@article {pmid42304926,
year = {2026},
author = {Mukherjee, S and Ray, SK and Mukherjee, S},
title = {Linking Neurodegeneration and Age-related Macular Degeneration: Unified Pathways and Intervention Strategies.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273450093260523224914},
pmid = {42304926},
issn = {1996-3181},
abstract = {Age-related macular degeneration (AMD) is caused by the degeneration of photoreceptors and retinal pigment epithelium (RPE) along with drusen deposition and is the leading cause of vision loss in older adults. Both these structures within the central nervous system (CNS) utilize common neuro-inflammatory mechanisms because the retina is an outgrowth of the brain. Like the brain, the eye has its own physical characteristics and surface molecules as well as a tendency towards specific immune reactions. Numerous distinct neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and Frontotemporal dementia (FTD) that impact the brain present as eye symptoms, and the conventional diagnosis of these neurodegenerative disorders (NDs) is often preceded by ocular symptoms. Furthermore, several eye-specific disorders have characteristics in common with other CNS disorders. NDs and AMD share common key features, such as tau and amyloid-β deposits, oxidative stress response, chronic inflammation, and dysregulation of microglia and müller glia. Common pathological mechanisms include complement activation, amyloid aggregation, neuroinflammation, vascular impairment, and cell death, providing a basis for a convergent neuroimmune axis between retinal and cerebral degeneration. Comparing these age-related diseases will facilitate the identification of shared risk factors, convergent molecular pathways, and potential cross-applicable therapeutic strategies, such as anti-inflammatory, anti-complementary, anti-apoptotic, and anti-VEGF-based approaches. This knowledge may enhance understanding of neurodegenerative diseases, help identify early biomarker development for diagnosis, and enable the design of targeted therapeutic strategies.},
}

@article {pmid42305210,
year = {2026},
author = {Sabnis, RW and Sabnis, AR},
title = {Novel Compounds as TREM2 Modulators for Treating Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, and Nasu-Hakola Disease.},
journal = {ACS medicinal chemistry letters},
volume = {17},
number = {6},
pages = {1236-1237},
pmid = {42305210},
issn = {1948-5875},
abstract = {Provided herein are novel compounds as TREM2 modulators, pharmaceutical compositions, use of such compounds in treating Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and Nasu-Hakola disease, and processes for preparing such compounds.},
}

@article {pmid42307135,
year = {2026},
author = {Frycz, S and Więcławski, W and Skotniczny, M and Binder, M},
title = {Brain activity in an end-stage ALS patient suggests the presence of an unresponsive wakefulness syndrome.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/21678421.2026.2688249},
pmid = {42307135},
issn = {2167-9223},
abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease primarily affecting motor neurons. It is widely assumed that cortical structures beyond motor neurons are relatively preserved, and patients in the end-stage ALS are regarded as being in complete locked-in syndrome (cLIS). However, emerging evidence suggests substantial heterogeneity in cognitive functioning among ALS patients, indicating possible extra-motor cortical involvement and impaired levels of consciousness. We report a case study assessing electrophysiological markers and auditory system integrity to evaluate the presence of covert consciousness in end-stage ALS.

METHODS: The patient was a 42-year-old woman with bulbar-onset, end-stage ALS, a six-year disease duration, and no means of communication. She underwent several EEG-based protocols, including resting-state EEG (RS-EEG), a passive auditory oddball paradigm, and 40 Hz auditory steady-state responses (ASSR). Audiological evaluation comprised transient-evoked and distortion-product otoacoustic emissions, as well as auditory brainstem responses (ABR).

RESULTS: RS-EEG was dominated by prefrontal 1-3 Hz activity resembling frontal intermittent rhythmic delta activity. Power spectra were poorly differentiated and consistent with a 1/f profile. No event-related potentials were observed in the oddball paradigm, and no ASSR responses were detected. Audiological testing revealed absent otoacoustic emissions and ABR indicating severe to profound hearing loss.

CONCLUSIONS: Our findings indicate severe cortical dysfunction and provide no electrophysiological evidence of covert consciousness. The electrophysiological profile closely resembles that observed in unresponsive wakefulness syndrome. This case supports the hypothesis that advanced ALS following cLIS onset may be more appropriately conceptualized as a disorder of consciousness rather than persistent cLIS.},
}

@article {pmid42309005,
year = {2026},
author = {Rugarli, EI and Langer, T},
title = {Limiting neurodegeneration in ALS: A phosphatase paves the way.},
journal = {Neuron},
volume = {114},
number = {12},
pages = {2073-2075},
doi = {10.1016/j.neuron.2026.04.030},
pmid = {42309005},
issn = {1097-4199},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/enzymology/metabolism ; Animals ; Motor Neurons/metabolism ; *Nerve Degeneration ; Mitochondria/metabolism ; *Phosphoric Monoester Hydrolases/metabolism ; },
abstract = {Zheng et al. identify phosphatase PGAM5 as a novel promising target for the treatment of different amyotrophic lateral sclerosis subtypes. PGAM5 dephosphorylates and activates the stress-regulated mitochondrial peptidase OMA1, which elicits a maladaptive mitochondrial integrated stress response in motor neurons.},
}

Humans
*Amyotrophic Lateral Sclerosis/pathology/enzymology/metabolism
Animals
Motor Neurons/metabolism
*Nerve Degeneration
Mitochondria/metabolism
*Phosphoric Monoester Hydrolases/metabolism

@article {pmid42309130,
year = {2026},
author = {Patel, RJ and Bryson, B and Carlson, T and Demosthenous, A and Jiang, D},
title = {Stability and neurophysiological validity of graph connectivity features for non-stationary motor imagery BCIs.},
journal = {Journal of neural engineering},
volume = {},
number = {},
pages = {},
doi = {10.1088/1741-2552/ae7ead},
pmid = {42309130},
issn = {1741-2552},
abstract = {Motor imagery (MI) Electroencephalography (EEG) Brain-computer interfaces (BCI) degrade under longitudinal non-stationarity, especially in amyotrophic lateral sclerosis (ALS). Functional connectivity (FC) has been proposed as an alternative feature space, but it remains unclear which FC estimators yield stable, class-informative features across sessions. Approach: Using a multi-session ALS EEG dataset, we computed a broad family of FC estimators per trial to form weighted graphs. We extracted edge weights and node strength features, and quantified (i) feature reproducibility and (ii) LH-RH separability using coefficient of variation and symmetric Kullback-Leibler divergence, respectively. We assessed neurophysiological plausibility via spatial topographies, distance-dependence controls, and evaluated selected feature sets in a strictly temporal cross-session decoding protocol against Common Spatial Patterns, Band Power and Riemannian Methods. Main Results: Coherence-based estimators, particularly magnitude-squared coherence, most consistently produced features exhibiting favourable reproducibility-separability trade-offs across subjects. Node-strength discriminability maps showed lateralised sensorimotor structure consistent with known MI physiology. In temporal generalisation, Magnitude Squared Coherence derived features achieved more consistent test performance than baseline methods for most subjects. Significance: Joint reproducibility-separability profiling provides a principled way to select FC feature spaces for longitudinal MI-BCIs and suggests coherence-based connectivity is a stronger sensor-space candidate under drift.},
}

@article {pmid42309840,
year = {2026},
author = {Oliveira Santos, M and de Carvalho, M},
title = {Enhanced spinal motoneuron excitability as a marker of motor neuron dysfunction in primary lateral sclerosis.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {},
number = {},
pages = {2111978},
doi = {10.1016/j.clinph.2026.2111978},
pmid = {42309840},
issn = {1872-8952},
abstract = {OBJECTIVE: To investigate F-wave parameters as markers of spinal motoneuron excitability in patients with primary lateral sclerosis (PLS).

METHODS: We prospectively evaluated F-waves and M-waves from the abductor pollicis brevis (APB), first dorsal interosseous (FDI), and abductor digiti minimi (ADM) muscles. The study included three groups: 27 patients with PLS, 36 with amyotrophic lateral sclerosis with normal right-hand function (ALS-NH), and 30 healthy controls (HC). Recorded parameters included M-wave amplitude, F-wave frequency, latencies, amplitude, and the F/M-waves amplitude ratio. Upper motor neuron (UMN) clinical scores were also assessed. Statistical analysis was performed using One-way ANOVA or Kruskal-Wallis tests for group comparisons, and Spearman's rank test for correlations.

RESULTS: PLS had a significantly higher UMN score than ALS-NH (p < 0.001). F-wave amplitudes were significantly higher in PLS compared to both ALS-NM and HC across all muscles (APB, p = 0.01 and p = 0.03; FDI, p = 0.002 and p < 0.001; ADM, p = 0.03 and p < 0.001, respectively). F/M-waves amplitude ratio was also significantly higher in PLS vs. ALS-NH/HC (APB, p = 0.01 and p = 0.03; FDI, p < 0.001 and p < 0.001; ADM, p = 0.03 and p = 0.001, respectively). No significant differences were found between ALS-NM and HC for these parameters (p > 0.05). M-wave amplitudes and other F-wave parameters remained comparable across all groups (p > 0.05). No correlation was found between F-wave amplitude and UMN scores in PLS patients (p > 0.05).

CONCLUSIONS: Patients with PLS exhibit significantly increased F-wave amplitudes and F/M amplitudes ratios compared to ALS-NH and HC.

SIGNIFICANCE: Increased F-waves size serves as a neurophysiological marker of enhanced spinal motoneuron excitability in PLS.},
}

@article {pmid42310079,
year = {2026},
author = {Nouraei, H and Amirzadeh, N and Shabanzadeh, S and Zareshahrabadi, Z and Shamsdin, N and Nouraei, M and Naeimi, B and Pakshir, K},
title = {Effect of subsequent passages on biofilm formation intensity, ALS genes expression, and cell surface hydrophobicity variability in clinical Candida albicans isolates.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-58680-y},
pmid = {42310079},
issn = {2045-2322},
support = {32536//Vice-Chancellor for Research, Shiraz University of Medical Sciences/ ; },
abstract = {Candida albicans is an opportunistic yeast pathogen that have several virulence factors included biofilm formation, cell surface hydrophobicity (CSH), and the expression of adhesion genes. Concerns exist that serial laboratory subculturing may diminish these traits, leading to inaccurate research findings. Aim of this study was evaluated the effect of subsequently subcultures on biofilm formation intensity, ALS gene expression, and surface hydrophobicity properties in clinical C. albicans isolates. Ten clinical C. albicans isolates were serially subcultured up to 20 passages (P). We used qPCR to quantify ALS1 and ALS3 gene expression, the Crystal Violet assay to measure biofilm formation intensity (P1, P5, P10, P15, P20), and a water-octane partitioning assay for CSH variability at different passages. Serial subculturing caused gradual downregulation of gene expression for both ALS1 and ALS3 (p < 0.001). This condition was accompanied by a biofilm-forming capacity that became progressively reduced in 90% of isolates, whereas 60% at P20 were already biofilm-negative (vs. 10% at P1). Cell surface hydrophobicity also decreased progressively, with 100% of isolates displaying low CSH at P15, compared with 40% in the initial P1 state. Serial subculturing leads to a rapid reduction of C. albicans pathogenic fitness with decreased expression of certain key adhesion genes, diminished biofilm formation, and lower CSH. These results highlight the plasticity of the organism and thus strongly suggest that low-passage clinical isolates should be used in studies to reflect true pathogenicity in vivo accurately.},
}

@article {pmid42310298,
year = {2026},
author = {Diaz Escarcega, R and M J, VK and Arizmendez, A and Tan, C and Urayama, A and Marrelli, SP and Morales, R and Wefel, JS and Zhang, C and McCullough, LD and Kim, N and Monchaud, D and Jung, SY and Tsvetkov, AS},
title = {Sex-linked helicases DDX3X and DDX3Y regulate G-quadruplex-associated stress in neurons.},
journal = {Cell death & disease},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41419-026-08971-z},
pmid = {42310298},
issn = {2041-4889},
support = {4R01AG068292//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; AFAR BIG21042//Glenn Family Foundation/ ; AFAR BIG21042//American Federation for Aging Research (American Federation for Aging Research, Inc.)/ ; },
abstract = {G-quadruplexes (G4s) are four-stranded nucleic acid structures that regulate virtually all nucleic acid-dependent cellular processes. At present, most functional studies involving G4s have focused on cancer cells. This study investigated how neurons respond to genotoxic stress induced by quarfloxin (CX-3543), a small molecule that stabilizes G4s. We found that quarfloxin treatment induced DNA damage in neurons, with double-strand breaks enriched in the nucleolus. Proteomic analysis revealed that quarfloxin promoted substantial protein changes, affecting networks associated with Alzheimer's, Parkinson's, and Huntington's diseases, and amyotrophic lateral sclerosis. Among the affected proteins, the G4 helicase DDX3X, encoded on the X chromosome, was upregulated, prompting further investigation of DDX3X and its Y-linked homolog DDX3Y in male and female neurons, respectively. RNA sequencing identified DDX3X- and DDX3Y-regulated gene networks involved in DNA damage responses, inflammation, cell cycle regulation, and stress-associated pathways, with notable sex-dependent differences. In human brain tissue, DDX3X expression and nuclear enrichment were increased in neurons from older females compared to younger individuals, with further elevation observed in Alzheimer's disease. Taken together, these findings identify DDX3X and DDX3Y as modulators of neuronal stress responses downstream of G4 stabilization and indicate that their induction is accompanied by activation of DNA damage response genes, as well as cell cycle- and inflammation-associated pathways, suggesting that sustained activation of these pathways may disrupt neuronal homeostasis. Our study provides insight into G4-dependent stress mechanisms in neurons and highlights sex-linked pathways that may contribute to brain aging and neurodegenerative disease vulnerability.},
}

@article {pmid42310450,
year = {2026},
author = {Deo, DR and Okorokova, EV and Pritchard, AL and Hahn, NV and Card, NS and Nason-Tomaszewski, SR and Jude, J and Hosman, T and Choi, EY and Qiu, D and Meng, Y and Wairagkar, M and Nicolas, C and Kamdar, FB and Iacobacci, C and Acosta, A and Hochberg, LR and Cash, SS and Williams, ZM and Rubin, DB and Brandman, DM and Stavisky, SD and AuYong, N and Pandarinath, C and Downey, JE and Bensmaia, SJ and Henderson, JM and Willett, FR},
title = {A mosaic of whole-body representations on the human precentral gyrus.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {42310450},
issn = {1476-4687},
abstract = {Understanding how the body is represented in the motor cortex is key to understanding how the brain controls movement. Although the motor cortex has been mapped in animal models at a fine scale[1-10], characterization in humans remains primarily limited to low-resolution recording[11-16] and stimulation techniques[17-20]. Here we created a comprehensive map of the human motor cortex at single-neuron resolution, spanning microelectrode array recordings from 20 arrays across 8 individuals with paralysis from spinal cord injury, amyotrophic lateral sclerosis or brainstem stroke, all enrolled in brain-computer interface clinical trials. These arrays broadly sample the crown of the precentral gyrus (PCG; thought to be composed largely of the premotor cortex (Brodmann area 6)). We found that body parts were highly intermixed, such that the entire body was represented in all sampled locations of the PCG, although the relative strength of body parts was roughly consistent with the motor homunculus[17,18]. We also found two speech-preferential areas with a broadly tuned, orofacial-dominant area in between them. Throughout the PCG, movement representations of the four limbs were interlinked, with homologous movements of different limbs (for example, toe curl and hand close) having correlated representations. These data provide evidence consistent with an intermixed, interrelated and behaviour-centred organization of the motor cortex[3,21]. The resulting map also provides important targeting information for brain-computer interfaces that seek to restore motor function.},
}

@article {pmid42310788,
year = {2026},
author = {Wood, C and Brown, G and Chalk, K and Smith, SH and Williams, H and Broadhurst, G and Ealing, J and Hamdalla, H and Breen, C and Macleod, R and Chaouch, A},
title = {Co-development of a genetic care pathway for ALS: real-world perspectives from the North of England.},
journal = {Orphanet journal of rare diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13023-026-04417-z},
pmid = {42310788},
issn = {1750-1172},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a rare, progressive neurodegenerative disorder, with a substantial proportion of cases attributed to genetic factors. Recent advances in gene discovery and genomic technologies have transformed ALS care by enabling genomic testing to inform prognosis, assess familial risk, and facilitate access to novel therapies. However, guidance on the delivery of genetic testing and counselling in ALS remains limited, leading to variability in clinical practice. In response, the Manchester Motor Neuron Disease (MND) Care Centre and the Manchester Centre for Genomic Medicine co-developed a structured genetic care pathway for ALS, drawing on real-world data, patient engagement, and multidisciplinary collaboration.

RESULTS: A retrospective evaluation of 326 ALS patients at the Manchester MND Care Centre identified significant variability in genetic testing uptake, counselling practices, and record-keeping. Patient survey and engagement sessions revealed uncertainty regarding key genetic concepts and inconsistent recall of pre- and post-test discussions. Priorities for improvement included clearer communication, standardised discussions, and enhanced support for families following genetic findings. Consequently, the Greater Manchester ALS Genetic Testing Pathway was developed by a multidisciplinary team, incorporating consensus-based steps for patient identification, pre-test conversations, consent, testing, results disclosure, and post-test support. This pathway integrates genetic testing into routine ALS care, clarifies team responsibilities, and establishes a framework for ongoing evaluation using key performance indicators. Patient and staff feedback is used to support continuous improvement.

CONCLUSIONS: The co-developed ALS genetic testing pathway provides a scalable model for standardising genomic care in mainstream clinical settings. By establishing clear processes for genetics discussions, consent, and follow-up, the pathway seeks to improve equity, transparency, and person-centred care. Ongoing evaluation and collaboration with patients, clinicians, and genetic services are essential to ensure the pathway remains responsive to scientific advances and evolving patient needs. Wider adoption of structured genetic pathways may facilitate the integration of genomics into care for rare diseases across healthcare systems.},
}

@article {pmid42310801,
year = {2026},
author = {Fernandes, JB and Almeida, AS and Magsi, F and Maia, AC and Fernandes, S},
title = {Motivations and barriers to engaging in peer review: a qualitative study.},
journal = {Research integrity and peer review},
volume = {11},
number = {1},
pages = {},
pmid = {42310801},
issn = {2058-8615},
abstract = {BACKGROUND: Peer review is a central mechanism of scientific communication. However, despite its critical role in safeguarding research quality and integrity, there is limited evidence on how reviewers themselves perceive the factors that motivate or hinder their engagement. This study explored reviewers' perceptions of the motivations and barriers shaping participation in peer review.

METHODS: A qualitative, exploratory-descriptive design was adopted. Semi-structured interviews were conducted between June and September 2025 with participants holding an academic title in health sciences who had completed at least one peer review for a scientific journal. Participants were recruited through purposive sampling. Interviews were audio-recorded, transcribed verbatim, and analysed inductively using thematic analysis following Braun et al.'s framework. Data collection and analysis proceeded iteratively until thematic saturation was reached.

RESULTS: Twenty-seven academics from seven health science disciplines participated in the study. Participants were predominantly female (63%), with similar proportions holding doctoral (52%) and master's degrees (48%), and peer-review activity in the previous 12 months ranging from 1 to more than 10 reviews. Findings were organised into two domains, motivations and barriers, comprising ten themes. Motivations included contribution to science, scientific development, career development, personal satisfaction, and financial incentives. Barriers included high workload, lack of recognition and incentives, perceived competence, research integrity, and editorial shortcomings.

CONCLUSION: Reviewer engagement appears to be a negotiated process in which academics weigh motivations against barriers when deciding whether to participate in peer review. These trade-offs shape decisions to accept or decline review invitations. Strengthening recognition, transparency, and editorial support may help sustain reviewer participation in the health sciences.},
}

@article {pmid42311066,
year = {2026},
author = {Dubbioso, R and Pappatà, S},
title = {Amyotrophic lateral sclerosis as a network disease: from metabolic decline to network failure.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag211},
pmid = {42311066},
issn = {1460-2156},
}

@article {pmid42311422,
year = {2026},
author = {Fayez, SM},
title = {Nanomedicine in 2026: Illustrative Quantitative Analyses of EPR Heterogeneity, Clinical Trial Attrition, and Emerging Horizons for Active Nanotherapeutics.},
journal = {International journal of nanomedicine},
volume = {21},
number = {},
pages = {618407},
pmid = {42311422},
issn = {1178-2013},
mesh = {Humans ; *Nanomedicine/trends/methods ; Animals ; Clinical Trials as Topic ; Nanoparticles/chemistry/therapeutic use ; Neoplasms ; Mice ; Immunotherapy ; },
abstract = {2026 is a turning point for nanomedicine, marking the field's transition from decades of preclinical promise toward tangible clinical impact. This narrative review provides a forward-oriented synthesis of the most significant clinical breakthroughs achieved during 2025-2026, critically examines persistent barriers to clinical translation, and projects future horizons for the coming decade. To support the discussion, the review includes illustrative quantitative analyses drawn from selected published data: a comparison of EPR effect heterogeneity across human and murine tumors (23 studies, 412 patients), a funnel of nanomedicine clinical trials extracted from ClinicalTrials.gov (847 trials, 2010-2020), a comparative overview of regulatory guidance from four major agencies, and a simplified life-cycle assessment of three nanomedicine classes. These analyses are intended to highlight trends, not to replace a formal systematic review. We identify four important clinical advances: first Phase II data for hafnium oxide nanoparticle radioenhancers in inoperable lung cancer; logic-gated STING-agonistic nanoparticles for metastasis-specific immunotherapy; ultrasmall silica nanoparticles that remodel suppressive tumor microenvironments independent of a drug cargo; and CNM-Au8 gold nanocrystals advancing toward regulatory submission for amyotrophic lateral sclerosis. Collectively, these developments illustrate a major change in thinking: nanoparticle formulations no longer serve merely as delivery vehicles but increasingly function as active therapeutic agents that engage biological pathways, respond to disease-associated stimuli, and generate therapeutic effects independently of any drug cargo. This shift from passive delivery to active nanotherapeutics fundamentally changes how the field should evaluate and develop nanomedicines. Nevertheless, the number of nanomedicines that have achieved global clinical approval remains very low, estimated at only 50-80 products by 2025, underscoring a persistent translational gap. We analyze principal obstacles to clinical success, including the limited predictive validity of the enhanced permeability and retention (EPR) effect in humans, batch-to-batch manufacturing variability, safety concerns arising from bio-corona formation and organ accumulation, and the absence of harmonized regulatory frameworks. Looking forward, we identify emerging horizons: AI-driven digital twins for predictive manufacturing, carrier-free self-assembled nanomedicines from natural small molecules, nanotheranostic platforms that integrate therapy with real-time imaging, and sustainable nanomedicine designs incorporating environmental impact assessments. By bridging clinical reality with future potential, this review aims to inform researchers, clinicians, and regulatory stakeholders navigating the rapidly evolving landscape of nanomedicine.},
}

Humans
*Nanomedicine/trends/methods
Animals
Clinical Trials as Topic
Nanoparticles/chemistry/therapeutic use
Neoplasms
Mice
Immunotherapy

@article {pmid42300806,
year = {2026},
author = {Calma, AD and Pavey, N and Tsuji, Y and Ghapar, AA and Bos, MAJVD and Orden, B and Lee, G and Mekhael, L and Ryder, J and Silva, CS and McDonald, D and Kakar, F and Yiannikas, C and Kiernan, MC and Brown, DA and Menon, P and Vucic, S},
title = {Integration of Serum Neurofilament Light Chain and Cortical Dysfunction Improves Diagnostic Accuracy in ALS.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.70454},
pmid = {42300806},
issn = {2328-9503},
abstract = {OBJECTIVE: To determine whether integration of serum neurofilament light chain (NfL) and cortical dysfunction improves diagnostic accuracy in amyotrophic lateral sclerosis (ALS) when applied alongside the Gold Coast criteria (GCC).

