 matched pairs) using a mixed-effects model, ALSFRS-R progression rate at baseline, 6 months, and 12 months after baseline, showed no statistically significant differences between groups P=.30, whereas longitudinal ALSFRS-R scores differed significantly between groups (time-treatment interaction P=.006). The mean survival of the PS matched population was longer in the Tofersen Cohort (42.6 months) than the Historical Cohort (31.8 months) P=.004. Time-dependent adjusted cox analysis showed that Tofersen was associated with a reduction in mortality risk (adjusted HR=0.34; 95% CI, 0.12-0.91; P=.03).

CONCLUSION: Tofersen seems to be associated with slower functional decline and reduced NfL levels. While limitations of retrospective design and ALSFRS-R sensitivity must be acknowledged, these findings provide real-world evidence suggesting a clinical benefit of Tofersen.},
}

@article {pmid42549498,
year = {2026},
author = {Iijima, N and Hagiwara, Y and Ishii, S and Kaneko, W and Araga, T and Yamano, Y},
title = {Quantitative Assessment of Tongue Atrophy in Amyotrophic Lateral Sclerosis Using Transoral Tongue Ultrasonography (TOTU): A Retrospective Single-Center Study.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70370},
pmid = {42549498},
issn = {1097-4598},
support = {25ek0109735//Japan Agency for Medical Research and Development/ ; 25fk0108733//Japan Agency for Medical Research and Development/ ; 25bm1423033//Japan Agency for Medical Research and Development/ ; 25ek0109617//Japan Agency for Medical Research and Development/ ; 25ek0109759//Japan Agency for Medical Research and Development/ ; 25FC1012//Ministry of Health, Labour and Welfare/ ; JP25K02584//Japan Society for the Promotion of Science/ ; JP24K10542//Japan Society for the Promotion of Science/ ; },
abstract = {INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease accompanied by bulbar dysfunction, in which tongue atrophy contributes to dysarthria and dysphagia. Conventional tongue assessments rely on inspection, palpation, or electrophysiological testing but are limited by subjectivity and invasiveness. A rapid, objective, and repeatable imaging-based method for evaluating tongue size would be valuable. We quantified tongue atrophy in ALS using a standardized protocol for transoral tongue ultrasonography (TOTU) and assessed discrimination.

METHODS: This retrospective, cross-sectional study included 15 patients with ALS and 15 controls who underwent TOTU. Using standardized mid-sagittal images, tongue cross-sectional area (cm[2]) and tongue thickness (mm) were measured three times per subject and averaged. Associations with age, body mass index (BMI), disease duration, and ALS Functional Rating Scale-Revised (ALSFRS-R) scores were explored. Discrimination was evaluated using receiver operating characteristic (ROC) analyses.

RESULTS: Both tongue cross-sectional area (6.26 ± 1.37 vs. 9.44 ± 1.02 cm[2]) and tongue thickness (31.47 ± 3.0 vs. 39.44 ± 1.39 mm) were significantly lower in the ALS group than in controls (both p < 0.001). These indices showed no significant associations with age, BMI, disease duration, or ALSFRS-R scores. ROC analyses showed high discriminative ability, with an area under the curve of 0.982 for tongue cross-sectional area and 1.000 for tongue thickness.

DISCUSSION: Standardized TOTU enables rapid, quantitative, noninvasive assessment of tongue size and reliably detects tongue atrophy in ALS, supporting bedside evaluation of bulbar involvement.},
}

@article {pmid42549723,
year = {2026},
author = {Buthelezi, U and Lubuzo, B and Tingen, M and Chiya, H and Gigaba, SG and Goeieman, B and Ramotsela, S and Luvuno, Z},
title = {Adapting a United States cancer education programme for South Africa: A participatory, culturally tailored approach using Card's Seven-Step adaptation framework.},
journal = {African journal of primary health care & family medicine},
volume = {18},
number = {1},
pages = {e1-e10},
doi = {10.4102/phcfm.v18i1.5442},
pmid = {42549723},
issn = {2071-2936},
mesh = {Humans ; South Africa ; *Neoplasms/prevention & control ; Primary Health Care ; United States ; Community-Based Participatory Research ; *Health Education/methods/organization & administration ; Implementation Science ; Female ; },
abstract = {BACKGROUND: South Africa faces a growing cancer burden characterised by late-stage presentation, limited screening uptake and disparities in access to cancer education. While evidence-based cancer education programmes developed in high-income countries demonstrate effectiveness, direct transfer without contextual modification may compromise relevance and acceptability within resource-constrained health settings.

AIM:  To systematically adapt the United States (US)-based Cancer-Community Awareness Access Research Education (c-CARE) programme as a multi-cancer education intervention for implementation within the South African primary health care (PHC) context using Card et al.'s seven-step adaptation framework.

SETTING:  The adaptation was conducted in KwaZulu-Natal (iLembe District) and Gauteng (Johannesburg), South Africa, in collaboration with provincial Departments of Health, community health workers, traditional health practitioners and faith-based leaders.

METHODS:  This implementation science study employed Participatory Action Research integrated with Card's framework to guide a structured adaptation process (January 2023 - January 2024). Thirty-eight consultative meetings were conducted to review programme materials, identify linguistic, cultural and structural mismatches and implement iterative revisions while preserving core intervention components.

RESULTS:  Key adaptations included the addition of cervical cancer as a priority module; incorporation of South African epidemiological data and referral pathways; translation into isiZulu and Sesotho; integration of mental health, spirituality and palliative care content; and restructuring of delivery to align with the South African Health System. Core evidence-based content, modular design and interactive pedagogical strategies were retained.

CONCLUSION:  Framework-guided adaptation enabled contextual recalibration of c-CARE while maintaining fidelity to core components.Contribution: This study provides a transparent model for adapting evidence-based cancer education interventions for culturally diverse, resource-constrained PHC systems.},
}

Humans
South Africa
*Neoplasms/prevention & control
Primary Health Care
United States
Community-Based Participatory Research
*Health Education/methods/organization & administration
Implementation Science
Female

@article {pmid42549923,
year = {2026},
author = {Takahashi, M and Abe, T and Fujii, M},
title = {Targeting Ubiquitinated Protein Aggregates in Neurodegenerative Diseases: current Status and Future Directions.},
journal = {Molecular and cellular biology},
volume = {},
number = {},
pages = {1-19},
doi = {10.1080/10985549.2026.2705871},
pmid = {42549923},
issn = {1098-5549},
abstract = {Various cellular stressors inhibit translation initiation and promote ribosome disassembly, thereby transiently inducing stress granules (SGs), dynamic ribonucleoprotein condensates that contain mRNAs and RNA-binding proteins. Although SG assembly is usually reversible, dysregulated SG dynamics can trigger the formation of persistent ubiquitin-positive protein inclusions. There is increasing evidence that this conversion of SGs into insoluble aggregates represents a central pathogenic mechanism in neurodegenerative proteinopathies, such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). TAR DNA-binding protein 43 (TDP-43) and Tau are causative factors in ALS and AD, respectively, and both localize to SGs under stress conditions. During disease progression, TDP-43 or Tau within SGs undergoes pathological changes that promote the formation of neurotoxic inclusions, which propagate neuronal dysfunction and death. This review summarizes recent advances in understanding the molecular factors that regulate SG assembly and disassembly, as well as the pathological processes that drive the conversion of SGs into aggregates associated with neurodegenerative diseases. Particular emphasis is placed on the role of the ubiquitin-specific protease 10 (USP10), which modulates SG dynamics and has been mechanistically implicated in both ALS and AD. Finally, we discuss the therapeutic potential of targeting these pathways to mitigate neurodegenerative disease progression.},
}

@article {pmid42550987,
year = {2026},
author = {Waters-Harvey, B and Kane, K and Griffiths, AW and Smith, G and Bartlett, CM and Sproson, L and Smith, S and Starkey, J and Clift, A and Stavroulakis, T and Hobson, E and Mayberry, E and O'Cathain, A and Bidder, C and Kennedy, K and Gibson, J and McDermott, C and Knox, L},
title = {Co-Designing a Care Coordination Intervention for People With Motor Neuron Disease: Protocol for a Mixed Methods Study.},
journal = {JMIR research protocols},
volume = {15},
number = {},
pages = {e96327},
pmid = {42550987},
issn = {1929-0748},
mesh = {Humans ; *Motor Neuron Disease/therapy/psychology ; Amyotrophic Lateral Sclerosis/therapy ; England ; United Kingdom ; Wales ; },
abstract = {BACKGROUND: Motor neuron disease (MND), also known as amyotrophic lateral sclerosis (ALS), is a rapidly progressive neurological condition that requires complex multidisciplinary care. Within the United Kingdom, specialist centers provide expert interventions, while day-to-day support often relies on local nonspecialist community health and social care professionals. This is due to the distance between people's homes and specialist centers, as well as the availability of specialist health and social care professionals. This can lead to fragmented communication and emotional, physical, and financial burdens, and it can be time-consuming for people living with MND, their carers, and the health care professionals involved in their care. Despite the recognized need for better care coordination, it remains inadequate in practice, with a current lack of specific evidence-based interventions for achieving this.

OBJECTIVE: The MND Together project aims to address these systemic gaps by (1) developing a national picture of care coordination in England and Wales, (2) identifying barriers and facilitators to coordination within specialist and nonspecialist settings, and (3) co-designing a practical care coordination tool with key stakeholders.

METHODS: This protocol outlines the co-design of an intervention underpinned by the Behavior Change Wheel and the Socioecological Model. First, a mixed methods, multicenter study will be conducted to develop a national picture, comprising focus groups with people living with MND, carers, and health and social care professionals. Second, focused ethnography will be conducted in 5 MND specialist centers and their catchment areas, involving 25 people living with MND, to explore the barriers and facilitators to coordination in practice. Finally, a series of co-design workshops will be conducted to identify key priorities for care coordination and to develop a new intervention, the MND Together tool.

RESULTS: The project started in September 2025 and will run until October 2027. Workstream 1 started in December 2025, with recruitment beginning at the first site in February 2026. To date, we have recruited 23 people living with MND and carers as well as 16 health and social care professionals across 4 of the 9 sites. Workstream 1 will end in August 2026, with results published at the end of 2026. Workstream 2 began in May 2026 and will run until February 2027, with results published in the summer of 2027. Workstream 3 will begin in March 2027 and conclude with the co-design intervention developed by late 2027. This will then be piloted in practice.

CONCLUSIONS: By combining several methodologies with meaningful patient and public involvement and engagement, MND Together seeks to bridge the gap between specialist and community-based services. The MND Together tool aims to improve the quality of care and ensure that expert MND support is accessible as close as possible to every patient's home.},
}

Humans
*Motor Neuron Disease/therapy/psychology
Amyotrophic Lateral Sclerosis/therapy
England
United Kingdom
Wales

@article {pmid42539252,
year = {2026},
author = {Wieland, CM and Wright, SE and Willey, S and Purwar, I and Grudzien, SJ and Krans, A and Laimon, E and Asher, MJ and Isaacs, A and Garner, AL and Todd, PK},
title = {Altered neuronal start codon stringency favors cap-independent repeat-associated non-AUG translation.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.07.16.739042},
pmid = {42539252},
issn = {2692-8205},
abstract = {Intronic GGGGCC repeat expansions in C9orf72 cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This expansion supports a non-canonical form of translational initiation known as repeat-associated non-AUG (RAN) translation to produce toxic dipeptide repeat proteins that contribute to neurodegeneration. Here, we find that the efficiency of RAN translation and its dependency on the 5' 7-methylguanosine mRNA cap are variable across cell types, with both rodent neurons and human iNeurons favoring cap-independent RAN translation from two distinct repeats (CGG and GGGGCC) across multiple reading frames. Treatment with an eIF4E inhibitor that blocks global cap-dependent translation enhances RAN translation specifically in neurons. Intriguingly, cap-independent RAN translation exhibits less reliance on near-cognate codons for initiation than cap-dependent RAN translation. This finding led us to identify a surprising global increase in start codon stringency in neurons as a contributor to the relatively higher cap-independent RAN translation in this cell type. This effect correlates with a cytoplasmic redistribution of eIF1 in neurons and is reversed with neuronal overexpression of the eukaryotic initiation factor eIF5, which relaxes start codon stringency and selectively enhances cap-dependent RAN translation. Taken together, these findings reveal several neuron-specific features of translational regulation that favor cap-independent RAN translation with implications for nucleotide repeat expansion disorder pathogenesis and neuronal translational regulation.},
}

@article {pmid42539319,
year = {2026},
author = {Zhou, Y and Luster, CB and Pinto, SM and Feigel, ED and Paganoni, S and Izzy, S and Zafonte, RD and Giacino, JT and Hammond, FM and Daneshvar, DH},
title = {Traumatic Brain Injury and Risk of Amyotrophic Lateral Sclerosis Mortality: A Traumatic Brain Injury Model Systems Study.},
journal = {Neurotrauma reports},
volume = {7},
number = {},
pages = {2689288X261450846},
pmid = {42539319},
issn = {2689-288X},
abstract = {Emerging evidence suggests that amyotrophic lateral sclerosis (ALS) mortality is elevated following traumatic brain injury (TBI), reflecting a consequence of potential prodromal ALS, though the temporal patterns and underlying mechanisms remain unclear. We aimed to evaluate ALS mortality among individuals with TBI and examine temporal patterns. This study leveraged a retrospective cohort study of 20,250 individuals with complicated mild-to-severe TBI enrolled in the TBI Model Systems (TBIMS) from 1987 to 2024, with a cumulative 198,662 person-years (mean [standard deviation] = 9.8 [7.1] years) of follow-up. Standardized mortality ratios (SMRs) were calculated using the National Institute for Occupational Safety and Health Life Table Analysis System R package, adjusting for age, sex, race, and calendar year. Secondary analyses evaluated temporal patterns and injury severity differences in ALS mortality. Among 4,313 decedents in TBIMS, 11 died of ALS, representing significantly elevated mortality from ALS (SMR = 2.39; 95% confidence interval [CI]: 1.19-4.27) compared with the general population. Time-stratified analyses showed elevated ALS mortality within 2 years post-injury (SMR = 4.30; 95% CI: 1.17-11.01), but not after 2 years (SMR = 1.90; 95% CI: 0.76-3.92). Elevated ALS mortality was also observed within 2 years post-injury among those with severe TBI (SMR = 5.00; 95% CI: 1.03-14.61) and when including individuals with ALS at admission (SMR = 6.45; 95% CI: 2.37-14.04). ALS mortality was higher in the TBIMS cohort than in the general population, and this association was confined to within 2 years of injury. This pattern suggests potential reverse causality, whereby some TBIs in the cohort may have occurred in the setting of prodromal or pre-symptomatic ALS. Further investigation into TBI as a sign of subclinical ALS is warranted.},
}

@article {pmid42540536,
year = {2026},
author = {Wang, S and Lin, Y and Che, Y and Zhao, J and Xu, L and He, W and Zhang, W},
title = {Genetically inferred effects of brain structure and gene expression on neurodegenerative diseases: a Mendelian randomization study.},
journal = {Archives of medical science : AMS},
volume = {22},
number = {3},
pages = {1663-1677},
pmid = {42540536},
issn = {1734-1922},
abstract = {INTRODUCTION: Against the backdrop of accelerating population aging, the risk of neurodegenerative diseases (NDDs) has risen significantly. While brain structure plays a critical role in NDDs, the interplay between them remains unclear. This study employed Mendelian randomization (MR) to investigate potential causal relationships between brain structure, region-specific gene expression, and four NDDs - Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS) - providing new directions and genetically informed hypotheses for disease research.

MATERIAL AND METHODS: MR analyses were conducted using inverse-variance weighted (IVW), MR-Egger, weighted median, weighted mode, and Wald ratio methods. Summary-data-based MR (SMR) was applied to identify brain genes influencing NDDs. We calculated F-statistics, 95% confidence intervals (CIs), odds ratios, and p-values. Sensitivity analyses included the heterogeneity I[2] statistic, Cochran's Q test, Egger intercept test, MR-PRESSO, and leave-one-out validation.

RESULTS: Data from 512 unsupervised deep-learning imaging phenotypes (UDIPs) were analyzed. Thirty-four UDIPs showed associations consistent with a potential causal role in AD, 56 in PD, 22 in ALS, and 92 in MS. After false discovery rate (FDR) correction, 4 remained significant for AD and PD, 3 for ALS, and 28 for MS (p < 0.05). Brain regions (excluding the cervical spinal cord C-1) exhibited shared causal genetic features across all four NDDs, primarily involving HLA-class genes.

CONCLUSIONS: This study provides genetic evidence suggestive of potential causal associations between UDIPs, brain gene expression, and NDDs. These findings offer genetically predicted evidence that may generate hypotheses and inform future mechanistic research into NDD pathogenesis.},
}

@article {pmid42541368,
year = {2026},
author = {Hirano, Y},
title = {Long-term trajectories of physical, psychological, and psychosocial experiences among people living with amyotrophic lateral sclerosis using tracheostomy invasive ventilation: An 18-year longitudinal study.},
journal = {Journal of health psychology},
volume = {},
number = {},
pages = {13591053261474390},
doi = {10.1177/13591053261474390},
pmid = {42541368},
issn = {1461-7277},
abstract = {Advances in respiratory care have enabled people living with amyotrophic lateral sclerosis (PALS) using tracheostomy invasive ventilation (TIV) to live for many years with the disease. However, longitudinal evidence describing their psychosocial trajectories remains limited. This study explored the long-term trajectories of three PALS using TIV through repeated face-to-face assessments over an approximately 18 year period. Psychological state, subjective physical symptoms, and hope followed similar patterns across participants, worsening after illness onset and reaching their lowest levels between diagnosis and TIV initiation before improving and becoming increasingly individual over time. Perceived psychological support and sources of joy peaked after TIV initiation before fluctuating, whereas perceived financial status remained relatively stable. These findings demonstrate a shared pattern of early adaptation followed by increasingly individual long-term trajectories, providing a foundation for trajectory-informed holistic care.},
}

@article {pmid42541567,
year = {2026},
author = {Estevez-Fraga, C and Alvarez-Velasco, R and Afroz, T and Costa, MR and Jovičić, A and Yeh, FL and McColgan, P and Malaspina, A and McCampbell, A},
title = {Targeting TDP-43 in sporadic amyotrophic lateral sclerosis.},
journal = {Journal of neurology},
volume = {273},
number = {8},
pages = {},
pmid = {42541567},
issn = {1432-1459},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/therapy/pathology ; *DNA-Binding Proteins/metabolism/genetics ; Animals ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder characterized by motor neuron degeneration leading to early mortality. Despite advances in understanding genetic and molecular contributors, effective disease-modifying therapies for sporadic ALS are of limited utility. The identification of the accumulation of TAR DNA-binding protein 43 (TDP-43) in 97% of total ALS cases represents a critical pathogenic hallmark. This review examines key biological mechanisms underlying TDP-43 pathology, emerging therapeutic strategies, and evolving approaches to clinical trial design and biomarker development. TDP-43 loss of nuclear function, leading to widespread RNA missplicing, and inclusion of cryptic exons, represents an early and critical event in ALS pathogenesis causing downstream dysregulation of key neuronal genes such as STMN2 and UNC13A contributing to axonal degeneration and synaptic dysfunction. Therapeutic strategies targeting these pathways are currently under investigation. Additional approaches aim to ameliorate TDP-43 gain-of-function through cytoplasmic TDP-43 aggregation or modulating processes such as stress responses and RNA metabolism, although clinical translation has been challenging. Advances in biomarkers, including neurofilament light chain and cryptic exon-derived peptides, provide tools for developing efficient clinical trials. However, heterogeneity in disease progression and limitations of available clinical endpoints complicate trial design. Integration of biological insights with biomarker-driven patient stratification and optimized trial methodologies is essential to improve clinical trial outcomes. Emerging biomarkers may enable earlier diagnosis, monitoring of therapeutic response, and personalized treatment approaches. Continued alignment of biological discovery with innovative clinical trial design holds promise for advancing effective therapies and transforming the future of ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/metabolism/genetics/therapy/pathology
*DNA-Binding Proteins/metabolism/genetics
Animals

@article {pmid42541645,
year = {2026},
author = {Chu, M and Tan, M and Gan, X and Cui, S and Shi, L},
title = {Targeting Mitochondrial Dysfunction in Microglia: A New Frontier for Treating Neurodegenerative Diseases.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42541645},
issn = {1559-1182},
mesh = {*Microglia/metabolism/pathology/drug effects ; Humans ; *Neurodegenerative Diseases/metabolism/pathology/therapy/drug therapy ; *Mitochondria/metabolism/pathology/drug effects ; Animals ; },
abstract = {Neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) pose an urgent global health challenge. Growing evidence establishes microglia-driven neuroinflammation as a key driver of disease onset and progression, with mitochondrial dysfunction emerging as an early trigger of microglial activation. This review comprehensively summarizes current progress on how mitochondrial alterations regulate microglial activation across AD, PD, and ALS. We identify conserved mechanisms including metabolic reprogramming, impaired mitophagy, and inflammatory signaling, though Aβ, α-synuclein, and TDP-43 engage these pathways through disease-specific molecular routes. Therapeutic strategies targeting microglial mitochondria, including cGAS-STING and NLRP3 inhibitors, TREM2 agonists, and mitochondrial transplantation, remain largely preclinical. Emerging targets such as OLFML3 and GPNMB require functional validation in microglia. Collectively, this review underscores that preserving microglial mitochondrial health represents a promising therapeutic frontier and identifies key priorities for translating these strategies toward clinical application.},
}

*Microglia/metabolism/pathology/drug effects
Humans
*Neurodegenerative Diseases/metabolism/pathology/therapy/drug therapy
*Mitochondria/metabolism/pathology/drug effects
Animals

@article {pmid42542073,
year = {2026},
author = {Oriquat, G and Rizaev, J and Abdulqader, AF and Kadhim, AA and Jamuna, KV and Singhal, D and Bainsal, N and Mansurova, N},
title = {Gut microbiota and brain health: Disease-specific pathways and emerging therapeutic strategies.},
journal = {Multiple sclerosis and related disorders},
volume = {113},
number = {},
pages = {107407},
doi = {10.1016/j.msard.2026.107407},
pmid = {42542073},
issn = {2211-0356},
abstract = {The microbiota-gut-brain axis (MGBA) has emerged as a dynamic, bidirectional communication system linking the gastrointestinal tract and the central nervous system (CNS) through neural, immune, endocrine, and metabolic mechanisms. Increasing evidence indicates that alterations in gut microbial communities are associated with a wide range of neurological disorders; however, the strength of this association varies across diseases, and many mechanistic observations still rely predominantly on experimental models rather than human studies. This review provides an overview of current evidence regarding the role of the gut microbiota in maintaining CNS homeostasis, with particular emphasis on intestinal barrier function, immune modulation, vagal and enteric communication, and the generation of biologically active microbial metabolites, including short-chain fatty acids, bile acids, and neurotransmitter-related compounds. Studies in both clinical and experimental settings have reported disease-specific microbial signatures in conditions such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, autism spectrum disorders, and amyotrophic lateral sclerosis. In parallel, microbiota-directed interventions-including probiotics, prebiotics, dietary approaches, fecal microbiota transplantation, and strategies targeting microbial metabolites-have produced encouraging findings in preclinical studies and early-stage clinical investigations. Nevertheless, considerable heterogeneity in study populations, experimental methodologies, and therapeutic protocols continues to limit the translation of these findings into routine clinical practice. Collectively, current evidence supports the MGBA as a valuable framework for understanding neurological diseases while underscoring the need for rigorously designed longitudinal studies and well-controlled clinical trials to define its therapeutic relevance better.},
}

