@article {pmid42387584,
year = {2026},
author = {He, M and Wu, C and Hu, M and Shi, X and Liu, R and Tong, Y and Wang, H and Hu, H and Liao, H},
title = {SGK1-mediated deficits in microglial phagocytosis drive pathological progression in amyotrophic lateral sclerosis.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-026-03925-w},
pmid = {42387584},
issn = {1742-2094},
support = {82372577; 82073831//National Natural Science Foundation of China/ ; },
abstract = {Alterations in microglial function and transcriptomic profiles are major pathological hallmarks of amyotrophic lateral sclerosis (ALS). However, the dynamics and regulatory mechanisms underlying microglial phagocytic activity during disease progression remain unclear. In this study, we observed stage-dependent alterations in microglial phagocytic activity during disease progression in SOD1[G93A] mice. Single-cell RNA sequencing suggested that this change was associated with a reduced abundance of microglial subpopulations enriched for phagocytosis-related pathways. Transcriptomic analysis identified serum- and glucocorticoid-regulated kinase 1 (SGK1) as a potential mediator of this process. Notably, sgk1 knockout in SOD1[G93A] mice was associated with improved microglial clearance of myelin debris and reduced aberrant engulfment of neuronal material after disease onset. Our results further showed that, after disease onset, the accumulation of myelin debris and apoptotic neurons induced SGK1 upregulation in microglia from SOD1[G93A] mice. Mechanistically, SGK1 appeared to promote lipid accumulation in microglia by suppressing lipophagy, thereby impairing the ability of microglia to clear cellular debris. Moreover, pharmacological inhibition of SGK1 with GSK650394 attenuated motor deficits and prolonged survival in SOD1[G93A] mice. Together, our findings provide evidence for a previously unrecognized role of SGK1 in regulating microglial phagocytosis in ALS models and support SGK1 as a potential therapeutic target in SOD1 mutation-associated ALS models.},
}

@article {pmid42387593,
year = {2026},
author = {Trad, G and Lenglet, T and Ledoux, I and Querin, G and Blancho, S and Marchand-Pauvert, V and Hogrel, JY and Pradat, PF},
title = {Safety, feasibility and preliminary effects of Atalante exoskeleton-assisted gait training in amyotrophic lateral sclerosis: a prospective ABA pilot study.},
journal = {Journal of neuroengineering and rehabilitation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12984-026-02046-y},
pmid = {42387593},
issn = {1743-0003},
abstract = {BACKGROUND: In amyotrophic lateral sclerosis (ALS), progressive weakness makes walking practice increasingly unsafe and difficult, accelerating loss of mobility and autonomy. Lower-limb exoskeletons could preserve task-specific stepping in a controlled setting, but evidence in ALS remains scarce. This study evaluated the safety of an intensive Atalante exoskeleton gait-training program and explored its effects on walking and related clinical outcomes.

METHODS: In this prospective, monocentric ABA pilot study, 10 ambulatory persons with ALS underwent three consecutive 6-week phases over 18 weeks: A1 (baseline, usual care), B (intervention: Atalante exoskeleton gait training added to usual care; 18 sessions, 3 times/week), and A2 (withdrawal, usual care), with repeated assessments every 3 weeks. The primary endpoint was safety, assessed by adverse events (AE). Secondary endpoints included ALS Functional Rating Scale-Revised, forced vital capacity, standardized walking tests (6-minute walk test, 10-meter walk test, Timed Up and Go test), Berg Balance Scale, postural control on a force platform, lower-limb strength with dynamometry, spasticity with isokinetic dynamometer, Fatigue Severity Scale, Modified Fatigue Impact Scale, ALS Assessment Questionnaire-40, and Hospital Anxiety and Depression Scale. Exoskeleton-specific patient-reported outcomes (PROs) included intrinsic motivation, participants' attitudes toward the intervention, perceived subjective impact of the training, perceived efficacy and interactivity of the exoskeleton. The results were analyzed with linear mixed-effects models.

RESULTS: No serious AE occurred, and one mild AE was certainly related to the intervention. No outcome showed significant phase-specific slopes or slope contrasts, although several measures displayed directionally consistent trends compatible with attenuated decline during phase B and a return toward a less favorable trajectory after withdrawal. Exoskeleton-specific PROs indicated high intrinsic motivation and acceptability (usefulness for standing, perceived safety, ease of participation, and ease of installation/uninstallation rated very highly), with perceived gait-training efficacy generally positive. Participants frequently reported reduced immobility and increased accomplishment (80% each) and postural improvement (70%), and the Net Promoter Score of recommendation was + 40.

CONCLUSIONS: Atalante exoskeleton gait training was safe and feasible in ambulatory ALS. These pilot data can guide the optimization of future studies to test whether it preserves function. Trial registration ClinicalTrials.gov, NCT06199284. Registered on 29/12/2023.},
}

@article {pmid42387809,
year = {2026},
author = {Jensen, SM and Vergoossen, DLE and Huijbers, MG},
title = {Muscle-Specific Kinase Signaling and Its Therapeutic Potential.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70129},
pmid = {42387809},
issn = {1097-4598},
abstract = {The function of the neuromuscular junction (NMJ) is compromised in many neuromuscular diseases (NMDs) such as autoimmune or congenital myasthenia gravis (MG), amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and muscular dystrophies. The NMJ contains muscle-specific kinase (MuSK), which is a critical regulator of NMJ integrity and function. Activating the MuSK signaling cascade may have therapeutic potential in several of these NMDs that are characterized by impaired neuromuscular communication. The MuSK signaling cascade consists of different components and can be activated with interventions at different levels. In the past years, different therapeutic strategies using an engineered recombinant agrin comprised of the C-terminal fragment of the protein (mini-agrin), gene therapy of key proteins in this pathway, agonist MuSK antibodies, and SRC homology 2 domain-containing phosphotyrosine phosphatase 2 (SHP2) inhibitors have been further developed for this purpose. Each of these strategies engages distinct signaling components: mini-agrin, both as recombinant protein and gene therapy, enhances agrin-Lrp4-MuSK interaction; Dok7 gene therapy amplifies MuSK phosphorylation; Lrp4 gene therapy enhances agrin responsiveness; MuSK agonist antibodies bypass upstream defects and promote downstream signaling; SHP2 inhibitors prolong the duration of active MuSK signaling. These therapeutic strategies have ameliorated NMJ integrity and function in several preclinical models of MG, motor neuron diseases, and muscular dystrophies. In this review, we highlight MuSK signaling as a possible therapeutic target, describe the therapeutic efficacy of intervention in MuSK signaling in different NMDs, and present an outlook on future clinical development.},
}

@article {pmid42388323,
year = {2026},
author = {Almeida, S and Song, Y and Marques, F and Sharma, N},
title = {Editorial: Emerging mechanisms in neurodegenerative disease pathogenesis: vertebrate and invertebrate model organisms.},
journal = {Frontiers in molecular neuroscience},
volume = {19},
number = {},
pages = {1891031},
doi = {10.3389/fnmol.2026.1891031},
pmid = {42388323},
issn = {1662-5099},
}

@article {pmid42388560,
year = {2026},
author = {L'habitant, SF and Schenk, A and Thudium, M and Coburn, M and Lechleuthner, A and Piekarski, F},
title = {Influence of team size on the efficiency of time-critical ALS interventions in prehospital cardiac arrest - A prospective randomised multicentre simulation study.},
journal = {Resuscitation plus},
volume = {30},
number = {},
pages = {101384},
pmid = {42388560},
issn = {2666-5204},
abstract = {OBJECTIVE: To determine whether increasing emergency medical service (EMS) team size improves the efficiency of time-critical invasive procedures during advanced life support (ALS) for out-of-hospital cardiac arrest (OHCA).

DESIGN: Randomised prospective multicentre simulation study with a parallel-group comparison of four predefined team sizes.

SETTING: Three accredited EMS training centres in North Rhine-Westphalia, Germany.

PARTICIPANTS: 210 ALS-trained paramedic students allocated to 59 teams of two to five members.

INTERVENTIONS: Teams managed a standardised adult ALS scenario (persistent ventricular fibrillation) requiring five invasive procedures: manual defibrillation, supraglottic airway insertion, intravenous access, preparation of amiodarone (300 mg), and preparation of epinephrine (1 mg).