METHODS: In this prospective study, 148 participants with suspected ALS were recruited (101 ALS and 47 with ALS mimicking disorders). Participants taking medications known to influence TMS measures were excluded. Serum NfL levels were quantified using a single-molecule array assay. Cortical function was assessed using threshold tracking transcranial magnetic stimulation, with cortical dysfunction defined by reduced mean short interval intracortical inhibition or motor cortex inexcitability. Diagnostic performance was evaluated using sensitivity, specificity, and diagnostic odds ratios (DOR), with 95% confidence intervals (CI).

RESULTS: Serum NfL demonstrated excellent discrimination (area under the curve 0.92, p < 0.001), with cut-off ≥ 33.5 pg/mL providing a sensitivity of 0.85 (95% CI 0.77-0.91) and specificity 0.87 (95% CI 0.75-0.94). Cortical dysfunction demonstrated very good diagnostic performance (sensitivity 0.77 [95% CI 0.68-0.84], specificity 0.77 [95% CI 0.63-0.86]). The GCC achieved a sensitivity of 0.89 (95% CI 0.82-0.94) and specificity 0.89 (95% CI 0.77-0.95). Combining GCC with elevated NfL or cortical dysfunction increased the specificity to 0.98 (95% CI 0.89-1.00) while maintaining high sensitivity at 0.87 (95% CI 0.79-0.92), yielding the highest DOR.

INTERPRETATION: Integration of serum NfL and cortical dysfunction with the Gold Coast criteria improves diagnostic accuracy in ALS, particularly by increasing specificity. This multimodal approach provides a practical framework for earlier and more definitive diagnosis that may facilitate more efficient clinical trial recruitment.},
}

@article {pmid42300933,
year = {2026},
author = {Gray, VP and Cui, Z and Klepsig, M and Letteri, RA},
title = {Designing polymer-peptide conjugates to target dipeptide repeat aggregates implicated in amyotrophic lateral sclerosis.},
journal = {Journal of materials chemistry. B},
volume = {},
number = {},
pages = {},
pmid = {42300933},
issn = {2050-7518},
abstract = {Toxic dipeptide repeats such as the aggregating glycine-alanine (GA)n peptide are implicated in the progression of amyotrophic lateral sclerosis (ALS), a lethal neuromuscular disease with an urgent need for new therapeutics. Here, we report polymer-peptide conjugates that prevent aggregation of (GA)10. Optical density measurements and transmission electron microscopy demonstrate that conjugates prevent aggregation when co-incubated with (GA)10 and disperse pre-aggregated (GA)10. These results represent an important step toward a new generation of therapeutics for ALS and contribute to a growing body of literature demonstrating the potential of polymer-peptide conjugates as therapeutics.},
}

@article {pmid42301686,
year = {2026},
author = {Jomaa, AM and Khalid, H and Abozait, HJ and Mudassar, H and Kaur, R},
title = {Efficacy of Sodium Phenylbutyrate-Taurursodiol in Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.},
journal = {Annals of Indian Academy of Neurology},
volume = {29},
number = {3},
pages = {343-352},
doi = {10.4103/aian.aian_1101_25},
pmid = {42301686},
issn = {0972-2327},
abstract = {OBJECTIVE: To evaluate the efficacy and safety of sodium phenylbutyrate-taurursodiol (PB-TURSO) and its components in slowing disease progression and improving survival in patients with amyotrophic lateral sclerosis (ALS).

METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies comparing PB-TURSO or its components to placebo or standard of care in adults with ALS were included. The primary outcomes were functional decline (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised [ALSFRS-R]) and survival. Two reviewers independently screened studies, extracted data, and assessed the risk of bias. A random-effects model was used for the meta-analysis, and a narrative synthesis was conducted for Tauroursodeoxycholic Acid (TUDCA) monotherapy and secondary analyses from the CENTAUR trial.

RESULTS: Two RCTs (n = 801) were included in the meta-analysis. The pooled analysis demonstrated no statistically significant difference in either ALSFRS-R decline (mean difference [MD] 1.51, 95% confidence interval [CI] -1.01 to 4.02; P = 0.24; I² =71%) or survival (hazard ratio [HR] 0.90, 95% CI 0.73-1.11; P = 0.31; I² = 61%). A separate trial of TUDCA monotherapy (n = 34) demonstrated significant functional benefits. Post hoc analyses of the CENTAUR trial reported a survival benefit of 6.5-10.6 months and delayed progression to major disease milestones. Biomarker analyses suggested anti-inflammatory effects. The risk of bias was moderate to high, and the certainty of evidence was rated very low by GRADE.

CONCLUSIONS: Based on very low certainty evidence, the available RCT data do not support a definitive conclusion regarding the efficacy of PB-TURSO in ALS. Post hoc exploratory analyses suggest a potential survival benefit, which requires confirmation in adequately powered, prospectively designed trials; current results are hypothesis-generating rather than practice-defining.},
}

@article {pmid42301697,
year = {2026},
author = {Jomaa, AM and Khalid, H and Abozait, HJ and Mudassar, H and Kaur, R},
title = {Efficacy of Sodium Phenylbutyrate-Taurursodiol in Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.},
journal = {Annals of Indian Academy of Neurology},
volume = {},
number = {},
pages = {},
doi = {10.4103/aian.aian_1101_25},
pmid = {42301697},
issn = {0972-2327},
abstract = {OBJECTIVE: To evaluate the efficacy and safety of sodium phenylbutyrate-taurursodiol (PB-TURSO) and its components in slowing disease progression and improving survival in patients with amyotrophic lateral sclerosis (ALS).

METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies comparing PB-TURSO or its components to placebo or standard of care in adults with ALS were included. The primary outcomes were functional decline (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised [ALSFRS-R]) and survival. Two reviewers independently screened studies, extracted data, and assessed the risk of bias. A random-effects model was used for the meta-analysis, and a narrative synthesis was conducted for Tauroursodeoxycholic Acid (TUDCA) monotherapy and secondary analyses from the CENTAUR trial.

RESULTS: Two RCTs (n = 801) were included in the meta-analysis. The pooled analysis demonstrated no statistically significant difference in either ALSFRS-R decline (mean difference [MD] 1.51, 95% confidence interval [CI] -1.01 to 4.02; P = 0.24; I² =71%) or survival (hazard ratio [HR] 0.90, 95% CI 0.73-1.11; P = 0.31; I² = 61%). A separate trial of TUDCA monotherapy (n = 34) demonstrated significant functional benefits. Post hoc analyses of the CENTAUR trial reported a survival benefit of 6.5-10.6 months and delayed progression to major disease milestones. Biomarker analyses suggested anti-inflammatory effects. The risk of bias was moderate to high, and the certainty of evidence was rated very low by GRADE.

CONCLUSIONS: Based on very low certainty evidence, the available RCT data do not support a definitive conclusion regarding the efficacy of PB-TURSO in ALS. Post hoc exploratory analyses suggest a potential survival benefit, which requires confirmation in adequately powered, prospectively designed trials; current results are hypothesis-generating rather than practice-defining.},
}

@article {pmid42301897,
year = {2026},
author = {Peters, GA and Misra, AJ and Samadian, KD and Chang, W and Chandran, KG and Hurwitz, JA and Muszalski, C and Granich, N and Goldberg, SA and Cash, RE},
title = {Cardiac arrest during interfacility transport with emergency medical services: a preliminary nationwide cross-sectional study.},
journal = {Prehospital emergency care},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/10903127.2026.2690618},
pmid = {42301897},
issn = {1545-0066},
abstract = {OBJECTIVES: We aimed to provide the first national study of out-of-hospital cardiac arrests (OHCA) witnessed by emergency medical services (EMS) during interfacility transport (IFT).

METHODS: We used a nationwide prehospital patient care report dataset from 2023 to complete a cross-sectional observational study of EMS encounters for IFT during which OHCA occurred. Descriptive statistics were computed, stratified by level of EMS care provided. Multivariable logistic regression analysis was completed to evaluate factors associated with return of spontaneous circulation (ROSC) at the end of the IFT encounter upon transfer of care to the receiving facility. Finally, we completed a similar multivariable logistic regression analysis restricted to the subgroup of patients with an unshockable initial rhythm.

RESULTS: A total of 1,466 OHCA incidents occurred during an IFT with EMS: 7.5% with basic life support (BLS), 53.6% with advanced life support (ALS), and 38.9% with critical care transport (CCT). Among these incidents 11.8% were associated with trauma, 9.2% involved cardiopulmonary resuscitation (CPR) prior to EMS unit arrival, 14.7% involved a mechanical device to perform CPR, 22.2% had a shockable initial rhythm, and 58.1% were transported via ground as opposed to air. At the conclusion of the IFT EMS encounter, 50.3% had sustained ROSC. Geriatric age (aOR 0.64, 95%CI 0.44-0.94), BLS care (aOR 0.45, 95%CI 0.22-0.90), and ground transport (aOR 0.58, 95%CI 0.38-0.89) were associated with worse outcomes on adjusted analysis, whereas shockable initial rhythm (aOR 3.86, 95%CI 2.42-6.36) and CCT care (aOR 2.21, 95%CI 1.42-3.48) were associated with better outcomes. The sub-analysis for OHCA during IFT with an unshockable initial rhythm also showed greater odds of ROSC when managed by CCT relative to ALS (aOR 2.65, 95%CI 1.64-4.33) while adjusting for other key factors.

CONCLUSIONS: Using a large nationwide sample of OHCA incidents that occurred during IFT, we found that higher level of EMS care was associated with superior short-term outcomes while controlling for other key factors. These findings underscore the importance of accurate patient triage at sending facilities and the value of CCT for high-risk patients.},
}

@article {pmid42302423,
year = {2026},
author = {Almenara Abellán, JL and Lagares Franco, C and Bordes Bustamante, F and Gracia Romero, MÁ and Santisteban Espejo, AL},
title = {Impact of a simulation-based training program on the acquisition of ultrasound window competencies for the initial assessment of polytrauma patients in advanced prehospital nursing care.},
journal = {Enfermeria intensiva},
volume = {37},
number = {3},
pages = {500604},
doi = {10.1016/j.enfie.2026.500604},
pmid = {42302423},
issn = {2529-9840},
abstract = {INTRODUCTION: Point-of-care ultrasound is essential in the initial assessment of polytrauma patients. The E-FAST protocol enables rapid detection of intra-abdominal free fluid, pericardial effusion, and pneumothorax, with particular usefulness in prehospital settings. However, ultrasound training among emergency nursing staff remains limited, especially within Advanced Life Support (ALS) mobile units.

OBJECTIVE: To evaluate the effect of a brief, structured training program on the acquisition of competencies for obtaining E-FAST windows in ALS mobile units nurses, assessing knowledge, technical skills, scanning sequence, and perceived confidence.

METHOD: A quasi-experimental pre-post intervention study was conducted with nurses with ≥6 months of experience in emergency or prehospital care. The intervention included baseline assessment, a 2-h theoretical module, high-fidelity simulation with Ultrasound Mentor®, and hands-on practice with human models. Final assessment combined a theoretical test, simulator-based practical evaluation, and scanning with a real ultrasound device. Knowledge, execution times, and confidence levels were recorded.

RESULTS: Fourteen nurses participated, most without previous ultrasound training (85.7%). Initial confidence was low and improved significantly after the intervention. Theoretical performance increased in 5 of the 6 evaluated items, reaching up to 92.9% accuracy in key content areas. Practical assessment demonstrated an organized scanning sequence and appropriate times for prehospital care (medians of 118 s [IQR 24.5] in advanced simulation and 237 s [IQR 33.3] using a real ultrasound device).

DISCUSSION: The program enabled the acquisition of essential skills even in professionals without prior ultrasound experience. The combination of theory, simulation, and hands-on practice facilitated rapid competency transfer and protocol standardization.

CONCLUSIONS: A brief training program improves ALS mobile units nurses' competence and confidence in obtaining E-FAST windows, supporting the safe integration of point-of-care ultrasound into prehospital care.},
}

@article {pmid42302677,
year = {2026},
author = {Gong, X and Xie, Y and Deng, X and Sun, Z and Fu, S and Wang, H and Hou, Y and Dong, Z and Zhou, W},
title = {Hydrolytic evolution of propyrisulfuron: wlectronic differentiation and spectroscopic fingerprints of transformation products.},
journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy},
volume = {362},
number = {},
pages = {128245},
doi = {10.1016/j.saa.2026.128245},
pmid = {42302677},
issn = {1873-3557},
abstract = {Propyrisulfuron (PRS), a sulfonylurea herbicide used in paddy systems, undergoes hydrolysis to form structurally distinct transformation products. This study combined DFT/TDDFT calculations with experimental UV-Vis, FTIR, and Raman spectroscopy to characterise PRS and six experimentally identified products (HP1-HP6). Relative electronic descriptors showed that cleavage of the sulfonylurea bridge increased the HOMO-LUMO gaps from 4.572 eV for PRS to 5.978 and 6.229 eV for HP1 and HP2, respectively, whereas HP3-HP5 retained moderate gaps of 4.846-4.923 eV. HP5 showed the most negative Vmin (-71.524 kcal mol[-1]) and the largest dipole moment (16.67 D). Calculated and experimental spectra were consistent, with major UV-Vis peak deviations below 10 nm and characteristic FTIR and Raman deviations generally below 20 and 15 cm[-1], respectively. A validated 1YBH-based docking workflow reproduced the co-crystallized CIE pose with an RMSD of 0.320 Å; within this internally standardized comparison, PRS, HP3, HP5, and HP4 gave scores of -8.480, -7.212, -7.076, and - 6.979 kcal mol[-1], respectively. Docking results are interpreted as relative ALS/AHAS-recognition tendencies rather than direct evidence of toxicity or inhibitory potency. Overall, this work establishes a structure-spectrum framework for tracking PRS hydrolysis and differentiating its major products.},
}

@article {pmid42302791,
year = {2026},
author = {Sahu, SK and Memczak, S and Thakurela, S and Lu, J and Gupta, P and Mutukula, N and Hirano, A and Zhang, Y and Hishida, T and Kurita, M and Wang, C and Shao, Y and Williams, A and Shokhirev, M and Tiwari, VK and Rodriguez Esteban, C and Reddy, P and Meissner, A and Li, M and Izpisua Belmonte, JC},
title = {ZNF512B safeguards genome integrity at regulatory regions to repress the SASP and inflammation.},
journal = {Cell stem cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.stem.2026.05.009},
pmid = {42302791},
issn = {1875-9777},
abstract = {Cellular senescence drives aging and disease largely through the senescence-associated secretory phenotype (SASP), yet its regulatory mechanisms remain unclear. Using a SASP reporter combined with a CRISPR-Cas9 screen targeting active regulatory elements, we identify the zinc-finger protein ZNF512B as a key suppressor of the SASP. ZNF512B loss induces DNA damage, activates cGAS-STING signaling, and triggers inflammatory transcriptional reprogramming. In contrast, ZNF512B promotes preferential DNA repair at regulatory genomic regions, limiting SASP induction. Mechanistically, ZNF512B is rapidly recruited to DNA-damage sites via distinct zinc-finger domains and facilitates NuRD complex targeting to damaged chromatin, enabling precise repair. In human neuromuscular organoids, ZNF512B deficiency induces inflammation, lineage imbalance, and cytokine secretion resembling amyotrophic lateral sclerosis (ALS)-associated pathology. In vivo, ZNF512B overexpression reduces DNA damage and inflammation following acute liver injury. Together, these findings support a mechanism of preferential DNA repair that contributes to maintaining genome integrity, suppressing SASP and inflammation.},
}

@article {pmid42303396,
year = {2026},
author = {Akers, E and Ameratunga, S and Wilkinson-Meyers, L and Adams, M and Te Ao, B},
title = {Perspectives on the injured child's hospital discharge process and opportunities for improvement: a scoping review protocol.},
journal = {BMJ open},
volume = {16},
number = {6},
pages = {e119916},
doi = {10.1136/bmjopen-2026-119916},
pmid = {42303396},
issn = {2044-6055},
mesh = {Humans ; Scoping Reviews as Topic ; *Patient Discharge/standards ; Child ; *Wounds and Injuries/therapy ; Caregivers/psychology ; Research Design ; },
abstract = {INTRODUCTION: Unintentional injury is a leading cause of hospitalisation and disability in children globally. Families may experience a second crisis of injury after the child's discharge from the hospital, with the traumatic nature of injuries affecting physical and psychosocial recovery. This scoping review aims to summarise the literature on the perspectives of injured children's caregivers and service providers on the hospital discharge process, the challenges and opportunities to improve discharge planning evident from qualitative and interventional studies, and the investigation of inequities in these studies using the Conceptual Framework of Access to healthcare proposed by Levesque et al in 2013.

METHODS AND ANALYSIS: A scoping review will be conducted involving a search across four databases: CINAHL Plus, Cochrane Library, Embase and Ovid MEDLINE. Empirical literature published in English between 2000 and 2025 will be eligible for inclusion. Included studies will report caregiver or service provider perspectives on current hospital discharge practice for injured children under 18 years old, investigated a priori as a study objective or a posteriori as a finding, or will report the design, implementation or evaluation of interventions intended to improve hospital discharge for injured children. Levesque et al's framework will be used to guide data extraction from the selected studies into predefined data charting forms, informing the review questions. Findings will be presented narratively and in tables to highlight the key characteristics of the studies, the perspectives of caregivers and service providers, the challenges and opportunities to improve hospital discharge, the proposed discharge interventions, the investigation of inequities and the gaps in the literature.

ETHICS AND DISSEMINATION: The scoping review only uses data in the public domain and does not require ethics approval.},
}

Humans
Scoping Reviews as Topic
*Patient Discharge/standards
Child
*Wounds and Injuries/therapy
Caregivers/psychology
Research Design

@article {pmid42304808,
year = {2026},
author = {Smith, SE and Hughes, B and Miller, TM and Bucelli, RC},
title = {Amyotrophic Lateral Sclerosis Recovery: A New Model System of Care Integrating Neuromuscular Rehabilitation With Clinical Stabilization in ALS.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70320},
pmid = {42304808},
issn = {1097-4598},
abstract = {There is currently no consensus on how to define recovery for individuals with amyotrophic lateral sclerosis (ALS). Tofersen treatment for superoxide dismutase-1-related (SOD1) ALS marks a pivot in clinical management: for the first time, clinicians can target disease stabilization and functional recovery in some individuals. This advancement shifts the focus of ALS care toward optimizing functional recovery alongside symptomatic management. However, there are no evidence-based guidelines for prescribing neuromuscular rehabilitation (NMR) to improve functional recovery. Building on our preliminary single-center data of integrated NMR with tofersen, we propose a new ALS Recovery Model System of Care, utilizing a hub-and-spoke infrastructure to combine NMR with novel therapies. This model aims to define ALS recovery, characterize recovery profiles, standardize NMR protocols, and establish a rehabilitation framework adaptable to future disease-stabilizing therapies.},
}

@article {pmid42304913,
year = {2026},
author = {Wang, T and Wu, M and Liang, L and Pei, L and Wang, D},
title = {Nicotine Versus Non-Nicotine Constituents in Neurodegenerative Risk: Evidence from Multivariable Mendelian Randomization.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X503957260608154111},
pmid = {42304913},
issn = {1875-6190},
abstract = {BACKGROUND: Nicotine has complex neuropharmacological actions through nicotinic acetylcholine receptors, but its independent role in neurodegenerative diseases remains unclear because tobacco smoke contains many non-nicotine toxicants. This uncertainty limits the interpretation of nicotine- and nAChR-targeted therapeutic strategies, especially as electronic nicotine delivery sys-tems become more common. We used Mendelian randomization to genetically separate nicotine-related effects from smoking-related non-nicotine effects on major neurodegenerative diseases and related prodromal conditions.

METHODS: We performed univariable two-sample Mendelian randomization (MR) and multivariable MR (MVMR) analyses. Summary-level exposure data for cigarettes per day (CPD) and the nicotine metabolite ratio (NMR) were analyzed against individual-level, smoking-stratified outcome data derived from 337,334 UK Biobank participants, to evaluate their respective causal effects across six neurodegenerative outcomes: Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), tremor, early cognitive impairment (EC), and other neurodegenerative diseases (OND).

FINDINGS: MVMR analyses revealed that nicotine exposure was a causal risk factor for AD (ever smokers: OR=0.90, 95% CI 0.83-0.98; current smokers: OR=0.76, 95% CI 0.64-0.91). Nicotine exerted a causal protective effect against tremor (OR=1.24, 95% CI 1.03-1.49) and EC (OR=1.14, 95% CI 1.04-1.24) in current smokers. Non-nicotine tobacco constituents were identified as risk factors among former smokers for EC (OR=1.61, 95% CI 1.04-2.50).

CONCLUSIONS: Exposure to nicotine can increase the risks of AD, while conferring protective effects against tremor and EC. Furthermore, exposure to non-nicotine tobacco constituents acts as a risk factor for the incidence of EC.},
}

@article {pmid42020473,
year = {2026},
author = {García-Camacho, M and Martínez-Subiela, S and Tvarijonaviciute, A and Cerón, JJ and Rubio, CP and Muñoz-Prieto, A},
title = {Analytical validation of aldolase, microalbumin and myeloperoxidase in canine saliva and their evaluation in canine gingivitis.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {42020473},
issn = {2045-2322},
support = {22724/FPI/24//Fundación Séneca/ ; PID2023-149944OB-I00//Agencia Estatal de Investigación/ ; PID2023-149944OB-I00//FEDER, EU/ ; RYC2021-034764-I//Ramón y Cajal/ ; RYC2021-033660-I//Ramón y Cajal/ ; },
abstract = {UNLABELLED: Saliva is a biological fluid that offers potential practical advantages for biomarker assessment in dogs due to its non-invasive nature. This study evaluated aldolase (ALS), microalbumin (mALB), and myeloperoxidase (MPO) in canine saliva using automated assays. All assays showed acceptable analytical performance, with adequate precision (coefficients of variation < 15%), accuracy (coefficients of determination close to 1 after serial sample dilutions), and sensitivity (lower limits of quantification of 5.6 IU/L, 2.05 mg/dL, and 26.3 IU/L for ALS, mALB and MPO, respectively). The effect of gingivitis on these salivary analytes was also assessed. Dogs with gingivitis showed significantly higher salivary ALS and mALB results — ALS, 21.9 (14.2–37.3) IU/L; mALB, 13.15 (5.89–25.71) mg/dL — compared with controls — ALS, 7.65 (2.2-12.23) IU/L; mALB, 3.51 (2.32–5.21) mg/dL— (p < 0.0001). Moreover, increasing gingivitis severity was associated with progressively higher levels of ALS and mALB. In contrast, no significant differences were observed in MPO activity between groups. These findings suggest that ALS and mALB may serve as salivary biomarkers for gingivitis assessment. Further studies are warranted to explore their potential applicability in other local and systemic inflammatory conditions in dogs.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-48816-5.},
}

@article {pmid42293743,
year = {2026},
author = {Mavillonio, A and Rizzini, D and Detassis, S and Denti, MA},
title = {Neurodegenerative spliceosomopathies.},
journal = {Frontiers in cell and developmental biology},
volume = {14},
number = {},
pages = {1787859},
pmid = {42293743},
issn = {2296-634X},
abstract = {Spliceosomal syndromes are a group of disorders caused by pathogenic variants in core spliceosomal RNAs or proteins, leading to defective pre-mRNA splicing and tissue-specific disease vulnerability. Although the spliceosome is ubiquitously expressed, its dysfunction preferentially affects highly splicing-dependent tissues such as the retina and the nervous system. This mini-review focuses on neurodegenerative spliceosomopathies, including spinal muscular atrophy, amyotrophic lateral sclerosis, and retinitis pigmentosa, highlighting how alterations in snRNP biogenesis, spliceosome assembly, and splicing fidelity drive neuronal and photoreceptor degeneration. We discuss shared and distinct molecular mechanisms, unresolved questions on tissue specificity, and emerging therapeutic strategies targeting RNA splicing.},
}

@article {pmid42295247,
year = {2026},
author = {Panagos, I and Bedi, RP},
title = {Attempting to validate a group psychotherapy session taxonomy: A conceptual replication and extension.},
journal = {Journal of counseling psychology},
volume = {},
number = {},
pages = {},
doi = {10.1037/cou0000890},
pmid = {42295247},
issn = {0022-0167},
support = {//Social Sciences and Humanities Research Council of Canada/ ; },
abstract = {This study attempted to conceptually replicate the five-category typology system for group psychotherapy sessions developed by Li et al. (2021) and aimed to identify whether sessions of one type and one climate valence were more likely to follow sessions of the same type (perseveration effect) and similar valence (climate valence continuity), respectively. Ninety-eight individuals with a history of problematic alcohol use attended one of 19 six-session groups, which were either focused on identity transitions or career development. Following each session, individuals' perceptions of the group climate were assessed on the three dimensions of engagement, avoiding, and conflict. A k-means cluster analysis was performed in an attempt to replicate Li et al.'s taxonomy but failed. As a result, an exploratory hierarchical cluster analysis was conducted followed by a confirmatory k-means cluster analysis. Findings identified three types of group sessions: cohesively collaborative, unenthusiastically detached, and politely aloof. Results did not identify a perseveration effect or climate valence continuity. This new typology identified was inconsistent with that of Li et al., indicating that one classification system may not be suitable for all types of groups. The results provide an alternate session typology that may be used to characterize structured group sessions for individuals with problematic alcohol use. (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}

@article {pmid42295687,
year = {2026},
author = {Jürs, AV and Naumann, M and Lehto, A and Schön, H and Kurth, J and Prudlo, J and Hermann, A and Kasper, E},
title = {Cognitive and Neuroimaging Divergence Between Juvenile and Adult FUS Amyotrophic Lateral Sclerosis.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.70447},
pmid = {42295687},
issn = {2328-9503},
support = {//Hermann und Lilly Schilling-Stiftung für medizinische Forschung im Stifterverband/ ; //Clinician Scientist Program of the Center for Transdisciplinary Neuroscience Rostock/ ; },
abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive motor neuron degeneration. Fused in sarcoma (FUS)-associated juvenile ALS (jALS) represents a distinct and aggressive subgroup with rapid deterioration and poor prognosis. Certain FUS mutations have been associated with comorbid intellectual disability, suggesting neurodevelopmental involvement. We compared FUS-jALS with adult-onset FUS-ALS cases (aALS) to evaluate the association between premorbid cognitive impairment, genetic and clinical features incorporating neuroimaging data.