@article {pmid42543118,
year = {2026},
author = {Du, L and Yan, J},
title = {Lineage-calibrated peripheral monocyte-derived myeloid states in neurodegenerative disease: Recruitment, lesion decoding, and state persistence.},
journal = {Neurobiology of disease},
volume = {228},
number = {},
pages = {107556},
doi = {10.1016/j.nbd.2026.107556},
pmid = {42543118},
issn = {1095-953X},
abstract = {Peripheral monocytes and monocyte-derived macrophages are increasingly implicated in neurodegenerative disease, yet interpretation remains limited by phenotypic convergence with resident microglia, inconsistent lineage attribution, and strong dependence on experimental model and disease stage. We present a structured, lineage-calibrated framework that separates three linked processes: a recruitment gate controlling access to CNS borders and lesions; a lesion-decoding hub through which aggregate, lipid, cytokine, complement, antigenic, hypoxic, and danger-associated inputs are interpreted; and a state-persistence layer in which metabolic and epigenetic reinforcement stabilizes inflammatory, repair-supportive, or hybrid repair-restrictive programs. To make the framework operational, we first provide a cross-disease synthesis and then map representative models of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis to their specific recruitment routes, lesion cues, lineage confidence, and functional outcomes. We also distinguish what single-cell or spatial data can infer from what only origin-resolving approaches can establish, and propose practical terminology for studies that cannot perform fate mapping or parabiosis. A worked therapeutic example illustrates why the same recruitment pathway may be harmful during lesion expansion but useful during debris clearance and recovery. The central question is therefore not whether monocytes are present, but which model, compartment, time point, evidentiary tier, and stabilized state justify a disease-modifying claim. This framework links mechanistic evidence to biomarkers, patient stratification, and stage-aware intervention while reducing over-attribution of peripheral origin.},
}

@article {pmid42543164,
year = {2026},
author = {Wang, CY and Taylor, S and Pandya, VA and Clarke, BE and Pal, K and Shelkovnikova, TA and Wang, Y and Luisier, R and Patani, R},
title = {Intron retention in health and amyotrophic lateral sclerosis.},
journal = {Brain : a journal of neurology},
volume = {149},
number = {8},
pages = {2604-2618},
pmid = {42543164},
issn = {1460-2156},
support = {Patani/Dec22/957-793/MNDA_/Motor Neurone Disease Association/United Kingdom ; MN5DF/2022/003//My Name'5 Doddie Foundation/ ; BB-2024-c4-l4//Target ALS/ ; //Francis Crick Institute/ ; FC010110/CRUK_/Cancer Research UK/United Kingdom ; FC010110//UK Medical Research Council/ ; FC010110/WT_/Wellcome Trust/United Kingdom ; },
abstract = {Intron retention (IR) is the molecular phenomenon by which introns, historically thought to represent non-coding 'junk', remain unspliced within pre-mRNA transcripts, resulting in their incorporation into the mature mRNA molecule. While the role of IR is well established in species of plant, fungi, insects and viruses, it remains relatively understudied in mammalian biology. It was previously assumed that IR only played a limited role in downregulating a transcript's translation potential through downstream initiation of nuclear detention or nonsense mediated decay (NMD). However, recent studies highlight IR's significantly more complex and dynamic contribution to cellular physiology and disease. In particular, a role for IR is emerging in both health and neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), a rapidly progressive and invariably fatal disease that renders patients paralysed and unable to eat, speak or breathe. Significant technological advances now permit a comprehensive interrogation of previously unrecognized aspects of RNA metabolism in clinically relevant human cell types. In this review, we focus on the differential role(s) of nuclear and cytoplasmic intron retaining transcripts (nIRTs and cIRTs, respectively), as well as how IRTs may influence subcellular localization of ribonucleoprotein (RNP) complexes, loss of function of bound RNA binding proteins (RBPs) and liquid-liquid phase separation (LLPS) in physiology and disease. Additionally, we discuss the potential of IRTs as independent regulatory elements beyond their protein-coding functions and highlight how artificial intelligence is poised to accelerate discoveries in this area. In the context of IR's increasing appreciation, we also highlight its potential as a therapeutic target and explore current and future challenges in this burgeoning field.},
}

@article {pmid42544409,
year = {2026},
author = {Tsang, LPM and Tan, MS and Foo, YY and Lee, CS},
title = {Professional identity formation of family medicine residents in Singapore: a qualitative study to identify influencing factors.},
journal = {Annals of medicine},
volume = {58},
number = {1},
pages = {2698271},
doi = {10.1080/07853890.2026.2698271},
pmid = {42544409},
issn = {1365-2060},
mesh = {Humans ; Singapore ; *Internship and Residency ; Qualitative Research ; *Social Identification ; Male ; *Family Practice/education ; Female ; *Burnout, Professional/psychology/prevention & control ; Job Satisfaction ; *Physicians, Family/psychology ; Adult ; Community of Practice ; },
abstract = {BACKGROUND: Physician burnout and retention are critical challenges in Family Medicine (FM). Professional Identity Formation (PIF) in family physicians (FP) fosters resilience and job satisfaction but is often overlooked in residency training, particularly in predominantly hospital-based programs where residents are disconnected from the primary care community.

AIM AND METHODS: This qualitative study explored FP PIF in a predominantly hospital-based FM residency program in Singapore and identified factors influencing its development. Individual in-depth semi-structured interviews were conducted with FM residents and post-residency FPs selected through maximum variation purposive sampling. Data was collected and analysed iteratively using Braun and Clarke's reflexive thematic analysis. Cruess et al.'s conceptual model for PIF was used as a sensitising framework, alongside Lankveld et al.'s framework describing psychological processes underlying identity formation.

RESULTS: Thirteen participants were interviewed. Three themes were constructed. First, FP PIF wasunderpinned by four psychological 'senses' of competence, connectedness, appreciation, and career trajectory. Second, reflection and socialization drove development of these senses by enabling meaning-making, learning and belonging within the FM community of practice (CoP). Third, residency program features both enabled and/or constrained PIF; while some components scaffolded PIF, more intentional support was needed.

DISCUSSION AND CONCLUSION: PIF is a dynamic, context-dependent psychological process shaped by reflective practice, social participation, and program structure. Intentional support through curriculum design and faculty practices may strengthen PIF. These findings extend existing PIF frameworks and have implications for curriculum design, faculty development, program evaluation, and future research on fostering PIF in hospital-based residency training.},
}

Humans
Singapore
*Internship and Residency
Qualitative Research
*Social Identification
Male
*Family Practice/education
Female
*Burnout, Professional/psychology/prevention & control
Job Satisfaction
*Physicians, Family/psychology
Adult
Community of Practice

@article {pmid42545188,
year = {2026},
author = {Poletti, B and Aiello, EN and Consonni, M and Iazzolino, B and Torre, S and Faltracco, V and Telesca, A and Palumbo, F and Curti, B and De Luca, G and Moreschi, A and Frisco, F and Bella, ED and Bersano, E and Riva, N and Verde, F and Messina, S and Doretti, A and Maranzano, A and Morelli, C and Cappa, SF and Calvo, A and Strong, MJ and Silani, V and Lauria, G and Chiò, A and Ticozzi, N},
title = {Neuropsychological Sub-Phenotypes in Amyotrophic Lateral Sclerosis.},
journal = {European journal of neurology},
volume = {33},
number = {8},
pages = {e70706},
pmid = {42545188},
issn = {1468-1331},
support = {2015-0023//Fondazione Regionale per la Ricerca Biomedica, Regione Lombardia/ ; 1157625//Fondo Europeo di Sviluppo Regionale, Regione Lombardia/ ; RF-2016-02362405//Ricerca Sanitaria Finalizzata - Ministero della Salute/ ; 2017SNW5MB//"Progetti di Rilevante Interesse Nazionale" programme of the Ministry of Education, University and Research/ ; 101017598//Horizon 2020/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/psychology ; Female ; *Cognitive Dysfunction/etiology/diagnosis/epidemiology/psychology ; Neuropsychological Tests ; Male ; Aged ; Middle Aged ; Phenotype ; Retrospective Studies ; },
abstract = {BACKGROUND: This study aimed at identifying neuropsychological sub-phenotypes in amyotrophic lateral sclerosis (ALS) within the mild cognitive impairment (MCI) and mild behavioral impairment (MBI) frameworks.

METHODS: We used individual task-/item-level data from the cognitive and behavioral sections of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) from 901 non-demented ALS to derive neuropsychological sub-phenotypes pursuant to classical MCI and MBI frameworks and in accordance with an expanded version of Strong's criteria, which also addressed memory and visuo-spatial measures.

RESULTS: The prevalence of MCI and MBI was 39% and 37%, respectively in this retrospective review. The following MCI sub-phenotypes were identified: dysexecutive MCI-single- and multiple-domain (dMCI-sd: 63%; dMCI-md: 24%, respectively); non-dysexecutive MCI-single- and multiple-domain (ndMCI-sd: 12%; ndMCI-md: 1%, respectively). MBI was classified as follows: apathetic MBI-single- and multiple-domain (aMBI-sd: 40%; aMBI-md: 20%, respectively); apathetic-disinihibited/perseverative MBI-multiple domain (ad/pMBI-md: 21%); disinihibited/perseverative MBI-multiple domain (d/pMBI-md: 7%); psychotic MBI-single- and multiple-domain (psyMBI-sd: 2%; psyMBI-md: 3%, respectively); unclassifiable MBI-multiple domain (uMBI-md: 1%). 143 (16%) of patients exhibited mild cognitive and behavioral impairment (MCBI).

CONCLUSIONS: This study delivers a provisional, ECAS-based classification for the neuropsychological sub-phenotyping of non-demented ALS patients, which, with further validation, might be useful for both research and clinical purposes.},
}

Humans
*Amyotrophic Lateral Sclerosis/complications/psychology
Female
*Cognitive Dysfunction/etiology/diagnosis/epidemiology/psychology
Neuropsychological Tests
Male
Aged
Middle Aged
Phenotype
Retrospective Studies

@article {pmid42546549,
year = {2026},
author = {Silvagi, R and Rodriguez-Fohn, E and Reece, RJ and Cranford, JA and Alangaden, K and Byrd, M and Klausner, H and Pravin, R and Li, J and Conn, C and Dunne, R and O'Neil, BJ},
title = {Advanced vs basic life support outcomes in treatment of out-of-hospital-cardiac-arrest: A registry-based cohort study.},
journal = {The American journal of emergency medicine},
volume = {109},
number = {},
pages = {263-267},
doi = {10.1016/j.ajem.2026.07.021},
pmid = {42546549},
issn = {1532-8171},
abstract = {IMPORTANCE: The absolute effect on outcomes with Advanced, (ALS) as compared to Basic Life Support, (BLS) care in Out of Hospital Cardiac Arrest, (OHCA) remains unclear.

OBJECTIVE: To assess the association of ALS compared to BLS alone prehospital care on return of spontaneous circulation, (ROSC), survival to hospital discharge, and neurological outcome in OHCA in Detroit, MI.

METHODS: Retrospective analysis of 6746 patients from the Cardiac Arrest Registry to Enhance Survival database from January 2016 to December 2021 who had non-traumatic OHCA and received cardiopulmonary resuscitation. Cohorts were grouped by ALS v BLS care then initial rhythm and then compared by chi-squared, multivariable logistic, and multinomial regression analysis for outcomes of sustained ROSC, survival to hospital discharge and favorable neurological outcome at hospital discharge. The BLS cohort is defined by units that provided manual CPR, automated rhythm and defibrillation, airway management, but no endotracheal intubation or parenteral medications. ALS care was defined as manual rhythm interpretation, manual defibrillation, intravenous or intraosseous drug administration or endotracheal intubation.

RESULTS: Mean age was 62.6 years (SD-16.7), with 56.3% male and 84.6% Black. Cohort breakdown: shockable ALS (S-ALS; n = 330, 4.9%); shockable BLS (S-BLS; n = 466, 6.9%); non-shockable ALS (NS-ALS; n = 2793, 41.4%); non-shockable BLS (NS-BLS; n = 3157, 46.8%). ROSC rates by cohort: S-ALS (37.9%); S-BLS (19.5%); NS-ALS (18.6%); NS-BLS (9.3%). ALS was associated with increased sustained ROSC for all initial rhythms (p < .001). S-ALS was associated with increased survival (p = .03), and neurologic outcome (p = .01) when compared to S-BLS.

CONCLUSION & RELEVANCE: Advanced Life Support, relative to Basic Life Support alone, was associated with improved sustained return of spontaneous circulation across all initial rhythms, and improved survival to discharge and favorable neurologic outcome in shockable initial rhythms.},
}

@article {pmid42546822,
year = {2026},
author = {Ghaderi, S and Mohammadi, S and Iturria-Medina, Y},
title = {Quantitative susceptibility mapping in neurodegenerative diseases: An umbrella review of iron-related biomarkers and mechanisms.},
journal = {Magnetic resonance imaging},
volume = {},
number = {},
pages = {110765},
doi = {10.1016/j.mri.2026.110765},
pmid = {42546822},
issn = {1873-5894},
abstract = {Pathological iron accumulation is a common pathophysiological hallmark across multiple neurodegenerative diseases (NDDs), motivating the need for accurate, non-invasive quantification methods. Quantitative susceptibility mapping (QSM) is an advanced magnetic resonance imaging (MRI) technique that enables in vivo measurement of tissue magnetic susceptibility (χ), providing a sensitive proxy for iron content. This umbrella review systematically evaluates the diagnostic accuracy, clinical correlations, and distinct iron distribution patterns of QSM in major NDDs, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and atypical Parkinsonism. We included 15 (13/15 were rated Low or Critically Low on AMSTAR 2) systematic reviews and meta-analyses (through July 15, 2026); however, the findings should be interpreted cautiously because of heterogeneity and the low methodological quality. A Corrected Covered Area (CCA) analysis demonstrated only slight overlap of primary studies across the included reviews (CCA = 5.42%). Collectively, the evidence indicates that QSM provides comparable or higher diagnostic sensitivity and reliability than conventional R2* and SWI techniques, particularly for deep gray matter structures. The findings support significant iron overload in the substantia nigra, particularly in the pars compacta, as a robust biomarker for PD that correlates with motor severity and disease duration. Furthermore, regional iron profiling in the basal ganglia is critical for differential diagnosis; specifically, elevated χ in the putamen and globus pallidus effectively distinguishes multiple system atrophy and progressive supranuclear palsy from idiopathic PD. Distinctively, AD and ALS exhibit specific χ alterations in the thalamus, motor cortex, and hippocampus, reflecting divergent iron-related pathophysiological mechanisms, which correlate with cognitive impairment and upper motor neuron signs. Overall, QSM shows diagnostic promise and offers mechanistic insights into iron-related neurodegenerative processes.},
}

@article {pmid42547743,
year = {2026},
author = {Tse, CS},
title = {Letter to the Editor Regarding Barkan et al.'s Article, "Randomized Trial of Intensive Nurse‑Led Follow‑up Versus Standard Care in Inflammatory Bowel Disease".},
journal = {Digestive diseases and sciences},
volume = {},
number = {},
pages = {},
pmid = {42547743},
issn = {1573-2568},
}

@article {pmid42547788,
year = {2026},
author = {Wo, XM and Zhang, GM},
title = {Interpreting the clinical utility and generalizability of a multitask perioperative prediction model.},
journal = {NPJ digital medicine},
volume = {9},
number = {1},
pages = {},
pmid = {42547788},
issn = {2398-6352},
abstract = {This Matters Arising comments on Yoon et al.'s multitask gradient boosting model for predicting acute kidney injury, postoperative respiratory failure and in-hospital mortality after non-cardiac surgery. We ask for clarification on the clinical decision context and threshold ranges in the decision curve analyses, the absolute impact of the model for rare outcomes, and calibration and potential recalibration in external cohorts to support implementation.},
}

@article {pmid42547898,
year = {2026},
author = {Domke, N and Geue, K and Schlichte, I and Ullsperger, M and Meyer, T and Petri, S and Schreiber, S and Vielhaber, S and Junne, F and Vogt, S},
title = {Depressive symptoms in amyotrophic lateral sclerosis: associations with quality of life, disease progression and perceived social support-a German multicenter study.},
journal = {BMC psychology},
volume = {14},
number = {1},
pages = {},
pmid = {42547898},
issn = {2050-7283},
mesh = {Humans ; *Social Support ; *Quality of Life/psychology ; *Amyotrophic Lateral Sclerosis/psychology/complications ; Female ; Male ; Disease Progression ; Cross-Sectional Studies ; Middle Aged ; *Depression/psychology ; Aged ; Germany ; Adult ; },
abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive, fatal neurodegenerative disease. Patients with ALS are at increased risk of developing depressive symptoms. A clearer understanding of the associations between depressive symptoms, disease progression, health-related quality of life and perceived social support is needed to advance intervention-oriented research and improve psychosocial care in ALS.

METHODS: In a multicenter cross-sectional study, patients with ALS were asked to complete patient-reported outcomes (PROs) to evaluate depressive symptoms (ALS-Depression-Inventory, ADI-12), health-related quality of life (ALS-Assessment-Questionnaire, ALSAQ-5/ALSAQ-40), physical functioning (ALS-Functional Rating Scale-Extension, ALSFRS-EX) and perceived social support (Multidimensional Scale of Perceived Social Support, MSPSS). To evaluate associations between demographic/clinical variables and PROs, we performed Pearson's, Spearman's, and partial correlation analyses. In addition, a multiple regression was run to identify predictors of depressive symptoms. Comparisons of patient groups were performed with chi-squared tests for categorical variables and Student t-tests or one-way analysis of variance (ANOVA) for continuous variables, followed by post-hoc tests.

RESULTS: Out of the 150 patients examined, 60% reported depressive symptoms, with half of them exhibiting clinically relevant depressive symptoms. Depressive symptoms were significantly associated with disease progression (r = .466, p < .001), various aspects of health-related quality of life (mobility: r = .394, activities of daily living: r = .268 and emotional well-being: r = .793, all p < .001), the MSPSS sum score (partial r = -.234, p  = .007), and the ALSFRS-EX sum score (r = -.352, p < .001). Patients with depressive symptoms reported significantly more physical impairments (p = .002) and less perceived social support by their families (p = .016) and friends (p < .001) compared to patients without depressive symptoms.

CONCLUSIONS: Depressive symptoms are prevalent in patients with ALS and are closely associated with faster disease progression, reduced physical functioning, poorer health-related quality of life, and lower perceived social support. Further studies, particularly using qualitative methods, are needed to elucidate protective factors, clarify psychosocial mechanisms, and support the conceptualization of specialized and integrated psychosocial care for patients with ALS in Germany.},
}

Humans
*Social Support
*Quality of Life/psychology
*Amyotrophic Lateral Sclerosis/psychology/complications
Female
Male
Disease Progression
Cross-Sectional Studies
Middle Aged
*Depression/psychology
Aged
Germany
Adult

@article {pmid42537332,
year = {2026},
author = {Silva Santos, M and Castro, J and de Carvalho, M},
title = {F-wave responses and recruitment at low intensities: Muscle-specific excitability profiles of intrinsic hand muscles.},
journal = {Neurophysiologie clinique = Clinical neurophysiology},
volume = {56},
number = {5},
pages = {103185},
doi = {10.1016/j.neucli.2026.103185},
pmid = {42537332},
issn = {1769-7131},
abstract = {OBJECTIVES: F-waves are late motor responses traditionally elicited via supramaximal stimulation. However, submaximal stimulation may offer a more sensitive probe for assessing spinal motoneuron excitability. This study characterizes F-wave recruitment curves using graded submaximal stimulation across various intrinsic hand muscles.

METHODS: F-waves were recorded from the abductor pollicis brevis (APB), abductor digiti minimi (ADM), and first dorsal interosseous (FDI) in 15 healthy subjects (ages 35-78). Four stimulus intensities were employed-10%, 20%, 30%, and 100% of the maximal compound muscle action potential (CMAP) amplitude-with 20 stimuli delivered per intensity. Analysis focused on F-wave frequency, amplitude, and matched F-wave/CMAP ratios (F-wave/CMAPm), where the F-wave and CMAP were recorded at identical stimulus intensities.

RESULTS: Most parameters correlated positively with stimulus intensity; however, F-wave/CMAPm consistently decreased as intensity increased. The ADM exhibited a distinct recruitment profile, with F-wave persistence rising steeply at low intensities and reaching near-saturation at 30%, while showing no significant amplitude differences between submaximal levels. In contrast, the APB and FDI displayed more linear recruitment patterns for both persistence and amplitude.

DISCUSSION: Submaximal stimulation reliably elicits F-waves and reveals muscle-specific excitability profiles. The ADM's high excitability suggests a more readily recruitable motoneuron pool. Furthermore, the inverse relationship between F-wave/CMAPm and stimulus intensity suggests the early recruitment of larger, highly excitable Type II motoneurons. This refined recruitment curve approach may provide valuable insights into the "split-hand" phenomenon observed in amyotrophic lateral sclerosis.},
}

@article {pmid42538529,
year = {2026},
author = {Marcus, B},
title = {Invited Commentary on: Azizzadeh et al.'s "The Multilevel Facial Anatomic Classification System: A Comprehensive Framework for Contemporary Facelift and Neck Rejuvenation Surgery".},
journal = {Facial plastic surgery & aesthetic medicine},
volume = {},
number = {},
pages = {26893614261466756},
doi = {10.1177/26893614261466756},
pmid = {42538529},
issn = {2689-3622},
}

@article {pmid42538750,
year = {2026},
author = {Krutovs, V and Grosmane, A and Kažmere, RR and Roddate, M and Ķauķe, G and Grosa, DP and Šetlere, S and Dīriks, M and Karelis, G and Ķēniņa, V},
title = {Nationwide Epidemiology of Motor Neuron Diseases in Latvia (2020-2024): Incidence, Prevalence, and Clinical Characteristics.},
journal = {European journal of neurology},
volume = {33},
number = {8},
pages = {e70710},
pmid = {42538750},
issn = {1468-1331},
mesh = {Humans ; Latvia/epidemiology ; Prevalence ; Female ; Incidence ; *Motor Neuron Disease/epidemiology/physiopathology ; Male ; Retrospective Studies ; Adult ; Middle Aged ; Aged ; Muscular Atrophy, Spinal/epidemiology ; Adolescent ; Young Adult ; Child ; Amyotrophic Lateral Sclerosis/epidemiology/physiopathology ; Aged, 80 and over ; },
abstract = {BACKGROUND: Motor neuron diseases (MNDs), including amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and spinal and bulbar muscular atrophy (SBMA), are rare, progressive neurodegenerative conditions. Although well-studied in Western Europe, no nationwide epidemiological data have been published from Latvia. This study aimed to assess the incidence, prevalence, and clinical characteristics of MNDs in the Latvian population.

METHODS: A retrospective, hospital-based analysis was performed using records from Pauls Stradiņš Clinical University Hospital, Riga East University Hospital, and the Children's Clinical University Hospital between January 2020 and December 2024. Patients were identified through relevant ICD-10 codes. Incidence and prevalence rates were calculated per 100,000 population and age-standardized to the 2013 European Standard Population.

RESULTS: A total of 181 prevalent MND cases were identified: 131 with ALS or related phenotypes, 10 with adult-onset SMA, 33 with pediatric SMA, and 7 with SBMA. The age-standardized incidence of ALS was 1.22 per 100,000 person-years, and the prevalence was 4.69 per 100,000. Limb weakness or paresis was the most common initial symptom (48.1%). The mean diagnostic delay was 13.4 months for ALS, 43.8 months for PLS, 206.8 months for SBMA and 17.3 months for pediatric SMA. The prevalence of pediatric SMA was 9.91 per 100,000, with type II being the most frequent subtype. All SMA and SBMA cases were genetically confirmed.