MEASUREMENTS AND MAIN RESULTS: The primary endpoint was total scenario time from start to completion of the final procedure. Secondary endpoints were start and completion times for each intervention. Mean total times (mm:ss) decreased progressively with team size: two-person 6:33 ± 0:33 min, three-person 4:13 ± 0:40 min, four-person 2:54 ± 0:24 min, and five-person 2:14 ± 0:19 min (ANOVA, p < 0.001). All pairwise differences were statistically significant (Bonferroni-corrected p adj < 0.01). Earlier initiation of intravenous access and drug preparation accounted for most time savings. All teams completed every task successfully.

CONCLUSIONS: Larger EMS teams performed time-critical ALS procedures significantly faster, with optimal efficiency observed in four- to five-member crews. These findings highlight the operational importance of team composition for prehospital resuscitation performance and may inform staffing policies and simulation-based training.},
}

@article {pmid42389275,
year = {2026},
author = {Zhang, P and Zhuang, YD and Lv, WW and Zhao, Y and Wang, JH and Zhang, JY and Wu, LL},
title = {Role of gut microbiota in melanosis coli: from anthraquinone biotransformation to mucosal homeostasis dysbiosis.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1791164},
pmid = {42389275},
issn = {1663-9812},
abstract = {Melanosis coli (MC) is a benign and usually reversible condition characterized by brownish-black pigmentation of the colonic mucosa and is commonly associated with chronic exposure to anthraquinone laxatives (ALs). The best-established histopathological sequence involves AL-related epithelial apoptosis, phagocytosis of apoptotic bodies by macrophages, and subsequent lipofuscin deposition. Emerging evidence suggests that the gut microbiota (GM) may contribute to this process by converting pharmacologically inactive anthraquinone glycosides into active anthrone metabolites, including rhein anthrone. This narrative review summarizes available MC-specific findings and clearly distinguishes them from mechanistic hypotheses extrapolated from constipation, intestinal barrier, and microbiome literature. We discuss microbial β-glucosidases and reductases involved in AL biotransformation, reported changes in microbial diversity and SCFA-producing taxa in MC or constipation-associated cohorts, and plausible links with barrier dysfunction, bile-acid metabolism, tryptophan-derived metabolites, and LPS-TLR4 signaling. We therefore present the "Microbiota-Apoptosis Axis" as a proposed framework rather than a validated causal pathway. Finally, we review GM-targeted strategies, including probiotics, synbiotics, and fecal microbiota transplantation, while emphasizing that direct clinical evidence in MC remains limited and that cessation of anthraquinone laxatives remains the primary management strategy.},
}

@article {pmid42389895,
year = {2026},
author = {Pickett, D and Purvinsh, Y and Skrehot, JT and Warren, D and Kurouski, D},
title = {Nanoscale morphological and structural analysis of round and donut oligomers formed by C-terminal domain of TDP-43.},
journal = {Physical chemistry chemical physics : PCCP},
volume = {},
number = {},
pages = {},
pmid = {42389895},
issn = {1463-9084},
abstract = {Amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease (AD), limbic predominant age-related TDP-43 encephalopathy (LATE), and Parkinson's disease are associated with an abrupt aggregation of TAR DNA-binding protein 43 (TDP-43). Although molecular mechanisms of this pathological aggregation remain unclear, accumulated evidence suggests that the C-terminus domain (C-terminal domain (CTD)) is the trigger of TDP-43 self-assembly into toxic oligomers and fibrils. While the secondary structure and morphology of protein fibrils have been well documented, very little is known about TDP-43 oligomers. This is primarily because of the transient nature and low concentrations of these protein species. In the current study, we utilize nano-infrared spectroscopy, also known as atomic force microscopy-infrared (AFM-IR) spectroscopy, to investigate the morphology and secondary structure of CTD of TDP-43 oligomers formed at the early and middle stages of protein aggregation. This innovative technique allows us to resolve both morphology and secondary structure of individual protein aggregates. We found that at the early stage of protein aggregation, CTD of TDP-43 formed two morphologically different protein aggregates: donut-like (DO) and round (RO) oligomers. DO yielded fibrillar species, while RO persisted throughout the entire course of CTD TDP-43 self-assembly.},
}

@article {pmid42391298,
year = {2026},
author = {Ramgopal, S and Martin-Gill, C},
title = {Characterizing pediatric trauma patients and EMS agencies that are optimal targets for prehospital pediatric blood transfusion programs.},
journal = {Prehospital emergency care},
volume = {},
number = {},
pages = {1-15},
doi = {10.1080/10903127.2026.2696013},
pmid = {42391298},
issn = {1545-0066},
abstract = {OBJECTIVES: Trauma is a leading cause of death among children the United States. Prehospital blood product administration is a potentially lifesaving measure for injured children. We evaluated how often injured children meet physiological criteria for transfusion, determined the use of prehospital blood products in this sample, and identified agency characteristics that can inform the implementation of additional prehospital transfusion programs.

METHODS: We conducted a retrospective analysis of the 2021-2024 National Emergency Medical Services Information System (NEMSIS) datasets. We included children (<18 years) with injury. We identified patients who may be eligible for prehospital blood transfusion based on (a) a combination of a systolic blood pressure (SBP) below the 5[th] centile for age and elevated heart rate above the 85[th] centile or (b) a systolic blood pressure below the 1[st] centile. We characterized encounters potentially eligible for prehospital blood transfusion, the use of blood products in this group, and the EMS agencies that cared for these patients.

RESULTS: Of 2,492,731 encounters, 34,221 (1.37%, 95% confidence interval [CI] 1.36%, 1.39%) were potentially eligible for blood transfusion. Patients meeting these criteria were more frequently adolescents (71.1%) and were involved in falls (23.4%) or motor vehicle collisions (22.6%). Blood products were administered in 669 (0.027%; 95% CI 0.025%, 0.029%) encounters overall and to 1.01% (95% CI 0.91%, 1.13%) of encounters meeting criteria for blood transfusion eligibility. In agency-level analysis, 240/16,848 (1.4%) agencies provided blood products to children, and 84.4% of eligible patients were cared for by agencies whose most common level of service was advanced life support (ALS). In multivariable analysis, agencies caring for pediatric trauma patients meeting physiologic criteria for transfusion were more likely to have higher levels of service (ALS or critical care); rural; mixed volunteer/non-volunteer; and governmental non-fire, hospital, or private, non-hospital (vs fire departments).

CONCLUSIONS: In a nationally representative prehospital sample, many injured children appeared eligible for transfusion. Prehospital blood product use was uncommon and varied by system factors. Expanding access will require implementation of blood programs among EMS agencies most likely to treat these patients, and consideration for equipment and protocols that allow for administration of blood to children.},
}

@article {pmid42391458,
year = {2026},
author = {Philbert, SA and Church, SJ and Unwin, RD and Cooper, GJS},
title = {Elevated urea levels in human frontotemporal dementia and amyotrophic lateral sclerosis post-mortem brain tissue: Evidence of a multi-dementia pathogenic mechanism.},
journal = {Molecular omics},
volume = {},
number = {},
pages = {},
doi = {10.1093/molecular-omics/aaiag019},
pmid = {42391458},
issn = {2515-4184},
abstract = {Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) represent two neurodegenerative diseases on opposite sides of a movement disorder continuum. However, like many other neurodegenerative diseases, the molecular pathogenesis of FTD and ALS is not fully understood. Our group has previously reported evidence for a pervasive elevation of brain urea levels in five other dementia-causing diseases. However, brain urea levels have yet to be measured in ALS and FTD. Here, we employed ultra-high-performance liquid chromatography-tandem mass spectrometry to characterise brain urea differences between control (n = 14/12) and ALS/FTD (FTD: n = 8/9; ALS: n = 13/14) cases in post-mortem tissue from two brain regions with different levels of neuropathological burden (high versus low). Elevated urea levels were observed in both the frontal cortex (high neuropathological burden) and primary visual cortex (low neuropathological burden) in cases with FTD. Contrastingly, in cases with ALS, elevated urea was observed in the primary motor cortex (high neuropathological burden), but not the dentate nucleus (low neuropathological burden). These results not only suggest that elevated urea levels are also present in ALS and FTD but imply that elevated brain urea is linked to a multi-dementia pathogenic mechanism. In contrast to ALS, the observation of elevated urea in regions of both high and low neuropathological burden in FTD implies that this phenotype is likely widespread and, therefore, may play a larger role in the pathogenesis of disease. Such a mechanism could offer new directions for developing treatments targeting this underlying pathology.},
}