METHODS: Patients with genetically confirmed FUS-ALS were classified as jALS (onset < 25 years) or aALS (onset ≥ 25 years). Neuropsychological assessment used Mehrfachwahl-Wortschatz-Test (MWT) for verbal IQ, and the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), with cognitive impairment classified according to Strong criteria. Volumetric analysis was conducted on structural MRI and FDG-PET data.

RESULTS: All three jALS (P525L [n = 2], H517_Q519del [n = 1]) showed rapid progression with early severe clinical events. Neuropsychological assessment revealed global cognitive deficits (ALS-ci) with widespread dysfunction beyond typical ALS-specific patterns and reduced verbal IQ, pointing towards premorbid cognitive impairment. aALS demonstrated slower progression and were predominantly cognitively unimpaired (ALS-ni) or showed an ALS-specific impairment. Neuroimaging revealed distinct patterns: jALS cases demonstrated posterior cortical atrophy and hypometabolism on FDG-PET, while aALS showed largely preserved brain volumes and limbic-subcortical hypometabolism.

INTERPRETATION: Specific FUS mutations (P525L, H517_Q519del) predispose to jALS with severe progression and premorbid cognitive impairments, supporting a genotype-phenotype association. Posterior cortical findings suggest neurodevelopmental delay rather than disease-related neurodegeneration. Genetic FUS screening may be warranted in patients with intellectual disability and motor signs, given emerging targeted therapies.},
}

@article {pmid42295787,
year = {2026},
author = {Zangrando, L and Buratti, E and Paron, F},
title = {TDP-43 Aggregation: The Healthy-Toxic Balance of the Prion-Like Domain.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e76119},
doi = {10.1002/advs.76119},
pmid = {42295787},
issn = {2198-3844},
support = {//AriSLA 2022-NOSRESCUEALS/ ; },
abstract = {TAR DNA-binding protein 43 (TDP-43) is a ubiquitously expressed RNA-binding protein that plays essential roles in RNA metabolism, including transcription, splicing, transport, and stability. Pathological TDP-43 aggregates have become a defining hallmark of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and a large subset of frontotemporal lobar degeneration (FTLD). In the last decade, increasing evidence has challenged the initial thought of TDP-43 condensates as a purely pathological event, highlighting instead the physiological relevance of reversible self-association, polymerization and liquid-liquid phase separation (LLPS) in regulating TDP-43 functions. In this review, we provide an integrated overview of the structural determinants governing TDP-43 two-faced polymerization, with a particular focus on the prion-like domain and its parallelism with prion proteins. Indeed, while physiological assemblies support normal RNA processing, the dysregulation of LLPS by either disease-associated mutations, altered RNA-binding, aberrant post-translational modifications, or proteolytic cleavage can promote the transition toward irreversible, pathogenic aggregates. Finally, we summarize strategies aimed at eliminating TDP-43 aggregates or modulating its phase-separation behavior. Altogether, this review frames TDP-43 polymerization in both healthy and pathological conditions, offering a prion-like centered view of TDP-43 proteinopathies.},
}

@article {pmid42296226,
year = {2026},
author = {Naumann, M and Kretschmer, S and Dorst, J and Lapp, H and Peikert, K and Petri, S and Gess, B and Wolf, C and Rödiger, A and Smesny, U and Pan-Montojo, F and Kerschen, P and Grehl, T and Prudlo, J and Regensburger, M and Ludolph, A and Günther, R and Brenner, D and Lee-Kirsch, MA and Hermann, A},
title = {Innate immune signaling as a potential pathomechanistic biomarker for distinct subtypes in amyotrophic lateral sclerosis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/21678421.2026.2663910},
pmid = {42296226},
issn = {2167-9223},
abstract = {Stimulation of the innate immune system has been implicated in ALS and particularly in distinct monogenic forms of ALS. To address whether this is of diagnostic value, we performed a proof-of concept study using qPCR to assess the Interferon score in blood samples of genetic ALS. 56.5% of genetic ALS patients showed significant IFN activation, highest in C9orf72HRE patients (77.3%). About half of FUS-ALS (52.2%), but none of SOD1-ALS patients demonstrated pathological IFN scores. The IFN score significantly correlated with the ALSFRS-R slope and inversely with the time to severe event as a survival surrogate in this genetic ALS cohort. IFN + patients were more likely to be male, showed more rapid disease progression and higher neurofilament levels. The IFN score might have the potential as a stratification and readout tool for biomarker-guided individualized therapy in ALS.},
}

@article {pmid42296263,
year = {2026},
author = {Fabry, V and Faruch-Bilfeld, M and El Khalfi, R and Acket, B and Al Achram, Y and Cintas, P},
title = {Whole-body muscle MRI improves diagnostic certainty in amyotrophic lateral sclerosis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/21678421.2026.2685160},
pmid = {42296263},
issn = {2167-9223},
abstract = {Introduction: Early diagnosis of amyotrophic lateral sclerosis (ALS) remains challenging due to the absence of a definitive biomarker and the difficulty of demonstrating widespread lower motor neuron (LMN) involvement. Whole-body muscle MRI (WB-MRI) enables comprehensive assessment of muscle involvement and may improve detection of LMN dysfunction. This study aimed to evaluate whether WB-MRI improves diagnostic certainty in ALS when combined with clinical and electromyography (EMG) assessment. Methods: In this prospective single-center study, 47 patients with ALS underwent clinical examination, EMG, and WB-MRI. Diagnostic classification according to the Awaji criteria was assessed using clinical and EMG data alone and after integration of MRI markers of LMN involvement, including fatty infiltration and muscle edema, or muscle edema alone as a surrogate marker. Results: WB-MRI identified additional LMN-involved regions in 27.7% of patients when both fatty infiltration and muscle edema were considered, and in 42.6% when considering muscle edema alone. This resulted in diagnostic upgrading in 14.9% and 25.5% of patients, respectively. The proportion of definite ALS increased from 8.5% to 17.0% when muscle edema alone was considered. MRI had limited impact on diagnostic classification according to the Gold Coast criteria. Among patients without LMN involvement on clinical and EMG assessment (all with bulbar-onset), 50% were reclassified after MRI. Conclusion: WB-MRI improves detection of LMN involvement and increases diagnostic certainty according to the Awaji criteria, with muscle edema appearing to be the most relevant MRI marker for integration into ALS diagnostic assessment.},
}

@article {pmid42297978,
year = {2026},
author = {Card, NS and Singer-Clark, T and Peracha, H and Iacobacci, C and Hou, X and Wairagkar, M and Fogg, Z and Offenberg, EC and Hochberg, LR and Stavisky, SD and Brandman, DM},
title = {Long-term independent use of an intracortical brain-computer interface for speech and cursor control.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {42297978},
issn = {1546-170X},
support = {N/A//Burroughs Wellcome Fund (BWF)/ ; N/A//Burroughs Wellcome Fund (BWF)/ ; N/A//Achievement Rewards for College Scientists Foundation (ARCS Foundation)/ ; A2295-R//VHA Office of Research and Development | Rehabilitation Research and Development Service (Rehabilitation Research & Development Service)/ ; 1DP2DC021055//U.S. Department of Health & Human Services | NIH | NIH Office of the Director (OD)/ ; AL220043//United States Department of Defense | Office of the Secretary of Defense (OSD)/ ; 23-SGP-652//Amyotrophic Lateral Sclerosis Association (ALS Association)/ ; },
abstract = {Brain-computer interfaces (BCIs) can provide naturalistic communication and digital access to people with severe paralysis by decoding neural activity associated with attempted speech and movement. Recent work has demonstrated highly accurate intracortical BCIs for speech and cursor control, but two critical capabilities needed for practical viability were unmet: independent at-home operation without researcher assistance and reliable long-term performance supporting accurate speech and cursor decoding. Here we demonstrate the independent and near-daily use of a multimodal BCI with novel brain-to-text speech and computer cursor decoders by a man with paralysis and severe dysarthria due to amyotrophic lateral sclerosis. Over nearly 2 years, the participant used the BCI for more than 3,800 h at home with no researchers present to maintain rich interpersonal communication with his family and friends, independently control his personal computer and sustain full-time employment-despite being paralyzed. He communicated 183,060 sentences-totaling 1,960,163 words-at an average rate of 56 words per minute. He labeled 92% of sentences as being decoded at least mostly correctly. In formal quantifications of performance where he was asked to say words presented on a screen, attempted speech was consistently decoded with more than 99% word accuracy (125,000 word vocabulary). The participant also used the speech BCI as keyboard input and the cursor BCI as mouse input to control his personal computer, enabling him to send text messages and emails and to browse the internet. These results demonstrate that intracortical BCIs have the potential to support independent use in the home, marking a critical step toward practical assistive technology for people with severe motor impairment.},
}

@article {pmid42297981,
year = {2026},
author = {Ding, DY and Bot, VA and Chen, KL and Groves, JW and Pálovics, R and Masuda, D and Farinas, A and Oh, HS and Wagner, V and Lu, N and , and Cruchaga, C and Isakova, A and Schott, JM and Wyss-Coray, T},
title = {Plasma proteomic signatures of cellular aging predict human disease.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {42297981},
issn = {1546-170X},
support = {AG072255//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; ARUK-PG2017-1946//Alzheimer's Research UK (ARUK)/ ; SG-666374-UK BIRTH COHORT/ALZ/Alzheimer's Association/United States ; },
abstract = {Aging is asynchronous across cells and organs. Here we tested whether plasma proteomics can be used to analyze cell type-specific aging. From analyses of over 7,000 plasma proteins measured in 60,542 individuals, we developed machine learning models to estimate the biological age of over 40 cell types spanning neuronal, immune, glial, endocrine, epithelial and musculoskeletal origins. We observed that 20-25% of individuals exhibited accelerated aging in a single cell type and 1-3% in 10 or more cell types. Cellular aging signatures were associated with disease status and predicted incident disease and mortality over 15 years of follow-up. Individuals with the APOE4 genotype showed older astrocytes but younger macrophages compared to APOE3 carriers, whereas the APOE2 genotype had inverse associations. Moreover, extreme astrocyte aging tripled the risk of incident Alzheimer's Disease in individuals with two APOE4 alleles, while youthful astrocytes reduced risk. Individuals with extremely aged compared to youthful skeletal myocytes exhibited a 12.7-fold higher risk of developing amyotrophic lateral sclerosis. In individuals who smoked, extreme respiratory epithelial cell aging was associated with a 58% higher lung cancer risk compared to smoking alone. Specific cellular vulnerabilities and cumulative cellular aging burden influenced survival, with youthful immune and neuronal cell types conferring protective effects. Finally, we developed a polycellular aging risk score that stratified mortality risk across cohorts and proteomics platforms. These findings establish a framework for quantifying human physiology at cellular resolution, revealing heterogeneous aging trajectories and their impact on disease susceptibility and resilience.},
}

@article {pmid42298083,
year = {2026},
author = {Al-Shami, AS and Anwar, MM},
title = {The lung-brain axis in neurodegeneration: inflammatory, immune, and vascular mechanisms with therapeutic implications.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {42298083},
issn = {1568-5608},
abstract = {Neurodegenerative and chronic pulmonary diseases represent major global health challenges and have widely been investigated separately. Emerging evidence indicates the existence of a lung-brain axis, through which pulmonary pathology and environmental exposures can influence neurological health. The current review highlights the mechanistic and clinical evidence linking chronic lung inflammation, air pollution, and immune dysregulation to the onset and progression of Alzheimer's disease (AD), Parkinson's disease (PD), Multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). A pathway-based framework is presented in which lung inflammation, systemic cytokine release, oxidative stress, blood-brain barrier disruption, immune priming, and protein misfolding mediate lung-to-brain communication. Associations between chronic obstructive pulmonary disease, asthma, particulate matter exposure, and adverse neurological outcomes including cognitive decline, brain atrophy, disease progression, and elevated neurodegenerative risk are emphasized. Specific mechanisms are addressed, including immune-mediated effects in multiple sclerosis, inhalation-driven protein aggregation in Parkinson's disease, and vascular and oxidative injury contributing to dementia and amyotrophic lateral sclerosis. COVID-19 is considered a clinical model of acute lung-brain axis disruption, demonstrating inflammation-driven neurocognitive consequences, and its role in this context was also highlighted. Additionally, potential preventive and therapeutic strategies are discussed, highlighting pulmonary health and environmental exposure reduction as modifiable factors that may help mitigate neurological disease. This integrative review underscores the clinical relevance of the lung-brain axis and calls for interdisciplinary strategies to improve neurological outcomes through pulmonary and environmental interventions.},
}

@article {pmid42299008,
year = {2026},
author = {Singh, NK and Singh, A},
title = {Mechanistic Perspectives of Icariin against Neuroinflammation: Taming Glial Activation.},
journal = {Mini reviews in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0113895575448388260306051328},
pmid = {42299008},
issn = {1875-5607},
abstract = {Glial-mediated neuroinflammation significantly contributes to major neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis. Inhibition of glial-mediated neuroinflammation is effective in treating neurodegenerative diseases. Although no permanent cure exists, considerable research aims to identify natural compounds that may slow the disease progression. Icariin is a naturally occurring flavonoid derived from the herb Herba epimedii and has been shown to have several medicinal benefits, including anti-aging, antioxidant, anti-inflammatory, and anti-apoptotic properties. Recent studies have indicated that Icariin, a potent prenylated flavonol glycoside, exhibits neuroprotective effects against glial-mediated neuroinflammation. Icariin attenuates glial pro-inflammatory responses and prevents neurotoxicity in cellular and animal models. Additionally, Icariin is speculated to facilitate neuronal functioning and survival in experimental conditions. The present review highlights the remarkable role of glial cells in neuroinflammatory processes subsequently neurodegeneration, and the potential of icariin to suppress glial-mediated neuroinflammation. We hope that this review will accelerate the pharmacological development of icariin as a potential therapeutic compound against glial-mediated neuroinflammation, which triggers the pathogenesis of several neurodegenerative disorders.},
}

@article {pmid42299014,
year = {2026},
author = {Kaur, H and Kaur, M and Sethi, GK and Kaur, AS and Mishra, A and Sharma, N},
title = {Pathogenic Proteins Driving ALS Pathogenesis: Molecular Mechanisms and Translational Therapeutic Perspectives.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273440191260226063811},
pmid = {42299014},
issn = {1996-3181},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of motor neurons, with protein aggregation as a central pathological hallmark. Key pathogenic proteins, including TDP-43, SOD1, FUS, and dipeptide repeat proteins (DPRs) from C9orf72 expansions, drive disease progression through diverse but converging mechanisms. TDP-43 proteinopathy, present in nearly all ALS cases, involves cytoplasmic mislocalization, misfolding, and aggregation, disrupting RNA processing, protein transport, and DNA repair. Similarly, SOD1 and FUS mutations promote toxic protein aggregation, impairing cellular homeostasis and contributing to neuronal dysfunction. C9orf72-derived DPRs exert toxicity by interfering with nucleocytoplasmic transport. The propagation of these pathogenic proteins between neurons and glia, often via prion-like mechanisms, underlies the characteristic spread of ALS pathology throughout the nervous system. Cellular protective responses, such as molecular chaperones and the ubiquitin-proteasome system, attempt to mitigate aggregation but are often overwhelmed in disease states. Mitochondrial dysfunction, oxidative stress, and disturbances in calcium homeostasis are also implicated, with evidence showing that SOD1 mutations can alter redox balance and mitochondrial function in both neurons and non-neuronal cells. Impaired DNA repair mechanisms, involving proteins such as TDP-43, FUS, NEK1, and VCP, have emerged as important contributors to ALS pathogenesis, linking protein aggregation to genomic instability. Recent therapeutic strategies focus on directly targeting misfolded proteins using small molecules, peptides, or antisense oligonucleotides to inhibit aggregation or enhance clearance, offering hope for disease modification. Understanding the interplay between protein aggregation, impaired RNA metabolism, and cellular stress responses is crucial for developing effective translational therapies for ALS.},
}

@article {pmid42299015,
year = {2026},
author = {Singh, G and Singh, S and Sarkar, A and Sandhu, NK},
title = {Amyotrophic Lateral Sclerosis: Therapeutic Innovations and Evolving Regulatory Approaches.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273438968260318203940},
pmid = {42299015},
issn = {1996-3181},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive degeneration of upper and lower motor neurons, leading to muscle weakness, paralysis, and respiratory failure. Despite extensive research, riluzole and edaravone remain the only globally approved disease-modifying therapies, offering modest survival benefits. This review summarizes current understanding of ALS pathogenesis, approved pharmacological treatments, and emerging gene-, RNA-, and cell-based therapeutic strategies. Particular emphasis is placed on regulatory considerations and evolving clinical trial designs in ALS drug development. The accelerated approval and subsequent withdrawal of sodium phenylbutyrate-taurursodiol (AMX0035) are discussed as a critical case study highlighting the challenges of regulatory flexibility in rare, fatal diseases. Advances in biomarker development, especially neurofilament light chain, are examined for their growing role in trial design and therapeutic evaluation. Collectively, these insights underscore a shift toward biomarker- informed and precision-based approaches that may improve future ALS therapeutic development.},
}

@article {pmid41160352,
year = {2026},
author = {Bae, K and Park, Y and Ryu, H and Lee, J and Park, SW},
title = {A Longitudinal Study of the Relationship between Identity Development Processes and Self-Esteem among Korean College Freshmen.},
journal = {Journal of youth and adolescence},
volume = {55},
number = {3},
pages = {780-794},
pmid = {41160352},
issn = {1573-6601},
support = {NRF-2023S1A5A2A01078792//the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea/ ; },
abstract = {Self-esteem may serve both as a psychological resource that facilitates personal identity development processes and as an outcome of a consolidated identity. However, longitudinal evidence remains limited. This study tracked 641 South Korean first-year college students (48.0% women; Mage = 19.13) across four waves spaced three months apart during their first academic year to test bidirectional links between Luyckx et al.’s (2008) five dimensions of personal identity processes (exploration in breadth, exploration in depth, commitment making, identification with commitment, ruminative exploration) and self-esteem. Random-intercept cross-lagged panel models were used to examine how changes in each of the processes may follow and be followed by changes in self-esteem. Results highlight initial volatility and gradually increasing engagement in personal identity development processes. Higher self-esteem predicted greater engagement in identity processes, and a stronger sense of identification with commitment predicted higher self-esteem later in the year but not earlier. By demonstrating that self-esteem is not merely an outcome of identity development but also a psychological resource facilitating identity development, these findings contribute to the literature on the development of the self-system in youth.},
}

@article {pmid41267135,
year = {2025},
author = {Zreik, M and Redding, A and Santarossa, S},
title = {From engagement to evidence: a scoping review of qualitative and quantitative measures of adult patient engagement in research.},
journal = {Research involvement and engagement},
volume = {11},
number = {1},
pages = {136},
pmid = {41267135},
issn = {2056-7529},
support = {SOE-2022C2-28911/PCORI/Patient-Centered Outcomes Research Institute/United States ; },
abstract = {BACKGROUND: Patient engagement in research has been found to improve the quality and relevance of research findings. Quantifying levels of patient engagement may be beneficial in measuring engagement quality, yet tools for this purpose remain scarce. A scoping review was conducted to summarize and analyze existing tools used to measure patient engagement in research for the purpose of assessing the content validity of Hamilton et al.’s Patient Engagement In Research Scale (PEIRS). METHODS: The electronic database Ovid MEDLINE was used to conduct a search related to keywords and controlled vocabulary from 2017 - November 10, 2023, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews checklist. Articles were included if they quantitatively or qualitatively measured any outcome of patient engagement in research, exclusively with patients as participants. Data extraction, completed in Microsoft Excel, included the name of the research engagement tool, the type of tool (i.e., questionnaire, survey, or scale), sample size, source, and characteristics, and time frame of data collection. RESULTS: Five articles were ultimately included in this scoping review after an initial search returned 1719 citations. The most common reason for exclusion during the full text review stage was that articles were review articles. Of selected articles that included demographic data, the majority of participants were women and White. Articles highlighted areas for improvement in existing tools, including the need for patient collaboration at each stage of the research process and stronger communication between researchers and patient partners. CONCLUSIONS: Efforts to effectively measure patient engagement in research remain scant. Included studies were limited by inconsistency in defining “patient engagement” and a lack of demographic data collection.},
}