CONCLUSION: This first nationwide study of MNDs in Latvia highlights diagnostic delays and possible under-recognition of adult SMA and SBMA. Genetic testing, a national registry, and equitable therapy access should be prioritized.},
}

Humans
Latvia/epidemiology
Prevalence
Female
Incidence
*Motor Neuron Disease/epidemiology/physiopathology
Male
Retrospective Studies
Adult
Middle Aged
Aged
Muscular Atrophy, Spinal/epidemiology
Adolescent
Young Adult
Child
Amyotrophic Lateral Sclerosis/epidemiology/physiopathology
Aged, 80 and over

@article {pmid42538773,
year = {2026},
author = {Calvo, A and Moglia, C and Canosa, A and Manera, U and Vasta, R and Matteoni, E and Maccabeo, A and Cabras, S and Pellegrino, G and Minerva, E and Giudici, AD and Passidomo, V and Palumbo, F and Iazzolino, B and Mora, G and Chiò, A},
title = {Early Cognitive and Behavioral Changes in Primary Lateral Sclerosis: A Population-Based Study.},
journal = {European journal of neurology},
volume = {33},
number = {8},
pages = {e70720},
pmid = {42538773},
issn = {1468-1331},
support = {RF-2016-02362405//Ministero della Salute/ ; 2017SNW5MB//Ministero dell'Università e della Ricerca/ ; 20228N7573//Ministero dell'Università e della Ricerca/ ; 259867//Seventh Framework Programme/ ; 101017598//Horizon 2020 Framework Programme/ ; 101137074//HORIZON EUROPE Framework Programme/ ; DIG-ALS//Agenzia di Ricerca per la Sclerosi Laterale Amiotrofica/ ; },
mesh = {Humans ; Female ; Male ; *Motor Neuron Disease/complications/psychology/physiopathology ; Middle Aged ; Aged ; Amyotrophic Lateral Sclerosis/psychology/complications/physiopathology ; *Cognitive Dysfunction/etiology/physiopathology ; Executive Function/physiology ; Neuropsychological Tests ; },
abstract = {OBJECTIVE: Primary lateral sclerosis (PLS) is a rare upper motor neuron neurodegenerative disorder whose cognitive profile, particularly at early stages, remains incompletely defined. We aimed to characterize cognitive and behavioral features of PLS at diagnosis and compare them with predominant upper motor neuron amyotrophic lateral sclerosis (PUMN-ALS) and healthy controls (HCs).

METHODS: Patients diagnosed with PLS between 2007 and 2021 were identified from the population-based Piemonte and Valle d'Aosta ALS Register. Diagnoses were established according to consensus criteria, including early, probable, and definite PLS. All patients underwent comprehensive neuropsychological and behavioral assessment within 3 months of their first ALS center visit. Cognitive-behavioral status was classified using ALS-frontotemporal dementia (FTD) consensus criteria.

RESULTS: Thirty-two PLS patients were included (mean disease duration, 25 months). Cognitive and/or behavioral impairment was identified in 29.3% of patients, most commonly affecting executive function, memory, and social cognition, including 21.1% early PLS. Compared with HCs, PLS patients showed poorer performance across several cognitive domains and higher anxiety and depression scores. Compared with matched PUMN-ALS patients, PLS patients demonstrated slightly worse executive performance, while the overall frequency of cognitive-behavioral impairment was similar. Behavioral profiles differed qualitatively, with apathy more frequent in PUMN-ALS. No PLS patient met criteria for frontotemporal dementia.

INTERPRETATION: Cognitive and behavioral impairments are already detectable at the time of diagnosis in a substantial proportion of patients with PLS, including early PLS, supporting the view of PLS as a multidimensional neurodegenerative disorder with early extramotor involvement.},
}

Humans
Female
Male
*Motor Neuron Disease/complications/psychology/physiopathology
Middle Aged
Aged
Amyotrophic Lateral Sclerosis/psychology/complications/physiopathology
*Cognitive Dysfunction/etiology/physiopathology
Executive Function/physiology
Neuropsychological Tests

@article {pmid42539086,
year = {2026},
author = {Lee, BH and Chan, J and Leung, YY and McMillan, CT and , and Song, Y and Amado, DA and Wang, K},
title = {Dissecting the relationship between haplotypes around ATXN2 CAG repeats and the number of CAA interruptions by long-read sequencing.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.03.11.26348169},
pmid = {42539086},
abstract = {BACKGROUND: CAG repeat expansions in ATXN2 are implicated as risk factors for several neurological diseases, including spinocerebellar ataxia type 2 (SCA2) when >=33 CAG repeats are present, and amyotrophic lateral sclerosis (ALS) when 27-33 CAG repeats are present. However, how haplotypes around the repeats and CAA interruptions within the repeats are associated with disease phenotypes remains poorly understood. Previous studies on haplotypes around ATXN2 were limited to SNPs very close to the repeats (<5kb) or were based on statistical inference only.

METHODS: Here, we used long-read sequencing on the Oxford Nanopore Technologies (ONT) platform to simultaneously infer haplotypes around ATXN2 , the number of CAG repeats, and the number of CAA interruptions, along with NYGC ALS Consortium NGS dataset. We further sequenced 41 individuals (EUR = 39) with neurological diseases with intermediate repeats by ONT.

RESULTS: We found that haplotypes around ATXN2 and the number of interruptions show ethnicity-specific and ALS-specific distribution. Three CAA interruptions are present at low prevalence (∼1%) in control populations in multiple ancestry groups, but high prevalence (∼55%) in ALS individuals with intermediate repeats. Furthermore, we examined 159 individuals with ALS (∼90% European ancestry) with intermediate ATXN2 repeats and found a unique haplotype in ALS individuals with three CAA interruptions, which can be tagged by an SNV, rs148019457. We also validated that the rs148019457-G allele is only present in haplotypes with three CAA interruptions.

CONCLUSIONS: In summary, our study shows that 3 CAA interruptions are rarely seen in healthy controls but are common in those with expanded ATXN2 CAG repeats who have neurological disorders, and that rs148019457 tags a specific haplotype with 3 CAA interruptions within expanded ATXN2 CAG repeats in individuals of European ancestry. These results have implications for the development of precision genomic medicine for neurological disorders, and the tag SNP may help identify those with interruptions from existing population genotyping data.},
}

@article {pmid42534468,
year = {2026},
author = {Luster, CB and Abdolmohammadi, B and Mastrodicasa, MJ and Nowinski, CJ and Feigel, ED and Finegan, B and White, AJ and Connors, EJ and Rovito, CA and Zafonte, RD and Alosco, ML and McKee, AC and Mez, J and Daneshvar, DH},
title = {Neurodegenerative mortality among National Football League Players.},
journal = {EClinicalMedicine},
volume = {97},
number = {},
pages = {104051},
pmid = {42534468},
issn = {2589-5370},
abstract = {BACKGROUND: Empirical research demonstrates elevated neurodegenerative mortality among individuals with repetitive head impact (RHI) exposure, including National Football League (NFL) players. This investigation addressed prior methodological limitations, including selection bias, subjective diagnoses, and retrospective reporting, by analyzing the relationship between RHI exposure and neurodegenerative mortality in a fully enumerated, 5.8-fold larger cohort of NFL players.

METHODS: A population-based retrospective cohort study was conducted comprising all current and former NFL athletes who debuted between 1960 and 2019 and played at least one regular or postseason NFL game, with National Death Index records (1979-2023) matched to Sports Reference, LLC data. Standardized mortality ratios (SMRs) were calculated from National Institute for Occupational Safety and Health data compared to an age-, sex-, race-, and calendar-year-standardized general population. Sensitivity analysis assessed whether the observed excess neurodegenerative mortality could be attributed to competing risks using a cause-specific hazard simulation.

FINDINGS: A total of 19,824 athletes had a cumulative 518,833 person-years (mean = 26.2 years, SD = 16.2), with 1994 decedents. NFL players exhibited lower all-cause mortality (SMR = 0.70; 95% CI: 0.67-0.74) but higher neurodegenerative mortality (SMR = 3.94; 95% CI: 3.38-4.56), including amyotrophic lateral sclerosis (SMR = 4.55; 95% CI = 3.13-6.38), all-cause dementia (SMR = 3.80; 95% CI = 3.11-4.60), and Parkinson's disease (SMR = 3.88; 95% CI: 2.76-5.30). Cause-specific hazard simulation indicated that competing risks alone would inflate the expected NDD SMR by a factor of 1.30, yielding a residual neurodegenerative SMR of 3.04 (95% CI: 2.63-3.50).

INTERPRETATION: Neurodegenerative mortality was nearly four times higher in NFL players compared to the general population and remained threefold higher after accounting for competing risks. Together, these findings strengthen the evidence for RHI exposure-related neurodegenerative mortality in NFL players that cannot be explained by differential survivorship.

FUNDING: The National Institute of Neurological Disorders and Stroke [U54NS115266; U01NS086659], the National Institute on Aging [P30AG13846; P30AG072978], and the Maloney/Carpenter Trauma-Related Neurodegenerative Disease Research Fund.},
}

@article {pmid42536230,
year = {2026},
author = {Naktinytė, E and Vilimienė, R and Valančius, D and Baronas, K and Zagorskienė, I and Utkus, A and Klimašauskienė, A and Burnytė, B},
title = {Genetic variants among patients with motor neuron disease in Lithuania - a retrospective single-center study.},
journal = {Neurogenetics},
volume = {27},
number = {1},
pages = {},
pmid = {42536230},
issn = {1364-6753},
mesh = {Humans ; *Motor Neuron Disease/genetics/epidemiology ; Female ; Retrospective Studies ; Lithuania/epidemiology ; Male ; Middle Aged ; *Genetic Variation ; C9orf72 Protein/genetics ; Aged ; Adult ; Phenotype ; Amyotrophic Lateral Sclerosis/genetics ; DNA Repeat Expansion ; },
abstract = {Motor neuron disease (MND) comprises several clinical phenotypes, with amyotrophic lateral sclerosis (ALS) being the most common. Despite the identification of over 40 ALS-associated genes, the pathogenesis remains complex and polygenic. This study evaluated the clinical phenotypes and prevalence of genetic causes in MND patients in Lithuania. We conducted a retrospective single-center study at a tertiary care clinic on patients with MND. Clinical and molecular genetic data were analyzed. The study included 53 patients with a mean age at symptom onset of 55 years. Most patients (43/53; 77.4%) were diagnosed with ALS, and the most common onset was spinal (39/53; 73.6%). The frequency of pathogenic or likely pathogenic genetic variants was 15.7% (8/51). C9orf72 hexanucleotide repeat expansion was detected in 5.9% (3/51) of patients. Next-generation sequencing was performed in 49 patients, of whom 5 (10.2%) had pathogenic or likely pathogenic variants, including pathogenic variants in the SOD1 and NEK1 genes and likely pathogenic variants in the FUS. The most common finding was C9orf72 hexanucleotide repeat expansion, followed by variants in SOD1 and FUS genes. The genetic spectrum was broadly similar to internationally recognized MND-associated genes, though formal comparisons were not performed due to the absence of a control group. These results emphasize the importance of systematic genetic testing in clinical practice and contribute to the limited data on the genetic spectrum of MND in the Baltic region.},
}

Humans
*Motor Neuron Disease/genetics/epidemiology
Female
Retrospective Studies
Lithuania/epidemiology
Male
Middle Aged
*Genetic Variation
C9orf72 Protein/genetics
Aged
Adult
Phenotype
Amyotrophic Lateral Sclerosis/genetics
DNA Repeat Expansion

@article {pmid42528478,
year = {2026},
author = {Palumbo, F and Iazzolino, B and Moglia, C and Manera, U and Matteoni, E and Cabras, S and Pellegrino, G and Minerva, E and Passidomo, V and Vasta, R and Mora, G and D'Ovidio, F and Canosa, A and Calvo, A and Chiò, A},
title = {Toward a Behavioral Reserve Model in Amyotrophic Lateral Sclerosis.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78315},
pmid = {42528478},
issn = {1531-8249},
abstract = {OBJECTIVE: Behavioral impairment is common in amyotrophic lateral sclerosis (ALS) and strongly affects autonomy, caregiver burden, and outcomes, yet predictors of vulnerability remain unclear. We investigated whether premorbid regulatory traits and socio-educational exposures are associated with behavioral phenotypes in ALS within a behavioral reserve framework.

METHODS: We analyzed 965 consecutively assessed patients with ALS from a prospective tertiary-center cohort. Behavioral impairment was measured using the Frontal Systems Behavior Scale (FrSBe; family-rated before and after onset) and, in a subset (n = 633), the Edinburgh Cognitive and Behavioural ALS Screen-Carer Interview (ECAS-CI). Theory-driven hierarchical logistic regression models tested associations between behavioral outcomes and premorbid behavioral regulation, education, occupation, and a Social Interaction Index, including interaction effects. Prespecified sensitivity analyses addressed potential bias in premorbid estimates.

RESULTS: Premorbid behavioral regulation showed the strongest associations with behavioral impairment across all FrSBe models. Higher combined educational attainment and social exposure were associated with lower odds of impairment, with a significant interaction across multiple behavioral domains. These patterns persisted in restricted sensitivity analyses. Reserve proxies were not significantly associated with ECAS-CI total impairment, although domain-specific effects were observed.

INTERPRETATION: These findings provide empirical support for a behavioral reserve framework in ALS, in which premorbid regulatory traits and socio-educational exposures are associated with behavioral vulnerability. Although causal inference is limited, reserve-related factors may contribute to non-motor heterogeneity in ALS and may inform future approaches to early behavioral risk stratification. ANN NEUROL 2026.},
}

@article {pmid42528798,
year = {2026},
author = {Gao, X and Chen, S and Mahabub, S and Cao, B and Deng, J and Ye, W and Yang, H and Zou, Z},
title = {A modified frailty index to identify high-risk groups for amyotrophic lateral sclerosis.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1879866},
pmid = {42528798},
issn = {1664-2295},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by progressive muscle weakness and poor prognosis, which requires early detection to optimize therapeutic outcomes. This study aims to develop a risk stratification tools for ALS and to assist in identifying high-risk groups.

METHODS: A prospective cohort study was conducted using the UK Biobank (500,033 participants), which were split into training sets and validation sets. We calculated the frailty index (FI) and modified frailty index (MFI) for the participants and estimated their association with ALS. Finally, two risk stratification tools were constructed and the time-dependent ROC curve was utilized to evaluate the discriminatory performance of each model.

RESULTS: Among the 49 deficits in FI, we identified five deficits that were significantly associated with ALS, including falls, whole-body pain, long-standing illness, disability or infirmity, self-rated health and tiredness or lethargy in last 2 weeks, which together constructed the MFI. Both the FI and MFI were associated with a higher risk of ALS (HRFI = 4.58, 95% CI = 1.31-16.07, HRMFI = 4.59, 95% CI = 2.79-7.53). Finally, a combination of MFI, gender, age and BMI demonstrated the best discriminative ability. Specifically, on the validation set, it achieved a C-index of 0.696.

CONCLUSION: By focusing on deficits associated with ALS, the MFI may improve the ability to identify individuals at elevated risk of the disease. It could therefore serve as a valuable screening tool for risk stratification in the general population.},
}

@article {pmid42529618,
year = {2026},
author = {Fiskum, V and Winter-Hjelm, N and Christiansen, N and Sandvig, A and Sandvig, I},
title = {Microscale dysfunction and mesoscale compensation in degenerating neuronal networks.},
journal = {Network neuroscience (Cambridge, Mass.)},
volume = {10},
number = {3},
pages = {594-612},
pmid = {42529618},
issn = {2472-1751},
abstract = {Progressive neurodegenerative diseases involve neuronal dysfunction across cellular, circuit, and whole-brain levels. Despite differences in anatomical origins, vulnerable neuronal subtypes, and specific misfolded proteins, these diseases share key features. In presymptomatic phases, neural networks engage compensatory processes to maintain function, including increased centralization and reliance on a rich-club of hub nodes. While such mechanisms have supporting evidence in some disorders, they remain less established in amyotrophic lateral sclerosis (ALS), limiting understanding of potential shared presymptomatic responses. To address this, we investigated structural and functional properties of ALS patient-derived motor neuron networks compared with healthy controls using longitudinal multielectrode array recordings and graph theory-based analysis. We observed microscale dysfunction marked by TAR DNA-binding protein 43 proteinopathy, hyperactivity, and reduced spike amplitude. Structurally, ALS networks exhibited neurite hypertrophy, suggesting attempts to form new connections. Mesoscale analyses revealed functional reconfigurations, including increased rich-club connectivity and network assortativity, indicating compensatory centralization. Our findings provide novel evidence that ALS network features can be recapitulated in in vitro models, and that these networks progressively become more centralized to preserve computational capacity, imposing growing demands on hub nodes and predisposing them to further damage. These results support models proposing common network reconfiguration mechanisms across neurodegenerative diseases.},
}

@article {pmid42529685,
year = {2026},
author = {Cheung, N},
title = {Cellular Logistics and Synaptic Vesicle Vulnerability in Major Depressive Disorder and Amyotrophic Lateral Sclerosis Comorbidity: Insights From Nicotinamide Mononucleotide Rescue and Transcriptome-Wide Association Study Integration.},
journal = {Cureus},
volume = {18},
number = {7},
pages = {e113549},
pmid = {42529685},
issn = {2168-8184},
abstract = {BACKGROUND: Major depressive disorder (MDD) and amyotrophic lateral sclerosis (ALS) are usually treated as unrelated, yet depressive symptoms occur in a substantial minority of people with ALS and may appear early. These symptoms are heterogeneous and may reflect syndromal MDD, psychological and functional burden, fatigue, apathy, pseudobulbar affect, frontotemporal involvement, sleep or respiratory disturbance, medication effects, or shared affective vulnerability. A proposed pruning-continuum model suggests both disorders may share vulnerability in microglia-mediated synaptic pruning, with ALS amplified by autophagy and protein-quality-control failure and MDD by RNA-processing, stress, and immune dysregulation. We performed an exploratory secondary transcriptome-wide association study (TWAS)/pathway-integration analysis to test whether predefined nicotinamide mononucleotide (NMN)-nominated pathways map onto this vulnerability.

METHODS: We integrated precomputed S-PrediXcan outputs for MDD and ALS across available brain-relevant tissues. Ten Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were predefined from a prior re-analysis of NMN-associated transcriptional programs in aged mouse metabolic tissues. Mouse-derived candidates were represented by human ortholog symbols before the human TWAS screen. The analysis tested nominated pathways rather than the 35-gene NMN-robust list as a standalone set. Cross-tissue screening used Stouffer Z aggregation, tissue-level Wilcoxon testing, competitive permutation testing, percentile bootstrap intervals, pairwise disease statistics, Levene variance tests, concordance measures, and leave-one-out sensitivity analysis. No analysis was treated as confirmatory or evidence of causal mediation.

RESULTS: MDD showed the strongest Stouffer-based exploratory signal in the synaptic vesicle cycle pathway, with a meta-across-tissue Stouffer Z of 3.41 and a wide bootstrap 95% confidence interval of -0.46 to 7.40. This signal did not survive competitive permutation testing (p = 0.1222) or Wilcoxon testing (p = 0.1926). The strongest tissue-level result occurred in the amygdala (Z = 4.057; nominal Wilcoxon p = 0.0093), although tissue-level permutation testing was not performed in the multi-gene-set run. ALS showed no significant meta-across-tissue enrichment among the 10 nominated pathways but displayed candidate gene-level signals in autophagy, endosomal, and vesicle-related genes, including TBK1 and C9orf72. Exploratory Levene tests indicated variance heterogeneity in the regulation of the actin cytoskeleton, endocytosis, and neuroactive ligand-receptor interaction; the actin cytoskeleton and endocytosis remained significant in pooled global false discovery rate (FDR) analysis. Fourteen genes were influential in at least two focus pathways, including EGF, KNG1, FGF8, RAC1, PAK1, PAK2, RAF1, MAPK1, and FGFR1.

CONCLUSIONS: These findings are hypothesis-generating. MDD and ALS may stress overlapping cellular logistics processes while engaging largely different genes. MDD showed the strongest exploratory pathway-level signal in synaptic vesicle biology, whereas ALS showed candidate gene-level coherence in autophagy and endosomal processes without significant meta-pathway enrichment. NMN/NAD+ repletion is not established as a treatment for MDD, ALS, or their comorbidity. These findings generate hypotheses about NAD+-linked cellular stress pathways for future preclinical and clinical studies.},
}

@article {pmid42530312,
year = {2026},
author = {Ndungo, E and Islam, D and Gonwong, S and Ruamsap, N and Milletich, PL and Agnememel, A and Demons, ST and Pasetti, MF},
title = {Protective immunity against Shigella sonnei in vaccinated and challenged adult Thai volunteers.},
journal = {mSphere},
volume = {},
number = {},
pages = {e0026926},
doi = {10.1128/msphere.00269-26},
pmid = {42530312},
issn = {2379-5042},
abstract = {A safe, effective, and affordable vaccine that can prevent Shigella-induced diarrhea could have a significant impact on reducing morbidity and mortality in populations at risk. WRSS1, a live attenuated Shigella sonnei vaccine candidate, was well tolerated and immunogenic in adult Thai volunteers, achieving 40% efficacy against wild-type (WT) S. sonnei. We performed an in-depth analysis of mucosal and systemic antibodies in these individuals following WRSS1 vaccination and S. sonnei challenge, including a broader analysis of antibody specificity, functional features, and associations with clinical protection. IgG and IgA against Shigella proteins IpaB, IpaC, IpaD, IpaH, VirG, and LPS from multiple strains, as well as complement-mediated bactericidal and opsonophagocytic killing activity, were assessed in serum, fecal extracts, and antibodies in lymphocyte supernatants. Shigella-specific serum and ALS IgG and IgA increased after WRSS1 vaccination and S. sonnei challenge, particularly in naïve individuals, and most robustly post-challenge. Shedding the vaccine or infecting strain was associated with ALS responses. Fecal IgA was broadly reactive to most antigens, while fecal IgG was specific for S. sonnei LPS. Functional antibodies were detected prominently in fecal extracts; the highest responders were naïve individuals post-challenge. Notably, higher protein-specific serum IgA titers before challenge were associated with clinical protection against disease. Our results highlight the nuanced immunity to Shigella in endemic regions and the importance of understanding the elements that mediate protection in these settings to inform effective vaccine implementation.IMPORTANCEUnderstanding the immune response in Shigella-endemic regions is critical for the design and implementation of vaccines for the target population. We characterized the breadth of systemic and mucosal antibody responses to WRSS1 vaccination and WT S. sonnei challenge in Thai adult volunteers. Antigen-specific IgG and IgA in ALS were elevated only in individuals who shed the vaccine or challenge strain, indicating exposure. Serum IgA responses to Shigella proteins were associated with clinical protection. Our findings underscore the value of serosurveillance in guiding public health interventions and support the concept of protein-based vaccines to prevent disease in high-burden settings.},
}

@article {pmid42530583,
year = {2026},
author = {Graco, M and Russo, K and Grivell, N and Carey, K and Zaga, C and Saravanan, K and Sheers, NL and Berlowitz, DJ and , },
title = {A qualitative investigation of the factors influencing the uptake of noninvasive ventilation among Australians with motor neurone disease.},
journal = {Disability and rehabilitation},
volume = {},
number = {},
pages = {1-20},
doi = {10.1080/09638288.2026.2704454},
pmid = {42530583},
issn = {1464-5165},
abstract = {PURPOSE: Non-invasive ventilation (NIV) improves quality of life and extends survival for people with motor neurone disease (pwMND); however, uptake in Australia remains modest. This study explored the factors that influence the uptake of NIV from the perspectives of pwMND, caregivers, and healthcare professionals.

METHODS: Thirty-nine semi-structured interviews were conducted with pwMND (n = 8), family caregivers of pwMND (n = 4), and healthcare professionals (n = 27). A two-stage deductive-inductive analysis was performed to identify common themes that influence the uptake of NIV in MND.