@article {pmid42392626,
year = {2026},
author = {Beulen, V and Noben, C and Smits, M and Mertens, H and Paulus, A and Van Mook, W},
title = {Workforce shortages and supported access to medical care for hospital employees: a scoping review.},
journal = {BMJ open},
volume = {16},
number = {7},
pages = {e117423},
doi = {10.1136/bmjopen-2026-117423},
pmid = {42392626},
issn = {2044-6055},
mesh = {Humans ; *Health Services Accessibility ; COVID-19 ; SARS-CoV-2 ; *Personnel, Hospital ; Pandemics ; },
abstract = {OBJECTIVES: This scoping review synthesises peer-reviewed and grey literature on supported access to medical care for hospital employees with existing physical health complaints to understand how it may reduce sickness absenteeism by promoting sustainable employability and to identify gaps and opportunities to inform the design and implementation of organisational supported care frameworks.

DESIGN: We conducted this scoping review following the Arksey and O'Malley framework and Levac et al's methodological recommendations, reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extensions for Scoping Reviews (PRISMA-ScR).

DATA SOURCES: MEDLINE (Ovid), Embase (Elsevier), CINAHL (EBSCO) and Web of Science were searched from database inception to 8 November 2024. The search was updated on 18 May 2026. This was supplemented by forward and backward citation tracking of included peer-reviewed articles and targeted hand searching of Dutch grey literature in Medisch Contact , a leading Dutch professional journal for the medical profession, focusing on clinical practice, medical policy and professional issues.

ELIGIBILITY: English-language or Dutch-language peer-reviewed publications and well-argued opinion pieces on healthcare workers' access to care (COVID-19 and beyond) in hospital or transferable settings were included. Sources focused on mental health or health promotion, financial aspects, personal protective equipment, patient access or healthcare worker utilisation, as well as non-English/Dutch sources, webpages and papers without full text, were excluded.

DATA EXTRACTION: ASReview was used for title and abstract screening following the SAFE procedure and full-text screening was conducted with team consensus.

RESULTS: 27 publications were included from 36 685 identified records. The literature was predominantly qualitative in nature and COVID-19-focused, yielding four themes (ethical considerations, multilevel challenges, target groups and strategies and outcomes). It also highlighted limited evidence on evaluated supported-access interventions and workforce outcomes beyond crises.

CONCLUSIONS: Although supported access to medical care for hospital employees appears a promising multilevel, system-embedded strategy to reduce sickness absenteeism and promote sustainable employability in general, the evidence to substantiate and justify such strategies beyond acute crises is limited. Moreover, current literature lacks clear conceptualisation, operationalisation as well as robust implementation and evaluation frameworks. Addressing these gaps is a priority for future research to scientifically scaffold policies and frameworks to sustain a healthy and stable future hospital workforce.},
}

Humans
*Health Services Accessibility
COVID-19
SARS-CoV-2
*Personnel, Hospital
Pandemics

@article {pmid42392979,
year = {2026},
author = {Pant, DC and Lone, MA and Parameswaran, J and Ma, F and Ziak, N and Dutta, P and Wang, Z and Pun, D and Verma, S and Hornemann, T and Jiang, J},
title = {Deletion of exon 2 in ALS-linked Sptlc1 causes lethality in homozygous mice but not in heterozygotes.},
journal = {Life science alliance},
volume = {9},
number = {9},
pages = {},
doi = {10.26508/lsa.202503605},
pmid = {42392979},
issn = {2575-1077},
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics ; *Exons/genetics ; Mice ; Heterozygote ; Homozygote ; Disease Models, Animal ; Humans ; *Sequence Deletion/genetics ; Mutation ; Genes, Lethal ; CRISPR-Cas Systems ; Male ; Gene Knock-In Techniques ; },
abstract = {Mutations in the human SPTLC1 gene have recently been linked to early-onset amyotrophic lateral sclerosis (ALS), characterized by global atrophy, motor impairments, and symptoms such as tongue fasciculations. All known ALS-linked SPTLC1 mutations cluster within exon 2, and a specific variant, c.58G>T, results in exon 2 skipping. However, it is unclear how the exon 2 deletion affects SPTLC1 function in vivo and contributes to ALS pathogenesis. Leveraging the high genomic sequence similarity between mouse and human SPTLC1, we created a novel knock-in mouse model with a CRISPR/Cas9-mediated deletion of exon 2 in the endogenous murine Sptlc1 locus. Although heterozygous mice did not develop motor defects or ALS-like neuropathology, homozygous mutants died prematurely. These findings provide valuable insights into SPTLC1 exon 2 biology and serve as a useful resource for future mechanistic studies.},
}

Animals
*Amyotrophic Lateral Sclerosis/genetics
*Exons/genetics
Mice
Heterozygote
Homozygote
Disease Models, Animal
Humans
*Sequence Deletion/genetics
Mutation
Genes, Lethal
CRISPR-Cas Systems
Male
Gene Knock-In Techniques

@article {pmid42393685,
year = {2026},
author = {Luan, J and Yun, Y and Jiao, Y and Wang, Y and Ma, M and Shan, D and Wang, H and Ji, X and Tang, Y and Li, J and Zhan, Z and Sun, X and Gao, N and Lin, P and Yan, C and Yu, D and Liu, S and Liu, F},
title = {Structural-functional network decoupling in early stage amyotrophic lateral sclerosis reveals cell-type specific transcriptional signatures.},
journal = {BMC medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12916-026-04932-7},
pmid = {42393685},
issn = {1741-7015},
support = {2025M782111//the China Postdoctoral Science Foundation/ ; 2025CXPT133//the Key R&D Program of Shandong Province/ ; 2022ZLGX03//the Key R&D Program of Shandong Province/ ; ZR2023ZD14//the Shandong Provincial Natural Science Foundation Major Basic Research Project/ ; ZR2023MH180//the Natural Science Foundation of Shandong Province/ ; 20201125//Qilu Young Schorship of Shandong University/ ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) involves widespread brain network dysfunction, yet the molecular mechanisms linked to these alterations remain poorly understood. We investigated macroscopic structural-functional coupling abnormalities in early-stage ALS (ALS-ES) and their underlying transcriptomic signatures.

METHODS: We analyzed multimodal MRI data from 73 patients with sporadic ALS-ES and 74 age- and sex-matched healthy controls. Structural-functional (SC-FC) coupling was quantified using diffusion tensor imaging and resting-state functional MRI. Machine learning models were constructed to distinguish patients from controls based on network features. Coupling alterations were spatially correlated with neurotransmitter receptor maps and gene expression profiles from the Allen Human Brain Atlas. Key transcriptomic findings were validated using independent single-cell RNA sequencing datasets.

RESULTS: While structural connectivity remained largely preserved, functional connectivity was significantly reduced in the somatomotor network (SMN). This mismatch manifested as significant SC-FC network decoupling, particularly within the SMN (pFDR = 0.001). A gradient boosting machine model accurately classified patients, identifying SC-FC coupling in the left precentral gyrus as a primary statistical contributor to the classification model. Decoupling spatially correlated with 5-HT2A and mGluR5 receptor distributions. Imaging-transcriptomics linked network failure to a gene signature enriched for synaptic pathways and microglial markers. Single-cell analysis identified FMN1 as a candidate gene whose glial expression spatially associates with network decoupling.