@article {pmid41372737,
year = {2025},
author = {Shah, A and Doshi, G},
title = {Stress and neurodegeneration: mechanistic insights and therapeutic opportunities for preserving brain resilience.},
journal = {Acta neurologica Belgica},
volume = {},
number = {},
pages = {},
pmid = {41372737},
issn = {2240-2993},
abstract = {Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and Amyotrophic Lateral Sclerosis are strongly influenced by persistent stress, which accelerates both their onset and progression. This review explores the intricate interplay between chronic stressors, oxidative and metabolic imbalances, protein misfolding, inflammatory responses, and psychosocial adversity, and their cumulative impact on the aging brain’s capacity for homeostasis. The loss of cellular resilience due to prolonged stress leads to maladaptive outcomes, including mitochondrial dysfunction, sustained neuroinflammation, breakdown in proteostasis, and disruption of hypothalamic-pituitary-adrenal axis signaling, all of which amplify neuronal vulnerability. The detailed molecular pathways that underlie these phenomena, the article identifies key mediators such as Reactive Oxygen species, mitochondrial regulators, heat shock proteins, and proinflammatory cytokines that drive neurodegeneration. A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar up to 2025. Eligible publications included original research articles, clinical studies, and systematic reviews focusing on stress-related molecular pathways, oxidative metabolism, proteostasis, neuroinflammation, and therapeutic interventions in aging and neurodegenerative diseases. A qualitative synthesis of these studies was performed to identify key mechanisms, biomarkers, and emerging treatment strategies relevant to stress-induced neurodegeneration. Further, the review evaluates both established and emerging interventions aimed at mitigating these stress-driven processes. Lifestyle modifications such as aerobic exercise, calorie restriction, and cognitive behavioural therapies complement pharmacological agents like antioxidants, chaperone modulators, and anti-inflammatory drugs to enhance brain resilience and delay disease onset. Recent advances in the field, including integrated multi-omics profiling, biomarker discovery, and medicine approaches, promise to refine our ability to satisfy patients and deliver targeted therapies based on individual stress profiles. Additionally, the article discusses the neuroimmune-gut axis and the potential for interventions targeting microbiome-related inflammation. Early detection of stress-related biomarkers and personalized strategies holds considerable promise for improving clinical outcomes, enabling earlier diagnosis, and fostering tailored therapies that preserve cognitive function and independence in aging populations.},
}

@article {pmid41511493,
year = {2026},
author = {Yu, J and Zhang, J and Jiang, Y and Ma, C and Wang, W and Zhang, K and Tian, R and Chen, H and Han, H and Sun, H and Peng, C and Zhang, H and Xu, X},
title = {Identification of a novel nonsense variant in ARR3 in a family with early-onset high myopia.},
journal = {Genes & genomics},
volume = {48},
number = {3},
pages = {409-418},
pmid = {41511493},
issn = {2092-9293},
support = {81873677//Natural Science Foundation of China/ ; },
abstract = {BACKGROUNDS: Early-onset high myopia (EoHM) is a severe refractive error that can result in significant vision loss. A known genetic cause involves mutations in the X-linked Arrestin-3 (ARR3) gene, which typically presents with a female-limited inheritance pattern, in which asymptomatic fathers transmit the variant to their affected daughters. OBJECTIVE: This study aims to present a unique case of EoHM characterized by paternal transmission of a novel ARR3 variant and to explore potential underlying molecular mechanisms through an exploratory bioinformatic analysis. METHODS: We collected the clinical phenotypes for the family and sequenced the blood using NGS and Sanger sequencing. Bioinformatic analysis of the GSE5338 dataset revealed a potential interaction network involving ARR3, NR2E3 (a photoreceptor development regulator), and OPN1MW (a cone opsin gene). RESULTS: The proband exhibited severe EoHM with stretched axial lengths (ALs) (24.09 and 24.43 mm) and pronounced myopic astigmatism. The asymptomatic father passed on a new nonsense variation in the ARR3 gene, c.7A > T (p.K3Ter). Exploratory bioinformatic analysis of a murine retinal dataset hinted at a possible regulatory relationship, wherein overexpression of the photoreceptor transcription factor Nr2e3 might be linked to the downregulation of Arr3 and the cone opsin gene Opn1mw. CONCLUSIONS: This study reports a novel ARR3 mutation within a family affected by EoHM, expanding the known mutational spectrum of this disease and offering vital insights for genetic counseling. Furthermore, our bioinformatic analysis has generated a hypothesis that NR2E3-mediated downregulation of both ARR3 and OPN1MW may contribute to the disease phenotype, a link that warrants future investigation in human models.},
}

@article {pmid41530568,
year = {2026},
author = {Qingqing, Z and Ruiyi, L and Zaijun, L},
title = {Graphene-oxide dual-stabilized Mg0.3AlVCuZn lightweight high-entropy alloy nanoparticles with ultrahigh catalytic activity, selectivity and stability for electrochemical detection of doxorubicin in human urine.},
journal = {Mikrochimica acta},
volume = {193},
number = {2},
pages = {90},
pmid = {41530568},
issn = {1436-5073},
support = {2021YFA0910200//National Key Research and Development Program of China,China/ ; 2021YFA0910200//National Key Research and Development Program of China,China/ ; },
abstract = {The practical applications of lightweight high-entropy alloys (HEAs) in catalysis and electrochemical sensors are hindered by inadequate chemical stability and catalytic activity. This study presents one groundbreaking synthesis strategy for fabricating Mg0.3AlVCuZn HEA nanoparticles by integrating histidine/serine-functionalized boron-doped graphene quantum dot (HSB-GQD). Mg2+, Al3+, V5+, Cu2+ and Zn2+ are coordinated with HSB-GQD to Me-HSB-GQD complex,followed by thermal annealing and controlled oxidative post-treatment. The resulting Mg0.3AlVCuZn shows single-phase octahedral morphology with a small size of about 50 nm and dual graphene-oxide shielding. Unique structure fully exposes active sites and enhances structural and chemical stability across acidic/alkaline media, interface electron transfer, and improves the affinity with polar electrolyte. The s-p-d orbital hybridization among Mg/Al (s, p) and V/Cu/Zn (s, d) induces electron redistribution to optimize adsorption energetics and catalytic specificity. Mg0.3AlVCuZn shows ultrahigh catalytic activity that is more than 2-fold that of Au nanoparticles. The electrochemical sensor with Mg0.3AlVCuZn exhibits a broad linear range (0.01–100 µM), ultra-low detection limit (0.0057 µM, S/N = 3), and robust selectivity and long-term stability for electrochemical detection of doxorubicin in human urine. This study also offers a generalizable platform for engineering lightweight HEAs with tailored stability and multifunctional efficacy, bridging advances in catalysis, sensing and energy storage.},
}

@article {pmid41697604,
year = {2026},
author = {Tutan, MB and Tutan, D},
title = {A bibliometric analysis of diverticulitis: global trends and future directions.},
journal = {Updates in surgery},
volume = {},
number = {},
pages = {},
pmid = {41697604},
issn = {2038-3312},
abstract = {Diverticulitis, an inflammation of colonic diverticula, poses significant clinical challenges due to its rising global incidence and potential complications. Modern dietary habits, sedentary lifestyles, and aging populations contribute to its increasing prevalence, with a notable rise among younger adults. Despite extensive research, a comprehensive assessment of global research trends remains limited. This study conducts a bibliometric and statistical analysis of diverticulitis research (1980–2024) to identify key trends, influential studies, international collaborations, and the correlation between national GDP and research output while projecting future publication trends. A bibliometric analysis of the Web of Science database identified 4459 publications, with 3653 articles, reviews, and meeting abstracts included. The United States led global research contributions (34.22%), followed by Italy and Germany. A strong positive correlation was found between national GDP and research productivity (r = 0.900, P < 0.001). Future projections estimate 289 publications in 2025. The most cited study was Rafferty et al.‘s 2006 “Practice parameters for sigmoid diverticulitis.” Citation analysis revealed growing academic interest, particularly in the past two decades. Diverticulitis has become a global health concern, driven by lifestyle changes and aging demographics, with an increasing incidence among younger populations. This study highlights a marked rise in research activity, predominantly in economically developed nations, and underscores the need for further investigation into prevention, diagnosis, and management strategies. These findings offer valuable insights for clinicians and researchers, guiding future research directions in diverticulitis.},
}

@article {pmid41840453,
year = {2026},
author = {Morgan, TL and Carroll, K and Waqar, A and Hudek, N and Mosa, M and Richards, DP and Meeking, K and Granieri, M and Smith, M and Walz, M and Etherington, C and Marlin, S and Gillies, K and Presseau, J and Brehaut, JC},
title = {A meta-review of patient engagement, shared decision-making, and factors influencing equity-deserving populations' participation in clinical trials.},
journal = {Research involvement and engagement},
volume = {12},
number = {1},
pages = {},
pmid = {41840453},
issn = {2056-7529},
support = {PJT-169055/CAPMC/CIHR/Canada ; PJT-169055/CAPMC/CIHR/Canada ; },
abstract = {BACKGROUND: Many equity-deserving populations, including those facing structural health inequities, lack support to participate in clinical trials while facing barriers to participation. Two approaches—patient engagement (PE) and shared decision-making (SDM)—can help trialists better understand and address such barriers. PE can improve the relevance of trials to silenced communities while SDM can align participation decisions among socially disadvantaged groups with their values, needs, and preferences, which may help overcome health inequities. Further, Indigenous community engagement is vital to address the effects of colonialism and promote Indigenous self-determination and health equity. The extent to which existing reviews have identified common barriers, enablers, and strategies across equity-deserving groups and discussed PE and SDM concepts is unclear. PURPOSE: (1) To describe which equity-deserving populations have been the focus of reviews on clinical trial participation and which barriers, enablers, and strategies are relevant to them (2) to explore the extent to which PE and SDM are discussed in these reviews. METHODS: We searched for English-language reviews (including any study design) summarizing trial participation barriers, enablers, and/or strategies among equity-deserving populations in five peer-reviewed databases. We coded data on the (1) equity-deserving population(s) of focus, (2) barriers, enablers, or interventions/strategies mentioned, (3) PE reported, (4) Indigenous community engagement reported, and (5) SDM outcomes discussed. RESULTS: Findings from 100 reviews showed that some equity-deserving populations have been represented more than others (e.g., 76% on racially, ethnically, culturally, or linguistically diverse populations; 29% on sex and gender populations; 2% on educationally disadvantaged populations). More reviews described barriers (84%) than enablers (31%) or strategies to improve participation (69%). Forty-five reviews (45%) reported PE while 11 (11%) reported Indigenous community engagement. Many reviews (74%) mentioned SDM outcomes (i.e., 9/11 [81.8%] outcomes from Gillies et al.’s internationally agreed core outcome set); however, few reviews (29%) discussed SDM outcomes in detail. CONCLUSIONS: Our findings suggest that PE and SDM could be more broadly applied among multiple equity-deserving groups to better serve disadvantaged communities. We advocate for an expanded focus on less-researched equity-deserving groups, improved PE reporting, prioritization of patient outcomes, and engagement with patients and Indigenous communities.},
}

@article {pmid41863721,
year = {2026},
author = {Maidh, A and Kalra, P and Khan, H and Silakari, P and Grewal, AK},
title = {Circadian disruption as a driver and target in neurodegenerative diseases: from molecular mechanisms to chronotherapeutic strategies.},
journal = {Metabolic brain disease},
volume = {41},
number = {1},
pages = {},
pmid = {41863721},
issn = {1573-7365},
abstract = {The Circadian System is a complex network of coordinated clocks that regulates the organism’s internal clock in synchronisation with the outside world. These rhythms are controlled by genetically controlled positive and negative transcriptional-translational feedback loops (TTFL) that generate 24-hour oscillations in the protein level and mRNA of core circadian components. Circadian disruption is recognised as a significant contributor to the molecular pathogenesis of neurodegenerative illnesses, as disease-specific alterations in clock gene expression and melatoninergic signalling have been identified as possible early-stage molecular indicators. Emerging evidence suggests a link between dysregulated circadian rhythms and neurodegenerative diseases, implying that the changes in circadian function may play a critical role in the development and progression of neurodegenerative diseases. The correlation between circadian rhythm and neurodegeneration is highly promising for developing treatment and promoting healthy lifestyle measures. This review article primarily focuses on how abnormalities in circadian rhythms may increase the risk of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and Amyotrophic Lateral Sclerosis (ALS). Applying knowledge from pre-clinical and translational research on neurodegenerative diseases is crucial for lowering the risks of neurodegeneration and improving the symptoms and quality of life of people with neurodegenerative diseases through approaches that restore circadian rhythm in the context of precision medicine. Understanding this interaction holds promise for developing therapeutic approaches to support a healthy lifestyle.},
}

@article {pmid41870724,
year = {2026},
author = {Darwish, S and Ballout, S and Shi, L and Negron, R and Cooley, ME},
title = {Social Ties and Behavioral Diffusion of Tobacco Use in Arab American Networks.},
journal = {Journal of immigrant and minority health},
volume = {},
number = {},
pages = {},
pmid = {41870724},
issn = {1557-1920},
abstract = {Arab Americans (AAs) exhibit elevated rates of tobacco use, often influenced by their social networks (SN). Despite this, research has not comprehensively explored the mechanisms through which these relationships sustain tobacco use, and broader studies on social SNs provide limited insight into the influential SN attributes and interactions affecting AA communities. Guided by Berkman et al.’s (2000) SN and health framework, this study examined associations between SN structure, composition, relational and communication dynamics, and tobacco use among AAs. Variables included network size, density, SN compositional and demographic characteristics, contact modality and frequency, and relationship closeness. Data were collected through a cross-sectional survey of 178 AA adults in Massachusetts and analyzed using multivariate logistic regression. Overall, 51.7% of participants were current tobacco users; 45.5% reported hookah use, 13.5% cigarette use, and 18.5% used multiple products. Features of SNs associated with decreased odds of tobacco use included having larger SNs (OR = 0.38, 95% CI: 0.20–0.70), higher proportions of non-tobacco users (OR = 0.98), frequent in-person interactions with non-tobacco users (OR = 0.71), and stronger ties to non-tobacco users (OR = 0.074). Networks with greater Arab representation initially appeared protective but, in adjusted models, were associated with higher use (OR = 1.45), suggesting cultural identity and affiliation may reinforce smoking norms. Gender patterns also differed : networks with more women initially appeared protective, but after adjustment this association reversed (OR = 1.53), highlighting nuanced sociocultural impacts on behavioral change among Arab men and women following migration. Conversely, increased tobacco use was associated with greater contact with tobacco users, particularly through virtual modalities (OR = 1.027), and closer relationships with tobacco users (OR = 5.54). The findings suggest that tobacco use is propagated through both imitation and social reinforcement within strongly connected, homogenous networks. The study offers valuable insights into overlooked SN attributes and relational mechanisms relevant to understanding the transmission of tobacco use behaviors within AA populations. Identifying specific relational attributes may inform culturally tailored cessation interventions that leverage influential network members and key actors, strong social ties, and targeted modes of interaction, both in-person and digital, to enhance tobacco control strategies in AA communities.},
}

@article {pmid41894075,
year = {2026},
author = {Kuwar, OK and Tejpal, S and Sharma, V and Sharma, A and Rao, A and Attri, M and Pallavi, and Dhingra, MS},
title = {Therapeutic potential of sulforaphane in neurodegenerative diseases: mechanistic Insights into Nrf2, NF-κB, TrkB, SIRT1, MAPK, and JAK/STAT signalling pathways.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {},
pmid = {41894075},
issn = {1573-4978},
abstract = {Neurodegenerative diseases, including Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis, are chronic and progressive disorders distinguished by neuronal dysfunction, oxidative stress, neuroinflammation, and abnormal protein aggregation. Due to the multifactorial nature of these disorders, current pharmacotherapies provide limited symptomatic relief without altering disease progression. Sulforaphane, a naturally occurring isothiocyanate abundant in cruciferous vegetables like broccoli, has emerged as a potent neuroprotective compound owing to its pleiotropic effects on key cellular signalling pathways. This review provides a thorough overview of the mechanistic insights underlying SFN’s neuroprotective potential, with a focus on the modulation of key signalling pathways such as Nrf2/ARE, NFĸB, BDNF/TrkB, SIRT1, MAPK, and JAK/STAT. Through the activation of antioxidant defenses and suppression of inflammatory cascades, SFN effectively mitigates neuronal damage and supports cellular homeostasis. Preclinical studies consistently demonstrate SFN’s ability to attenuate oxidative stress, inhibit apoptosis, preserve mitochondrial function, and improve neurobehavioral outcomes. While limited clinical evidence supports its safety and bioactivity, further investigations are needed to establish its therapeutic utility in human populations. Overall, SFN represents a promising natural compound with significant potential for the prevention and management of neurodegenerative diseases through multi-targeted pathway modulation.},
}

@article {pmid42009918,
year = {2026},
author = {G Diebo, B and E Nassar, J and Lafage, R and Challier, V and Pesenti, S and Lafage, V},
title = {Distinguishing reactive scoliosis: clinical presentation, pathophysiology and a proposed clinical framework.},
journal = {European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society},
volume = {},
number = {},
pages = {},
pmid = {42009918},
issn = {1432-0932},
abstract = {Purpose: This study introduces "reactive scoliosis" as an umbrella term formalizing various scoliosis subtypes that arise secondary to lumbar disc herniation, spondylolisthesis, and benign tumors. It aims to synthesize current evidence on the clinical presentations, pathophysiology, and surgical management of these subtypes, and to propose a preliminary clinical framework to guide their differentiation and treatment.Methods: A comprehensive literature search was conducted in PubMed/MEDLINE, Embase, and Scopus from inception through October 2025, following PRISMA guidelines. Search terms included combinations of "scoliosis" with "lumbar disc herniation", "spondylolisthesis", "osteoid osteoma", "osteoblastoma", and "ganglioneuroma". Studies were included if they addressed pathophysiology, clinical presentation, radiographic features, or surgical outcomes of reactive scoliosis subtypes. Two independent reviewers extracted data on curve magnitude, vertebral rotation, trunk shift, and surgical response.Results: Each reactive scoliosis subtype demonstrates distinct clinical and radiographic characteristics. Spasm scoliosis from lumbar disc herniation presents with short lumbosacral curves, minimal apical rotation, and significant coronal imbalance, typically resolving after discectomy. Pure spasm scoliosis from spondylolisthesis similarly resolves following fusion alone, while olisthetic scoliosis, characterized by vertebral rotation at the slip site rather than the curve apex, requires additional rotational correction. Tumor-driven scoliosis, including osteoid osteomas, osteoblastomas, and ganglioneuromas, demands individualized imaging and surgical strategies, with staged approaches warranted in structurally destructive cases.Conclusion: Accurate identification of reactive scoliosis subtypes is critical for surgical planning. The proposed expanded clinical framework, building upon Guo et al.'s modified Crostelli classification, offers surgeons a structured approach to differentiate these etiologies and optimize management. Prospective studies are needed to validate the algorithm and refine its clinical applicability.Keywords: Reactive scoliosis; Spasm scoliosis; Olisthetic scoliosis; Spondylolisthesis; Lumbar disc herniation},
}

@article {pmid42036486,
year = {2026},
author = {Assefa, M and Tsegaye, A and Addissie, A and Worku, A},
title = {Establishing population-based reference intervals for hematological parameters among apparently healthy adults in Northwest Ethiopia, 2023.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-50237-3},
pmid = {42036486},
issn = {2045-2322},
support = {VPRTT/PY-002/20021//Addis Ababa University Thematic Research Fund/ ; VPRTT/PY-002/20021//Addis Ababa University Thematic Research Fund/ ; VPRTT/PY-002/20021//Addis Ababa University Thematic Research Fund/ ; VPRTT/PY-002/20021//Addis Ababa University Thematic Research Fund/ ; },
abstract = {Ethiopian diagnostic facilities currently use Western hematological reference ranges, lacking national standardization. This study establishes hematological reference values for healthy adults in Northwest Ethiopia through a population-based cross-sectional study conducted from June to August 2023. Whole blood samples from 759 participants were analyzed using the Siemens ADVIA-560 hematology analyzer. Data were processed with Stata 17.0, and reference intervals (RIs) were calculated for the central 95% of the distribution, with gender & altitude differences assessed via the Mann-Whitney U test (p < 0.05). Sex and altitude based partitioning was done using Harris & Boyd’s Z-test and Lahti et al.’s proportion criteria. Results showed significant variations by sex and altitude, with males exhibiting higher median values for several hematological parameters. The combined 95% reference intervals (RIs) were: WBC (3.11–9.89 × 10[9]/L), NEU (0.96–6.54 × 10[9]/L), LYM (0.69–2.89 × 10[9]/L), MON (0.31–1.46 × 10[9]/L), and BAS (0.05–0.42 × 10[9]/L), with corresponding differential percentages also established. Sex-specific RIs were defined for key parameters. In men: RBC (4.54–6.39 × 10[12]/L), HGB (13.68–19.21 g/dL), HCT (41.39–57.01%), MCHC (32.01–34.91 g/dL), and PLT (127.10–367.10 × 10[9]/L); and in women: RBC (4.17–5.55 × 10[12]/L), HGB (12.51–16.39 g/dL), HCT (37.91–48.89%), MCHC (31.51–34.70 g/dL), and PLT (146.22–411.00 × 10[9]/L). Altitude-based stratification further revealed higher values at high altitude. In men, monocytes, eosinophils, RBC, HGB, HCT, and PLT were elevated, while in women, higher values were observed for neutrophils, monocytes, basophils, HGB, HCT, MCV, and MCH. These findings demonstrate that hematological reference intervals vary by sex and altitude among healthy adults in Northwest Ethiopia. The study highlights the potential value of using locally derived and context-specific reference intervals to improve interpretation of laboratory results. Further multicenter validation studies across diverse Ethiopian populations are recommended to support their application in clinical practice and research.},
}

@article {pmid42260986,
year = {2026},
author = {Sun, X and Dong, J and Liang, X and Peng, J and Chen, Y and Yin, R and Tan, T and Bai, L and Lan, K},
title = {PFN1 inhibits lytic replication of Kaposi sarcoma-associated herpesvirus through SQSTM1/p62-mediated selective autophagy targeting the KSHV helicase.},
journal = {Autophagy},
volume = {},
number = {},
pages = {1-16},
doi = {10.1080/15548627.2026.2686417},
pmid = {42260986},
issn = {1554-8635},
abstract = {Kaposi sarcoma-associated herpesvirus (KSHV), an oncogenic virus associated with several malignancies, including Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease, harbors a DNA replication helicase encoded by ORF44 that is crucial for viral replication and pathogenesis. In this study, we identified the host PFN1 (profilin 1), a well-known actin-binding factor, as an inhibitor of KSHV lytic replication functioning via the macroautophagy/autophagy-lysosomal degradation pathway targeting ORF44. Mechanistic analyses revealed that PFN1 interacts with ORF44, leading to enhanced polyubiquitination of PFN1. Notably, the E3 ubiquitin ligase TRIM37 (tripartite motif containing 37) facilitates the polyubiquitination of lysine residues at position 116 of PFN1, which serves as a critical recognition motif for the cargo receptor SQSTM1/p62 (sequestosome 1), which is pivotal for the subsequent autophagic degradation of ORF44. Overall, our findings revealed a previously uncharacterized antiviral function of PFN1, highlighting its potential as a novel therapeutic avenue for the treatment of KSHV-associated malignancies.Abbreviations: ALS: amyotrophic lateral sclerosis; Baf A1: bafilomycin A1; co-IP: co-immunoprecipitation; KSHV: Kaposi sarcoma-associated herpes virus; LIR: LC3-interacting region; PFN1: profilin 1; SQSTM1/p62: sequestosome 1; TRIM37: tripartite motif containing 37; UBA: ubiquitin-associated domain.},
}

@article {pmid42282797,
year = {2026},
author = {Yusuf, IO and Silva, RLA and Amoako, GG and Thompson, PR and Xu, Z},
title = {PAD2 knockout reduces myelin protein aggregates, modulates neuroinflammation and protects motor neurons, axons and neuromuscular junction in a SOD1-ALS mouse model.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.05.30.729013},
pmid = {42282797},
issn = {2692-8205},
abstract = {BACKGROUND: Dysregulated peptidyl deiminase 2 (PAD2) and aberrant protein citrullination (PC), a posttranslational modification (PTM), are involved in various inflammatory and neurodegenerative diseases. We previously showed in transgenic mice and postmortem human tissues that PC and PAD2 are altered in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by motor neurons loss, paralysis, and death. Herein, we investigated the role of PAD2 in ALS by PAD2 knockout in a SOD1-ALS mouse model.