RESULTS: Twenty-six key influencing factors were identified, relating to three major themes: influences on the pwMND's decision to trial NIV; healthcare professional knowledge, beliefs and behaviors; and inequity and lack of responsiveness in the healthcare system. Inductive analysis also identified a fourth theme, disparities in NIV uptake. Within this theme, women, older people, and First Nations Australians were acknowledged as demographic groups experiencing challenges to NIV uptake that warrant further investigation.

CONCLUSION: This research identified multiple modifiable factors influencing the uptake of NIV that can inform the design of targeted interventions to reduce inequitable access to NIV, increase uptake, and optimize quality of life for pwMND.},
}

@article {pmid42531420,
year = {2026},
author = {Burke, KM and Brown, R and Calcagno, N and Gupta, AS and Gajos, KZ and Scheier, Z and Clark, A and Iyer, A and Higgins, MP and Keegan, M and Royse, TB and Remington, E and Connaghan, KP and Johnson, SA and Chew, S and Erb, MK and Berry, JD},
title = {Digital Remote Assessment of Motor and Speech Changes in Amyotrophic Lateral Sclerosis: Longitudinal Observational Study.},
journal = {JMIR formative research},
volume = {10},
number = {},
pages = {e85142},
pmid = {42531420},
issn = {2561-326X},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis/complications ; Female ; Longitudinal Studies ; Male ; Middle Aged ; Aged ; Disease Progression ; Remote Patient Monitoring ; Digital Health ; *Speech/physiology ; Adult ; Reproducibility of Results ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with an active trial landscape that relies on the sensitivity of selected clinical trial endpoints. Traditional clinical outcome assessments perform well in trials but lack strong psychometric properties and may not detect small but clinically meaningful disease progression. Digital health technologies offer a promising alternative for tracking ALS disease progression.

OBJECTIVE: This study assessed the feasibility of remote digital monitoring in ALS using a comprehensive battery of prescribed home-based assessments via a smartphone, a wearable device, and a computer-based mouse-clicking task.

METHODS: Participants completed weekly remote assessments, including motor and speech tasks via a smartphone app and a computer mouse-clicking task for 24 weeks. They also participated in 3 remote telephone visits in weeks 1, 13, and 25. Reliability, minimal detectable change, and correlations with self-reported ALS Functional Rating Scale-Revised subdomain scores were calculated for 8 features across the speech, fine motor, and gross motor smartphone app tasks and for all 32 features from the computer mouse-clicking task. Sensitivity to longitudinal change was assessed for the 8 smartphone-derived features and for a representative subset of 8 computer mouse-clicking features.

RESULTS: Forty-two participants (19 with ALS and 23 controls) completed 10,237 smartphone assessments and 459 computer mouse-clicking sessions. Baseline discriminative models differentiated ALS from controls with AUC values of 0.75-0.92. Digital measures correlated strongly with self-reported ALS Functional Rating Scale-Revised subdomain scores. Both participants with ALS and controls demonstrated improvement in fine motor and speech measures, with the exception of nondominant-hand pegboard performance, which declined in the ALS group. Improvements were smaller in participants with ALS, leading to increasing group differences over time, although only one feature showed a statistically significant separation over the 24 weeks. Gait and balance performance declined in both groups, with greater but nonsignificant separation observed for balance measures.

CONCLUSIONS: These findings support the feasibility of digital remote assessments in ALS, demonstrate the ability to discriminate between ALS and controls based on certain features collected from speech, fine, and gross motor tasks, and in some cases, quantify functional decline over time. Further research is necessary to explore the natural history of these features longitudinally in larger cohorts of participants with ALS over extended periods to enable their potential integration into clinical trials.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/diagnosis/complications
Female
Longitudinal Studies
Male
Middle Aged
Aged
Disease Progression
Remote Patient Monitoring
Digital Health
*Speech/physiology
Adult
Reproducibility of Results

@article {pmid42532824,
year = {2026},
author = {Lin, YT and Yang, HL},
title = {[Applying Developmental Care Theory to the Improvement of Self-Regulation and Feeding Difficulties in a Late Preterm Infant Receiving Cardiac Surgery: A Nursing Experience].},
journal = {Hu li za zhi The journal of nursing},
volume = {73},
number = {4},
pages = {},
doi = {10.6224/JN.26413},
pmid = {42532824},
issn = {0047-262X},
mesh = {Humans ; Female ; Infant, Newborn ; *Infant, Premature ; *Self-Control ; *Cardiac Surgical Procedures ; *Feeding Behavior ; },
abstract = {When preterm infants present with organ anomalies that require immediate surgical intervention after birth, their immature nervous systems often limit their ability to cope with the stress of surgery and subsequent treatments. This often results in difficulties with self-regulation and related health issues. The case described in this study involves a late preterm female infant born at 36+4 weeks of gestation who underwent cardiac surgery on the fifth day after birth. Postoperatively, she exhibited neonatal neurodevelopmental disorganization, ineffective suck-swallow reflexes, and inadequate nutritional intake. The first author provided nursing care between April 22 to May 10, 2025, with a telephone follow-up on May 14. The provided interventions were guided by Als' Synactive Theory of Development and integrated the Seven Neuroprotective Core Measures of the Neonatal Integrative Developmental Care Model, encompassing environmental regulation, sleep and positioning support, stress and pain management, and family-centered care. Objective evaluation was conducted using the Preterm Infant Oral Feeding Readiness Assessment Scale (POFRAS). The results demonstrated improvements in both self-regulation and feeding difficulties. Notably, the incidence of crying episodes decreased, the infant was able to sustain a calm state for longer periods, coordination of suck-swallow-breathing improved, and oral intake increased. Consequently, the amount of supplemental gavage feeding was reduced, caregivers were able to provide effective care, and the POFRAS score rose from 21 to 32. The comprehensive care approach described in this study integrates theoretical frameworks with behavioral cue-based observations to effectively improve feeding difficulties and self-regulation in preterm infants undergoing invasive surgery while simultaneously enhancing caregiver competence and confidence.},
}

Humans
Female
Infant, Newborn
*Infant, Premature
*Self-Control
*Cardiac Surgical Procedures
*Feeding Behavior

@article {pmid42533344,
year = {2026},
author = {Bublitz, SK and Becker, B and Demleitner, AF and Dietz-Laukemann, P and Lingor, P and Littger, B and Lorenzl, S and Feddersen, B},
title = {Ethical challenges in treatment-goal transitions in invasively ventilated ALS: a case-based topical review.},
journal = {Neurological research and practice},
volume = {8},
number = {1},
pages = {},
pmid = {42533344},
issn = {2524-3489},
abstract = {INTRODUCTION: In advanced amyotrophic lateral sclerosis (ALS), eye movements often represent the last channel for intentional communication. While oculomotor function has traditionally been considered relatively preserved, emerging evidence indicates progressive impairment in long-term survivors on tracheostomy-invasive ventilation (TIV). As a result, eye-based communication may become increasingly unreliable before complete loss, challenging clinical decision-making and advance care planning (ACP).

METHODS: We conducted a case-based topical review integrating clinical observation and literature to examine the trajectory of oculomotor decline, its impact on communication, and implications for treatment decisions. Three patients with ALS receiving TIV in a home-care setting illustrate key clinical and ethical challenges.

RESULTS: Across cases and literature, oculomotor decline followed a gradual trajectory from effective eye-tracking communication to a complete locked-in syndrome. We identify a transitional phase of communicative ambiguity, in which residual ocular signals persist but can no longer be reliably attributed to intentional, patient-controlled communication. This phase is characterized by increasing inconsistency of signals and a divergence between observable responses and their interpretive certainty, creating uncertainty in assessing patient preferences.

IMPLICATIONS: Communicative ambiguity represents a clinically underrecognized but critical threshold in advanced ALS, marking the transition from direct patient autonomy to interpretative and surrogate-based decision-making. Failure to recognize this phase risks misinterpretation of patient intent and may undermine goal-concordant care. Timely and iterative ACP, initiated before communication becomes unreliable, is essential. We further propose four clinical pathways for treatment goal conversations, highlighting their differing implications for timing, symptom burden, and ethical decision-making.},
}

@article {pmid42533374,
year = {2026},
author = {Rotteau, L and Wong, BM and Mukerji, G and Moser, A and Feldman, S and Shojania, KG and Goldman, J},
title = {Qualitative study of the implementation of long-term care plus: An intervention-in-systems approach.},
journal = {Journal of health services research & policy},
volume = {},
number = {},
pages = {13558196261470275},
doi = {10.1177/13558196261470275},
pmid = {42533374},
issn = {1758-1060},
abstract = {ObjectivesReducing resident transfers from long-term care (LTC) to emergency departments (ED) is a well-established quality target. LTC plus (LTC+) provides medical consultations, healthcare navigation, rapid diagnostics, and education to LTC home providers, based on the logic that providing enhanced medical care in LTC homes will decrease ED transfers. LTC+ was implemented across six hospital-hubs and 54 homes in Toronto, Canada. An evaluation demonstrated positive program satisfaction and impacts on care, however limited program uptake and impact on ED transfers. We examine LTC+ intervention components and their implementation and adaptations to understand these discrepancies and identify improvement opportunities.MethodsWe conducted 32 qualitative interviews with LTC home providers and administrators and consultant physicians, and three focus groups with residents and family members, at six LTC homes and three hospital-hubs. Analysis drew on Lennox et al.'s conceptualization of "intervention-in-systems" which outlines four spheres to categorize intervention components (accessibility of evidence base, process of enactment, dependent processes and sociocultural issues) and their interconnectedness and adaptations when implemented and spread in complex systems.ResultsLTC+ design and implementation was centered within the accessibility of evidence base (e.g., educating about LTC+) and process of enactment (e.g., identify residents being considered for ED transfer) spheres to support program goals. LTC+ use was aligned with original program logic, however, providers also accessed LTC+ in cases where an ED transfer was not being considered highlighting limitations of a logic focused solely on ED transfers. LTC+ design and implementation was less attentive to intervention components in the dependant processes and sociocultural issues spheres (e.g., staffing models, interprofessional interactions) impacting adoption.ConclusionThe "intervention-in-systems" analytic lens was useful in examining intervention components across the four spheres, including their gaps, adaptations and interconnections. Study findings informed revisions to program goals, intervention components, and evaluative approach, reinforcing program and financial sustainability.},
}

@article {pmid42533837,
year = {2025},
author = {Edwards, CM},
title = {Response to Young et al.'s 'Letter to the Editor'.},
journal = {Journal of military, veteran and family health},
volume = {11},
number = {3},
pages = {198-201},
pmid = {42533837},
issn = {2368-7924},
}

@article {pmid42524305,
year = {2026},
author = {Longo, UG and Merone, M and Schena, E and Bandini, B and Nicodemi, G and Zsidai, B and Hilkert, AS and Senorski, EH and Grassi, A and Ley, C and Herbst, E and Hirschmann, MT and Kopf, S and Seil, R and Tischer, T and Feldt, R and Samuelsson, K and Oettl, FC},
title = {A practical guide to the implementation of AI in orthopaedic research-Part 4: Prerequisites for a successful orthopedics AI-driven project in terms of interdisciplinary collaboration, data management, ethical approval and technology.},
journal = {Journal of experimental orthopaedics},
volume = {13},
number = {3},
pages = {e70863},
pmid = {42524305},
issn = {2197-1153},
abstract = {UNLABELLED: Translating artificial intelligence (AI) research in orthopedics from proof-of-concept studies into production-grade clinical systems requires the systematic satisfaction of four prerequisite domains: interdisciplinary team architecture, technical data management, ethical and regulatory governance and production-grade technology and deployment infrastructure. Despite a tenfold increase in orthopedic AI publications, fewer than 6% of studies reach routine clinical deployment, reflecting persistent gaps in each of these domains. This article provides a technically rigorous, evidence-based framework organized around these four pillars. The interdisciplinary team may be structured using a product-centric topology that decouples stream-aligned clinical teams from platform infrastructure teams, following Huffman et al.'s six-step AI project lifecycle: obtain/curate/label data; establish a reference standard; develop the model; evaluate performance; externally validate and iteratively reinforce until clinical implementation is viable. Data management requires data extraction protocols, integration for bulk exports and a multi-component de-identification pipeline. A multi-stage Institutional Review Board framework governs ethical oversight, scaling from Exempt review for retrospective de-identified studies to Full Board Review with prospective validation and mandatory human-override mechanisms for interventional deployment. Responsible clinical deployment requires a multi-layer Clinical Machine Learning Operations framework, implementing privacy-preserving deployment, clinical observability, compliance audit trails and human-in-the-loop governance. Model drift has to be monitored with a degradation threshold triggering mandatory human review.

LEVEL OF EVIDENCE: Level V.},
}

@article {pmid42524894,
year = {2026},
author = {Guo, W and Cai, S and Li, Y and McGarry, BE and Caprio, TV and Temkin-Greener, H},
title = {User-Generated Google Maps Ratings, State Staffing and Training Regulations, and the Quality of Hospice Care in Assisted Living Communities.},
journal = {Journal of the American Geriatrics Society},
volume = {},
number = {},
pages = {},
doi = {10.1111/jgs.70609},
pmid = {42524894},
issn = {1532-5415},
support = {Another Look 2020//Patrick and Catherine Weldon Donaghue Medical Research Foundation/ ; R01HS026893/HS/AHRQ HHS/United States ; },
abstract = {BACKGROUND: Hospice services are growing among Medicare beneficiaries, yet concerns remain about the hospice quality for residents in assisted living (AL) communities. Little is known about how AL characteristics and state regulations are associated with hospice care in these settings.

OBJECTIVES: To examine (1) whether AL user-generated google maps ratings (AL google maps ratings) and (2) state-level regulations on AL staffing are associated with hospice ratings: METHODS: We conducted a cross-sectional analysis of 15,947 AL communities. We included data on AL-specific direct care worker (DCW) state staffing and staff training regulations. Logistic regression models were used to assess associations, adjusting for AL, hospice, and market-level characteristics.

RESULTS: A one-star increase in an AL google maps rating was associated with 6% higher odds of being served by hospices with higher HIS scores (OR = 1.06, p = 0.032), but not with CAHPS scores. AL communities in states with higher regulatory specificity for DCW staffing had higher odds of being served by hospices with higher CAHPS (OR = 1.46, p < 0.001) and HIS scores (OR = 1.35, p < 0.001). ALs in states mandating more than 21 h of DCW training, AL communities were more likely to be served by hospices with higher CAHPS scores (OR = 1.33, p < 0.001).

CONCLUSION: Higher AL google maps ratings were associated with higher hospice HIS performance. DCW staffing regulations were associated with both CAHPS and HIS, and DCW training regulations were associated with CAHPS only. These findings underscore the role of organizational quality and state regulatory policies in guiding end-of-life care in AL communities.},
}

@article {pmid42525902,
year = {2026},
author = {Roberts, AL and Vilela Braga, AD and Tang, IW and Rotem, RS and Moo, LR and Miller, DR and Shirk, SD and Weisskopf, MG},
title = {Association of Military Branch and Rank With Amyotrophic Lateral Sclerosis Incidence Among United States Veterans.},
journal = {Neurology},
volume = {107},
number = {4},
pages = {e218303},
doi = {10.1212/WNL.0000000000218303},
pmid = {42525902},
issn = {1526-632X},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology ; Male ; United States/epidemiology ; *Veterans/statistics & numerical data ; Female ; *Military Personnel/statistics & numerical data ; Incidence ; Middle Aged ; Longitudinal Studies ; Adult ; Risk Factors ; Aged ; Cohort Studies ; Proportional Hazards Models ; },
abstract = {BACKGROUND AND OBJECTIVES: Military service is one of the most consistent risk factors for the development of amyotrophic lateral sclerosis (ALS), but little is known about what aspects of military service matter. Understanding the distribution of ALS risk in military personnel may help identify key risk factors. We aimed to ascertain the association of United States (US) military branch and rank with incident ALS.

METHODS: We conducted a longitudinal cohort study including all veterans with a Veterans Health Administration encounter from January 1, 2000, through October 1, 2024, and more than 2 years of follow-up. Incident ALS was identified through medical records. Exposures included military branch (Army, Navy, Air Force, Marine Corps, Coast Guard, or multiple branches), military rank (officer, enlisted, or both), and length of service. Risk was estimated with Cox proportional hazards models, controlled for age, adjusted for race/ethnicity, and stratified by sex.

RESULTS: The analytic sample comprised 9,157,938 men (13,935 incident ALS cases, mean age = 56.9 years) and 784,941 women (484 cases, mean age = 42.4 at start of follow up). Among men, compared with service in the Army, service in the Air Force (hazard ratio [HR] = 1.29, 95% CI 1.23-1.35), Navy (HR = 1.15, 95% CI 1.10-1.20), and Coast Guard (HR = 1.26, 95% CI 1.06-1.50) was associated with higher rates of ALS and service in the Marines a lower rate (HR = 0.78, 95% CI 0.68-0.88). Officers had higher rates than enlisted personnel (men, HR = 1.64, 95% CI 1.53-1.74; women, HR = 1.72, 95% CI 1.31-2.27). Longer service was associated with lower rates of ALS. In age-stratified models, differences in hazard rates between Army veterans and Air Force, Navy, and Coast Guard veterans were greatest for the youngest men (17-61 years, HR range = 1.26 to 1.51) and smallest for the oldest (>75-104 years, HR range = 0.99 to 1.12).

DISCUSSION: ALS rates varied considerably by branch and rank in the US military, with larger differences among younger veterans. Officers and those serving in the Air Force, Navy, or Coast Guard may incur exposure to military environments that increase risk of ALS. It is imperative to identify relevant exposures to reduce harm to service members and, potentially, civilians with similar exposures.},
}

Humans
*Amyotrophic Lateral Sclerosis/epidemiology
Male
United States/epidemiology
*Veterans/statistics & numerical data
Female
*Military Personnel/statistics & numerical data
Incidence
Middle Aged
Longitudinal Studies
Adult
Risk Factors
Aged
Cohort Studies
Proportional Hazards Models

@article {pmid42525906,
year = {2026},
author = {Hardiman, O},
title = {Amyotrophic Lateral Sclerosis in the Military: A Uniform Risk?.},
journal = {Neurology},
volume = {107},
number = {4},
pages = {e218481},
doi = {10.1212/WNL.0000000000218481},
pmid = {42525906},
issn = {1526-632X},
}

@article {pmid42526364,
year = {2026},
author = {Stevenson, C and McNamara, N and John, R and Gallagher, S},
title = {Local community identification improves wellbeing by reducing loneliness: Longitudinal evidence from two studies.},
journal = {Social science & medicine (1982)},
volume = {406},
number = {},
pages = {119543},
doi = {10.1016/j.socscimed.2026.119543},
pmid = {42526364},
issn = {1873-5347},
abstract = {Loneliness is a significant determinant of mental and physical health which has many root causes at local community level. Building on the Social Identity Approach to Health we test a longitudinal version of McNamara et al.'s (2021) neighbourhood identity model of wellbeing, which links local community identification to wellbeing via reduced loneliness. Study 1 was a two-wave survey of residents in mid-Nottinghamshire, UK (T1 N = 879; T2 N = 216). Mediation analyses showed that, over a one-year period, changes in community identification predicted increases in wellbeing via increases in perceived support and reductions in loneliness while controlling for a range of demographic factors. In Study 2, a secondary analysis of a large population-based UK study, i.e. Understanding Society (UKHLS; Waves 9 and 12; n = 38,056) showed that over a three-year period, increases in identification predicted improvements in GHQ-12 mental health and self-rated general health, again via increases in perceived support and reductions in loneliness. Across studies, the effect of neighbourhood identification on wellbeing occurred primarily through loneliness reduction. We discuss implications for reducing health inequalities through local community identity-building and social infrastructure, and outline priorities for policy and future research.},
}

@article {pmid42526365,
year = {2026},
author = {Ahsan, A and Ou, JC and Majumder, P and Chiang, YH and Huang, JK and Huang, CS},
title = {A systematic review and meta-analysis of OCT-based ophthalmic changes in amyotrophic lateral sclerosis.},
journal = {Journal of neuroimmunology},
volume = {420},
number = {},
pages = {579028},
doi = {10.1016/j.jneuroim.2026.579028},
pmid = {42526365},
issn = {1872-8421},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease marked by motor decline and respiratory failure. Optical coherence tomography (OCT), a non-invasive imaging technique, has been explored for detecting retinal structural changes that may reflect neurodegeneration in ALS. While some studies report thinning of retinal layers, findings remain inconsistent. Therefore, a meta-analysis is needed to clarify the extent of retinal involvement and the potential of OCT as a biomarker in ALS.

METHODS: A systematic literature search was conducted across PubMed, EMBASE, and Cochrane databases for studies published between 2010 and May 2025. Study quality was assessed using the Newcastle-Ottawa Scale (NOS), and publication bias was evaluated through funnel plot asymmetry and Egger's test. Pooled effect sizes were calculated using random-effects models to account for between-study heterogeneity, and differences in OCT parameters between ALS patients and healthy controls were expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). Statistical heterogeneity was quantified using the I[2] statistic.

RESULTS: A total of 17 studies were included in the present meta-analysis. The primary unadjusted global model demonstrated significant reduction of retinal nerve fibre layer (RNFL) thickness in ALS patients compared to controls (unadjusted SMD = -0.295, 95% CI: -0.522, -0.068). Upon applying a Design Effect variance inflation model to address fellow-eye non-independence, the pooled estimate remained robustly significant across a conservative range of intraclass correlations (SMD ranged from -0.256 to -0.249). Subgroup analyses revealed that RNFL thinning was particularly pronounced in spinal-onset ALS (SMD = -0.54, 95% CI: (-0.98, -0.10). When studies were stratified by the region of conduct, RNFL and macular thinning reached statistical significance only within the non-Asian subgroup, though the formal test for subgroup differences was not significant.

CONCLUSION: This meta-analysis demonstrates significant bilateral RNFL thinning in ALS, with relative preservation of the Inner Nuclear Layer and Ganglion Cell Layer - Inner Plexiform Layer, supporting retinal neurodegeneration as a feature of this multisystem disorder.