CONCLUSIONS: Early-stage ALS is characterized by significant structural-functional network decoupling, primarily in motor systems. This macroscopic failure is linked to specific microglial dysregulation, particularly FMN1 downregulation, providing a multiscale framework bridges statistical neuroimaging signatures with potential cellular pathology.},
}

@article {pmid42393788,
year = {2026},
author = {Marynen, F and van Bijsterveld, MG and Van In, J and Roosen, J and Fieuws, S and Vanhonacker, D and van Mook, WN and van der Horst, ICC and Dewolf, P},
title = {Comparing two post-resuscitation debriefing frameworks: a randomized cross-over simulation study.},
journal = {Advances in simulation (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1186/s41077-026-00460-9},
pmid = {42393788},
issn = {2059-0628},
support = {R-aiders Grant (2023).//BESEDIM/ ; },
abstract = {BACKGROUND: Post-resuscitation debriefing (PRD) enhances individual and team performance in emergency care, thereby improving patient outcomes and provider well-being. Despite support from the European Resuscitation Council and the American Heart Association, the optimal PRD framework remains undefined. This study compares how team members experience PRD when conducted using either the DISCERN or Post-Code Pause (PCP) debriefing framework in pre-hospital cardiac arrest simulations.

METHODS: In a randomized cross-over study, 40 medical doctors participated in four advanced life support (ALS) simulation scenarios. Participants acted exclusively within their usual roles as team leaders, while the remaining team members performed standardized roles in accordance with the scenario scripts. Each participant experienced two DISCERN and two PCP debriefings, with the order randomized. The primary outcome was the total score on the Debriefing Experience Scale (DES), with item scores as secondary outcomes. Linear models with generalized estimating equations (GEE) were used to account for repeated measures when comparing the mean scores between the debriefing frameworks.

RESULTS: A total of 158 DES questionnaires were analyzed. Mean total DES scores were 4.15 (4.02; 4.28) for PCP and 4.16 (4.02; 4.29) for DISCERN (p = 0.93 for the comparison). These scores indicate a favorable debriefing experience for both frameworks. At the DES item level, no statistically significant differences were observed between frameworks, except for perceived physical comfort in the debriefing environment, which was rated significantly higher for DISCERN (DISCERN = 4.44 (4.27; 4.62), PCP = 4.13 (3.96; 4.30), p = < 0.0001).

CONCLUSION: DISCERN and PCP provide similarly favorable debriefing experiences following simulated cardiac arrest scenarios, with no significant difference in overall DES scores. These findings suggest that both frameworks can be implemented without compromising perceived debriefing quality. Further research should include more professionally diverse participant samples and assess long-term debriefing outcomes.

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

@article {pmid42393897,
year = {2026},
author = {Anachad, O and Taha, W and Saadoune, C and Ezaouine, A and Nouadi, B and Bennis, F and Chegdani, F},
title = {Bioinformatic Identification of Shared Gene Networks Between Weaning- Induced Intestinal Inflammation and Neuroinflammatory-Related Pathways.},
journal = {Central nervous system agents in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715249457554260605114916},
pmid = {42393897},
issn = {1875-6166},
abstract = {INTRODUCTION: Weaning is a critical developmental stage that can trigger intestinal inflammation through disruption of microbial homeostasis, immune responses, and epithelial barrier integrity. While numerous studies have explored gene expression changes during weaning in animals, no comparable analyses have been conducted in humans. Given the close physiological and genetic similarity between pigs and humans, piglet data were employed to investigate the molecular mechanisms underlying weaning-induced intestinal inflammation and its potential links to neurological pathways.

METHODS: A curated set of 117 differentially expressed genes related to gut inflammation was collected from bibliographic sources. Protein-protein interaction network analysis was performed using NetworkAnalyst and Cytoscape, followed by hub gene selection and functional enrichment using KOBAS, ClusterProfiler, and StringApp.

RESULTS: Among the identified hub genes, SOD1, CAT, TNF, CXCR4, TLR2, and TGFB1 play key roles in oxidative stress, immune response, glial regulation, and neuroinflammatory signaling. Enrichment analysis revealed significant associations with pathways such as Amyotrophic Lateral Sclerosis, TGF-β signaling, Folate and Vitamin B12 metabolism, and Inflammatory Bowel Disease, as well as biological processes like gliogenesis, hypoxia response, and cytokine signaling.

DISCUSSION: These findings suggest that intestinal inflammation during weaning may have systemic implications, highlighting shared molecular pathways relevant to neuroinflammatory-related processes.

CONCLUSION: This study provides new insight into the genetic and molecular landscape of weaning-induced inflammation and its broader systemic effects. The identified shared molecular pathways may provide a foundation for future experimental studies investigating the broader biological implications of early-life intestinal inflammation.},
}

@article {pmid42394053,
year = {2026},
author = {Lee, KC and Kushniruk, AW and Borycki, EM},
title = {Use and Usability of Wearable Devices in Assistive Living: A Scoping Review.},
journal = {Studies in health technology and informatics},
volume = {338},
number = {},
pages = {487-491},
doi = {10.3233/SHTI260891},
pmid = {42394053},
issn = {1879-8365},
mesh = {*Wearable Electronic Devices/statistics & numerical data ; *Self-Help Devices/statistics & numerical data ; Humans ; Digital Health ; Aged ; },
abstract = {This paper describes a scoping review that explored the use and usability of wearable devices in assistive living with a focus on barriers to the real-world use of this technology in the home for the elderly. Published research was reviewed from the databases: PubMed, CINAHL, IEEE Xplore, and Web of Science. Using Arksey's et al.'s scoping review methodology relevant studies were identified, resulting in 37 reviewed for thematic analysis. The thematic analysis resulted in specific themes to barriers and facilitators in usability. Themes include privacy and security, technical challenges, providing a sense of safety and continued independence, and knowing connection to support is available if required. Wearable technology can positively contribute to elder care but a number of key issues and barriers remain.},
}

*Wearable Electronic Devices/statistics & numerical data
*Self-Help Devices/statistics & numerical data
Humans
Digital Health
Aged

@article {pmid42394165,
year = {2026},
author = {Hwang, M and Rist, TM},
title = {Invited Commentary on: Dey et al.'s "Comparing Patient and Casual Observer Perceptions of Complete Facial Paralysis and Facial Synkinesis".},
journal = {Facial plastic surgery & aesthetic medicine},
volume = {},
number = {},
pages = {26893614261465155},
doi = {10.1177/26893614261465155},
pmid = {42394165},
issn = {2689-3622},
}

@article {pmid42394299,
year = {2026},
author = {Asghar, A and Mustafa, H},
title = {Letter to the Editor in Response to "Age and Nocturnal Polyuria in Nocturia: A Multicenter Voiding Diary Cohort Study".},
journal = {Neurourology and urodynamics},
volume = {},
number = {},
pages = {},
doi = {10.1002/nau.70359},
pmid = {42394299},
issn = {1520-6777},
abstract = {Kawase et al.'s recent multicenter cohort study offers significant evidence about the relationship between nocturnal polyuria (NP) in nocturia patients and aging. The study shows that overactive bladder, maximal voided volume, and 24-h urine volume are significant predictors of NP and that both the nocturnal polyuria index and the prevalence of NP rise with age. Although these results significantly advance our knowledge of age-related urinary dysfunction, a number of methodological issues need to be addressed. The reported relationships may have been impacted by the retrospective design, reliance on self-reported voiding diaries, and lack of information on renal function, sleep problems, hydration status, and diuretic use. Furthermore, using a single diagnostic criteria for NP across all age groups might not accurately represent aging-related physiological changes. To better diagnose and treat nocturnal polyuria in older persons, future prospective studies that take these factors into account and assess age-specific diagnostic criteria are required.},
}