METHODS: To investigate the role of PAD2-induced citrullination in ALS pathogenesis, we generated PAD2 knockout (PAD2KO) in SOD1 [G93A] ALS mouse model and investigated the consequent modulation on the neuropathology and clinical symptoms, using molecular biology techniques such as qPCR, Western blotting, confocal microscopy, and electron microscopy. Additionally, we identified C3 as being citrullinated in human ALS using ionFinder.

RESULTS: Our results show that PAD2KO blocked the increased PC and reduced myelin basic protein (MBP) aggregates in the ALS model. PAD2KO also improved motor neuron survival and the integrity of myelin, axons, and neuromuscular junctions, and reduced microgliosis in the white matter and C3 protein levels in astrocytes. Clinically, data from monitoring the body weight changes suggests that PAD2KO modulates the course of the disease in the ALS mouse model, accelerating the onset while slowing the progression after the onset, and modestly extending the survival of male mice.

CONCLUSION: These results show that PAD2 is responsible for the increased PC in ALS and PC contributes to neuroinflammation and degeneration of motor neurons and myelinated axons. The modest modulation of the disease phenotype suggests that the role of PC in ALS is complex, involving altered PC in numerous proteins and in multiple cell types. Future studies are needed to investigate how PC modulates individual protein functions in various cell types to understand the contribution of PC to ALS pathogenesis.},
}

@article {pmid42283221,
year = {2026},
author = {Scozzari, S and Columbro, SF and Favagrossa, M and Tortarolo, M and Cagnotto, A and Salmona, M and De Marco, G and Bendotti, C and Calvo, A and Pasetto, L and Bonetto, V},
title = {Effects of Lysine Deacetylation Inhibition Alone or in Combination With Arimoclomol on TDP-43 Proteinopathy.},
journal = {Journal of neurochemistry},
volume = {170},
number = {6},
pages = {e70493},
pmid = {42283221},
issn = {1471-4159},
support = {RF-2018-12365614//Ministero della Salute/ ; GATTALS//AriSLA/ ; },
mesh = {Animals ; *Histone Deacetylase Inhibitors/administration & dosage/pharmacology ; Humans ; Mice ; Acetylation/drug effects ; *Lysine/metabolism/antagonists & inhibitors ; *TDP-43 Proteinopathies/drug therapy/metabolism/pathology ; Mice, Transgenic ; Vorinostat/administration & dosage ; *DNA-Binding Proteins/metabolism ; Male ; },
abstract = {Cytoplasmic inclusions containing TAR DNA-binding protein 43 kDa (TDP-43) are recognized as a major pathological feature of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Peptidyl-prolyl cis-trans isomerase A (PPIA) interacts with TDP-43 and influences its aggregation and function. This interaction is facilitated by PPIA Lys-acetylation. Here, we investigated whether restoring lysine acetylation homeostasis exerts protective effects on TDP-43 proteinopathy in vitro and in vivo and how this relates with PPIA. We found that vorinostat/SAHA, a broad-spectrum histone deacetylase (HDAC) inhibitor that increases PPIA acetylation, is able to reverse TDP-43 mislocalization in a cellular model of TDP-43 proteinopathy. We confirmed its effects in peripheral blood mononuclear cells from ALS patients and explored its impact on TDP-43 proteinopathy and PPIA acetylation in the Thy1-hTDP-43 mouse model. Thy1-hTDP-43 mice treated with SAHA showed a delayed onset of TDP-43 pathology, associated with PPIA nucleus-cytoplasm redistribution, lower neurodegeneration and neuroinflammation, and improved neuromuscular function markers. However, these effects were transient. When combined with arimoclomol, a heat shock protein co-inducer, a mitigation of the neurodegeneration was sustained. A synergistic effect was observed in periphery, greatly enhancing tubulin acetylation and reducing phosphorylated TDP-43 accumulation in the sciatic nerve and acetylcholine receptor γ-subunit expression in gastrocnemius muscle. This study suggests that HDAC inhibition could be beneficial in restoring TDP-43 localization and function through multiple mechanisms, including modulation of PPIA acetylation. The combination of lysine deacetylation inhibition and arimoclomol shows a synergistic effect in vivo and has potential as a therapeutic approach for patients.},
}

Animals
*Histone Deacetylase Inhibitors/administration & dosage/pharmacology
Humans
Mice
Acetylation/drug effects
*Lysine/metabolism/antagonists & inhibitors
*TDP-43 Proteinopathies/drug therapy/metabolism/pathology
Mice, Transgenic
Vorinostat/administration & dosage
*DNA-Binding Proteins/metabolism
Male

@article {pmid42283246,
year = {2026},
author = {Fikry, H and Saleh, LA and Sadek, DR},
title = {Histological and Tissue-Level Outcomes of Stem Cell Therapies in Neurodegenerative Disorders: A Systematic Review.},
journal = {Clinical anatomy (New York, N.Y.)},
volume = {},
number = {},
pages = {},
doi = {10.1002/ca.70147},
pmid = {42283246},
issn = {1098-2353},
abstract = {Neurodegenerative diseases, which afflict millions worldwide and threaten public health, have no cure. Neurodegenerative diseases lack effective therapies, burdening society and the economy. Over the past 20 years, regenerative cell therapy (stem cell therapy) has advanced, opening novel neurodegenerative disease treatments. Thus, the current review aimed to systematically highlight experimental and clinical studies of potentially effective therapeutic strategies for stem cells and report histological, cellular, or ultrastructural outcomes following stem cell interventions in neurodegenerative diseases. PRISMA-compliant computerized literature searches of PubMed, Scopus, and Web of Science identified studies on embryonic, induced pluripotent, mesenchymal, or neural stem cells (NSCs) in neurodegenerative disease models and histological and tissue-level outcomes. Search terms included nervous system diseases, histology, neuron regeneration, stem cells, stem cell treatment, and transplantation. Peer-reviewed articles published between 2000 and 2025 were selected. Experimental animal and clinical studies that reported histological or tissue-level results after stem cell treatments were included. Eighty-six studies met the eligibility criteria, covering models of Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and Huntington's disease. Across these studies, stem cell therapies were linked to improved neuron survival, better synaptic structure, diminished gliosis, and some restoration of tissue structure. These effects depended on the type of stem cell used, the disease model, and how the treatment was given. Overall, the evidence suggests that stem cell therapies can lead to significant histological and tissue-level improvements in neurodegenerative diseases, supporting their potential for regeneration. Further standardized and translational studies are needed to clarify the underlying mechanisms and improve treatment strategies.},
}

@article {pmid42283497,
year = {2026},
author = {Turner, ED and Twelvetrees, AE},
title = {The Long Haul: Microtubule Motors as the Essential Supply Line for Neuronal Longevity.},
journal = {Journal of neurochemistry},
volume = {170},
number = {6},
pages = {e70496},
pmid = {42283497},
issn = {1471-4159},
support = {220192/Z/20/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; *Microtubules/metabolism/physiology ; Animals ; *Neurons/metabolism/physiology ; *Molecular Motor Proteins/metabolism/genetics ; Mutation ; },
abstract = {The extreme morphology and polarised architecture of neurons require the highly sophisticated microtubule transport system for both construction and lifelong survival. Genomic evidence from an expanding landscape of human mutations supports the essential role of the microtubule transport machinery. During neurodevelopment, mutations disrupt the proliferation and migration of neuronal precursors, as well as the initial establishment of polarity. In the mature nervous system, the reliance on microtubule transport shifts to the long-term maintenance of axon integrity and synaptic proteostasis. Across the motor proteins responsible for long distance transport in neurons, mutations highlight a specific vulnerability of long axons to transport failure in Hereditary Spastic Paraplegia (HSP), Charcot Marie Tooth disease Type 2 (CMT2), Spinal Muscular Atrophy (SMA), Perry Syndrome, and Amyotrophic Lateral Sclerosis (ALS) amongst others. Due to the role of microtubule motors in development and maintenance, there is frequently a phenotypic spectrum within a single gene of the microtubule transport system. For example, mutations in dynein motors are linked both to malformations of cortical development and specific motor neuron loss in SMA-LED (Spinal Muscular Atrophy with Lower Extremity Predominance). By synthesising genetic evidence, this review illustrates how specific molecular failures, ranging from motor-domain kinetics to cargo binding, can inform our understanding of neuronal homeostasis. Ultimately, we argue that microtubule transport is not merely a cellular utility, but a key determinant of neuronal longevity.},
}

Humans
*Microtubules/metabolism/physiology
Animals
*Neurons/metabolism/physiology
*Molecular Motor Proteins/metabolism/genetics
Mutation

@article {pmid42283699,
year = {2026},
author = {El-Wahsh, S and Bogart, E and Bonnor, S and El-Wahsh, S and Graco, M and Hogden, A and Paynter, C and Raykar, V and Signorelli, M and Thomson, E and Vucic, S and White, S},
title = {Supporting gastrostomy decision-making in motor neurone disease (MND): an Australian survey of healthcare professionals' beliefs, practices, and needs.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/17582024.2026.2687483},
pmid = {42283699},
issn = {1758-2032},
abstract = {INTRODUCTION: Gastrostomy decision-making for people living with motor neurone disease (MND) is complex. While international studies report healthcare professionals' (HCPs) beliefs and practices in this area, little is known about the Australian context.

AIM: To examine Australian HCPs' beliefs, clinical practices, and support needs regarding gastrostomy decision-making in MND.

METHODS: A national cross-sectional online survey of Australian HCPs involved in gastrostomy discussions (n = 123) was conducted, exploring five domains: 1) initiating discussions and timing; 2) patient education; 3) multidisciplinary coordination; 4) guideline use; 5) and professional development needs. Descriptive statistics were applied.

RESULTS: Most HCPs initiated discussions about gastrostomy (74%), commonly prompted by swallowing difficulty, weight loss, or patient request. Although 72% believed discussions should occur before clinical indications, only 40% reported doing so. Earlier placement was favored in the context of respiratory decline compared with swallowing impairment, and 56% considered gastrostomy to be performed too late. Almost 40% used no formal guidelines, and 74% wanted further professional development.

CONCLUSION: Australian HCPs valued person-centered practice, but belief-practice gaps highlight opportunities to improve consistency, timing, and quality of gastrostomy decision-making support. Enhanced national guidelines, improved multidisciplinary communication, and targeted professional development may help reduce delays and better align practice with evidence-based recommendations.},
}

@article {pmid42285406,
year = {2026},
author = {Mendoza-Camacho, DM and Espinoza-Gutiérrez, HA and Viveros-Paredes, JM and Flores-Soto, ME and Tejeda-Martínez, AR},
title = {Recent advances in neurodegenerative diseases therapeutics: The inhibition of monoacylglycerol lipase strategy.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2026.06.011},
pmid = {42285406},
issn = {1873-7544},
abstract = {Neurodegenerative diseases share common pathophysiological mechanisms, including chronic neuroinflammation, glutamatergic excitotoxicity, oxidative stress, mitochondrial dysfunction, and disruptions in synaptic and lipid homeostasis. In this context, the endocannabinoid system has emerged as a key modulator of neuroimmune communication and neuronal survival. Within this system, Monoacylglycerol Lipase (MAGL) plays a central role by regulating the levels of the endocannabinoid 2-Arachidonoylglycerol (2-AG) while simultaneously contributing to the generation of arachidonic acid and pro-inflammatory eicosanoids. Pharmacological or genetic inhibition of MAGL increases 2-AG levels and concurrently reduces the biosynthesis of pro-inflammatory lipid mediators, thereby modulating microglial activation, astrocytic responses, and neuronal excitotoxicity. Preclinical studies in models of Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis consistently demonstrate that MAGL blockade attenuates neuroinflammation, preserves synaptic and neuronal integrity, improves motor and cognitive function, and, in some cases, delays disease progression. Although clinical evidence remains limited, the available data position MAGL as a metabolic convergence point between inflammation and neurodegeneration, suggesting that its modulation may represent a therapeutic strategy with disease-modifying potential.},
}

@article {pmid42286474,
year = {2026},
author = {Seuren, LM and Versloot, J and Taneja, S and Zeeshan, MF and Wodchis, WP},
title = {Adoption and sustainability of a virtual interprofessional team for primary care in Ontario: a qualitative study.},
journal = {BMC primary care},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12875-026-03411-5},
pmid = {42286474},
issn = {2731-4553},
abstract = {BACKGROUND: Primary care providers across Canada face challenges caring for patients with increasingly complex care needs. Team-based care has been identified as an approach to improve care for patients with complex needs. The Mississauga Ontario Health Team recently adopted SCOPE, a telephone-based support line to improve care coordination between primary care, hospital and community services. To understand how Mississauga Health SCOPE supports primary care providers and how it can be improved, this study addresses the following research question: why do primary care providers adopt or not adopt Mississauga Health SCOPE, and what motivates sustained use or abandonment?

METHODS: Semi-structured interviews were conducted over Zoom with three stakeholder groups: primary care providers (n = 20), general internal medicine physicians (n = 3), and members of the project team (n = 6). Interviews focused on the adoption and continued use of Mississauga Health SCOPE. Data were analyzed inductively, using Proctor et al.'s Adoption and Sustainability concepts.

RESULTS: Within the broad concepts of Adoption and Sustainability, we identified seven themes that shaped whether PCPs would use and continue to use MHSCOPE: Broken healthcare system, Awareness of Mississauga Health SCOPE, Service misalignment, Useful and usable, Trying it out, Breaking the habit, and Making PCPs feel heard.

CONCLUSIONS: Telemedicine support services like Mississauga Health SCOPE can help primary care providers deliver appropriate and timely care to patient in the community. Succcesful implementation requires that clinicians feel supported in using the intervention, have a clear understanding of procedures and benefits, and are prepared to take time to learn to work with new tools to overcome hurdle of initial adoption.},
}

@article {pmid42286604,
year = {2026},
author = {Forster, L and Byrne, S and Spielmann-Burkard, H and Weber, S and von Strachwitz, M and Kuehlmeyer, K and Kugler, C},
title = {Linguistic and psychometric validation of a German version of the measure of moral distress for healthcare professionals (MMD-HP GER): results of a study with intensive care nurses.},
journal = {BMC medical ethics},
volume = {27},
number = {1},
pages = {},
pmid = {42286604},
issn = {1472-6939},
mesh = {Humans ; Ethical Dilemmas ; Germany ; *Psychometrics ; Female ; Adult ; Surveys and Questionnaires ; Male ; Reproducibility of Results ; Translating ; *Critical Care Nursing/ethics ; *Stress, Psychological/diagnosis ; *Morals ; Middle Aged ; },
abstract = {BACKGROUND: Moral distress is an increasingly studied phenomenon in nursing science and ethics. It refers to the psychological discomfort experienced when an individual is prevented from acting on a course of action that they recognize as ethically correct. Nurses who work in intensive care are at high risk of experiencing moral distress. Various instruments to assess moral distress, most recently Epstein et al.'s measure of moral distress for health care professionals (MMD-HP), have been developed. At present, there is no validated German language version of the instrument for assessing moral distress in Germany. Therefore, this study aimed, at (1) translating and linguistically validating the instrument, as well as (2) psychometrically validating it among intensive care nurses in Germany.

METHODS: According to the ISPOR (International Society for Pharmacoeconomics and Outcomes Research) guidelines, the MMD‑HP was translated, linguistically validated, and psychometrically tested. The German version of the moral distress thermometer (MDT) and the German Nursing Workload Scale (NWS) were used to measure the construct validity of the translated instrument. Institutional ethics review boards of two universities approved the study protocols.

RESULTS: A total of 187 questionnaires of intensive care nurses remained for analysis after listwise deletion. The mean sum‑score was 106.9 (± 62) (minimum = 3, maximum = 325; range = 0-400). Criterion validity was supported by a high positive correlation between the German version of the MMD‑HP and the validated German-language moral distress thermometer (ρ = 0.598, p = 0.001, n = 168). Factor analyses revealed a four‑factor solution with correlating factors for the German version. The instrument showed high reliability (ωH = 0.91, 95 % CI = 0.88-0.93).

CONCLUSIONS: Our findings demonstrate that the German adaptation of the MMD-HP shows potential for measuring moral distress among intensive care nurses in Germany. In addition, its psychometric properties preliminarily support its reliability and validity in this cultural context. Further independent validation studies are needed to provide support for the proposed four-factor model.},
}

Humans
Ethical Dilemmas
Germany
*Psychometrics
Female
Adult
Surveys and Questionnaires
Male
Reproducibility of Results
Translating
*Critical Care Nursing/ethics
*Stress, Psychological/diagnosis
*Morals
Middle Aged

@article {pmid42286839,
year = {2026},
author = {Wheeler, A and Mehta, K and Sanders, D and Chin, C and Zivalic, H and Carey, J and McCaffrey, A and Pant, P and Lewenhaupt, C and Luppino, S and Jacobs, G and Golden, S and Gifford, R and Scirocco, E and Keegan, M and Hatem, M and Yazdanian, T and Uysal, SP and Susco, N and Schwartzman, S and Branch, K and Hall, KE and Barnas, J and Lam, J and Hagar, J and Hannan, CA and Paganoni, S and Berry, JD and Garret, M and Scalia, J and Babu, S},
title = {Optimizing Research Operations and Resource Utilization in ALS Care: Insights From the Tofersen Antisense Oligonucleotide Expanded Access Protocol.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70310},
pmid = {42286839},
issn = {1097-4598},
abstract = {INTRODUCTION/AIMS: Tofersen is a gene-targeted therapy for individuals with superoxide dismutase 1 (SOD1) (+) amyotrophic lateral sclerosis (ALS). Prior to U.S. Food and Drug Administration (FDA) approval, tofersen was made available through expanded access protocol. This study describes the clinical and operational experience of administering tofersen through expanded access protocols at a single academic medical center in the U.S.

METHODS: Individuals with symptomatic SOD1(+) ALS (≥ 18 years), who were ineligible for traditional ALS clinical trials, received tofersen via bedside lumbar punctures at Massachusetts General Hospital. Treatment was provided through single-patient and intermediate-sized expanded access protocols prior to FDA approval. Demographic and clinical characteristics, referral-to-treatment timelines, safety outcomes, and operational costs were collected.

RESULTS: Eleven individuals with SOD1(+) ALS received monthly intrathecal tofersen over a two-year period (July 2021 to July 2023). Most participants were female, and 81.8% had leg-onset ALS. The mean (SD) referral-to-first dose duration was 36 (22.4) days. A total of 120 doses were administered over a two-year period. Tofersen was safe and well tolerated, with no treatment-related serious adverse events. Operational costs totaled $336,620, supported by philanthropy and insurance. The company provided the drug for free.

DISCUSSION: This experience demonstrates the feasibility of implementing a resource-intensive expanded access protocol within an academic medical center using a mixed funding model to facilitate early access to emerging ALS therapies.},
}

@article {pmid42287757,
year = {2026},
author = {Jaberi, KR and Haghighi, MR and Aligholi, H and Takallu, S and Asadi, P and Mirzaei, E and Jaberi, AR and Sahraian, A},
title = {Focused ultrasound-mediated nanocarrier delivery across the blood-brain barrier for neurodegenerative diseases.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {201},
number = {},
pages = {119622},
doi = {10.1016/j.biopha.2026.119622},
pmid = {42287757},
issn = {1950-6007},
abstract = {The development of effective therapies for neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis remains a major challenge due to the restrictive nature of the blood-brain barrier (BBB). Conventional systemic drug delivery strategies often fail to achieve sufficient central nervous system (CNS) penetration while avoiding peripheral toxicity. Focused ultrasound (FUS), particularly when combined with microbubbles or nanocarriers, has emerged as a non-invasive approach to transiently and precisely open the BBB, enabling targeted delivery of therapeutics to the brain parenchyma. This review provides a comprehensive overview of the mechanisms by which FUS enhances CNS drug delivery, with a dedicated focus on its integration with nanoparticle-based systems, including liposomes, polymeric nanoparticles, dendrimers, metallic nanoparticles, and exosomes. We discuss how these nanocarriers can be engineered for improved stability, targeting specificity, and stimulus-responsive release upon FUS exposure. Recent advances in ultrasound technology, image guidance (particularly MRI), and therapeutic formulations are summarized, along with preclinical and clinical evidence across key neurodegenerative conditions. Despite promising results, several challenges remain, including long-term BBB stability, regulatory standardization, and scalability for broad clinical application. By integrating principles from acoustics, pharmacology, and nanotechnology, FUS-mediated drug delivery, especially in combination with smart nano systems, represents a significant advancement in precision neurotherapeutics, offering new hope for previously untreatable CNS diseases.},
}

@article {pmid42287763,
year = {2026},
author = {Mah, SJ and Bergeron, AM and Hanley, G and Yang, I and Bogach, J and Nguyen, L and Huerne, K and Morais, M and Stuart, H},
title = {Opportunistic salpingectomy during non-gynecologic surgery: Canadian surgeons' experience, barriers and facilitators.},
journal = {Gynecologic oncology},
volume = {211},
number = {},
pages = {1-7},
doi = {10.1016/j.ygyno.2026.06.005},
pmid = {42287763},
issn = {1095-6859},
abstract = {BACKGROUND: Opportunistic salpingectomy during concurrent abdominopelvic surgery has been shown to significantly reduce ovarian cancer risk. Uptake by non-gynecologic surgeons could increase population impact. We conducted a national survey of general and urologic surgeons using Michie et al.'s implementation framework of Capability, Motivation, Opportunity-Behaviour to understand understand current experience with opportunistic salpingectomy, and facilitators and barriers to adoption.

METHODS: An online survey was administered to Canadian general and urologic surgeons and postgraduate trainees from January-June 2024. A multivariable logistic regression model assessed relationship between demographic factors and motivation to adopt opportunistic salpingectomy.

RESULTS: 269 surveys were completed by 226 general surgeons and 43 urologists. Although 88% reported motivation to perform opportunistic salpingectomy for cancer prevention, practice duration ≥21 years and province of practice were associated with decreased motivation. Only 44% were aware of recommendations endorsing the procedure, and 19% had performed it. Commonly reported barriers to adoption were Capability (consenting patients regarding permanent contraception and ovarian function, and intraoperative technique/complications), and Opportunity (reimbursement). A surgical video was the preferred method to learn salpingectomy by 94%, and patient consent handouts and intraoperative training by a gynecologist were facilitators. Most (92%) stated that opportunistic salpingectomy training should be offered to postgraduate trainees.

DISCUSSION: Most general and urologic surgeons in Canada were unaware of and have not performed opportunistic salpingectomy but were motivated to offer it. Providing consent resources and training opportunities with gynecologist support, and addressing cultural and regulatory factors may improve uptake by surgeons and decrease ovarian cancer incidence.},
}

@article {pmid42288074,
year = {2026},
author = {Tackaert, T and Hemeryck, J and Duchatelet, C and Vanwulpen, M and Hachimi-Idrissi, S},
title = {Mean airway pressure as the missing link in CPR physiology: A prehospital comparison of manual and mechanical chest compressions.},
journal = {The American journal of emergency medicine},
volume = {108},
number = {},
pages = {80-85},
doi = {10.1016/j.ajem.2026.06.012},
pmid = {42288074},
issn = {1532-8171},
abstract = {BACKGROUND: The impact of manual versus mechanical chest compressions on mean airway pressure (mPAW) during cardiopulmonary resuscitation (CPR) is poorly understood. This exploratory pilot study assessed intratracheal airway pressures during prehospital CPR in out-of-hospital cardiac arrest (OHCA).

METHODS: Adult OHCA patients treated by the prehospital Medical Emergency Team of the Ghent University Hospital (Belgium) were prospectively enrolled. Intratracheal pressure was recorded immediately after intubation, mPAW was calculated for both the first and last minutes of advanced life support (ALS). The results were compared between mechanical compressions using the Stryker LUCAS3® device and manual chest compressions (with chest compression feedback).