PROSPERO identifier CRD420251076035.},
}

@article {pmid42526625,
year = {2026},
author = {Guth, MAS},
title = {Targeting TDP-43 in ALS: Regulatory hurdles, trial design deficiencies, and the causal evidence gap for CTx1000.},
journal = {Drug discovery today},
volume = {},
number = {},
pages = {104752},
doi = {10.1016/j.drudis.2026.104752},
pmid = {42526625},
issn = {1878-5832},
abstract = {The therapeutic landscape for amyotrophic lateral sclerosis (ALS) has been characterized by decades of clinical trial failures, often attributed to biological heterogeneity, end-point insensitivity, and a profound evidence gap regarding target engagement. With TAR DNA-binding protein 43 (TDP-43) aggregation emerging as a hallmark feature in the vast majority of ALS cases, new precision-medicine modalities - most notably the proteolysis-targeting chimera (PROTAC) CTx1000 - aim to address the underlying causal pathology through selective degradation of mislocalized TDP-43. This review critically evaluates the regulatory hurdles and trial design deficiencies that have historically undermined ALS clinical development, and incorporates the dual sequestration hypothesis as a framework to interpret the convergence of TDP-43 pathology across neurodegenerative diseases. It concludes that it is imperative that the field adopts more rigorous biomarker-led methodologies, and that although target-specific degraders offer a sophisticated technological leap, their success depends on addressing fundamental knowledge gaps in target engagement, age-dependent vector tropism, and trial design architecture.},
}

@article {pmid42520340,
year = {2026},
author = {Morgan-Jack, BR and Katz, ML and Kick, GR and Johnson, GC and Delgado, K and Makinen, M and Coates, JR},
title = {Pathology of general proprioception in a canine disease model of amyotrophic lateral sclerosis.},
journal = {Journal of the neurological sciences},
volume = {489},
number = {},
pages = {126108},
doi = {10.1016/j.jns.2026.126108},
pmid = {42520340},
issn = {1878-5883},
abstract = {Some forms of amyotrophic lateral sclerosis (ALS) are associated with sequence variants in the superoxide dismutase 1 gene (SOD1). The mechanisms by which these variants contribute to ALS disease pathogenesis are poorly understood. Degenerative myelopathy (DM), a naturally occurring canine disease, shares similarities with some forms of SOD1-associated ALS, especially cases with sensory impairment. While motor pathway involvement in ALS has been extensively studied, sensory pathology has received comparatively less attention. To investigate whether pathology in the general proprioceptive pathway is associated with pelvic limb general proprioceptive ataxia, an early DM sign, we examined sensory system components of this pathway from Pembroke Welsh Corgis with early- and late-stage DM and age-matched controls. The disease was characterized by axonal pathology in the spinocerebellar tracts and the fasciculus gracilis, pronounced accumulation of SOD1-positive inclusions in nucleus thoracicus and dorsal root ganglia (DRG) neurons, and altered SOD1 immunolabeling in dorsal and ventral root axons and ensheathing myelin. Axonal pathology was also observed in a pelvic limb sensory nerve. These findings suggest that pathology in the proprioceptive sensory pathways may play a significant role in general proprioceptive ataxia in DM. Some dogs that were homozygous for the SOD1 risk allele did not develop clinical disease or the associated neuropathology, indicating that other factors in addition to the SOD1 mutation influence disease onset and progression.},
}

@article {pmid42521602,
year = {2026},
author = {Pathapati, N and Nguyen, M and Ju, J and Maddukuri, M and Kiehl, J and Kvale, E and Thrift, AP and Berth, S and Grouls, A},
title = {Capturing Financial Burden Concerns in an ALS Multidisciplinary Clinic.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70364},
pmid = {42521602},
issn = {1097-4598},
abstract = {INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) is associated with substantial financial burden. How financial concerns are documented or addressed in ALS multidisciplinary clinics (MDC) is unclear. We aimed to characterize financial concerns among people living with ALS (pALS) and how they are identified and documented by multidisciplinary clinic staff.

METHODS: We performed a retrospective electronic medical record (EMR) review for people living with ALS (pALS) attending at least two visits at the MDC, identifying documentation of financial concerns across all MDC notes throughout 2024. Semi-structured interviews with MDC staff explored experiences with financial concern discussions and documentation. Rapid qualitative analysis was used to analyze interview content.

RESULTS: Among 67 pALS with at least 2 MDC visits, 45 (67.2%) had ≥ 1 documented financial concerns. Financial concerns were most documented in neurology physician notes and portal messages (both 77.8%) and included insurance denials, medication costs, disability/Medicare navigation, caregiving expenses, and home modifications. Social work and patient portal notes provided greater detail than other staff notes. Staff interviews highlighted insurance and equipment costs as frequent financial concerns. Four qualitative themes emerged: insurance challenges and reliance on non-insurance resources, financial barriers limiting care and quality of life, limited proactive conversations/documentation, and the central role of social work.

DISCUSSION: Financial concerns are common among pALS but are inconsistently discussed and documented in the EMR, often arising through asynchronous communication or social work. Integrating financial screening and promoting proactive multidisciplinary documentation may improve identification of financial concerns and support more equitable, person-centered ALS care.},
}

@article {pmid42521811,
year = {2026},
author = {Willemse, SW and Demaegd, KC and Koole, W and van Eijk, RPA and van Rheenen, W and Veldink, JH and van den Berg, LH and van Es, MA},
title = {Tofersen treatment in respiratory onset amyotrophic lateral sclerosis and a variant of uncertain significance in SOD1; a case report.},
journal = {European journal of human genetics : EJHG},
volume = {},
number = {},
pages = {},
pmid = {42521811},
issn = {1476-5438},
support = {09150161810018//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)/ ; V0000319//ZonMw (Netherlands Organisation for Health Research and Development)/ ; },
abstract = {The antisense oligonucleotide tofersen is available for treating amyotrophic lateral sclerosis (ALS) caused by pathogenic SOD1 variants. However, it is unknown whether Variants of Uncertain Significance (VUS) are a viable treatment target. We assessed clinical and biomarker trajectories prior to and after initiation of tofersen in a patient with respiratory onset ALS and a novel c.234_236del p.(Glu79del) VUS in SOD1. After six months of treatment, cerebrospinal fluid (CSF) SOD1 protein decreased by 47%, CSF NfL by 55% and serum NfL by 50%, with trajectories comparable to known pathogenic variants. Functional decline on the ALSFRS-R slowed from 1.52 points per month pre-treatment to 0.52 points per month post-treatment, muscle strength remained stable, and EQ-VAS quality of life scores remained between 60 and 70. The ability to evaluate treatment response on an individual level will help to determine the clinical relevance of VUS as new gene-targeted treatments for ALS become available.},
}

@article {pmid42521895,
year = {2026},
author = {Abidar, S and Nhiri, M and Bianchi, V},
title = {Suicide in neurodegenerative diseases: a systematic review.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {8},
pages = {},
pmid = {42521895},
issn = {1590-3478},
mesh = {Humans ; *Neurodegenerative Diseases/psychology ; *Suicide/psychology/statistics & numerical data ; Amyotrophic Lateral Sclerosis/psychology ; Multiple Sclerosis/psychology ; },
abstract = {BACKGROUND AND OBJECTIVE: Suicide is a public health issue, which differs from suicidality, the continuum from suicidal ideation to the suicidal act, including suicide attempts and completed suicide. The main goal of the present study is to determine the relationship between Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS) with suicidality.

METHODS: This is a systematic review aiming to determine the relationship between AD, PD, ALS, and MS with suicidality following PRISMA 2020 guidelines by collecting cross-sectional, case-control, and cohort studies; case series; case reports; and retrospective and prospective studies from Google Scholar, PubMed, and Cochrane Library. The protocol of this systematic review was registered on PROSPERO; the registration number is CRD420261422354.

RESULTS: From 2247 records identified from electronic databases, only 24 articles were included: three studies focusing on AD, nine on PD, and six studies focusing on ALS and MS, respectively. These studies exhibited moderate to low risk of bias. Despite the broad differences regarding the neurochemistry, pathophysiology, diagnosis, symptoms, and treatments of the selected diseases, patients are at a higher risk of suicidality. Depression and low social connectivity are the most prevalent risk factors. Suicidality is mainly detected during the first years post-diagnosis in PD, ALS, and MS patients, while the results in AD are confusing.

CONCLUSIONS: Data about this topic is scarce and largely varying. Further research is required to elucidate this paradigmatic realm, fostering awareness, enhancing therapies, and providing explanations and interpretations of the mechanisms involved.},
}

Humans
*Neurodegenerative Diseases/psychology
*Suicide/psychology/statistics & numerical data
Amyotrophic Lateral Sclerosis/psychology
Multiple Sclerosis/psychology

@article {pmid42522587,
year = {2026},
author = {Wood, P},
title = {Beyond procedural justice: Power, identity and the asymmetric architecture of public trust in security services.},
journal = {The British journal of social psychology},
volume = {65},
number = {4},
pages = {e70114},
pmid = {42522587},
issn = {2044-8309},
mesh = {*Trust/psychology ; Humans ; *Power, Psychological ; *Social Identification ; *Social Justice ; Social Group ; *Security Measures ; },
abstract = {Public trust in security services is a critical social-psychological phenomenon, yet existing theoretical accounts remain fragmented and insufficiently attentive to the structural power asymmetries characterising security-public relations. This article argues that the dominant paradigm, procedural justice theory, requires fundamental revision within intergroup and institutional power dynamics. Drawing upon procedural justice theory (Why people obey the law, 1990, Yale University Press; Why people obey the law, 2nd ed., 2006, Princeton University Press), social identity and self-categorisation theory (The social psychology of intergroup relations, 1979, 33, Brooks/Cole; Rediscovering the social group: A self-categorization theory, 1987, Blackwell), the integrative model of organisational trust (Academy of Management Review, 1995, 20, 709), intergroup contact theory (The nature of prejudice, 1954, Addison-Wesley), system justification theory (British Journal of Social Psychology, 1994, 33, 1), institutional betrayal theory (American Psychologist, 2014, 69, 575) and the political trust tradition (A systems analysis of political life, 1965, Wiley; Trust and trustworthiness, 2002, Russell Sage Foundation; Annual Review of Political Science, 2000, 3, 475), the article advances three propositions. First, trust formation is asymmetric: trust erodes faster than it accrues, with the asymmetry amplified for subordinate-status groups. Second, procedural justice effects are identity-contingent: perceived fairness operates differently depending on whether the authority is categorised as in-group protector or out-group enforcer. Third, trustworthiness appraisal under institutional betrayal requires reconceptualising Mayer et al.'s integrity dimension as epistemic credibility. A four-pathway model is proposed, with power asymmetry as a structural moderator and recursive feedback producing virtuous or vicious trust spirals.},
}

*Trust/psychology
Humans
*Power, Psychological
*Social Identification
*Social Justice
Social Group
*Security Measures

@article {pmid42522997,
year = {2026},
author = {Stanley, LM and Scott, JA},
title = {Single-case design interventions for deaf disabled students: a systematic literature review.},
journal = {Journal of deaf studies and deaf education},
volume = {},
number = {},
pages = {},
doi = {10.1093/jdsade/enag045},
pmid = {42522997},
issn = {1465-7325},
abstract = {This systematic review examined single-case design (SCD) interventions for Deaf and Hard-of-Hearing students with co-occurring disabilities (i.e., who are Deaf Disabled). Ten peer-reviewed studies met the inclusion criteria, targeting communication, behavior, or academic outcomes. Behavioral interventions demonstrated more durable generalization, while academic gains often required continued reinforcement. Study quality evaluated using Horner et al.'s indicators revealed two high-quality studies, four acceptable, and four below minimum standards, indicating notable methodological limitations. Findings highlight a significant gap in rigorous, language-focused SCD research. Improved methodological quality is needed to better inform multidisciplinary teams in designing individualized, evidence-based supports, while also considering how normative assumptions shape definitions of "improvement" and influence interpretations of effectiveness.},
}

@article {pmid42523377,
year = {2026},
author = {Breevoort, A and Ivanov, D and Horan-Portelance, L and Nana, A and Vatsavayai, S and Miravet, ÀT and Wallace, JL and Ding, JW and Pereira, FL and Fernhoff, K and Gorno-Tempini, ML and Spina, S and Yokoyama, JS and Rosen, HJ and Grinberg, LT and Jacobs, FMJ and Miller, BL and Seeley, WW and Pollen, AA},
title = {Single-cell transcriptomic atlas of frontoinsular cortex reveals molecular correlates of selective neuronal vulnerability in FTD.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42523377},
issn = {2692-8205},
abstract = {Frontotemporal dementia (FTD) is characterized by selective neuronal vulnerability, yet the features that predispose specific neuron types to degeneration remain unclear. We performed single-nucleus RNA sequencing of frontoinsular cortex, a region affected early in behavioral variant FTD, across individuals with C9orf72-associated and sporadic FTD-MND spectrum disease. By enriching for large projection neurons, we resolved molecular subtypes of layer 5 extratelencephalic neurons, including von Economo neurons, and identified selective depletion of specific layer 2/3 and layer 5 neuron subtypes, convergent across genotypes. Despite selective neuronal loss, disease-associated transcriptional changes were convergent across excitatory neuron populations, suggesting that they reflect upstream pathophysiology or shared responses to local neurodegeneration. By relating neighborhood-level depletion in disease to gene expression in controls, we found that baseline cellular respiration and ATP synthesis predict neuronal vulnerability in disease. These findings define molecular correlates of selective neuronal vulnerability in FTD and provide a framework linking cell type and state to neurodegeneration.},
}

@article {pmid42523442,
year = {2026},
author = {Jonk, SM and Nicol, A and Braun, A and Wang, W and Tribble, JR and Swoboda, P and Williams, PA},
title = {Supplementation via DAF-16 and pnk-1 driven pantothenate-coenzyme A flux improves disease related stress resistance in C. elegans.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.07.08.737381},
pmid = {42523442},
issn = {2692-8205},
abstract = {Metabolic pathways are increasingly recognized as tractable targets in aging and disease. Building on prior work demonstrating that supplementation with low-molecular weight metabolites (amino acids, vitamins, and their intermediates) can extend lifespan in Caenorhabditis elegans , we focused on pantothenate (vitamin B 5), which is dysregulated in sarcopenic muscle and in several neurodegenerative and metabolic disorders. Pantothenate is the obligate precursor of coenzyme A through a short, highly conserved biosynthetic pathway in which loss-of-function mutations can cause neurodegeneration with brain iron accumulation. In C. elegans , the longevity curtailing transcription factor DAF-16/FOXO has a conserved binding element in the promoter region of pnk-1 , encoding the first enzyme (PNK-1) in the coenzyme A pathway, and pnk-1 is markedly upregulated in long-lived daf-2 (insulin/-like receptor) mutants, implicating coenzyme A metabolism in longevity. Here, we demonstrate that CoA levels naturally increase during early life and decrease towards older age in C. elegans . Dietary pantothenate supplementation increases coenzyme A levels with minimal effects on lifespan but systemic effects on lipid metabolism, mitochondrial dynamics, and muscle structure under basal conditions. Under DAF-16-associated stress conditions, including heat and oxidative stress, pnk-1 expression is upregulated and pantothenate supplementation robustly extends lifespan and improves mobility. Finally, we demonstrate dysregulation of daf-16 and pnk-1 expression in amyotrophic lateral sclerosis (ALS) models, in which pantothenate supplementation confers both lifespan extension and cholinergic neuroprotection.},
}

@article {pmid42523591,
year = {2026},
author = {Balanis, T and Doulberis, M and Tutuian, R},
title = {EUS-guided transmural treatment of afferent loop syndrome: a systematic review and meta-analysis.},
journal = {Frontiers in gastroenterology (Lausanne, Switzerland)},
volume = {5},
number = {},
pages = {1853386},
pmid = {42523591},
issn = {2813-1169},
abstract = {BACKGROUND: Afferent loop syndrome (ALS) is an uncommon but clinically relevant complication after pancreaticobiliary or upper gastrointestinal reconstruction, most often in patients with recurrent malignant disease. Endoscopic ultrasound-guided creation of a transmural bypass, either as gastroenterostomy or enteroenterostomy, has emerged as a minimally invasive alternative to surgery or percutaneous drainage. We aimed to systematically review the available evidence and provide a pooled descriptive analysis of the efficacy and safety of EUS-guided treatment for ALS.

METHODS: A systematic review was performed in accordance with PRISMA principles. PubMed/MEDLINE, Embase and the Cochrane Library were searched up to 15 May 2025 for studies reporting EUS-guided gastroenterostomy or enteroenterostomy for ALS. Case reports, case series and observational studies with extractable outcome data were eligible. Data on study design, indication, stent type, technical success, clinical success, adverse events and follow-up were extracted and synthesized.

RESULTS: Twelve studies involving 134 patients were included. On crude analysis, technical success was achieved in 132/134 patients (98.5%), clinical success in 127/134 (94.8%), and adverse events were reported in 13/134 (9.7%). In the pooled random-effects analysis, the technical success rate was 93.5% (95% CI 87.1-96.8; I²=0%), the clinical success rate was 91.0% (95% CI 84.5-94.9; I²=0%), and the overall adverse-event rate was 14.6% (95% CI 9.1-22.5; I²=0%). Adverse events were mainly procedure-related pain, fever, stent misdeployment, peritonitis or intra-abdominal infection. Electrocautery-enhanced lumen-apposing metal stents were used in most studies, whereas fully covered self-expandable metal stents were used in a smaller subset. Reported follow-up ranged from 1 to 15 months.

CONCLUSIONS: EUS-guided transmural bypass represents a promising, minimally invasive, and technically feasible alternative for the management of ALS. However, given the retrospective nature and small sample sizes of the available evidence, larger comparative trials are warranted to define its definitive role.},
}

@article {pmid42512450,
year = {2026},
author = {Yogi, S and Singh, A},
title = {Molecular Mechanisms of Neurodegenerative Diseases: Emerging Biomarkers and Therapeutic Targets.},
journal = {Brain sciences},
volume = {16},
number = {7},
pages = {},
pmid = {42512450},
issn = {2076-3425},
abstract = {Neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), involve the gradual loss of structure or function of neurons in the nervous system and are an increasing threat to the aging population worldwide. Although these disorders have different clinical features which affect cognition, movement and other vital body functions, they share key underlying molecular and cellular processes. This starts with protein misfolding and aggregation, mitochondrial dysfunction, oxidative stress, dysregulated protein homeostasis, neuroinflammation, and disrupted cell death pathways. Recent findings have added disease-specific processes, like amyloid-β and tau aggregates in AD, α-synuclein aggregation and mitophagy failure in PD's, TDP-43-related impaired RNA metabolism in ALS, and mutant huntingtin causing transcription aberrations in HD. Protein interactome network analysis showed mechanistic crosstalk between pathogenic proteins of AD and PD. New evidence highlights how lysosomal dysfunction, endoplasmic reticulum stress, and microglial activation, act as a common axis in neurodegeneration. Advancements in genomics and epigenomics have found shared genetic risk loci and regulatory processes that affect how diseases develop and progress. Simultaneously, new biomarkers like circulating microRNAs, exosome-related pathological proteins, neurofilament light chain, inflammatory cytokines, and microglial activation markers are powering early diagnosis tools and disease variations. New imaging techniques also allow for the identification of protein aggregations before symptoms appear. Overall, these findings are accelerating targeted treatments and personalized medicine aimed at disease progression. This review highlights current insights into the molecular mechanisms of NDs and discusses new biomarkers and treatment targets that help future diagnostic and treatment strategies.},
}

@article {pmid42512540,
year = {2026},
author = {Manzo, J and Hernández-Aguilar, ME},
title = {Autism and Neurodegeneration: Distinct Disorders or a Shared Biological Continuum?.},
journal = {Brain sciences},
volume = {16},
number = {7},
pages = {},
pmid = {42512540},
issn = {2076-3425},
abstract = {BACKGROUND/OBJECTIVES: Autism spectrum disorder (ASD) is traditionally classified as a neurodevelopmental condition, whereas neurodegenerative diseases are defined by progressive neuronal decline in later life. This separation has shaped research and clinical practice, yet emerging evidence suggests potential biological overlap. This review aims to evaluate whether ASD and neurodegenerative disorders represent distinct entities or are linked through shared mechanisms operating across the lifespan.

METHODS: This narrative review synthesizes findings from genetic, molecular, cellular, circuit-level, and epidemiological studies examining ASD and major neurodegenerative conditions, including Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis. Emphasis is placed on identifying convergent pathways and evaluating evidence within a lifespan-oriented framework.

RESULTS: Across multiple levels of analysis, ASD and neurodegenerative diseases share partially overlapping biological mechanisms, including mitochondrial dysfunction, impaired proteostasis, neuroimmune alterations, and network-level instability. Genetic and molecular data reveal pleiotropic pathways influencing both early neurodevelopment and later neuronal resilience. Circuit-level studies highlight shared principles of network vulnerability, including cerebellar involvement and excitation-inhibition imbalance. Epidemiological data further indicate increased risk of dementia and parkinsonian features in autistic adults. These convergences suggest that early neurodevelopmental alterations may establish latent vulnerabilities that, under specific conditions, intersect with neurodegenerative processes later in life.

CONCLUSIONS: ASD and neurodegenerative diseases are best understood as distinct clinical conditions that share partially overlapping biological substrates. Rather than implying a deterministic progression, the evidence supports a model of lifespan convergence in which timing, context, and individual susceptibility shape outcomes. This framework highlights the need for integrated research and clinical approaches that consider brain health as a continuous process from development through aging.},
}

@article {pmid42513190,
year = {2026},
author = {Funsueb, S and Thanavanich, C and Chudoung, C and Jomnong, P and Theanjumpol, P and Kittiwachana, S},
title = {Comprehensive and Non-Destructive Sweet Corn Shelf-Life Prediction Using Near-Infrared (NIR) Spectroscopy Coupled with Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) Spectral Resolution.},
journal = {Molecules (Basel, Switzerland)},
volume = {31},
number = {14},
pages = {},
doi = {10.3390/molecules31142512},
pmid = {42513190},
issn = {1420-3049},
support = {Proactive Researcher Program//Chiang Mai University/ ; },
mesh = {*Zea mays/chemistry ; Spectroscopy, Near-Infrared/methods ; Least-Squares Analysis ; *Food Storage ; Multivariate Analysis ; Temperature ; Kinetics ; },
abstract = {Accurate shelf-life prediction of perishable products remains challenging because quality deterioration involves multiple physicochemical changes that are not adequately captured by conventional univariate approaches. This study proposes a multivariate shelf-life prediction framework for sweet corn based on near-infrared (NIR) spectroscopy coupled with multivariate curve resolution-alternating least squares (MCR-ALS). NIR spectra were collected from sweet corn samples and analyzed using MCR-ALS to extract chemically interpretable concentration and spectral profiles. A total of 100 and 85 corn samples were used for model training and validation, respectively. The dominant MCR-ALS component showed strong correlations with total soluble solids, dry matter, and individual sugar contents (sucrose, glucose, and fructose), effectively describing the overall quality degradation process. Based on the zero-order kinetic model, the predicted shelf lives were 41.3, 11.0, and 8.9 days at 4, 13, and 25 °C, respectively. Arrhenius analysis of the MCR-ALS concentration profile yielded a temperature-dependent degradation rate with an activation energy of 54.05 kJ mol[-1] (R[2] = 0.8387). The practical applicability of the proposed framework was further examined using a separate harvest batch of sweet corn that underwent repeated non-destructive NIR measurements throughout storage. Overall, the proposed NIR-MCR-ALS framework provides a rapid, non-destructive, and chemically interpretable approach for shelf-life prediction and postharvest quality monitoring of perishable produce.},
}

*Zea mays/chemistry
Spectroscopy, Near-Infrared/methods
Least-Squares Analysis
*Food Storage
Multivariate Analysis
Temperature
Kinetics

@article {pmid42513312,
year = {2026},
author = {Kordas, B},
title = {Multimodal Assessment of Consciousness with Brain-Computer Interfaces and Artificial Intelligence: From Acquired Brain Injury to Neurodegenerative Disease.},
journal = {Journal of clinical medicine},
volume = {15},
number = {14},
pages = {},
pmid = {42513312},
issn = {2077-0383},
support = {2023/49/N/NZ4/03958//National Science Centre/ ; },
abstract = {The assessment of consciousness has been shaped largely by research on acquired disorders of consciousness after acute or chronic brain injury, but similar problems of unreliable behavioral expression increasingly arise in neurodegenerative disease. This translational overlap is especially relevant when preserved cognition, awareness, or intentionality cannot be reliably expressed because of severe motor impairment, fluctuating arousal, cognitive decline, aphasia, apraxia, or impaired cooperation. In neurodegenerative disease, degeneration of arousal systems, large-scale brain networks, cognition, and motor pathways may similarly make observable behavior an unreliable measure of awareness. The challenge is not only to determine if a patient responds, but also to ask if residual awareness, intentionality, or covert cognition can still be detected through physiological signals. This review discusses how contemporary modalities reshape this assessment. Electroencephalography has moved from a descriptive measure of background activity to a bedside tool capable of probing event-related responses, network organization, and cortical complexity. Magnetic resonance methods reveal altered connectivity within thalamocortical and default mode network systems, while functional near-infrared spectroscopy adds a portable hemodynamic approach that may be repeated at the bedside and integrated with active paradigms. Brain-computer interfaces provide a translational step by converting neural responses into evidence of command following or, in selected patients, into communication, and artificial intelligence strengthens these approaches by extracting clinically meaningful patterns from complex neural and hemodynamic data. Additionally, autonomic measures, including heart rate variability and baroreflex indices, are considered as auxiliary physiological context for arousal and engagement, and not as direct markers of awareness. Because the most mature evidence for covert awareness and cognitive-motor dissociation comes from acquired disorders of consciousness, this review treats brain injury literature as a methodological foundation instead of as directly interchangeable evidence for neurodegenerative disease. It then examines how these approaches may be adapted to neurodegenerative contexts, especially ALS, severe dementia, Lewy body disease with fluctuating cognition, and conditions in which communication or motor output becomes unreliable.},
}