@article {pmid42394935,
year = {2026},
author = {Leone, L and Kiernan, TJ and Kuwabara, S and Barnett, M and Devenney, E and Ahmed, RM and Lin, CS},
title = {A convergence of global epidemics: diabetes as a modulator of neurodegenerative and neuro-inflammatory disorders.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1824840},
pmid = {42394935},
issn = {1664-2295},
abstract = {Diabetes mellitus (DM) and neurological disorders are rapidly converging global health burdens, driven by population ageing, the growing prevalence of metabolic syndrome, and limited early detection and disease-modifying therapies for many neurological syndromes. Beyond its established role in diabetes-related peripheral neuropathy, DM is increasingly implicated as a modifier of risk, phenotype, and prognosis across a wide range of central and peripheral nervous system diseases. In this narrative review, we synthesize current epidemiological, clinical, genetic, and mechanistic evidence examining the relationship between DM and 10 clinically important neurological disorders: Alzheimer's disease (AD), vascular dementia (VaD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multiple sclerosis (MS), myasthenia gravis (MG), and neuromyelitis optica spectrum disorder (NMOSD). Across these conditions, DM acts as a context-dependent disease modifier, increasing risk in some disorders, appearing protective or delaying onset in others, and influencing disease phenotype, progression, and treatment response. We highlight potential areas of mechanistic convergence, such as insulin resistance, inflammation, disrupted energy homeostasis, and genetic predisposition, alongside important divergences shaped by disease-specific pathology. We also discuss the clinical and translational implications of this interface, including diagnostic challenges, opportunities for improved risk stratification, and growing interest in repurposing antidiabetic therapies, particularly metformin, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors, for neurological benefit. As the global burden of diabetes and neurological disease escalates, it is crucial to better understand the interplay between metabolic dysfunction, neurodegeneration, and neuro-immune pathways. The integration of insights across diseases may inform prevention strategies and support the development of therapeutic interventions at the metabolic-neurological interface.},
}

@article {pmid42394962,
year = {2026},
author = {Tachiyama, K and Nakamori, M and Fujii, Y and Hokkoku, K and Agari, D and Hemmi, S and Nomura, E and Hatanaka, Y and Kurokawa, K and Sonoo, M and Maruyama, H},
title = {Decremental responses following repetitive nerve stimulation in spinal and bulbar muscular atrophy.},
journal = {Clinical neurophysiology practice},
volume = {11},
number = {},
pages = {522-527},
pmid = {42394962},
issn = {2467-981X},
abstract = {OBJECTIVE: The presence of decremental responses following repetitive nerve stimulation (RNS) in amyotrophic lateral sclerosis (ALS) is well established. However, in spinal and bulbar muscular atrophy (SBMA), a rare X-linked recessive lower motor neuron disease, the incidence and distribution of decremental responses across different muscles have not been thoroughly investigated.

METHODS: Patients with SBMA were retrospectively identified in our database. RNS at a frequency of 3 Hz was performed on five muscles: the abductor pollicis brevis (APB), abductor digiti minimi (ADM), upper trapezius, deltoid, and facial muscles (frontalis or nasalis).

RESULTS: A total of forty patients were identified. A significant (> 5%) decremental response in at least one muscle was observed in all patients. It was observed more frequently in proximal muscles than in distal muscles: deltoid (86%), trapezius (70%), facial muscles (44%), APB (37%) and ADM (25%). The magnitude of the decremental response in the deltoid was significantly higher than that in the other muscles.

CONCLUSIONS: Our results demonstrated that decremental responses were frequently observed in patients with SBMA, with a distribution pattern similar to that in ALS. The fact that the decremental responses are observed in SBMA having an extremely chronic course would be relevant for the pathophysiological mechanism of the decremental response.

SIGNIFICANCE: The RNS findings provide valuable insights into the pathological mechanisms of SBMA and may contribute to the development of future treatments.},
}

@article {pmid42395430,
year = {2026},
author = {Moore, S and Julian, DL and Alsop, E and Gittings, LM and Lorenzini, I and McMillan, M and Macklin-Isquierdo, S and Lehmkuhl, E and Kalab, P and de Paula Moreira, D and Hayes, L and Donnelly, C and Barmada, SJ and Zarnescu, DC and Van Keuren-Jensen, K and Sattler, R},
title = {ADAR2-Mediated RNA Editing Promotes TDP-43 Nuclear Export and Alters RNA Binding.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.06.22.730622},
pmid = {42395430},
issn = {2692-8205},
abstract = {BACKGROUND: TAR DNA binding protein - 43 (TDP-43) nuclear loss is a pathological hallmark of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and related neurodegenerative disorders. While the consequences of TDP-43 dysfunction have been well-characterized, the mechanisms driving TDP-43 mislocalization remain poorly understood. Previous observations of altered localization and function of the adenosine-to-inosine (A-to-I) RNA editing enzyme adenosine deaminase acting on RNA 2 (ADAR2) in ALS/FTD tissue prompted us to investigate whether dysregulated RNA editing contributes to pathological TDP-43 nucleocytoplasmic trafficking.

METHODS: TDP-43 cytoplasmic mislocalization was assessed following ADAR2 and TDP-43 co-overexpression in HEK293T cells and a Drosophila model co-overexpressing human TDP-43 and dADAR in motor neurons. We further evaluated TDP-43 mislocalization through both HeLa cell assays and interspecies heterokaryon assays. Next, we assessed TDP-43 binding to A-to-I edited RNA oligomers through electrophoretic mobility shift assays (EMSAs), and investigated inosine-containing RNAs in vivo via TDP-43 RNA immunoprecipitation followed by sequencing (RIP-seq) datasets from human TDP-43-expressing Drosophila . Finally, RNAseq and enhanced cross-linking and immunoprecipitation (eCLIP-seq) were performed in SH-SY5Y cells overexpressing three ADAR2 variants with differing editing activity to identify editing-related transcriptional alterations and RNAs differentially bound to TDP-43.

RESULTS: ADAR2 overexpression reduced the nucleocytoplasmic (N:C) ratio of TDP-43 in HEK293T cells in a ADAR2 catalytic activity- and TDP-43 RNA-binding capacity-dependent manner. Drosophila motor neurons overexpressing dADAR also exhibited decreased nuclear TDP-43. Interspecies heterokaryons and permeabilized HeLa cell assays demonstrated that catalytically active ADAR2 and synthetic inosine-containing RNA oligomers, respectively, enhance nuclear export of endogenous TDP-43. EMSAs revealed preferential binding of TDP-43 to inosine-containing RNAs relative to unedited RNAs, and analysis of Drosophila RIP-seq datasets demonstrated enrichment of edited transcripts within TDP-43-bound RNAs. Finally, RNAseq and eCLIP-seq analyses identified editing-dependent alterations in gene expression and TDP-43 RNA-binding profiles in SH-SY5Y cells overexpressing active ADAR2 variants.

CONCLUSIONS: Together, our findings identify A-to-I RNA editing as a previously unrecognized regulator of TDP-43 localization and RNA interactions. These results support a model where altered RNA editing modifies TDP-43-RNA interactions, promoting increased nuclear export of TDP-43. Broadly, our work highlights RNA editing dysregulation as a potential contributor to early pathogenic mechanisms underlying TDP-43 proteinopathies.},
}

@article {pmid42395866,
year = {2026},
author = {Sidharth, A and Shin, D},
title = {The role of SUMOylation in regulating proteins that drive neuronal disease progression.},
journal = {Biochemistry and biophysics reports},
volume = {47},
number = {},
pages = {102687},
pmid = {42395866},
issn = {2405-5808},
abstract = {SUMOylation is a post-translational modification in which a Small Ubiquitin-like Modifier (SUMO) protein is reversibly attached to a lysine residue on a target protein in an ATP-dependent process. This modification can affect the function of target proteins by enhancing their stability or changing cellular translocation, thereby making SUMOylation a critical regulator in the pathogenesis of multiple diseases. The functional consequences of SUMOylation, however, are highly context dependent. In Alzheimer's disease, SUMOylation stabilizes proteins that drive disease progression and enhances neurotoxicity, thereby exacerbating these conditions. Similarly, in Progressive Supranuclear Palsy, SUMO-1 conjugation stabilizes truncated tau and blocks its ubiquitination, whereas SUMO-2/3 conjugation promotes Tau clearance and recovery from neuroinflammation, illustrating how distinct SUMO paralogues can exert opposing effects within the same disease. Conversely, increased SUMOylation can be neuroprotective in cerebral ischemia and Parkinson's disease by promoting autophagic clearance of pathogenic proteins. Beyond alterations in protein stability, aberrant SUMOylation can also lead to mis-localization of target proteins, which has been identified as a pathogenic mechanism in disorders such as Huntington's disease and Amyotrophic Lateral Sclerosis that results in impaired clearance and pathogenic buildup, which results in neuronal death. From a therapeutic standpoint, the SUMO inhibitor TAK-981 has shown promise in both Multiple Sclerosis and in pre-clinical glioblastoma models, underscoring the translational potential of targeting of this pathway. This review examines the multifaceted role of SUMOylation across diverse neurological conditions, evaluates the therapeutic potential of SUMO inhibitors and activators, and highlights the opportunities and challenges of modulating this pathway in currently incurable neurological disorders.},
}