RESULTS: Nineteen patients were included (manual n = 10; mechanical n = 9). Initial median mPAW was low (7.74 mbar) and showed a slight increase over time. Mechanical compressions generated higher early mPAW than manual compressions (8.96 vs. 6.54 mbar). mPAW increased over time with manual compressions and decreased with mechanical compressions. Patients who achieved return of spontaneous circulation (ROSC) showed higher mPAW, though this difference was not statistically significant.

CONCLUSIONS: Prehospital mPAW values were substantially lower than those reported in previous ED-based studies. While airway pressure patterns differed between compression modalities, overall pressures were similar. These findings highlight complex airway mechanics during CPR and support further research into whether higher airway pressures could improve airway patency, oxygenation, and hemodynamics in selected OHCA patients.},
}

@article {pmid42288493,
year = {2026},
author = {Wang, N and Li, Y and Li, N and Shen, L and Wang, C and Zhu, H and Zhou, Z and Ding, Y and Zhang, J and Fang, L and Bai, B},
title = {Quantitative Proteomics Unveils Comprehensive Tissue-Specific VCP Interaction Networks in Mice.},
journal = {Scientific data},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41597-026-07626-0},
pmid = {42288493},
issn = {2052-4463},
support = {32071256//National Natural Science Foundation of China/ ; 82172354//National Natural Science Foundation of China/ ; },
abstract = {Valosin-containing protein (VCP), a conserved AAA ATPase hexamer, participates in multiple biological processes including ERAD, ubiquitin-dependent degradation by extracting misfolded proteins for proteasomal degradation. Although its interactions with cofactors are well-characterized, and its dysregulation is implicated in multisystem proteinopathy, amyotrophic lateral sclerosis, and cancer, the tissue-specific VCP interactomes underlying its functional versatility remain elusive. Here, we generated HA-N-tagged VCP knock-in mice via CRISPR/Cas9 strategy and performed affinity purification coupled with data-independent acquisition (DIA) mass spectrometry to systematically profile VCP interactors across eight mouse tissues, yielding a high-confidence dataset. We identified 923 robust VCP-binding partners, including established interactors (UBX2B, UFD1, proteasomal subunits) and novel candidates implicated in energy metabolism (TCA cycle, oxidative phosphorylation) and protein quality control (proteasome, ERAD). Notably, we validated the interaction of VCP to two hepatic candidate proteins, DAXX and PRKAG2 (AMPK γ2 regulatory subunit), using HepG2 cells. This study establishes the first in vivo atlas of the VCP interaction network, providing mechanistic insights into its tissue-specific roles and highlighting potential therapeutic avenues for VCP-related disorders.},
}

@article {pmid42289132,
year = {2026},
author = {Jamil, V and Aldoski, M and Selivany, B and Jameel, D},
title = {MORPHOLOGY AND PREVALENCE OF C-SHAPED CANALS IN MANDIBULAR FIRST MOLARS OF AN IRAQI KURDISTAN REGION POPULATION: A CONE-BEAM COMPUTED TOMOGRAPHY ASSESSMENT.},
journal = {Georgian medical news},
volume = {},
number = {373},
pages = {215-218},
pmid = {42289132},
issn = {1512-0112},
mesh = {Humans ; Female ; Male ; *Cone-Beam Computed Tomography ; Iraq/epidemiology ; *Molar/diagnostic imaging/anatomy & histology ; Adult ; Adolescent ; Middle Aged ; *Dental Pulp Cavity/diagnostic imaging/anatomy & histology ; *Tooth Root/diagnostic imaging/anatomy & histology ; Retrospective Studies ; *Mandible/diagnostic imaging/anatomy & histology ; Young Adult ; Prevalence ; },
abstract = {BACKGROUND: Root canal morphology variations, particularly C-shaped canal configurations, pose substantial challenges to successful endodontic therapy. Accurate preoperative assessment of these complex anatomical patterns remains essential, with cone-beam computed tomography (CBCT) offering superior three-dimensional visualization compared to conventional radiography.

OBJECTIVES: This study aimed to determine the prevalence and morphological characteristics of C-shaped canals and comprehensively evaluate root and canal configurations of mandibular first molars within an Iraqi Kurdish population using CBCT imaging.

METHODS: In this retrospective analysis, CBCT images from 323 patients (186 males, 137 females; aged 18-50 years) originating from Duhok, Erbil, and Suleimani underwent evaluation. Two calibrated endodontists independently examined axial, sagittal, and coronal reconstructions to document root numbers, canal counts, and configurations. Root canal morphology was classified according to Vertucci's system, while Fan et al.'s classification was applied only to confirmed true C-shaped canals. Chi-square analysis assessed gender-based differences, with statistical significance set at p≤0.05.

RESULTS: Two-rooted molars predominated (94.1%), typically exhibiting three (64.4%) or four canals (28.8%). Gender differences proved non-significant for root (p=0.653) and canal numbers (p>0.05). Mesial roots consistently demonstrated Vertucci Type IV morphology (90.1%), while distal roots displayed greater diversity: Type I (58.5%), Type IV (20.1%), and Type II (18.6%). Cross-sectional morphology was not analyzed using Fan classification for non-C-shaped canals. True C-shaped canal configurations were rare (0.6%; 2/323 teeth), with no significant gender association (p>0.05).

CONCLUSION: Iraqi Kurdish mandibular first molars typically exhibit predictable mesial root Type IV anatomy alongside variable distal root morphology requiring careful clinical exploration. The low true C-shaped canal prevalence (0.6%) underscores ethnicity-specific anatomical patterns. These findings advocate judicious CBCT utilization for complex endodontic cases while emphasizing systematic distal canal detection protocols.},
}

Humans
Female
Male
*Cone-Beam Computed Tomography
Iraq/epidemiology
*Molar/diagnostic imaging/anatomy & histology
Adult
Adolescent
Middle Aged
*Dental Pulp Cavity/diagnostic imaging/anatomy & histology
*Tooth Root/diagnostic imaging/anatomy & histology
Retrospective Studies
*Mandible/diagnostic imaging/anatomy & histology
Young Adult
Prevalence

@article {pmid42289668,
year = {2026},
author = {Pillay, S and Head, J and Horn, A and de Wet, W and Davidge, R and Dickson-Hall, M and Felix, G and Kali, G and Khan, W and Klein, B and Nakwa, F and Venter, M and Vlok, N and Wege, M and Stassen, W},
title = {The development of a consensus-based curriculum for a Bespoke Online Neonatal Education for Transfers (BONNETs) course.},
journal = {BMC medical education},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12909-026-09377-3},
pmid = {42289668},
issn = {1472-6920},
abstract = {BACKGROUND: High neonatal mortality in Sub-Saharan Africa (SSA) is driven by multiple systemic barriers, including insufficient neonatal transport infrastructure and limited provider training. Although specially trained neonatal retrieval teams are recommended for interfacility neonatal transfers, resource constraints lead to non-specialist emergency medical services (EMS) cadres performing these roles, potentially compromising the safe transport of critically ill neonates.

OBJECTIVE: To develop a bespoke, online neonatal interfacility transfer curriculum, informed by expert consensus and South African research to address critical gaps in provider knowledge and confidence, thereby improving neonatal transfer outcomes.

METHODS: Building on Kern's Six-Step Framework for curriculum development, an initial curriculum was derived through a comprehensive literature review, a retrospective chart analysis of neonatal cases in South Africa, and detailed interviews with experts and learners. Consequently, consensus on this curriculum was sought using a virtual, modified Nominal Group Technique (NGT) over two consensus rounds. A refined course curriculum is proposed.

RESULTS: Fourteen expert participants (neonatologists, paediatricians, neonatal nurses, and Advanced Life Support (ALS) providers with ≥ 3 years of experience) allocated potential outcomes to Core, Extended, or Advanced tiers based on EMS scope of practice. A 75% consensus threshold was applied. Eleven experts completed both rounds (21% attrition). Most were ALS providers (43%), largely employed in the public sector (71%). The final curriculum consists of three sequential courses (Core, Extended, Advanced) which scaffolds learning. The Core course consists of five modules, with each curriculum item achieving > 90% agreement on foundational skills including basic assessment, recognition of critical instability, and escalation pathways. This open-access online course is tailored to resource-limited settings.

CONCLUSION: A consensus-driven neonatal interfacility transfer curriculum for South Africa was successfully developed, providing a tiered, evidence-based approach to reinforce provider knowledge and confidence. By leveraging expanding internet accessibility, the Bespoke Online NeoNatal Education for Transfers (BONNETs) framework mitigates geographic disparities while integrating best practices for safe neonatal transfer. However, rigorous validation across diverse contexts and attention to broader systemic challenges, is essential to achieving sustained improvements. Future research should assess the curriculum's performance in improving knowledge and confidence, as well as long-term clinical impact on neonatal outcomes.},
}

@article {pmid42290091,
year = {2026},
author = {Khamies, MS and Mortada-Mahmoud, A and Laklouk, M},
title = {Naviculectomy combined with 'à la carte' soft-tissue releases: is it a practical solution for congenital vertical talus in adolescence?.},
journal = {Journal of pediatric orthopedics. Part B},
volume = {},
number = {},
pages = {},
doi = {10.1097/BPB.0000000000001364},
pmid = {42290091},
issn = {1473-5865},
abstract = {Neglected congenital vertical talus in adolescents often necessitates extensive soft-tissue dissection, leading to increased surgical trauma and worsening outcomes. We propose that excising the navicular bone can shorten the foot's medial column and loosen the ligaments around the talonavicular joint, thus improving reduction. This study aimed to evaluate whether naviculectomy and 'à la carte' soft-tissue releases could enhance the outcomes in these patients or not. A retrospective case series study was conducted on 15 adolescent patients (average age 10.67 years) with neglected congenital vertical talus from June 2020 to 2025, with a median follow-up of 24 months. All cases were idiopathic, neglected, virginal feet that had not undergone any manipulative casting before. Clinical assessments followed Zorer et al.'s criteria, and pain levels were evaluated using the visual analog scale (VAS). There were 11 boys and 4 girls. The median Zorer score increased from 2 preoperatively to 11 postoperatively, with a mean difference of 10 (P < 0.001), reflecting marked functional recovery. The median VAS score showed significant improvement at the final follow-up from 7 to 2 (P < 0.001). Significant improvement was observed in all radiographic measurements. Naviculectomy combined with 'à la carte' soft-tissue releases could be a practical, effective solution for adolescents with neglected congenital vertical talus in terms of pain relief, clinical, and radiological improvement while reducing complications associated with extensive surgical soft-tissue releases on short-term outcomes.},
}

@article {pmid42290559,
year = {2026},
author = {Martyniuk, О and Mushii, O and Pavlova, A},
title = {Integrated Analysis of hsa-miR-26b-5p and hsa-miR-186-5p in Blood Serum and Tumor Tissue Reveals their Prognostic and Predictive Significance in Breast Cancer.},
journal = {Experimental oncology},
volume = {48},
number = {1},
pages = {31-39},
doi = {10.15407/exp-oncology.2026.01.031},
pmid = {42290559},
issn = {2312-8852},
mesh = {Humans ; *MicroRNAs/genetics/blood ; Female ; *Breast Neoplasms/genetics/blood/pathology/mortality ; Prognosis ; *Biomarkers, Tumor/genetics/blood ; Middle Aged ; Adult ; Gene Expression Regulation, Neoplastic ; },
abstract = {BACKGROUND: Breast cancer (BC) heterogeneity signifi antly complicates diagnosis, prognosis, and prediction of treatment response. MicroRNAs (miRNAs) have emerged as promising biomarkers due to their involvement in tu- mor progression and in regulating therapy sensitivity. however, the combined clinical signifi ance of circulating and tumor-associated miRNAs, such as hsa-miR-26b-5p and hsa-miR-186-5p, remains insuffi tly elucidated. Materi- als and Methods. Expression levels of hsa-miR-26b-5p and hsa-miR-186-5p were analyzed in serum and tumor tis- sue of 124 BC patients. Associations with clinicopathological parameters were assessed. The prognostic signifi ance was evaluated based on disease progression and recurrence within 3 years. The predictive value was determined in patients receiving neoadjuvant chemotherapy (4AC regimen) using response assessment and ROC analysis. Re- sults. young BC patients (≤45 years) demonstrated signifi antly lower circulating levels of both miRNAs. Serum hsa-miR-186-5p expression was associated with early-stage disease, tumor size, lymph node status, and molecular subtype. Increased circulating hsa-miR-26b-5p levels were linked to disease progression, whereas decreased hsa- miR-186-5p levels were observed in patients with unfavorable outcomes. In tumor tissue, hsa-miR-26b-5p expres- sion correlated with tumor grade, size, and metastatic status, showing elevated levels in poorly differentiated tumors and reduced expression in metastatic disease. In contrast, hsa-miR-186-5p was associated with the molecular sub- type and lymph node involvement, with the highest expression observed in hER2-positive tumors and in patients with recurrence. Elevated levels of hsa-miR-186-5p in both serum and tumor tissue were associated with reduced sensitivity to doxorubicin-based neoadjuvant chemotherapy. ROC analysis confi med its predictive value (AUC = 0.750 for serum and 0.818 for tumor tissue). No signifi ant association between hsa-miR-26b-5p and chemothe- rapy response was observed.

CONCLUSIONS: hsa-miR-26b-5p and hsa-miR-186-5p demonstrate complementary roles in BC biology. hsa-miR-26b-5p is primarily associated with tumor aggressiveness and cancer progression, whereas hsa-miR-186-5p refl cts its molecular characteristics and response to chemotherapy. Their combined assessment in serum and tumor tissue represents a promising approach for improving prognostic stratifi ation and predicting treatment effi acy in BC patients.},
}

Humans
*MicroRNAs/genetics/blood
Female
*Breast Neoplasms/genetics/blood/pathology/mortality
Prognosis
*Biomarkers, Tumor/genetics/blood
Middle Aged
Adult
Gene Expression Regulation, Neoplastic

@article {pmid42290625,
year = {2026},
author = {Tenenbein, M},
title = {Author response to: Mullins et al. comment on, "We need a standardized North American acetylcysteine dosing regimen for the treatment of paracetamol (acetaminophen) poisoning".},
journal = {Clinical toxicology (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/15563650.2026.2679164},
pmid = {42290625},
issn = {1556-9519},
abstract = {INTRODUCTION: I have reviewed Mullins et al's critique of my commentary "We need a standardized North American acetylcysteine dosing regimen for the treatment of paracetamol (acetaminophen) poisoning".

DISCUSSION: I concur regarding this need, and I agree that the original three-bag regimen should be retired. However, we disagree upon its replacement. They challenge my recommendation for a two-bag regimen, and they favour the one-bag two-step approach. The impetus for a replacement acetylcysteine regimen is to decrease the adverse effects and errors associated with the three-bag protocol. However, the one-bag two-step regimen was not designed to decrease adverse effects, and their published reports do not find a decrease of errors. And a fatal adverse effect, acetylcysteine overdose, has emerged with use experience of this regimen.

CONCLUSIONS: The one-bag two-step regimen should be dismissed from the quest for a standardized North American acetylcysteine dosing regimen for the treatment of paracetamol (acetaminophen) poisoning.},
}

@article {pmid42293320,
year = {2026},
author = {Novikova, L and Lang, C and Tumani, H and Klose, V and Kassubek, J and Dreyhaupt, J and Dupuis, L and Wabitsch, M and Ludolph, A},
title = {Thyroid hormones and energy metabolism in amyotrophic lateral sclerosis.},
journal = {Brain communications},
volume = {8},
number = {3},
pages = {fcag198},
pmid = {42293320},
issn = {2632-1297},
abstract = {Weight loss, partially caused by hypermetabolism, represents a well-documented and therapeutically relevant feature of the amyotrophic lateral sclerosis phenotype worldwide. In this study, we retrospectively analysed the association between thyroid function and clinical, prognostic and metabolic parameters in a cohort of patients with amyotrophic lateral sclerosis in an experienced centre in Germany (n = 1754). Specifically, we examined the relationship between thyroid stimulating hormone levels, age, glucose and body mass index and-in subgroups-phosphorylated neurofilament heavy chain levels in CSF. There was no association between thyroid stimulating hormone levels and body mass index in patients with amyotrophic lateral sclerosis (n = 954). In contrast with other cohorts, thyroid stimulating hormone levels decreased with age in patients with amyotrophic lateral sclerosis indicating hypothalamic deficiency in the ageing patients. There was no association between thyroid stimulating hormone and phosphorylated neurofilament heavy chain (prognostic marker) in CSF of a subcohort (n = 646). Thyroid stimulating hormone levels correlated with glucose levels, an effect more pronounced in male patients. In conclusion, our results suggest that thyroid metabolism does not significantly contribute to amyotrophic lateral sclerosis-related weight loss or disease prognosis as estimated by phosphorylated neurofilament heavy chain; thyroid dysfunction is unlikely to be a primary driver of the metabolic dysregulation observed in amyotrophic lateral sclerosis. Most interestingly, thyroid stimulating hormone levels show an unexpected negative relation to age in patients with amyotrophic lateral sclerosis.},
}

@article {pmid42293321,
year = {2026},
author = {Ma, M and Zhao, B and Gao, N and Sun, X and Shao, K and Lin, P and Li, W and Zhao, Y and Yu, D and Yan, C and Liu, S and Yun, Y},
title = {Quantitative susceptibility mapping reveals widespread brain iron abnormalities in sporadic patients with early-stage amyotrophic lateral sclerosis.},
journal = {Brain communications},
volume = {8},
number = {3},
pages = {fcag190},
pmid = {42293321},
issn = {2632-1297},
abstract = {In the present study, using the novel quantitative susceptibility mapping technique, we aimed to systematically investigate brain iron alterations in a large group of sporadic early-stage amyotrophic lateral sclerosis patients and their correlation with clinical disability. In this study, amyotrophic lateral sclerosis patients at King's stage 1 were defined as early-stage amyotrophic lateral sclerosis patients, and 53 newly diagnosed early-stage amyotrophic lateral sclerosis patients and 50 healthy controls were included. Voxel-based whole-brain quantitative susceptibility mapping analysis was used to explore brain iron alterations. Voxel-based morphometry analysis was also performed. Longitudinal follow-up was performed in amyotrophic lateral sclerosis patients, and the follow-up progression rate was calculated. We found that, compared with healthy controls, early-stage amyotrophic lateral sclerosis patients presented significantly increased susceptibility values, mainly in the motor cortex, prefrontal cortex, hippocampus and cerebellar regions, while volumetric alterations were not detected. Moreover, motor and extra-motor cortex susceptibility values were significantly correlated with upper motor neuron scores and follow-up progression rate (r = 0.452-0.504, P < 0.01) in early-stage amyotrophic lateral sclerosis patients. We demonstrated a clear profile of early motor and extra-motor iron depositions and their important roles in early-stage amyotrophic lateral sclerosis patients. We suggest that quantitative susceptibility mapping is likely a promising neuroimaging approach for assessing early upper motor neuron damage and detecting early extra-motor alterations in amyotrophic lateral sclerosis patients.},
}

@article {pmid42281996,
year = {2026},
author = {Cooper-Knock, J and Bonsall, S and Kazu, R and King, M and Leung, D and Mahiddine, F and Highley, J and Strange, A and Chen, Y and Sassani, M and Eldahshoury, M and Boyne, J and Collins, M and Monte, E and Harvey, C and Gornall, S and Jangid, A and Treanor, C and Moll, T and van Dijk, C and Cabras, S and Urban, A and Bowden, K and Wareing, H and Huang, Y and Shaw, P and West, R and Kenna, K and Hornstein, E and Zhang, S and Zhou, J and Snyder, M},
title = {Single-nucleus multiomic atlas of ALS primary motor cortex nominates neuroprotective WDR49-expressing astrocytes.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-9853460/v1},
pmid = {42281996},
issn = {2693-5015},
abstract = {Amyotrophic lateral sclerosis (ALS) causes selective neurodegeneration in primary motor cortex, yet cell-type-specific molecular changes driving this vulnerability remain poorly understood. We present an integrated single-nucleus RNA- and ATAC-sequencing atlas of 778,330 nuclei from the primary motor cortex of 140 genetically characterised donors. ALS is associated with widespread transcriptional reprogramming driven by a common set of transcription factors (TFs) across multiple cell-types. Astrocytes harbour the most differentially expressed genes. Within astrocytes, a WDR49-expressing subpopulation is spatially associated with TDP-43 pathology, and genetic variants within WDR49 confer risk for both sporadic and monogenic autosomal dominant ALS. In patient-derived induced astrocytes, WDR49 protein abundance predicts the survival of co-cultured neurons. WDR49 localises to PML nuclear bodies, where it regulates astrocyte reactivity and secretion of EVs containing protein chaperones. Together, these in vivo and in vitro findings suggest that WDR49+ astrocytes mount a compensatory secretory response to extracellular protein aggregates, and that loss of this capacity lowers the threshold for ALS pathogenesis.},
}

@article {pmid42282536,
year = {2026},
author = {Cortez, JD and Avalos, JL},
title = {Heterologous iron-sulfur cluster biogenesis and delivery for cytosolic isobutanol and isopentanol production in Saccharomyces cerevisiae.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.05.29.728687},
pmid = {42282536},
issn = {2692-8205},
abstract = {Saccharomyces cerevisiae is an excellent microbial platform for sustainable production of next generation biofuels such as the branched chain higher alcohols (BCHAs) isobutanol and isopentanol. A cytosolic pathway for BCHA production is generated from expression of prokaryotic orthologs of branched-chain amino acid (BCAA) enzymes acetolactate synthase (ALS), mutant NADH-dependent ketol-acid reductoisomerase (KARI [P2D1-A1]), and dihydroxy-acid dehydratase (DHAD). The potential for this pathway has been hindered by the availability of iron-sulfur clusters, particularly the 2Fe-2S cluster, required for DHAD to function in the cytosol. ILV3 , the endogenous yeast DHAD located in the mitochondria, can be deleted to create a valine auxotroph. In this study we use bioinformatics, heterologous gene library synthesis, and a valine complementation assay to find prokaryotic iron-sulfur cluster biosynthetic gene clusters (BGC) and accessory genes that aid DHAD function in the yeast cytosol. This work presents, to our knowledge, the first functional BGC that enhances the cytosolic activity of prokaryotic DHADs in S. cerevisiae . The SUF BGC from Bacillus subtilis combined with a ferritin-like protein (FTNB) from Escherichia coli and the Lactococcus lactis DHAD enhanced the production of BCHAs. Combined expression gave an average isobutanol titer of 412mg/L, 1.8-fold greater than L. lactis DHAD expressed alone. This work establishes a blueprint for better biofuel production by improving iron-sulfur cluster dependent enzyme activity in the yeast cytosol.},
}