@article {pmid42514481,
year = {2026},
author = {Xie, P and Wang, J and Tong, B and Di, C and Zhou, F and Wang, W},
title = {Genome-Wide Characterization of the HaALS Gene Family Reveals Its Potential Roles in Imazethapyr Tolerance in Sunflower (Helianthus annuus L.).},
journal = {Plants (Basel, Switzerland)},
volume = {15},
number = {14},
pages = {},
doi = {10.3390/plants15142113},
pmid = {42514481},
issn = {2223-7747},
support = {CARS-14-1-06//Project of China Agriculture Research System/ ; CX25JC27//Heilongjiang Agricultural Science and Technology Innovation Leap Project/ ; },
abstract = {Acetolactate synthase (ALS; EC 2.2.1.6) catalyzes the first committed step in branched-chain amino acid (BCAA) biosynthesis and is the molecular target of multiple herbicide classes, including the imidazolinones. Here, we performed a genome-wide characterization of the HaALS gene family in sunflower (Helianthus annuus L.) and investigated genotype-dependent transcriptional responses to imazethapyr. A total of 11 HaALS genes were identified and classified into three phylogenetic clades (Groups A-C). All HaALS proteins contained the conserved TPP_enzyme domains (TPP_enzyme_N, TPP_enzyme_M, and TPP_enzyme_C), and purifying selection (Ka/Ks < 1) indicated strong evolutionary constraint on their core enzymatic function. Promoter analyses revealed abundant cis-regulatory elements associated with diverse stress and signaling inputs, supporting regulatory potential for herbicide-triggered transcriptional modulation. qRT-PCR analysis following imazethapyr application (0, 24, and 48 h) showed pronounced genotype-dependent expression reprogramming between the susceptible (S) and resistant (R) cultivars. In the R genotype, multiple HaALS members were strongly induced after treatment; specifically, HaALS4 reached a ~6-fold increase at 24 h and a >10-fold increase at 48 h, and HaALS11 increased to ~6-7-fold at 24 h while remaining above the baseline at 48 h; several additional paralogs exhibited intermediate induction (~3-8-fold by 48 h). In contrast, the S genotype showed limited changes (typically ~0.8-2-fold). Collectively, these findings define the evolutionary features of the sunflower HaALS family and identify herbicide-responsive paralogs that may contribute to imidazolinone tolerance, providing candidates for functional validation and molecular breeding.},
}

@article {pmid42514807,
year = {2026},
author = {Cazacu, G and Pamfil, D and Chirilă, O and Totolin, M and Ciolacu, D and Ghilan, A and Niţă, L and Niţă, T and Vasile, C},
title = {Chemical Treatment of Some Lignosulfonates Under DBD Plasma Conditions-II: Characterization of the Modified Lignosulfonates Microparticles.},
journal = {Polymers},
volume = {18},
number = {14},
pages = {},
doi = {10.3390/polym18141756},
pmid = {42514807},
issn = {2073-4360},
abstract = {The chemically modified ammonium lignosulfonate (ALS) powders with carboxylic acids such as, oleic (OA) and lactic acid (LA) and γ-butyrolactone (BL) under dielectric barrier plasma discharge (DBD) have been characterized by average molecular weight and particle size determinations, morphology examination by optical and electronic microscopy (SEM), the study of the thermal properties by thermogravimetry (TG/DTG), differential scanning calorimetry (DSC), differential thermal analysis (DTA) and antioxidant activity tests by DPPH method. The thermal characterization of the modified lignosulfonates reveals their improved thermal stability comparatively with ALS. It has been established that the obtained microparticles are aggregates of particles, covered by modified polymer and exhibit a particular behavior depending on the chemical structure of the used modifier, leading to multifunctional active lignin-based products with better homogeneity. By surface modification, the antioxidant capacity of modified lignosulfonate powders has been maintained.},
}

@article {pmid42515387,
year = {2026},
author = {Megalingam, RK and Kuttankulangara Manoharan, S and Cheriyan Manjooran, D and Kamble, D},
title = {Thrivaad: A Multilingual, Predictive Eye-Sign-Based AAC System Powered by Optimized Deep Learning.},
journal = {Sensors (Basel, Switzerland)},
volume = {26},
number = {14},
pages = {},
doi = {10.3390/s26144503},
pmid = {42515387},
issn = {1424-8220},
mesh = {Humans ; *Deep Learning ; *Communication Devices for People with Disabilities ; *Eye Movements/physiology ; Brain-Computer Interfaces ; Multilingualism ; },
abstract = {Around 1.5% of the global population is suffering from speech impairments; the major causes for this are cerebral palsy and ALS, and the only way for these individuals to communicate is through Augmentative and Alternative Communication (AAC). These systems are either electronic or non-electronic. Based on new study developments, electronic methods, such as Brain-Computer Interaction (BCI) and eye-gaze-based communication, are assessed as the best choices, but they have their own limitations, incorporating limited adaptability to changing conditions, such as setup variations and user fatigue, which reduces the system's robustness. Our previous study, Netravad, shows potential for addressing these gaps, but it lacks multilingual support and will not yield the same results under changing lighting conditions. This study, Thrivaad, provides multilingual support and text prediction and integrates optimized deep learning to accurately capture eye movements even in varying environmental lighting conditions. Thrivaad uses eye movements as input from a webcam, and the Optuna-optimized YOLOv5 model is used to detect the eye direction accurately. Then communication is established in English, Malayalam, and Hindi. The text-prediction feature of this system improves communication by reducing the number of eye gestures required to form a message. This study included a total of 60 participants across three age groups with 35,263 eye-sign images collected. With this data, the YOLOv5 model is trained and then optimized by Optuna. The proposal system provides accurate eye direction, text prediction, multilingual support, and improved adaptability to changing conditions for eye-based AAC.},
}

Humans
*Deep Learning
*Communication Devices for People with Disabilities
*Eye Movements/physiology
Brain-Computer Interfaces
Multilingualism

@article {pmid42515735,
year = {2026},
author = {Rosiak, N and Stojceski, F and Maroni, G and Piontek, B and Cielecka-Piontek, J},
title = {Integrative Network Pharmacology and Molecular Docking Analysis Reveals the Multitarget Mechanisms of Pterostilbene in Neurodegenerative Diseases.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {19},
number = {7},
pages = {},
doi = {10.3390/ph19071053},
pmid = {42515735},
issn = {1424-8247},
support = {UMO-2020/37/B/NZ7/03975//National Science Centre/ ; },
abstract = {Background: Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), differ in etiology but share several convergent pathological mechanisms. Pterostilbene (PTR) is a natural stilbene with reported antioxidant, anti-inflammatory, and neuroprotective properties. This study aimed to prioritize putative PTR-associated targets and biological processes potentially relevant to shared neurodegenerative mechanisms. Methods: An integrative in silico workflow combining network pharmacology, protein-protein interaction (PPI) analysis, GO Biological Process (GO BP) enrichment, molecular docking, and molecular dynamics (MD) simulations was applied. GO BP terms were filtered, focused on neurodegeneration- and neuroprotection-related processes, and subjected to REVIGO-based redundancy reduction. Selected targets were further evaluated by docking and 500 ns MD simulations. Results: A total of 181, 165, 128, and 109 shared PTR-disease targets were identified for AD, PD, HD, and ALS, respectively. Redundancy-reduced GO BP analysis indicated associations with neuroinflammation, oxidative stress and reactive oxygen species-related responses, programmed cell death, MAPK/ERK- and PI3K/AKT-related signaling, ion and calcium transport, and lipid-, steroid-, or hormone-associated regulation. PPI topology prioritized SRC, ESR1, and HSP90AA1 as recurrent hub-bottleneck proteins, whereas MD-based structural interpretation focused on ESR1 and HSP90AA1. MD analyses indicated stable PTR interactions with both proteins, with ESR1 showing the most favorable predicted interaction profile. Conclusions: These findings suggest that PTR may interact with shared neurodegeneration-relevant molecular systems, particularly through ESR1- and HSP90AA1-associated mechanisms. However, the results are exclusively computational and should be interpreted as hypothesis-generating, requiring further experimental validation.},
}

@article {pmid42516233,
year = {2026},
author = {Sancho-Castillo, S and Bargues-Navarro, G and Cárdenas Salazar, RG and Privado, J and Sanchis-Sanchis, E and Sancho-Cantus, D and Sanchis-Sanchis, CE and Cubero-Plazas, L and Cano Mateu, M and de la Rubia Ortí, JE},
title = {Influence of micronutrients on anxiety and depression in patients with amyotrophic lateral sclerosis.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1790327},
pmid = {42516233},
issn = {2296-861X},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a progressive loss of motor function, with respiratory failure representing the leading cause of death. Beyond motor deterioration, ALS involves extramotor manifestations, including prominent anxiety and depression symptoms. The intake of certain micronutrients has been associated with these emotional symptoms, due to their role in monoaminergic and peptidic neurotransmitter synthesis pathways; furthermore, these emotional symptoms can severely reduce patients' quality of life. Therefore, this study aims to analyze the relationship between the intake of key micronutrients related to neurotransmitter activity and anxiety and depression symptoms in ALS patients.

METHODS: A cross-sectional study was conducted with 61 patients with bulbar- or spinal-onset ALS. Dietary micronutrient intake (iodine, magnesium, vitamin B6, vitamin B9, and vitamin C) was assessed using a seven-day dietary record and a Food Frequency Questionnaire. Depression was assessed using the ALS Depression Inventory-12 (ADI-12), while anxiety-related symptoms were assessed using the Beck Anxiety Inventory (BAI).

RESULTS: A path analysis was conducted to examine the statistical prediction of emotional measures from nutrient intake. The model showed a good fit to the data: NFI = 1.000, GFI = 1.000, and SRMR = 0.001. Considering the magnitude of the effect of the regression weights (β ≥ 0.14), depression scores exhibited exploratory associations with iodine (β = -0.21) and magnesium (β = 0.22), while vitamin B9 (β = -0.32) emerged as an inferentially significant predictor (p < 0.05). Anxiety-related symptom severity (BAI scores) showed exploratory associations with iodine (β = -0.31), vitamin B6 (β = 0.24), and vitamin C (β = -0.15), whereas depression scores (β = 0.51) were an inferentially significant predictor (p < 0.05), with 41% of explained variance.

CONCLUSION: In this sample, lower vitamin B9 intake was statistically associated with depression scores in patients with ALS, while lower iodine and higher magnesium intake showed exploratory associations. Regarding anxiety-related symptoms assessed using the Beck Anxiety Inventory (BAI), higher scores were statistically associated with lower iodine and vitamin C intake, higher vitamin B6 intake, and elevated depression scores, and showed exploratory associations with lower iodine and vitamin C intake, and higher vitamin B6 intake.},
}

@article {pmid42517609,
year = {2026},
author = {Dillenburg, RF and Lopatina, A and Ruan, H and Scheidt, T and Mosna, S and Pekbilir, E and Bieber, J and Schäfer-Depoix, F and Landfester, K and Schmidt, C and Möckel, MM and Morsbach, S and Schmid, F and Dormann, D and Stelzl, L and Girard, M and Lemke, EA},
title = {A Phosphorylation-Induced Micellization Switch in the Low-Complexity Domain of TDP-43.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e76625},
pmid = {42517609},
issn = {2198-3844},
support = {464588647//Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)/ ; },
abstract = {Phase separation (PS) of the low-complexity domain (LCD) of TAR DNA-binding protein 43 kDa (TDP-43) is linked to pathogenic aggregates in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP). Here, we show that extensive phosphorylation of the LCD C-terminus redirects its self-assembly. Coarse-grained Monte Carlo simulations predicted that 12 Ser phosphorylations partition the 148-residue LCD into a hydrophobic N-terminal and highly charged C-terminal block, favouring finite-sized micellization over macroscopic PS. In vitro, LCD phosphorylated by casein kinase 1 delta (CK1δ; mean of 12 phosphorylations by native mass spectrometry) and phosphomimetic 12D/12DD mutants formed spherical nanoparticles (≈ 20-50 nm) above a low-micromolar critical micelle concentration, whereas the unphosphorylated LCD underwent reversible PS that matured into fibrils. Increasing ionic strength shifted the mutants toward anisotropic morphologies (wormlike 12D micelles and rigid 12DD nanocylinders). Turbidity assays and confocal imaging directly visualized the absence of PS in the phosphorylated form. Negative-stain and cryo-electron microscopy (cryo-EM) confirmed the spherical micellar architecture for the phosphorylated LCD and 12D/12DD mimics. Our data identify phosphorylation as a molecular switch tuning macrophase separation and fibril formation of TDP-43 LCD, providing a framework for an aggregation-protective role through microphase separation into size-limited micelles. Whether these assemblies are stable or kinetically trapped on pathological timescales remains unclear.},
}

@article {pmid42520183,
year = {2026},
author = {Simão, S and Oliveira Santos, M and Gromicho, M and Martins, IP and de Carvalho, M},
title = {Evidence of stage-specific cognitive reserve effects on longitudinal cognition in amyotrophic lateral sclerosis.},
journal = {Journal of neuropsychology},
volume = {},
number = {},
pages = {},
doi = {10.1111/jnp.70066},
pmid = {42520183},
issn = {1748-6653},
abstract = {About 50% of amyotrophic lateral sclerosis (ALS) patients develop cognitive-behavioural impairment, yet longitudinal studies diverge on onset and extent of decline. Cognitive reserve (CR) may modulate cognitive trajectories, although longitudinal evidence remains limited. We aim to characterize cognitive trajectories in ALS and healthy aging and to examine the role of CR proxies in shaping cognitive change over time. About 268 participants (169 patients, 99 controls) were evaluated twice over 6 to 18 months using the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Mixed models were used to predict initial ECAS performance (ECAS1), and cognitive slope (ECAS2-ECAS1) using CR proxies (education, work and leisure), ECAS21-ECAS12 interval, demographics (age, sex, psychiatric medication) and clinical factors (disease duration, onset-region, respiratory capacity, functional decline, C9orf72 mutation and behavioural symptoms). In patients, education (p < .001) and leisure (p < .001) positively predicted ECAS1. However, longitudinally, education and leisure had negative main effects on cognition, protecting against decline through interactions with clinical variables. In controls, more education and leisure predicted better cognition through main effects and interactions. CR appears to exhibit a dynamic, phase-dependent influence in patients and controls, supporting initial cognitive performance and potentially offering subtle protection as disease progresses. The observed non-linear effects of all CR proxies and subgroup-specific effects highlight the importance of considering clinical context, time and initial cognition when evaluating CR's role in ALS.},
}

@article {pmid42504602,
year = {2026},
author = {Eisen, A and Durham, HD and Pioro, E},
title = {The aging brain that doesn't fail: how neural resilience masks neurodegeneration.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-15},
doi = {10.1080/21678421.2026.2705693},
pmid = {42504602},
issn = {2167-9223},
abstract = {Neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease are usually framed as consequences of aging-related pathogenic processes, including impaired proteostasis with protein aggregation, mitochondrial dysfunction, oxidative stress, and neuroinflammation. Yet, most individuals, even into advanced age, do not develop clinically significant neurodegenerative disease. This discrepancy suggests that the nervous system possesses robust and redundant protective mechanisms that maintain neural integrity despite cumulative molecular and cellular stress. In this perspective, we propose that neurodegenerative diseases arise not simply from the presence of pathogenic processes, but when integrated resilience systems fail to maintain homeostasis or when reserve mechanisms no longer compensate for accumulated pathology. We have synthesized a threshold-based model of disease emergence based on evidence across proteostasis, mitochondrial function, neuroimmune regulation, glial biology, network-level compensation, and barrier integrity, while integrating genetic, environmental, developmental, and stochastic modifiers. We distinguish biological resilience, which actively limits or repairs pathology, from reserve, which permits function despite pathology. We further propose that clinical disease emerges only when age-related cumulative stress exceeds the combined capacity of resilience and reserve. Reframing neurodegeneration as a failure of preservation systems offers new directions for prevention and therapeutic development.},
}

@article {pmid42505224,
year = {2026},
author = {Collaço, N and Kennington, A and Greenberg, N and Imber, T and Warne, D and Sodergren, S},
title = {Mapping Support-Seeking After Cancer Treatment: A Co-Designed Model of Triggers, Timing and Support Pathways in Young People with Lived Experience of Cancer.},
journal = {Current oncology (Toronto, Ont.)},
volume = {33},
number = {7},
pages = {},
pmid = {42505224},
issn = {1718-7729},
mesh = {Humans ; *Neoplasms/psychology/therapy ; *Social Support ; Female ; Male ; Young Adult ; Adolescent ; *Help-Seeking Behavior ; Adult ; },
abstract = {Post cancer treatment, many young people often live with ongoing emotional, social, and physical difficulties, but support is not always accessed when it is needed. This study aimed to co-produce a conceptual model of support-seeking after cancer treatment with young people with lived experience of cancer, to better understand the triggers, timing, and pathways influencing engagement with support. This co-design work, informed by Bird et al.'s generative framework for co-production, built upon a prior study involving interviews and co-design workshops with young people and healthcare/allied health professionals, and informed a preliminary model of support-seeking. The current work involved two further co-production stages through an online survey and workshop to refine this model. Data were analysed using a thematic approach to support conceptual model development. Four interconnected themes shaped support-seeking: (1) readiness to engage: recognition, emotional readiness, and relational safety; (2) access and appraisal of support: visibility, fit, feasibility, and burden; (3) pathways to support: multi-modal, layered, and non-linear engagement; and (4) support trajectory: changing needs and recurrent engagement. Engagement in support-seeking depended on the alignment of readiness, recognition of need, and relational safety. This model offers a framework to improve how post-treatment support is designed and delivered in practice.},
}

Humans
*Neoplasms/psychology/therapy
*Social Support
Female
Male
Young Adult
Adolescent
*Help-Seeking Behavior
Adult

@article {pmid42505342,
year = {2026},
author = {Yang, CS and Ma, Y and Xie, JL and Lou, XY and Lv, YT and Wu, TX and Xu, HF and Zou, SM and Wu, ZY and Li, HF},
title = {Pathogenicity Classification of TARDBP Variants of Uncertain Significance: An Integrative Clinical Characterization and Functional Validation.},
journal = {Cells},
volume = {15},
number = {14},
pages = {},
pmid = {42505342},
issn = {2073-4409},
support = {2025ZD1802600//Innovative Drug Research and Development National Science and Technology Major Project/ ; },
mesh = {Humans ; *DNA-Binding Proteins/genetics/chemistry/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Mutation/genetics ; Female ; Genetic Variation ; },
abstract = {TAR DNA binding protein (TARDBP) is one of the major causative genes of amyotrophic lateral sclerosis (ALS), which drives disease progression through both gain-of-toxicity (GOT) and loss-of-function (LOF) mechanisms. The mutant TDP-43 exhibits aberrant nucleocytoplasmic distribution and forms cytotoxic hyperphosphorylated aggregates, a process that can be robustly recapitulated in vitro. Thus, functional assays in cell lines serve as a reliable metric for the pathogenicity classification of TARDBP variants. In this study, we performed in vitro experiments to classify the pathogenicity of 28 TARDBP variants of uncertain significance (VUS) among the 172 previously reported TARDBP variants. 22 of these VUS were determined to be functionally abnormal, of which 12 could be further classified as likely pathogenic (LP) variants according to American College of Medical Genetics (ACMG) and the ClinGen Sequence Variant Interpretation (SVI) Working Group guidelines. We also summarized the clinical characteristics of 35 ALS patients carrying 12 variants in the TARDBP gene. Pathogenic missense variants were predominantly clustered in the C-terminal domain (CTD) of TARDBP. Variants in TARDBP exon 6 may lead to an earlier age at onset. ALS caused by TARDBP mutations exhibits marked phenotypic heterogeneity, along with incomplete penetrance in carriers. Patient-derived primary skin fibroblasts serve as a feasible cellular model for the functional assessment of variant pathogenicity. Our findings expand the TARDBP mutation spectrum, and provides a preliminary basis for preclinical research on TARDBP-targeted therapies for ALS.},
}

Humans
*DNA-Binding Proteins/genetics/chemistry/metabolism
*Amyotrophic Lateral Sclerosis/genetics/pathology
Mutation/genetics
Female
Genetic Variation

@article {pmid42505348,
year = {2026},
author = {Liu, B and Zhang, L and Lv, B and Xu, C and Han, L and Yan, Q and Wang, X},
title = {Copper Homeostasis and Cuproptosis in Neurodegenerative Diseases.},
journal = {Cells},
volume = {15},
number = {14},
pages = {},
pmid = {42505348},
issn = {2073-4409},
mesh = {Humans ; *Copper/metabolism ; *Cuproptosis ; *Homeostasis ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; Mitochondria/metabolism ; Proteotoxic Stress ; },
abstract = {Copper is an essential trace element required for numerous enzymatic processes in the brain, including mitochondrial metabolism, antioxidant defense, and gene expression regulation. Recent studies have further implicated copper in a newly defined form of regulated cell death termed cuproptosis, providing a mechanistic framework for copper-dependent cytotoxicity. Increasing evidence indicates that copper dyshomeostasis is a common feature of major neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), where it is associated with protein misfolding, redox imbalance, and neuronal vulnerability. Nevertheless, the mechanistic link between copper dysregulation and neuronal cell death remains incompletely defined. In this review, we systematically summarize the molecular mechanisms governing copper homeostasis and intracellular copper trafficking, while providing a timely, updated, and in-depth overview of the mechanistic basis and emerging biology of cuproptosis. We further comprehensively evaluate the current evidence linking copper dysregulation and cuproptosis-related pathways to neurodegenerative diseases, with particular emphasis on distinguishing mechanistic causation from pathological correlation. Importantly, we discuss current therapeutic strategies and emerging clinical efforts targeting copper metabolism, while highlighting the major challenges in defining the pathological significance and mechanistic contribution of cuproptosis in neurodegenerative diseases. Collectively, this review provides an updated framework for understanding the pathological significance and translational potential of cuproptosis in neurodegenerative diseases.},
}

Humans
*Copper/metabolism
*Cuproptosis
*Homeostasis
*Neurodegenerative Diseases/metabolism/pathology
Animals
Mitochondria/metabolism
Proteotoxic Stress

@article {pmid42506061,
year = {2026},
author = {Zeng, CW},
title = {Protein-First, but Not Protein-Only: Rethinking Neurodegenerative Diseases Through Transgenic Mouse Models.},
journal = {Neurology international},
volume = {18},
number = {7},
pages = {},
doi = {10.3390/neurolint18070139},
pmid = {42506061},
issn = {2035-8385},
abstract = {Neurodegenerative diseases represent a major and growing global health burden. Although these disorders are often clinically defined by symptoms and affected brain regions, many are mechanistically linked to abnormal protein accumulation, misfolding, impaired proteostasis, RNA dysregulation, mitochondrial dysfunction, and neuroinflammation. In this Perspective article, I discuss major neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, amyotrophic lateral sclerosis, frontotemporal dementia, Huntington's disease, prion diseases, spinocerebellar ataxias, and spinal muscular atrophy, through the lens of disease-associated proteins and experimental modeling. I argue that a protein-centered framework provides a useful approach for understanding disease mechanisms and selecting transgenic mouse models, while recognizing that aging, cellular context, neuroinflammation, mitochondrial dysfunction, vascular dysfunction, and other disease modifiers also shape neurodegeneration. Transgenic and genetically engineered mouse models have been essential for dissecting the pathogenic roles of amyloid-β, tau, α-synuclein, TDP-43, SOD1, FUS, C9ORF72-associated dipeptide repeat proteins, mutant huntingtin, prion protein, ataxins, and SMN deficiency. However, these models have important limitations, including artificial overexpression, familial mutation bias, species differences, and incomplete representation of aging-related sporadic diseases. Rather than seeking a single "best" model, a more productive strategy is to adopt model portfolios tailored to specific biological questions and to integrate mouse studies with human cellular models, postmortem tissue, omics approaches, and biomarker-based validation. Such an approach may improve mechanistic insight, strengthen translational relevance, and enhance the predictive value of preclinical neurodegenerative disease research.},
}