@article {pmid42396027,
year = {2026},
author = {Saidi, C and Debbichi, M and Chaaben, N},
title = {Lead-Free Sr3MCl3 (M = Sb, P) Perovskite Solar Cells: from First-Principles Calculations to Recombination-Aware Device Simulations.},
journal = {ACS omega},
volume = {11},
number = {25},
pages = {37467-37485},
pmid = {42396027},
issn = {2470-1343},
abstract = {In this study, first-principles calculations were performed to explore structural, mechanical, electronic, carrier transport, and optical properties of strontium-based perovskites (Sr3MCl3 (M = Sb, P)) using density functional theory (DFT). These calculations reveal that both materials are thermodynamically and mechanically stable. Employing the GGA-PBE functional, they possess a direct-band-gap semiconductor behavior with an energy of 1.704 eV (Sr3SbCl3) and 1.677 eV (Sr3PCl3). The analysis of the density of states (DOS) further corroborates the semiconducting behavior. Carrier mobility calculations indicate that electron/hole mobilities of 89.15/110.52 cm[2]/V·s are achieved for Sr3SbCl3 and 137.16/100.60 cm[2]/V·s for Sr3PCl3. In the visible region, a light absorption coefficient above 10[5] cm[-1] is reached for both materials, highlighting their suitability as an absorber layer (AL) in perovskite solar cells (PSCs). Considering band-to-band recombination (radiative and Auger), SCAPS-1D was used to conduct an inquiry into the photovoltaic performance of various devices, integrating different electron and hole transport layers (ETL/HTL): Ag/FTO/ETL/uniform-AL/HTL/Ni. Among all configurations examined in this study, the Ag/FTO/IGZO/uniform-AL/Cu2O/Ni architecture achieves the highest photovoltaic performance parameters, upon optimization of AL thickness, AL-doping concentration, AL-bulk and interface defect densities, radiative recombination coefficient, and series/shunt resistances. The Sr3SbCl3-based PSC (Device I) attains a power conversion efficiency (PCE) of ∼25.80%, with an open-circuit voltage (V OC) of 1.31 V, a short-circuit current density (J SC) of 21.82 mA/cm[2], and a fill factor (FF) of 90.27%, whereas the Sr3PCl3-based PSC (Device II) achieves a PCE of approximatively 26.22%, with V OC = 1.28 V, J SC = 22.71 mA/cm[2], and FF = 90.09%. Finally, replacing the single uniform-AL with a graded-Sr3Sb1-x P x Cl3 AL (Device III), adopting linear and parabolic graded physical parameters, does not demonstrate marked improvements in device performance. Consequently, this study positions Sr3MCl3 (M = Sb, P) perovskites as alternatives to lead-based ALs, which can constitute a suitable pathway for real-time experimentation of PSC.},
}

@article {pmid42396333,
year = {2026},
author = {Yasui, D and Weatherill, D and Dugom, L and Weiner, S and Gopalakrishnan, L and Tran, H and Oskarsson, B and Nagle, K and Miller, T and Gutierrez, G and Ravits, J and Hoover, B and Harms, M and Shneider, N and Neylon, L and Dailey, W and Ladha, S and Holmes, C and Lee, J and Streicher, N and Nayar, S and Harris, BT and Raisinghani, M and Zetterberg, H and Gobom, J and Easton, A and Bowser, R and Ly, CV},
title = {The Target ALS Global Natural History Study: Cross-platform proteomics to accelerate biofluid biomarker and drug target discovery in amyotrophic lateral sclerosis.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.06.13.26355379},
pmid = {42396333},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal, rapidly progressive neurodegenerative disease of motor neurons for which therapeutics are limited. Improved biomarkers are imperative to improve patient care and therapeutic development. Here, we employed 35-plex isobaric tandem mass tag labeling based on isobutyl-proline reporter group (TMTpro) to perform unbiased proteomic analysis of cerebrospinal fluid (CSF) and plasma from control (n= 28, n= 31) and sporadic ALS (sALS) (n= 39, n= 41), from the Target ALS Global Natural History Study (TALS GNHS). We identified 2,875 proteins in CSF and 1,118 proteins in plasma and identified known and novel differentially expressed proteins (DEPs) between controls and sALS, some of which were orthogonally validated using immunoassay. Comparison of TMTpro-MS and Olink proximity extension assay proteomics revealed common and non-overlapping differentially expressed proteins illustrating strengths unique to each platform. This initial cross-sectional proteomic study of biofluids from the TALS GNHS, with unrestricted availability of study results to the research community, highlights the potential of this resource as a potent platform for ALS biomarker discovery.},
}

@article {pmid42396678,
year = {2026},
author = {Gernsbacher, MA and Akhtar, N and Dinishak, J},
title = {An inclusive developmental science requires attention to neurodiversity.},
journal = {The Behavioral and brain sciences},
volume = {49},
number = {},
pages = {e268},
doi = {10.1017/S0140525X25104020},
pmid = {42396678},
issn = {1469-1825},
mesh = {Humans ; *Cultural Diversity ; Individuality ; },
abstract = {Bard et al.'s WILD framework calls for cultural inclusivity in developmental science. We argue for extending this framework to neurodiversity, emphasizing equifinality and individual differences. Including neurodivergent populations enriches developmental theory and avoids harm caused by neurotypical benchmarks. A truly inclusive science must recognize developmental pathways that vary by culture and neurotype as valid and meaningful.},
}

Humans
*Cultural Diversity
Individuality

@article {pmid42383305,
year = {2026},
author = {Christoforidou, E and McFagan, E and McLaughlin, M and Hafezparast, M},
title = {TDP-43 proteinopathy as a biomarker and therapeutic target in amyotrophic lateral sclerosis.},
journal = {Biochemical Society transactions},
volume = {54},
number = {7},
pages = {901-913},
doi = {10.1042/BST20260896},
pmid = {42383305},
issn = {1470-8752},
support = {Hafezparast/Apr21/880-791//Motor Neurone Disease Association (MNDA)/ ; //LifeArc/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/therapy/genetics/pathology ; Biomarkers/metabolism ; *DNA-Binding Proteins/metabolism/genetics ; Animals ; *TDP-43 Proteinopathies/metabolism/genetics ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is the most common form of adult-onset motor neuron disease, characterised by the degeneration of upper and lower motor neurons. The cytoplasmic aggregation of TDP-43 (TAR DNA-binding protein 43), an RNA-binding protein, is considered a hallmark of ALS pathology, found in nearly all postmortem cases of ALS. TDP-43 is normally primarily nuclear, where it has a widespread role in gene regulation. Mutations, extrinsic stressors, and alterations in RNA homeostasis in ALS lead to nuclear depletion of TDP-43 and the formation of cytosolic TDP-43 aggregates. This causes multiple downstream effects on neuronal function and degeneration as well as gene expression. TDP-43 is a promising target as a biomarker, as it is found to be elevated in the biofluids of ALS patients, and its cytoplasmic aggregation can also be observed in peripheral tissues; however, methodological variability and technical limitations currently preclude the establishment of TDP-43 as a standalone biomarker. There are also promising therapeutic strategies in development targeting TDP-43 pathology, but a critical challenge that remains is achieving a balance between eliminating toxic aggregates and preserving the essential functions of TDP-43. In summary, with further research, considering TDP-43 pathology in ALS gives hope for finding future novel diagnostics and therapeutics for ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/metabolism/therapy/genetics/pathology
Biomarkers/metabolism
*DNA-Binding Proteins/metabolism/genetics
Animals
*TDP-43 Proteinopathies/metabolism/genetics

@article {pmid42383366,
year = {2026},
author = {Serag, RM and El-Gazar, HE and AbdElgayed, MH and Gouda, RA and Berdida, DJE and Mohamed, AA},
title = {Response to Yu et al.'s Commentary on Effectiveness of Oral Care Intervention and Safe Swallowing Education on Post-Extubation Dysphagia in ICU Patients: A Nurse-Led Quasi-Experimental Study.},
journal = {Nursing in critical care},
volume = {31},
number = {4},
pages = {e70557},
doi = {10.1111/nicc.70557},
pmid = {42383366},
issn = {1478-5153},
}