@article {pmid42282588,
year = {2026},
author = {Kochen, NN and Zafari, S and Renaud, A and Schneider, N and Vunnam, N and Liao, EE and Dutton, JR and Braun, AR and Sachs, JN},
title = {From anti-fungal to potential neurotherapeutic: Posaconazole as an effective inhibitor of cellular TDP-43 pathology.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.06.01.728552},
pmid = {42282588},
issn = {2692-8205},
abstract = {Recently, we showed that ketoconazole, a known anti-fungal inhibitor of CYP51, stabilized TAR DNA-binding protein 43 (TDP-43) native self-interactions, reduced TDP-43 pathology and rescued TDP-43-induced SREBP2 downregulation. Despite its promising effects, ketoconazole is not viable for repurposing for ALS due to liver toxicity side effects that occur when orally delivered. To address this, we tested the activities of seven additional known azole-based CYP51 inhibitors in order identify a viable alternative to ketoconazole. Using our established TDP-43 mislocalization and aggregation assay in HEK293T cells, we identified posaconazole, an FDA-approved, CNS-penetrant and orally delivered anti-fungal, as the strongest inhibitor of TDP-43 pathology. Posaconazole was able to reduce insoluble TDP-43 and restore SREBP2 levels, outperforming ketoconazole. Mechanism of action (MOA) experiments suggest posaconazole is able to outperform ketoconazole by inducing a significantly stronger activation of autophagy and upregulation of heat shock proteins known to clear TDP-43. Further MOA experiments show that the effects of posaconazole on TDP-43 are dependent on its known ability to lower cellular cholesterol levels. By correlating our experimental results on the eight CYP51 inhibitors tested, we show that predicted affinity towards human CYP51 strongly correlates with the inhibitors' ability to lower TDP-43 aggregation and mislocalization. Finally, we tested posaconazole in a low dose sodium arsenite ALS model in iPSC-derived motor neurons, showing that it is efficacious at inhibiting TDP-43 pathology in the nanomolar range. Altogether, these results support the repurposing of posaconazole for ALS/FTD as a means to prevent TDP-43 pathology.},
}

@article {pmid42274592,
year = {2026},
author = {Sgalletta, B and Agostini, F and Bisaglia, M},
title = {The Role of Iron in Neuronal Homeostasis: A Double-Edged Sword.},
journal = {Cells},
volume = {15},
number = {11},
pages = {},
pmid = {42274592},
issn = {2073-4409},
mesh = {Humans ; *Iron/metabolism ; *Homeostasis ; Animals ; *Neurons/metabolism ; Neurodegenerative Diseases/metabolism/pathology ; Neurogenesis ; Neurodevelopment ; Brain/metabolism ; },
abstract = {Iron is an essential micronutrient that plays a central role in numerous biological processes. Despite its relatively low abundance in the human body, iron is particularly critical for brain function. Systemic and cerebral iron homeostasis is tightly regulated through coordinated mechanisms involving absorption, transport, storage, and recycling. Within the brain, iron metabolism is further controlled by the blood-brain barrier and specialized neural cell populations, including neurons, astrocytes, oligodendrocytes, and microglia. Iron is indispensable for neurodevelopment, supporting neurogenesis, myelination, and neurotransmitter synthesis. However, both iron deficiency and iron overload have detrimental consequences. Early-life iron deficiency disrupts neural development and leads to long-lasting cognitive, motor, and behavioral impairments, whereas excessive iron accumulation promotes oxidative stress, ferroptosis, and neuroinflammation. These mechanisms have been described to contribute to the pathogenesis of major neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, neurodegeneration with brain iron accumulation, and amyotrophic lateral sclerosis. This review first outlines systemic and brain iron metabolism, highlighting how neural cells regulate homeostasis. Next, it examines iron's physiological roles, particularly in neurogenesis and neurodevelopment. Finally, it explores iron's involvement in neurodegenerative diseases, emphasizing neuroinflammation as a primary mechanism of iron toxicity.},
}

Humans
*Iron/metabolism
*Homeostasis
Animals
*Neurons/metabolism
Neurodegenerative Diseases/metabolism/pathology
Neurogenesis
Neurodevelopment
Brain/metabolism

@article {pmid42274906,
year = {2026},
author = {He, Y and Yi, T and Min, M and Xu, K and Lin, H and Xu, R and Deng, D and Xiao, X},
title = {Environmental Factors Drive Neurodegenerative Diseases Through Glutamate Excitotoxicity: A Convergent Mechanistic Pathway.},
journal = {Neuroscience bulletin},
volume = {},
number = {},
pages = {},
pmid = {42274906},
issn = {1995-8218},
abstract = {This review illustrates how environmental stressors disrupt glutamate homeostasis via specific mechanisms: lead-induced thiol modification, manganese mediated yin yang 1 (YY1)-histone deacetylases (HDAC) repression, PM2.5-triggered microglia-astrocyte crosstalk, and advanced glycation end products (AGEs)-receptor for advanced glycation end products (RAGE)-nuclear factor kappa-B (NF-κB) signaling from high-sugar diets. Together with genetic susceptibility and pigment epithelium-derived factor (PEDF), these factors impair astrocytic glutamate uptake, promoting synaptic glutamate accumulation. Subsequent N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor overactivation triggers calcium overload, mitochondrial dysfunction, oxidative stress, and neuroinflammation-termed "degenerative excitotoxicity". Excitotoxicity manifests in Alzheimer's disease (amyloid-beta-excitatory amino acid transporter 2 (EAAT2) interplay), Parkinson's disease (subthalamic nucleus-driven excitatory storm), and amyotrophic lateral sclerosis (astrocytic failure versus neuronal cell-autonomous mechanisms). Future interventions need multi-target strategies, emerging technologies, and lifestyle modifications. This convergent framework offers a unified understanding linking environmental exposure to neurodegeneration and charts a roadmap toward mechanism-based prevention and treatment.},
}

@article {pmid42274979,
year = {2026},
author = {Ojha, GJ and Talwar, T},
title = {Exploring the Role of Spirituality in Neuropalliative Care: An Integrative Review.},
journal = {Journal of religion and health},
volume = {},
number = {},
pages = {},
pmid = {42274979},
issn = {1573-6571},
abstract = {Neuropalliative care aims to address the physical, psychosocial and spiritual needs of persons with progressive and life-limiting neurological conditions, while spiritual care fosters hope and meaning in life. Progressive neurological disorders with an uncertain disease trajectory present a set of complex challenges that have far-reaching consequences on the patient's self-belief, questioning the very existence, self-identity, and belongingness. A typical neuropalliative care team consists of neurologists, nurses, psychologists, occupational therapists, and spiritual care providers. Previous research indicates that spiritual care improves coping and quality of life in persons with Parkinson's disease and Amyotrophic lateral sclerosis. This study aimed to explore how spiritual needs are addressed in the area of neuropalliative care, examining the theoretical frameworks and empirical studies that incorporate spirituality as a component of neuropalliative care. The databases PubMed, PsycINFO, Cochrane Library, Scopus and two peer-reviewed journals were searched using a strategy based on three sets of terms "spirituality," "progressive neurological conditions" and "neuropalliative care." Articles included were in the English language, and mentioned spirituality in the context of neuropalliative care or palliative care for neurological conditions. Initial screening yielded 744 articles, of which 29 were selected for synthesis. Results highlighted the various challenges in ascertaining and meeting the spiritual needs in neuropalliative care. The review concludes that palliative services should be initiated early following the diagnosis of a progressive neurological condition so that the patient and family have enough time to reflect, create memories, and prepare in advance for the inevitable through dignity and resilience.},
}

@article {pmid42275159,
year = {2026},
author = {Ito, D and Iida, M and Iguchi, Y and Hashizume, A and Yamada, S and Kishimoto, Y and Komori, S and Obara, K and Nishisaki, S and Yokoi, S and Shimamura, T and Takemoto, Y and Nakatochi, M and Akashi, T and Hinohara, K and Lee-Okada, HC and Okada, Y and Niwa, J and Sobue, G and Tanaka, S and Takashina, K and Yokomizo, T and Katsuno, M},
title = {Fatty acid amide hydrolase inhibition for treatment of amyotrophic lateral sclerosis.},
journal = {JCI insight},
volume = {},
number = {},
pages = {},
doi = {10.1172/jci.insight.198842},
pmid = {42275159},
issn = {2379-3708},
abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease caused by the selective loss of upper and lower motor neurons. There is a considerable variability in the disease progression of sporadic ALS, but the molecular basis for phenotypic heterogeneity remains largely unknown. ALS patients often manifest systemic metabolic abnormalities such as glucose intolerance and hypermetabolic state. We conducted reverse translational research to explore therapeutic targets in ALS based on the systemic metabolic alterations in patients and identified several metabolites associated with the disease progression, including metabolites involved in the expanded endocannabinoid system (ECS). In particular, the levels of N-acyl taurines (NATs) were correlated with the longitudinal change in the revised ALS functional rating scale and survival. Experiments with ALS cellular models, iPS cells derived from ALS patients and SOD1G93A transgenic mice revealed that PF-04457845, a fatty acid amide hydrolase inhibitor, upregulated the expanded ECS, particularly the levels of NATs and ameliorated motor neuron degeneration through the regulation of microglial environment, synapse plasticity, and neuronal development. These results collectively indicate that dysregulation of NATs is associated with ALS progression and PF-04457845 may represent a potential disease-modifying therapy for ALS.},
}

@article {pmid42276279,
year = {2026},
author = {Gurung, N and Choi, DY and Park, PH},
title = {Naringenin as a Multi-Target Neuroprotective Agent in Neurodegenerative Diseases.},
journal = {Neurochemistry international},
volume = {},
number = {},
pages = {106203},
doi = {10.1016/j.neuint.2026.106203},
pmid = {42276279},
issn = {1872-9754},
abstract = {Neurodegenerative diseases (ND) such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS) are characterized by progressive neuronal loss driven by complex and multifactorial pathogenic mechanisms. Naringenin (NAR), a citrus-derived flavanone, has attracted considerable interest as a neuroprotective molecule due to its pleiotropic pharmacological activities such as antioxidant, anti-inflammatory and ability to modulate multiple cellular targets. This review provides a comprehensive overview of NAR pharmacokinetic profile, mechanistic actions, and therapeutic potential across major ND. We highlight how NAR's multi-target effects-including redox homeostasis maintenance, suppression of neuroinflammation, protein aggregation inhibition, and modulation of signaling pathways-contribute to neuroprotection in various experimental models of AD, PD, HD, ALS, and MS. Preclinical studies demonstrate that NAR can ameliorate cognitive and motor deficits in toxin and transgenic models of neurodegeneration, attenuate pathological hallmarks such as amyloid-beta toxicity, dopaminergic neuronal loss, and neuroinflammation, and induce cytoprotective pathways including Nrf2-mediated antioxidant response and autophagy. However, NAR's clinical translation is challenged by poor bioavailability; thus, novel delivery systems are being explored to enhance brain uptake. NAR emerges as a promising multi-functional neuroprotective agent that can simultaneously target diverse pathogenic processes in ND. Further research including advanced formulation development and well-designed clinical trials is warranted to fully establish NAR's therapeutic efficacy and safety in humans.},
}

@article {pmid42276329,
year = {2026},
author = {Abzhanova, E and Kawae, Y and Mizuno, H and Umemoto, T and Ciftci, H and Tsuboi, M and Hirabayashi, Y and Mizuno, H},
title = {ALS-associated protein TDP-43 disturbs axonal projections in the somatosensory cortex.},
journal = {Neuroscience research},
volume = {},
number = {},
pages = {105079},
doi = {10.1016/j.neures.2026.105079},
pmid = {42276329},
issn = {1872-8111},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by loss of upper and lower motor neurons that gradually causes muscle weakness and paralysis, eventually resulting in death. While ALS was once believed to specifically target motor neurons, recent clinical studies have revealed sensory involvement. The pathological hallmark of ALS is TAR DNA-binding protein 43 (TDP-43) aggregation in cytoplasm, with increasing evidence of its presence in both motor and sensory neurons. However, sensory abnormalities remain poorly characterized. To address this research gap, we analyzed the effects of TDP-43 expression on layer 2/3 (L2/3) pyramidal neurons of the primary somatosensory cortex in mice projecting through corpus callosum. In utero electroporation (IUE) was performed to express GFP alone (control) or in combination with TDP-43. Compared with the control, mice co-expressing GFP and TDP-43 showed disturbed callosal axonal projections of L2/3 neurons. Mutant TDP-43 variants displayed a more pronounced phenotype, indicating pathogenic role during fetal cortical development. To distinguish developmental from maintenance effects, tamoxifen-inducible TDP-43 expression was used to initiate postnatal TDP-43 expression. Postnatal induction resulted in shorter axonal length and reduced branching rather than gross projections disturbance. Taken together, these results demonstrate that TDP-43 expression can disturb the integrity of axonal projections, such as callosal projections of L2/3 neurons in the somatosensory cortex.},
}

@article {pmid42276614,
year = {2026},
author = {Karthikeyan, K and Velmurugan, G and Upadhyay, R and Sevanan, M and Chinnathambi, S},
title = {Glutamate and glutamine metabolism in neurodegenerative diseases.},
journal = {International review of neurobiology},
volume = {186},
number = {},
pages = {1-24},
doi = {10.1016/bs.irn.2026.01.008},
pmid = {42276614},
issn = {2162-5514},
mesh = {Humans ; *Glutamic Acid/metabolism ; *Glutamine/metabolism ; *Neurodegenerative Diseases/metabolism/drug therapy ; Animals ; },
abstract = {Glutamate is known as the most important excitatory neurotransmitter in brain. Glutamate and glutamine recycling is very essential to maintain the nitrogen metabolism. Despite of its major functions, its dysregulation is a basic pathology which is common to neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), and Amyotrophic lateral sclerosis (ALS). Amyloid-β and Tau in AD disrupt glutamate uptake and the glutamate-glutamine cycle, accelerating synaptic failure, whereas loss of astrocytic EAAT2 in ALS generates unrelenting excitotoxicity and motor neuron demise. Toxic α-synuclein aggregation in PD exacerbates dopamine-glutamate imbalance through destabilizing corticostriatal transmission. This review explores on the key mechanisms by which glutamate impairment leads to the pathogenies of neurogenerative disorders and also about current medications like amantadine, memantine, and riluzole which are glutamate antagonists, are shown to partially alleviative but cannot halt the advancement of the disease. One of the potential targets for disease-modifying treatments could be the receptor modulation, astrocytic function, and elimination of excess glutamate.},
}

Humans
*Glutamic Acid/metabolism
*Glutamine/metabolism
*Neurodegenerative Diseases/metabolism/drug therapy
Animals

@article {pmid42276630,
year = {2026},
author = {McRae, M and Hart, L and Wolf, L},
title = {Accreditation as opportunity: Preparing future nursing leaders through faculty collaboration and succession planning.},
journal = {Journal of professional nursing : official journal of the American Association of Colleges of Nursing},
volume = {65},
number = {},
pages = {137-141},
doi = {10.1016/j.profnurs.2026.04.007},
pmid = {42276630},
issn = {1532-8481},
abstract = {Preparing for Commission on Collegiate Nursing Education (CCNE) accreditation requires extensive faculty engagement, yet the literature offers limited guidance on operational strategies to cultivate collaboration and mentorship during this process. This article describes the Keigwin School of Nursing's adaptation of Benner's novice to expert framework and Haverkamp et al.'s (2018) "map for accreditation" to design a collaborative approach for developing the self-study report and preparing for a site visit. Junior faculty were paired with experienced mentors in dyads, assigned to analyze key elements of the CCNE Standards, and reported findings back to cross-program Standard Teams. This structure fostered faculty development, enhanced understanding of accreditation processes, and promoted succession planning. Standardized meeting minutes, end-of-year committee reports, and the use of stoplight tracking tools provided systematic evidence of continuous quality improvement. Faculty-wide meetings and individualized support further strengthened readiness and confidence for site visit engagement. The outcome was full faculty participation, successful alignment of undergraduate and graduate program reaccreditation cycles, and no accreditation compliance concerns reported for any program. These results underscore the value of mentorship, collaboration, and succession planning in accreditation preparation and highlight the potential to address national challenges in faculty shortages, destabilization of higher education, and the need for a unified nursing faculty voice in academic advocacy.},
}

@article {pmid42276908,
year = {2026},
author = {Covas Moschovas, M and Falagario, U and Pellegrino, F and Wiklund, P and Patel, V},
title = {Reply to Alexander Light, Max Peters, Manit Arya, et al's Salvage Focal Therapy vs Radical Prostatectomy for Localized Radiorecurrent Prostate Cancer. JAMA Oncol 2026;12:364-73. https://doi.org/10.1001/jamaoncol.2025.6448.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2026.05.031},
pmid = {42276908},
issn = {1873-7560},
}

@article {pmid42279231,
year = {2026},
author = {Mesches, MH and Granholm, AC and Paredes, D and Mesches, K and Oguma, Y and Dezawa, M},
title = {Stem Cell Therapy for Parkinson's Disease: A Mechanistically Distinct Role for Muse Cells.},
journal = {Journal of clinical medicine},
volume = {15},
number = {11},
pages = {},
doi = {10.3390/jcm15114370},
pmid = {42279231},
issn = {2077-0383},
abstract = {Cell replacement therapy is a promising investigational approach for Parkinson's disease (PD), a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra. Although current PD therapies provide symptomatic relief, none halt or reverse disease progression. Early transplantation studies using fetal dopaminergic neurons provided proof of concept for PD cell replacement, with recent efforts focusing on pluripotent stem cell-derived dopaminergic progenitors that are now entering clinical testing. These strategies face challenges, however, including immune compatibility, tumorigenic risk, and the need for controlled differentiation and functional integration. Multi-lineage differentiating stress-enduring (Muse) cells are endogenous, non-tumorigenic pluripotent-like stem cells that home to sites of tissue injury and differentiate in response to the host microenvironment. A targeted literature search of PubMed and Scopus, however, did not identify prior reviews specifically addressing Muse cells in the context of PD, highlighting a gap in the literature. Here, we examine current limitations of established cell-replacement approaches and consider whether Muse cells may represent a mechanistically distinct cell source. Early clinical studies of Muse cell therapy in stroke and amyotrophic lateral sclerosis suggest an encouraging safety profile and preliminary signals of potential therapeutic benefit, although these findings are based on small, early-stage trials and require confirmation. The evidence supporting Muse cell therapy in PD is currently limited to a single preclinical animal study, supported by mechanistic in vitro findings and indirect evidence from other neurologic disease models; therefore, its relevance to PD remains to be established, and current evidence is insufficient to support conclusions regarding clinical efficacy. Together, these observations provide a rationale for further targeted preclinical investigation and support the systematic evaluation of Muse cells as a mechanistically distinct candidate for regenerative therapy in PD.},
}

@article {pmid42280649,
year = {2026},
author = {Liu, Q and Zhang, R and Sun, L and Lu, X and Xu, G and Tong, H and Zhang, B and Liu, X and Du, S},
title = {Mechanism of Echinochloa crus-galli Resistance to the ALS-Inhibiting Herbicide Pyrazosulfuron-ethyl in China.},
journal = {Plants (Basel, Switzerland)},
volume = {15},
number = {11},
pages = {},
doi = {10.3390/plants15111611},
pmid = {42280649},
issn = {2223-7747},
abstract = {Rice (Oryza sativa L.) is a staple food crop, feeding more than 3.5 billion people. With the increasing demand for food in the 21st century, weed infestation poses the most significant biotic threat to global food security, and herbicides remain the most effective and economic way to manage it in field. However, weeds can rapidly adapt under herbicide selection pressure due to their high competitiveness, rapid growth, and reproductive capacity. Hence, we collected Echinochloa crus-galli populations from Heilongjiang and Hebei provinces in China and investigated their resistance mechanisms to pyrazosulfuron-ethyl (PSE), a sulfonylurea herbicide that inhibits acetolactate synthase (ALS). Dose-response experiments confirm that the resistant (R) population exhibits 52.9-fold resistance to PSE compared with the susceptible (S) population. Inhibitor bioassays with malathion and NBD-Cl, together with ALS activity assays, ALS gene sequencing, and molecular docking, collectively suggest that resistance is strongly associated with the ALS Trp-574-Leu target-site substitution, with a possible additional contribution from enhanced herbicide metabolism. However, because the S and R populations originate from geographically distinct locations, some of the observed physiological and molecular differences may also reflect inherent population variation. Specifically, the ALS W574L substitution is predicted to reduce key interactions between ALS and PSE. This study provides valuable evidence for the risk of PSE resistance evolution in E. crus-galli and elucidates the molecular mechanism conferring resistance to ALS inhibitors.},
}

@article {pmid42281786,
year = {2026},
author = {Tsai, AC},
title = {Defining a shift estimand on forgivingness without domesticating forgiveness: Comment on Cowden et al.},
journal = {SSM. Mental health},
volume = {9},
number = {},
pages = {},
pmid = {42281786},
issn = {2666-5603},
abstract = {This commentary responds to Cowden et al.'s (2026) careful epidemiologic study of the population-wide changes in well-being that might follow from two explicitly defined "shift" scenarios applied to a three-item forgivingness measure. I value the paper's candor about its counterfactual aim: it is not asking whether forgiveness is good in the abstract, but what could plausibly happen if the distribution of measured forgivingness were moved in specified ways. I argue that Cowden et al.'s (2026) methodological clarity surfaces what remains ethically and theologically decisive. In Christian thought, forgiveness is not simply an emotion-regulation technique or a general prosocial disposition; it is a demanding practice formed by grace and ordered toward truth, justice, mercy, and (where possible) repair. When we compress that "thick" practice into a several-item scale for administration in population surveys, we risk treating qualitatively different moral realities as interchangeable. This thinning is subject to the same critique when applied to intervention: a shift estimand tells us what might follow from a distributional change but not how to bring it about; and different ways of cultivating forgiveness may not be morally or practically interchangeable, even if they produce the same numerical shift. While the rigor Cowden et al. (2026) bring to this literature is commendable, the remaining challenge is to connect distributional shifts in forgivingness scores to the concrete practices and communal disciplines that form forgiveness as a moral reality rather than a psychological technique.},
}

@article {pmid42265995,
year = {2026},
author = {Ozlu, C and Schwaede, A and McGowan, B and Zhang, L and Finch, M and Wolfe, LF and Ajroud-Driss, S and Franz, C and Kuntz, N},
title = {Two Patients With Juvenile-Onset, Rapidly Progressive Amyotrophic Lateral Sclerosis Associated With an SOD1 Variant (p.Asp125Gly) With Incomplete Penetrance.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70314},
pmid = {42265995},
issn = {1097-4598},
abstract = {INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) patients are rarely encountered before age 25 years, often associated with genetic variants. SOD1 gene variants are well-known to account for a subset of adult-onset ALS but have only been described in a handful of early onset patients. Variants affecting residue 125 in SOD1 have been described in adult-onset ALS patients with a rapid progression. Here we report two such patients.

METHODS: The clinical, genetic, and electrodiagnostic findings of two unrelated adolescents with juvenile onset rapidly progressive SOD1-ALS are described.

RESULTS: Patient 1 presented at 16 and patient 2 at 15 years-of-age with lower limb onset of weakness, lower motor neuron examination findings, and rapid progression over months to involve all body regions. Both patients underwent extensive laboratory, electrophysiologic, and radiologic testing ruling out any alternate etiologies. For both patients, whole-exome sequencing revealed the pathogenic variant p.Asp125Gly in the SOD1 gene inherited from asymptomatic fathers.

DISCUSSION: These two patients expand the phenotypic spectrum of SOD1-ALS, demonstrating a rapidly progressive juvenile lower limb onset phenotype associated with the p.Asp125Gly variant inherited with incomplete penetrance. Recognition and further characterization of juvenile SOD1-ALS are important in light of the advances in targeted therapies.},
}

@article {pmid42266360,
year = {2026},
author = {Ilczak, T and Ćwiertnia, M and Sumera, K and Babik, P and Białoń, P and Dutka, M and Malinowska-Lipień, I and Augustyn, M and Majewski, M and Lis, A and Leszczyński, P and Stasicki, A and Abramczyk, P and Kukla, P and Pollok-Waksmańska, W and Trojak-Piętka, J and Kawecki, M},
title = {Nontechnical Skills (NTS) and the Quality of Conducting Prehospital Advanced Cardiopulmonary Resuscitation Among Paramedics.},
journal = {Emergency medicine international},
volume = {2026},
number = {},
pages = {2207053},
pmid = {42266360},
issn = {2090-2840},
abstract = {INTRODUCTION: It is common knowledge that the correct application of cardiopulmonary resuscitation (CPR) requires technical skills such as defibrillation, high-quality chest compressions, and efficient airway management. However, scientific research is increasingly underlining the role of appropriate training in nontechnical skills (NTS).