@article {pmid42506583,
year = {2026},
author = {Remus, S and Donelle, L and Bauer, M and Nagle, L},
title = {A Nursing Homecare Data Science Investigation Using "Persons with ALS" (PALS) Electronic Health Records (EHRs).},
journal = {The Canadian journal of nursing research = Revue canadienne de recherche en sciences infirmieres},
volume = {},
number = {},
pages = {8445621261469904},
doi = {10.1177/08445621261469904},
pmid = {42506583},
issn = {1705-7051},
abstract = {BackgroundData science, rooted in computer science, statistics, and information science is advancing healthcare research by unlocking "insights" from big data to discover knowledge about patient experiences and answer previously unanswerable questions. The comparatively limited engagement of Canadian nurse researchers in this field, relative to counterparts in other jurisdictions (e.g., United States) served as a key impetus for initiating this data science study.PurposeTo investigate homecare electronic health records (EHRs) of "persons with ALS" (PALS) disease and identify care-related factors that influence their preferences and ability to be safely supported at home.MethodGuided by a nursing informatics' data, information, knowledge, wisdom (DIKW) framework and the knowledge discovery in databases (KDD) methodology, a retrospective, secondary analysis of an integrated dataset (1159 clinical assessments and administrative data) documenting 240 PALS's homecare encounters (April 1, 2009 - July 31, 2019) was conducted. EHR data was analyzed using correlations and logistic regression to model institutionalization risk factors of PALS.ResultsFive significant models were generated that accurately distinguished PALS institutionalization status (at home/not home) while offering comparable predictive performance. The final model featuring six factors offers homecare providers real-time insights into PALS clinical status at the point of care. Four relate to ALS clinical manifestations of disease decline and two assessment outcome measures (MAPLe and CHESS), strongly predicting institutionalization and caregiver burden.ConclusionBig data science offers nurse researchers a transformative way to advance knowledge development that supports high-quality, sustainable healthcare delivery while fulfilling an intended benefit of EHRs.},
}

@article {pmid42507931,
year = {2026},
author = {Ozguney, B and Puterbaugh, RZ and Viswanathan, R and Shenoy, J and Mohanty, P and Mittal, J and Fawzi, NL},
title = {Methionine oxidation alters both helical assembly and disordered contacts in human TDP-43 C-terminal domain phase separation.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {31},
pages = {e2537431123},
doi = {10.1073/pnas.2537431123},
pmid = {42507931},
issn = {1091-6490},
support = {R01NS116176//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; not applicable//Radala Foundation/ ; },
abstract = {TAR DNA binding protein 43 (TDP-43), a key protein linked to ALS pathology, undergoes phase separation and forms functional assemblies via condensation within cells. The conserved region (CR) within its C-terminal domain (CTD) mediates self-assembly through helix-helix interactions, while the flanking intrinsically disordered regions (IDRs) contribute to phase separation through transient interactions involving aromatic and hydrophobic residues. The CTD contains ten methionine residues distributed equally between these regions, making it particularly susceptible to oxidative modifications. While methionine oxidation is known to impair TDP-43 phase separation, neither the precise mechanism nor the specific contribution of methionines in the CR compared to the IDRs has been determined. Here, we combine NMR spectroscopy and molecular dynamics (MD) simulations to reveal if and how methionine oxidation in each region differentially affects CTD structure and phase separation. To assess the change of secondary structure caused by oxidation, we measured NMR random coil chemical shift values for methionine sulfoxide. Oxidation of CR methionines disrupts helical structure and directly impairs intermolecular helical association, while oxidation of IDR methionines disrupts long-range contacts. Hence, oxidation of methionines in both regions contributes to impaired phase separation, albeit through different mechanisms. These findings establish methionines as critical redox-sensitive modulators in TDP-43 phase behavior and provide molecular insights into how oxidative stress may contribute to TDP-43 dysregulation in neurodegenerative diseases.},
}

@article {pmid42508294,
year = {2026},
author = {Liu, X and Fu, W and Cui, X and Feng, Y and Wen, B and Shan, L and Xu, X and Yang, J and Zhang, J and He, L and Zang, Y and Zhao, S and Yao, X and Liu, Y and Ma, M and Du, B and Dang, J and Zou, Z and Feng, H and Lu, Z and Zhang, Y and Wu, Z and Shang, H and Yin, P and Fan, D},
title = {Huoling Shengji granule in amyotrophic lateral sclerosis: A multicenter, randomized, double-blind, riluzole-controlled trial.},
journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics},
volume = {23},
number = {5},
pages = {e00953},
doi = {10.1016/j.neurot.2026.e00953},
pmid = {42508294},
issn = {1878-7479},
abstract = {Currently, no curative therapies exist for Amyotrophic Lateral Sclerosis (ALS). This study aimed to evaluate the efficacy and safety of Huoling Shengji granules (HLSJ), a traditional Chinese medicine (TCM), compared to the standard treatment riluzole. A multicenter, randomized, double-blind, double-dummy, active-controlled Phase II clinical trial was conducted across 11 centers in China. A total of 140 ALS patients were randomly assigned (1:1) to receive either HLSJ or riluzole for 48 weeks. The primary endpoint, analyzed in the full analysis set (FAS), was the change in the ALS Functional Rating Scale-Revised (ALSFRS-R) score from baseline to Week 48. Safety profiles were comparable between groups, with no significant difference in adverse events (80.28% vs. 80.56%, P = 0.9671). Analysis using the pre-specified Last Observation Carried Forward (LOCF) method showed a numerical advantage for HLSJ (1.07 points) but lacked statistical superiority. However, a more scientific analysis using the Mixed Model for Repeated Measures (MMRM), recommended for progressive diseases, indicated that HLSJ was significantly superior to riluzole in slowing ALSFRS-R score decline (Least Squares Mean Difference [LSMD]: 2.29 points; 95% confidence interval [CI]: 0.52 to 4.06; P = 0.0114). While the LOCF model showed no statistical difference, the MMRM analysis confirmed that HLSJ demonstrated significant efficacy superior to riluzole with a favorable safety profile. These findings provide a critical basis for conducting pivotal Phase III confirmatory trials of HLSJ for ALS treatment.},
}

@article {pmid42508356,
year = {2026},
author = {Wu, W and Lalli, GS and Wu, H},
title = {Linking Big Five personality traits to L2 willingness to communicate with GenAI chatbots: A mixed-methods study of the mediating role of regulatory focus.},
journal = {Acta psychologica},
volume = {269},
number = {},
pages = {107516},
doi = {10.1016/j.actpsy.2026.107516},
pmid = {42508356},
issn = {1873-6297},
abstract = {Generative artificial intelligence (GenAI) chatbots are increasingly used for second language (L2) speaking practice, yet learners' willingness to communicate (WTC) with them remains insufficiently understood. Building on MacIntyre et al.'s (1998) Pyramid Model, this study examined how the Big Five personality traits and regulatory focus jointly shape L2 WTC in GenAI-mediated interaction. Survey data from 426 Chinese university learners were analyzed using Partial Least Squares Structural Equation Modeling, complemented by qualitative thematic analysis. Openness emerged as the only trait directly predicting WTC and was positively associated with both promotion and prevention focus. Agreeableness positively predicted prevention focus, whereas Extraversion showed a negative association; Conscientiousness and Neuroticism were unrelated to regulatory focus. Prevention focus, but not promotion focus, significantly predicted WTC. Indirect effects indicated that Openness and Agreeableness enhanced WTC through prevention focus, while Extraversion exerted a negative indirect effect. Qualitative analysis identified four themes, with psychological safety and controllability explaining why prevention-focused learners favored GenAI. Together, the findings suggest that GenAI's de-socialized, low-risk interaction environment reshapes how personality and motivational dispositions translate into L2 WTC, offering implications for both L2 pedagogy and the design of GenAI-supported speaking tools.},
}

@article {pmid42508391,
year = {2026},
author = {Gao, W and Lee, HY and Min, KJ},
title = {Aging-Related Metaflammation and Mitochondrial Dysfunction in Neurodegenerative Diseases.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2026.0366},
pmid = {42508391},
issn = {2152-5250},
abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are increasingly recognized as manifestations of aging-associated systemic dysfunction, rather than isolated brain disorders. Central to this dysfunction is the interplay among metaflammation, mitochondrial breakdown, and chronic neuroinflammation. Metaflammation, driven by peripheral metabolic stress, may prime the brain's immune environment through cytokine signaling and blood-brain barrier compromise. This metabolic-inflammatory crosstalk is thought to impair mitochondrial integrity in neurons and glial cells, promoting oxidative stress and the release of pro-inflammatory mitochondrial components. These mitochondrial signals, in turn, may activate microglial and astrocytic innate immune responses, creating a potentially self-reinforcing cycle of neuroinflammation and energy failure that may contribute to neuronal loss. This review outlines a proposed framework linking metaflammation to neurodegeneration, emphasizing shared mechanisms across AD, PD, and ALS. We further examine preclinical and clinical advances in therapeutic strategies that target this axis including anti-inflammatory agents, caloric restriction, mitophagy enhancers, mitochondrial antioxidants, and senescence-targeted therapies. Together, these interventions reflect a shift from symptom management to systemic metabolic and immune modulation, offering a unified framework for understanding and potentially influencing age-related neurodegeneration.},
}

@article {pmid42508540,
year = {2026},
author = {Sun, R and Duan, X and Wang, X and Liu, J and Li, Z and Wang, Y},
title = {R-loops: Biological Functions, Regulatory Mechanisms, and Therapeutic Implications in Brain Diseases-A Review.},
journal = {Molecular and cellular probes},
volume = {},
number = {},
pages = {102081},
doi = {10.1016/j.mcp.2026.102081},
pmid = {42508540},
issn = {1096-1194},
abstract = {BACKGROUND: R-loops are three-stranded nucleic acid structures formed by a DNA-RNA hybrid and a displaced single-stranded DNA. They regulate transcription, replication, and DNA repair, but their dysregulation causes genomic instability and inflammation, contributing to brain diseases. The nervous system exhibits selective vulnerability to R-loop stress due to ultra-long gene transcription, post-mitotic longevity, and high metabolic demands.

METHODS: This review synthesizes current literature from PubMed, Scopus, Web of Science, and Embase (2010-2026) on R-loop biology, with a focus on brain-specific mechanisms, regulatory factors (SETX, ZPR1, METTL3, TDP-43/FUS), and disease models.

RESULTS: In neurodegeneration, R-loop accumulation drives repeat expansion disorders (Fragile X, Huntington's disease) and loss-of-function SETX mutations (AOA2), whereas gain-of-function SETX (L389S) causes pathological R-loop depletion in ALS4, disrupting TGF-β signaling. TDP-43/FUS and SMN are integral to R-loop resolution, unifying ALS/FTD and SMA. In brain cancers, METTL3-mediated m[6]A modification of TERRA stabilizes telomeric R-loops in ALT-positive neuroblastoma, creating a therapeutic vulnerability to METTL3 inhibitors (STM2457, STC-15). Glioma stem cells rely on m[6]A-modified circPOLR2B to regulate R-loop formation and malignancy. Clinical-stage agents (EP102, TUG1ASO, ATX-559) and R-loop-derived prognostic signatures (RLPI) are emerging, but translation is hindered by a lack of non-invasive biomarkers and the dual physiological/pathological roles of R-loops.

CONCLUSIONS: R-loops are central to brain disease pathogenesis, offering promising therapeutic targets. Future research should prioritize precision R-loop modulators, non-invasive biomarkers, and combinatorial strategies.},
}

@article {pmid42508631,
year = {2026},
author = {Alanazi, SM and Al-Kuraishy, HM and Alexiou, A and Papadakis, M and Faheem, SA and Batiha, GE},
title = {Isoform-selective HSP90 inhibition as a precision therapeutic strategy for neurodegenerative and metabolic diseases.},
journal = {Progress in neuro-psychopharmacology & biological psychiatry},
volume = {149},
number = {},
pages = {111834},
doi = {10.1016/j.pnpbp.2026.111834},
pmid = {42508631},
issn = {1878-4216},
abstract = {Heat shock protein 90 (HSP90) is a central regulator of cellular proteostasis, coordinating the folding, stabilization, and turnover of a wide range of client proteins in the cytosol, endoplasmic reticulum, and mitochondria. Accumulating evidence indicates that the four HSP90 paralogs HSP90α, HSP90β, GRP94, and TRAP1 have distinct pathological roles in neurodegenerative and metabolic diseases. In neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, aberrant HSP90 activity contributes to the persistence of toxic protein conformers, defective autophagy, mitochondrial dysfunction, and chronic neuroinflammation. In metabolic disorders such as obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease, GRP94- and TRAP1-dependent signaling promotes endoplasmic reticulum stress, impaired mitochondrial metabolism, insulin resistance, and inflammatory remodeling. These mechanistic insights have accelerated the development of a new generation of HSP90 inhibitors with improved selectivity, tissue targeting, and brain penetration. Unlike earlier pan-HSP90 inhibitors, these compounds are designed to exploit paralog-specific vulnerabilities and may enable safer long-term modulation of disease-relevant chaperone networks. This review summarizes current advances in the biology and pharmacology of HSP90 paralogs and proposes isoform-selective HSP90 targeting as a promising therapeutic strategy at the intersection of neurodegeneration and metabolic dysfunction.},
}

@article {pmid42508735,
year = {2026},
author = {Piccolo, LL and Panto, C and Yeewa, R and Yubolphan, R and Poound, P and Potikanond, S and Jantrapirom, S},
title = {Context-dependent YEATS-domain inhibition enhances neuronal resilience and improves ALS phenotypes.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107549},
doi = {10.1016/j.nbd.2026.107549},
pmid = {42508735},
issn = {1095-953X},
abstract = {Neuronal loss in neurodegenerative disease is driven in part by maladaptive stress signaling and impaired adaptation to proteotoxic challenges. ENL and AF9 are YEATS-domain acyl-lysine reader proteins best characterized in leukemia, but their functions in neurons remains unclear. Here, we defined the role of the ENL/AF9 YEATS domain using complementary chemical and genetic perturbations. We applied the selective YEATS inhibitor SR-0813 in differentiated human neurons and modulated ENL/AF9 activity in Drosophila using either SR-0813 or ENL/AF9 knockdown. In flies, SR-0813 phenocopied ENL/AF9 knockdown by extending lifespan and enhancing stress tolerance. To test disease-context specificity, we performed a Drosophila genetic modifier screen across neurodegeneration models. ENL/AF9 reduction was beneficial in UBQLN2[P497H] and SOD1[G94A] but showed reduced efficacy or became detrimental in chronic aggregation or mitochondrial stress models such as (GGGGCC)49 and polyQ disease. In human neurons, SR-0813 improved survival across multiple stress conditions, with the strongest protection during endoplasmic reticulum stress. Mechanistically, ENL/AF9 YEATS inhibition dampened PERK-dependent integrated stress response signaling and reduced apoptotic commitment without broadly enhancing proteostasis capacity. Together, these findings identified ENL/AF9 as modulators of neuronal stress-response dynamics and established ENL/AF9 YEATS-domain inhibition as a context-dependent strategy to enhance neuronal resilience with relevance to ALS and related proteotoxic disorders.},
}

@article {pmid42509371,
year = {2026},
author = {Ran, X and Wuu, J and Qin, ZS and McDermott, MP and Cooper-Knock, J and Li, Y and Granit, V and Grignon, AL and Lin, E and Fernandez, MC and Colato, D and Carberry, N and Lill, CM and Piazza, P and Malaspina, A and Benatar, M},
title = {Longitudinal plasma proteomics predict phenoconversion to clinically manifest ALS.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {42509371},
issn = {1546-170X},
support = {R01 NS105479, U54 NS092091//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01 NS105479, U54 NS092091//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01 NS105479/NS/NINDS NIH HHS/United States ; R01 NS105479/NS/NINDS NIH HHS/United States ; R01 NS105479, U54 NS092091//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 4365, 172123//Muscular Dystrophy Association (Muscular Dystrophy Association Inc.)/ ; 4365, 172123//Muscular Dystrophy Association (Muscular Dystrophy Association Inc.)/ ; 4365, 172123//Muscular Dystrophy Association (Muscular Dystrophy Association Inc.)/ ; 2015, 16-TACL-242//Amyotrophic Lateral Sclerosis Association (ALS Association)/ ; 2015, 16-TACL-242//Amyotrophic Lateral Sclerosis Association (ALS Association)/ ; 2015, 16-TACL-242//Amyotrophic Lateral Sclerosis Association (ALS Association)/ ; },
abstract = {The study of pre-symptomatic amyotrophic lateral sclerosis (ALS) and the design of disease prevention trials are greatly hampered by our inability to predict which unaffected carriers of ALS-associated pathogenic variants will phenoconvert to clinically manifest disease and when. In this longitudinal Olink Explore, high-throughput, proteomic study, 516 serially collected plasma samples from 33 phenoconverters, 35 patients with ALS, 10 pre-symptomatic pathogenic variant carriers and 59 controls were included. Here we identified 92 proteins with concentrations that changed before phenoconversion; characterized the longitudinal trajectory of these proteins and identified a core panel of 19 proteins which, collectively, predicted phenoconversion over the 0.5-year to 5-year time horizons (crossvalidated areas under the curve 0.80-0.89) and yielded estimates of time to phenoconversion with a mean absolute error of 1.6 years. These findings were partially replicated in UK Biobank data, confirming pre-symptomatic increases in several proteins (for example, NEFL, EDA2R and CA3) and that a multi-protein panel outperformed NEFL alone in estimating time to phenoconversion. This work sheds light on the biology of pre-symptomatic ALS. Moreover, our identification of a panel of new susceptibility/risk biomarkers based on empirical longitudinal data furthers the ultimate goal of ALS prevention.},
}

@article {pmid42509459,
year = {2026},
author = {Sellin, J and Öijerstedt, L and von der Gablentz, J and Chamoun, S and Kläppe, U and Press, R and Samuelsson, K and Grosskreutz, J and Ingre, C},
title = {Plasma cardiac troponin T complements neurofilament light chain by reflecting disease phase and phenotypic variation in amyotrophic lateral sclerosis.},
journal = {Journal of neurology},
volume = {273},
number = {8},
pages = {},
pmid = {42509459},
issn = {1432-1459},
support = {GR 1578/6-1//Deutsche Forschungsgemeinschaft/ ; GR 1578/9-1//Deutsche Forschungsgemeinschaft/ ; EXC 2167/2 - 390884018//Germany`s Excellence Strategy/ ; },
abstract = {BACKGROUND: Neurofilament light chain (NfL) is an established marker of neuronal injury and disease aggressiveness in amyotrophic lateral sclerosis (ALS). In contrast, the clinical and biological significance of cardiac troponin T (cTnT) in ALS is not fully understood. We aimed to evaluate the relationship between plasma cTnT and disease aggressiveness, progression stage, and clinical phenotype in comparison with NfL.

METHODS: Plasma cTnT and cerebrospinal fluid (CSF) NfL were analysed at diagnosis in a population-based cohort of 526 patients with ALS. Disease aggressiveness was modelled using the D50 framework, which quantifies the time taken to lose 50% of functional capacity (ALSFRS-R) and normalises individual disease trajectories. Biomarker associations with disease aggressiveness, phase, and clinical variables were assessed through group comparisons, logistic and linear regression, and receiver operating characteristic analyses.

RESULTS: Neurofilament light chain in CSF was strongly associated with disease aggressiveness, with higher levels in patients with more aggressive disease. In contrast, plasma hs-cTnT did not correlate with D50. Across disease phases, CSF NfL remained relatively stable, whereas plasma hs-cTnT increased with advancing rD50, suggesting accumulation with disease progression. Plasma hs-cTnT levels were higher in patients with spinal compared to bulbar onset. Combined biomarker models improved sensitivity and negative predictive value for identifying less aggressive disease.