@article {pmid42383392,
year = {2026},
author = {Sabouri, E and Shahmoradi, T and Keshvari, NZ and Khodaee, P and Saleki, K and Rezaei, N},
title = {Role of Toll-like receptors and oral-gut-brain axis in neurodegenerative and neuropsychiatric disorders.},
journal = {Reviews in the neurosciences},
volume = {},
number = {},
pages = {},
pmid = {42383392},
issn = {2191-0200},
abstract = {The oral-gut-brain axis is a path connecting the gastrointestinal tract and the central nervous system (CNS). The gut microbiota influences the immune system, metabolism, and nerve cells through the production of neurotransmitters and microbial metabolites that can cross the blood-brain barrier (BBB). The interplay between neuroinflammation and altered oral and gut microbiota is a bidirectional complex path modulated by inflammatory mediators. Recent studies suggest a potential role for Toll-like receptor (TLR) signaling pathways in the induction of neuroinflammation via the oral-gut-brain axis. As neuroinflammation is one of the key elements in the pathophysiology of neurodegenerative and neuropsychiatric disorders, this review was conducted to reflect on the pathophysiological pathways and clinical evidence on the role of TLR and inflammasome signaling pathways via oral-gut-brain axis in neurodegenerative diseases such as cognitive impairment, Alzheimer's disease, Multiple sclerosis, Parkinson's disease, Huntington's disease, and Amyotrophic lateral sclerosis, and psychiatric disorders such as major depressive disorder, anxiety disorders, schizophrenia, bipolar disorders, and Autism spectrum disorders. Because the contributing factors have not been fully understood yet, further studies could help provide novel therapeutic opportunities.},
}

@article {pmid42383500,
year = {2026},
author = {Carlo, C and Giovanni, C},
title = {On the clinical anatomy of technological cognition.},
journal = {Cognitive neuroscience},
volume = {17},
number = {3},
pages = {136-138},
doi = {10.1080/17588928.2025.2573257},
pmid = {42383500},
issn = {1758-8936},
mesh = {Humans ; *White Matter/diagnostic imaging/physiology ; Diffusion Tensor Imaging ; *Cognition/physiology ; *Brain/physiology/diagnostic imaging ; Neural Pathways/physiology/diagnostic imaging ; Digital Media ; *Nerve Net/diagnostic imaging ; },
abstract = {This commentary emphasizes the critical role of white matter tracts in technological cognition, complementing Federico et al.'s (2025) hub-and-processor model focused on cortical regions. Diffusion tensor imaging highlights white matter pathways as essential for integrating visuospatial, semantic, and motor information, underpinning complex tool use and technological interaction. The disconnectionist perspective reveals that cognitive deficits often arise from disrupted white matter connectivity. Additionally, the emerging concept of "digital dementia" underscores the impact of excessive digital exposure on brain networks. Integrating white matter connectivity advances clinical understanding and informs rehabilitation strategies for technological cognition deficits.},
}

Humans
*White Matter/diagnostic imaging/physiology
Diffusion Tensor Imaging
*Cognition/physiology
*Brain/physiology/diagnostic imaging
Neural Pathways/physiology/diagnostic imaging
Digital Media
*Nerve Net/diagnostic imaging

@article {pmid42384233,
year = {2026},
author = {Kotambail, A and Arunachal, G and Keerthipriya, MS and Mahima, R and Sukrutha, R and Ramyashree, MB and Deekshitha, M and Rao, BM and Biswas, P and Polavarapu, K and Preethish-Kumar, V and Reddy, P and Gray, O and Wasik, KA and Emde, AK and Angadi, S and Bhattacharya, B and Zacharia, M and Jeevitha, KV and Kumar, KD and Masaraddi, NH and Nashi, S and Chetan, GK and Vengalil, S and Nalini, A},
title = {Genome-wide spectrum of coding DNA variations in Indian patients with amyotrophic lateral sclerosis.},
journal = {Journal of neurology},
volume = {273},
number = {7},
pages = {},
pmid = {42384233},
issn = {1432-1459},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; India ; Female ; Male ; Superoxide Dismutase-1/genetics ; Adult ; C9orf72 Protein/genetics ; Middle Aged ; Cell Cycle Proteins/genetics ; Transcription Factor TFIIIA/genetics ; Genome-Wide Association Study ; Aged ; Ataxin-2/genetics ; Exome Sequencing ; Genetic Variation/genetics ; Young Adult ; Genetic Predisposition to Disease ; Membrane Transport Proteins ; Janus Kinase 2 ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with limited therapies, emphasizing the need for deeper understanding of disease pathogenesis. While more than 40 ALS-associated genes have been identified, their contribution varies significantly across populations and the data from the Indian population remains scarce. We aimed to comprehensively characterize the spectrum of coding DNA variations in ALS-associated genes and identify novel genetic contributors in an Indian cohort. Whole-exome sequencing on 761 ALS patients and 917 in-house healthy controls and repeat-primed PCR for expansions (C9orf72, ATXN2, NOTCH2NLC, NOP56) were performed. Variants were classified using ACMG guidelines, and rare variant association testing was conducted. Overall diagnostic yield was 15.90%, with pathogenic/likely pathogenic variants. Familial ALS showed higher diagnostic yield (36.95%) than sporadic ALS (12.96%). SOD1 dominated familial cases (53.85%), while OPTN, SOD1 and FIG4 were prevalent in sporadic cases. Homozygous SOD1 variants in six patients correlated with juvenile/young onset (< 30 years). C9orf72 expansions (4%) and ATXN2 repeats (1.7%) were identified at frequencies comparable with Asian cohorts. Rare variant analysis identified JAK2 as a novel genome-wide significant signal (FDR = 3.5 × 10[-5]). This first large-scale genomic survey of Indian ALS patients showed SOD1 being the predominant cause of fALS, while OPTN, FIG4, and other genes drive disease amidst low C9orf72 frequency. The novel JAK2 association suggests a potential neuroinflammatory mechanism, highlighting the importance of studying diverse populations to uncover distinct genetic etiologies.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics
India
Female
Male
Superoxide Dismutase-1/genetics
Adult
C9orf72 Protein/genetics
Middle Aged
Cell Cycle Proteins/genetics
Transcription Factor TFIIIA/genetics
Genome-Wide Association Study
Aged
Ataxin-2/genetics
Exome Sequencing
Genetic Variation/genetics
Young Adult
Genetic Predisposition to Disease
Membrane Transport Proteins
Janus Kinase 2

@article {pmid42385017,
year = {2026},
author = {Huynh, A and Cranley, L and Barnett-Tapia, C and Abrahao, A and Zinman, L and Yunusova, Y},
title = {Understanding patients' experiences and needs around decision-making for bulbar symptom management at a multidisciplinary ALS clinic.},
journal = {Disability and rehabilitation},
volume = {},
number = {},
pages = {1-16},
doi = {10.1080/09638288.2026.2693395},
pmid = {42385017},
issn = {1464-5165},
abstract = {PURPOSE: This study explored the decision-making experiences of people living with amyotrophic lateral sclerosis (ALS) for managing bulbar symptoms and their perceived needs for decision-making support from healthcare professionals.

METHODS: An interpretive, descriptive qualitative study was conducted. We recruited adult patients with ALS with and without any bulbar symptoms from a multidisciplinary ALS clinic in Central Canada. Patients were interviewed using a semi-structured guide. Reflexive thematic analysis was used to analyze study data. Recruitment ceased when information power was reached.

RESULTS: Twelve participants were interviewed. Three themes were identified for patient's decision-making experiences and needs: (1) Disease uncertainty hinders decision-making; (2) Quality information triggers decision-making; and (3) Personal values and beliefs inform decision-making.