RESEARCH AIM: This exploratory study aimed to assess the relationship between NTS and the quality of advanced CPR among paramedics.

MATERIALS AND METHODS: The research involved 51 paramedics randomly assigned to 17 three-person teams. Each team participated in a 15-min cardiac arrest scenario. After the first session, the teams were divided into two groups: the intervention group (Group 1), which underwent specialized NTS training, and the control group (Group 2), which did not receive the initial training. Directly after the training phase, all teams from both groups carried out a second attempt during a simulated sudden cardiac arrest (SCA) scenario identical to the first one.

RESULTS: The lowest CPR result in the intervention group (Group 1) was Min = -3.00, and the highest Max = 13.00, while in the control group (Group 2), the lowest result was Min = -42.00, and the highest Max = 8.00 (p < 0.05). In Group 1, a statistically significant correlation (p < 0.05) was noted between the change in the NTS score and the change in the CPR result. A higher NTS score was accompanied by a higher CPR score.

CONCLUSIONS: A short NTS training session was associated with improved NTS application by paramedic resuscitation teams. Furthermore, higher chest compression quality positively correlated with NTS proficiency.},
}

@article {pmid42267592,
year = {2026},
author = {Malik, MMUD},
title = {Moral Injury, Peer Support and Allied Health Integration: Three Extensions to Gilmore et al.'s Account of Mental Health Crisis Care in Homelessness.},
journal = {Journal of psychiatric and mental health nursing},
volume = {},
number = {},
pages = {},
doi = {10.1111/jpm.70156},
pmid = {42267592},
issn = {1365-2850},
}

@article {pmid42267597,
year = {2026},
author = {Held-Bradford, EC and DeMarco, E and Zocher, S and Weaver, K and Forsman, K and Hayat, G and Subramaniam, DS and Doherty, M},
title = {Functional Motor Change Across Time and Phenotypes in Patients With Amyotrophic Lateral Sclerosis: A Descriptive Study.},
journal = {Neurorehabilitation and neural repair},
volume = {},
number = {},
pages = {15459683261445435},
doi = {10.1177/15459683261445435},
pmid = {42267597},
issn = {1552-6844},
abstract = {PURPOSE: Progressive disability occurs in persons with amyotrophic lateral sclerosis (pALS), but change over time across phenotypes remains understudied, limiting clinical decision-making. This descriptive study describes functional motor change with detailed measures across ALS phenotypes to enhance clinical decision making.

MATERIALS AND METHODS: Electronic health record data from an interdisciplinary ALS clinic (n = 109 pALS, 2018-2022) including demographics, disability (ALS Functional Rating Scale-[ALSFRS-R]), and functional motor scores (10 m Walk, Handheld dynamometry [grip and ankle]) was utilized. Phenotype groups were defined by site of onset (bulbar, limb onset; upper limb or lower limb). Analysis was conducted using R and included changes scores and measures of central tendency in 3-month intervals.

RESULTS: PALS included n = 43 bulbar, n = 32 upper limb, n = 34 lower limb onset, age 65, 60 to 71 (median, interquartile range). ALFSRS-R decline was greatest in bulbar, and similar in upper and lower limb. Patterns of change within motor scores suggest greatest loss of grip strength in bulbar and upper limb, ankle strength in upper limb, walking speed in lower limb, and preservation of community ambulation in upper limb.

CONCLUSION: While ALSFRS-R scores were similar in upper and lower limb, detailed functional motor measures indicated differences in groups. These patterns provide insight to guide clinical decision making and future research to enhance care in pALS.},
}

@article {pmid42267908,
year = {2026},
author = {Donati Della Lunga, I and Cerutti, L and Barabino, V and Figus, GG and Callegari, F and Oneto, L and Tedesco, M and Bacchetti, F and Milanese, M and Massobrio, P and Brofiga, M},
title = {Developmental circuit instability in amyotrophic lateral sclerosis: from hyperexcitability to network collapse.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag185},
pmid = {42267908},
issn = {1460-2156},
abstract = {Amyotrophic lateral sclerosis (ALS) is traditionally viewed as a late-onset motor neuron disease, yet how cortical dysfunction originates and contributes to pathogenesis remains unresolved. In this study, we reconstruct the developmental trajectory of cultured cortical networks derived from SOD1G93A mouse embryos using a multimodal approach, by combining morphometric, electrophysiological, pharmacological, molecular, computational, and machine-learning techniques. We prove that ALS neurons fail to acquire mature polarization and connectivity, displaying a transient phase of hyperexcitability that precedes a progressive collapse of network organization. Astrocytic dysfunction emerges early and impairs synchronization, establishing a causal link between glial dysfunction and neuronal instability. The analysis of synaptic transmission reveals an excitatory bias followed by maladaptive inhibitory recruitment and GABA/glutamate co-release, causing fragmented and inefficient network topologies. Finally, in silico modelling identified deficient intrinsic adaptation as a key driver of hyperexcitability. Together, our findings position ALS as a developmentally rooted disorder of cultured cortical network homeostasis, driven by glial, synaptic, and intrinsic adaptation failures. By demonstrating that cortical dysfunction is embedded before degeneration, this work provides a unifying framework connecting early network instability to disease progression and establishes electrophysiological network signatures, detected by machine learning classifiers, as candidate biomarkers for early diagnosis and therapeutic screening.},
}

@article {pmid42268433,
year = {2026},
author = {Sytwu, HP and Jih, KY and Tsai, YS and Fang, SY and Liao, YC and Lee, YC},
title = {FUS-associated ALS in Taiwan: genetic spectrum, clinical features, and a founder haplotype of p.H517D.},
journal = {Journal of neurology},
volume = {273},
number = {7},
pages = {},
pmid = {42268433},
issn = {1432-1459},
support = {112-2314-B-075-034-MY3//National Science and Technology Council/ ; 114-2314-B-075-021-MY3//National Science and Technology Council/ ; 113-2314-B-075-018-MY3//National Science and Technology Council/ ; },
abstract = {OBJECTIVE: To characterize the genetic spectrum and clinical features of FUS-associated amyotrophic lateral sclerosis (ALS) in a Taiwanese cohort and to investigate whether the recurrent p.H517D variant represents a founder mutation.

METHODS: All coding exons and flanking intronic regions of FUS were analyzed by Sanger sequencing in 650 unrelated Taiwanese patients with ALS. Clinical characteristics of patients carrying FUS variants were evaluated. Haplotype analysis using polymorphic microsatellite markers flanking FUS was performed to assess a potential founder effect of the p.H517D variant.

RESULTS: Eight distinct heterozygous pathogenic FUS variants were identified in 11 probands and five affected relatives, including six missense and two frameshift variants. The most frequent variant was p.H517D, detected in four probands. A novel frameshift variant, p.G499Vfs*30, was identified as a de novo mutation in a juvenile-onset ALS patient. Compared with the non FUS-associated ALS cohort, patients with FUS-associated ALS had a significantly younger mean age at onset (40.1 vs 56.6 years) and more frequent bulbar onset (50% vs 19%). Haplotype analysis suggested a common founder for the p.H517D variant.

CONCLUSIONS: FUS mutations accounted for 1.7% of ALS cases in this Taiwanese cohort. The recurrent p.H517D variant appears to represent a population-specific founder mutation. Patients with FUS variants presented with earlier disease onset and heterogeneous clinical phenotypes, and de novo variants contributed to juvenile-onset disease.},
}

@article {pmid42268660,
year = {2026},
author = {Roy, É and Blais, M and Dion, P and Rouleau, GA and Dupré, N and Picher-Martel, V},
title = {Oligogenic variants in NEK1 and ATXN2 in amyotrophic lateral sclerosis: report of two cases and review of the literature.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/21678421.2026.2685158},
pmid = {42268660},
issn = {2167-9223},
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that affects the upper and lower motor neurons and leads to progressive paralysis. More than 40 genes have been implicated in familial ALS, which represents about 10% of ALS cases. Some genes, including C9orf72, SOD1, FUS and TARDBP are undoubtedly considered causative, but many others have uncertain pathogenicity and low penetrance. Here, we described the cases of two siblings affected by ALS and carrying both an ATXN2 heterozygous 32 CAG trinucleotide repeat expansion and a novel NEK1 heterozygous c.1674_1677dup. The segregation of both variants in this large family with thirteen siblings may support a role for these variants as susceptibility alleles within an oligogenic model. Our review of the literature suggests that NEK1 variants are frequently found in combination with other variants and repeats expansion in the ATXN2 gene appears to be more associated with monogenic ALS, but also frequently combined with C9orf72 repeat expansion.},
}

@article {pmid42269975,
year = {2026},
author = {Ma, M and Cui, B and Sun, X and Liu, S and Shao, K and Liu, F and Lin, P and Li, W and Zhao, Y and Yu, D and Lou, J and Yun, Y},
title = {Progressive choroid plexus enlargement across disease stages in patients with sporadic amyotrophic lateral sclerosis.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107481},
doi = {10.1016/j.nbd.2026.107481},
pmid = {42269975},
issn = {1095-953X},
abstract = {BACKGROUND: The choroid plexus (CP), a key structure involved in cerebrospinal fluid homeostasis and glymphatic function, is increasingly recognized as an interface for neuroimmune communication. Recent studies have identified CP abnormalities as potential neuroimaging markers in several neurodegenerative disorders, including sporadic amyotrophic lateral sclerosis (sALS). However, whether CP enlargement occurs early and progresses across clinical stages or over time in patients with sALS remains unclear. Given the role of the CP in peripheral-central nervous system immune crosstalk, the association between neuroinflammation and CP abnormalities in sALS also requires clarification. In this prospective study, we used structural MRI to examine cross-sectional and longitudinal CP volume changes in patients with sALS and to evaluate their associations with CSF inflammatory markers.

METHODS: This prospective study included 161 newly diagnosed patients with sALS who underwent genetic testing and structural MRI, and 64 healthy controls (HCs) who underwent structural MRI. Disease stage in patients with sALS was assessed using the King's staging system. Longitudinal MRI was performed in a subset of 42 patients, of whom 38 also underwent baseline CSF inflammatory protein assessment.

RESULTS: Compared with HCs, patients with sALS at all King's stages showed significantly larger CP volumes after Bonferroni correction (all p < 0.05). CP volumes were significantly greater in patients at King's stage 3 than in those at King's stage 1 or stage 2 after Bonferroni correction (all p < 0.05). In the longitudinal subgroup, CP volume increased significantly from baseline to follow-up. Multivariable analysis showed that higher CSF CHIT1 and IL-6 levels were independently associated with larger CP volume in patients with sALS (β = 0.348-0.456; p < 0.01).

CONCLUSIONS: Our findings provide evidence that CP enlargement occurs early and progresses across disease stages and over time in patients with sALS. Higher CSF CHIT1 and IL-6 levels were associated with larger CP volume, supporting a potential link between neuroinflammation and CP abnormalities in sALS. These findings support CP enlargement as a promising neuroimaging marker for monitoring disease progression and neuroinflammatory processes in patients with sALS.},
}

@article {pmid42270846,
year = {2026},
author = {Wood, H and Hamdi, N},
title = {Advancing amyotrophic lateral sclerosis research in Egypt.},
journal = {Nature reviews. Neurology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41582-026-01230-x},
pmid = {42270846},
issn = {1759-4766},
}

@article {pmid42271582,
year = {2026},
author = {Ito, M},
title = {[Re-evaluating ALS Medical Care in Japan: An International Comparison of Japan, Europe, the United States, and Canada-Insights from Mechanical Ventilation, Support for Social Participation, End-of-Life Care Options, Approved Drugs, and Precision Medicine].},
journal = {Brain and nerve = Shinkei kenkyu no shinpo},
volume = {78},
number = {6},
pages = {654-657},
doi = {10.11477/mf.188160960780060654},
pmid = {42271582},
issn = {1881-6096},
abstract = {Amyotrophic lateral sclerosis (ALS) care in Japan should be re-evaluated not simply as a matter of clinical choice but as a function of the public support system structure. In Japan, care is distinguished by a publicly funded model that supports home-based living and social participation following tracheostomy invasive ventilation. In contrast, Europe reflects a model centered on non-invasive ventilation and palliative care, and the United States reflects a system in which precision therapies are approved earlier but access remains highly unequal. Further, Canada reflects a model integrating multidisciplinary ALS clinics with Medical Assistance in Dying within a shared policy framework. These differences extend beyond treatment preferences and instead reflect broader social, institutional, and ethical configurations that shape the future of individuals with ALS. As access to emerging disease-modifying therapies increasingly depends on genetic testing, the central challenge in ALS care is shifting from end-of-life decision-making to the equitable distribution of precision medicine. Comparative reappraisal of national care models is therefore critical for understanding ALS not only as a neurological disease but also as a condition shaped by welfare systems, care infrastructure, and policy design.},
}

@article {pmid42271589,
year = {2026},
author = {Kunieda, K},
title = {[Clinical Management of Dysphagia and Nutritional Disorders in Neurodegenerative Diseases].},
journal = {Brain and nerve = Shinkei kenkyu no shinpo},
volume = {78},
number = {6},
pages = {695-700},
doi = {10.11477/mf.188160960780060695},
pmid = {42271589},
issn = {1881-6096},
abstract = {Dysphagia is common in patients with neuro degenerative diseases. It is associated with aspiration pneumonia, malnutrition, and reduced quality of life. Swallowing assessment should incorporate therapeutic perspectives, including the use of compensatory strategies. In conditions such as amyotrophic lateral sclerosis, weight loss is associated with a poor prognosis, and nutritional therapy may function as a disease-modifying intervention. Clinical ethical issues may arise, including decisions regarding gastrostomy or care for patients with impaired decision-making capacity. A multidisciplinary team approach is essential for managing dysphagia and nutritional problems in these patients.},
}

@article {pmid42272352,
year = {2026},
author = {Lizio, A and Farè, M and Gerardi, F and Collesi, M and Sansone, VA and Lunetta, C and Diamanti, L and Cerri, F},
title = {Impact of treatment burden on medication adherence and quality of life in amyotrophic lateral sclerosis: a prospective multicentre study.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/21678421.2026.2683691},
pmid = {42272352},
issn = {2167-9223},
abstract = {BACKGROUND: Patients with amyotrophic lateral sclerosis (ALS) face substantial barriers to medication adherence as disease progression necessitates complex drug formulation adjustments, such as crushing tablets, mixing with liquids, or delivering via feeding tubes. These modifications may not only increase the time and effort required but could also impact drug efficacy and safety.

OBJECTIVE: To evaluate the prevalence and the impact of treatment burden on medication adherence and patient-reported quality of life (QoL) in ALS.

METHODS: This prospective multicenter study enrolled ALS patients across three Italian reference centers, with assessments at baseline, 6, and 12 months. Key measures included the Multimorbidity Treatment Burden Questionnaire (MTBQ), ALSFRS-R, DYALS (dysphagia), Morisky Medication Adherence Scale, SSS-8 (somatic symptoms), INQoL (QoL), SWAMECO (swallowing/medication difficulties), alongside comorbidities and current therapies. Associations between treatment burden, QoL, and adherence were analyzed using multivariable models.

RESULTS: A total of 114 consecutive ALS patients were enrolled. Clinically significant treatment burden was observed in 69.3% of patients, with over half reporting moderate-to-high levels according to the MTBQ classification. Elevated burden was independently related to greater somatic symptom severity and formulation modification needs. Moreover, higher burden associated with poorer QoL and diminished adherence after confounder adjustment. Longitudinally, patients experiencing worsening burden over 1 year showed accelerated QoL decline compared to those remaining stable, though adherence trajectories were unaffected.

CONCLUSION: Treatment burden, particularly driven by drug formulation complexities and somatic symptoms, emerges as a pivotal, modifiable determinant of adherence and QoL in ALS. Targeted interventions to alleviate modifiable burden components hold promise for optimizing clinical outcomes and enhancing patient-centred care.},
}

@article {pmid42272365,
year = {2025},
author = {Mishra, V and Shekhar, S and Bisht, S and Chatterjee, R and Pandey, L and Pandey, A},
title = {Incidental Radiation Exposure to the Internal Mammary Lymph Nodes in Breast Cancer Patients Undergoing Intensity-Modulated Radiation Therapy: A Retrospective Analysis.},
journal = {The Gulf journal of oncology},
volume = {1},
number = {49},
pages = {16-21},
pmid = {42272365},
issn = {2521-3881},
mesh = {Humans ; Female ; *Radiotherapy, Intensity-Modulated/methods/adverse effects ; Retrospective Studies ; Middle Aged ; Adult ; *Breast Neoplasms/radiotherapy/pathology ; *Lymph Nodes/radiation effects/pathology ; *Radiation Exposure ; Radiotherapy Planning, Computer-Assisted/methods ; Radiotherapy Dosage ; },
abstract = {BACKGROUND: Breast cancer (BC) remains the most common malignancy among Indian women, with Stage III being the most frequent at diagnosis. While radiation therapy (RT) plays a pivotal role in the adjuvant treatment of breast cancer, the inclusion of internal mammary lymph nodes (IMLNs) in the radiation field remains controversial due to potential cardiopulmonary toxicity. However, the extent of incidental radiation to the IMLNs, especially with forward planning intensity-modulated radiation therapy (IMRT), remains under-explored.

OBJECTIVE: This study aimed to evaluate the incidental radiation dose received by the IMLNs in patients with leftsided breast cancer treated with forward planning IMRT.

MATERIALS AND METHODS: A total of 36 left-sided breast cancer patients, aged 35-60 years, who underwent modified radical mastectomy followed by adjuvant RT using IMRT, were retrospectively analyzed. CT-based planning and contouring were performed according to RTOG guidelines, with IMLNs contoured retrospectively using Jetwa et al.'s method. Dosimetric parameters for the planning target volume (PTV) and IMLNs were extracted and analyzed using dose-volume histograms. Statistical comparisons were made using the dependent Student's t-test.

RESULTS: The PTV received effective radiation coverage with a mean D95 of 38.47 Gy and a mean Dmean of 40.10 Gy. The IMLNs, although not directly targeted, received significant incidental radiation, with a mean D95 of 8.49 Gy, D50 of 21.59 Gy, and Dmean of 21.40 Gy. The maximum dose to the IMLNs (Dmax) reached 38.14 Gy. Comparative analysis revealed statistically significant differences in both Dmax and Dmean between PTV and IMLNs (p = 0.004 and p < 0.001, respectively).

CONCLUSION: Forward planning IMRT provides substantial incidental radiation exposure to the IMLNs, which may have therapeutic implications in reducing recurrence risk. However, this exposure also necessitates careful consideration of potential long-term toxicities to adjacent organs. Further prospective studies are warranted to evaluate the clinical outcomes associated with incidental IMLN irradiation.},
}

Humans
Female
*Radiotherapy, Intensity-Modulated/methods/adverse effects
Retrospective Studies
Middle Aged
Adult
*Breast Neoplasms/radiotherapy/pathology
*Lymph Nodes/radiation effects/pathology
*Radiation Exposure
Radiotherapy Planning, Computer-Assisted/methods
Radiotherapy Dosage

@article {pmid42274555,
year = {2026},
author = {Khan, MS and Zafar, I and Noman, M and Yang, G and Kang, KS and Bopassa, JC},
title = {Polypharmacology of Pathway Crosstalk in Neurodegenerative Diseases: Chemical Modulation of Interconnected Signaling Networks.},
journal = {Cells},
volume = {15},
number = {11},
pages = {},
pmid = {42274555},
issn = {2073-4409},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology ; *Signal Transduction/drug effects ; *Polypharmacology ; Animals ; Oxidative Stress ; Mitochondria/metabolism ; },
abstract = {Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), arise from highly interconnected molecular and cellular abnormalities that progressively lead to neuronal dysfunction, synaptic failure, and cell death. This review provides a unified framework to understand the interrelated molecular mechanisms driving these diseases, with a focus on identifying key disease-specific intervention nodes. Core contributors include oxidative stress, mitochondrial dysfunction, protein aggregation, neuroinflammation, and emerging roles of peroxisomal dysfunction in redox imbalance, lipid dysregulation, and inflammatory amplification. Single-target therapies often show limited efficacy due to the complex, interconnected nature of these pathways. In contrast, polypharmacology, which targets multiple disease-relevant mechanisms simultaneously, offers a more promising therapeutic strategy. This review critically examines how pathway crosstalk drives neurodegenerative progression, with particular emphasis on mitochondrial-ROS-inflammatory signaling, aggregation-proteostasis failure, synaptic-neuroimmune dysfunction, and gut-brain communication. It evaluates various multi-node intervention strategies, including multi-target-directed ligands (MTDLs), molecular hybrids, natural products, drug repurposing, and nanocarrier-based delivery systems. Advances in network pharmacology, artificial intelligence (AI), bioinformatics, and multi-omics have enhanced the identification of actionable therapeutic nodes, candidate compounds, and brain-targeted delivery platforms. Notably, the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathways-play distinct roles in neuroinflammation, amplifying neuronal damage by releasing inflammatory cytokines and inducing mitochondrial dysfunction. However, successful translation into clinical practice remains constrained by challenges such as blood-brain barrier penetration, patient heterogeneity, and biomarker limitations. The review advocates for a shift towards mechanism-informed, patient-stratified polypharmacological strategies to better address the network pathology of neurodegeneration, despite significant translational hurdles.},
}

Humans
*Neurodegenerative Diseases/drug therapy/metabolism/pathology
*Signal Transduction/drug effects
*Polypharmacology
Animals
Oxidative Stress
Mitochondria/metabolism

@article {pmid42274577,
year = {2026},
author = {Schuldt, ON and Leitch, SR and Jones, LK and Buckley, PR and Morrison, BE},
title = {Neuroinflammatory Remodeling by Type 2 Immune Pathways Links Allergic Signaling to Neurodegenerative Disease.},
journal = {Cells},
volume = {15},
number = {11},
pages = {},
pmid = {42274577},
issn = {2073-4409},
support = {R15HL165397//National Heart Lung and Blood Institute/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/immunology/pathology ; Animals ; *Signal Transduction/immunology ; *Hypersensitivity/immunology ; *Neuroinflammatory Diseases/immunology ; },
abstract = {The hallmarks of allergic diseases are Type 2 immunity, including IL-4 and IL-13 production, IgE antibody generation, mast cell and basophil activation, histamine release, and eosinophil activation. There are many routes by which such mediators can influence CNS biology, including cytokine entry or signaling via brain barrier receptors; leukocyte trafficking across activated barriers; cytokine signaling via circumventricular organ sites or dural immune compartments; vagus nerve afferent signaling; mast cell degranulation; and histamine neuromodulation. Neuroinflammation is a common hallmark of many neurodegenerative diseases, but whether and to what degree allergic/type 2 immune biology may be involved depends on the specific disease stage and pathology. Here, we assess studies connecting the roles of IL-4/IL-13 signaling, IgE/mast cell activation, eosinophil-attractive chemokines, and histamines in Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, dementia with Lewy bodies, Huntington's disease, prion disease, and tauopathy/atypical parkinsonism. Mechanisms appear most clear in the case of Parkinson's disease, where epidemiology suggests an important role in dementia/Alzheimer's disease, while for other neurodegenerative conditions the evidence is less compelling and may be either mechanistic or modulatory. Confounding issues include sex differences, drug exposures, comorbid conditions, socioeconomic factors, and coexisting inflammatory diseases. Finally, we suggest a strategy based on longitudinal immune phenotyping, CNS biomarkers, and pathway manipulation to assess the relationship between allergic immune signaling and neurodegeneration.},
}

Humans
*Neurodegenerative Diseases/immunology/pathology
Animals
*Signal Transduction/immunology
*Hypersensitivity/immunology
*Neuroinflammatory Diseases/immunology