CONCLUSION: Plasma hs-cTnT and CSF NfL capture distinct but complementary dimensions of ALS pathology. While NfL reflects disease aggressiveness, hs-cTnT aligns with disease phase and clinical phenotype, supporting its use as a complementary biomarker for ALS characterisation and monitoring.},
}

@article {pmid42510076,
year = {2026},
author = {Uzun, E and İçöz, D and Apaydın, BK and Orhan, K},
title = {Investigation of the Use of Artificial Intelligence in Anterior Loop Detection: A Panoramic Radiography Study.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {16},
number = {14},
pages = {},
pmid = {42510076},
issn = {2075-4418},
support = {2024HZDP003//Pamukkale University/ ; },
abstract = {Background/Objectives: The accurate detection of the anterior loop (AL) of the inferior alveolar nerve is critical to avoid neurosensory complications during surgical procedures in the interforaminal region, and panoramic radiography continues to be widely used in routine dental diagnostics due to its accessibility and cost-effectiveness. This study aimed to evaluate the performance of a deep learning approach in automatic detection of the AL in panoramic radiographs. Methods: A total of 305 anonymised panoramic radiographs containing 413 annotated ALs were used to train a YOLOv8x-based model for automatic AL detection. The dataset was divided into training, validation, and test sets consisting of 245 images (332 AL annotations), 30 images (40 AL annotations), and 30 images (41 AL annotations). Labelling was carried out by using the polygonal annotation method. The model's performance in identifying the AL region was measured using precision, recall, F1 score, and mean average precision (mAP@0.5). Results: The model achieved a precision of 0.75, a recall of 0.6585, and a F1 score of 0.7013. The average precision at an intersection over union (IoU) threshold of 0.5 (mAP@0.5) was 0.739. Conclusions: This study demonstrates the feasibility of using a YOLOv8x-based detection model to detect ALs in panoramic radiographs. Although further improvements are needed to enhance model sensitivity and generalisability, the findings demonstrate the potential to support clinical decision-making.},
}

@article {pmid42510722,
year = {2026},
author = {Avitabile, A and Rusciano, D and Amato, R and Cannizzaro, L and Gagliano, C},
title = {Sex-Dependent Brain Plasticity in Neurological Disease: From Biological Variability to Adaptive, Compensatory, and Maladaptive Trajectories.},
journal = {Biology},
volume = {15},
number = {14},
pages = {},
doi = {10.3390/biology15141176},
pmid = {42510722},
issn = {2079-7737},
abstract = {Brain plasticity is often described as the capacity of the nervous system to change in response to development, experience, injury, disease, or treatment. That definition is useful, but it can obscure two clinically important points: plasticity is biologically constrained, and change is not always beneficial. This narrative review examines sex-dependent brain plasticity as a context-sensitive process rather than as a simple male-female contrast. We distinguish four operational outcomes of plasticity: (i) reparative plasticity, which restores structure or function; (ii) compensatory plasticity, which preserves performance through alternative or more costly strategies; (iii) insufficient plasticity, in which reorganization is too weak or unstable to sustain function; and (iv) maladaptive plasticity, in which plastic change reinforces dysfunction, pain, excitability, rigidity, or decline. We also define adaptive reserve as the integrated capacity of neural, glial, vascular, immune, metabolic, endocrine, and gene-regulatory systems to support useful reorganization under stress. The review evaluates endocrine, synaptic, neuroimmune, mitochondrial, vascular, stress-related, and epigenetic mechanisms, indicating where evidence for sex-dependent effects is relatively strong and where it remains indirect, inconsistent, or context-dependent. Disease examples include autism spectrum disorder, attention-deficit/hyperactivity disorder, epilepsy, intellectual disability, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, traumatic and ischemic injury, multiple sclerosis, chronic pain, aging, and systemic metabolic or inflammatory disorders. Throughout, biological sex is separated from gender-related social, diagnostic, and health-care determinants. We conclude that therapeutic strategies should not aim simply to enhance plasticity, but to guide it by matching intervention, timing, dose, biological readiness, and monitoring to the patient's adaptive state.},
}

@article {pmid42511587,
year = {2026},
author = {Korošec, T and Rogelj, B and Župunski, V},
title = {LINE-1 Retrotransposons and Amyotrophic Lateral Sclerosis.},
journal = {International journal of molecular sciences},
volume = {27},
number = {14},
pages = {},
pmid = {42511587},
issn = {1422-0067},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of upper and lower motor neurons. While monogenic causes account for a minority of cases, in most cases, ALS is sporadic and likely arises from multilayer interactions of genetic architecture, aging-associated loss of genome regulation, and inflammatory stress. Long interspersed nuclear element-1 (LINE-1) retrotransposons are endogenous mobile elements that are tightly controlled through various cellular mechanisms under normal conditions. When abnormally active, they are involved in gene inactivation, expression regulation, and genomic instability, leading to cellular processes such as innate immunity and cell death. Here, we present mechanistic links between LINE-1 and ALS. These include evidence that the burden of retrotransposition-competent LINE-1s (RC-L1s) is increased in ALS genomes, positioning RC-L1 load as a candidate contributor to missing heritability in sporadic disease. We also integrate emerging data showing that LINE-1 RNA can be intrinsically toxic independently of new insertions, as it promotes chromatin opening and transcriptional epigenetic noise, particularly when nuclear RNA surveillance pathways fail in TDP-43 pathology. Finally, we review how LINE-1-derived DNA/RNA intermediates can engage innate immune sensors, highlighting the cGAS-STING axis as a plausible route from LINE-1 de-repression to neuroinflammation. Together, these concepts support a model in which genetic RC-L1 load and age-/pathology-driven LINE-1 de-repression converge on nuclear dysfunction and inflammatory amplification, suggesting concrete molecular nodes for therapeutic intervention.},
}

@article {pmid42511680,
year = {2026},
author = {Podshivalova, ES and Kutsev, SI and Shestopalov, AV},
title = {The Kynurenine Pathway: Unraveling Its Role in Neurological Disorders via Mammalian Cellular Models.},
journal = {International journal of molecular sciences},
volume = {27},
number = {14},
pages = {},
pmid = {42511680},
issn = {1422-0067},
abstract = {The kynurenine pathway (KP) constitutes the primary route of tryptophan catabolism, generating a spectrum of neuroactive metabolites that profoundly influence central nervous system function. Dysregulation of the KP is increasingly recognized as a critical pathogenic mechanism underlying diverse neuropathological conditions. This review critically evaluates the most widely cited mammalian cellular models currently utilized to delineate the causal role of KP alterations in neurological disease. Specifically, this article examines primary cell cultures, immortalized and tumor-derived cell lines, stem cell-derived systems, and ex vivo organotypic brain slices and tissues, highlighting their distinct methodological advantages, translational limitations, and specific enzymatic profiles. Across the described cellular systems, a recurring mechanistic theme emerges: quinolinic acid-driven mitochondrial dysfunction, oxidative stress, and NAD+ depletion converge in neurodegenerative conditions such as Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Conversely, kynurenic acid exhibits disorder-dependent-and at times opposing-roles, attenuating dopaminergic neurotoxicity in Parkinson's disease models while contributing to synaptic pruning deficits in schizophrenia models. Furthermore, cellular models demonstrate that IDO1/TDO induction and downstream metabolite shifts are frequently cell type- and species-dependent, complicating direct extrapolation to human pathology. Because no single experimental system achieves complete physiological fidelity, elucidating the complex dynamics of the KP and identifying novel therapeutic targets requires the integration of data across complementary platforms.},
}

@article {pmid42512084,
year = {2026},
author = {Assialioui, A and Povedano, M and Senau, M and Ferrer, I and Arias, L},
title = {Retinal Thickness and Vascular Density Changes in Amyotrophic Lateral Sclerosis Assessed by Optical Coherence Tomography Angiography.},
journal = {Biomedicines},
volume = {14},
number = {7},
pages = {},
doi = {10.3390/biomedicines14071612},
pmid = {42512084},
issn = {2227-9059},
abstract = {Background: Amyotrophic lateral sclerosis (ALS) is increasingly recognized as a multisystem disorder involving neurovascular dysfunction. The retina allows in vivo assessment of neurovascular changes. This study evaluated retinal structural and microvascular alterations in ALS using optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A). Methods: This cross-sectional study included 46 participants with ALS and 19 healthy controls. Retinal thickness and vascular density in the superficial and deep retinal capillary plexuses and the choriocapillaris were quantified using OCT and OCT-A. Group comparisons and logistic regression analyses were performed to assess associations with ALS. Subgroup analyses were conducted according to clinical phenotype. Results: In total, 124 eyes were analyzed. ALS was associated with increased average retinal thickness (p = 0.023) and reduced vascular density in the superficial retinal capillary plexus (p = 0.005), deep retinal capillary plexus (p < 0.001), and choriocapillaris (p = 0.004). In logistic regression analyses, retinal thickness was positively associated with ALS status (OR = 1.42, p = 0.023), whereas higher vascular density in the superficial plexus, deep plexus, and choriocapillaris was associated with lower odds of ALS. No significant differences were observed between bulbar- and spinal-onset ALS phenotypes. Conclusions: ALS is associated with structural and microvascular retinal alterations detectable by OCT and OCT-A. These findings support the presence of systemic neurovascular dysfunction and highlight retinal imaging as a promising, non-invasive approach for investigating disease mechanisms and developing potential biomarkers.},
}

@article {pmid42493742,
year = {2026},
author = {Criss, S and Abim-Karmon, RS and Teel, J and Rodríguez, V and Bennon, A and Wills, S and Gonzales, S and Nayreau, DD and Bharadwaj, V and Kim, HG and Woollery, J and Fair, ML},
title = {Trust, Participation, and Power: Community Perspectives from the Equity in Public Health Initiative.},
journal = {Journal of community health},
volume = {},
number = {},
pages = {},
pmid = {42493742},
issn = {1573-3610},
abstract = {Health disparities arise from unequal power relations shaping resource allocation, governance, and community agency. Community power is a key mechanism for addressing disparities. This study examines how visible, hidden, and invisible power operate within a U.S. county to inform inclusive governance. We conducted seven focus groups with Black and Hispanic residents (n = 68) and sixteen semi-structured interviews with elected officials, government staff, and advocacy leaders in Greenville County, South Carolina. Data were collected between March and December 2024. Transcripts were collaboratively coded in NVivo and analyzed using thematic analysis guided by Heller et al.'s Three Faces of Power framework. Visible power appeared through inequitable resource distribution, limited transparency, and barriers to civic participation. Hidden power functioned through faith based organizations, schools, nonprofits, and social media, connecting residents with decision makers. Invisible power reflected how socioeconomic status, race and ethnicity, immigration, and language shaped perceptions of agency and trust. Participants called for participatory structures that move beyond consultation toward shared authority and sustained engagement. Strengthening community power through structural reforms, inclusive governance practices, and targeted civic engagement may improve health outcomes and reduce disparities. Future research should examine scalable co-governance models.},
}

@article {pmid42493871,
year = {2026},
author = {Torabi, SJ and Tollefson, TT},
title = {Invited Commentary on: Fincher et al.'s "Biochemical, Mechanical, and Warping Behavior of Fresh Frozen Costal Cartilage Allograft": A Look into Rib Grafts to Be Used for Rhinoplasty from Human Donors.},
journal = {Facial plastic surgery & aesthetic medicine},
volume = {},
number = {},
pages = {26893614261472664},
doi = {10.1177/26893614261472664},
pmid = {42493871},
issn = {2689-3622},
}

@article {pmid42494173,
year = {2026},
author = {Sellin, J and Waldorf, S and von der Gablentz, J and Grehl, T and Nazlican, H and Meyer, T and Grosskreutz, J and Weydt, P and Bernsen, S},
title = {Troponin T and Neurofilament Light Chain Levels as Complementary Biomarkers of Disease Accumulation and Aggressiveness in Amyotrophic Lateral Sclerosis.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
pmid = {42494173},
issn = {2328-9503},
abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a clinically heterogeneous neurodegenerative disease requiring reliable biomarkers to improve patient stratification and trial design. While serum neurofilament light chain (sNfL) reflects neuroaxonal stress and disease aggressiveness, troponin T (TnT) may capture complementary aspects of neuromuscular involvement. We assessed the associations of TnT and sNfL with D50-derived measures of disease aggressiveness (D50) and disease accumulation (rD50) in ALS.

METHODS: In this retrospective observation, TnT and sNfL levels from ALS patients in two independent German cohorts were analyzed using the D50 disease progression model; discovery cohort (Essen, n = 433) and an independent replication cohort (Bonn, n = 185).

RESULTS: TnT levels were strongly associated with rD50-defined disease phases in the discovery cohort (p < 0.001). While not all subgroup-specific associations were replicated, the overall relationship between TnT and disease accumulation was supported in the independent replication cohort. In contrast, sNfL showed no consistent relationship with rD50-derived disease phases. sNfL concentrations demonstrated a significant inverse association with D50, supporting a relationship with disease aggressiveness across both cohorts (p < 0.001). Associations between TnT levels and D50-defined disease aggressiveness were generally weaker and less consistent.

INTERPRETATION: TnT was associated with measures of disease accumulation (rD50), whereas sNfL was more closely associated with disease aggressiveness (D50). Our results suggest that TnT and sNfL capture different dimensions of disease status within the D50 framework. Further longitudinal studies are needed to determine whether combining these biomarkers improves disease stratification or prognostic assessment in clinical practice and therapeutic trials.},
}

@article {pmid42494493,
year = {2026},
author = {Kennedy, J and Al Khleifat, A and King, A and Al-Sarraj, S and Al-Chalabi, A and Mitchell, JC and Troakes, C},
title = {Strenuous physical activity is associated with a younger age of amyotrophic lateral sclerosis onset in two independent cohorts.},
journal = {Brain communications},
volume = {8},
number = {4},
pages = {fcag272},
pmid = {42494493},
issn = {2632-1297},
abstract = {Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease characterized predominantly by degeneration of both upper and lower motor neurons, thought to occur due to an interplay between genetics and environmental factors. Physical activity has been suggested as a potential risk factor for ALS; however, the exact role of exercise in the onset and progression of the disease is still unclear. We assessed lifetime physical activity in two independent ALS cohorts: post-mortem brain donors from the London Neurodegenerative Diseases Brain Bank (n = 139) and patients from the Motor Neurone Disease (MND) Register of England, Wales and Northern Ireland (n = 166 cases, 196 controls). In both cohorts, highly active individuals developed ALS symptoms at a significantly younger age, 54.2 years (mean, standard deviation = 7.5) in the post-mortem cohort and 58.0 years (median, interquartile range = 15) in the MND Register, compared with 63.9 years (mean, standard deviation = 11.5) and 63.0 years (median, interquartile range = 17.5) in inactive individuals, respectively [one-way analysis of variance (ANOVA), F(2, 136) = 6.10, P = 0.003, η 2 = 0.08, 95% confidence interval (CI) 0.02-1.00 and Kruskal-Wallis, H(2) = 7.39, P = 0.02, η 2 = 0.03, 95% CI 0.003-0.12]. Cox regression showed a higher hazard of earlier onset in highly active patients [post-mortem: hazard ratio (HR) 2.84, 95% CI 1.55-5.26, P = 0.0008; MND Register: HR 2.34, 95% CI 1.30-4.23, P = 0.005]. Our findings suggest that strenuous physical activity may be associated with a significantly younger age of ALS onset, replicated in both the post-mortem and MND Register cohorts, but not with an increased risk of developing ALS. Logistic regression analysis confirmed that neither highly active [odds ratio (OR) 1.43, 95% CI 0.69-2.99, P = 0.333] nor being active (OR 1.30, 95% CI 0.72-2.37, P = 0.386) was significantly associated with ALS risk, whereas a history of head injury was (OR 1.72, 95% CI 1.03-2.88, P = 0.038). These results suggest that strenuous exercise may accelerate disease onset in predisposed individuals, while the role of head injury requires further study and the findings may in fact indicate reverse causality.},
}

@article {pmid42495327,
year = {2026},
author = {Zhan, K and Wang, Y and Lin, J and Chen, F and Fan, X and Hu, P and Wen, J and Gong, F and Zhang, N},
title = {From Simplified Pretreatment to Sensitive Analysis: An Immobilization-Free Cathodic Photoelectrochemical Assay for Sulfonylurea Herbicide Residue and Its Accumulation.},
journal = {ACS omega},
volume = {11},
number = {28},
pages = {42504-42514},
pmid = {42495327},
issn = {2470-1343},
abstract = {Sensitive and selective detection of agricultural chemicals in complex matrices necessitates streamlined workflows without performance loss. By combining the inherent high sensitivity of photoelectrochemical (PEC) analysis with the high selectivity of enzymatic recognition, an immobilization-free PEC assay for the sulfonylurea herbicide chlorsulfuron (Chs) was developed, with purification steps omitted and analytical procedure simplified. Specifically, BiOI nanoflakes (NFs)/NiO heterojunction was fabricated as a sensing platform, generating strong and stable cathodic photocurrent in the presence of dissolved O2. The catalytic reaction of acetolactate synthase (ALS) consumed O2, quenching the photocurrent response. Conversely, upon addition of the model target Chs, a representative sulfonylurea herbicide and effective inhibitor of ALS, the signal was recovered. By monitoring the photocurrent change before and after the enzymatic reaction, Chs was quantified over a linear range of 0.25-100 μg/L, with a limit of detection (LOD) of 0.16 μg/L. The assay avoids laborious probe-immobilization steps by directly adding the enzyme into the electrolyte, significantly simplifying the detection protocol. Furthermore, by omitting traditional purification procedures, the overall workflow was further optimized. The method was successfully applied to detect Chs residues in wheat powder and to evaluate its accumulation in wheat seedlings, with accuracy and reliability validated by high-performance liquid chromatography (HPLC). This work achieves highly sensitive and immobilization-free PEC analysis of Chs and offers a feasible approach for sulfonylurea herbicide detection in selected agricultural samples, with streamlined pretreatment process and enhanced analytical efficiency.},
}

@article {pmid42495582,
year = {2026},
author = {Yu, Z and Ross, JP and Rochefort, D and Li, B and Bornais, K and Chum, M and Farhan, SMK and Dion, PA and Rouleau, GA},
title = {Erratum: Consequences of the Novel ALS-Associated KIF5A Variant c.2993-6C>A for Exon 27 Splicing and Axonal Transport of SFPQ.},
journal = {Neurology. Genetics},
volume = {12},
number = {4},
pages = {e200410},
pmid = {42495582},
issn = {2376-7839},
abstract = {[This corrects the article DOI: 10.1212/NXG.0000000000200362.].},
}

@article {pmid42497114,
year = {2026},
author = {Yasuda, K},
title = {Functional constraint, not evolutionary domain expansion, is a stronger correlate of pathogenic variant burden in human RNA-binding proteins.},
journal = {Human molecular genetics},
volume = {35},
number = {15},
pages = {},
doi = {10.1093/hmg/ddag067},
pmid = {42497114},
issn = {1460-2083},
support = {23 K05147//JSPS/ ; },
mesh = {Humans ; Evolution, Molecular ; *RNA-Binding Proteins/genetics/chemistry/metabolism ; Animals ; Protein Domains/genetics ; Genetic Variation ; Amyotrophic Lateral Sclerosis/genetics ; Ribonuclease, Pancreatic/genetics ; },
abstract = {Whether evolutionary innovation predisposes genes to pathogenic variation is a fundamental question in evolutionary medicine. RBP domain family diversity correlates with neural complexity across metazoans via vertebrate-specific domain expansions. Here, we tested whether such expanded RBP domains harbor elevated pathogenic variant burden relative to evolutionarily conserved domains. We classified 2961 human RBP-encoding genes into expanded (n = 25 genes, 8 Pfam domains; vertebrate/invertebrate gene count ratio ≥ 3.0) and non-expanded control (n = 231 genes, 89 Pfam domains) groups, and integrated ClinVar pathogenic variants with gnomAD v4.1 constraint metrics. Contrary to our hypothesis, expanded domains showed lower median pathogenic variant density than non-expanded domains (P = .140, rank-biserial r = 0.180, 95% CI [-0.089, 0.444]), consistent across sensitivity analyses and count-based models. In multivariable analysis, functional constraint (pLI) was a stronger predictor of variant density than evolutionary expansion status. At the family level, no expanded domain showed significantly elevated burden; instead, the most prominent outliers were conserved non-expanded domains associated with established neurodegenerative diseases (SMN, Nop). The RNaseA family, despite 26-fold vertebrate expansion, harbored ClinVar pathogenic variants in only 1 of 15 members-fewer than expected by chance (binomial P = 0.030). The sole exception, ANG (Angiogenin), concentrates all seven ALS9-associated variants at its catalytic triad and nuclear localization signal, reflecting functional specialization rather than expansion per se. These findings indicate that evolutionary domain expansion does not confer generalized disease vulnerability in RBPs, and that pathogenic variant burden is more closely linked to functional constraint and lineage-specific subfunctionalization than to evolutionary novelty.},
}

Humans
Evolution, Molecular
*RNA-Binding Proteins/genetics/chemistry/metabolism
Animals
Protein Domains/genetics
Genetic Variation
Amyotrophic Lateral Sclerosis/genetics
Ribonuclease, Pancreatic/genetics

@article {pmid42497626,
year = {2026},
author = {Lee, JY and Hong, S and Kim, E},
title = {Soft skills education and training across the nursing continuum: A scoping review.},
journal = {Nurse education today},
volume = {166},
number = {},
pages = {107287},
doi = {10.1016/j.nedt.2026.107287},
pmid = {42497626},
issn = {1532-2793},
abstract = {AIMS: Soft skills are essential for safe and effective nursing practice, supporting communication, collaboration, and professional judgment in complex care settings. Despite their importance, new graduate nurses often struggle with core soft skills, highlighting a persistent gap between education and clinical demands. This scoping review maps current evidence on soft skills education and training for nursing students and nurses, focusing on core concepts, teaching approaches, and evaluation methods.

DESIGN: This scoping review was conducted following the PRISMA Scoping Review guidelines.

DATA SOURCES: Five databases-MEDLINE, CINAHL, Embase, Cochrane Library, and PsycINFO-were searched for studies published 2015-2025.

REVIEW METHODS: Eligible studies used experimental designs to deliver soft skill-focused education or training to nursing students or nurses. Data extraction followed the TIDieR checklist, and soft skills were classified using an adapted version of Song et al.'s framework.

RESULTS: Twenty-four studies met the inclusion criteria; most involved nursing students and quasi-experimental designs. Effective Interaction and Professionalism were the most frequently addressed skill domains. Student-focused programs emphasized interpersonal and cognitive skills, whereas nurse programs concentrated on preparedness, work management, and teamwork. Traditional lectures predominated, while participatory and emerging approaches such as virtual reality, escape rooms, and game-based learning were less common. Nurse training was typically single-session, whereas student programs were more longitudinal. Most studies relied on self-report measures and included limited follow-up.

CONCLUSIONS: A distinctive pattern emerged between students and nurses, suggesting that student-focused programs tend to emphasize foundational interpersonal skills while nurse-focused interventions are more likely to address clinically integrated competencies. This gap underscores the need to better align nursing curricula with real-world competency requirements. Educational programs on soft skills should incorporate active, learner-centered teaching strategies, rigorous evaluation methods with long-term follow-up, and validated assessment tools to better prepare nurses for contemporary healthcare demands.},
}

@article {pmid42498430,
year = {2026},
author = {Desai, KM and Thakkar, MD and Somaiya, TS and Thomas, DC},
title = {Neurodegenerative Diseases and Sleep Disorders: The Bidirectional Relationship.},
journal = {The Medical clinics of North America},
volume = {110},
number = {5},
pages = {889-905},
doi = {10.1016/j.mcna.2025.12.001},
pmid = {42498430},
issn = {1557-9859},
mesh = {Humans ; *Sleep Wake Disorders/diagnosis/complications/etiology/therapy/physiopathology ; *Neurodegenerative Diseases/complications/diagnosis/physiopathology ; Parkinson Disease/complications ; },
abstract = {Neurodegeneration is mostly irreversible and progressive. Neurodegenerative diseases (NDDs) represent a large group of disorders that have varied clinical and pathologic representations. These include Alzheimer's disease, Parkinson's disease, vascular dementia, and amyotrophic lateral sclerosis, among others. A common factor in all these NDDs is sleep disorders (SDs). NDDs and SDs are bidirectional. Screening for SDs should be an integral part of a workup of NDDs. Management of one can improve the prognosis of the other.},
}

Humans
*Sleep Wake Disorders/diagnosis/complications/etiology/therapy/physiopathology
*Neurodegenerative Diseases/complications/diagnosis/physiopathology
Parkinson Disease/complications

@article {pmid42498658,
year = {2026},
author = {Palm, A and Ekström, M and Einarsson, J and Ersson, K and Ingre, C and Kläppe, U and Lindberg, E and Ljunggren, M and Nygren, I and Sundh, J and Grote, L},
title = {Home mechanical ventilation for amyotrophic lateral sclerosis-a national study of survival and treatment trends across 27 years.},
journal = {Annals of the American Thoracic Society},
volume = {},
number = {},
pages = {},
doi = {10.1093/annalsats/aaoag219},
pmid = {42498658},
issn = {2325-6621},
abstract = {RATIONALE: Home mechanical ventilation (HMV) improves survival in Amyotrophic lateral sclerosis (ALS) and may be provided non-invasively (NIV) or invasively (IV). While NIV is guideline-recommended, the role of IV remains controversial, and data on long-term outcomes and NIV-to-IV transitions are limited.

OBJECTIVES: To examine survival across HMV strategies in people with ALS (pwALS) in Sweden over 27 years, factors associated with IV initiation, temporal trends in IV use and survival, and regional variation in IV utilisation.

METHODS: A longitudinal cohort study of pwALS in the Swedish National Registry of Ventilatory Failure (Swedevox) 1996-2022, cross-linked with national registries. Factors associated with mortality and treatment patterns were assessed using multivariable regression models.

RESULTS: Among 1,360 pwALS, initial NIV was most common (92%), followed by IV (5%) and NIV-to-IV transitions (3%). Most IV initiations were non-elective (77% vs. 18% NIV, p < 0.001). NIV-to-IV transitions occurred mainly in metropolitan areas (OR 5.11; 95% CI 2.30-11.4). Median survival differed across observed treatment pathways (p < 0.001): 1.7 years with NIV, 4.9 years with IV, and 6.5 years with NIV-to-IV. Mortality was associated with higher age (aHR 1.33 per decade; 95% CI 1.26-1.41), female sex (aHR 1.15; 95% CI 1.02-1.29), and acute initiation (aHR 1.26; 95% CI 1.08-1.47). Longer time from diagnosis to NIV initiation was associated with reduced mortality risk (aHR 0.58 per year; 95% CI 0.55-0.62). Over time, patients initiated HMV at older age with better lung function and lower PaCO2 values among those with available measurements, whereas overall survival remained unchanged.

CONCLUSION: Patients receiving IV had longer observed survival, likely reflecting the benefits of a secured airway as well as patient selection and underlying disease trajectory. Most IV initiations were unplanned. Over three decades, HMV was initiated in older patients at an earlier stage of respiratory decline, but overall survival remained unchanged. IV use increased with marked regional variation.},
}