CONCLUSIONS: To reduce psychological consequences of disease uncertainty and complexity on bulbar-related decision-making, patients emphasized the need for specific and contextualized information and healthcare professional supports aligned with their decision-making styles and approaches, highlighting the importance of a person- and family-centred approach to ALS care.},
}

@article {pmid42385702,
year = {2026},
author = {Zhou, Z and Luquette, LJ and Dong, G and Kim, J and Ku, J and Kim, K and Ramesh, N and Bae, M and Caplin, A and Shao, DD and Sahile, B and Essuman, K and Goodman, E and Miller, MB and Huang, AY and Nathan, WJ and Nussenzweig, A and Park, PJ and Lagier-Tourenne, C and Lee, EA and Walsh, CA},
title = {Recurrent patterns of TOP1-mediated neuronal genomic damage shared by major neurodegenerative disorders.},
journal = {Cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cell.2026.06.013},
pmid = {42385702},
issn = {1097-4172},
abstract = {Amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD) represent two major categories of neurodegenerative disorders-TAR DNA-binding protein 43 (TDP-43) and tau proteinopathies-for which the mechanisms driving neuronal death remain unclear. Single-cell whole-genome sequencing of 469 neurons from C9ORF72 ALS, C9ORF72 FTD, AD, and control brains revealed increased somatic single-nucleotide variants (sSNVs) and insertions/deletions (sIndels) in all three diseases. Mutational signature analysis identified a disease-associated sSNV signature consistent with oxidative damage and an sIndel process affecting 22% of ALS, 76% of FTD, and 61% of AD neurons-but only 2% of control neurons-resembling signature ID4, previously linked to topoisomerase 1 (TOP1)-mediated mutagenesis. Rapid approach to DNA adduct recovery (RADAR) assays confirmed increased TOP1-DNA covalent complexes, and duplex sequencing confirmed the increased sIndels and identified single-strand events as likely precursor lesions. TOP1-associated sIndel mutagenesis and genome instability thus represent a mechanism shared by both TDP-43 and tau neurodegeneration.},
}

@article {pmid42385894,
year = {2026},
author = {Guo, B and Zhang, X},
title = {Response to Huang et al.'s "Real-world efficacy and safety of tofacitinib on the progression of skin sclerosis in patients with systemic sclerosis: an analysis of national multicenter data from the CRDC.".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.06.122},
pmid = {42385894},
issn = {1097-6787},
}

@article {pmid42385897,
year = {2026},
author = {Yuan, L and Huang, H and Hui, M and Xu, S and Xu, D},
title = {Response to Guo et al., "Response to Huang et al.'s 'Real-world efficacy and safety of tofacitinib on the progression of skin sclerosis in patients with systemic sclerosis: an analysis of national multicenter data from the CRDC.'".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.06.121},
pmid = {42385897},
issn = {1097-6787},
}

@article {pmid42386387,
year = {2026},
author = {Salmon, K and Ilieva, H and Kelly, D},
title = {NMES-Facilitated Mandibular Rehabilitation for Spasticity-Related Trismus in ALS.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70332},
pmid = {42386387},
issn = {1097-4598},
support = {//Salus University through an Internal Faculty Research/ ; },
}

@article {pmid42386657,
year = {2026},
author = {Shimakura, K and Oka, A and Yudahira, H and Hama, Y and Otomo, A and Hadano, S},
title = {The SQSTM1 L341V Variant Associated With Sporadic ALS Promotes the Accumulation of Enlarged Ubiquitin-Positive SQSTM1 Bodies.},
journal = {Genes to cells : devoted to molecular & cellular mechanisms},
volume = {31},
number = {4},
pages = {e70134},
pmid = {42386657},
issn = {1365-2443},
support = {26290018//Japanese Society for Promotion of Science/ ; 24650189//Japanese Society for Promotion of Science/ ; 19H03551//Japanese Society for Promotion of Science/ ; //Tokai University School of Medicine Research Aid/ ; },
mesh = {*Sequestosome-1 Protein/genetics/metabolism ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Autophagy ; Microtubule-Associated Proteins/metabolism ; *Ubiquitin/metabolism ; Mutation, Missense ; Lysosomes/metabolism ; Animals ; },
abstract = {SQSTM1 is one of the causative genes of neurodegenerative disorders, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The SQSTM1 protein regulates the degradation of polyubiquitinated proteins and autophagosome formation through its interaction with microtubule-associated protein light chain 3 (MAP1LC3/LC3). However, the molecular mechanisms by which SQSTM1-LC3 binding regulates the autophagy-endolysosomal system (APELS) remain unclear. To elucidate the spatiotemporal role of SQSTM1, we transiently expressed wild-type SQSTM1 or missense mutants carrying mutations in the LC3-interacting region (LIR), fused with the photoconvertible fluorescent protein Dendra2. Live-cell fluorescence imaging and co-localization analyses with markers of the APELS were then performed. Particle analysis of photoconverted or non-photoconverted SQSTM1-positive structures in live cells revealed that the pathogenic L341V variant formed larger structures than the wild-type. Co-localization analyses further showed that both the L341V and artificial LIR3A mutants accumulated in large ubiquitin-positive structures, likely due to impaired localization to autophagosomes. These results suggest that mutations within the LIR differentially affect autophagosome formation and cargo degradation within APELS-related compartments, highlighting the importance of SQSTM1 structural integrity in ALS/FTD pathogenesis.},
}

*Sequestosome-1 Protein/genetics/metabolism
Humans
*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology
Autophagy
Microtubule-Associated Proteins/metabolism
*Ubiquitin/metabolism
Mutation, Missense
Lysosomes/metabolism
Animals

@article {pmid42387528,
year = {2026},
author = {Chau, LW and Murphy, JK and Nguyen, VC and Tran, HN and Minas, H and Lam, RW and Hayashi, K and Nguyen, TTX and Krebs, E and O'Neil, J},
title = {Fidelity in the context of adapting a digital intervention for depression from an evidence-based in-person format in Vietnam.},
journal = {BMC health services research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12913-026-15031-x},
pmid = {42387528},
issn = {1472-6963},
support = {R-TTS-2205-52454//Grand Challenges Canada/ ; 178156/CAPMC/CIHR/Canada ; },
abstract = {BACKGROUND: Digital interventions have emerged as a promising way to better meet growing population mental health needs. Our team developed a digital depression intervention (VMood; smartphone app) in Vietnam. VMood is adapted from an evidence-based in-person intervention (SSM) developed in Canada and uses cognitive behaviour therapy (CBT) principles with remote coaching by non-specialist providers. Fidelity-adaptation is a major tension in implementation science. Fidelity is the degree an intervention is designed and delivered as intended. Conversely, adaptations are sometimes made for specific contexts. This paper aims to identify key elements of fidelity-adaptation - the degree VMood is consistent theoretically with the SSM intervention and practically with implementing digitally in the Vietnamese setting.

METHODS: This study uses Perez et al.'s modified version of Carroll et al.'s Implementation Fidelity Framework, focusing on Objective 1: Conceptualizing what intervention fidelity means in this specific context (across modes and cultures) and Objective 2: Conducting fidelity testing to identify key elements along the fidelity-adaptation continuum. Ethnographic data from team meetings explored essential components that must remain intact and necessary adaptations. Non-specialist providers and app users from Vietnam tested VMood. Experts familiar with CBT provided theoretical feedback. Interviews or focus groups were conducted with all participants to gain insights into the adaptive intervention. Qualitative data were analyzed using thematic content analysis.

RESULTS: Participants agreed that VMood captures the essential theoretical components from SSM, noting certain elements of SSM (e.g., change in human contact to online) could not be replicated digitally. Participants also presented adaptation suggestions unique for the digital format to strengthen VMood's acceptability, including keeping the app simple by reducing the amount of text; incorporating more dynamic content (e.g., animations) to increase engagement; and including more culturally appropriate scenarios. Finally, key potential moderators to fidelity reported included quality of program delivery and participant responsiveness.

CONCLUSIONS: Findings identified intervention specific elements of fidelity-adaptation and showed that VMood retained essential components of SSM while incorporating adaptations to support implementation within the Vietnamese context. With the global increase in digital health services adapted from in-person delivery, understanding how to balance fidelity with necessary adaptations is important both theoretically and practically.},
}

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

CLINICAL TRIAL NUMBER: Not applicable.},
}

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

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

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

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

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

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

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

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